query: how long can the coronavirus live outside the body

positive: Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.

positive: COVID-19 and gastrointestinal endoscopies: Current insights and emergent strategies A new coronavirus emerged in December 2019 in Wuhan city of China, named as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the disease was called coronavirus disease-2019 (COVID-19). The infection due to this virus spread exponentially throughout China and then spread across >205 nations, including the United States (US). Gastrointestinal (GI) endoscopies are routinely performed in the US and globally. Previous reports of isolated infection outbreaks were reported with endoscopes acting as potential vectors. While multidrug-resistant organisms have been reported to be spread by endoscopes, few cases of viruses such as hepatitis B and C are noted in the literature. COVID-19 is predominately spread by droplet transmission, although recent evidence has showed that shedding in feces and feco-oral transmission could also be possible. It is unclear if COVID-19 could be transmitted by endoscopes, but it could theoretically happen due to contact with mucous membranes and body fluids. GI endoscopies involve close contact with oral and colonic contents exposing endoscopy staff to respiratory and oropharyngeal secretions. This can increase the risk of contamination and contribute to virus transmission. Given these risks, all major GI societies have called for rescheduling elective non-urgent procedures and perform only emergent or urgent procedures based on the clinical need. Furthermore, pre-screening of all individuals prior to endoscopy is recommended. This article focuses on the risk of COVID-19 transmission by GI shedding, the potential role of endoscopes as a vector of this novel virus, including transmission during endoscopies, and prevention strategies including deferral of elective non-urgent endoscopy procedures.

positive: Body fluids may contribute to human-to-human transmission of severe acute respiratory syndrome coronavirus 2: evidence and practical experience BACKGROUND: In December 2019, an unbelievable outbreak of pneumonia associated with coronavirus was reported in the city of Wuhan, Hubei Province. This virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although much effort has been spent on clarifying the transmission route of SARS-CoV-2, but, very little evidence is available regarding the relationship between human body fluids and transmission of SARS-CoV-2 virus. Considerable evidence from hospital in Wuhan indicates that strict rules to avoid occupational exposure to patients’ body fluids in healthcare settings, particularly among every medical staff, limited person-to-person transmission of nosocomial infections by direct or indirect contact. CONCLUSION: We tried to provide important information for understanding the possible transmission routes of SARS-CoV-2 via body fluids including bronchoalveolar-lavage, saliva, blood, urine, feces, sputum, tears, and semen in order to control coronavirus disease 2019 (COVID-19) occurrences.

positive: Issues Concerning Survival of Viruses on Surfaces Viruses are the causative agents of an estimated 60% of human infections worldwide. The most common viral illnesses are produced by enteric and respiratory viruses. Transmission of these viruses from an infected person or animal to a new host can occur via several routes. Existing studies strongly suggest that contaminated fomites or surfaces play an important role in the spreading of viral diseases. The potential of viral spreading via contaminated surfaces depends particularly on the ability of the virus to maintain infectivity whilst it is in the environment. This is affected by a combination of biological, physical and chemical factors. This review summarises current knowledge about the influence of environmental factors on the survival and spread of viruses via contaminated surfaces.

positive: Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies In the aftermath of the SARS epidemic, there has been significant progress in understanding the molecular and cell biology of SARS-CoV. Some of the milestones are the availability of viral genome sequence, identification of the viral receptor, development of an infectious cDNA clone, and the identification of viral antigens that elicit neutralizing antibodies. However, there is still a large gap in our understanding of how SARS-CoV interacts with the host cell and the rapidly changing viral genome adds another variable to this equation. Now the SARS-CoV story has entered a new phase, a search for preventive strategies and a cure for the disease. This review highlights the progress made in identifying molecular aspects of SARS-CoV biology that is relevant in developing disease prevention strategies. Authors conclude that development of successful SARS-CoV vaccines and antivirals depends on the progress we make in these areas in the immediate future.

positive: Development and laboratory evaluation of a compact swirling aerosol sampler (SAS) for collection of atmospheric bioaerosols Abstract Inhalation of infectious bioaerosols has been linked to a variety of respiratory diseases. However, efficient sampling techniques to allow high temporal resolution sampling are limited to collect and study bioaerosols in the various occupational and ambient micro–environmental atmospheres. This study introduces a medium flow swirling bioaerosol sampler (SAS) approach that collects atmospheric bioaerosols at the flow rate of 167 Lpm (10 cubic meter per hour). The collection of bioaerosols is achieved through a combination of impaction and cyclonic centrifugal motion. Aerosol deposition efficiency tests were performed with monodispersive polystyrene latex (PSL) particles ranging from 0.1 to 10 μm. Results have shown that the sampler has cut–off size of 0.7 μm and 1.5 μm, with and without the assistance of added water vapor, respectively. The bioaerosol collection and viability tests were performed with comparison to the commercially–available BioSampler, and the results show that the collection efficiency of the SAS is 97% at the designed flow rate, while the higher flow of the new system yields more than 13 times of the collection rate compared to the BioSampler. The high collection efficiency and observed viability preservation of the SAS make it an attractive alternative for high time resolution bioaerosol sampling for atmospheric, occupational and indoor air quality monitoring.

positive: Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1-4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.

positive: Modelling aerosol transport and virus exposure with numerical simulations in relation to SARS-CoV-2 transmission by inhalation indoors We provide research findings on the physics of aerosol dispersion relevant to the hypothesized aerosol transmission of SARS-CoV-2. We utilize physics-based modeling at different levels of complexity, and literature on coronaviruses, to investigate the possibility of airborne transmission. The previous literature, our 0D-3D simulations by various physics-based models, and theoretical calculations, indicate that the typical size range of speech and cough originated droplets (d<20microns) allows lingering in the air for O(1h) so that they could be inhaled. Consistent with the previous literature, numerical evidence on the rapid drying process of even large droplets, up to sizes O(100microns), into droplet nuclei/aerosols is provided. Based on the literature and the public media sources, we provide evidence that the infected individuals could have been exposed to aerosols/droplet nuclei by inhaling them in significant numbers e.g. O(100). By 3D computational fluid dynamics (CFD) simulations, we give examples on the transport and dilution of aerosols (d<20microns) over distances O(10m) in generic environments. We study susceptible and infected individuals in generic public places by Monte-Carlo modeling. The model accounts for the locally varying aerosol concentration levels which the susceptible accumulate via inhalation. The introduced concept, 'exposure time' to virus containing aerosols is proposed to complement the traditional 'safety distance' thinking. We show that the exposure time to inhale O(100) aerosols could range from O(1s) to O(1min) or even to O(1h) depending on the situation. The Monte Carlo analysis provides clear quantitative insight to the exposure time in different public indoor environments.

positive: Airborne transmission of severe acute respiratory syndrome coronavirus‐2 to healthcare workers: a narrative review Healthcare workers are at risk of infection during the severe acute respiratory syndrome coronavirus‐2 pandemic. International guidance suggests direct droplet transmission is likely and airborne transmission occurs only with aerosol‐generating procedures. Recommendations determining infection control measures to ensure healthcare worker safety follow these presumptions. Three mechanisms have been described for the production of smaller sized respiratory particles (‘aerosols’) that, if inhaled, can deposit in the distal airways. These include: laryngeal activity such as talking and coughing; high velocity gas flow; and cyclical opening and closure of terminal airways. Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5‐μm diameter threshold used to differentiate droplet from airborne is an over‐simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol‐generating procedures comes largely from low‐quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to severe acute respiratory syndrome coronavirus‐1 patients with respiratory symptoms, rather than the procedures per se. There is no proven relation between any aerosol‐generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for severe acute respiratory syndrome coronavirus‐2 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several aerosol‐generating procedures may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.

positive: BOARD-INVITED REVIEW: Fate and transport of bioaerosols associated with livestock operations and manures Airborne microorganisms and microbial by-products from intensive livestock and manure management systems are a potential health risk to workers and individuals in nearby communities. This report presents information on zoonotic pathogens in animal wastes and the generation, fate, and transport of bioaerosols associated with animal feeding operations and land applied manures. Though many bioaerosol studies have been conducted at animal production facilities, few have investigated the transport of bioaerosols during the land application of animal manures. As communities in rural areas converge with land application sites, concerns over bioaerosol exposure will certainly increase. Although most studies at animal operations and wastewater spray irrigation sites suggest a decreased risk of bioaerosol exposure with increasing distance from the source, many challenges remain in evaluating the health effects of aerosolized pathogens and allergens in outdoor environments. To improve our ability to understand the off-site transport and diffusion of human and livestock diseases, various dispersion models have been utilized. Most studies investigating the transport of bioaerosols during land application events have used a modified Gaussian plume model. Because of the disparity among collection and analytical techniques utilized in outdoor studies, it is often difficult to evaluate health effects associated with aerosolized pathogens and allergens. Invaluable improvements in assessing the health effects from intensive livestock practices could be made if standardized bioaerosol collection and analytical techniques, as well as the use of specific target microorganisms, were adopted.

positive: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24–3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.

positive: Survival of Coronaviruses in Water and Wastewater The advent of severe acute respiratory syndrome and its potential environmental transmission indicates the need for more information on the survival of coronavirus in water and wastewater. The survival of representative coronaviruses, feline infectious peritonitis virus, and human coronavirus 229E was determined in filtered and unfiltered tap water (4 and 23°C) and wastewater (23°C). This was compared to poliovirus 1 under the same test conditions. Inactivation of coronaviruses in the test water was highly dependent on temperature, level of organic matter, and presence of antagonistic bacteria. The time required for the virus titer to decrease 99.9% (T(99.9)) shows that in tap water, coronaviruses are inactivated faster in water at 23°C (10 days) than in water at 4°C (>100 days). Coronaviruses die off rapidly in wastewater, with T(99.9) values of between 2 and 4 days. Poliovirus survived longer than coronaviruses in all test waters, except the 4°C tap water.

positive: Human coronaviruses: Clinical features and phylogenetic analysis Abstract Strains of human coronavirus (HCoV), namely HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1, primarily infect the upper respiratory and gastrointestinal tracts and are the most common cause of non-rhinovirus-induced common cold in humans. Although the manifestations of coronavirus infection (i.e., rhinorrhea, sneezing, cough, nasal obstruction, and bronchitis) are generally self-limiting in healthy adults, certain strains such as HCoV-NL63 and HCoV-HKU1 can cause severe lower respiratory tract infection and febrile seizure, especially in infants, people of advanced age, and immunocompromised hosts. In 2003, a novel HCoV strain was identified as the causative agent of the severe acute respiratory syndrome (SARS) epidemic that began in Asia in 2002. The strain has hence been referred to as SARS-CoV. In addition, as recently as September 2012, another novel HCoV, human betacoronavirus 2c EMC2012, was identified as being the cause of fever, renal failure, pneumonia, and severe respiratory distress in two patients in the Middle East. Phylogenetic analysis has revealed highly conserved sequences of ORF1ab, spike, nucleocapsid, and envelope protein genes, but not membrane protein genes, between human betacoronavirus 2c EMC2012 and SARS-CoV. This review focuses on the differences in the genomes of certain HCoV strains, the pathogenesis of said strains, and recent developments in the establishment of therapeutic agents that might aid in the treatment of patients with such infections.

positive: Replication of SARS-CoV-2 in human respiratory epithelium SARS-CoV-2 emerged by the end of 2019 to rapidly spread in 2020. At present, it is of utmost importance to understand the virus biology and to rapidly assess the potential of existing drugs and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in the Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on the SARS-CoV-2. Further, we also provide basic characteristics of the system.

positive: Infection Control in Dental Practice During the COVID-19 Pandemic COVID-19 is the disease supported by SARS-CoV-2 infection, which causes a severe form of pneumonia. Due to the pathophysiological characteristics of the COVID-19 syndrome, the particular transmissibility of SARS-CoV-2, and the high globalization of our era, the epidemic emergency from China has spread rapidly all over the world. Human-to-human transmission seems to occur mainly through close contact with symptomatic people affected by COVID-19, and the main way of contagion is via the inhalation of respiratory droplets, for example when patients talk, sneeze or cough. The ability of the virus to survive outside living organisms, in aerosol or on fomites has also been recognized. The dental practitioners are particularly exposed to a high risk of SARS-CoV-2 infection because they cannot always respect the interpersonal distance of more than a meter and are exposed to saliva, blood, and other body fluids during surgical procedures. Moreover, many dental surgeries can generate aerosol, and the risk of airborne infection is to be considered higher. The aim of this paper is to provide practical advice for dentists based on the recent literature, which may be useful in reducing the risk of spreading COVID-19 during clinical practice.

positive: Effect of ultraviolet germicidal irradiation on viral aerosols. Ultraviolet (UV) germicidal air disinfection is an engineering method used to control the airborne transmission of pathogenic microorganisms in high-risk settings. Despite the recent emergence of respiratory viral pathogens such as SARS and avian influenza viruses, UV disinfection of pathogenic viral aerosols has not been examined. Hence, we characterized the UV disinfection of viral aerosols using the bacteriophage MS2, adenovirus, and coronavirus. Our objectives were to characterize the effect of nebulization and air sampling on the survival of important viral pathogens, quantitatively characterize and estimate the UV susceptibility of pathogenic viral aerosols, and evaluate the effect of relative humidity (RH) on the susceptibility of viral aerosols, to 254 nm UV-C. The viruses were aerosolized into an experimental chamber using a six-jet Collison nebulizer, exposed to 254 nm UV, and sampled using an AGI-30 liquid impinger. Both the MS2 and adenovirus aerosols were very resistant to UV air disinfection, with a reduction of less than 1 logarithm in viable viral aerosols at a UV dose of 2608 microW s/cm2. The susceptibility of coronavirus aerosols was 7-10 times that of the MS2 and adenovirus aerosols. Unlike bacterial aerosols, there was no significant protective effect of high RH on UV susceptibility of the tested viral aerosols. We confirmed that the UV disinfection rate differs greatly between viral aerosols and viruses suspended in liquid.

positive: Coronavirus Disease (COVID-19) and Pediatric Patients: A Review of Epidemiology, Symptomatology, Laboratory and Imaging Results to Guide the Development of a Management Algorithm Coronavirus disease (COVID-19) has been declared a worldwide pandemic. Compared to adults, there has been a significantly smaller number of reported cases of COVID-19 in the pediatric population, although the incidence is increasing every day. This article looks to review specific epidemiological factors, symptomatology, laboratory and imaging workup, and other relevant metrics derived from the limited published literature that are specific to the pediatric population, to provide a review for the pediatric practitioner and guide, in part, the creation of a clinical algorithm for the management of COVID-19 in the pediatric population that can be utilized by pediatric institutions.

positive: SARS-CoV-2: air/aerosols and surfaces in laboratory and clinical settings

positive: Increasing Temperature and Relative Humidity Accelerates Inactivation of SARS-CoV-2 on Surfaces Coronavirus disease 2019 (COVID-19) was first identified in China in late 2019 and is caused by newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies had reported the stability of SARS-CoV-2 in cell culture media and deposited onto surfaces under a limited set of environmental conditions. Here, we broadly investigated the effects of relative humidity, temperature, and droplet size on the stability of SARS-CoV-2 in a simulated clinically relevant matrix dried on nonporous surfaces. The results show that SARS-CoV-2 decayed more rapidly when either humidity or temperature was increased but that droplet volume (1 to 50 μl) and surface type (stainless steel, plastic, or nitrile glove) did not significantly impact decay rate. At room temperature (24°C), virus half-life ranged from 6.3 to 18.6 h depending on the relative humidity but was reduced to 1.0 to 8.9 h when the temperature was increased to 35°C. These findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and have implications for assessment of the risk posed by surface contamination in indoor environments. IMPORTANCE Mitigating the transmission of SARS-CoV-2 in clinical settings and public spaces is critically important to reduce the number of COVID-19 cases while effective vaccines and therapeutics are under development. SARS-CoV-2 transmission is thought to primarily occur through direct person-to-person transfer of infectious respiratory droplets or through aerosol-generating medical procedures. However, contact with contaminated surfaces may also play a significant role. In this context, understanding the factors contributing to SARS-CoV-2 persistence on surfaces will enable a more accurate estimation of the risk of contact transmission and inform mitigation strategies. To this end, we have developed a simple mathematical model that can be used to estimate virus decay on nonporous surfaces under a range of conditions and which may be utilized operationally to identify indoor environments in which the virus is most persistent.

positive: Airborne/Droplet Infection Isolation Airborne/droplet infection is caused by infected agents in the air around a person. Microbial pathogenic agents that are mainly transmitted airborne are aerosols, re-aerosols, microbe-carrying particles, huge amounts of bacteria-carrying airborne skin cells, dust, droplets and droplet nuclei. At the same time, there is always a contact transmission from contaminated environment, equipment, textiles and waste. Droplet nuclei are small evaporated droplet residues (<5 μm) produced by coughing, sneezing, shouting, singing and speaking very distinct—especially the consonants. Droplet nuclei remain for many hours in the air and may be carried by normal air currents in long distances outside the room. Therefore, “droplet isolation and droplet precaution” is included in the airborne isolation regime. The source of infection is usually a patient but may also be a healthy carrier. The patient should be placed in isolate dedicated for airborne infections.

positive: Will COVID-19 pandemic diminish by summer-monsoon in India? Lesson from the first lockdown The novel Coronavirus (2019-nCoV) was identified in Wuhan, Hubei Province, China, in December 2019 and has created a medical emergency worldwide. It has spread rapidly to multiple countries and has been declared a pandemic by the World Health Organization. In India, it is already reported more than 18 thousand cases and more than 600 deaths due to Coronavirus disease 2019 (COVID-19) till April 20, 2020. Previous studies on various viral infections like influenza have supported an epidemiological hypothesis that the cold and dry (low absolute humidity) environments favor the survival and spread of droplet-mediated viral diseases. These viral transmissions found attenuated in warm and humid (high absolute humidity) environments. However, the role of temperature, humidity, and absolute humidity in the transmission of COVID-19 has not yet been well established. Therefore the study to investigate the meteorological condition for incidence and spread of COVID-19 infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease is required for India. In this work, we analyze the local weather patterns of the Indian region affected by the COVID-19 virus for March and April months, 2020. We have investigated the effect of meteorological parameters like Temperature, relative humidity, and absolute humidity on the rate of spread of COVID-19 using daily confirm cases in India. We have used daily averaged meteorological data for the last three years (2017-2019) for March and April month and the same for the year 2020 for March 1 to April 15. We found a positive association (Pearsons r=0.56) between temperature and daily COVID-19 cases over India. We found a negative association of humidity (RH and AH) with daily COVID-19 Cases (Persons r=-0.62, -0.37). We have also investigated the role of aerosol in spreading the pandemic across India because its possible airborne nature. For this, we have investigated the association of aerosols (AOD) and other pollutions (NO2) with COVID-19 cases during the study period and also during the first lockdown period (25 March-15 April) in India. We found a negative association in March when there were few cases, but in April, it shows positive association when the number of cases is more (for AOD it was r=-0.41 and r=0.28 respectively). During the lockdown period, aerosols (AOD) and other pollutants (NO2; an indicator of PM2.5) reduced sharply with a percentage drop of about 36 and 37, respectively. This reduction may have reduced the risk for COVID-19 through air transmission due to the unavailability of aerosol particles as a base. HYSPLIT forward trajectory model also shows that surface aerosols may travel up to 4 km according to wind and direction within three h of its generation. If coronavirus becomes airborne as suggested by many studies, then it may have a higher risk of transmission by aerosols particles. So relaxing in the lockdown and environmental rules in terms of pollutant emissions from power plants, factories, and other facilities would be a wrong choice and could result in more COVID-19 incidences and deaths in India. Therefore the current study, although limited, suggests that it is doubtful that the spread of COVID-19 would slow down in India due to meteorological factors, like high temperature and high humidity. Because a large number of cases have already been reported in the range of high Tem, high Relative, and high absolute humidity regions of India. Thus our results in no way suggest that COVID-19 would not spread in warm, humid regions or during summer/monsoon. So effective public health interventions should be implemented across India to slow down the transmission of COVID-19. If COVID-19 is indeed sensitive to environmental factors, it could be tested in the coming summer-monsoon for India. So the only summer is not going to help India until monsoon is coming. Only government mitigations strategies would be helpful, whether its lockdown, aggressive and strategic testing, medical facilities, imposing social distancing, encouraging to use face mask or monitoring by a mobile application (Aarogya Setu).

positive: Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: A global health emergency Abstract According to data compiled by researchers at Johns Hopkins University in Baltimore, Maryland, more than two and half million cases of coronavirus disease 2019 (COVID-19), caused by a newly discovered virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed on April 20, 2020 (Nature, 2020b). Since the emergence of this infectious disease in Asia (Wuhan, China) late last year, it has been subsequently span to every continent of the world except Antarctica (Rodríguez-Morales et al., 2020). Along with a foothold in every country, the current disease pandemic is disrupting practically every aspect of life all over the world. As the outbreak are continuing to evolve, several research activities have been conducted for better understanding the origin, functions, treatments, and preventions of this novel coronavirus. This review will be a summa of the key features of novel coronavirus (nCoV), the virus causing disease 2019 and the present epidemic situation worldwide up to April 20, 2020. It is expected that this record will play an important role to take more preventive measures for overcoming the challenges faced during this current pandemic.

positive: Lack of SARS-CoV-2 RNA environmental contamination in a tertiary referral hospital for infectious diseases in Northern Italy

positive: Severe Acute Respiratory Syndrome Coronavirus on Hospital Surfaces Background. Health care workers continued to contract severe acute respiratory syndrome (SARS), even after barrier precautions were widely implemented. Methods. We explored the possible contribution of contaminated hospital surfaces to SARS transmission by swabbing surfaces in 2 hospitals and testing the swab samples by reverse-transcriptase polymerase chain reaction (RT-PCR) and viral culture. Results. Twenty-six of 94 swab samples tested positive for viral RNA. Swab samples of respiratory secretions from each of the 4 patients examined tested positive by RT-PCR, as were 12 of 43 swabs from patient rooms and 10 of 47 swabs from other parts of the hospital, including the computer mouses at 2 nursing stations and the handrail of the public elevator. Specimens from areas with patients with SARS in the most infectious phase of illness (days 5–15 after onset) were more likely to be RNA positive than were swab specimens from elsewhere (24 of 63 samples vs. 2 of 31 samples; P = .001). All cultures showed no growth. Conclusions. Although the viruses identified may have been noninfectious, health care workers should be aware that SARS coronavirus can contaminate environmental surfaces in the hospital, and fomites should be considered to be a possible mode of transmission of SARS.

positive: SARS-CoV-2 in the environment: Modes of transmission, early detection and potential role of pollutions Abstract The coronavirus disease 2019 (COVID-19) is spreading globally having a profound effect on lives of millions of people, causing worldwide economic disruption. Curbing the spread of COVID-19 and future pandemics may be accomplished through understanding the environmental context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and adoption of effective detection tools and mitigation policies. This article aims to examine the latest investigations on SARS-CoV-2 plausible environmental transmission modes, employment of wastewater surveillance for early detection of COVID-19, and elucidating the role of solid waste, water, and atmospheric quality on viral infectivity. Transmission of SARS-CoV-2 via faecal-oral or bio-aerosols lacks robust evidence and remains debatable. However, improper disinfection and defected plumbing systems in indoor environments such as hospitals and high-rise towers may facilitate the transport of virus-laden droplets of wastewater causing infection. Clinical and epidemiological studies are needed to present robust evidence that SARS-CoV-2 is transmissible via aerosols, though quantification of virus-laden aerosols at low concentrations presents a challenge. Wastewater surveillance of SARS-CoV-2 can be an effective tool in early detection of outbreak and determination of COVID-19 prevalence within a population, complementing clinical testing and providing decision makers guidance on restricting or relaxing movement. While poor air quality increases susceptibility to diseases, evidence for air pollution impact on COVID-19 infectivity is not available as infections are dynamically changing worldwide. Solid waste generated by households with infected individuals during the lockdown period may facilitate the spread of COVID-19 via fomite transmission route but has received little attention from the scientific community. Water bodies receiving raw sewage may pose risk of infection but this has not been investigated to date. Overall, our understanding of the environmental perspective of SARS-CoV-2 is imperative to detecting outbreak and predicting pandemic severity, allowing us to be equipped with the right tools to curb any future pandemic.

positive: Survival of influenza A virus on contaminated student clothing The role of contaminated clothing in the transmission of influenza A virus during an epidemic period was investigated by examining the recovery of infectious influenza virus from experimentally virus-contaminated clothing, which had been subejected to routine wearing and washing for several months or years. The amount of infectious virus recovered from the nine types of clothing decreased with time and was shown to differ widely between clothing samples, when the contaminated clothing samples were maintained in uncovered glass Petri dishes in a safety cabinet under air blowing. These results indicate a dependence of virus transmissibility on the nature of the contaminated clothes. The difference in recovery was shown to have no significant correlation with the thickness or the materials of the clothing; however, a correlation was observed with the residual amount of water in the deposited virus preparation on the test clothing.

positive: Transmission routes of respiratory viruses among humans Respiratory tract infections can be caused by a wide variety of viruses. Airborne transmission via droplets and aerosols enables some of these viruses to spread efficiently among humans, causing outbreaks that are difficult to control. Many outbreaks have been investigated retrospectively to study the possible routes of inter-human virus transmission. The results of these studies are often inconclusive and at the same time data from controlled experiments is sparse. Therefore, fundamental knowledge on transmission routes that could be used to improve intervention strategies is still missing. We here present an overview of the available data from experimental and observational studies on the transmission routes of respiratory viruses between humans, identify knowledge gaps, and discuss how the available knowledge is currently implemented in isolation guidelines in health care settings.

positive: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.

positive: Significance of fomites in the spread of respiratory and enteric viral disease.

positive: Estimation of SARS-CoV-2 emissions from non-symptomatic cases Importance: Cases of the coronavirus disease 2019 (COVID-19) with no or mild symptoms were reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome virus (SARS-COV-2) was found at very high concentrations in swab and sputum of such cases. Objective: We aimed to estimate virus release from such cases into different aerosol sizes by normal breathing and coughing, and what exposure can result from this in a room shared with such as case. Data Sources and Model: We combined the size-distribution of exhaled breath aerosols for coughing and normal breathing with viral sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50m3, the size of a small office or medical exam room. Results: The estimated viral load in aerosols emitted by patients while breathing normally was on average 0.34 copies/cm3 and could go up to 11.5 copies/cm3. The corresponding numbers for coughing patients were 10,900 copies/cm3 and 366,000 copies/cm3, respectively, per cough. The resulting concentrations in a room with a coughing emitter were always very high, up to 2.02*10^9 copies/m3. However, also regular breathing aerosol from high emitters was predicted to lead to several thousand copies/m3. Conclusions and Relevance: These very high predicted virus concentrations may provide an explanation why for COVID-19, frequent community transmissions from non-symptomatic cases and also high infection rates in medical staff in hospital settings were reported. Our findings suggest that strict respiratory protection is needed when there is a chance to be in the same room with a patient - whether symptomatic or not - especially if this was for a prolonged time.

positive: Indirect Virus Transmission in Cluster of COVID-19 Cases, Wenzhou, China, 2020 To determine possible modes of virus transmission, we investigated a cluster of coronavirus disease cases associated with a shopping mall in Wenzhou, China. Data indicated that indirect transmission of the causative virus occurred, perhaps resulting from virus contamination of common objects, virus aerosolization in a confined space, or spread from asymptomatic infected persons.

positive: [Transmission routes of 2019-novel coronavirus (2019-nCoV)] Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.

positive: Novel coronavirus transmission to water bodies; risk of COVID-19 pneumonia to aquatic mammals [Figure: see text]

positive: Transmission routes of 2019-nCoV and controls in dental practice A novel ß-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal-oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.

positive: Disposable masks: Disinfection and sterilization for reuse, and non-certified manufacturing, in the face of shortages during the COVID-19 pandemic The COVID-19 pandemic is posing a huge global health threat. To deal with this problem, in addition to research and work in the medical field, the main health measures being taken in the workplace and at home involve the establishment of safety protocols, which include distance measures, hygiene and the use of personal protective equipment, such as masks, etc. The WHO still does not recommend the use of masks for the general population. However, their successful use in China, South Korea and the Czech Republic has encouraged their widespread use, and the shortage that already existed. This has caused that companies and individuals are looking at the best way to reuse them, and to manufacture, homemade or not, of non-certified masks. This paper is based on two objectives: to consult the scientific literature to identify the main strategies for disinfecting them, and to determine the effectiveness of non-certified disposable masks. A rapid review has been conducted in which the main publications and other information available online have been analyzed. Results showed that the most promising methods are those that use hydrogen peroxide vapor, ultraviolet radiation, moist heat, dry heat and ozone gas. Soapy water, alcohol, bleach immersion, ethylene oxide, ionizing radiation, microwave, high temperature, autoclave or steam are not fully recommended. Regarding the effectiveness of surgical masks compared to PPE, the former have been seen to be slightly less effective than PPE. As for other types of masks the effectiveness of homemade or non-certified masks is very low.

positive: Inactivation of influenza A viruses in the environment and modes of transmission: A critical review Summary Objectives The relative importance of airborne, droplet and contact transmission of influenza A virus and the efficiency of control measures depends among other factors on the inactivation of viruses in different environmental media. Methods We systematically review available information on the environmental inactivation of influenza A viruses and employ information on infectious dose and results from mathematical models to assess transmission modes. Results Daily inactivation rate constants differ by several orders of magnitude: on inanimate surfaces and in aerosols daily inactivation rates are in the order of 1–102, on hands in the order of 103. Influenza virus can survive in aerosols for several hours, on hands for a few minutes. Nasal infectious dose of influenza A is several orders of magnitude larger than airborne infectious dose. Conclusions The airborne route is a potentially important transmission pathway for influenza in indoor environments. The importance of droplet transmission has to be reassessed. Contact transmission can be limited by fast inactivation of influenza virus on hands and is more so than airborne transmission dependent on behavioral parameters. However, the potentially large inocula deposited in the environment through sneezing and the protective effect of nasal mucus on virus survival could make contact transmission a key transmission mode.

positive: Monitoring of viable airborne SARS virus in ambient air Abstract Due to recent SARS related issues (Science 300 (5624) 1394; Nature 423 (2003) 240; Science 300 (5627) 1966), the development of reliable airborne virus monitoring procedures has become galvanized by an exceptional sense of urgency and is presently in a high demand (In: Cox, C.S., Wathers, C.M. (Eds.), Bioaerosols Handbook, Lewis Publishers, Boca Raton, FL, 1995, pp. 247–267). Based on engineering control method (Aerosol Science and Technology 31 (1999) 249; 35 (2001) 852), which was previously applied to the removal of particles from gas carriers, a new personal bioaerosol sampler has been developed. Contaminated air is bubbled through porous medium submerged into liquid and subsequently split into multitude of very small bubbles. The particulates are scavenged by these bubbles, and, thus, effectively removed. The current study explores its feasibility for monitoring of viable airborne SARS virus. It was found that the natural decay of such virus in the collection fluid was around 0.75 and 1.76lg during 2 and 4h of continuous operation, respectively. Theoretical microbial recovery rates of higher than 55 and 19% were calculated for 1 and 2h of operation, respectively. Thus, the new sampling method of direct non-violent collection of viable airborne SARS virus into the appropriate liquid environment was found suitable for monitoring of such stress sensitive virus.

positive: Coronavirus testing indicates transmission risk increases along wildlife supply chains for human consumption in Viet Nam, 2013-2014 Outbreaks of emerging coronaviruses in the past two decades and the current pandemic of a novel coronavirus (SARS-CoV-2) that emerged in China highlight the importance of this viral family as a zoonotic public health threat. To gain a better understanding of coronavirus presence and diversity in wildlife at wildlife-human interfaces in three southern provinces in Viet Nam 2013-2014, we used consensus Polymerase Chain Reactions to detect coronavirus sequences. In comparison to previous studies, we observed high proportions of positive samples among field rats (34.0%, 239/702) destined for human consumption and insectivorous bats in guano farms (74.8%, 234/313) adjacent to human dwellings. Most notably among field rats, the odds of coronavirus RNA detection significantly increased along the supply chain from field rats sold by traders (reference group; 20.7% positivity, 39/188) by a factor of 2.2 for field rats sold in large markets (32.0%, 116/363) and 10.0 for field rats sold and served in restaurants (55.6%, 84/151). Coronaviruses were detected in the majority of wildlife farms (60.7%, 17/28) and in the Malayan porcupines (6.0%, 20/331) and bamboo rats (6.3%, 6/96) that are farmed. We identified six known coronaviruses in bats and rodents, clustered in three Coronaviridae genera, including the Alpha-, Beta-, and Gammacoronaviruses. Our analysis also suggested either mixing of animal excreta in the environment or interspecies transmission of coronaviruses, as both bat and avian coronaviruses were detected in rodent feces in the trade. The mixing of multiple coronaviruses, and their apparent amplification along the wildlife supply chain into restaurants, suggests maximal risk for end consumers and likely underpins the mechanisms of zoonotic spillover to people.

positive: Stability of the COVID-19 virus under wet, dry and acidic conditions COVID-19 has become a pandemic and is spreading fast worldwide. The COVID-19 virus is transmitted mainly through respiratory droplets and close contact. However, the fecal-oral transmission of the virus has not been ruled out and it is important to ascertain how acidic condition in the stomach affects the infectivity of the virus. Besides, it is unclear how stable the COVID-19 virus is under dry and wet conditions. In the present study, we have shown that the COVID-19 virus is extremely infectious as manifested by the infection of Vero-E6 cells by one PFU (Plaque Forming Unit) of the virus. We then investigated the stability of the COVID-19 virus in wet, dry and acidic (pH2.2) environments at room temperature. Results showed that the COVID-19 virus could survive for three days in wet and dry environments, but the dry condition is less favorable for the survival of the virus. Our study also demonstrated that the COVID-19 virus at a relative high titer (1.2 x 103 PFU) exhibits a certain degree of tolerance to acidic environment at least for 60 minutes. When the virus titer was ≤1.0 x 103 PFU, acid treatment (pH2.2) for 30 or 60 minute resulted in virus inactivation. It suggests that the virus at a high concentration may survive in the acidic environment of the stomach. The finding of the present study will contribute to the control of the spread of the COVID-19 virus.

positive: Do Humidity and Temperature Impact the Spread of the Novel Coronavirus?

positive: Protections against the Risk of Airborne SARS-CoV-2 Infection

positive: Survival of aerosolized coronavirus in the ambient air Abstract An inactivation of airborne pathogenic Middle East Respiratory Syndrome (MERS-CoV) virus was investigated under controlled laboratory conditions. Two sets of climatic conditions were used in the experiments; (1) representing common office environment (25°C and 79% RH) and (2) climatic conditions of the Middle Eastern region where the virus was originated from (38°C and 24% RH). At the lower temperature, the virus demonstrated high robustness and strong capability to survive with about 63.5% of microorganisms remaining infectious 60min after aerosolisation. Fortunately, virus decay was much stronger for hot and dry air scenario with only 4.7% survival over 60min procedure.

positive: Public health might be endangered by possible prolonged discharge of SARS-CoV-2 in stool • The published data, which showed the COVID-19 patients with low digestive. • manifestation, might be misleading. Case with negative URT test showed positive in. • rectal scarab which challenge the isolation protocol. • As fomite transmission caused clusters of infection of SARS, adequate disinfection. • operations should be adopted in SARS-CoV-2 outbreak.

positive: Airborne route and bad use of ventilation systems as non-negligible factors in SARS-CoV-2 transmission Summary The world is facing a pandemic of unseen proportions caused by a corona virus named SARS-CoV-2 with unprecedent worldwide measures being taken to tackle its contagion. Person-to-person transmission is accepted but WHO only considers aerosol transmission when procedures or support treatments that produce aerosol are performed. However, transmission mechanisms are not fully understood and there is evidence for an airborne route to be considered as the virus remains viable in aerosols for at least 3h and that mask usage was the best intervention to prevent infection. Heating, Ventilating and Air Conditioning Systems (HVAC) are used as a primary infection disease control measure. However, they may contribute to the transmission/spreading of airborne diseases as proposed in the past for SARS. The authors believe that airborne transmission is possible and that HVAC systems when not adequately used may contribute to the transmission of the virus, as suggested by descriptions of from Japan, Germany, and the Diamond Princess Cruise Ship. Previous SARS outbreaks reported at Amoy Gardens, Emergency Rooms and Hotels, for example, also suggested airborne transmission. Further studies are warranted to confirm our hypotheses but the assumption of such way of transmission would cause a major shift in measures recommended to prevent infection such as the disseminated use of masks and structural changes to hospital and other facilities HVAC systems.

positive: Severe acute respiratory syndrome coronavirus 2 (the cause of COVID 19) in different types of clinical specimens and implications for cytopathology specimen: An editorial review with recommendations

positive: Transmission Dynamics of COVID-19 and Impact on Public Health Policy In this work we construct a mathematical model for the transmission and spread of coronavirus disease 2019 or COVID-19. Our model features delay terms to account for (a) the time lapse or latency period between contracting the disease and displaying symptoms, and (b) the time lag in testing patients for the virus due to the limited numbers of testing facilities currently available. We find that the delay introduces a significant disparity between the actual and reported time-trajectories of cases in a particular region. Specifically, the reported case histories lag the actual histories by a few days. Hence, to minimize the spread of the disease, lockdowns and similarly drastic social isolation measures need to be imposed some time before the reported figures are approaching their peak values. We then account for the social reality that lockdowns can only be of a limited duration in view of practical considerations. We find that the most effective interval for imposing such a limited-time lockdown is one where the midpoint of the lockdown period coincides with the actual peak of the spread of the disease in the absence of the lockdown. We further show that the true effectivity of imposing a lockdown may be misrepresented and grossly underestimated by the reported case trajectories in the days following the action.

positive: The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2 The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern.

positive: Upper-room ultraviolet air disinfection might help to reduce COVID-19 transmission in buildings As the world economies get out of the lockdown imposed by the COVID-19 pandemic, there is an urgent need to assess the suitability of known technologies to mitigate COVID-19 transmission in confined spaces such as buildings. This feasibility study looks at the method of upper-room ultraviolet (UV) air disinfection that has already proven its efficacy in preventing the transmission of airborne diseases such as measles and tuberculosis. Using published data from various sources it is shown that the SARS-CoV-2 virus, which causes COVID-19, is highly likely to be susceptible to UV damage while suspended in air irradiated by UV-C at levels that are acceptable and safe for upper-room applications. This is while humans are present in the room. Both the expected and worst-case scenarios are investigated to show the efficacy of the upper-room UV-C approach to reduce COVID-19 air transmission in a confined space with moderate but sufficient height. Discussion is given on the methods of analysis and the differences between virus susceptibility to UV-C when aerosolised or in liquid or on a surface.

positive: Forensic DNA testing during the SARS-CoV-2 pandemic The aggressive nature of the new SARS-2 corona virus now referred to as SARS-CoV-2 ; the seriousness and length of the period of infection; the fast and far-reaching transmissibility via liquid droplets that become air-borne when someone coughs, sneezes or speaks with increasing evidence to support actual airborne transmission; the presence of viral particles especially in body fluids and tissues, of viral positive individuals; and the persistence of the virus on different types of surfaces pose serious concerns for forensic practitioners, including forensic DNA analysts. Many forensic laboratories and law enforcement agencies need to address the inevitable changes that must be made in forensic DNA testing. In this article, we explore the effects of the COVID-19 pandemic on the collection, handling, storage and transport of biological samples for downstream DNA testing. This paper aims to open discussions on the urgency of balancing the need to conduct investigations in order to maintain public order with the requirements of effective biosafety protocols specifically formulated to protect human resources within the forensic science community.

positive: Presence of Live SARS-CoV-2 Virus in Feces of Coronavirus Disease 2019 (COVID-19) Patients: A Rapid Review Coronavirus disease 2019 (COVID-19) is a rapidly escalating pandemic that has spread to many parts of the world. The disease has already affected over 6 million individuals, with over 400,000 fatalities. Recent studies have confirmed the presence of SARS-CoV-2 nucleic acids in feces of Coronavirus disease 2019 (COVID-19) patients using RT-PCR tests. It is however, still unclear as to whether or not live SARS-CoV-2 virus is actually present in feces of these patients. In this rapid review, we systematically analyzed literature to establish any evidence of live SARS-CoV-2 virus in fecal samples of COVID-19 patients. We identified 4 studies (one case report, 2 case series and 1 cohort study) where the SARS-CoV-2 was successfully isolated from fecal samples of COVID-19 patients using culture techniques. Therefore, there is some evidence COVID-19 could shed live SARS-CoV-2 virus via the gastro-intestinal tract. Larger studies are needed to corroborate these findings, as well as to determine its potential for disease transmission and infection, and possible implications for COVID-19 discharge and isolation policies.

positive: Biocides and Novel Antimicrobial Agents for the Mitigation of Coronaviruses In December, 2019, a highly infectious and rapidly spreading new pneumonia of unknown cause was reported to the Chinese WHO Country Office. A cluster of these cases had appeared in Wuhan, a city in the Hubei Province of China. These infections were found to be caused by a new coronavirus which was given the name “2019 novel coronavirus” (2019-nCoV). It was later renamed “severe acute respiratory syndrome coronavirus 2,” or SARS-CoV-2 by the International Committee on Taxonomy of Viruses on February 11, 2020. It was named SARS-CoV-2 due to its close genetic similarity to the coronavirus which caused the SARS outbreak in 2002 (SARS-CoV-1). The aim of this review is to provide information, primarily to the food industry, regarding a range of biocides effective in eliminating or reducing the presence of coronaviruses from fomites, skin, oral/nasal mucosa, air, and food contact surfaces. As several EPA approved sanitizers against SARS-CoV-2 are commonly used by food processors, these compounds are primarily discussed as much of the industry already has them on site and is familiar with their application and use. Specifically, we focused on the effects of alcohols, povidone iodine, quaternary ammonium compounds, hydrogen peroxide, sodium hypochlorite (NaOCl), peroxyacetic acid (PAA), chlorine dioxide, ozone, ultraviolet light, metals, and plant-based antimicrobials. This review highlights the differences in the resistance or susceptibility of different strains of coronaviruses, or similar viruses, to these antimicrobial agents.

positive: A Laboratory Risk Assessment during the Coronavirus (COVID-19) Pandemic

positive: A new transmission route for the propagation of the SARS-CoV-2 coronavirus We explore here how variation in the SARS-CoV-2 virus tropism could influence epidemic spread. We use a compartmental model fit to the existing data. The model indicates that Wuhan quarantine measures were effective but that alternative virus forms (gut tropism) and a second propagation route (through environment) was present. For Singapore and Shenzhen region the secondary route does not seem to be active yet. Adequate prevention measures taking into account both routes should be implemented.

positive: Extensive Viable Middle East Respiratory Syndrome (MERS) Coronavirus Contamination in Air and Surrounding Environment in MERS Isolation Wards Background. The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) outside the Middle East occurred in South Korea in 2015 and resulted in 186 laboratory-confirmed infections, including 36 (19%) deaths. Some hospitals were considered epicenters of infection and voluntarily shut down most of their operations after nearly half of all transmissions occurred in hospital settings. However, the ways that MERS-CoV is transmitted in healthcare settings are not well defined. Methods. We explored the possible contribution of contaminated hospital air and surfaces to MERS transmission by collecting air and swabbing environmental surfaces in 2 hospitals treating MERS-CoV patients. The samples were tested by viral culture with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA) using MERS-CoV Spike antibody, and electron microscopy (EM). Results. The presence of MERS-CoV was confirmed by RT-PCR of viral cultures of 4 of 7 air samples from 2 patients' rooms, 1 patient's restroom, and 1 common corridor. In addition, MERS-CoV was detected in 15 of 68 surface swabs by viral cultures. IFA on the cultures of the air and swab samples revealed the presence of MERS-CoV. EM images also revealed intact particles of MERS-CoV in viral cultures of the air and swab samples. Conclusions. These data provide experimental evidence for extensive viable MERS-CoV contamination of the air and surrounding materials in MERS outbreak units. Thus, our findings call for epidemiologic investigation of the possible scenarios for contact and airborne transmission, and raise concern regarding the adequacy of current infection control procedures.

positive: COVID-19 and Diabetes: Knowledge in Progress Abstract Aims We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. Methods We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: “SARS-CoV-2”, “COVID-19”, “infection”, “pathogenesis”, “incubation period”, “transmission”, “clinical features”, “diagnosis”, “treatment”, “diabetes”, with interposition of the Boolean operator “AND”. Results The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. Conclusions Suggestions are made on the possible pathological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted.

positive: Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.

positive: Modelling the thermal inactivation of viruses from the Coronaviridae family in suspensions or on surfaces with various relative humidities. Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data of coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D-values (time to obtain a log10 reduction of virus infectivity), including values for SARS-CoV-2, were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global dataset of D-values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points or new coronavirus strains.

positive: MERS-CoV: Understanding the Latest Human Coronavirus Threat Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012, a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure; (ii) clinical features; (iii) diagnosis of infection; and (iv) treatment and vaccine development.

positive: COVID-19 faecal-oral transmission: Are we asking the right questions? Abstract Detection of the SARS-CoV-2 virus in stools and sewage has recently been reported, raising the hypothesis of faecal-oral transmission. If confirmed, this could have far-reaching consequences for public health and for pandemic control strategies. In this paper, we argue that a comprehensive and more nuanced analysis is required to test this hypothesis, taking into consideration both taking into consideration both environmental dynamics and the persistence of viral infectivity. First, we examine the evidence regarding the presence of the virus in stools and sewage. Then we discuss the current framework of disease transmission through water and excreta and how the transmission of a respiratory disease fits into it. Against this background, we propose a framework to test the faecal-oral hypothesis, unpacking the different environmental routes from faeces to the mouth of a susceptible person. This framework should not be seen as a confirmation of the hypothesis but rather as an expanded view of its complexities, which could help shaping an agenda for research into a number of unanswered questions. Finally, the paper briefly discusses practical implications, based on current knowledge, for containment of the pandemic.

positive: Spatial-temporal variations of atmospheric factors contribute to SARS-CoV-2 outbreak The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) reached over two million confirmed cases worldwide, and numbers are still growing at a fast rate. The majority of new infections are now being reported outside of China, where the outbreak officially originated in December 2019 in Wuhan. Despite the wide outbreak of the infection, a remarkable asymmetry is observed in the number of cases and in the distribution of the severity of the COVID-19 symptoms in patients with respect to the countries/regions. In the early stages of a new pathogen outbreak, it is critical to understand the dynamics of the infection transmission, in order to follow contagion over time and project the epidemiological situation in the near future. While it is possible to reason that observed variation in the number and severity of cases stem from the initial number of infected individuals, the difference in the testing policies and social aspects of community transmissions, the factors that could explain high discrepancy in areas with a similar level of healthcare still remain unknown. Here we introduce a binary classifier based on an artificial neural network that can help in explaining those differences and that can be used to support the design of containment policies. We propose that air pollutants, and specifically particulate matter (PM) 2.5 and ozone, are oppositely related with the SARS-CoV-2 infection frequency and could serve as surrogate markers to complement the infection outbreak anticipation.

positive: Airborne transmission of SARS-CoV-2: the world should face the reality Abstract Hand washing and maintaining social distance are the main measures recommended by the World Health Organization (WHO) to avoid contracting COVID-19. Unfortunately, these measured do not prevent infection by inhalation of small droplets exhaled by an infected person that can travel distance of meters or tens of meters in the air and carry their viral content. Science explains the mechanisms of such transport and there is evidence that this is a significant route of infection in indoor environments. Despite this, no countries or authorities consider airborne spread of COVID-19 in their regulations to prevent infections transmission indoors. It is therefore extremely important, that the national authorities acknowledge the reality that the virus spreads through air, and recommend that adequate control measures be implemented to prevent further spread of the SARS-CoV-2 virus, in particularly removal of the virus-laden droplets from indoor air by ventilation.

positive: Global outbreak of severe acute respiratory syndrome (SARS)

positive: An evaluation of porcine epidemic diarrhea virus survival in individual feed ingredients in the presence or absence of a liquid antimicrobial BACKGROUND: Contaminated complete feed and porcine plasma are risk factors for PEDV introduction to farms and a liquid antimicrobial has been proven useful for reducing risk. This study provides information on the survivability of PEDV across common swine feed ingredients in the presence or absence of the liquid antimicrobial. RESULTS: Eighteen ingredients commonly included in commercial swine diets were selected, including 3 grain sources (corn, soybean meal (SBM), dried distillers grains with solubles (DDGS)), 5 porcine by-products (spray-dried plasma, purified plasma, intestinal mucosa, meat and bone meal and red blood cells (RBCs)), 3 vitamin/trace mineral (VTM) mixes (sow, nursery, finishing), 2 fat sources (choice white grease and soy oil), 3 synthetic amino acids (lysine HCL, D/L methionine, threonine), as well as limestone and dry choline chloride. Complete feed and stock PEDV served as controls. Thirty grams of each ingredient were inoculated with 2 mL PEDV. A matched set of samples were treated with the formaldehyde-based liquid antimicrobial SalCURB® (LA). All samples (n = 320) were stored outdoors under winter time ambient conditions for 30 days. Samples were submitted on 1, 7, 14 and 30 days post-inoculation (DPI) and tested by PCR and virus isolation (VI). All VI-negative samples were tested by swine bioassay. Viable PEDV was detected by VI or swine bioassay at 1, 7, 14 and 30 DPI from SBM, DDGS, meat & bone meal, RBCs, lysine HCL, D/L methionine, choice white grease, choline chloride, complete feed and stock virus control and at 7 DPI in limestone and at 14 DPI in threonine. Supplementary testing of complete feed and SBM indicated viable virus out to 45 and 180 DPI, respectively. All other samples were negative by VI and bioassay. In contrast, treatment with LA inactivated PEDV across all ingredients on 1 DPI and induced RNA reduction over time. CONCLUSIONS: Under the conditions of this study, PEDV viability in feed was influenced by ingredient with extended survival in SBM. Furthermore, LA treatment rendered virus inactive, independent of ingredient type.

positive: Infections nosocomiales à coronavirus humains chez le nouveau-né 1 Travail financé en partie par la Société française de pédiatrie (bourse de DEA), le ministère de la santé (PHRC 97) et le CCLIN–Ouest. A. Gagneur est boursier de la Société française de pédiatrie. Résumé Les coronavirus humains sont des virus enveloppés à ARN de la famille des Coronaviridae avec deux sérogroupes identifiés : 229-E et OC-43. Ces virus possèdent le plus grand ARN viral connu. Ce génome est un ARN simple brin positif associé à une protéine phosphorylée de la nucléocapside, la protéine N. L’enveloppe des coronavirus humains contient deux ou trois glycoprotéines membranaires : S ou spike protein, M ou protéine de membrane et HE ou hémagglutine-estérase. Le rôle pathogène de ces virus est mal connu en raison des difficultés diagnostiques. Cependant la mise au point de l’immunofluorescence avec anticorps monoclonaux et des techniques d’amplification génique permet de nouvelles recherches épidémiologiques. Les coronavirus peuvent survivre jusqu’à six jours en suspension et trois heures après séchage, ce qui suggère un rôle nosocomial potentiel. Deux études prospectives réalisées dans une unité de réanimation néonatale et pédiatrique ont révélé une relation significative entre l’existence de prélèvement nasopharyngés positifs et la survenue de symptômes respiratoires. Des prélèvements positifs chez le personnel suggèrent une contamination patient-personnel ou personnel–patient. En raison de leur survie possible sur les surfaces et de l’efficacité démontrée des agents désinfectants, des mesures universelles de prévention associant lavage des mains et désinfection des surfaces peuvent être proposées. Abstract Human coronaviruses, with two known serogroups named 229-E and OC-43, are enveloped positive-stranded RNA viruses. The large RNA is surrounded by a nucleoprotein (protein N). The envelop contains 2 or 3 glycoproteins: spike protein (or protein S), matrix protein (or protein M) and a hemagglutinin (or protein HE). Their pathogen role remains unclear because their isolation is difficult. Reliable and rapid methods as immunofluorescence with monoclonal antibodies and reverse transcription-polymerase chain reaction allow new researches on epidemiology. Human coronaviruses can survive for as long as 6 days in suspension and 3 hours after drying on surfaces, suggesting that they could be a source of hospital-acquired infections. Two prospective studies conducted in a neonatal and paediatric intensive care unit demonstrated a significant association of coronavirus-positive naso-pharyngal samples with respiratory illness in hospitalised preterm neonates. Positive samples from staff suggested either a patient-to-staff or a staff-to-patient transmission. No cross-infection were observed from community-acquired respiratory-syncitial virus or influenza-infected children to neonates. Universal precautions with hand washing and surface desinfection could be proposed to prevent coronavirus transmission.

positive: Generic aspects of the airborne spread of human pathogens indoors and emerging air decontamination technologies Indoor air can be an important vehicle for a variety of human pathogens. This review provides examples of airborne transmission of infectious agents from experimental and field studies and discusses how airborne pathogens can contaminate other parts of the environment to give rise to secondary vehicles leading air-surface-air nexus with possible transmission to susceptible hosts. The following groups of human pathogens are covered because of their known or potential airborne spread: vegetative bacteria (staphylococci and legionellae), fungi (Aspergillus, Penicillium, and Cladosporium spp and Stachybotrys chartarum), enteric viruses (noro- and rotaviruses), respiratory viruses (influenza and coronaviruses), mycobacteria (tuberculous and nontuberculous), and bacterial spore formers (Clostridium difficile and Bacillus anthracis). An overview of methods for experimentally generating and recovering airborne human pathogens is included, along with a discussion of factors that influence microbial survival in indoor air. Available guidelines from the U.S. Environmental Protection Agency and other global regulatory bodies for the study of airborne pathogens are critically reviewed with particular reference to microbial surrogates that are recommended. Recent developments in experimental facilities to contaminate indoor air with microbial aerosols are presented, along with emerging technologies to decontaminate indoor air under field-relevant conditions. Furthermore, the role that air decontamination may play in reducing the contamination of environmental surfaces and its combined impact on interrupting the risk of pathogen spread in both domestic and institutional settings is discussed.

positive: The SARS-CoV-2 outbreak: What we know Abstract There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.

positive: Survival of human coronaviruses 229E and OC43 in suspension and after drying onsurfaces: a possible source ofhospital-acquired infections Abstract Strains OC43 and 229E of human coronaviruses (HCoV) cause one-third of common colds and hospital-acquired upper respiratory tract HCoV infections have been reported in premature newborns. To evaluate possible sources of infection, virus survival was studied in aqueous suspensions and on absorptive and non-absorptive surfaces representative of a hospital environment. Virus susceptibility to chemical disinfection with standard products was also characterized. Virus survived in saline solution for as long as six days but less in culture medium, with or without added cells. After drying, HCoV-229E infectivity was still detectable after 3h on various surfaces (aluminum, sterile latex surgical gloves, sterile sponges) but HCoV-OC43 survived 1h or less. Of the various chemical disinfectants tested, Proviodine® reduced the virus infectious titre by at least 50%. This study suggests that surfaces and suspensions can be considered as possible sources of contamination that may lead to hospital-acquired infections with HCoV and should be appropriately disinfected.

positive: The effects of regional climatic condition on the spread of COVID-19 at global scale The pandemic outbreak of the novel coronavirus epidemic disease (COVID-19) is spreading like a diffusion-reaction in the world and almost 208 countries and territories are being affected around the globe. It became a sever health and socio-economic problem, while the world has no vaccine to combat this virus. This research aims to analyze the connection between the fast spread of COVID-19 and regional climate parameters over a global scale. In this research, we collected the data of COVID-19 cases from the time of 1st reported case to the 5th June 2020 in different affected countries and regional climatic parameters data from January 2020 to 5th June 2020. It was found that most of the countries located in the relatively lower temperature region show a rapid increase in the COVID-19 cases than the countries locating in the warmer climatic regions despite their better socio-economic conditions. A correlation between metrological parameters and COVID-19 cases was observed. Average daylight hours are correlated to total the COVID-19 cases with a coefficient of determination of 0.42, while average high-temperature shows a correlation of 0.59 and 0.42 with total COVID-19 cases and death cases respectively. The finding of the study will help international health organizations and local administrations to combat and well manage the spread of COVID-19.

positive: How much reduction of virus is needed for recycled water: A continuous changing need for assessment? Abstract To ensure the safety of wastewater reuse for irrigation of food crops and drinking water pathogenic viruses must be reduced to levels that pose no significant risk. To achieve this goal minimum reduction of viruses by treatment trains have been suggested. For use of edible crops a 6-log reduction and for production of potable drinking water a 12-log reduction has been suggested. These reductions were based on assuming infective virus concentrations of 105 to 106 per liter. Recent application of molecular methods suggests that some pathogenic viruses may be occurring in concentrations of 107 to 109 per liter. Factors influencing these levels include the development of molecular methods for virus detection, emergence of newly recognized viruses, decrease in per capita water use due to conservation measures, and outbreaks. Since neither cell culture nor molecular methods can assess all the potentially infectious virus in wastewater conservative estimates should be used to assess the virus load in untreated wastewater. This review indicates that an additional 2- to 3-log reduction of viruses above current recommendations may be needed to ensure the safety of recycled water. Information is needed on peak loading of viruses. In addition, more virus groups need to be quantified using better methods of virus quantification, including more accurate methods for measuring viral infectivity in order to better quantify risks from viruses in recycled water.

positive: Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV) ? The outbreak of 2019-nCoV pneumonia (COVID-19) in the city of Wuhan, China has resulted in more than 70,000 laboratory confirmed cases, and recent studies showed that 2019-nCoV (SARS-CoV-2) could be of bat origin but involve other potential intermediate hosts. In this study, we assembled the genomes of coronaviruses identified in sick pangolins. The molecular and phylogenetic analyses showed that pangolin Coronaviruses (pangolin-CoV) are genetically related to both the 2019-nCoV and bat Coronaviruses but do not support the 2019-nCoV arose directly from the pangolin-CoV. Our study also suggested that pangolin be natural host of Betacoronavirus, with a potential to infect humans. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. Conservation of wildlife and limits of the exposures of humans to wildlife will be important to minimize the spillover risks of coronaviruses from wild animals to humans.

positive: A Novel Box for Aerosol and Droplet Guarding and Evacuation in Respiratory Infection (BADGER): A Potential Mitigating Strategy for the COVID-19 Pandemic and Future Outbreaks The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected millions and killed hundreds of thousands of people worldwide as of May 2020. Healthcare providers are at increased risks of infection when caring for patients with COVID-19. The mechanism of transmission of SARS-CoV-2 is still not fully understood. However, there is growing evidence for airborne transmission of SARS-CoV-2, in addition to direct droplet spread and indirect contact. Here, we report on the design, construction, and testing of the BADGER (Box for Aerosol and Droplet Guarding and Evacuation in Respiratory Infection), an affordable, scalable device that can contain droplets and aerosol particles. The BADGER has multiple hand-ports for healthcare providers to perform essential tasks on a patient's airway and head. A semi-sealed environment is created inside the BADGER, which maintains at least twelve-air changes per hour using in-wall vacuum suction. Qualitative testing demonstrates that under conditions typical of non-invasive supplemental oxygen treatment, the BADGER can contain nebulized denatonium benzoate and smoke. Quantitative aerosol testing shows more than 90% containment of sub-micrometer aerosolized particles. Overall, the BADGER has the potential to contain large droplets and small airborne particles, and to provide an additional layer of protection for healthcare providers treating COVID-19 patients.

positive: SARS-CoV-2 RNA contamination of inanimate surfaces and virus viability in a health care emergency unit OBJECTIVES: To detect possible SARS-CoV-2 RNA contamination of inanimate surfaces in areas at high risk of aerosol formation by patients with COVID-19. METHODS: Sampling was performed in the emergency unit and the sub-intensive care ward. SARS-CoV-2 RNA was extracted from swabbed surfaces and objects and subjected to real-time reverse transcriptase–polymerase chain reaction (RT-PCR) targeting RNA-dependent RNA polymerase and E genes. Virus isolation from positive samples was attempted in vitro on Vero E6 cells. RESULTS: Twenty-six samples were collected and only two were positive for low-level SARS-CoV-2 RNA, both collected on the external surface of Continuous Positive Airway Pressure (CPAP) helmets. All transport media were inoculated onto susceptible cells, however, none induced a cytopathic effect on day 7 of culture. CONCLUSIONS: Even though daily contact with inanimate surfaces and patient fomites in contaminated areas may be a medium of infection, our data obtained in real life conditions suggest that it might be less extensive than hitherto recognized.

positive: COVID-19 pandemic: Impact of lockdown, contact and non-contact transmissions on infection dynamics COVID-19 coronavirus pandemic has virtually locked down the entire world of human population, and through its rapid and unstoppable spread COVID-19 has essentially compartmentalised the population merely into susceptible, exposed, infected and recovered classes. Adapting the classical epidemic modelling framework, two distinct routes of COVID-19 transmission are incorporated into a model: (a) direct person-to-person contact transmission, and (b) indirect airborne and fomites-driven transmission. The indirect non-contact transmission route needs to explored in models of COVID-19 spread, because evidences show that this route of transmission is entirely viable with hugely uncertain level of relative contribution. This theoretical study based on model simulations demonstrates the following: (1) Not incorporating indirect transmission route in the model leads to underestimation of the basic reproduction number, and hence will impact on the COVID-19 mitigation decisions; (2) Lockdown measures can suppress the primary infection peak, but will lead to a secondary peak whose relative strength and time of occurrence depend on the success and duration of the lockdown measures; (3) To make lockdown effective, a considerable level of reduction in both contact and non-contact transmission rates over a long period is required; (4) To bring down the infection cases below any hypothetical health-care capacity, reduction of non-contact transmission rate is key, and hence active measures should be taken to reduce non-contact transmission (e.g., extensive uses of areal and aerosol disinfectant in public spaces to improve contaminated surfaces and air); (5) Any premature withdrawal of lockdown following the sign of a brief retracement in the infection cases can backfire, and can lead to a quicker, sharper and higher secondary peak, due to reactivation of the two transmission routes. Based on these results, this study recommends that any exit policy from lockdown, should take into account the level of transmission reduction in both routes, the absolute scale of which will vary among countries depending on their health-service capacity, but should be computed using accurate time-series data on infection cases and transmission rates.

positive: Editorial: Stay safe during this coronavirus crisis

positive: COVID-19: POSTMORTEM DIAGNOSTIC AND BIOSAFETY CONSIDERATIONS As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (e.g. cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with—but not of—COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have been issued regarding scene investigative protocol, and there are a paucity of publications characterizing COVID-19 postmortem gross and histologic findings. A case of sudden unexpected death due to COVID-19 is presented as a means of illustrating common autopsy findings, as well as diagnostic and biosafety considerations. We also review and summarize the current COVID-19 literature in an effort to provide practical evidence-based biosafety guidance for ME/C offices encountering COVID-19 at autopsy.

positive: COVID-19 Surface Persistence: A Recent Data Summary and Its Importance for Medical and Dental Settings Recently, due to the coronavirus pandemic, many guidelines and anti-contagion strategies continue to report unclear information about the persistence of coronavirus disease 2019 (COVID-19) in the environment. This certainly generates insecurity and fear in people, with an important psychological component that is not to be underestimated at this stage of the pandemic. The purpose of this article is to highlight all the sources currently present in the literature concerning the persistence of the different coronaviruses in the environment as well as in medical and dental settings. As this was a current study, there are still not many sources in the literature, and scientific strategies are moving towards therapy and diagnosis, rather than knowing the characteristics of the virus. Such an article could be an aid to summarize virus features and formulate new guidelines and anti-spread strategies.

positive: Sample sizes for surveillance of S. aureus transmission to monitor effectiveness and provide feedback on intraoperative infection control including for COVID-19 Reductions in perioperative surgical site infections are obtained by a multifaceted approach including patient decolonization, hand hygiene, use of closed lumen intravenous systems and hub disinfection, and environmental cleaning. Associated surveillance of S. aureus transmission quantifies the effectiveness of the basic measures to prevent the transmission to patients and clinicians of pathogenic bacteria and viruses, including Coronavirus Disease 2019 (COVID-19). To measure transmission, the observational units are pairs of successive surgical cases in the same operating room on the same day. We evaluated appropriate sample sizes and strategies for measuring transmission. We used historical cohort data from multiple hospitals. There was absence of serial correlation among observed counts of transmitted isolates within each of several periods (all P ≥.18). Similarly, observing transmission within or between cases of a pair did not increase the probability that the next sampled pair of cases also had observed transmission (all P ≥.23). Most pairs of cases had no detected transmitted isolates. Also, although transmission (yes/no) was associated with surgical site infection (P =.004), among cases with transmission, there was no detected dose response between counts of transmitted isolates and probability of infection (P =.25). Therefore, we recommend analyzing the presence/absence of transmission. The first of a fixed series of tests is to use the binomial test to compare the proportion of pairs of cases with S. aureus transmission to an acceptable threshold. An appropriate sample size for this screening is N =25 pairs. If significant, more samples are obtained while additional measures are implemented to reduce transmission and infections. Subsequent sampling is done to evaluate effectiveness. The two independent binomial proportions are compared using Boschloo's exact test. The total sample size for the 1(st) and 2(nd) stage is N =100 pairs. Because S. aureus transmission is invisible without testing, when choosing what population(s) to screen for surveillance, another endpoint needs to be used (e.g., infections). Only 10/298 combinations of specialty and operating room were relatively common (≥1.0% of cases) and had expected incidence ≥0.20 infections per 8 hours of sampled cases. The 10 combinations encompassed ≅17% of cases, showing the value of targeting surveillance of transmission to a few combinations of specialties and rooms. In conclusion, we created a sampling protocol and appropriate sample sizes for using S. aureus transmission within and between pairs of successive cases in the same operating room, the purpose being to monitor the quality of prevention of intraoperative spread of pathogenic bacteria and viruses.

positive: A rate equation approach to model the denaturation or replication behavior of the SARS coronavirus As a newly emerging virus, little is known about the SARS coronavirus, whose outbreak has brought away several hundred people’s lives over the world in the year of 2003 and is seriously imperiling the human health. Revealing the denaturation and replication mechanisms of SARS coronavirus has great importance for successfully fighting SARS. However, experiments related to SARS coronavirus are extremely dangerous and therefore restricted only to certain specific labs with high safety standard. Clearly, predicting the behaviors of SARS coronavirus in a wide variety of environmental conditions, which are not easily accessible, are thus critically necessary. In this study, we proposed to quantify the survival time of SARS coronavirus either in vitro or in vivo, through introducing thermal rate process models established from the well-known Arrhenius law. The complex physical and chemical behaviors of the SARS coronavirus can then be attributed to its activation energy, frequency factor, damage function as well as the surrounding environmental conditions. Based on the first data on stability and resistance of SARS coronavirus measured by members of WHO laboratory network, the rate coefficients involved in the above equations were estimated for the first time. Predictions on the survival time of SARS coronavirus in different temperature scale were then performed. It was found theoretically that, such survival time falls in an extremely wide range, say from several seconds in high temperature to an almost infinitely long time in a low temperature environment, which has already or is being supported by the currently available tests data. Applications of the present theory to interpret several existing phenomena were presented and their implementations in developing new technical ways for SARS prevention and clinical therapy were discussed. Uncertainties involved in the theoretical models were also analyzed and predicted. Parametric studies were performed to test the effects of the rate coefficients to the survival time of SARS coronavirus. Some important factors, which can significantly vary the denaturation or replication process of SARS coronavirus were pointed out. Through regulating the parameters involved in the equation, certain potential therapies either through drug delivery or engineering approach to treat the SARS disease can possibly be established. Extension of the present model for further studies was also suggested. This study opens a new theoretical way for probing into the complex behaviors of SARS coronavirus. Modellierung der Denaturierung oder Repliziryng von SARS-Korona-Viren Zusammenfassung Der Kenntnisstand über die Eigenschaften des in 2003 neu aufgetretenen SARS Korona Virus, der einige Hundert Menschenleben gekostet hat, ist relativ gering. Die Ermittlung des Denaturierungs- und Replizierungsmechanismuses des SARS Virus ist für seine Bekämpfung von hoher Bedeutung. Experimentelle Untersuchungen an diesem extrem gefährlichen Virus dürfen nur durch Laboratorien mit einem hohen Sicherheitsstandard erfolgen. Die Vorhersage des Verhaltens des SARS Virus in unterschiedlichen Umgebungsbedingungen ist dabei erforderlich. In der vorliegenden Studie wird die überlebensdauer des Virus unter Labor- und realen Bedingungen durch Anwendung der bekannten Arrhenius-Beziehung für temperaturabhängige Vorgänge ermittelt. Das physikalische und chemische Verhalten des SARS Virus wird anhand der zugrundeliegenden Modell- Parameter beschrieben. Basierend auf den ersten Messungen von Mitgliedern des WHO-laboratory-network über die Stabilität und Widerstandsfähigkeit des Virus wurden erstmalig die Geschwindigkeitskoeffizienten des Berechnungsmodells bestimmt. Vorhersagen der Überlebensdauer des SARS-Virus unter unterschiedlichen Temperaturbedingungen wurden ausgeführt. Das sich hieraus ergebende, sehr unterschiedliche Ausmaß der Überlebensfähigkeit in Abhängigkeit der Umgebungstemperatur ist durch den Vergleich mit verfügbaren experimentellen Ergebnissen bestätigt worden. Die Anwendung der vorgestellten Modellierung zur Interpretation realer Phänomene und zur Entwicklung technischer Maßnahmen zur Vorbeugung und klinischen Therapierung von SARS wird diskutiert. Der Einfluß von Unsicherheiten des Modells wird analysiert und abgeschätzt. Parametrische Studien sind durchgeführt worden, um den Einfluß der Geschwindigkeitskoeffizienten auf die Überlebensdauer des SARS Virus darzustellen. Einige wichtige Einflußgrößen auf die Denaturierung und Replikationsfähigkeit des SARS Virus werden aufgezeigt. Durch eine Variation der Modellparameter kann die potentielle Wirksamkeit medikamentöser oder physikalischer Therapien abgeschätzt werden. Erweiterungsmöglichkeiten des vorgestellten Modells werden vorgeschlagen. Die vorliegende Studie ermöglicht neue, theoretische Vorgehensweisen zur Untersuchung des komplexen Verhaltensmusters des SARS Virus.

positive: Enteric involvement of coronaviruses: is faecal–oral transmission of SARS-CoV-2 possible?

positive: Role of the Eye in Transmitting Human Coronavirus: What We Know and What We Do Not Know The outbreak of the current 2019 novel coronavirus (2019-nCoV, now named SARS-CoV-2) infection has become a worldwide health threat. Currently, more information is needed so as to further understand the transmission and clinical characteristics of 2019-nCoV infection and the infection control procedures required. Recently, the role of the eye in transmitting 2019-nCoV has been intensively discussed. Previous investigations of other highly infectious human CoVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide useful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, and mechanisms of human CoV infection, and recommendations for infection control procedures. The role of the eye in the transmission of 2019-nCoV is discussed in detail. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct and share the same entry receptors for some respiratory viruses, the eye is rarely involved in human CoV infection, conjunctivitis is quite rare in patients with 2019-nCoV infection, and the CoV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with 2019-nCoV and SARS-CoV infection is also extremely low. This suggests that the eye is neither a preferred organ of human CoV infection nor a preferred gateway of entry for human CoVs for infecting the respiratory tract. However, pathogens that the ocular surface is exposed to might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through the lacrimal duct system and then cause respiratory tract infection. Considering that close doctor-patient contact is quite common in ophthalmic practice and is apt to transmit human CoVs by droplets and fomites, strict hand hygiene and proper personal protection are highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

positive: Contamination, Disinfection, and Cross-Colonization: Are Hospital Surfaces Reservoirs for Nosocomial Infection? Despite documentation that the inanimate hospital environment (e.g., surfaces and medical equipment) becomes contaminated with nosocomial pathogens, the data that suggest that contaminated fomites lead to nosocomial infections do so indirectly. Pathogens for which there is more-compelling evidence of survival in environmental reservoirs include Clostridium difficile, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, and pathogens for which there is evidence of probable survival in environmental reservoirs include norovirus, influenza virus, severe acute respiratory syndrome—associated coronavirus, and Candida species. Strategies to reduce the rates of nosocomial infection with these pathogens should conform to established guidelines, with an emphasis on thorough environmental cleaning and use of Environmental Protection Agency—approved detergent-disinfectants.

positive: Likelihood of survival of coronavirus in a respiratory droplet deposited on a solid surface We predict and analyze the drying time of respiratory droplets from a COVID-19 infected subject, which is a crucial time to infect another subject. Drying of the droplet is predicted by using a diffusion-limited evaporation model for a sessile droplet placed on a partially wetted surface with a pinned contact line. The variation in droplet volume, contact angle, ambient temperature, and humidity are considered. We analyze the chances of the survival of the virus present in the droplet based on the lifetime of the droplets under several conditions and find that the chances of the survival of the virus are strongly affected by each of these parameters. The magnitude of shear stress inside the droplet computed using the model is not large enough to obliterate the virus. We also explore the relationship between the drying time of a droplet and the growth rate of the spread of COVID-19 in five different cities and find that they are weakly correlated.

positive: Transmission of Influenza A in a Student Office Based on Realistic Person-to-Person Contact and Surface Touch Behaviour Influenza A viruses result in the deaths of hundreds of thousands of individuals worldwide each year. In this study, influenza A transmission in a graduate student office is simulated via long-range airborne, fomite, and close contact routes based on real data from more than 3500 person-to-person contacts and 127,000 surface touches obtained by video-camera. The long-range airborne, fomite and close contact routes contribute to 54.3%, 4.2% and 44.5% of influenza A infections, respectively. For the fomite route, 59.8%, 38.1% and 2.1% of viruses are transmitted to the hands of students from private surfaces around the infected students, the students themselves and other susceptible students, respectively. The intranasal dose via fomites of the students’ bodies, belongings, computers, desks, chairs and public facilities are 8.0%, 6.8%, 13.2%, 57.8%, 9.3% and 4.9%, respectively. The intranasal dose does not monotonously increase or decrease with the virus transfer rate between hands and surfaces. Mask wearing is much more useful than hand washing for control of influenza A in the tested office setting. Regular cleaning of high-touch surfaces, which can reduce the infection risk by 2.14%, is recommended and is much more efficient than hand-washing.

positive: Properties of Coronavirus and SARS-CoV-2. were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (α,β,γ,δ), human coronaviruses (HCoVs) are classified under α-CoV (HCoV-229E and NL63) and β-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a β-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.

positive: Shell disorder analysis predicts greater resilience of the SARS-CoV-2 (COVID-19) outside the body and in body fluids Abstract The coronavirus (CoV) family consists of viruses that infects a variety of animals including humans with various levels of respiratory and fecal-oral transmission levels depending on the behavior of the viruses' natural hosts and optimal viral fitness. A model to classify and predict the levels of respective respiratory and fecal-oral transmission potentials of the various viruses was built before the outbreak of MERS-CoV using AI and empirically-based molecular tools to predict the disorder level of proteins. Using the percentages of intrinsic disorder (PID) of the nucleocapsid (N) and membrane (M) proteins of CoV, the model easily clustered the viruses into three groups with the SARS-CoV (M PID = 8%, N PID = 50%) falling into Category B, in which viruses have intermediate levels of both respiratory and fecal-oral transmission potentials. Later, MERS-CoV (M PID = 9%, N PID = 44%) was found to be in Category C, which consists of viruses with lower respiratory transmission potential but with higher fecal-oral transmission capabilities. Based on the peculiarities of disorder distribution, the SARS-CoV-2 (M PID = 6%, N PID = 48%) has to be placed in Category B. Our data show however, that the SARS-CoV-2 is very strange with one of the hardest protective outer shell, (M PID = 6%) among coronaviruses. This means that it might be expected to be highly resilient in saliva or other body fluids and outside the body. An infected body is likelier to shed greater numbers of viral particles since the latter is more resistant to antimicrobial enzymes in body fluids. These particles are also likelier to remain active longer. These factors could account for the greater contagiousness of the SARS-CoV-2 and have implications for efforts to prevent its spread.

positive: Saliva is a non-negligible factor in the spread of COVID-19 SARS-CoV-2, a novel emerging coronavirus, has caused severe disease (COVID-19), and rapidly spread worldwide since the beginning of 2020. SARS-CoV-2 mainly spreads by coughing, sneezing, droplet inhalation, and contact. SARS-CoV-2 has been detected in saliva samples, making saliva a potential transmission route for COVID-19. The participants in dental practice confront a particular risk of SARS-CoV-2 infection due to close contact with the patients and potential exposure to saliva-contaminated droplets and aerosols generated during dental procedures. In addition, saliva-contaminated surfaces could lead to potential cross-infection. Hence, the control of saliva-related transmission in the dental clinic is critical, particularly in the epidemic period of COVID-19. Based on our experience of the COVID-19 epidemic, some protective measures that can help reduce the risk of saliva-related transmission are suggested, in order to avoid the potential spread of SARS-CoV-2 among patients, visitors, and dental practitioners.

positive: Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002–2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.

positive: Survival of Respiratory Viruses on Fresh Produce In addition to enteric viruses of fecal origin, emerging zoonotic viruses such as respiratory coronaviruses and influenza viruses may potentially be transmitted via contaminated foods. The goal of this study was to determine the recovery efficiencies and the survival of two respiratory viruses, namely, adenovirus 2 (Ad2) and coronavirus 229E (CoV229E), on fresh produce in comparison to the enteric poliovirus 1 (PV1). Adenovirus was recovered with efficiencies of 56.5, 31.8, and 34.8 % from lettuce, strawberries, and raspberries, respectively. Coronavirus was recovered from lettuce with an efficiency of 19.6 % yet could not be recovered from strawberries. Poliovirus was recovered with efficiencies of 76.7 % from lettuce, but only 0.06 % from strawberries. For comparison purposes, the survival of Ad2, CoV229E, and PV1 was determined for periods up to 10 days on produce. The enteric PV1 survived better than both respiratory viruses on lettuce and strawberries, with only ≤1.03 log(10) reductions after 10 days of storage at 4 °C compared to CoV229E not being recovered after 4 days on lettuce and reductions of 1.97 log(10) and 2.38 log(10) of Ad2 on lettuce and strawberries, respectively, after 10 days. Nevertheless, these respiratory viruses were able to survive for at least several days on produce. There is therefore the potential for transfer to the hands and subsequently to the mucosa via rubbing the eyes or nose. In addition, some respiratory coronaviruses (e.g., severe acute respiratory syndrome coronavirus) and adenoviruses are also capable of replication in the gut and there is thus some potential for acquisition through the consumption of contaminated produce.

positive: How long does Coronavirus survive on different surfaces? Dental practices now need to be more vigilant than ever and pay extra attention to hygiene in the surgery Hospitals are currently operating an hourly total clean policy and it would be prudent for dental practices to look to operate something similar to reduce the possibility of viral transmission The Government is encouraging people to stay at home and maintain social distancing during the pandemic However, key workers must go to work, use public transport and mix with high risk people People also need to go to supermarkets to get their groceries The surfaces in these public places are likely to be contaminated;these germs can then be brought into homes or dental practices

positive: COVID-19: Current Knowledge and Best Practices for Orthopaedic Surgeons BACKGROUND: A mysterious cluster outbreak of pneumonia in Wuhan, China in December 2019 was traced to Severe Acute Respiratory Syndrome Coronavirus 2 and declared a Pandemic by WHO on 11th March 2020. The pandemic has spread rapidly causing widespread devastation globally. PURPOSE: This review provides a brief understanding of pathophysiology, clinical features, diagnosis and management of COVID-19 and highlights the current knowledge as well as best practices for orthopaedic surgeons. These are likely to change as knowledge and evidence is gained. RESULTS: Orthopaedic surgeons, like other front-line workers, carry the risk of getting infected during their practice, which as such is already substantially affected. Implementation of infection prevention and control as well as other safety measures for health care workers assumes great importance. All patients/visitors and staff visiting the hospital should be screened. Conservative treatment should be the first line of treatment except for those requiring urgent/emergent care. During lockdown all elective surgeries are to be withheld. All attempts should be made to reduce hospital visits and telemedicine is to be encouraged. Inpatient management of COVID-19 patients requires approval from concerned authorities. All patients being admitted to the hospital in and around containment zones should be tested for COVID-19. There are special considerations for anaesthesia with preference for regional anaesthesia. A separate Operation room with specific workflow should be dedicated for COVID-19 positive cases. CONCLUSIONS: Despite the magnitude of challenge, the pandemic offers significant lessons for the orthopaedic surgeon who should seek the opportunity within the adversity and use this time wisely to achieve his/her Ikigai. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s43465-020-00135-1) contains supplementary material, which is available to authorized users.

positive: Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management We describe an evidence-based approach for optimization of infection control and operating room management during the Coronavirus Disease 2019 (COVID-19) pandemic. Confirmed modes of viral transmission are primarily, but not exclusively, contact with contaminated environmental surfaces and aerosolization. Evidence-based improvement strategies for attenuation of residual environmental contamination involve a combination of deep cleaning with surface disinfectants and ultraviolet light (UV-C). (1) Place alcohol-based hand rubs on the intravenous (IV) pole to the left of the provider. Double glove during induction. (2) Place a wire basket lined with a zip closure plastic bag on the IV pole to the right of the provider. Place all contaminated instruments in the bag (eg, laryngoscope blades and handles) and close. Designate and maintain clean and dirty areas. After induction of anesthesia, wipe down all equipment and surfaces with disinfection wipes that contain a quaternary ammonium compound and alcohol. Use a top-down cleaning sequence adequate to reduce bioburden. Treat operating rooms using UV-C. (3) Decolonize patients using preprocedural chlorhexidine wipes, 2 doses of nasal povidone-iodine within 1 hour of incision, and chlorhexidine mouth rinse. (4) Create a closed lumen IV system and use hub disinfection. (5) Provide data feedback by surveillance of Enterococcus, Staphylococcusaureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp. (ESKAPE)transmission. (6) To reduce the use of surgical masks and to reduce potential COVID-19 exposure, use relatively long (eg, 12hours) staff shifts. If there are 8 essential cases to be done (each lasting 1–2 hours), the ideal solution is to have 2 teams complete the 8 cases, not 8 first case starts. (7) Do 1 case in each operating room daily, with terminal cleaning after each case including UV-C or equivalent. (8) Do not have patients go into a large, pooled phase I postanesthesia care unit because of the risk of contaminating facility at large along with many staff. Instead, have most patients recover in the room where they had surgery as is done routinely in Japan. These 8 programmatic recommendations stand on a substantial body of empirical evidence characterizing the epidemiology of perioperative transmission and infection development made possible by support from the Anesthesia Patient Safety Foundation (APSF).

positive: Nurture to nature via COVID-19, a self-regenerating environmental strategy of environment in global context Abstract Coronavirus Disease (COVID-19) has become the largest pandemic that has affected 210 countries. Rolling data indicate that 257,3605 people are infected by the disease, from which 701,838 have recovered and 178,562 have died. No specific medicine or vaccine is available yet to control the disease, hence, social distancing via lockdown is widely adopted as the only preventive measure. Social distancing is observed at different level of strictness in different counties but it almost made the world to stands still. Although scientific articles on this largest social move are scanty, it resulted in benefiting the deteriorated environment to revive back. Many environmental indices such as lowering NO2 and CO2 emissions and reduction in particulate matters in air as a result of less human activities have led to clean air and pollution free water in many countries. Undoubtedly, the world was experiencing pollution in several countries due to mainly human activities including urbanization, industrialization, fossil fuel exhaustion etc. Under such situation a special (natural) a protective measure was awaited to fix environmental issues. Probably, the lockdown is one of the natural effects expected by nature via introduction of COVID-19. It is because, introduction of COVID-19 to nature was an outcome of mutation from two of its pre-existing forms, although, debate on it is still continuing. Viability of CoV-19 virus found to have a lot of correlation with aquatic and terrestrial environmental parameters such as pH, surface type, temperature etc. Air pollution is found to increase the risk of COVID-19 infection, therefore, use of mask and alcohols based standard sterilisers is strongly recommended. However, the self-revival rate of nature shall continue during post-lockdown period and a master plan must be adapted by national and international (mostly political) bodies to revive the Mother Nature completely.

positive: Environmental chemistry is most relevant to study coronavirus pandemics

positive: Sustainability of SARS-CoV-2 in aerosols: Should we worry about airborne transmission?

positive: Relevance of SARS-CoV-2 in food safety and food hygiene: potential preventive measures, suggestions and nanotechnological approaches Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is easily transmitted from person to person, which has fueled the ongoing pandemic. Governments in different countries have taken drastic actions such as complete lockdown. However, little attention has been paid to food safety and its potential linkage with the coronavirus disease (COVID-19) pandemic. SARS-CoV-2 spread from staff to food products or food surfaces is conceivable. At least, instead of consuming unpackaged or uncovered foods, consumption of boiled or canned foods processed at high temperatures should be preferred. Before consumption, consumers should clean the surface of canned foods. In addition to recommending or enforcing simple precautions, such as using masks, governments must conduct mandatory SARS-CoV-2 tests regularly and intermittently for personnel who handle food materials or supporting materials (e.g., plastic pouches). Local markets, such as those in Wuhan, which sell live animals and exotic foods for consumption, are a concern. Trade of exotic or wild animals, unhygienic marketplace conditions, and not cooking at high temperatures ought to be prohibited. The consumption of vitamins, minerals, and other food-derived compounds such as omega fatty acids is a prudent way to improve the performance of the immune system. In addition, nano-encapsulated materials with controlled release properties may be useful in protecting food products and packaging from SARS-CoV-2 contamination.

positive: Possible environmental effects on the spread of COVID-19 in China Abstract At the end of 2019, a novel coronavirus, designated as SARS-CoV-2, emerged in Wuhan, China and was identified as the causal pathogen of COVID-19. The epidemic scale of COVID-19 has increased dramatically, with confirmed cases increasing across China and globally. Understanding the potential affecting factors involved in COVID-19 transmission will be of great significance in containing the spread of the epidemic. Environmental and meteorological factors might impact the occurrence of COVID-19, as these have been linked to various diseases, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), whose causative pathogens belong to the same virus family as SARS-CoV-2. We collected daily data of COVID-19 confirmed cases, air quality and meteorological variables of 33 locations in China for the outbreak period of 29 January 2020 to 15 February 2020. The association between air quality index (AQI) and confirmed cases was estimated through a Poisson regression model, and the effects of temperature and humidity on the AQI-confirmed cases association were analyzed. The results show that the effect of AQI on confirmed cases associated with an increase in each unit of AQI was statistically significant in several cities. The lag effect of AQI on the confirmed cases was statistically significant on lag day 1 (relative risk (RR) = 1.0009, 95% confidence interval (CI): 1.0004, 1.0013), day 2 (RR = 1.0007, 95% CI: 1.0003, 1.0012) and day 3 (RR = 1.0008, 95% CI: 1.0003, 1.0012). The AQI effect on the confirmed cases might be stronger in the temperature range of 10 °C ≤ T < 20 °C than in other temperature ranges, while the RR of COVID-19 transmission associated with AQI was higher in the relative humidity (RH) range of 10% ≤ RH < 20%. Results may suggest an enhanced impact of AQI on the COVID-19 spread under low RH.

positive: The antiviral action of common household disinfectants and antiseptics against murine hepatitis virus, a potential surrogate for SARS coronavirus BACKGROUND: The 2003 outbreak of severe acute respiratory syndrome (SARS) infected over 8000 people and killed 774. Transmission of SARS occurred through direct and indirect contact and large droplet nuclei. The World Health Organization recommended the use of household disinfectants, which have not been previously tested against SARS coronavirus (SARS-CoV), to disinfect potentially contaminated environmental surfaces. There is a need for a surrogate test system given the limited availability of the SARS-CoV for testing and biosafety requirements necessary to safely handle it. In this study, the antiviral activity of standard household products was assayed against murine hepatitis virus (MHV), as a potential surrogate for SARS-CoV. METHODS: A surface test method, which involves drying an amount of virus on a surface and then applying the product for a specific contact time, was used to determine the virucidal activity. The virus titers and log reductions were determined by the Reed and Muench tissue culture infective dose (TCID)(50) end point method. RESULTS: When tested as directed, common household disinfectants or antiseptics, containing either 0.050% of triclosan, 0.12% of PCMX, 0.21% of sodium hypochlorite, 0.23% of pine oil, or 0.10% of a quaternary compound with 79% of ethanol, demonstrated a 3-log reduction or better against MHV without any virus recovered in a 30-second contact time. CONCLUSION: Common household disinfectants and antiseptics were effective at inactivating MHV, a possible surrogate for SARS-CoV, from surfaces when used as directed. In an outbreak caused by novel agents, it is important to know the effectiveness of disinfectants and antiseptics to prevent or reduce the possibility of human-to-human transmission via surfaces.

positive: Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents Summary The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.

positive: Isothermal evaporation rate of deposited liquid aerosols and the SARS-CoV-2 coronavirus survival It is shown that the evaporation rate of a liquid sample containing the culture of coronavirus affects its survival on a substrate. Possible mechanisms of such influence can be due to the appearance of large, about 140 bar, non comprehensive capillary pressures and the associated dynamic forces during the movement of the evaporation front in a sample with the virus. A simulation of isothermal evaporation of a thin liquid sample based on the Stefan problem was performed. The comparison of simulation data and recent experiments on the coronavirus survival on various surfaces showed that the rate of isothermal evaporation of aqueous samples, which is higher for heat-conducting materials, correlates well with the lifetime of the coronavirus on these surfaces.

positive: [Transmission routes of 2019-novel coronavirus (2019-nCoV)]. Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.

positive: 2019 Novel Coronavirus (COVID-19) Pandemic: Built Environment Considerations To Reduce Transmission With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county, and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE)-mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. In this paper, we synthesize this microbiology of the BE research and the known information about SARS-CoV-2 to provide actionable and achievable guidance to BE decision makers, building operators, and all indoor occupants attempting to minimize infectious disease transmission through environmentally mediated pathways. We believe this information is useful to corporate and public administrators and individuals responsible for building operations and environmental services in their decision-making process about the degree and duration of social-distancing measures during viral epidemics and pandemics. Author Video: An author video summary of this article is available.

positive: A chronicle of SARS-CoV-2: Part-I - Epidemiology, diagnosis, prognosis, transmission and treatment Abstract In order to benefit the public, community workers and scientific community, we hereby present a chronicle of SARS-CoV-2 that leads to the unseen precedent of social distancing and lockdown owing to coronavirus disease (COVID-19). Information on this life-threatening pandemic of COVID-19 is sparse and discrete; and the urgency is such that the dissemination of information is increasing with numerous daily publications on the topic. Therefore, we developed a comprehensive review on various aspects of SARS-CoV-2 and COVID-19. We scientifically compiled published research, news, and reports from various sources to comprehend and summarize the information and findings on Coronaviruses. The review explicitly covers the aspects like genome and pedigree of SARS-CoV-2; epidemiology, prognosis, pathogenesis, symptoms and diagnosis of COVID-19 in order to catalog the right information on transmission route, and influence of environmental factors on virus transmissions, for the robust understanding of right strategical steps for proper COVID-19 management. We have explicitly highlighted several useful information and facts like: i) No established relationship between progression of SARS-CoV-2 with temperature, humidity and/or both, ii) The underlying mechanism of SARS-CoV-2 is not fully understood, iii) Respiratory droplet size determines drop and airborne-based transmission, iv) Prognosis of COVID-19 can be done by its effects on various body organs, v) Infection can be stopped by restricting the binding of S protein and AE2, vi) Hydroxychloroquine is believed to be better than chloroquine for COVID-19, vii) Ivermectin with Vero-hSLAM cells is able to reduce infection by ~5000 time within 2 days, and viii) Nafamostat mesylate can inhibit SARS-CoV-2 S protein-initiated membrane fusion. We have also suggested future research perspectives, challenges and scope.

positive: Features of enteric disease from human coronaviruses: Implications for COVID‐19 Coronaviruses have long been studied in both human and veterinary fields. Whereas the initial detection of endemic human respiratory coronaviruses was problematic, detection of these and newly discovered human coronaviruses has been greatly facilitated with major advances in the laboratory. Nevertheless, technological factors can affect the accuracy and timeliness of virus detection. Many human coronaviruses can be variably found in stool samples. All human coronaviruses have been variably associated with symptoms of gastroenteritis. Coronaviruses can occasionally be cultured from enteric specimens, but most detection is accomplished with genetic amplification technologies. Excretion of viral RNA in stool can extend for a prolonged period. Culture‐positive stool samples have been found to exceed a fourteen day period after onset of infection for some coronaviruses. Virus can also sometimes be cultured from patients' respiratory samples during the late incubation period. Relatively asymptomatic patients may excrete virus. Both viable and nonviable virus can be found in the immediate environment of the patient, the health care worker, and less often the public. These lessons from the past study of animal and human coronaviruses can be extended to presumptions for severe acute respiratory syndrome coronavirus 2. Already, the early reports from the coronavirus disease‐2019 pandemic are confirming some concerns. These data have the cumulative potential to cause us to rethink some current and common public health and infection control strategies.

positive: Put a lid on it: Are faecal bio-aerosols a route of transmission for SARS-CoV-2?

positive: Modeling the role of respiratory droplets in Covid-19 type pandemics In this paper, we develop a first principles model that connects respiratory droplet physics with the evolution of a pandemic such as the ongoing Covid-19. The model has two parts. First, we model the growth rate of the infected population based on a reaction mechanism. The advantage of modeling the pandemic using the reaction mechanism is that the rate constants have sound physical interpretation. The infection rate constant is derived using collision rate theory and shown to be a function of the respiratory droplet lifetime. In the second part, we have emulated the respiratory droplets responsible for disease transmission as salt solution droplets and computed their evaporation time, accounting for droplet cooling, heat and mass transfer, and finally, crystallization of the dissolved salt. The model output favourably compares with the experimentally obtained evaporation characteristics of levitated droplets of pure water and salt solution, respectively, ensuring fidelity of the model. The droplet evaporation/desiccation time is, indeed, dependent on ambient temperature and is also a strong function of relative humidity. The multi-scale model thus developed and the firm theoretical underpinning that connects the two scales—macro-scale pandemic dynamics and micro-scale droplet physics—thus could emerge as a powerful tool in elucidating the role of environmental factors on infection spread through respiratory droplets.

positive: Survival of Microorganisms on Inanimate Surfaces In healthcare settings microbial contaminated surfaces play an important role in indirect transmission of infection. Especially surfaces close to the patients’ environment may be touched at high frequencies, allowing transmission from animated sources to others via contaminated inanimate surfaces. Therefore, the knowledge on the survival of bacteria, fungi, viruses and protozoa on surfaces, and hence, in a broader sense, in the human environment, is important for implementing tactics for prevention of Healthcare-acquired Infections (HAI). This chapter will elaborate the role of surfaces in the transmission of pathogens. Particular emphasis is laid on the current knowledge of the survival time and conditions favouring survival of the pathogens. Finally, mechanisms of transmission from inanimate surfaces to patients are highlighted. Within the multi-barrier strategy of the prevention of HAI, environmental disinfection policies should be based on risk assessments for surfaces with different risks for cross contamination such as high- and low-touched surfaces with appropriate standards for adequate disinfection measures under consideration of the persistence and infectious dose of the pathogens. As a result, surface disinfection is indicated in the following situations: Frequently touched surfaces adjacent to patients. Surfaces with assumed or visible contamination. Terminal disinfection in rooms or areas where infected or colonized patients with easily transferable nosocomial pathogens are cared for, and in outbreak situations. Furthermore, the knowledge of the persistence of pathogens will also support ensuring the biosafety in microbiological and biomedical laboratories, food-handling settings, and for hygienic behaviour in the everyday life to prevent transmission of infectious diseases.

positive: Environmental and Decontamination Issues for Human Coronaviruses and Their Potential Surrogates Pandemic COVID‐19 gives ample reason to generally review coronavirus (CoV) containment. For establishing some preliminary views on decontamination and disinfection, surrogate CoVs have commonly been assessed. This review serves to examine the existing science in regards to CoV containment generically and then to translate these findings into timely applications for COVID‐19. There is widespread dissemination of CoVs in the immediate patient environment, and CoVs can potentially be spread via respiratory secretions, urine, and stool. Interpretations of the spread however must consider whether studies examine for viral RNA, virus viability by culture, or both. Pre‐symptomatic, asymptomatic, and post‐fourteen day virus excretion from patients may complicate the epidemiology. Whereas droplet spread is accepted, there continues to be controversy over the extent of possible airborne spread and especially now for SARS‐CoV‐2. CoVs are stable in body secretions and sewage at reduced temperatures. In addition to temperature, dryness or relative humidity, initial viral burden, concomitant presence of bioburden, and the type of surface can all affect stability. Generalizing, CoVs can be susceptible to radiation, temperature extremes, pH extremes, peroxides, halogens, aldehydes, many solvents, and several alcohols. Whereas detergent surfactants can have some direct activity, these agents are better used as complements to a complex disinfectant solution. Disinfectants with multiple agents and adverse pH are more likely to be best active at higher water temperatures. Real‐life assessments should be encouraged with working dilutions. The use of decontamination and disinfection should be balanced with considerations of patient and caregiver safety. Processes should also be balanced with considerations for other potential pathogens that must be targeted. Given some CoV differences and given that surrogate testing provides experimental correlates at best, direct assessments with SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 are required. This article is protected by copyright. All rights reserved.

positive: Stability and inactivation of SARS coronavirus The SARS-coronavirus (SARS-CoV) is a newly emerged, highly pathogenic agent that caused over 8,000 human infections with nearly 800 deaths between November 2002 and September 2003. While direct person-to-person transmission via respiratory droplets accounted for most cases, other modes have not been ruled out. Faecal shedding is common and prolonged and has caused an outbreak in Hong Kong. We studied the stability of SARS-CoV under different conditions, both in suspension and dried on surfaces, in comparison with other human-pathogenic viruses, including human coronavirus HCoV-229E. In suspension, HCoV-229E gradually lost its infectivity completely while SARS-CoV retained its infectivity for up to 9 days; in the dried state, survival times were 24 h versus 6 days. Thermal inactivation at 56°C was highly effective in the absence of protein, reducing the virus titre to below detectability; however, the addition of 20% protein exerted a protective effect resulting in residual infectivity. If protein-containing solutions are to be inactivated, heat treatment at 60°C for at least 30 min must be used. Different fixation procedures, e.g. for the preparation of immunofluorescence slides, as well as chemical means of virus inactivation commonly used in hospital and laboratory settings were generally found to be effective. Our investigations confirm that it is possible to care for SARS patients and to conduct laboratory scientific studies on SARS-CoV safely. Nevertheless, the agent’s tenacity is considerably higher than that of HCoV-229E, and should SARS re-emerge, increased efforts need to be devoted to questions of environmental hygiene.

positive: Chapter 3 Biological HRPs in wastewater Abstract Biological high-risk pollutants (HRPs) have become a serious threat to human health worldwide, and wastewater is one of the major sources of them in a natural environment. Despite the long history of wastewater research, comprehensive understanding of the role and behavior of HRPs during wastewater treatment is still limited owing to the complexity of the community. In recent decades, the rapid development of molecular tools, especially the wide application of next generation sequencing technologies, helps to unravel the community composition, structure, and dynamic variation in wastewater. Overall, this chapter mainly focuses on biological HRPs, including bacteria, viruses, protozoa, helminth, biotoxins, antibiotic resistance genes and antibiotic resistant bacteria in wastewater. The characteristics, classification, fates, functions, and health implications of these HRPs are introduced in detail. Moreover, the biogeography of HRPs is a research hotspot in recent years, and available information is also summarized in this chapter. Finally, we also propose the future research needs of HRPs in wastewater after the comprehensive summary of the existing research reports. This chapter is wished to be helpful for beginners to quickly understand the biological HRPs in wastewater.

positive: How long do nosocomial pathogens persist on inanimate surfaces? A systematic review BACKGROUND: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. METHODS: The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. RESULTS: Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. CONCLUSION: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed.

positive: Countermeasures against novel coronavirus in dental clinics The cause of acute respiratory disease first reported in December 2019 in Wuhan City, Hubei Province, China, was a coronavirus called "SARS-CoV-2", which quickly spread throughout the world In Japan, 8,116 people, including cruise ship passengers and crew, have been infected (as of 10:30 a m , April 13), and the number of infected people is rapidly increasing (Table 1) Notably, the basal reproduction number (infectivity) of this infection is estimated R0 2 0-2 5 [Report of the WHO-China Joint Mission on CoronavirusDisease 2019 (February 16-24, 2020)], which is slightly higher than the usual influenza (measles: 12-18, rubella: 5-7, influenza/Spanish flu: 2-3) In addition to droplet and contact infections, aerosol infections have been pointed out as possible routes of infection Coronaviruses can survive on metal, glass, and plastic surfaces for up to 9 days at room temperature, and have been found to infect health care workers who are supposed to be on the defensive In particular, the risk of coronavirus exposure among dentists is the most serious in all industries What should the dental office do about this infection? In this issue, we introduce a special part of this series, "Emergency Contribution: Countermeasures for novel Coronavirus Infection in Dental Clinics

positive: SARS‐CoV‐2 Virulence: Interplay of Floating Virus‐Laden Particles, Climate, and Humans With the emergence of COVID‐19, it is important to address the possible scenarios of SARS‐CoV‐2 virulence. Although several researchers have addressed the possible mechanisms of enveloped virus transfection, for example, influenza, here, the relationship between exhaled virus laden‐particles, the climate, and transfection probability is discussed by interpreting the findings of prior studies. Importantly, the higher probability of viral transfection in cold and dry public spaces such as near cold shelves of groceries is illustrated. Thus, additional protective measures in such spaces are recommended.

positive: Protecting against COVID-19 aerosol infection during intubation

positive: Viral survival How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this?

positive: Water matrices as potential source of SARS-CoV-2 transmission – An overview from environmental perspective Abstract Evidently, the emergence of novel coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has rapidly blowout across the world. Since, the presence of coronaviruses, including SARS-CoV-2 in the fecal specimens and anal swabs of some infected patients, has raised emerging concern with the likelihood of fecal-based spread must be inspected and clarified. Therefore, herein, an effort has been made to spotlight the current scenarios and possible solutions to better understand the risks associated with the wastewater matrices as a potential source of SARS-CoV-2 transmission in the environment. The information reviewed here constitutes a paramount intellectual basis to sustenance ongoing research to tackle the SARS-CoV-2 issue. Thus, this overview indicates the most accessible frontiers related to the detection, quantification, and possible transmission of SARS-CoV-2 in the environment through water routes. The regulatory authorities and policymakers must assure the society via dissemination of evidence-based guidelines that the water matrices, including groundwater and drinking water resources are safe. Finally, we have identified and enlisted a number of pressing questions concerning the ongoing SARS-CoV-2 transmission or COVID-19 emergence issue that must be carefully answered to put further and deeper insight into SARS-CoV-2/COVID-19 in future studies.

positive: The SARS-CoV-2 outbreak from a one health perspective Abstract The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. The virus shares a high level of identity with some bat coronaviruses and is recognised as a potentially zoonotic virus. We are utilizing the One Health concept to understand the emergence of the virus, as well as to point to some possible control strategies that might reduce the spread of the virus across the globe; thus, containment of such virus would be possible.

positive: Pandemic Human Coronavirus – Characterization and Comparison of Selected Properties of Hcov-sars and Hcov-mers It: Two Coronaviruses, HCoV-229E and HCoV-OC43, causing generally mild respiratory tract infections in humans, were described in the XX c Pandemic Coronaviruses were first discovered as late as in the XXI c : SARS-HCoV in 2002 – causing severe respiratory tract infections (SARS) in China;MERS-HCoV in 2012 – circulating mostly on the Arabian Peninsula The SARS epidemic ended in 2004 resulting in morbidity of >8000 and >770 deaths, while the MERS epidemic is still ongoing (>2000 ill, >700 deaths) although its intensity decreased Both viruses are zoonotic and require at least two “host jumps” for the transmission of the infection to humans: for HCoV-SARS – from bat to palm civet and then to human;for HCoV-MERS – from bats to camels and subsequently to humans Primary mode of transmission is droplet in close contact (<1 m), but both viruses remain active in aerosol (up to 24 h), so infection can be also spread by air (ventilation) The ability for human-to-human transmission is higher for HCoV-SARS than for HCoV-MERS (8 generations vs 4, respectively) Moreover, there are differences in genome structure and pathogenic mechanisms: different receptor, cell entry mechanism, different way of host response modulation (e g inhibition of IFNβ cascade), etc Probably, these differences influence the overall manifestation of the disease in humans Infection caused by HCoV-MERS might manifest itself as ARDS, a mild-mannered and asymptomatic disease HCoV-SARS infections seem to be associated with severe disease only In this paper, a comparison of the structure of these viruses, the mechanisms underlying their ability to cross the interspecies barrier and to multiply in the human body, including modulation of IFNβ cascade, as well as routes of infection transmission and symptoms caused, were presented

positive: Sustainability of Coronavirus on different surfaces COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.

positive: Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic Abstract It is an ugly fact that a significant amount of the world's population will contract SARS-CoV infection with the current spreading. While specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II.

positive: The influenza virus, SARS-CoV-2, and the airways: clarification for the otorhinolaryngologist Abstract The influenza virus and SARS-CoV-2 cause trivial upper and severe lower respiratory infections (Influenza virus 290,000 to 650,000 deaths/year). These viruses come into contact with the airways either by direct projection, by secondary inhalation of airborne droplets, or by handling (fomites). The objective of this article is to clarify the mechanisms of production and penetration of droplets of secretions emitted during all expiratory phenomena likely to transport these viruses and come into contact with the respiratory mucosa. The droplets > 5 µm follow the laws of ballistics, those < 5 µm follow Brownian motion and remain suspended in the air. The aerosols of droplets are very heterogeneous whether the subject is healthy or sick. During an infectious period, not all droplets contain viral RNA. If these RNAs are detectable around patients, on surfaces, and in the ambient air at variable distances according to the studies (from 0.5 m to beyond the patient’s room), this is without prejudice to the infectious nature (viability) of the virus and the minimum infectious dose. There is a time lag between the patient’s infectious period and that of RNA detection for both viruses. Subsequently, the inhaled particles must meet the laws of fluid dynamics (filtration) to settle in the respiratory tree. All of this partly explains the contagiousness and the clinical expression of these two viruses from the olfactory cleft to the alveoli.

positive: A new threat from an old enemy: Re-emergence of coronavirus (Review) The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus-associated disease, the spread and lethality of the 2019 outbreak (COVID-19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.

positive: Transmission of SARS-CoV-2 via fecal-oral and aerosols-borne routes: Environmental dynamics and implications for wastewater management in underprivileged societies The advent of novel human coronavirus (SARS-CoV-2) and its potential transmission via fecal-oral and aerosols-borne routes are upcoming challenges to understand the fate of the virus in the environment. In this short communication, we specifically looked at the possibilities of these transmission routes based on the available literature directly related to the SARS-CoV-2 as well as on the closer phylogenetic relatives such as SARS-CoV-1. The available data suggest that, in addition to human-to-human contact, the virus may spread via fecal-oral and aerosols-borne routes. Existing knowledge states that coronaviruses have low stability in the environment due to the natural action of oxidants that disrupt the viral envelope. Previous recommended dosage of chlorination has been found to be not sufficient to inactivate SARS-CoV-2 in places where viral load is high such as hospitals and airports. Although there is no current evidence showing that coronaviruses can be transmitted through contaminated drinking water, there is a growing concern on the impact of the current pandemic wave on underprivileged societies because of their poor wastewater treatment infrastructures, overpopulation, and outbreak management strategies. More research is encouraged to trace the actual fate of SARS-CoV-2 in the environment and to develop/revise the disinfection strategies accordingly.

positive: [Recommendations of the Society of Gastroenterology of Peru to avoid the spread of SARS-CoV-2 through digestive endoscopy procedures]. The SARS-CoV-2 coronavirus produces the disease called COVID-19, currently spreading in a rapidly evolving pandemic. It can be transmitted by contact, drops and aerosols, and has been isolated from gastrointestinal secretions and faeces. During digestive endoscopy, transmission by any of these mechanisms could occur. It is recommended to limit digestive endoscopy to cases of digestive bleeding, severe dysphagia, foreign body in the digestive tract, biliary obstruction with intractable pain or cholangitis, pseudocyst or complicated encapsulated pancreatic necrosis, gastrointestinal obstruction, and cases at risk of deterioration over time. It is recommended to screen patients based on temperature, symptoms, and epidemiological factors to classify them according to their risk of infection. For procedures in low risk patients, personnel must wear a disposable gown, gloves, eye or face shield, standard surgical mask, disposable hat, disposable shoe covers. In cases of intermediate or high risk, or confirmed COVID-19, protection should be increased using disposable waterproof gown, N95 respirator or similar, and double glove. In case of shortage it may be necessary to reuse N95 respirators for up to 5 uses, following CDC recommendations for donning, removing and storing to prevent secondary contact contamination. Likewise, all protective equipment should be put on and removed according to CDC recommendations. The presence of personnel in endoscopy should be limited to the bare minimum. Said personnel must have daily temperature control and if it is above 37.3ºC, the corresponding evaluation must be carried out. After each procedure, the stretcher and room surfaces should be properly disinfected. High-level disinfection of endoscopes eliminates SARS-CoV-2.

positive: Is SARS-CoV-2 Also an Enteric Pathogen with Potential Fecal-Oral Transmission: A COVID-19 Virological and Clinical Review Abstract In as short as 3 months, COVID-19 has spread and ravaged the world in an unprecedented speed in modern history rivaling the 1918 flu pandemic. SARS-CoV-2, the culprit virus, is highly contagious and stable in the environment and predominantly transmits among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that SARS-CoV-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.

positive: Maintenance of influenza virus infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings OBJECTIVES: The maintenance of infectivity of influenza viruses on the surfaces of personal protective equipment and clothing is an important factor in terms of controlling viral cross-infection in the environment and preventing contact infection. The aim of this study was to determine if laboratory-grown influenza A (H1N1) virus maintained infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings. METHODS: Influenza A virus (0.5 mL) was deposited on the surface of a rubber glove, an N95 particulate respirator, a surgical mask made of non-woven fabric, a gown made of Dupont Tyvek, a coated wooden desk, and stainless steel. Each sample was left for 1, 8, and 24 h, and hemagglutination (HA) and 50% tissue culture infective dose (TCID(50))/mL were measured. RESULTS: The HA titer of this influenza A virus did not decrease in any of the materials tested even after 24 h. The infectivity of influenza A virus measured by TCID(50) was maintained for 8 h on the surface of all materials, with the exception of the rubber glove for which virus infectivity was maintained for 24 h. CONCLUSIONS: Our results indicate that the replacement/renewal of personal protective equipment and clothing by healthcare professionals in cases of exposure to secretions and droplets containing viruses spread by patients is an appropriate procedure to prevent cross-infection.

positive: Stability of SARS-CoV-2 in different environmental conditions

positive: Animal Virus Ecology and Evolution Are Shaped by the Virus Host-Body Infiltration and Colonization Pattern The current classification of animal viruses is largely based on the virus molecular world. Less attention is given to why and how virus fitness results from the success of virus transmission. Virus transmission reflects the infection-shedding-transmission dynamics, and with it, the organ system involvement and other, macroscopic dimensions of the host environment. This study describes the transmission ecology of the world main livestock viruses, 36 in total, a mix of RNA, DNA and retroviruses. Following an iterative process, the viruses are virtually ranked in an outer- to inner-body fashion, by organ system, on ecological grounds. Also portrayed are the shifts in virus host tropism and virus genome. The synthesis of the findings reveals a predictive virus evolution framework, based on the outer- to inner-body changes in the interplay of host environment-transmission modes-organ system involvement-host cell infection cycle-virus genome. Outer-body viruses opportunistically respond to the variation in the external environment. For example, respiratory and enteric viruses tend to be associated with poultry and pig mass rearing. Ruminant and equine viruses tend to be more deep-rooted and host-specific, and also establish themselves in the vital inner-body systems. It is concluded that the framework may assist the study of new emerging viruses and pandemic risks.

positive: Infection control in the management of highly pathogenic infectious diseases: consensus of the European Network of Infectious Disease Summary The European Network for Infectious Diseases (EUNID) is a network of clinicians, public health epidemiologists, microbiologists, infection control, and critical-care doctors from the European member states, who are experienced in the management of patients with highly infectious diseases. We aim to develop a consensus recommendation for infection control during clinical management and invasive procedures in such patients. After an extensive literature review, draft recommendations were amended jointly by 27 partners from 15 European countries. Recommendations include repetitive training of staff to ascertain infection control, systematic use of cough and respiratory etiquette at admission to the emergency department, fluid sampling in the isolation room, and analyses in biosafety level 3/4 laboratories, and preference for point-of-care bedside laboratory tests. Children should be cared for by paediatricians and intensive-care patients should be cared for by critical-care doctors in high-level isolation units (HLIU). Invasive procedures should be avoided if unnecessary or done in the HLIU, as should chest radiography, ultrasonography, and renal dialysis. Procedures that require transport of patients out of the HLIU should be done during designated sessions or hours in secure transport. Picture archiving and communication systems should be used. Post-mortem examination should be avoided; biopsy or blood collection is preferred.

positive: Persistence of Bacteriophage Phi 6 on Porous and Non-Porous Surfaces; Potential for use as Ebola or Coronavirus Surrogate The infection of healthcare workers during the 2013 -2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the Coronavirus Disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage Phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of Phi 6 was evaluated as a surrogate for EBOV and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1 cm2 coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels; a low AH of 3.0 g/m3 and a high AH of 14.4 g/m3 Phi 6 declined at a slower rate on all materials under low AH conditions with a decay rate of 0.06 log10PFU/d to 0.11 log10PFU/d, as compared to the higher AH conditions with a decay rate of 0.65 log10PFU/h to 1.42 log10PFU/d. There was a significant difference in decay rates between porous and non-porous surfaces at both low AH (P < 0.0001) and high AH (P < 0.0001). Under these laboratory-simulated conditions, Phi 6 was found to be a conservative surrogate for EBOV under low AH conditions, in that it persisted longer than Ebola virus in similar AH conditions. Additionally, some coronaviruses persist longer than phi6 under similar conditions, therefore Phi6 may not be a suitable surrogate for coronaviruses.IMPORTANCE Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in healthcare facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated western indoor hospital conditions, Phi 6 was used to assess suitability as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses.

positive: A field indoor air measurement of SARS-CoV-2 in the patient rooms of the largest hospital in Iran Abstract The coronavirus disease 2019 (COVID-19) emerged in Wuhan city, China, in late 2019 and has rapidly spread throughout the world. The major route of transmission of SARS-CoV-2 is in contention, with the airborne route a likely transmission pathway for carrying the virus within indoor environments. Until now, there has been no evidence for detection of airborne severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and this may have implication for the potential spread of the COVID-19. We investigated the air of patient rooms with confirmed COVID-19 in the largest hospital in Iran, on March 17, 2020. To collect the SARS-CoV-2 particles, ten air samples were collected into the sterile standard midget impingers containing 20 mL DMEM with 100 μg/mL streptomycin, 100 U/mL penicillin and 1% antifoam reagent for 1 h. Besides, indoor particle number concentrations, CO2, relative humidity and temperature were recorded throughout the sampling duration. Viral RNA was extracted from samples taken from the impingers and Reverse-Transcription PCR (RT-PCR) was applied to confirm the positivity of collected samples based on the virus genome sequence. Fortunately, in this study all air samples which were collected 2 to 5 m from the patients' beds with confirmed COVID-19 were negative. Despite we indicated that all air samples were negative, however, we suggest further in vivo experiments should be conducted using actual patient cough, sneeze and breath aerosols in order to show the possibility of generation of the airborne size carrier aerosols and the viability fraction of the embedded virus in those carrier aerosols.

positive: Mechanistic Transmission Modeling of COVID-19 on the Diamond Princess Cruise Ship Demonstrates the Importance of Aerosol Transmission Background The current prevailing position is that coronavirus disease 2019 (COVID-19) is transmitted primarily through large respiratory droplets within close proximity (i.e., 1-2 m) of infected individuals. However, quantitative information on the relative importance of specific transmission pathways of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (i.e., droplets, aerosols, and fomites across short- and long-range distances) remains limited. Methods To evaluate the relative importance of multiple transmission routes for SARS-CoV-2, we leveraged detailed information available from the Diamond Princess Cruise Ship outbreak that occurred in early 2020. We developed a framework that combines stochastic Markov chain and negative exponential dose-response modeling with available empirical data on mechanisms of SARS-CoV-2 dynamics and human behaviors, which informs a modified version of the Reed-Frost epidemic model to predict daily and cumulative daily case counts on the ship. We modeled 21,600 scenarios to generate a matrix of solutions across a full range of assumptions for eight unknown or uncertain epidemic and mechanistic transmission factors, including the magnitude of droplet and aerosol emissions from infected individuals, the infectious dose for deposition of droplets and aerosols to the upper and lower respiratory tracts, and others. Findings A total of 132 model iterations met acceptability criteria (R2 > 0.95 for modeled vs. reported cumulative daily cases and R2 > 0 for daily cases). Analyzing only these successful model iterations yields insights into the likely values for uncertain parameters and quantifies the likely contributions of each defined mode of transmission. Mean estimates of the contributions of short-range, long-range, and fomite transmission modes to infected cases aboard the ship across the entire simulation time period were 35%, 35%, and 30%, respectively. Mean estimates of the contributions of large respiratory droplets and small respiratory aerosols were 41% and 59%. Short-range transmission was the dominant mode after passenger quarantine began, albeit due primarily to aerosol transmission, not droplets. Interpretation Our results demonstrate that aerosol inhalation was likely the dominant contributor to COVID-19 transmission among passengers aboard the Diamond Princess Cruise Ship. Moreover, close-range and long-range transmission likely contributed similarly to disease progression aboard the ship, with fomite transmission playing a smaller role. The passenger quarantine also affected the importance of each mode, demonstrating the impacts of the interventions. Although cruise ships represent unique built environments with high ventilation rates and no air recirculation, these findings underscore the importance of implementing public health measures that target the control of inhalation of aerosols in addition to ongoing measures targeting control of large droplet and fomite transmission, not only aboard cruise ships but in other indoor environments as well.

positive: On the airborne aspect of COVID-19 coronovirus It is a widely accepted view that COVID 19 is either transmitted via surface contamination or via close contact of an un-infected person with an infected person. Surface contamination usually happens when infected water droplets from exhalation/sneeze/cough of COVID sick person settle on nearby surfaces. To curb this, social distancing and good hand hygiene advise is advocated by World health Organization (WHO). We argue that COVID 19 coronovirus can also be airborne in a puff cloud loaded with infected droplets generated by COVID sick person. An elementary calculation shows that a $5~\mu m$ respiratory infected droplet can remain suspended for about 9.0 minutes and a $2~\mu m$ droplet can remain suspended for about an hour! And social distancing advise of 3 feet by WHO and 6 feet by CDC (Centers for Disease Control and Prevention) may not be sufficient in some circumstances as discussed in the text.

positive: Concentration and detection of SARS coronavirus in sewage from Xiao Tang Shan Hospital and the 309th Hospital of the Chinese People's Liberation Army. A worldwide outbreak of severe acute respiratory syndrome (SARS) had been reported. Over 8439 SARS cases and 812 SARS-related deaths were reported to the World Health Organization from 32 countries around the world up to 5 July 2003. The mechanism of transmission of SARS-CoV has been limited only to close contacts with patients. Attention was focused on possible transmission by the sewage system because laboratory studies showed that patients excreted coronavirus RNA in their stools in Amoy Gardens in Hong Kong. To explore whether the stool of SARS patients or the sewage containing the stool of patients would transmit SARS-CoV or not, we used a style of electropositive filter media particle to concentrate the SARS-CoV from the sewage of two hospitals receiving SARS patients in Beijing, as well as cell culture, semi-nested RT-PCR and sequencing of genes to detect and identify the viruses from sewage. There was no live SARS-CoV detected in the sewage in these assays. The nucleic acid of SARS-CoV was found in the sewage before disinfection from both hospitals by PCR. After disinfection, SARS-CoV RNA could be detected from some samples from the 309th Hospital of the Chinese People's Liberation Army, but not from Xiao Tang Shan Hospital after disinfection. In this study, we found that the virus can survive for 14 days in sewage at 4 degrees C, 2 days at 20 degrees C, and its RNA can be detected for 8 days though the virus had been inactivated. In conclusion, this study demonstrates that the RNA of SARS-CoV could be detected from the concentrates of sewage of both hospitals receiving SARS patients before disinfection and occasionally after disinfection though there was no live SARS-CoV; thus much attention should be paid to the treatment of stools of patients and the sewage of hospitals receiving SARS patients.

positive: Sanitizing agents for virus inactivation and disinfection Viral epidemics develop from the emergence of new variants of infectious viruses. The lack of effective antiviral treatments for the new viral infections coupled with rapid community spread of the infection often result in major human and financial loss. Viral transmissions can occur via close human‐to‐human contact or via contacting a contaminated surface. Thus, careful disinfection or sanitization is essential to curtail viral spread. A myriad of disinfectants/sanitizing agents/biocidal agents are available that can inactivate viruses, but their effectiveness is dependent upon many factors such as concentration of agent, reaction time, temperature, and organic load. In this work, we review common commercially available disinfectants agents available on the market and evaluate their effectiveness under various application conditions. In addition, this work also seeks to debunk common myths about viral inactivation and highlight new exciting advances in the development of potential sanitizing agents.

positive: Recommendations for the prevention of transmission of SARS during GI endoscopy

positive: Survivability, Partitioning, and Recovery of Enveloped Viruses in Untreated Municipal Wastewater [Image: see text] Many of the devastating pandemics and outbreaks of the 20th and 21st centuries have involved enveloped viruses, including influenza, HIV, SARS, MERS, and Ebola. However, little is known about the presence and fate of enveloped viruses in municipal wastewater. Here, we compared the survival and partitioning behavior of two model enveloped viruses (MHV and ϕ6) and two nonenveloped bacteriophages (MS2 and T3) in raw wastewater samples. We showed that MHV and ϕ6 remained infective on the time scale of days. Up to 26% of the two enveloped viruses adsorbed to the solid fraction of wastewater compared to 6% of the two nonenveloped viruses. Based on this partitioning behavior, we assessed and optimized methods for recovering enveloped viruses from wastewater. Our optimized ultrafiltration method resulted in mean recoveries (±SD) of 25.1% (±3.6%) and 18.2% (±9.5%) for the enveloped MHV and ϕ6, respectively, and mean recoveries of 55.6% (±16.7%) and 85.5% (±24.5%) for the nonenveloped MS2 and T3, respectively. A maximum of 3.7% of MHV and 2% of MS2 could be recovered from the solids. These results shed light on the environmental fate of an important group of viruses and the presented methods will enable future research on enveloped viruses in water environments.

positive: Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces The novel coronavirus respiratory syndrome (COVID-19) has now spread worldwide. The relative contribution of viral transmission via fomites is still unclear. SARS-CoV-2 has been shown to survive on inanimate surfaces for several days, yet the factors that determine its survival on surfaces are not well understood. Here we combine microscopy imaging with virus viability assays to study survival of three bacteriophages suggested as good models for human respiratory pathogens: the enveloped Phi6 (a surrogate for SARS-CoV-2), and the non-enveloped PhiX174 and MS2. We measured virus viability in human saliva microdroplets, SM buffer, and water following deposition on glass surfaces at various relative humidities (RH). Although saliva microdroplets dried out rapidly at all tested RH levels (unlike SM that remained hydrated at RH ≥ 57%), survival of all three viruses in dry saliva microdroplets was significantly higher than in water or SM. Thus, RH and hydration conditions are not sufficient to explain virus survival, indicating that the suspended medium, and association with saliva components in particular, likely affect physicochemical properties that determine virus survival. The observed high virus survival in dry saliva deposited on surfaces, under a wide range of RH levels, can have profound implications for human public health, specifically the COVID-19 pandemic.

positive: A Novel Approach for a Novel Pathogen: using a home assessment team to evaluate patients for 2019 novel coronavirus (SARS-CoV-2) Thousands of people in the United States have required testing for SARS-CoV-2. Evaluation for a special pathogen is resource intensive. We report an innovative approach to home assessment that, in collaboration with public health, enables safe evaluation and specimen collection outside the healthcare setting, avoiding unnecessary exposures and resource utilization.

positive: Modelling aerosol transport and virus exposure with numerical simulations in relation to SARS-CoV-2 transmission by inhalation indoors Abstract We provide research findings on the physics of aerosol and droplet dispersion relevant to the hypothesized aerosol transmission of SARS-CoV-2 during the current pandemic. We utilize physics-based modeling at different levels of complexity, along with previous literature on coronaviruses, to investigate the possibility of airborne transmission. The previous literature, our 0D-3D simulations by various physics-based models, and theoretical calculations, indicate that the typical size range of speech and cough originated droplets ( d ⩽ 20 μ m ) allows lingering in the air for O ( 1 h ) so that they could be inhaled. Consistent with the previous literature, numerical evidence on the rapid drying process of even large droplets, up to sizes O ( 100 μ m ) , into droplet nuclei/aerosols is provided. Based on the literature and the public media sources, we provide evidence that the individuals, who have been tested positive on COVID-19, could have been exposed to aerosols/droplet nuclei by inhaling them in significant numbers e.g. O ( 100 ) . By 3D scale-resolving computational fluid dynamics (CFD) simulations, we give various examples on the transport and dilution of aerosols ( d ⩽ 20 μ m ) over distances O ( 10 m ) in generic environments. We study susceptible and infected individuals in generic public places by Monte-Carlo modelling. The developed model takes into account the locally varying aerosol concentration levels which the susceptible accumulate via inhalation. The introduced concept, ’exposure time’ to virus containing aerosols is proposed to complement the traditional ’safety distance’ thinking. We show that the exposure time to inhale O ( 100 ) aerosols could range from O ( 1 s ) to O ( 1 min ) or even to O ( 1 h ) depending on the situation. The Monte-Carlo simulations, along with the theory, provide clear quantitative insight to the exposure time in different public indoor environments.

positive: Uncertainties about the transmission routes of 2019 novel coronavirus

positive: A COVID-19 Infection Risk Model for Frontline Health Care Workers The number of confirmed COVID-19 cases admitted in hospitals is continuously increasing in the Philippines. Frontline health care workers are faced with imminent risks of getting infected. In this study, we formulate a theoretical model to calculate the risk of being infected in health care facilities considering the following factors: the average number of encounters with a suspected COVID-19 patient per hour; interaction time for each encounter; work shift duration or exposure time; crowd density, which may depend on the amount of space available in a given location; and availability and effectiveness of protective gears and facilities provided for the frontline health care workers. Based on the simulation results, we recommend the following: (i) decrease the rate of patient encounter per frontline health care worker, e.g., maximum of three encounters per hour in a 12-hour work shift duration; (ii) decrease the interaction time between the frontline health care worker and the patients, e.g., less than 40 minutes for the whole day; (iii) increase the clean and safe space for social distancing, e.g., maximum of 10% crowd density, and if possible, implement compartmentalization of patients; and/or (iv) provide effective protective gears and facilities, e.g., 95% effective, that the frontline health care workers can use during their shift. Moreover, the formulated model can be used for other similar scenarios, such as identifying infection risk in public transportation, school classroom settings, offices, and mass gatherings.

positive: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.

positive: Evaluation of the survivability of MS2 viral aerosols deposited on filtering face piece respirator samples incorporating antimicrobial technologies BACKGROUND: Respiratory protective devices exposed to pathogenic microorganisms present a potential source of transmission of infection during handling. In this study, the efficacy of 4 antimicrobial respirators to decontaminate MS2, a surrogate for pathogenic viruses, was evaluated and compared with control N95 filtering face piece respirators, which did not contain any known antimicrobial components. METHODS: MS2 containing droplet nuclei were generated using a Collison nebulizer and loaded onto respirator coupons at a face velocity of 13.2 cm/seconds for 30 minutes. The coupons were incubated at 2 different temperature and relative humidity (RH) conditions and analyzed for viable MS2 at different time intervals. RESULTS: Results showed that log(10) reduction of MS2 was not statistically significant (P > .05) between the control and antimicrobial respirator coupons, when stored at 22°C and 30% RH up to 20 hours. Coupons from 1 of the 4 antimicrobial respirators showed an average MS2 log(10) reduction of 3.7 at 37°C and 80% RH for 4 hours, which was statistically significant (P ≤ .05) compared with coupons from the control respirators. CONCLUSION: Results from this study suggest that MS2 virus decontamination efficacy of antimicrobial respirators is dependent on the antimicrobial agent and storage conditions.

positive: Putting some context to the aerosolization debate around SARS-CoV-2

positive: Alert for SARS-CoV-2 infection caused by fecal aerosols in rural areas in China

positive: Persistence of Bacteriophage Phi 6 on Porous and Non-Porous Surfaces; Potential for use as Ebola or Coronavirus Surrogate. The infection of healthcare workers during the 2013 -2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the Coronavirus Disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage Phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of Phi 6 was evaluated as a surrogate for EBOV and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1 cm2 coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels; a low AH of 3.0 g/m3 and a high AH of 14.4 g/m3 Phi 6 declined at a slower rate on all materials under low AH conditions with a decay rate of 0.06 log10PFU/d to 0.11 log10PFU/d, as compared to the higher AH conditions with a decay rate of 0.65 log10PFU/h to 1.42 log10PFU/d. There was a significant difference in decay rates between porous and non-porous surfaces at both low AH (P < 0.0001) and high AH (P < 0.0001). Under these laboratory-simulated conditions, Phi 6 was found to be a conservative surrogate for EBOV under low AH conditions, in that it persisted longer than Ebola virus in similar AH conditions. Additionally, some coronaviruses persist longer than phi6 under similar conditions, therefore Phi6 may not be a suitable surrogate for coronaviruses.IMPORTANCE Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in healthcare facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated western indoor hospital conditions, Phi 6 was used to assess suitability as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses.

positive: Potential Risk of Virus Carryover by Fabrics of Personal Protective Gowns Personal protective gowns and coveralls are classified based on barrier efficiency that validates protection from fluid penetration under certain pressures. Materials standardized in this system have been found suitable for emergency medical practices confronting highly contagious diseases. Nevertheless, adhesion of blood, and body fluids from virus-infected patients to the surface of protective clothing still imposes a risk of pathogen transmission in the process of doffing, or undressing. We performed a small-scale experiment to test the possibility of infectious virus carryover on the surface of different fabrics used in commercially available protective gowns. Application of a lentivirus vector that expresses green fluorescent protein allowed easy monitoring of infectious viral loads on fabrics. Results indicate that fabrics of level-3 surgical gowns serve better to reduce virus transmission compared to fabrics of chemical protective clothing with the same or higher barrier efficiency. Analysis of sliding angles provided indexes of fluid repellency, which were inversely related to virus carryover potentials. Droplets of infectious body fluids may easily roll off fabrics with water-repellent finishing. Thus, virus carryover is a measurable risk factor to be considered for better choice of personal protective clothing.

positive: Toilets dominate environmental detection of SARS-CoV-2 virus in a hospital Background: Respiratory and faecal aerosols play a suspected role in transmitting the SARS-CoV-2 virus. We performed extensive environmental sampling in a dedicated hospital building for Covid-19 patients in both toilet and non-toilet environments, and analysed the associated environmental factors. Methods: We collected data of the Covid-19 patients. 107 surface samples, 46 air samples, two exhaled condensate samples, and two expired air samples were collected were collected within and beyond the four three-bed isolation rooms. We reviewed the environmental design of the building and the cleaning routines. We conducted field measurement of airflow and CO2 concentrations. Findings: The 107 surface samples comprised 37 from toilets, 34 from other surfaces in isolation rooms (ventilated at 30-60 L/s), and 36 from other surfaces outside isolation rooms in the hospital. Four of these samples were positive, namely two ward door-handles, one bathroom toilet-seat cover and one bathroom door-handle; and three were weakly positive, namely one bathroom toilet seat, one bathroom washbasin tap lever and one bathroom ceiling-exhaust louvre. One of the 46 air samples was weakly positive, and this was a corridor air sample. The two exhaled condensate samples and the two expired air samples were negative. Interpretation: The faecal-derived aerosols in patients' toilets contained most of the detected SARS-CoV-2 virus in the hospital, highlighting the importance of surface and hand hygiene for intervention.

positive: Severe Acute Respiratory Syndrome – a New Coronavirus from the Chinese Dragon's Lair The recent identification of a novel clinical entity, the severe acute respiratory syndrome (SARS), the rapid subsequent spread and case fatality rates of 14–15% have prompted a massive international collaborative investigation facilitated by a network of laboratories established by the World Health Organization (WHO). As SARS has the potential of becoming the first pandemic of the new millennium, a global warning by the WHO was issued on 12 March 2003. The disease, which is believed to have its origin in the Chinese Guangdong province, spread from Hong Kong via international airports to its current worldwide distribution. The concerted efforts of a globally united scientific community have led to the independent isolation and identification of a novel coronavirus from SARS patients by several groups. The extraordinarily rapid isolation of a causative agent of this newly emerged infectious disease constitutes an unprecedented scientific achievement. The main scope of the article is to provide the clinician with an overview of the natural history, epidemiology and clinical characteristics of SARS. On the basis of the recently published viral genome and structural features common to the members of the coronavirus family, a model for host cell–virus interaction and possible targets for antiviral drugs are presented. The epidemiological consequences of introducing a novel pathogen in a previously unexposed population and the origin and evolution of a new and more pathogenic strain of coronavirus are discussed.

positive: Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002–2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.

positive: Safety of foods, food supply chain and environment within the COVID-19 pandemic BACKGROUND: The COVID-19 pandemic has generated a new era in the world while we still figure out the consequences in different aspects of our daily life. The food supply chain and the food industry do not comprise an exception. SCOPE AND APPROACH: This review summarizes the possible transmission ways of COVID-19 through the foods, food supply chain, surfaces, and environment before exploring the development of corresponding detection tools of SARS-CoV-2. For the time being, the possibility of transmission through the food sector is considered negligible, and tracing of SARS-CoV-2 in working environments is not considered as a priority by public authorities. However, the adverse effects on the environment, food systems, and people along the food supply chain are already evident. KEY FINDINGS AND CONCLUSIONS: As long as we move from farm to fork, more safety measures are needed since more people (and subsequently more potential sources of infection) are involved in the process. The need for developing respective bioanalytical protocols for food and environmental safety applications to adapt in the post-lockdown period is also highlighted.

positive: COVID-19 Pandemic: Prevention and protection measures to be adopted at the workplace SARS-CoV-2, identified in Wuhan, China, for the first time in December 2019, is a new viral strain, which has not been previously identified in humans; it can be transmitted both by air and via direct and indirect contact; however, the most frequent way it spreads is via droplets. Like the other viruses belonging to the same family of coronaviruses, it can cause from mild flu-like symptoms, such as cold, sore throat, cough and fever, to more severe ones such as pneumonia and breathing difficulties, and it can even lead to death. Since no effective specific drug therapy has been found yet, nor any vaccine capable of limiting the spread of this pathogen, it is important for ways of preventing the spread of this infection to be established. The purpose of our research was to provide a protocol to prevent the spread of SARS-CoV-2 infection in light of the limited information related to this coronavirus. In detail, we analysed and searched targeted evidence-based guidelines issued in the various countries affected by this epidemic up till now. In addition, we analyzed the recommendations for the prevention and control of other epidemics caused by other pathogens belonging to the same family of coronaviruses or others that present the same mechanisms of transmission. General organizational measures regarding the containment and management of the epidemiological emergency of COVID-19 have been imposed by the competent authorities for an adequate and proportionate management of the evolution of the epidemiological situation. The prevention and protection organizational measures therefore aim to minimize the probability of being exposed to SARS-CoV-2. For this purpose, measures must also be taken at work to avoid new infections or even the spread of the virus where it has already been present. Furthermore, environmental measures are aimed at reducing the risk of transmission of SARS-CoV-2 to individuals through contact with infected subjects, objects, equipment, or contaminated environmental surfaces. Protective devices must be used whenever there is potentially close contact with a suspect case, especially when the potentially infected person does not wear a surgical mask that could reduce the spread of viruses in the environment. By adopting this specific prevention and protection measures recommended in the workplace, it will be possible to help overcome this COVID-19 pandemic.

positive: The COVID-19 Pandemic: Changing Lives and Lessons Learned

positive: Biological and social aspects of Coronavirus Disease 2019 (COVID-19) related to oral health The expansion of coronavirus disease 2019 (COVID-19) throughout the world has alarmed all health professionals. Especially in dentistry, there is a growing concern due to it's high virulence and routes of transmission through saliva aerosols. The virus keeps viable on air for at least 3 hours and on plastic and stainless-steel surfaces up to 72 hours. In this sense, dental offices, both in the public and private sectors, are high-risk settings of cross infection among patients, dentists and health professionals in the clinical environment (including hospital's intensive dental care facilities). This manuscript aims to compile current available evidence on prevention strategies for dental professionals. Besides, we briefly describe promising treatment strategies recognized until this moment. The purpose is to clarify dental practitioners about the virus history and microbiology, besides guiding on how to proceed during emergency consultations based on international documents. Dentists should consider that a substantial number of individuals (including children) who do not show any signs and symptoms of COVID-19 may be infected and can disseminate the virus. Currently, there is no effective treatment and fast diagnosis is still a challenge. All elective dental treatments and non-essential procedures should be postponed, keeping only urgent and emergency visits to the dental office. The use of teledentistry (phone calls, text messages) is a very promising tool to keep contact with the patient without being at risk of infection.

positive: Making Waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 °C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.

positive: Ultraviolet and COVID‐19 pandemic BACKGROUND: COVID‐19 virus causes coronavirus disease. AIMS: It is a highly contagious viral infection. PATIENTS/METHODS/RESULTS/CONCLUSION: In this article, we will discuss the potential phototherapy problems and also alternative options for dermatologists, ultraviolet treatment against COVID‐19 virus, and vitamin D–associated problems in these coronavirus days.

positive: Chapter One Supramolecular Architecture of the Coronavirus Particle Abstract Coronavirus particles serve three fundamentally important functions in infection. The virion provides the means to deliver the viral genome across the plasma membrane of a host cell. The virion is also a means of escape for newly synthesized genomes. Lastly, the virion is a durable vessel that protects the genome on its journey between cells. This review summarizes the available X-ray crystallography, NMR, and cryoelectron microscopy structural data for coronavirus structural proteins, and looks at the role of each of the major structural proteins in virus entry and assembly. The potential wider conservation of the nucleoprotein fold identified in the Arteriviridae and Coronaviridae families and a speculative model for the evolution of corona-like virus architecture are discussed.

positive: Viruses Present Indoors and Analyses Approaches Through human history viruses have shown enormous epidemiological and pandemic potential as the occurrence and spread of viruses in pandemic dimensions poses a threat to the health and lives of seven billion people worldwide. Scientific evidence has associated harmful health effects to indoor air hazards recognizing the existence of a vital concern in public health sector. Thus the assessment of human exposure to biological aerosols and droplets indoor became an imperative requirement of investigation. Environmental bioburden assessment of viruses relies in both culture-dependent approaches that comprise classical methodologies, still prominent and vital in the field of modern biotechnology, and culture-independent approaches based on nucleic acid amplification techniques, which are considered the gold standard in clinical virology. The main factor influencing indoor microbiology is the human being and their activities. Indoor environments to be considered are those regularly occupied by humans: residences, offices, schools, industrial buildings, health care facilities, farming activities and other settings occupied all the time, or in which occupant density is high. It’s well known that approximately 60% of total human respiratory and gastrointestinal infections are acquired indoor, since viruses have a rapid spread in the community and can be transmitted easily, especially in crowded and poorly ventilated environments, causing high morbidity and decline in quality of life and productivity. Studies have shown that respiratory syncytial virus, rhinovirus, metapneumovirus, influenza and parainfluenza virus, and human enterovirus infections may be associated with virus-induced asthma, leading to diseases such as pneumonia. Gastroenteritis infectious (about 30±40% of cases) is attributable to viruses. Rotavirus, Astrovirus, Norwalk-like viruses and other caliciviruses are responsible for 48% of all reported outbreaks of infectious intestinal disease. Safe working conditions are essential for healthy living, that’s why the programmes conceived as a result of strategic and preventive policy maintenance, in refrigeration and ventilation systems, are the determining factor for the control of biological pollutants. Moreover, the development of highly sensitive and specific detection and identification methodologies with capacity to be used in diverse applications, such as diagnosis, public health risk assessment, research and for the implementation of preventive measures and protocols are imperative.

positive: Transmission of SARS-CoV-2: an update of current literature Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for the 2019 coronavirus disease (COVID-19) pandemic, has caused a public health emergency. The need for additional research in viral pathogenesis is essential as the number of cases and deaths rise. Understanding the virus and its ability to cause disease has been the main focus of current literature; however, there is much unknown. Studies have revealed new findings related to the full transmission potential of SARS-CoV-2 and its subsequent ability to cause infection by different means. The virus is hypothesized to be of increased virulence compared with previous coronavirus that caused epidemics, in part due to its overall structural integrity and resilience to inactivation. To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. Additionally, the receptor by which the virus gains cellular entry, ACE2, has been found to be expressed in different human body systems, thereby potentiating its infection in those locations. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2—respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Understanding these different routes is important as they pertain to clinical practice, especially in taking preventative measures to mitigate the spread of SARS-CoV-2.

positive: Models of transmission of COVID-19 with time under the influence of meteorological determinants Based on the statistical analyses of the data on the number of confirmed COVID-19 cases and meteorological determinants in some of the severely affected cities in Spain, Italy and the USA, some models are constructed showing the relationship of I' (the number of infected individuals divided by the total population of a city) with temperature, relative humidity, wind velocity and time. Three models are based on the data before lockdown/travel restrictions in these cities, and the other three models are based on data both before and after lockdown/travel restrictions. These models, in general, indicate that the transmission of COVID-19 could be relatively high either for elevated temperatures with lower relative humidity or for lower temperatures with higher relative humidity conditions. Although one model indicates exponential increase in number of infection cases with time, the more statistically significant models show that the number of cases varies quadratically with time. We have discussed in short, how all these features could be linked with the alterations of structural characteristics of the SARS-CoV-2 virus. Finally, the possibility of natutal disappearance of COVID-19 pandemic, at the global level, has been discussed in the context of the most statistically significant model.

positive: Identification of SARS-CoV-2 RNA in Healthcare Heating, Ventilation, and Air Conditioning Units Available information on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission by small particle aerosols continues to evolve rapidly. To assess the potential role of heating, ventilation, and air conditioning (HVAC) systems in airborne viral transmission, this study sought to determine the viral presence, if any, on air handling units in a healthcare setting where Coronavirus Disease 2019 (COVID-19) patients were being treated. The presence of SARS-CoV-2 RNA was detected in approximately 25% of samples taken from nine different locations in multiple air handlers. While samples were not evaluated for viral infectivity, the presence of viral RNA in air handlers raises the possibility that viral particles can enter and travel within the air handling system of a hospital, from room return air through high efficiency MERV-15 filters and into supply air ducts. Although no known transmission events were determined to be associated with these specimens, the findings suggest the potential for HVAC systems to facilitate transmission by environmental contamination via shared air volumes with locations remote from areas where infected persons reside. More work is needed to further evaluate the risk of SARS-CoV-2 transmission via HVAC systems and to verify effectiveness of building operations mitigation strategies for the protection of building occupants. These results are important within and outside of healthcare settings and may present a matter of some urgency for building operators of facilities that are not equipped with high-efficiency filtration.

positive: SARS-CoV-2 RNA detection in the air and on surfaces in the COVID-19 ward of a hospital in Milan, Italy The COVID-19 outbreak has rapidly progressed worldwide finding the health system, scientists and society unprepared to face a little-known, fast spreading, and extremely deadly virus. Italy is one of the countries hardest hit by the pandemic, resulting in healthcare facilities bearing heavy burdens and severe restrictive measures. Despite efforts to clarify the virus transmission, especially in indoor scenarios, several aspects of SARS-CoV-2 spread are still rudimentary. This study evaluated the contamination of the air and surfaces by SARS-CoV-2 RNA in the COVID-19 isolation ward of a hospital in Milan, Italy. A total of 42 air and surface samples were collected inside five different zones of the ward including contaminated (COVID-19 patients' area), semi-contaminated (undressing room), and clean areas. SARS-CoV-2 RNA detection was performed using real time reverse transcription polymerase chain reaction. Overall, 24.3% of swab samples were positive, but none of these were collected in the clean area. Thus, the positivity rate was higher in contaminated (35.0%) and semi-contaminated (50.0%) areas than in clean areas (0.0%; P<0.05). The most contaminated surfaces were hand sanitizer dispensers (100.0%), medical equipment (50.0%), medical equipment touch screens (50.0%), shelves for medical equipment (40.0%), bedrails (33.3%), and door handles (25.0%). All the air samples collected from the contaminated area, namely the intensive care unit and corridor, were positive while viral RNA was not detected in either semi-contaminated or clean areas. These results showed that environmental contamination did not involve clean areas, but the results also support the need for strict disinfection, hand hygiene and protective measures for healthcare workers as well as the need for airborne isolation precautions.

positive: Roles of sunlight and natural ventilation for controlling infection: historical and current perspectives Summary Background Infections caught in buildings are a major global cause of sickness and mortality. Understanding how infections spread is pivotal to public health yet current knowledge of indoor transmission remains poor. Aim To review the roles of natural ventilation and sunlight for controlling infection within healthcare environments. Methods Comprehensive literature search was performed, using electronic and library databases to retrieve English language papers combining infection; risk; pathogen; and mention of ventilation; fresh air; and sunlight. Foreign language articles with English translation were included, with no limit imposed on publication date. Findings In the past, hospitals were designed with south-facing glazing, cross-ventilation and high ceilings because fresh air and sunlight were thought to reduce infection risk. Historical and recent studies suggest that natural ventilation offers protection from transmission of airborne pathogens. Particle size, dispersal characteristics and transmission risk require more work to justify infection control practices concerning airborne pathogens. Sunlight boosts resistance to infection, with older studies suggesting potential roles for surface decontamination. Conclusions Current knowledge of indoor transmission of pathogens is inadequate, partly due to lack of agreed definitions for particle types and mechanisms of spread. There is recent evidence to support historical data on the effects of natural ventilation but virtually none for sunlight. Modern practice of designing healthcare buildings for comfort favours pathogen persistence. As the number of effective antimicrobial agents declines, further work is required to clarify absolute risks from airborne pathogens along with any potential benefits from additional fresh air and sunlight.

positive: Infection and Rapid Transmission of SARS-CoV-2 in Ferrets The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease. SARS-CoV-2-infected ferrets exhibit elevated body temperatures and virus replication. Although fatalities were not observed, SARS-CoV-2-infected ferrets shed virus in nasal washes, saliva, urine, and feces up to 8 days post-infection. At 2 days post-contact, SARS-CoV-2 was detected in all naive direct contact ferrets. Furthermore, a few naive indirect contact ferrets were positive for viral RNA, suggesting airborne transmission. Viral antigens were detected in nasal turbinate, trachea, lungs, and intestine with acute bronchiolitis present in infected lungs. Thus, ferrets represent an infection and transmission animal model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines.

positive: Rapid evidence summary on SARS-CoV-2 survivorship and disinfection, and a reusable PPE protocol using a double-hit process In the COVID-19 pandemic caused by SARS-CoV-2, hospitals are stretched beyond capacity. There are widespread reports of dwindling supplies of personal protective equipment (PPE), which are paramount to protect frontline medical/nursing staff and to minimize further spread of the virus. We carried out a rapid review to summarize the existing evidence on SARS-CoV-2 survivorship and methods to disinfect PPE gear, particularly N95 filtering facepiece respirators (FFR). In the absence of data on SARS-CoV-2, we focused on the sister virus SARS-CoV-1. We propose a two-step disinfection process, which is conservative in the absence of robust evidence on SARS-CoV-2. This disinfection protocol is based on an initial storage of PPE for ≥4 days, followed by ultraviolet light (UVC), dry heat treatment, or chemical disinfection. Importantly, each of the two steps is based on independent disinfection mechanisms, so that our proposed protocol is a multiplicative system, maximising the efficacy of our disinfection process. This method could be rapidly implemented in other healthcare settings, while testing of each method is undertaken, increasing the frontline supply of PPE, and avoiding many of the upstream issues of supply chain disruption currently being faced.

positive: Environmental survival and microbicide inactivation of coronaviruses

positive: MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS – MERS, MERS CoV

positive: Pediatric Endoscopy in the Era of Coronavirus Disease 2019: A North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper The delivery of endoscopic care is changing rapidly in the era of Coronavirus Disease 2019 (COVID-19). The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Endoscopy and Procedures Committee has formulated this statement to offer practical guidance to help standardize endoscopy services for pediatric patients with the aim of minimizing COVID-19 transmission to staff, patients, and caregivers and to conserve personal protective equipment (PPE) during this critical time. Appropriate use of PPE is essential to minimize transmission and preserve supply. Pediatric endoscopic procedures are considered at high risk for COVID-19 transmission. We recommend that all pediatric endoscopic procedures are done in a negative pressure room with all staff using proper airborne, contact, and droplet precautions regardless of patient risk stratification. This includes appropriate use of a filtering face-piece respirator (N95, N99, FFP2/3, or PAPR), double gloves, facial protection (full visor and/or face shield), full body water-resistant disposable gown, shoe covers and a hairnet. In deciding which endoscopic procedures should proceed, it is important to weigh the risks and benefits to optimize healthcare delivery and minimize risk. To inform these decisions, we propose a framework for stratifying procedures as emergent (procedures that need to PROCEEED), urgent (PAUSE, weigh the benefits and risks in deciding whether to proceed) and elective (POSTPONE procedures). This statement was based on emerging evidence and is meant as a guide. It is important that all endoscopy facilities where pediatric procedures are performed follow current recommendations from public health agencies within their jurisdiction regarding infection prevention and control of COVID-19.

positive: A chronicle of SARS-CoV-2: Part-I - Epidemiology, diagnosis, prognosis, transmission and treatment In order to benefit the public, community workers and scientific community, we hereby present a chronicle of SARS-CoV-2 that leads to the unseen precedent of social distancing and lockdown owing to coronavirus disease (COVID-19). Information on this life-threatening pandemic of COVID-19 is sparse and discrete; and the urgency is such that the dissemination of information is increasing with numerous daily publications on the topic. Therefore, we developed a comprehensive review on various aspects of SARS-CoV-2 and COVID-19. We scientifically compiled published research, news, and reports from various sources to comprehend and summarize the information and findings on Coronaviruses. The review explicitly covers the aspects like genome and pedigree of SARS-CoV-2; epidemiology, prognosis, pathogenesis, symptoms and diagnosis of COVID-19 in order to catalog the right information on transmission route, and influence of environmental factors on virus transmissions, for the robust understanding of right strategical steps for proper COVID-19 management. We have explicitly highlighted several useful information and facts like: i) No established relationship between progression of SARS-CoV-2 with temperature, humidity and/or both, ii) The underlying mechanism of SARS-CoV-2 is not fully understood, iii) Respiratory droplet size determines drop and airborne-based transmission, iv) Prognosis of COVID-19 can be done by its effects on various body organs, v) Infection can be stopped by restricting the binding of S protein and AE2, vi) Hydroxychloroquine is believed to be better than chloroquine for COVID-19, vii) Ivermectin with Vero-hSLAM cells is able to reduce infection by ~5000 time within 2 days, and viii) Nafamostat mesylate can inhibit SARS-CoV-2 S protein-initiated membrane fusion. We have also suggested future research perspectives, challenges and scope.

positive: Covid-19: Impact on Perianesthesia Nursing Areas

positive: Environmental Contamination of SARS-CoV-2 in a Non-Healthcare Setting Revealed by Sensitive Nested RT-PCR Fomite-mediated transmission has been identified as a possible route for disease spread of the COVID-19 pandemic. In healthcare settings, evidence of environmental contamination by SARS-CoV-2 has been found in patients' rooms and toilets. Here, we investigate environmental contamination of SARS-CoV-2 in non-healthcare settings and assessed the efficacy of cleaning and disinfection in removing SARS-CoV-2 contamination. A total of 428 environmental swabs and six air samples was taken from accommodation rooms, toilets and elevators that have been used by COVID-19 cases. Through the use of a sensitive nested RT-PCR assay, we found two SARS-CoV-2 RNA positive samples from the room resided by a COVID-19 case, highlighting the risk of fomite-mediated transmission in non-healthcare settings and the importance of surface disinfection of spaces occupied by cases. Of note, we did not find evidence for air-borne transmission, nor of environmental contamination of elevators, which were transiently exposed to infected persons.

positive: On airborne transmission and control of SARS-Cov-2 Abstract The COVID-19 pandemic is creating a havoc situation across the globe that modern society has ever seen. Despite of their paramount importance, the transmission routes of SARS-Cov-2 still remain debated among various sectors. Evidences compiled here strongly suggest that the COVID-19 could be transmitted via air in inadequately ventilated environments that are housing the infected by SARS-Cov-2. Existing experimental data showed that coronavirus survival was negatively impacted by ozone, high temperature and low humidity. Here, regression analysis showed that the spread of SARS-Cov-2 was reduced by increasing ambient ozone concentration level (48.83–94.67 μg/m3) (p-value = 0.039) and decreasing relative humidity (23.33–82.67%) (p-value = 0.002) and temperature (−13.17-19 °C) (p-value = 0.003) observed for Chinese cities during Jan-March 2020. Besides using these environmental implications, social distancing and wearing a mask are strongly encouraged to maximize the fight against the COVID-19 transmission. At no other time than now are the scientists in various disciplines around the world badly needed by the society to collectively confront this disastrous pandemic.

positive: Air and surface contamination in non-health care settings among 641 environmental specimens of 39 COVID-19 cases Background Little is known about the SARS-CoV-2 contamination of environmental surfaces and air in non-health care settings among COVID-19 cases. Methods and findings We explored the SARS-CoV-2 contamination of environmental surfaces and air by collecting air and swabbing environmental surfaces among 39 COVID-19 cases in Guangzhou, China. The specimens were tested by RT-PCR testing. The information collected for COVID-19 cases included basic demographic, clinical severity, onset of symptoms, radiological testing, laboratory testing and hospital admission. A total of 641 environmental surfaces and air specimens were collected among 39 COVID-19 cases before disinfection. Among them, 20 specimens (20/641, 3.1%) were tested positive from 9 COVID-19 cases (9/39, 23.1%), with 5 (5/101, 5.0%) positive specimens from 3 asymptomatic cases, 5 (5/220, 2.3%) from 3 mild cases, and 10 (10/374, 2.7%) from 3 moderate cases. All positive specimens were collected within 3 days after diagnosis, and 10 (10/42, 23.8%) were found in toilet (5 on toilet bowl, 4 on sink/faucet/shower, 1 on floor drain), 4 (4/21, 19.0%) in anteroom (2 on water dispenser/cup/bottle, 1 on chair/table, 1 on TV remote), 1 (1/8, 12.5%) in kitchen (1 on dining-table), 1 (1/18, 5.6%) in bedroom (1 on bed/sheet pillow/bedside table), 1 (1/5, 20.0%) in car (1 on steering wheel/seat/handlebar) and 3 (3/20, 21.4%) on door knobs. Air specimens in room (0/10, 0.0%) and car (0/1, 0.0%) were all negative. Conclusions SARS-CoV-2 was found on environmental surfaces especially in toilet, and could survive for several days. We provided evidence of potential for SARS-CoV-2 transmission through contamination of environmental surfaces.

positive: Editorial JTH 16 –The Coronavirus Disease COVID-19 and implications for transport and health

positive: Exaggerated risk of transmission of COVID-19 by fomites

positive: Transmission of pathogen-laden expiratory droplets in a coach bus Abstract Droplet dispersion carrying viruses/bacteria in enclosed/crowded buses may induce transmissions of respiratory infectious diseases, but the influencing mechanisms have been rarely investigated. By conducting high-resolution CFD simulations, this paper investigates the evaporation and transport of solid-liquid mixed droplets (initial diameter 10 μm and 50 μm, solid to liquid ratio is 1:9) exhaled in a coach bus with 14 thermal manikins. Five air-conditioning supply directions and ambient relative humidity (RH = 35% and 95%) are considered. Results show that ventilation effectiveness, RH and initial droplet size significantly influence droplet transmissions in coach bus. 50 μm droplets tend to evaporate completely within 1.8 s and 7 s as RH = 35% and 95% respectively, while 0.2 s or less for 10 μm droplets. Thus 10 μm droplets diffuse farther with wider range than 50 μm droplets which tend to deposit more on surfaces. Droplet dispersion pattern differs due to various interactions of gravity, ventilation flows and the upward thermal body plume. The fractions of droplets suspended in air, deposited on wall surfaces are quantified. This study implies high RH, backward supply direction and passengers sitting at nonadjacent seats can effectively reduce infection risk of droplet transmission in buses. Besides taking masks, regular cleaning is also recommended since 85%-100% of droplets deposit on object surfaces.

positive: The intensity of COVID-19 outbreaks is modulated by variation in SARS-CoV-2 free-living survival and environmental transmission COVID-19 has circled the globe, rapidly expanding into a pandemic within a matter of weeks. While early studies revealed important features of SARS-CoV-2 transmission, the role of variation in free-living virus survival in modulating the dynamics of outbreaks remains unclear. Using an empirically determined understanding of SARS-CoV-2 natural history and detailed, country-level case data, we elucidate how variation in free-living virus survival influences key features of COVID-19 epidemics. Our findings suggest that COVID-19’s basic reproductive number ([Formula: see text]) and other key signatures of outbreak intensity are defined by transmission between infected individuals and the environment. Summarizing, we propose that variation in environmental transmission may explain observed differences in disease dynamics from setting to setting, and can inform public health interventions.

positive: SARS-CoV-2 Virulence: Interplay of Floating Virus-Laden Particles, Climate, and Humans With the emergence of COVID-19, it is important to address the possible scenarios of SARS-CoV-2 virulence. Although several researchers have addressed the possible mechanisms of enveloped virus transfection, for example, influenza, here, the relationship between exhaled virus laden-particles, the climate, and transfection probability is discussed by interpreting the findings of prior studies. Importantly, the higher probability of viral transfection in cold and dry public spaces such as near cold shelves of groceries is illustrated. Thus, additional protective measures in such spaces are recommended.

positive: Increasing Temperature and Relative Humidity Accelerates Inactivation of SARS-CoV-2 on Surfaces Coronavirus disease 2019 (COVID-19) was first identified in China in late 2019 and is caused by newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies had reported the stability of SARS-CoV-2 in cell culture media and deposited onto surfaces under a limited set of environmental conditions. Here, we broadly investigated the effects of relative humidity, temperature, and droplet size on the stability of SARS-CoV-2 in a simulated clinically relevant matrix dried on nonporous surfaces. The results show that SARS-CoV-2 decayed more rapidly when either humidity or temperature was increased but that droplet volume (1 to 50 µl) and surface type (stainless steel, plastic, or nitrile glove) did not significantly impact decay rate. At room temperature (24°C), virus half-life ranged from 6.3 to 18.6 h depending on the relative humidity but was reduced to 1.0 to 8.9 h when the temperature was increased to 35°C. These findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and have implications for assessment of the risk posed by surface contamination in indoor environments.IMPORTANCE Mitigating the transmission of SARS-CoV-2 in clinical settings and public spaces is critically important to reduce the number of COVID-19 cases while effective vaccines and therapeutics are under development. SARS-CoV-2 transmission is thought to primarily occur through direct person-to-person transfer of infectious respiratory droplets or through aerosol-generating medical procedures. However, contact with contaminated surfaces may also play a significant role. In this context, understanding the factors contributing to SARS-CoV-2 persistence on surfaces will enable a more accurate estimation of the risk of contact transmission and inform mitigation strategies. To this end, we have developed a simple mathematical model that can be used to estimate virus decay on nonporous surfaces under a range of conditions and which may be utilized operationally to identify indoor environments in which the virus is most persistent.

positive: A field indoor air measurement of SARS-CoV-2 in the patient rooms of the largest hospital in Iran The coronavirus disease 2019 (COVID-19) emerged in Wuhan city, China, in late 2019 and has rapidly spread throughout the world. The major route of transmission of SARS-CoV-2 is in contention, with the airborne route a likely transmission pathway for carrying the virus within indoor environments. Until now, there has been no evidence for detection of airborne severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and this may have implication for the potential spread of the COVID-19. We investigated the air of patient rooms with confirmed COVID-19 in the largest hospital in Iran, on March 17, 2020. To collect the SARS-CoV-2 particles, ten air samples were collected into the sterile standard midget impingers containing 20 mL DMEM with 100 µg/mL streptomycin, 100 U/mL penicillin and 1% antifoam reagent for 1 h. Besides, indoor particle number concentrations, CO2, relative humidity and temperature were recorded throughout the sampling duration. Viral RNA was extracted from samples taken from the impingers and Reverse-Transcription PCR (RT-PCR) was applied to confirm the positivity of collected samples based on the virus genome sequence. Fortunately, in this study all air samples which were collected 2 to 5 m from the patients' beds with confirmed COVID-19 were negative. Despite we indicated that all air samples were negative, however, we suggest further in vivo experiments should be conducted using actual patient cough, sneeze and breath aerosols in order to show the possibility of generation of the airborne size carrier aerosols and the viability fraction of the embedded virus in those carrier aerosols.

positive: An updated min-review on environmental route of the SARS-CoV-2 transmission The risk of newly emerging diseases is constantly present in a world where changes occur significantly in climatic, commercial, and ecological conditions, in addition to the development of biomedical investigations in new situations. An epidemic respiratory disease instigated by a new coronavirus was initially identified in and has resulted in the current global dissemination. This viral strain and its related disease has been termed “SARS-CoV-2” and “coronavirus disease 2019” (abbreviated “COVID-19” or “2019-nCoV”), respectively, which is transmitted simply between individuals. The World Health Organization (WHO) announced the COVID-19 outburst as a pandemic on March 11, which necessitates a cooperative endeavour globally for mitigating the spread of COVID-19. The absence of previous, and minimum present-day information, particularly concerning the path of contagion have precluded the control of this disease. The present article, therefore, describes the SARS-CoV-2 paths of contagion such as drinking water, solid waste, sewer water, ambient air, and the rest of emerging likely paths.

positive: Microbicides and the environmental control of nosocomial viral infections Abstract Viruses are important causes of acute and chronic diseases in humans. Newer viruses are still being discovered and those that are already known are being incriminated in the aetiology of clinical conditions with hitherto unknown causes. Apart from frequently causing infections in the general community, many types of viruses are also significant nosocomial pathogens. While it is generally agreed that we underestimate the proportion of nosocomial infections that are viral, due to a lack of routine monitoring, viruses easily account for more than 30% of the cases of hospital-acquired infections in many paediatric settings. Indeed, the relative importance of viruses in this respect is increasing due to a number of societal and demographic changes as well as alterations in healthcare practices. Safe vaccines against many common nosocomial viral agents are currently unavailable while there is also a virtual lack of effective and affordable chemotherapy against them. There is, therefore, renewed emphasis on preventive strategies by better understanding of the relative importance of various vehicles in the nosocomial spread of viruses and by infection control using microbicides. This, in turn, has stimulated considerable interest in the development of formulations that are not only safer but which also have demonstrated activity against major types of nosocomial viral pathogens. Further, much work is now underway to design better methods to assess the virucidal activity of microbicides used to decontaminate hands, reusable medical devices and environmental surfaces in critical areas of healthcare settings. It is anticipated that these approaches will result in reducing the health and economic impact of nosocomial infections due to viruses.

positive: COVID-19 - Toward a comprehensive understanding of the disease The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a compre-hensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on.

positive: Stability of SARS-CoV-2 on environmental surfaces and in human excreta At room temperature, SARS-CoV-2 was stable on environmental surfaces and remained viable up to 7 days on smooth surfaces. This virus could survive for several hours in feces and 3-4 days in urine.

positive: Factors affecting stability and infectivity of SARS-CoV-2 BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20â¼25oC). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.

positive: Inanimate surfaces as potential source of 2019-nCoV spread and their disinfection with biocidal agents The WHO has declared COVID-19 illness a global health concern which is caused by 2019-nCoV, causing severe respiratory tract infections in humans. Transmissibility among individual to individual have been reported through droplets and probably also via contaminated surfaces and hands. Human coronaviruses can persist on inanimate surfaces such as plastic, glass, fibers and metals up to nine days. 2019-nCoV remains infectious in air for 3 h and on inanimate surfaces such as cardboard, copper, plastic and steel up to 24, 4, 72 and 48 h respectively. Disinfectant activity of various biocidal agents against coronaviruses like ethanol (62–71%), sodium hypochlorite (0.1%) and hydrogen peroxide (0.5%) can be regarded effective against 2019-nCoV as well. As no vaccine and antiviral therapies have been discovered for 2019-nCoV, prevention of further spread will viable option to control the ongoing and future outbreaks.

positive: Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review Abstract Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23°C–25 °C than at 4 °C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.

positive: Factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises Summary The epidemics of severe acute respiratory syndrome (SARS) in 2003 highlighted both short- and long-range transmission routes, i.e. between infected patients and healthcare workers, and between distant locations. With other infections such as tuberculosis, measles and chickenpox, the concept of aerosol transmission is so well accepted that isolation of such patients is the norm. With current concerns about a possible approaching influenza pandemic, the control of transmission via infectious air has become more important. Therefore, the aim of this review is to describe the factors involved in: (1) the generation of an infectious aerosol, (2) the transmission of infectious droplets or droplet nuclei from this aerosol, and (3) the potential for inhalation of such droplets or droplet nuclei by a susceptible host. On this basis, recommendations are made to improve the control of aerosol-transmitted infections in hospitals as well as in the design and construction of future isolation facilities.

positive: Anaesthesia and COVID-19: infection control Summary The world is currently facing an unprecedented healthcare crisis caused by a pandemic novel beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogen is spread by human-to-human transmission via droplets exposure and contact transfer, causing mild symptoms in the majority of cases, but critical illness, bilateral viral pneumonia, and acute respiratory distress syndrome (ARDS) in a minority. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary public healthcare intervention used. The pace of transmission and global scale of SARS-CoV-2 infections has implications for strategic oversight, resource management, and responsiveness in infection control. This article presents a summary of learning points in epidemiological infection control from the SARS epidemic, alongside a review of evidence connecting current understanding of the virologic and environmental contamination properties of SARS-CoV-2. We present suggestions for how personal protective equipment policies relate to the viral pandemic context and how the risk of transmission by and to anaesthetists, intensivists, and other healthcare workers can be minimised.

positive: Sustainability of Coronavirus on different surfaces Abstract COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.

positive: Controls of SARS-CoV-2 transmission in orthodontic practice ABSTRACT The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide concerns because of its high person-to-person infectivity and lethality, and it was labeled as a pandemic as the rapid increase of confirmed cases in most areas around the world became evident. The SARS-CoV-2 is mainly transmitted through respiratory droplets and close contact. There are also evidences of transmission through aerosols and digestive tracts. Since orthodontic treatment involves large population who need routine return-visits, it was significantly affected and suspended because of the COVID-19 pandemic and the shutdown of the dental clinics and hospitals. Although the spread of COVID-19 has been effectively controlled in China and many areas have gradually resumed work and classes, orthodontic participants are still under high risks of SARS-CoV-2 infection. This is due to the asymptomatic carriers of SARS-CoV-2 or patients in the incubation period may cause the cross infection between orthodontic practitioners and patients. The close proximity between the practitioners and the patients, and the generation of droplets and aerosols that contain saliva and blood during treatment further increase the risks of transmission. In this review, we summarized the preventive strategies for controls of SARS-CoV-2 transmission to protect both staffs and patients during the orthodontic practice.

positive: Coronavirus Disease 2019 (COVID-19) and Pregnancy: Responding to a Rapidly Evolving Situation As the world confronts coronavirus disease 2019 (COVID-19), an illness caused by yet another emerging pathogen (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), obstetric care providers are asking what this means for pregnant women. The global spread has been swift, and many key questions remain. The case-fatality rate for persons cared for in the United States and whether asymptomatic persons transmit the virus are examples of questions that need to be answered to inform public health control measures. There are also unanswered questions specific to pregnant women, such as whether pregnant women are more severely affected and whether intrauterine transmission occurs. Although guidelines for pregnant women from the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention have been rapidly developed based on the best available evidence, additional information is critically needed to inform key decisions, such as whether pregnant health care workers should receive special consideration, whether to temporarily separate infected mothers and their newborns, and whether it is safe for infected women to breastfeed. Some current recommendations are well supported, based largely on what we know from seasonal influenza: patients should avoid contact with ill persons, avoid touching their face, cover coughs and sneezes, wash hands frequently, disinfect contaminated surfaces, and stay home when sick. Prenatal clinics should ensure all pregnant women and their visitors are screened for fever and respiratory symptoms, and symptomatic women should be isolated from well women and required to wear a mask. As the situation with COVID-19 rapidly unfolds, it is critical that obstetricians keep up to date.

positive: Lack of SARS-CoV-2 RNA environmental contamination in a tertiary referral hospital for infectious diseases in Northern Italy.

positive: Presence of SARS-CoV-2 RNA in Isolation Ward Environment 28 Days after Exposure

positive: Risk assessment of mixed and displacement ventilation (LAF) during orthopedic and trauma surgery on COVID-19 patients with increased release of infectious aerosols

positive: Coronaviruses widespread on nonliving surfaces: important questions and promising answers The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.

positive: Chapter 8 Transportation and _______ Abstract This chapter examines some topics that have not received as much attention, at least not concerning the potential roles for transportation in mitigating or avoiding public health impacts.

positive: SARS-CoV-2 in wastewater: State of the knowledge and research needs Abstract The ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a Public Health Emergency of International Concern, which was officially declared by the World Health Organization. SARS-CoV-2 is a member of the family Coronaviridae that consists of a group of enveloped viruses with single-stranded RNA genome, some of which have been known to cause common colds. Although the major transmission routes of SARS-CoV-2 are inhalation from person-to-person and aerosol/droplet transmission, currently available evidence indicates that the viral RNA is present in wastewater, suggesting the need to better understand wastewater as potential sources of epidemiological data and human health risks. Here, we review the current knowledge related to the potential of wastewater surveillance to understand the epidemiology of COVID-19, methodologies for the detection and quantification of SARS-CoV-2 in wastewater, and information relevant for human health risk assessment of SARS-CoV-2. There has been growing evidence of gastrointestinal symptoms caused by SARS-CoV-2 infections and the presence of viral RNA not only in feces of COVID-19 patients but in wastewater. One of the major challenges in SARS-CoV-2 detection/quantification in wastewater samples is the lack of an optimized and standardized protocol. Currently available data are also limited for conducting a quantitative microbial risk assessment (QMRA) for SARS-CoV-2 exposure pathways. However, modeling-based approaches have a potential role to play in reducing the impact of the ongoing COVID-19 outbreak, and QMRA parameters obtained from previous studies on relevant respiratory viruses help to inform risk assessments of SARS-CoV-2. Our understanding on the potential role of wastewater in SARS-CoV-2 transmission is largely limited by knowledge gaps in its occurrence, persistence, and removal in wastewater. There is an urgent need for further research to establish methodologies for wastewater surveillance and understand the implications of the presence of SARS-CoV-2 in wastewater.

positive: COVID-19 and climate: global evidence from 117 countries Visual inspection of world maps shows that coronavirus disease 2019 (COVID-19) is less prevalent in countries closer to the equator, where heat and humidity tend to be higher. Scientists disagree how to interpret this observation because the relationship between COVID-19 and climatic conditions may be confounded by many factors. We regress confirmed COVID-19 cases per million inhabitants in a country against the country’s distance from the equator, controlling key confounding factors: air travel, distance to Wuhan, testing intensity, cell phone usage, vehicle concentration, urbanization, and income. A one-degree increase in absolute latitude is associated with a 2.6% increase in cases per million inhabitants (p value <0.001). The Northern hemisphere may see a decline in new COVID-19 cases during summer and a resurgence during winter.

positive: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare and respond to COVID‐19 The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID‐19 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time‐based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short‐ and long‐term interventions to manage outbreaks at the international, national and sub‐national levels in the region. This article is protected by copyright. All rights reserved.

positive: Overview of transnational recommendations for COVID‐19 transmission control in dental care settings On 11 March 2020, the World Health Organization (WHO) declared the coronavirus disease (COVID‐19) caused by severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) as a pandemic. Until an effective treatment or a vaccine is developed, the current recommendations are to contain the disease, and control its transmission. It is now clear that the primary mode of SARS‐CoV‐2 transmission is aerosol/droplet spread, and by contacting virus‐contaminated surfaces acting as fomites (inanimate vectors). Furthermore, recent data indicate that the live virus particles are present in saliva, and, more alarmingly, asymptomatic individuals may transmit the infection. By virtue of the nature of the practice of dentistry where intrinsically, a high volume of aerosols is produced, as well as the close proximity of dentists and patients during treatment, dentists and allied health staff are considered the highest risk health professional group for acquiring SARS‐CoV‐2 during patient management. Therefore, several organizations and specialty associations have proposed guidelines and recommendations for limiting the transmission of SARS‐COV‐2 from carriers to dentists and vice versa. This paper aims to provide a review of these guidelines, and concludes with a brief look at how the practice of dentistry may be impacted by COVID‐19, in the post‐pandemic era.

positive: Optimal temperature zone for the dispersal of COVID-19 It is essential to know the environmental parameters within which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive to understand its global dispersal pattern. We found that 60.0% of the confirmed cases of coronavirus disease 2019 (COVID-19) occurred in places where the air temperature ranged from 5 °C to 15 °C, with a peak in cases at 11.54 °C. Moreover, approximately 73.8% of the confirmed cases were concentrated in regions with absolute humidity of 3 g/m3 to 10 g/m3. SARS-CoV-2 appears to be spreading toward higher latitudes. Our findings suggest that there is an optimal climatic zone in which the concentration of SARS-CoV-2 markedly increases in the ambient environment (including the surfaces of objects). These results strongly imply that the COVID-19 pandemic may spread cyclically and outbreaks may recur in large cities in the mid-latitudes in autumn 2020.

positive: Do established infection prevention and control measures prevent spread of SARS-CoV-2 to the hospital environment beyond the patient room? The role of the hospital environment in the transmission of infection is well described. With an emerging infection whose mode of transmission is under investigation, strict infection prevention and control measures, including patient isolation, hand hygiene, personal protective equipment that is doffed on exiting the patient room, and environmental cleaning should be implemented to prevent spread. Environmental testing demonstrated that COVID-19 patients contaminated the patient area (11/26, 42.3% of tests) but contamination of general ward areas was minimal (1/30, 3%) and the virus was detected after cleaning on one item only (1/25, 4%) which was noted to be in disrepair.

positive: Global implications of bio-aerosol in pandemic

positive: Coronaviruses and SARS-COV-2 Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19’s first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.

positive: Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation. OBJECTIVE The causal agent for SARS is considered as a novel coronavirus that has never been described both in human and animals previously. The stability of SARS coronavirus in human specimens and in environments was studied. METHODS Using a SARS coronavirus strain CoV-P9, which was isolated from pharyngeal swab of a probable SARS case in Beijing, its stability in mimic human specimens and in mimic environment including surfaces of commonly used materials or in household conditions, as well as its resistance to temperature and UV irradiation were analyzed. A total of 10(6) TCID50 viruses were placed in each tested condition, and changes of the viral infectivity in samples after treatments were measured by evaluating cytopathic effect (CPE) in cell line Vero-E6 at 48 h after infection. RESULTS The results showed that SARS coronavirus in the testing condition could survive in serum, 1:20 diluted sputum and feces for at least 96 h, whereas it could remain alive in urine for at least 72 h with a low level of infectivity. The survival abilities on the surfaces of eight different materials and in water were quite comparable, revealing reduction of infectivity after 72 to 96 h exposure. Viruses stayed stable at 4 degrees C, at room temperature (20 degrees C) and at 37 degrees C for at least 2 h without remarkable change in the infectious ability in cells, but were converted to be non-infectious after 90-, 60- and 30-min exposure at 56 degrees C, at 67 degrees C and at 75 degrees C, respectively. Irradiation of UV for 60 min on the virus in culture medium resulted in the destruction of viral infectivity at an undetectable level. CONCLUSION The survival ability of SARS coronavirus in human specimens and in environments seems to be relatively strong. Heating and UV irradiation can efficiently eliminate the viral infectivity.

positive: Decoding the global outbreak of COVID-19: the nature is behind the scene The sudden emergence of SARS-CoV-2 causing the global pandemic is a major public health concern. Though the virus is considered as a novel entity, it is not a completely new member. It is just a new version of previously emerged human SARS corona virus. The rapid evolving nature by changing host body environment and extreme environmental stability, collectively makes SARS-CoV-2 into an extremely virulent genetic variant. The evolution of the virus has been occurred by the continuous process of molecular genetic manipulation, through mutation, deletion and genetic recombinationevents. Different host body environment acts as the supportive system for the pathogen which creates extreme selective pressure. By the process of genetic evolution the pathogen developes new characters. Then the new version of the virus has been naturally selected by susceptible human host and adapt itself inside the host body causing deadly effect. Moreover, extreme environmental stability helps in the process of viral survival outside the host and its transmission. Thus both the host body or internal environment and the external environment performs equally as a source, responsible for shaping the genetic evolution of the SARS-CoV-2 towards theCOVID-19 disease fitness in nature in a pandemic form.

positive: Study on the resistance of severe acute respiratory syndrome-associated coronavirus Abstract In this study, the persistence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) was observed in feces, urine and water. In addition, the inactivation of SARS-CoV in wastewater with sodium hypochlorite and chlorine dioxide was also studied. In vitro experiments demonstrated that the virus could only persist for 2 days in hospital wastewater, domestic sewage and dechlorinated tap water, while 3 days in feces, 14 days in PBS and 17 days in urine at 20°C. However, at 4°C, the SARS-CoV could persist for 14 days in wastewater and at least 17 days in feces or urine. SARS-CoV is more susceptible to disinfectants than Escherichia coli and f2 phage. Free chlorine was found to inactivate SARS-CoV better than chlorine dioxide. Free residue chlorine over 0.5mg/L for chlorine or 2.19mg/L for chlorine dioxide in wastewater ensures complete inactivation of SARS-CoV while it does not inactivate completely E. coli and f2 phage.

positive: Investigating the airborne transmission pathway – different approaches with the same objectives

positive: Being a front-line dentist during the Covid-19 pandemic: a literature review Coronavirus is an enveloped virus with positive-sense single-stranded RNA. Coronavirus infection in humans mainly affects the upper respiratory tract and to a lesser extent the gastrointestinal tract. Clinical symptoms of coronavirus infections can range from relatively mild (similar to the common cold) to severe (bronchitis, pneumonia, and renal involvement). The disease caused by the 2019 novel coronavirus (2019-nCoV) was called Covid-19 by the World Health Organization in February 2020. Face-to-face communication and consistent exposure to body fluids such as blood and saliva predispose dental care workers at serious risk for 2019-nCoV infection. As demonstrated by the recent coronavirus outbreak, information is not enough. During dental practice, blood and saliva can be scattered. Accordingly, dental practice can be a potential risk for dental staff, and there is a high risk of cross-infection. This article addresses all information collected to date on the virus, in accordance with the guidelines of international health care institutions, and provides a comprehensive protocol for managing possible exposure to patients or those suspected of having coronavirus.

positive: Aerodynamic Characteristics and RNA Concentration of SARS-CoV-2 Aerosol in Wuhan Hospitals during COVID-19 Outbreak Background The ongoing outbreak of COVID-19 has spread rapidly and sparked global concern. While the transmission of SARS-CoV-2 through human respiratory droplets and contact with infected persons is clear, the aerosol transmission of SARS-CoV-2 has been little studied. Methods Thirty-five aerosol samples of three different types (total suspended particle, size segregated and deposition aerosol) were collected in Patient Areas (PAA) and Medical Staff Areas (MSA) of Renmin Hospital of Wuhan University (Renmin) and Wuchang Fangcang Field Hospital (Fangcang), and Public Areas (PUA) in Wuhan, China during COVID-19 outbreak. A robust droplet digital polymerase chain reaction (ddPCR) method was employed to quantitate the viral SARS-CoV-2 RNA genome and determine aerosol RNA concentration. Results The ICU, CCU and general patient rooms inside Renmin, patient hall inside Fangcang had undetectable or low airborne SARS-CoV-2 concentration but deposition samples inside ICU and air sample in Fangcang patient toilet tested positive. The airborne SARS-CoV-2 in Fangcang MSA had bimodal distribution with higher concentration than those in Renmin during the outbreak but turned negative after patients number reduced and rigorous sanitization implemented. PUA had undetectable airborne SARS-CoV-2 concentration but obviously increased with accumulating crowd flow. Conclusions Room ventilation, open space, proper use and disinfection of toilet can effectively limit aerosol transmission of SARS-CoV-2. Gathering of crowds with asymptomatic carriers is a potential source of airborne SARS-CoV-2. The virus aerosol deposition on protective apparel or floor surface and their subsequent resuspension is a potential transmission pathway and effective sanitization is critical in minimizing aerosol transmission of SARS-CoV-2.

positive: SARS-CoV-2 infection: the environmental endurance of the virus can be influenced by the increase of temperature The COVID-19 disease, a respiratory disease transmitted by a new betacoronavirus SARS-CoV-2. As for other viral respiratory agents, SARS-CoV-2 spreads by person to person through respiratory droplets and direct contact and potentially by indirect contact through fomites. The goal of the current study is to evaluate whether the increase of temperature can influence the environmental endurance of SARS-CoV-2.We tested SARS-CoV-2 environmental stability in parallel at room temperature (RT, 20-25 Celsius degrees) and at average maximum temperature of June (JT) estimated at 28 Celsius degrees in Italy. The virus inoculated on plastic surface was harvested at predefined time-points and tested to evaluate viral titres on Vero cells by TCID50. Our results confirm that fomite transmission of the emerging SARS-CoV2 is possible, since the virus remains viable on surfaces up to 84 hours at both RT and JT. Moreover, a remarkable difference between the two temperatures exists, suggesting that virus vitality can be influenced by the environmental temperature. Our results support the hypothesis that in the hot season the increase of temperature could influence the environmental endurance of SARS-CoV2 and reduce Covid-19 transmission probability.

positive: Survival of Severe Acute Respiratory Syndrome Coronavirus Background. The primary modes of transmission of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) appear to be direct mucus membrane contact with infectious droplets and through exposure to formites. Knowledge of the survival characteristics of the virus is essential for formulating appropriate infection-control measures. Methods. Survival of SARS-CoV strain GVU6109 was studied in stool and respiratory specimens. Survival of the virus on different environmental surfaces, including a laboratory request form, an impervious disposable gown, and a cotton nondisposable gown, was investigated. The virucidal effects of sodium hypochlorite, house detergent, and a peroxygen compound (Virkon S; Antec International) on the virus were also studied. Results. SARS-CoV GVU6109 can survive for 4 days in diarrheal stool samples with an alkaline pH, and it can remain infectious in respiratory specimens for >7 days at room temperature. Even at a relatively high concentration (10(4) tissue culture infective doses/mL), the virus could not be recovered after drying of a paper request form, and its infectivity was shown to last longer on the disposable gown than on the cotton gown. All disinfectants tested were shown to be able to reduce the virus load by >3 log within 5 min. Conclusions. Fecal and respiratory samples can remain infectious for a long period of time at room temperature. The risk of infection via contact with droplet-contaminated paper is small. Absorbent material, such as cotton, is preferred to nonabsorptive material for personal protective clothing for routine patient care where risk of large spillage is unlikely. The virus is easily inactivated by commonly used disinfectants.

positive: Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1 A novel human coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to as HCoV-19 here) that emerged in Wuhan, China in late 2019 is now causing a pandemic. Here, we analyze the aerosol and surface stability of HCoV-19 and compare it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of HCoV-19 and SARS-CoV-1 in aerosols and on different surfaces and estimated their decay rates using a Bayesian regression model

positive: Aerosol-generating otolaryngology procedures and the need for enhanced PPE during the COVID-19 pandemic: a literature review BACKGROUND: Adequate personal protective equipment is needed to reduce the rate of transmission of COVID-19 to health care workers. Otolaryngology groups are recommending a higher level of personal protective equipment for aerosol-generating procedures than public health agencies. The objective of the review was to provide evidence that a.) demonstrates which otolaryngology procedures are aerosol-generating, and that b.) clarifies whether the higher level of PPE advocated by otolaryngology groups is justified. MAIN BODY: Health care workers in China who performed tracheotomy during the SARS-CoV-1 epidemic had 4.15 times greater odds of contracting the virus than controls who did not perform tracheotomy (95% CI 2.75–7.54). No other studies provide direct epidemiological evidence of increased aerosolized transmission of viruses during otolaryngology procedures. Experimental evidence has shown that electrocautery, advanced energy devices, open suctioning, and drilling can create aerosolized biological particles. The viral load of COVID-19 is highest in the upper aerodigestive tract, increasing the likelihood that aerosols generated during procedures of the upper aerodigestive tract of infected patients would carry viral material. Cough and normal breathing create aerosols which may increase the risk of transmission during outpatient procedures. A significant proportion of individuals infected with COVID-19 may not have symptoms, raising the likelihood of transmission of the disease to inadequately protected health care workers from patients who do not have probable or confirmed infection. Powered air purifying respirators, if used properly, provide a greater level of filtration than N95 masks and thus may reduce the risk of transmission. CONCLUSION: Direct and indirect evidence suggests that a large number of otolaryngology-head and neck surgery procedures are aerosol generating. Otolaryngologists are likely at high risk of contracting COVID-19 during aerosol generating procedures because they are likely exposed to high viral loads in patients infected with the virus. Based on the precautionary principle, even though the evidence is not definitive, adopting enhanced personal protective equipment protocols is reasonable based on the evidence. Further research is needed to clarify the risk associated with performing various procedures during the COVID-19 pandemic, and the degree to which various personal protective equipment reduces the risk.

positive: Characterization of infectious aerosols in health care facilities: An aid to effective engineering controls and preventive strategies()()() Assessment of strategies for engineering controls for the prevention of airborne infectious disease transmission to patients and to health care and related workers requires consideration of the factors relevant to aerosol characterization. These factors include aerosol generation, particle sizes and concentrations, organism viability, infectivity and virulence, airflow and climate, and environmental sampling and analysis. The major focus on attention to engineering controls comes from recent increases in tuberculosis, particularly the multidrug-resistant varieties in the general hospital population, the severely immunocompromised, and those in at-risk and confined environments such as prisons, long-term care facilities, and shelters for the homeless. Many workers are in close contact with persons who have active, undiagnosed, or insufficiently treated tuberculosis. Additionally, patients and health care workers may be exposed to a variety of pathogenic human viruses, opportunistic fungi, and bacteria. This report therefore focuses on the nature of infectious aerosol transmission in an attempt to determine which factors can be systematically addressed to result in proven, applied engineering approaches to the control of infectious aerosols in hospital and health care facility environments. The infectious aerosols of consideration are those that are generated as particles of respirable size by both human and environmental sources and that have the capability of remaining viable and airborne for extended periods in the indoor environment. This definition precludes skin and mucous membrane exposures occurring from splashes (rather than true aerosols) of blood or body fluids containing infectious disease agents. There are no epidemiologic or laboratory studies documenting the transmission of bloodborne virus by way of aerosols. (AJIC Am J Infect Control 1998;26:453-64)

positive: Survival of surrogate coronaviruses in water Abstract The emergence of a previously unknown coronavirus infection, Severe Acute Respiratory Syndrome (SARS), demonstrated that fecally contaminated liquid droplets are a potential vehicle for the spread of a respiratory virus to large numbers of people. To assess potential risks from this pathway, there is a need for surrogates for SARS coronavirus to provide representative data on viral survival in contaminated water. This study evaluated survival of two surrogate coronaviruses, transmissible gastroenteritis (TGEV) and mouse hepatitis (MHV). These viruses remained infectious in water and sewage for days to weeks. At 25°C, time required for 99% reduction in reagent-grade water was 22 days for TGEV and 17 days for MHV. In pasteurized settled sewage, times for 99% reduction were 9 days for TGEV and 7 days for MHV. At 4°C, there was <1log10 infectivity decrease for both viruses after four weeks. Coronaviruses can remain infectious for long periods in water and pasteurized settled sewage, suggesting contaminated water is a potential vehicle for human exposure if aerosols are generated.

positive: Textile Masks and Surface Covers—A Spray Simulation Method and a “Universal Droplet Reduction Model” Against Respiratory Pandemics The main form of COVID-19 transmission is via “oral-respiratory droplet contamination” (droplet: very small drop of liquid) produced when individuals talk, sneeze, or cough. In hospitals, health-care workers wear facemasks as a minimum medical “droplet precaution” to protect themselves. Due to the shortage of masks during the pandemic, priority is given to hospitals for their distribution. As a result, the availability/use of medical masks is discouraged for the public. However, for asymptomatic individuals, not wearing masks in public could easily cause the spread of COVID-19. The prevention of “environmental droplet contamination” (EnvDC) from coughing/sneezing/speech is fundamental to reducing transmission. As an immediate solution to promote “public droplet safety,” we assessed household textiles to quantify their potential as effective environmental droplet barriers (EDBs). The synchronized implementation of a universal “community droplet reduction solution” is discussed as a model against COVID-19. Using a bacterial-suspension spray simulation model of droplet ejection (mimicking a sneeze), we quantified the extent by which widely available clothing fabrics reduce the dispersion of droplets onto surfaces within 1.8 m, the minimum distance recommended for COVID-19 “social distancing.” All textiles reduced the number of droplets reaching surfaces, restricting their dispersion to <30 cm, when used as single layers. When used as double-layers, textiles were as effective as medical mask/surgical-cloth materials, reducing droplet dispersion to <10 cm, and the area of circumferential contamination to ~0.3%. The synchronized implementation of EDBs as a “community droplet reduction solution” (i.e., face covers/scarfs/masks and surface covers) will reduce COVID-19 EnvDC and thus the risk of transmitting/acquiring COVID-19.

positive: Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23°C-25 °C than at 4 °C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.

positive: Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: A global health emergency According to data compiled by researchers at Johns Hopkins University in Baltimore, Maryland, more than two and half million cases of coronavirus disease 2019 (COVID-19), caused by a newly discovered virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed on April 20, 2020 (Nature, 2020b). Since the emergence of this infectious disease in Asia (Wuhan, China) late last year, it has been subsequently span to every continent of the world except Antarctica (Rodríguez-Morales et al., 2020). Along with a foothold in every country, the current disease pandemic is disrupting practically every aspect of life all over the world. As the outbreak are continuing to evolve, several research activities have been conducted for better understanding the origin, functions, treatments, and preventions of this novel coronavirus. This review will be a summa of the key features of novel coronavirus (nCoV), the virus causing disease 2019 and the present epidemic situation worldwide up to April 20, 2020. It is expected that this record will play an important role to take more preventive measures for overcoming the challenges faced during this current pandemic.

positive: Severe acute respiratory syndrome coronavirus 2 RNA contamination of inanimate surfaces and virus viability in a health care emergency unit OBJECTIVES: To detect possible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination of inanimate surfaces in areas at high risk of aerosol formation by patients with coronavirus disease 2019 (COVID-19). METHODS: Sampling was performed in the emergency unit and the sub-intensive care ward. SARS-CoV-2 RNA was extracted from swabbed surfaces and objects and subjected to real-time RT-PCR targeting RNA-dependent RNA polymerase and E genes. Virus isolation from positive samples was attempted in vitro on Vero E6 cells. RESULTS: Twenty-six samples were collected and only two were positive for low-level SARS-CoV-2 RNA, both collected on the external surface of continuous positive airway pressure helmets. All transport media were inoculated onto susceptible cells, but none induced a cytopathic effect on day 7 of culture. CONCLUSIONS: Even though daily contact with inanimate surfaces and patient fomites in contaminated areas may be a medium of infection, our data obtained in real-life conditions suggest that it might be less extensive than hitherto recognized.

positive: SARS-CoV-2 spread in Northern Italy: what about the pollution role? The recent epidemic of the new SARS-CoV-2 in the northern regions of Italy is putting the organization of the Italian health system under serious attack. The current emergency requires all possible efforts to stem the spread of the virus. In this context, it is clear that we have the urgent need to rely upon etiopathogenetic data, in order to do all possible efforts to block the epidemic. However, observing the trend of the infections in China and the geographic areas of the main outbreaks, it could be hypothesized that air pollution plays a role. In particular, it has been previously demonstrated, in specific populations, a role of particulate matter in worsening clinical presentation of virus infection in airways. Without prejudice to the ascertained virus spread by air droplets or contaminated surfaces, the factors that could have favored its spread remain to be investigated. Moreover, if these observations were to be confirmed, when the health emergency is resolved, it will be mandatory to redesign an economic-productive model in balance with the environment.

positive: Infection Control in Dental Practice During the COVID-19 Pandemic. COVID-19 is the disease supported by SARS-CoV-2 infection, which causes a severe form of pneumonia. Due to the pathophysiological characteristics of the COVID-19 syndrome, the particular transmissibility of SARS-CoV-2, and the high globalization of our era, the epidemic emergency from China has spread rapidly all over the world. Human-to-human transmission seems to occur mainly through close contact with symptomatic people affected by COVID-19, and the main way of contagion is via the inhalation of respiratory droplets, for example when patients talk, sneeze or cough. The ability of the virus to survive outside living organisms, in aerosol or on fomites has also been recognized. The dental practitioners are particularly exposed to a high risk of SARS-CoV-2 infection because they cannot always respect the interpersonal distance of more than a meter and are exposed to saliva, blood, and other body fluids during surgical procedures. Moreover, many dental surgeries can generate aerosol, and the risk of airborne infection is to be considered higher. The aim of this paper is to provide practical advice for dentists based on the recent literature, which may be useful in reducing the risk of spreading COVID-19 during clinical practice.

positive: Coronavirus Infection in Cats Cats are susceptible to natural infection with several strains of feline coronavirus that result in either effusive and noneffusive feline infectious peritonitis or enteritis. Excretion of coronavirus by infected cats into the environment occurs by way of feces, oronasal secretions, and possibly urine. Clinical diagnosis of coronavirus infection is made by evaluating the case history, physical findings, laboratory results, and coronavirus antibody titers as well as ruling out analogous diseases. An intranasal temperature-sensitive feline infectious peritonitis coronavirus vaccine is available for use in healthy cats 16 weeks of age or older.

positive: Distributions and risks of SARS-CoV-2 in hospital outdoor environment The outbreak of coronavirus infectious disease-2019 (COVID-19) pneumonia since 2019 has rapidly spread throughout over 200 countries around the world. Till 14th May 2020, there are over 4 million confirmed cases and 300,000 deaths globally. To date, numerous studies focus on the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in indoor areas for its main transmission routes via human respiratory droplets and direct contact. It remains unclear about the distribution and transmission risks of SARS-CoV-2 in outdoor environment despite its threats to healthy people and communities. Here, we investigated the presence of SARS-CoV-2 virus in 73 specimens from outdoor environment of three hospitals in Wuhan. We found SARS-CoV-2 in soils (205-550 copies/g), wastewaters (255 to 1.9x104 copies/L) and aerosols (285-1130 copies/m3) in locations close to departments receiving COVID-19 patients or in wastewater treatment sectors, which revealed significant viral spill-over in hospital outdoor environment that was possibly via respiratory droplets from patients or airborne aerosols from wastewater containing SARS-CoV-2. In contrast, SARS-CoV-2 was not detected in other areas or on surfaces with regular disinfection. Soils eventually behave as viral receptors through deposition and potentially a secondary source spreading SARS-CoV-2 for a prolonged time. Our findings map the high-risk areas in hospital outdoor environment possessing spread risks of SARS-CoV-2, which require particular attention and complete sanitation for preventing SARS-CoV-2 outdoor transmission.

positive: Efficacy of various disinfectants against SARS coronavirus Summary The recent severe acute respiratory syndrome (SARS) epidemic in Asia and Northern America led to broad use of various types of disinfectant in order to control the public spread of the highly contagious virus. However, only limited data were available to demonstrate their efficacy against SARS coronavirus (SARS-CoV). We therefore investigated eight disinfectants for their activity against SARS-CoV according to prEN 14476. Four hand rubs were tested at 30s (Sterillium, based on 45% iso-propanol, 30% n-propanol and 0.2% mecetronium etilsulphate; Sterillium Rub, based on 80% ethanol; Sterillium Gel, based on 85% ethanol; Sterillium Virugard, based on 95% ethanol). Three surface disinfectants were investigated at 0.5% for 30min and 60min (Mikrobac forte, based on benzalkonium chloride and laurylamine; Kohrsolin FF, based on benzalkonium chloride, glutaraldehyde and didecyldimonium chloride; Dismozon pur, based on magnesium monoperphthalate), and one instrument disinfectant was investigated at 4% for 15min, 3% for 30min and 2% for 60min [Korsolex basic, based on glutaraldehyde and (ethylenedioxy)dimethanol]. Three types of organic load were used: 0.3% albumin, 10% fetal calf serum, and 0.3% albumin with 0.3% sheep erythrocytes. Virus titres were determined by a quantitative test (endpoint titration) in 96-well microtitre plates. With all tested preparations, SARS-CoV was inactivated to below the limit of detection (reduction factor mostly ≥4), regardless of the type of organic load. In summary, SARS-CoV can be inactivated quite easily with many commonly used disinfectants.

positive: Current knowledge of COVID-19 and infection prevention and control strategies in healthcare settings: A global analysis OBJECTIVE: In the current absence of a vaccine for COVID-19, public health responses aim to break the chain of infection by focusing on the mode of transmission. We reviewed the current evidence on the transmission dynamics and on pathogenic and clinical features of COVID-19 to critically identify any gaps in the current infection prevention and control (IPC) guidelines. METHODS: In this study, we reviewed global COVID-19 IPC guidelines by organizations such as the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC). Guidelines from 2 high-income countries (Australia and United Kingdom) and from 1 middle-income country (China) were also reviewed. We searched publications in English on ‘PubMed’ and Google Scholar. We extracted information related to COVID-19 transmission dynamics, clinical presentations, and exposures that may facilitate transmission. We then compared these findings with the recommended IPC measures. RESULTS: Nosocomial transmission of SARS-CoV-2 in healthcare settings occurs through droplets, aerosols, and the oral–fecal or fecal–droplet route. However, the IPC guidelines fail to cover all transmission modes, and the recommendations also conflict with each other. Most guidelines recommend surgical masks for healthcare providers during routine care and N95 respirators for aerosol-generating procedures. However, recommendations regarding the type of face mask varied, and the CDC recommends cloth masks when surgical masks are unavailable. CONCLUSION: IPC strategies should consider all the possible routes of transmission and should target all patient care activities involving risk of person-to-person transmission. This review may assist international health agencies in updating their guidelines.

positive: SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes.

positive: Electrostatic Charged Nanofiber Filter for Filtering Airborne Novel Coronavirus (COVID-19) and Nano-aerosols Abstract The World Health Organization declared the novel coronavirus (COVID-19) outbreak as a pandemic on March 12, 2020. Within 3-1/2 months since outbreak in December 2019, over 1.3 million people have been infected across 206 countries with over 70,000 deaths. COVID-19 has a size of 60-140nm with mean size of the nano-aerosols, 100nm. The virus can be airborne by attaching to human secretion (fine particles, nasal/saliva droplets) of infected person or suspended fine particulates in air. While NIOSH has standardized N95 and N98 at 300nm, to-date there is no filter standards, nor special filter technologies, tailored for capturing airborne viruses and 100nm nano-aerosols. The latter also are present in high number concentration in atmospheric pollutants. This study addresses developing novel charged PVDF nanofiber filter technology to effectively capture the deadly airborne coronavirus with our target set at 100nm (nano-aerosol), and not 300nm. The virus and its attached particle were simulated by sodium chloride aerosols, 50-500nm, generated from sub-micron aerosol generator. PVDF nanofibers were produced with fiber diameters 84, 191, 349 and 525nm with excellent morphology. The fibers were subsequently charged by corona discharge. The amounts of charged fibers in a filter were increased to achieve high efficiency of 90% for the virus filter but the electrical interference between neighbouring fibers resulted in progressively marginal increase in efficiency and concurrently much higher pressure drop across the filter. The quality factor which measured the efficiency-to-pressure-drop kept decreasing. By redistributing the fibers in the filter into several modules, each separated by a permeable scrim material, the electrical interference was reduced, if not fully mitigated. Also, the additional scrim materials introduced macropores into the filter that further reduced the airflow resistance. With this approach, the quality factor can maintain relatively constant with increasing fiber amounts to achieve high filter efficiency. The optimal amounts of fiber in each module depended on the diameter of fibers in the module. Small fiber diameter that has already high performance required small amount of fibers per module. In contrast, large diameter fiber required more amounts of fiber per module to compensate for the poorer performance without incurring higher pressure drop. This approach was applied to develop four new nanofiber filters tailored for capturing 100nm airborne COVID-19 to achieve over 90% efficiency with pressure drop below 30Pa (3.1mm water). One filter developed meeting the 90% efficiency has ultralow pressure drop of only 18Pa (1.9mm water) while another filter meeting the 30Pa limit has high efficiency reaching 94%. These optimized filters based on rigorous engineering approach provide the badly needed technology for protecting the general public from the deadly airborne COVID-19 and other viruses, and nano-aerosols from air pollution which lead to chronic diseases.

positive: Transmission of SARS-CoV-2 via fecal-oral and aerosols–borne routes: Environmental dynamics and implications for wastewater management in underprivileged societies Abstract The advent of novel human coronavirus (SARS-CoV-2) and its potential transmission via fecal-oral and aerosols-borne routes are upcoming challenges to understand the fate of the virus in the environment. In this short communication, we specifically looked at the possibilities of these transmission routes based on the available literature directly related to the SARS-CoV-2 as well as on the closer phylogenetic relatives such as SARS-CoV-1. The available data suggest that, in addition to human-to-human contact, the virus may spread via fecal-oral and aerosols-borne routes. Existing knowledge states that coronaviruses have low stability in the environment due to the natural action of oxidants that disrupt the viral envelope. Previous recommended dosage of chlorination has been found to be not sufficient to inactivate SARS-CoV-2 in places where viral load is high such as hospitals and airports. Although there is no current evidence showing that coronaviruses can be transmitted through contaminated drinking water, there is a growing concern on the impact of the current pandemic wave on underprivileged societies because of their poor wastewater treatment infrastructures, overpopulation, and outbreak management strategies. More research is encouraged to trace the actual fate of SARS-CoV-2 in the environment and to develop/revise the disinfection strategies accordingly.

positive: Coronavirus survival on healthcare personal protective equipment.

positive: An overview of coronaviruses including the SARS-2 coronavirus – Molecular biology, epidemiology and clinical implications Abstract Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.

positive: What do we know about the SARS-CoV-2 coronavirus in the environment? In view of the current situation regarding the Covid-19 disease, a discussion is proposed on the need for research focusing on the presence and evolution of the SARS-CoV-2 virus in water, soils and other environmental compartments, reached through wastewater and sewage sludge spreading. Also, the evaluation of current treatments for wastewater and sewage sludge, as well as the eventual development of new specific techniques, based on sorption, nanotechnology, etc., would be of great interest for controlling the environmental dissemination of these viruses in the current and eventual future outbreaks.

positive: Assessing the relationship between surface levels of PM2.5 and PM10 particulate matter impact on COVID-19 in Milan, Italy The novel coronavirus disease (COVID-19) is a highly pathogenic, transmittable and invasive pneumococcal disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which emerged in December 2019 and January 2020 in Wuhan city, Hubei province, China and fast spread later on the middle of February 2020 in the Northern part of Italy and Europe. This study investigates the correlation between the degree of accelerated diffusion and lethality of COVID-19 and the surface air pollution in Milan metropolitan area, Lombardy region, Italy. Daily average concentrations of inhalable particulate matter (PM) in two size fractions PM2.5, PM10 and maxima PM10 ground level atmospheric pollutants together air quality and climate variables (daily average temperature, relative humidity, wind speed, atmospheric pressure field and Planetary Boundary Layer-PBL height) collected during 1 January-30 April 2020 were analyzed. In spite of being considered primarily transmitted by indoor bioaerosols droplets and infected surfaces, or direct human-to-human personal contacts, it seems that high levels of urban air pollution, weather and specific climate conditions have a significant impact on the increased rates of confirmed COVID-19 Total number, Daily New and Total Deaths cases, possible attributed not only to indoor but also to outdoor airborne bioaerosols distribution. Our analysis demonstrates the strong influence of daily averaged ground levels of particulate matter concentrations, positively associated with average surface air temperature and inversely related to air relative humidity on COVID-19 cases outbreak in Milan. Being a novel pandemic coronavirus (SARS-CoV-2) version, COVID-19 might be ongoing during summer conditions associated with higher temperatures and low humidity levels. Presently is not clear if this protein "spike" of the new coronavirus COVID-19 is involved through attachment mechanisms on indoor or outdoor airborne aerosols in the infectious agent transmission from a reservoir to a susceptible host in some agglomerated urban areas like Milan is.

positive: Soft matter science and the COVID-19 pandemic Much of the science underpinning the global response to the COVID-19 pandemic lies in the soft matter domain. Coronaviruses are composite particles with a core of nucleic acids complexed to proteins surrounded by a protein-studded lipid bilayer shell. A dominant route for transmission is via air-borne aerosols and droplets. Viral interaction with polymeric body fluids, particularly mucus, and cell membranes control their infectivity, while their interaction with skin and artificial surfaces underpins cleaning and disinfection and the efficacy of masks and other personal protective equipment. The global response to COVID-19 has highlighted gaps in the soft matter knowledge base. We survey these gaps and suggest questions that can (and need to) be tackled, both in response to COVID-19 and to better prepare for future viral pandemics.

positive: Spread of SARS-CoV-2 Coronavirus likely to be constrained by climate As new cases of COVID-19 are being confirmed pressure is mounting to increase understanding of the factors underlying the spread the disease. Using data on local transmissions until the 23rd of March 2020, we develop an ensemble of 200 ecological niche models to project monthly variation in climate suitability for spread of SARS-CoV-2 throughout a typical climatological year. Although cases of COVID-19 are reported all over the world, most outbreaks display a pattern of clustering in relatively cool and dry areas. The predecessor SARS-CoV-1 was linked to similar climate conditions. Should the spread of SARS CoV-2 continue to follow current trends, asynchronous seasonal global outbreaks could be expected. According to the models, temperate warm and cold climates are more favorable to spread of the virus, whereas arid and tropical climates are less favorable. However, model uncertainties are still high across much of sub- Saharan Africa, Latin America and South East Asia. While models of epidemic spread utilize human demography and mobility as predictors, climate can also help constrain the virus. This is because the environment can mediate human-to-human transmission of SARS-CoV-2, and unsuitable climates can cause the virus to destabilize quickly, hence reducing its capacity to become epidemic.

positive: Physiotherapy management for COVID-19 in the acute hospital setting: clinical practice recommendations Abstract This document outlines recommendations for physiotherapy management for COVID-19 in the acute hospital setting. It includes: recommendations for physiotherapy workforce planning and preparation; a screening tool for determining requirement for physiotherapy; and recommendations for the selection of physiotherapy treatments and personal protective equipment. It is intended for use by physiotherapists and other relevant stakeholders in the acute care setting caring for adult patients with confirmed or suspected COVID-19.

positive: Indoor transmission of SARS-CoV-2 Background: By early April 2020, the COVID-19 pandemic had infected nearly one million people and had spread to nearly all countries worldwide. It is essential to understand where and how SARS-CoV-2 is transmitted. Methods: Case reports were extracted from the local Municipal Health Commissions of 320 prefectural cities (municipalities) in China, not including Hubei province, between 4 January and 11 February 2020. We identified all outbreaks involving three or more cases and reviewed the major characteristics of the enclosed spaces in which the outbreaks were reported and associated indoor environmental issues. Results: Three hundred and eighteen outbreaks with three or more cases were identified, involving 1245 confirmed cases in 120 prefectural cities. We divided the venues in which the outbreaks occurred into six categories: homes, transport, food, entertainment, shopping, and miscellaneous. Among the identified outbreaks, 53.8% involved three cases, 26.4% involved four cases, and only 1.6% involved ten or more cases. Home outbreaks were the dominant category (254 of 318 outbreaks; 79.9%), followed by transport (108; 34.0%; note that many outbreaks involved more than one venue category). Most home outbreaks involved three to five cases. We identified only a single outbreak in an outdoor environment, which involved two cases. Conclusions: All identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk.

positive: Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London Objectives: To evaluate SARS-CoV-2 surface and air contamination during the peak of the COVID-19 pandemic in London. Design: Prospective cross-sectional observational study. Setting: An acute NHS healthcare provider. Participants: All inpatient wards were fully occupied by patients with COVID-19 at the time of sampling. Interventions: Air and surface samples were collected from a range of clinical areas and a public area of the hospital. An active air sampler was used to collect three or four 1.0 m3 air samples in each area. Surface samples were collected by swabbing approximately 25 cm2 of items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture using Vero E6 and Caco2 cells; additionally the limit of detection for culturing SARS-CoV-2 dried onto surfaces was determined. Main outcome measures: SARS-CoV-2 detected by PCR or culture. Results: Viral RNA was detected on 114/218 (52.3%) of surface and 14/31 (38.7%) air samples but no virus was cultured. The proportion of surface samples contaminated with viral RNA varied by item sampled and by clinical area. Viral RNA was detected on surfaces and in air in public areas of the hospital but was more likely to be found in areas immediately occupied by COVID-19 patients (67/105 (63.8%) in areas immediately occupied by COVID-19 patients vs. 29/64 (45.3%) in other areas (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Fishers exact test). The PCR Ct value for all surface and air samples (>30) indicated a viral load that would not be culturable. Conclusions: Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from surface and air contamination in managing COVID-19, and the need for effective use of PPE, social distancing, and hand/surface hygiene.

positive: Severe acute respiratory syndrome (SARS) in intensive care units (ICUs): limiting the risk to healthcare workers Abstract The global epidemic of severe acute respiratory syndrome (SARS) during the first half of 2003 resulted in over 8000 cases with more than 800 deaths. Many of those who eventually died, did so in the critical (intensive) care units of various hospitals around the world, and many secondary cases of SARS arose in healthcare workers looking after such patients in these units. Research on SARS coronavirus (SARS CoV) demonstrated that this virus belongs to the same family of viruses, the Coronaviridae that causes the common cold, with some important differences. Properties of this virus have been discovered which can be used to develop important infection control policies within hospitals to limit the number of secondary cases. These properties include environmental survival, transmissibility, viral load in various organs and fluids and periods of symptomatic illness during which infectivity is greatest. Various barrier methods were used throughout the epidemic to protect healthcare workers from SARS, with varying degrees of success. Treatment of SARS patients has mainly involved steroid therapy, with or without ribavirin, but there is no consensus on the best treatment protocol, as yet. This review focuses on the implications of SARS for healthcare workers and patients on critical care units.

positive: How long can nosocomial pathogens survive on textiles? A systematic review Aims: Healthcare-associated infections linked to contaminated textiles are rare but underline their potential role as a source for transmission. The aim of the review was to summarize the experimental evidence on the survival and persistence of the different types of nosocomial pathogens on textiles. Methods: A literature search was performed on MedLine. Original data on the survival of bacteria, mycobacteria, and fungi and persistence of viruses on textiles were evaluated. Results: The survival of bacteria at room temperature was the longest on polyester (up to 206 days), whereas it was up to 90 days for some species on cotton and mixed fibers. Only low inocula of 100 CFU were found on all types of textiles with a short survival time of ≤3 days. Most bacterial species survived better at elevated air humidity. The infectivity of viruses on textiles is lost much faster at room temperature, typically within 2–4 weeks. Conclusions: Contaminated textiles or fabrics may be a source of transmission for weeks. The presence of pathogens on the coats of healthcare workers is associated with the presence of pathogens on their hands, demonstrating the relevance of textile contamination in patient care.

positive: Pathogen survival in the external environment and the evolution of virulence Recent studies have provided evolutionary explanations for much of the variation in mortality among human infectious diseases. One gap in this knowledge concerns respiratory tract pathogens transmitted from person to person by direct contact or through environmental contamination. The sit‐and‐wait hypothesis predicts that virulence should be positively correlated with durability in the external environment because high durability reduces the dependence of transmission on host mobility. Reviewing the epidemiological and medical literature, we confirm this prediction for respiratory tract pathogens of humans. Our results clearly distinguish a high‐virulence high‐survival group of variola (smallpox) virus, Mycobacterium tuberculosis, Corynebacterium diphtheriae, Bordetella pertussis, Streptococcus pneumoniae, and influenza virus (where all pathogens have a mean percent mortality 0.01% and mean survival time >10 days) from a low‐virulence low‐survival group containing ten other pathogens. The correlation between virulence and durability explains three to four times of magnitude of difference in mean percent mortality and mean survival time, using both across‐species and phylogenetically controlled analyses. Our findings bear on several areas of active research and public health policy: (1) many pathogens used in the biological control of insects are potential sit‐and‐wait pathogens as they combine three attributes that are advantageous for pest control: high virulence, long durability after application, and host specificity; (2) emerging pathogens such as the‘hospital superbug’methicillin‐resistant Staphylococcus aureus (MRSA) and potential bioweapons pathogens such as smallpox virus and anthrax that are particularly dangerous can be discerned by quantifying their durability; (3) hospital settings and the AIDS pandemic may provide footholds for emerging sit‐and‐wait pathogens; and (4) studies on food‐borne and insect pathogens point to future research considering the potential evolutionary trade‐offs and genetic linkages between virulence and durability.

positive: Coronavirus disease 2019 (COVID-19): A literature review Abstract In early December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan City, Hubei Province, China. On January 30, 2020 the World Health Organization declared the outbreak as a Public Health Emergency of International Concern. As of February 14, 2020, 49,053 laboratory-confirmed and 1,381 deaths have been reported globally. Perceived risk of acquiring disease has led many governments to institute a variety of control measures. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In this literature review, the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and preventions strategies are all reviewed.

positive: Protection of Upper Respiratory Tract, Mouth and Eyes Pathogenic bacteria and viruses may invade via upper and lower respiratory tract and via eye mucosa. When an infected person coughs or sneezes heavily, small, invisible droplets with the infective agent may reach a good distance from the source. By using the right form of protection at the right time, infection and disease are prevented. The present chapter is focused on the protection against airborne infections.

positive: Ozone Treatment for Elimination of Bacteria and SARS-CoV-2 for Medical Environments Pathogenic bacteria and viruses in medical environments can lead to treatment complications and hospital-acquired infections (HAIs), and current cleaning protocols do not address hard-to-access areas or that may be beyond line-of-sight treatment such as with ultraviolet radiation. At the time of writing, the ongoing pandemic of the novel coronavirus known as novel coronavirus (2019-nCoV) has claimed over 4 million cases worldwide and is expected to have multiple peaks, with possible resurgences throughout 2020. It is therefore imperative that disinfection methods in the meantime be employed to keep up with the supply of personal protective equipment (PPE) and sterilize a wide array of surfaces as quarantine lockdowns begin to be lifted. Here, we tested the efficacy of Sani Sport ozone devices as a means to treat hospital equipment and surfaces for killing bacteria, degrading synthetic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, and RNA from non-replicative capsid enclosed SARS-CoV-2. We observed a rapid killing of medically-relevant and environmental bacteria (Escherichia coli, Enterococcus faecalis, Bacillus subtlis, and Deinococcus radiodurans) across four surfaces (blankets, catheter, remotes, and syringes) within 30 minutes, and up to a 99% reduction in viable bacteria at the end of 2-hour treatment cycles. Significant RNA degradation of synthetic SARS-CoV-2 RNA was seen an hour into the ozone treatment as compared to non-treated controls and a non-replicative form of the virus was shown to have significant RNA degradation at 30 minutes compared to a no treatment control and RNA degradation could be reliably detected at 10,000 and 1,000 copies of virus per sample. These results show the strong promise of ozone treatment for reducing risk of infection and HAIs.

positive: Disinfection of Endoscopy and Reusability of Accessories Corona viruses are a group of medium-sized positive-sense single-stranded RNA viruses with crown-like structure due to projections noted over the surface of the virus. The infection has been declared as a pandemic by the world health organization (WHO) in March 2020. Health care professionals in endoscopy are at high risk of infection by novel corona virus disease 2019 (COVID-19) from inhalation of droplets, conjunctival contact, feces, and touch contamination. Upper gastrointestinal (GI) endoscopy is considered to be a high-risk aerosol-generating procedures (AGPs) and the live virus has been found in patient stool. Flexible endoscopes when contaminated have been considered as the vector for transmission of infections. Infections related to the side viewing endoscopes and endoscopic ultrasound scopes are more frequent than upper GI scope and colonoscopes. Stratifying patients needing endoscopy and deferral of elective procedures will help to decrease the virus spread. Planning and revision of workflows is necessary for safety of patient and staff and to successfully provide infection prevention and control measures, for this a “three zones and two passages” concept should be followed. Manual cleaning followed by high-level disinfection (HLD), effectively eliminates nearly all microorganisms from endoscopes during reprocessing. Transmission of viral infections during endoscopy is quite rare and, it is usually the result of noncompliance from the essential steps of reprocessing. Reuse of any disposable GI endoscopic device is strongly discouraged. Environmental decontamination is essential to reduce the risk of fomite transmission. Noncritical environmental surfaces frequently touched by hands (e.g., bedside tables and bed rails) and endoscopy furniture and floor should be considered heavily contaminated in patients with intermediate or high risk of COVID-19 and should be thoroughly disinfected at the end of each procedure. If available, negative pressure rooms are preferred for endoscopy, as has been advised by Centers for Disease Control and Prevention (CDC). Staff involved in reprocessing and the cleaning of endoscopy rooms should utilize personal protective equipment (PPE) including N95 mask. Reprocessing staff should undergo necessary training and ongoing annual assessment of competency.

positive: Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Summary Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.

positive: Isolation and identification of human coronavirus 229E from frequently touched environmental surfaces of a university classroom that is cleaned daily Frequently touched surfaces of a university classroom that is cleaned daily contained viable human coronavirus 229E (CoV-229E). Tests of a CoV-229E laboratory strain under conditions that simulated the ambient light, temperature, and relative humidity conditions of the classroom revealed that some of the virus remained viable on various surfaces for 7 days, suggesting CoV-229E is relatively stable in the environment. Our findings reinforce the notion that contact transmission may be possible for this virus.

positive: Novel Coronavirus Disease (COVID-19) The present outbreak of the novel coronavirus initially called as “2019 novel coronavirus” or “2019-nCoV” by the World Health Organization (WHO), is also known as “Wuhan coronavirus” or “Wuhan pneumonia”, as it started in the Wuhan city of China in early December of 2019. This new coronavirus-associated acute respiratory deadly disease is now officially named as Corona Virus Disease-19 (COVID-19) by the WHO. From China, this epidemic has now spread to all over the world. On 11 March 2020, the WHO recognised COVID-19 as a pandemic. A pandemic refers to a disease that has spread to several countries, continents, if not worldwide. While the information available on this newly identified virus is limited and evolving, here is a quick run-down of what has been figured out so far.

positive: Factors affecting stability and infectivity of SARS-CoV-2 BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20∼25(o)C). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.

positive: Protection and disinfection policies against SARS-CoV-2 (COVID-19). In late December 2019, reports from China of the incidence of pneumonia with unknown etiology were sent to the World Health Organization (WHO). Shortly afterwards, the cause of this disease was identified as the novel beta-coronavirus, SARS-CoV-2, and its genetic sequence was published on January 12, 2020. Human-to-human transmission via respiratory droplets and contact with aerosol infected surfaces are the major ways of transmitting this virus. Here we attempted to collect information on virus stability in the air and on surfaces and ways of preventing of SARS-CoV-2 spreading.

positive: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces() The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.

positive: Epidemiology, virology, and clinical features of severe acute respiratory syndrome -coronavirus-2 (SARS-CoV-2; Coronavirus Disease-19) A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been 2 novel coronavirus outbreaks in the past 2 decades. The outbreak of severe acute respiratory syndrome (SARS) in 2002–2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 deaths), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 861 people out of a total 2,502 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features.

positive: Clinical Data on Hospital Environmental Hygiene Monitoring and Medical Staff Protection during the Coronavirus Disease 2019 Outbreak Background: The outbreak of coronavirus disease 2019 (COVID-19) has placed unprecedented challenges on hospital environmental hygiene and medical staff protection. It is crucial to assess hospital environmental hygiene to understand the most important environmental issues for controlling the spread of COVID-19 in hospitals. Objective: To detect the presence of COVID-19 in the samples from the area at risk of contamination in the First Hospital of Jilin University. Methods: Viruses in the air were collected by natural sedimentation and air particle sampler methods. Predetermined environmental surfaces were sampled using swabs at seven o'clock in the morning before disinfection. The real-time reverse-transcription PCR method was used to detect the existence of COVID-19 pathogens. Results: Viruses could be detected on the surfaces of the nurse station in the isolation area with suspected patients and in the air of the isolation ward with an intensive care patient. Conclusion: Comprehensive monitoring of hospital environmental hygiene during pandemic outbreaks is conducive to the refinement of hospital infection control. It is of great significance to ensure the safety of medical treatment and the quality of hospital infection control through the monitoring of environmental hygiene.

positive: Transmission routes of 2019-nCoV and controls in dental practice A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.

positive: Spillover of SARS-CoV-2 into novel wild hosts in North America: A conceptual model for perpetuation of the pathogen Abstract There is evidence that the current outbreak of the novel coronavirus SARS-CoV-2, which causes COVID-19, is of animal origin. As with a number of zoonotic pathogens, there is a risk of spillover into novel hosts. Here, we propose a hypothesized conceptual model that illustrates the mechanism whereby the SARS-CoV-2 could spillover from infected humans to naive wildlife hosts in North America. This proposed model is premised on transmission of SARS-CoV-2 from human feces through municipal waste water treatment plants into the natural aquatic environment where potential wildlife hosts become infected. We use the existing literature on human coronaviruses, including SARS CoV, to support the potential pathways and mechanisms in the conceptual model. Although we focus on North America, our conceptual model could apply to other parts of the globe as well.

positive: Personal Protective Equipment for Healthcare Workers during the COVID-19 Pandemic The coronavirus disease (COVID-19) pandemic has posed a challenge for healthcare systems, and healthcare workers (HCWs) are at high risk of exposure. Protecting HCWs is of paramount importance to maintain continuous patient care and keep healthcare systems functioning. Used alongside administrative and engineering control measures, personal protective equipment (PPE) is the last line of defense and the core component of protection. Current data suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mainly transmitted through respiratory droplets and close contact. Airborne transmission may occur during aerosol-generating procedures. However, the modes of transmission still remain uncertain, especially regarding the possibility of airborne transmission when aerosol-generating procedures are not performed. Thus, there are some inconsistencies in the respiratory protective equipment recommended by international and national organizations. In Korea, there have been several modifications to PPE recommendations offering options in choosing PPE for respiratory and body protection, which confuses HCWs; they are often unsure what to wear and when to wear it. The choice of PPE is based on the risk of exposure and possible modes of transmission. The level of protection provided by PPE differs based on standards and test methods. Thus, understanding them is the key in selecting the proper PPE. This article reviews evidence on the mode of SARS-CoV-2 transmission, compares the current PPE recommendations of the World Health Organization with those in Korea, and discusses standard requirements and the proper selection of PPE.

positive: Guide to forensic pathology practice for death cases related to coronavirus disease 2019 (COVID-19) (Trial draft)(‡) Autopsy is of great significance for elucidating the pathological changes, pathogenesis and cause of death of Coronavirus Disease 2019 (COVID-19) and can provide a theoretical basis for scientific and accurate prevention and control of its outbreak. Based on related laws and regulations, such as the Law of the People’s Republic of China on Prevention and Control of Infectious Diseases, clinical manifestations and epidemiological characteristics of COVID-19 and guidelines on the prevention and control of this epidemic, combined with the practical work of forensic pathology examinations, we developed the Guide to Forensic Pathology Practice for Death Cases Related to Coronavirus Disease 2019 (COVID-19) (Trial Draft). This guide describes the background investigation of the death cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy practices and auxiliary examinations, and thus offers a reference for forensic and pathological examination institutions and staff.

positive: Two mechanisms for accelerated diffusion of COVID-19 outbreaks in regions with high intensity of population and polluting industrialization: the air pollution-to-human and human-to-human transmission dynamics What is COVID-19? Coronavirus disease 2019 (COVID-19) is viral infection that generates a severe acute respiratory syndrome with serious pneumonia that may result in progressive respiratory failure and death. What are the goals of this investigation? This study explains the geo-environmental determinants of the accelerated diffusion of COVID-19 in Italy that is generating a high level of deaths and suggests general lessons learned for a strategy to cope with future epidemics similar to COVID-19 to reduce viral infectivity and negative impacts in economic systems and society. What are the results of this study? The main results are: o The accelerate and vast diffusion of COVID-19 in North Italy has a high association with air pollution. o Hinterland cities have average days of exceeding the limits set for PM10 (particulate matter 10 micrometers or less in diameter) equal to 80 days, and an average number of infected more than 2,000 individuals as of April 1st, 2020, coastal cities have days of exceeding the limits set for PM10 equal to 60 days and have about 700 infected in average. o Cities that average number of 125 days exceeding the limits set for PM10, last year, they have an average number of infected individual higher than 3,200 units, whereas cities having less than 100 days (average number of 48 days) exceeding the limits set for PM10, they have an average number of about 900 infected individuals. o The results reveal that accelerated transmission dynamics of COVID-19 in specific environments is due to two mechanisms given by: air pollution-to-human transmission and human-to-human transmission; in particular, the mechanisms of air pollution-to-human transmission play a critical role rather than human-to-human transmission. o The finding here suggests that to minimize future epidemic similar to COVID-19, the max number of days per year in which cities can exceed the limits set for PM10 or for ozone, considering their meteorological condition, is less than 50 days. After this critical threshold, the analytical output here suggests that environmental inconsistencies because of the combination between air pollution and meteorological conditions (with high moisture%, low wind speed and fog) trigger a take-off of viral infectivity (accelerated epidemic diffusion) with damages for health of population, economy and society. What is a socioeconomic strategy to prevent future epidemics similar to COVID-19? Considering the complex interaction between air pollution, meteorological conditions and biological characteristics of viral infectivity, lessons learned for COVID-19 have to be applied for a proactive socioeconomic strategy to cope with future epidemics, especially an environmental policy based on reduction of air pollution mainly in hinterland zones of countries, having low wind speed, high percentage of moisture and fog that create an environment that can damage immune system of people and foster a fast transmission of viral infectivity similar to the COVID-19. This study must conclude that a strategy to prevent future epidemics similar to COVID 19 has also to be designed in environmental and sustainability science and not only in terms of biology.

positive: Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9) Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility.

positive: Post-SARS infection control in the hospital and clinic Summary The recent severe acute respiratory syndrome (SARS) outbreak has almost mandated a re-evaluation of infection control practices in hospitals, clinics, schools and domestic environments, especially for patients with respiratory tract symptoms. Triage, early case detection followed by prompt isolation and quarantine are major preventive measures. Respiratory tract infections are the most common childhood illnesses and paediatric SARS poses special problems in diagnosis because of its non-specific presentation. The main lessons learnt from the outbreak were: (1) despite well established guidelines on infection control precautions, poor understanding of underlying principles and deficiencies in compliance are common among healthcare professionals, especially during emergencies; (2) even a slight lapse can be fatal; and (3) over-protection can be counterproductive. Hence it is important to: (1) be protected to protect others; (2) be vigilant and prepared for emerging infections; (3) be proficient and scrupulous in infection control measures; (4) be apposite and practical on personal protective equipments to ensure sustainability; and (5) be dutiful and prompt in informing of potential threats and work closely with others.

positive: COVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission The recent coronavirus disease (COVID-19), caused by SARS-CoV-2, is inarguably the most challenging coronavirus outbreak relative to the previous outbreaks involving SARS-CoV and MERS-CoV. With the number of COVID-19 cases now exceeding 2 million worldwide, it is apparent that (i) transmission of SARS-CoV-2 is very high and (ii) there are large variations in disease severity, one component of which may be genetic variability in the response to the virus. Controlling current rates of infection and combating future waves require a better understanding of the routes of exposure to SARS-CoV-2 and the underlying genomic susceptibility to this disease. In this mini-review, we highlight possible genetic determinants of COVID-19 and the contribution of aerosol exposure as a potentially important transmission route of SARS-CoV-2.

positive: Coronavirus Disease 2019 (COVID-19) pandemic, lessons to be learned! Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported as a worldwide emergency. Due to the extensiveness of spread and death, it has been declared as a pandemic. This review focused on the current pandemic situation and understanding the prevention and control strategies of COVID-19. Data presented here was by April 3, 2020. A total of 1,016,399 cases of COVID-19 with 53,238 deaths was reported from 204 countries and territories including two international conveyances over the world. After China, most of the new cases were from Europe, particularly Italy acting as the source of importation to many of the other countries around the world. China has obtained success by ascribing control strategies against COVID-19. The implementation of China’s strategy, as well as the development of a vaccine, may control the pandemic of COVID-19. Further robust studies are required for a clear understanding of transmission parameters, prevention, and control strategies of SARS-CoV-2. This review paper describes the nature of COVID-19 and the possible ways for the effective controlling of the COVID-19 or similar viral diseases that may come in the future.

positive: The COVID-19 pandemic: implications for the cytology laboratory The coronavirus disease 2019 (COVID-19) is a pandemic caused by the SARS-CoV-2 virus. The infection has predominantly respiratory transmission and is transmitted through large droplets or aerosols, and less commonly by contact with infected surfaces or fomites. The alarming spread of the infection and the severe clinical disease that it may cause have led to the widespread institution of social distancing measures. Because of repeated exposure to potentially infectious patients and specimens, health care and laboratory personnel are particularly susceptible to contract COVID-19. This review paper provides an assessment of the current state of knowledge about the disease and its pathology, and the potential presence of the virus in cytology specimens. It also discusses the measures that cytology laboratories can take to function during the pandemic, and minimize the risk to their personnel, trainees, and pathologists. In addition, it explores potential means to continue to educate trainees during the COVID-19 pandemic.

positive: Multi-route respiratory infection: when a transmission route may dominate The exact transmission route of many respiratory infectious diseases remains a subject for debate to date. The relative contribution ratio of each transmission route is largely undetermined, which is affected by environmental conditions, human behavior, the host and the microorganism. In this study, a detailed mathematical model is developed to investigate the relative contributions of different transmission routes to a multi-route transmitted respiratory infection. It is illustrated that all transmission routes can dominate the total transmission risk under different scenarios. Influential parameters considered include dose-response rate of different routes, droplet governing size that determines virus content in droplets, exposure distance, and virus dose transported to the hand of infector. Our multi-route transmission model provides a comprehensive but straightforward method to evaluate the transmission efficiency of different transmission routes of respiratory diseases and provides a basis for predicting the impact of individual level intervention methods such as increasing close-contact distance and wearing protective masks.

positive: Air purifiers: A supplementary measure to remove airborne SARS-CoV-2

positive: COVID-19 - toward a comprehensive understanding of the disease. The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a comprehensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on.

positive: What We Know So Far (As of March 26, 2020) About COVID-19 – An MRT Point of View

positive: MERS coronavirus: diagnostics, epidemiology and transmission The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0439-5) contains supplementary material, which is available to authorized users.

positive: Survival of Viruses in the Marine Environment It has been well established that human pathogenic viruses may be transmitted through the marine environment due to the release of sewage by polluted rivers, outfalls, or release from vessels. These wastes contain human enteric viruses, which if ingested, or in some cases inhaled, can cause a wide variety of illnesses. Their ability to be transmitted by this route is because of their capability to remain infectious long enough in the marine environment to come in contact with a susceptible host. Transmission routes may be fairly direct, such as ingested of contaminated seawater by a swimmer, or more complex by prolonged survival in sediments which are later resuspended and accumulated in shellfish during feeding. The virus is then transmitted during consumption of the shellfish. To understand the potential for human enteric virus transmission through the marine environment numerous studies have been conducted on factors which influence their persistence in this environment (Table 6.1). This reviewfocuses on factors that could play a role in the survival of human pathogenic viruses in the marine environment.

positive: Airborne Transmission Route of COVID-19: Why 2 Meters/6 Feet of Inter-Personal Distance Could Not Be Enough The COVID-19 pandemic caused the shutdown of entire nations all over the world. In addition to mobility restrictions of people, the World Health Organization and the Governments have prescribed maintaining an inter-personal distance of 1.5 or 2 m (about 6 feet) from each other in order to minimize the risk of contagion through the droplets that we usually disseminate around us from nose and mouth. However, recently published studies support the hypothesis of virus transmission over a distance of 2 m from an infected person. Researchers have proved the higher aerosol and surface stability of SARS-COV-2 as compared with SARS-COV-1 (with the virus remaining viable and infectious in aerosol for hours) and that airborne transmission of SARS-CoV can occur besides close-distance contacts. Indeed, there is reasonable evidence about the possibility of SARS-COV-2 airborne transmission due to its persistence into aerosol droplets in a viable and infectious form. Based on the available knowledge and epidemiological observations, it is plausible that small particles containing the virus may diffuse in indoor environments covering distances up to 10 m from the emission sources, thus representing a kind of aerosol transmission. On-field studies carried out inside Wuhan Hospitals showed the presence of SARS-COV-2 RNA in air samples collected in the hospitals and also in the surroundings, leading to the conclusion that the airborne route has to be considered an important pathway for viral diffusion. Similar findings are reported in analyses concerning air samples collected at the Nebraska University Hospital. On March 16th, we have released a Position Paper emphasizing the airborne route as a possible additional factor for interpreting the anomalous COVID-19 outbreaks in northern Italy, ranked as one of the most polluted areas in Europe and characterized by high particulate matter (PM) concentrations. The available information on the SARS-COV-2 spreading supports the hypothesis of airborne diffusion of infected droplets from person to person at a distance greater than two meters (6 feet). The inter-personal distance of 2 m can be reasonably considered as an effective protection only if everybody wears face masks in daily life activities.

positive: Airborne or droplet precautions for health workers treating COVID-19? Cases of COVID-19 have been reported in over 200 countries. Thousands of health workers have been infected and outbreaks have occurred in hospitals, aged care facilities and prisons. World Health Organization (WHO) has issued guidelines for contact and droplet precautions for Healthcare Workers (HCWs) caring for suspected COVID-19 patients, whilst the US Centre for Disease Control (CDC) has recommended airborne precautions. The 1 – 2 m (≈3 – 6 ft) rule of spatial separation is central to droplet precautions and assumes large droplets do not travel further than 2 m (≈6 ft). We aimed to review the evidence for horizontal distance travelled by droplets and the guidelines issued by the World Health Organization (WHO), US Center for Diseases Control (CDC) and European Centre for Disease Prevention and Control (ECDC) on respiratory protection for COVID-19. We found that the evidence base for current guidelines is sparse, and the available data do not support the 1 – 2 m (≈3 – 6 ft) rule of spatial separation. Of ten studies on horizontal droplet distance, eight showed droplets travel more than 2 m (≈6 ft), in some cases more than 8 meters (≈26 ft). Several studies of SARS-CoV-2 support aerosol transmission and one study documented virus at a distance of 4 meters (≈13 ft) from the patient. Moreover, evidence suggests infections cannot neatly be separated into the dichotomy of droplet versus airborne transmission routes. Available studies also show that SARS-CoV-2 can be detected in the air, 3 hours after aeroslisation. The weight of combined evidence supports airborne precautions for the occupational health and safety of health workers treating patients with COVID-19.

positive: The impact of cold on the respiratory tract and its consequences to respiratory health The increasing use, and sometimes the abuse, particularly in industrialized countries of air conditioning at home, in car, hotel and shopping centres has highlighted new emerging public health issues, resulting from exposure of the airways to cool air or, more properly, resulting from sudden temperature changes. This is part of a wider problem, relating to air quality in indoor environment, such as homes or offices, where people spend more than 90% of their time. In particular, if indoor exposure occurs quickly and without any gradual adaptation to a temperature 2°–3° lower than the external temperature and especially with a 5° difference (avoiding indoor temperature below 24°) and an humidity between 40 and 60%, there is a risk of negative consequences on the respiratory tract and the patient risks to be in a clinical condition characterized by an exacerbation of the respiratory symptoms of his chronic respiratory disease (asthma and COPD) within a few hours or days. Surprisingly, these effects of cold climate remain out of the focus of the media unless spells of unusually cold weather sweep through a local area or unstable weather conditions associated with extremely cold periods of increasing frequency and duration. Moreover, the energy consumed by air conditioning induces an increase of CO(2) in atmosphere with increase of global warming. There is a need to better define the consequences of repeated exposure to cold air and the mechanisms by which such exposure could modify airway function and affect the outcomes of patients with pre-existing airway disease. This could help to promote adequate policy and public health actions to face the incoming challenges induced by climate change and global warming.

positive: SARS-CoV-2 and human milk: what is the evidence? The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical, and public health communities have rapidly engaged to find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. While respiratory droplets are a known mechanism of transmission, other mechanisms are possible. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronavirus (including SARS-CoV-2) via human milk and/or breastfeeding. There is a single study providing some evidence of vertical transmission of human coronavirus 229E, a single study evaluating presence of SARS-CoV in human milk (it was negative), and no published data on MERS-CoV and human milk. There are 9 case studies of human milk tested for SARS-CoV-2; none detected the virus. Importantly, none of the published studies on coronaviruses and human milk report validation of their analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.

positive: Environmental contamination by SARS-CoV-2 in a designated hospital for coronavirus disease 2019 BACKGROUND: COVID-19 is characterized by risk of nosocomial transmission; however, the extent of environmental contamination and its potential contribution of environmental contamination to SARS-CoV-2 transmission are poorly understood. This study aimed to investigate whether environmental contamination may play a role in SARS-CoV-2 transmission. METHODS: Air samples were collected by natural precipitation, and environmental surface samples were collected by conventional surface swabbing. SARS-CoV-2 RNA detection was performed using reverse transcription polymerase chain reaction. RESULTS: Viral RNA was not detected in the 44 air samples. The positive rates in 200 environmental surface samples in medical areas (24.83%) was higher than that in living quarters (3.64%), with a significant difference (P<0.05). The positive rates were 25.00% and 37.50% for the general isolation ward and ICU, respectively, and no significant difference was observed between them (P=0.238). The top five sampling sites with a positive rate in medical areas were beepers (50.00%), water machine buttons (50.00%), elevator buttons (42.86%), computer mouses (40.00%), and telephones (40.00%). CONCLUSIONS: Most of the touchable surfaces in the designated hospital for COVID-19 were heavily contaminated, suggesting that the environment is a potential medium of disease transmission. These results emphasize the need for strict environmental surface hygiene practices and enhanced hand hygiene to prevent the spread of the virus.

positive: New and emerging infectious diseases (Ebola, Middle Eastern respiratory syndrome coronavirus, carbapenem-resistant Enterobacteriaceae, Candida auris): Focus on environmental survival and germicide susceptibility

positive: Infection control and anesthesia: Lessons learned from the Toronto SARS outbreak PURPOSE: To describe the outbreak of severe acute respiratory syndrome (SARS) in Toronto, its impact on anesthesia practice and the infection control guidelines adopted to manage patients in the operating room (OR) and to provide emergency intubation outside the OR. CLINICAL FEATURES: The SARS outbreak in Toronto was the result of a single index patient. The causative virus, SARS-CoV, is moderately contagious, and is spread by droplets and contact. The virus gains access to host through the mucosa of the respiratory tract and the eyes. It can affect both healthy and compromised patients. The use of several precautionary measures such as goggles, gloves, gowns and facemasks and the application of various infection control strategies designed to minimize the spread of the virus are discussed. CONCLUSION: In containing the spread of SARS, vigilance and strict infection control are important. This results in the rediscovery of standards of infection control measures in daily anesthesia practice.

positive: The influenza virus, SARS-CoV-2, and the airways: Clarification for the otorhinolaryngologist The influenza virus and SARS-CoV-2 cause trivial upper and severe lower respiratory infections (Influenza virus 290,000 to 650,000 deaths/year). These viruses come into contact with the airways either by direct projection, by secondary inhalation of airborne droplets, or by handling (fomites). The objective of this article is to clarify the mechanisms of production and penetration of droplets of secretions emitted during all expiratory phenomena likely to transport these viruses and come into contact with the respiratory mucosa. The droplets>5µm follow the laws of ballistics, those<5µm follow Brownian motion and remain suspended in the air. The aerosols of droplets are very heterogeneous whether the subject is healthy or sick. During an infectious period, not all droplets contain viral RNA. If these RNAs are detectable around patients, on surfaces, and in the ambient air at variable distances according to the studies (from 0.5m to beyond the patient's room), this is without prejudice to the infectious nature (viability) of the virus and the minimum infectious dose. There is a time lag between the patient's infectious period and that of RNA detection for both viruses. Subsequently, the inhaled particles must meet the laws of fluid dynamics (filtration) to settle in the respiratory tree. All of this partly explains the contagiousness and the clinical expression of these two viruses from the olfactory cleft to the alveoli.

positive: Exhaled breath is a significant source of SARS-CoV-2 emission Despite notable efforts in airborne SARS-CoV-2 detection, no clear evidence has emerged to show how SARS-CoV-2 is emitted into the environments. Here, 35 COVID-19 subjects were recruited; exhaled breath condensate (EBC), air samples and surface swabs were collected and analyzed for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR). EBC samples had the highest positive rate (16.7%, n=30), followed by surface swabs (5.4%, n=242), and air samples (3.8%, n=26). COVID-19 patients were shown to exhale SARS-CoV-2 into the air at an estimated rate of 103-105 RNA copies/min; while toilet and floor surfaces represented two important SARS-CoV-2 reservoirs. Our results imply that airborne transmission of SARS-CoV-2 plays a major role in COVID-19 spread, especially during the early stages of the disease.

positive: Biosafety in the preparation and processing of cytology specimens with potential coronavirus (COVID‐19) infection: Perspectives from Taiwan This commentary focuses on the cytopathology laboratory, the authors' experiences with coronavirus (COVID‐19) in Taiwan, and current guidelines on COVID‐19 infection prevention and control. The objective of this report is to provide cytopathology professionals a timely, in‐depth, evidence‐based review of biosafety practices for those at risk for coronavirus (COVID‐19) infection.

positive: Survival of porcine epidemic diarrhea virus (PEDV) in thermally treated feed ingredients and on surfaces BACKGROUND: Infection with Porcine Epidemic Diarrhea Virus (PEDV) causes vomiting, diarrhea, and dehydration in young pigs. The virus made its first appearance in the U.S. in 2013, where it caused substantial neonatal mortality and economic losses in the U.S. pork industry. Based on outbreak investigations, it is hypothesized that the virus could be transmitted through contaminated feed or contaminated feed surfaces. This potential risk created a demand for research on the inactivation kinetics of PEDV in different environments. Therefore, the objective of this study was to evaluate the survival of PEDV in 9 different feed ingredients when exposed to 60, 70, 80, and 90 °C, as well as the survival on four different surfaces (galvanized steel, stainless steel, aluminum, and plastic). RESULTS: Overall, there were no differences (P > 0.05) in virus survival among the different feed matrices studied when thermally processed at 60 to 90 °C for 5, 10, 15, or 30 min. However, the time necessary to achieve a one log reduction in virus concentration was less (P < 0.05) when ingredients were exposed to temperatures from 70 °C (3.7 min), 80 °C (2.4 min), and 90 °C (2.3 min) compared with 60 °C (4.4 min). The maximum inactivation level (3.9 log) was achieved when heating all ingredients at 90 °C for 30 min. There were no differences in the amount of time necessary to cause a one log reduction in PEDV concentration among the different surfaces. CONCLUSIONS: The results of this study showed that PEDV survival among the 9 feed ingredients evaluated was not different when exposed to thermal treatments for up to 30 min. However, different combinations of temperature and time resulted in achieving a 3 to 4 log reduction of PEDV in all feed ingredients evaluated. Finally, PEDV survival was similar on galvanized steel, stainless steel, aluminum and plastic.

positive: Anaesthesia and COVID-19: infection control The world is currently facing an unprecedented healthcare crisis caused by a pandemic novel beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogen is spread by human-to-human transmission via droplets exposure and contact transfer, causing mild symptoms in the majority of cases, but critical illness, bilateral viral pneumonia, and acute respiratory distress syndrome (ARDS) in a minority. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary public healthcare intervention used. The pace of transmission and global scale of SARS-CoV-2 infections has implications for strategic oversight, resource management, and responsiveness in infection control. This article presents a summary of learning points in epidemiological infection control from the SARS epidemic, alongside a review of evidence connecting current understanding of the virologic and environmental contamination properties of SARS-CoV-2. We present suggestions for how personal protective equipment policies relate to the viral pandemic context and how the risk of transmission by and to anaesthetists, intensivists, and other healthcare workers can be minimised.

positive: COVID‐19 and gastrointestinal endoscopies: current insights and emergent strategies A new coronavirus emerged in December 2019 in Wuhan city of China, named as the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), and disease was called as coronavirus disease‐2019 (COVID‐19). The infection due to this virus spread exponentially throughout China and then spread across >205 nations, including the United States (US). Gastrointestinal (GI) endoscopies are routinely performed in the US and globally. Previous reports of isolated infection outbreaks were reported with endoscopes acting as potential vectors. While multidrug‐resistant organisms have been reported to be spread by endoscopes, few cases of viruses such as Hepatitis B and C are noted in the literature. COVID‐19 predominately spread by droplet transmission, although recent evidence showed that shedding in feces and feco‐oral transmission could also be possible. It is unclear if COVID‐19 could be transmitted by endoscopes, but it could theoretically happen due to contact with mucous membranes and body fluids. GI endoscopies involve close contact with oral and colonic contents exposing endoscopy staff to respiratory and oropharyngeal secretions. This can increase the risk of contamination and contribute to virus transmission. Given these risks, all major GI societies have called for rescheduling elective non‐urgent procedures and perform only emergent or urgent based on the clinical need. Furthermore, pre‐screening of all individuals prior to endoscopy is recommended. This article focuses on the risk of COVID‐19 transmission by GI shedding, the potential role of endoscopes as a vector of this novel virus including transmission during endoscopies and prevention strategies including deferral of elective non‐urgent endoscopy procedures.

positive: Personal protective equipment doffing practices of healthcare workers During the doffing of personal protective equipment (PPE), pathogens can be transferred from the PPE to the bodies of healthcare workers (HCWs), putting HCWs and patients at risk of exposure and infection. PPE doffing practices of HCWs who cared for patients with viral respiratory infections were observed at an acute care hospital from March 2017 to April 2018. A trained observer recorded doffing performance of HCWs inside the patient rooms using a pre-defined checklist based on the Centers for Disease Control and Prevention (CDC) guideline. Doffing practices were observed 162 times during care of 52 patients infected with respiratory viral pathogens. Out of the 52 patients, 30 were in droplet and contact isolation, 21 were in droplet isolation, and 1 was in contact isolation. Overall, 90% of observed doffing was incorrect, with respect to the doffing sequence, doffing technique, or use of appropriate PPE. Common errors were doffing gown from the front, removing face shield of the mask, and touching potentially contaminated surfaces and PPE during doffing. Deviations from the recommended PPE doffing protocol are common and can increase potential for contamination of the HCW’s clothing or skin after providing care. There is a clear need to change the approach used to training HCWs in PPE doffing practices.

positive: Possible aerosol transmission of COVID-19 and special precautions in dentistry Since its emergence in December 2019, corona virus disease 2019 (COVID-19) has impacted several countries, affecting more than 90 thousand patients and making it a global public threat. The routes of transmission are direct contact, and droplet and possible aerosol transmissions. Due to the unique nature of dentistry, most dental procedures generate significant amounts of droplets and aerosols, posing potential risks of infection transmission. Understanding the significance of aerosol transmission and its implications in dentistry can facilitate the identification and correction of negligence in daily dental practice. In addition to the standard precautions, some special precautions that should be implemented during an outbreak have been raised in this review.

positive: The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) in Dentistry. Management of Biological Risk in Dental Practice The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in Wuhan, China, and the etiological agent of Coronavirus Disease-2019 (COVID-19). This infection spreads mainly through direct contact with Flügge micro droplets or core droplets that remain suspended as aerosol. Moreover, it has been reported that infected subjects, both with and without clinical signs of COVID-19, can transmit the virus. Since the infection typically enters through mouth, nose, and eyes, dentistry is one of the medical practices at highest risk of infection due to the frequent production of aerosol and the constant presence of saliva. The World Health Organization (WHO) has suggested that only emergency/urgent procedures should be performed during the coronavirus outbreak. Considering the virus’ route of transmission, a specific protocol should be applied to reduce the risk of infection in addition to measures that prevent the spread of infection from a patient to another person or medical tools and equipment (cross-infection). This protocol should be implemented by modifying both patient management and clinical practice, introducing particular devices and organizational practices. This paper aims to discuss and suggest the most appropriate procedures in every aspect of dental practice to reduce infection risk.

positive: Not even the air of empty spaces is coronavirus free (Two meters is not a safe distance) A key safety measure encouraged by health authorities to avoid the SARS-CoV-2 spreading is the distance of one to two meters between people. This recommended two-meters distance is mainly based on short-distance contagion, when infected drops are expelled during a speech, coughing, or sneezing and directly hit another person. The dangerous form of airway contamination caused by droplets that remain suspended in the air for several hours has been almost ignored. However, the theoretical calculations performed in this work, recent experiments, and the accumulated knowledge in this and other epidemics indicate that, because of the airborne transmission, there is no safe distance to the coronavirus, either indoors or in open places. Recent investigations have confirmed not only the presence of the coronavirus in droplets suspended in the air but that these viruses remain active for several hours. Furthermore, significant indirect evidence of this means of transmission is the great difference in contagion between Brazilian regions in the current outbreak. While the Amazonian states have a contamination rate greater than 20%, in the southern states of the country this rate is less than 1%, despite high temperatures in the Northern region. Notwithstanding the social and economic differences between these regions, it seems that the extremely high humidity of the forest air prolongs the survival of the viruses in the drops in the external environment. Our theoretical calculations explain empirical observations from recent epidemiological studies and strengthen the need to use, not only a mask but also protective glasses throughout the population in the same way that they are mandatory for health professionals. Besides, our calculations show how air conditioning and heating systems can increase contagion. Finally, we suggest measures that could reduce the spread of the pandemic.

positive: Effective Heat Inactivation of SARS-CoV-2 The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has quickly turned into a global pandemic. Infectious viruses had been isolated from oro- or naso-pharyngeal swabs, sputum and possibly stool samples of infected individuals. Handling these clinical specimens therefore poses a biosafety risk to both healthcare professionals and laboratory workers. In this study, we aimed to evaluate the stability of SARS-CoV-2 under different heat conditions and report that the virus is stable at 37 C for at least 24 hours. Heating at 56 C for 30 minutes, however, effectively inactivated the virus while preserved the stability of viral RNA in both human sera and sputum samples. These findings provide critical information regarding the biology of the virus as well as a practical way to inactivate infectious virus that is potentially found in clinical specimens.

positive: Survival characteristics of airborne human coronavirus 229E. The survival of airborne human coronavirus 229E (HCV/229E) was studied under different conditions of temperature (20 +/- 1 degree C and 6 +/- 1 degree C) and low (30 +/- 5%), medium (50 +/- 5%) or high (80 +/- 5%) relative humidities (RH). At 20 +/- 1 degree C, aerosolized HCV/229E was found to survive best at 50% RH with a half-life of 67.33 +/- 8.24 h while at 30% RH the virus half-life was 26.76 +/- 6.21 h. At 50% RH nearly 20% infectious virus was still detectable at 6 days. High RH at 20 +/- 1 degree C, on the other hand, was found to be the least favourable to the survival of aerosolized virus and under these conditions the virus half-life was only about 3 h; no virus could be detected after 24 h in aerosol. At 6 +/- 1 degree C, in either 50% or 30% RH conditions, the survival of HCV/229E was significantly enhanced, with the decay pattern essentially similar to that seen at 20 +/- 1 degree C. At low temperature and high RH (80%), however, the survival pattern was completely reversed, with the HCV/229E half-life increasing to 86.01 +/- 5.28 h, nearly 30 times that found at 20 +/- 1 degree C and high RH. Although optimal survival at 6 degree C still occurred at 50% RH, the pronounced stabilizing effect of low temperature on the survival of HCV/229E at high RH indicates that the role of the environment on the survival of viruses in air may be more complex and significant than previously thought.

positive: Airborne SARS-CoV-2: Weighing the Evidence for Its Role in Community Transmission

positive: 9 Natural persistence of food- and waterborne viruses Abstract: This chapter summarises data on the persistence of food-and waterborne viruses in the natural environment and discusses the different factors which can affect this persistence. Conventional and alternative methods by which persistence can be studied are described, and the natural factors influencing virus persistence outside the host organism are discussed. Available data concerning virus persistence in water, soil, on surfaces and in food products are reviewed.

positive: Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient.

positive: SARS-CoV-2 human disinfection chambers: a critical analysis

positive: Collection and disinfection of forensic biological specimens in five cases concerning COVID-19 in Guangzhou, China There have been many cases of pneumonia caused by novel coronavirus infections in China and around the world. This will inevitably lead to a rise in the number of patients. At the present time, clinical and forensic autopsies have given guidance and explanations in relation to the problem of COVID-19 transmission and defense. However, less attention is paid to the handling of COVID-19 biological samples in forensic practice. Particularly, COVID-19 can survive on some surfaces for days. Since there were many cases involving COVID-19 during the epidemic, this article shares the methods and strategies for handling such inspection materials and the biological samples related specifically to COVID-19 cases.

positive: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update Coronaviruses (CoVs) belong to the family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. They are the largest group of viruses causing respiratory and gastrointestinal infections. Morphologically, CoVs are enveloped viruses containing a non-segmented positive-sense, single-stranded ribonucleic acid (RNA) viruses. CoVs are categorized into four important genera that include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. A novel member of human CoV that has recently emerged in Wuhan, China, is now formally named as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This is a unique strain of RNA viruses that have not been previously observed in humans. The virus has wide host adaptability and is capable of causing severe diseases in humans, masked palm civets, mice, dogs, cats, camels, pigs, chickens, and bats. The SARS-CoV-2 typically causes respiratory and gastrointestinal sickness in both humans and animals. It can be transmitted through aerosols and direct/indirect contact, as well as during medical cases and laboratory sample handling. Specific structural proteins, which might be found on the surface of the virus, play an important role in the pathogenesis and development of the complications. The disease is characterized by distinct medical signs and symptoms that include high fever, chills, cough, and shortness of breath or difficulty in breathing. The infected people may also present with other symptoms such as diarrhea, myalgia, fatigue, expectoration, and hemoptysis. It is important from the public health and economic point of view as it affects the growth of the country, which is majorly attributed to the restriction in the movement of the people and the cost associated with the control and prevention of the disease. Since there is no specific therapeutic intervention nor a vaccine available against the virus, supportive management and treatment with non-specific therapeutic agents (repurposed drugs) may provide relief to the patients. Some preventive strategies of the disease include blocking the routes of transmission of the infections, disinfection of instruments used during medical case handling, using personal protective equipment, proper and early diagnosis of the disease, avoiding contact with the sick patients, and quarantine of the infected/exposed people.

positive: Resilient and Agile Engineering Solutions to Address Societal Challenges such as Coronavirus Pandemic The world is witnessing tumultuous times as major economic powers including the US, UK, Russia, India, and most of Europe continue to be in a state of lockdown. The worst-hit sectors due to this lockdown are sales, production (manufacturing), transport (aerospace and automotive) and tourism. Lockdowns became necessary as a preventive measure to avoid the spread of the contagious and infectious “Coronavirus Disease 2019” (COVID-19). This newly identified disease is caused by a new strain of the virus being referred to as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2; formerly called 2019-nCoV). We review the current medical and manufacturing response to COVID-19, including advances in instrumentation, sensing, use of lasers, fumigation chambers and development of novel tools such as lab-on-the-chip using combinatorial additive and subtractive manufacturing techniques and use of molecular modelling and molecular docking in drug and vaccine discovery. We also offer perspectives on future considerations on climate change, outsourced versus indigenous manufacturing, automation, and antimicrobial resistance. Overall, this paper attempts to identify key areas where manufacturing can be employed to address societal challenges such as COVID-19.

positive: Stability and infectivity of coronaviruses in inanimate environments Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can transmit through respiratory droplets, aerosols, or contacts. Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission. The inanimate surfaces have often been described as a source of nosocomial infections. However, summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present. This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces. The literature was systematically searched on Medline without language restrictions. All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included. Most viruses from the respiratory tract, such as coronaviruses, influenza, SARS-CoV, or rhinovirus, can persist on surfaces for a few days. Persistence time on inanimate surfaces varied from minutes to up to one month, depending on the environmental conditions. SARS-CoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity. The most common coronaviruses may well survive or persist on surfaces for up to one month. Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature. Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection. The risk of transmission via touching contaminated paper is low. Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.

positive: Environmental and decontamination issues for human coronaviruses and their potential surrogates Pandemic coronavirus disease-2019 (COVID-19) gives ample reason to generally review coronavirus (CoV) containment. For establishing some preliminary views on decontamination and disinfection, surrogate CoVs have commonly been assessed. This review serves to examine the existing science in regard to CoV containment generically and then to translate these findings into timely applications for COVID-19. There is widespread dissemination of CoVs in the immediate patient environment, and CoVs can potentially be spread via respiratory secretions, urine, and stool. Interpretations of the spread however must consider whether studies examine for viral RNA, virus viability by culture, or both. Presymptomatic, asymptomatic, and post-14 day virus excretion from patients may complicate the epidemiology. Whereas droplet spread is accepted, there continues to be controversy over the extent of possible airborne spread and especially now for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CoVs are stable in body secretions and sewage at reduced temperatures. In addition to temperature, dryness or relative humidity, initial viral burden, concomitant presence of bioburden, and the type of surface can all affect stability. Generalizing, CoVs can be susceptible to radiation, temperature extremes, pH extremes, peroxides, halogens, aldehydes, many solvents, and several alcohols. Whereas detergent surfactants can have some direct activity, these agents are better used as complements to a complex disinfectant solution. Disinfectants with multiple agents and adverse pH are more likely to be best active at higher water temperatures. Real-life assessments should be encouraged with working dilutions. The use of decontamination and disinfection should be balanced with considerations of patient and caregiver safety. Processes should also be balanced with considerations for other potential pathogens that must be targeted. Given some CoV differences and given that surrogate testing provides experimental correlates at best, direct assessments with SARS-CoV, Middle East respiratory syndrome-related coronavirus (MERS-CoV), and SARS-CoV-2 are required.

positive: Assessing the relationship between ground levels of ozone (O3) and nitrogen dioxide (NO2) with coronavirus (COVID-19) in Milan, Italy Abstract This paper investigates the correlation between the high level of coronavirus SARS-CoV-2 infection accelerated transmission and lethality, and surface air pollution in Milan metropolitan area, Lombardy region in Italy. For January–April 2020 period, time series of daily average inhalable gaseous pollutants ozone (O3) and nitrogen dioxide (NO2), together climate variables (air temperature, relative humidity, wind speed, precipitation rate, atmospheric pressure field and Planetary Boundary Layer) were analyzed. In spite of being considered primarily transmitted by indoor bioaerosols droplets and infected surfaces or direct human-to-human personal contacts, it seems that high levels of urban air pollution, and climate conditions have a significant impact on SARS-CoV-2 diffusion. Exhibited positive correlations of ambient ozone levels and negative correlations of NO2 with the increased rates of COVID-19 infections (Total number, Daily New positive and Total Deaths cases), can be attributed to airborne bioaerosols distribution. The results show positive correlation of daily averaged O3 with air temperature and inversely correlations with relative humidity and precipitation rates. Viral genome contains distinctive features, including a unique N-terminal fragment within the spike protein, which allows coronavirus attachment on ambient air pollutants. At this moment it is not clear if through airborne diffusion, in the presence of outdoor and indoor aerosols, this protein “spike” of the new COVID-19 is involved in the infectious agent transmission from a reservoir to a susceptible host during the highest nosocomial outbreak in some agglomerated industrialized urban areas like Milan is. Also, in spite of collected data for cold season (winter-early spring) period, when usually ozone levels have lower values than in summer, the findings of this study support possibility as O3 can acts as a COVID-19 virus incubator. Being a novel pandemic coronavirus version, it might be ongoing during summer conditions associated with higher air temperatures, low relative humidity and precipitation levels.

positive: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a review In recent years, the prevalence and spread of coronavirus has had a huge impact on global public health. Due to the incomplete understanding of the pathogenic mechanism of the virus, it is difficult for humans to fight against the virus quickly and effectively once the outbreak occurs. In early 2020, a novel coronavirus was discovered in Wuhan, China. Soon after, similar cases were found in other countries around the world, and the number of infected people increased rapidly. So far, the global cumulative number of infected people has exceeded 3 million, and more than 200,000 people have died, which has had a huge impact on global human health and economic development. Every outbreak of disease makes a deep impression on mankind. Herein, we summarize the virology, epidemiology, clinical manifestations, diagnosis, treatment and prevention of SARS-CoV-2, and hope that countries can control the outbreak as soon as possible to minimize the loss.

positive: A Practical Decontamination Framework for COVID-19 Front-line Workers Returning Home Supplemental Digital Content is available in the text

positive: Environmental contamination by SARS-CoV-2 in a designated hospital for coronavirus disease 2019 BACKGROUND: Coronavirus disease 2019 (COVID-19) is characterized by risk of nosocomial transmission; however, the extent of environmental contamination and its potential contribution of environmental contamination to SARS-CoV-2 transmission are poorly understood. This study aimed to investigate whether environmental contamination may play a role in SARS-CoV-2 transmission. METHODS: Air samples were collected by natural precipitation, and environmental surface samples were collected by conventional surface swabbing. SARS-CoV-2 RNA detection was performed using reverse transcription polymerase chain reaction. RESULTS: Viral RNA was not detected in the 44 air samples. The positive rates in 200 environmental surface samples in medical areas (24.83%) was higher than that in living quarters (3.64%), with a significant difference (P < .05). The positive rates were 25.00% and 37.50% for the general isolation ward and intensive care unit, respectively, and no significant difference was observed between them (Pâ¯=â¯.238). The top 5 sampling sites with a positive rate in medical areas were beepers (50.00%), water machine buttons (50.00%), elevator buttons (42.86%), computer mouses (40.00%), and telephones (40.00%). CONCLUSIONS: Most of the touchable surfaces in the designated hospital for COVID-19 were heavily contaminated, suggesting that the environment is a potential medium of disease transmission. These results emphasize the need for strict environmental surface hygiene practices and enhanced hand hygiene to prevent the spread of the virus.

positive: Droplet evaporation residue indicating SARS-COV-2 survivability on surfaces SARS-CoV-2 survives and remains viable on surfaces for several days under different environments as reported in recent studies. However, it is unclear how the viruses survive for such a long time and why their survivability varies across different surfaces. To address these questions, we conduct systematic experiments investigating the evaporation of droplets produced by a nebulizer and human-exhaled gas on surfaces. We found that these droplets do not disappear with evaporation, but instead shrink to a size of a few micrometers (referred to as residues), persist for more than 24 hours, and are highly durable against changes of environmental conditions. The characteristics of these residues change significantly across surface types. Specifically, surfaces with high thermal conductivity like copper do not leave any resolvable residues, while stainless steel, plastic, and glass surfaces form residues from a varying fraction of all deposited droplets at 40% relative humidity. Lowering humidity level suppresses the formation of residues while increasing humidity level enhances it. Our results suggest that these microscale residues can potentially insulate the virus against environmental changes, allowing them to survive inhospitable environments and remain infectious for prolonged durations after deposition. Our findings can also be extended to other viruses transmitted through respiratory droplets (e.g., SARS-CoV, flu viruses, etc.), and can thus lead to practical guidelines for disinfecting surfaces and other prevention measures (e.g., humidity control) for limiting viral transmission.

positive: Middle East respiratory syndrome coronavirus on inanimate surfaces: A risk for health care transmission The Middle East Respiratory syndrome coronavirus (MERS-CoV) has been responsible for multiple health care–associated outbreaks. We investigated whether high-touch surfaces in 3 rooms of laboratory-confirmed MERS-CoV patients were contaminated with MERS-CoV RNA. We found 2 out of 51 surfaces were contaminated with MERS-CoV viral genetic material. Hence, environmental contamination may be a potential source of health care transmission and outbreaks. Meticulous environmental cleaning may be important in preventing transmission within the health care setting.

positive: A new infectious disease challenge: Urbani severe acute respiratory syndrome (SARS) associated coronavirus

positive: Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination Summary Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.

positive: The COVID-19 Pandemic: A Comprehensive Review of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, and Control A pneumonia outbreak with unknown etiology was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. The causative agent of the outbreak was identified by the WHO as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), producing the disease named coronavirus disease-2019 (COVID-19). The virus is closely related (96.3%) to bat coronavirus RaTG13, based on phylogenetic analysis. Human-to-human transmission has been confirmed even from asymptomatic carriers. The virus has spread to at least 200 countries, and more than 1,700,000 confirmed cases and 111,600 deaths have been recorded, with massive global increases in the number of cases daily. Therefore, the WHO has declared COVID-19 a pandemic. The disease is characterized by fever, dry cough, and chest pain with pneumonia in severe cases. In the beginning, the world public health authorities tried to eradicate the disease in China through quarantine but are now transitioning to prevention strategies worldwide to delay its spread. To date, there are no available vaccines or specific therapeutic drugs to treat the virus. There are many knowledge gaps about the newly emerged SARS-CoV-2, leading to misinformation. Therefore, in this review, we provide recent information about the COVID-19 pandemic. This review also provides insights for the control of pathogenic infections in humans such as SARS-CoV-2 infection and future spillovers.

positive: COVID-19: Disease, management, treatment, and social impact Abstract COVID-19 was originated from Wuhan city of Hubei Province in China in December 2019. Since then it has spread in more than 210 countries and territories. It is a viral disease due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. The patients show flu-like symptoms with a dry cough, sore throat, high fever, and breathing problems. The disease due to SARS-CoV-2 was named as COVID-19. About 2.2 million people have been infected with more than 0.15 million deaths globally. The United States of America is the most affected country with the highest patients of about 0.7 million. Despite great efforts, there is no treatment of this disease. However, prevention and management are the best options. This article describes SARS-CoV-2, disease, prevention and management, treatment and social impact on society. It was analyzed that a combination of antiviral drugs with hydroxyl-chloroquine and azithromycin (with the consultation of a medical practitioner) may be the best option to treat the patients, depending on the patient's conditions and symptoms. However, Unani therapy may be useful along with allopathic treatment. It is urgently advised and requested that all the persons should follow the preventive measures, managements and quarantine strictly without any religious discrepancy otherwise the situation may be the worst. Also, there is an urgent requirement to educate our new generation for science and technology to fight against any such disaster in future; if any. There is no need to be panic and proper prevention and management are essential to combat this disease. This article may be useful to create awareness among the public, to prevent, manage and treat COVID-19.

positive: Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.

positive: COVID-19 pandemic and the stethoscope: don't forget to sanitize

positive: Preventing SARS-CoV-2 transmission in rehabilitation pools and therapeutic water environments. SARS-CoV-2 is mainly transmitted by respiratory droplets and contact with contaminated surfaces. It can be retrieved in faeces but there is no evidence of faecal-oral transmission, which is the main route of contamination in recreational waters. Standard cleaning and disinfecting procedure, microbiologic control and health rules aim to prevent infectious risk regardless of the microorganisms. In the context of progressive lockdown exit and hospital activities recovery, we assessed the risk of SARS-CoV-2 transmission in rehabilitation pools and therapeutic water environments in order to provide specific recommendations to control the spread of SARS-CoV-2 while ensuring essential rehabilitation cares for patients.

positive: The impact of the undetected COVID-19 cases on its transmission dynamics Objective: The COVID-19 pandemic is currently ongoing. Presently, due to the unavailability of a definitive vaccine to decrease its acquiring, it is essential to understand its transmissibility in the community by undetected cases to control its transmission. This study aims to study this context using mathematical modelling. Methods: A COVID-19 transmission model was framed that estimated the basic reproduction number (R_0, a measurement of disease risk) using the next-generation method. It explored the contribution of exposed and infected (detected and undetected) individuals, and environmental pathogen to the overall risk of infection spreading, utilizing the publicly reported data of this infection in Maharashtra between March 22, 2020, and May 4, 2020. A sensitivity analysis was performed to study the effect of a rising number of undetected cases to R_0. Results: The estimated basic reproduction number is R_0=4.63, which increases rapidly with the rise in the undetected COVID-19 cases. Although the exposed individuals made the largest contribution to infection transmission (R_1=2.42), the contaminated environment also played a significant role. Conclusions: It is crucial to identify the individuals exposed and infected to COVID-19 disease and isolate them to control its transmission. The awareness of the role of fomites in infection transmission is also important in this regard.

positive: Dental care and infection-control procedures during the COVID-19 pandemic: the experience in Taipei City Hospital, Taiwan Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now widely spread globally. The main transmission routes of SARS-CoV-2 comprise human-to-human droplet infection, including inhalation and contact infection of patient’s saliva, blood and other body fluids through oral mucosa, nasal mucosa, and the eyes, and orofecal transmission. Dental treatment necessitates close-proximity, face-to-face practices and can generate droplets or aerosols containing water, saliva, blood, microorganisms, and other debris during the procedure. Therefore, dental professionals are at a high risk of SARS-CoV-2 infection. To prevent nosocomial SARS-CoV-2 spread during dental procedures, Taipei City Hospital established a dental patient triage and workflow algorithm for the provision of dental services during the COVID-19 pandemic. Given the highly contagious nature of SARS-CoV-2, it is imperative to institute an appropriate standard procedural policy for patient management and recommendation of dental treatment at hospitals during the COVID-19 pandemic.

positive: Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries Abstract The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time and the greatest challenge facing the world. Meteorological parameters are reportedly crucial factors affecting respiratory infectious disease epidemics; however, the effect of meteorological parameters on COVID-19 remains controversial. This study investigated the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, which has useful implications for policymakers and the public. Daily data on meteorological conditions, new cases and new deaths of COVID-19 were collected for 166 countries (excluding China) as of March 27, 2020. Log-linear generalized additive model was used to analyze the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, with potential confounders controlled for, including wind speed, median age of the national population, Global Health Security Index, Human Development Index and population density. Our findings revealed that temperature and relative humidity were both negatively related to daily new cases and deaths. A 1 °C increase in temperature was associated with a 3.08% (95% CI: 1.53%, 4.63%) reduction in daily new cases and a 1.19% (95% CI: 0.44%, 1.95%) reduction in daily new deaths, whereas a 1% increase in relative humidity was associated with a 0.85% (95% CI: 0.51%, 1.19%) reduction in daily new cases and a 0.51% (95% CI: 0.34%, 0.67%) reduction in daily new deaths. The results remained robust when different lag structures and the sensitivity analysis were used. These findings provide preliminary evidence that the COVID-19 pandemic may be partially suppressed with temperature and humidity increases. However, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19.

positive: SARS-CoV-2 in wastewater treatment plants As for the SARS coronavirus in the 2003 epidemic, the presence of SARS-CoV-2 has been demonstrated in faeces and, in some cases, urine of infected people, as well as in wastewater. This paper proposes a critical review of the state of the art regarding studies on the presence of SARS-CoV-2 in wastewater and sewage sludge, the factors affecting its inactivation and the main proposed treatments, with the aim to provide useful information at operative level in order to better and safer manage wastewater and sewage sludge. Given the lack of literature on SARS-CoV-2, studies involving other HCoVs such as SARS-CoV and HCoV-229E have been also considered. In wastewater, the resistance of SARS-CoV has proven to be very limited, especially at temperatures above 20 {degrees}C, and the virus has been easily removed with the use of chlorine (> 0.5 mg L-1 for 30 min). For sewage sludge, based on in vitro experiments, it is suggested to increase the retention times before a possible reuse in agriculture only for precautionary purposes, since SARS-CoV-2 is unlikely to occur in the sludge. SARS-CoV-2 in wastewater might track the epidemic trends: although being extremely promising, an effective and wide application of this approach requires a deeper knowledge of the amounts of viruses excreted through the faeces and the actual detectability of viral RNA in sewage.

positive: Risks of viral contamination in healthcare professionals during laparoscopy in the Covid-19 pandemic Abstract The Covid-19 pandemic has markedly changed our practices. This article analyses the risks of contamination among healthcare professionals (HCPs) during laparoscopic surgery on patients with Covid-19. Harmful effects of aerosols from a pneumoperitoneum with the virus present have not yet been quantified. Measures for the protection of HCPs are an extrapolation of those taken during other epidemics. They must still be mandatory to minimise the risk of viral contamination. Protection measures include personal protection equipment for HCPs, adaptation of surgical technique (method for obtaining pneumoperitoneum, filters, preferred intracorporeal anastomosis, precautions during the exsufflation of the pneumoperitoneum), and organisation of the operating room.

positive: Infection prevention and control in ultrasound - best practice recommendations from the European Society of Radiology Ultrasound Working Group OBJECTIVES: The objective of these recommendations is to highlight the importance of infection prevention and control in ultrasound (US), including diagnostic and interventional settings. METHODS: Review of available publications and discussion within a multidisciplinary group consistent of radiologists and microbiologists, in consultation with European patient and industry representatives. RECOMMENDATIONS: Good basic hygiene standards are essential. All US equipment must be approved prior to first use, including hand held devices. Any equipment in direct patient contact must be cleaned and disinfected prior to first use and after every examination. Regular deep cleaning of the entire US machine and environment should be undertaken. Faulty transducers should not be used. As outlined in presented flowcharts, low level disinfection is sufficient for standard US on intact skin. For all other minor and major interventional procedures as well as all endo-cavity US, high level disinfection is mandatory. Dedicated transducer covers must be used when transducers are in contact with mucous membranes or body fluids and sterile gel should be used inside and outside covers. CONCLUSIONS: Good standards of basic hygiene and thorough decontamination of all US equipment as well as appropriate use of US gel and transducer covers are essential to keep patients safe. MAIN MESSAGES: • Transducers must be cleaned/disinfected before first use and after every examination. • Low level disinfection is sufficient for standard US on intact skin. • High level disinfection is mandatory for endo-cavity US and all interventions. • Dedicated transducer covers must be used for endo-cavity US and all interventions. • Sterile gel should be used for all endo-cavity US and all interventions.

positive: COVID‐19: a brief history and treatments in development Coronavirus disease (COVID‐19) is now dominating the lives of everyone, and its history is constantly being rewritten. This article gives a brief account of the story so far: where SARS‐CoV‐2 might have originated, how it compares with other viruses that cause major respiratory disease, and some of the treatments and vaccines currently being investigated to combat it.

positive: Stability of SARS-CoV-2 on Critical Personal Protective Equipment The spread of COVID-19 in healthcare settings is concerning, with healthcare workers representing a disproportionately high percentage of confirmed cases. Although SARS-CoV-2 virus has been found to persist on surfaces for a number of days, the extent and duration of fomites as a mode of transmission, particularly in healthcare settings, has not been fully characterized. To shed light on this critical matter, the present study provides the first comprehensive assessment of SARS-CoV-2 stability on experimentally contaminated personal protective equipment (PPE) widely used by healthcare workers and the general public. Persistence of viable virus was monitored over 21 days on eight different materials, including nitrile medical examination gloves, reinforced chemical resistant gloves, N-95 and N-100 particulate respirator masks, Tyvek, plastic, cotton, and stainless steel. Unlike previous reports, viable SARS-CoV-2 in the presence of a soil load persisted for up to 21 days on experimentally inoculated PPE, including materials from filtering facepiece respirators (N-95 and N-100 masks) and a plastic visor. Conversely, when applied to 100% cotton fabric, the virus underwent rapid degradation and became undetectable in less than 24 hours. These findings underline the importance of appropriate handling of contaminated PPE during and following use in high-risk settings and provide interesting insight into the potential utility of cotton, including cotton masks, in limiting COVID-19 transmission.

positive: COVID-19 in air suspensions We analyse the stability of virus-carrying particles in air at equilibrium after the dissipation of the initial turbulent process produced by sneezing, coughing, breathing or speaking. Because the viruses are expelled mainly attached to small droplets, with diverse sizes and weights, and the external environmental conditions can also be diverse, the subsequent motion spannes different spatial and temporal scales. For droplet sizes larger than $100\,\mu m$, computing the time of decay to the ground and the distance travelled with a simple free fall model with empirical data extracted from the literature, we obtain distances in the range between $1$ to $3$ meters from the emitter, with a falling time of less than $1\,s$, similar to known recommendations for safe social distancing. For droplets sizes less than $100\,\mu m$ a simple model of motion in a viscous medium predicts that isolated viruses could remain suspended in quiet air for more than a month, while small droplets of $1\,\mu m$ in size can remain suspended for several hours, in agreement with recent experimental results on virus stability in aerosols. These results give solid background for the discussion of prevention strategies, like the use of masks in closed environments.

positive: COVID19: A Systematic Approach to Early Identification and Healthcare Worker Protection The COVID-19 outbreak spread rapidly throughout the globe, with worldwide infections and deaths continuing to increase dramatically. To control disease spread and protect healthcare workers, accurate information is necessary. We searched PubMed and Google Scholar for studies published from December 2019 to March 31, 2020 with the terms “COVID-19,” “2019-nCoV,” “SARS-CoV-2,” or “Novel Coronavirus Pneumonia.” The main symptoms of COVID-19 are fever (83–98.6%), cough (59.4–82%), and fatigue (38.1–69.6%). However, only 43.8% of patients have fever early in the disease course, despite still being infectious. These patients may present to clinics lacking proper precautions, leading to nosocomial transmission, and infection of workers. Potential COVID-19 cases must be identified early to initiate proper triage and distinguish them quickly from similar infections. Early identification, accurate triage, and standardized personal protection protocols can reduce the risk of cross infection. Containing disease spread will require protecting healthcare workers.

positive: Survival of Influenza A(H1N1) on Materials Found in Households: Implications for Infection Control BACKGROUND: The majority of influenza transmission occurs in homes, schools and workplaces, where many frequently touched communal items are situated. However the importance of transmission via fomites is unclear since few data exist on the survival of virus on commonly touched surfaces. We therefore measured the viability over time of two H1N1 influenza strains applied to a variety of materials commonly found in households and workplaces. METHODOLOGY AND PRINCIPAL FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. Virus genome was measured by RT-PCR; plaque assay (for PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the survival of viable virus. CONCLUSIONS/SIGNIFICANCE: The genome of either virus could be detected on most surfaces 24 h after application with relatively little drop in copy number, with the exception of unsealed wood surfaces. In contrast, virus viability dropped much more rapidly. Live virus was recovered from most surfaces tested four hours after application and from some non-porous materials after nine hours, but had fallen below the level of detection from all surfaces at 24 h. We conclude that influenza A transmission via fomites is possible but unlikely to occur for long periods after surface contamination (unless re-inoculation occurs). In situations involving a high probability of influenza transmission, our data suggest a hierarchy of priorities for surface decontamination in the multi-surface environments of home and hospitals.

positive: On airborne transmission and control of SARS-Cov-2 The COVID-19 pandemic is creating a havoc situation across the globe that modern society has ever seen. Despite of their paramount importance, the transmission routes of SARS-Cov-2 still remain debated among various sectors. Evidences compiled here strongly suggest that the COVID-19 could be transmitted via air in inadequately ventilated environments. Existing experimental data showed that coronavirus survival was negatively impacted by ozone, high temperature and low humidity. Here, regression analysis showed that the spread of SARS-Cov-2 was reduced by increasing ambient ozone concentration level from 48.83 to 94.67 µg/m3 (p-value = 0.039) and decreasing relative humidity from 23.33 to 82.67% (p-value = 0.002) and temperature from -13.17 to 19 °C) (p-value = 0.003) observed for Chinese cities during Jan-March 2020. Besides using these environmental implications, social distancing and wearing a mask are strongly encouraged to maximize the fight against the COVID-19 airborne transmission. At no other time than now are the scientists in various disciplines around the world badly needed by the society to collectively confront this disastrous pandemic.

positive: [SARS: diagnosis, therapy, and especially prevention]. The main purpose of this review is to analyze some aspects of the severe acute respiratory syndrome, SARS, in order to obtain useful data to suggest preventive actions to reduce the spreading of the disease. Many elements have been examined to reach some conclusions and to allow an updated discussion. Surgical masks protect more the patient than the caregiver. Simple or double surgical masks may be useful, as double gloving protects the hands of the surgical personnel against percutaneous transmission of HIV eventually present in contaminated blood. The frequent substitution of the external masks with a new one will improve the filtering activity against droplets produced by cough or sneezes of the patient. The use of respiratory masks may be suggested in hospitals or in restricted ventilated areas where, even if coronavirus variant is considered an environmental contaminant more than a respiratory risk, droplets nuclei may persist in the air and add consistent dangers to the heath-care givers. Considering that large and medium droplets may infect floors and surfaces, in addition to gloves, gowns, masks and eyes protection, the available list of viral and bacterial factors implicated in SARS ethiology suggests a better hand antisepsis using frequently the alcohol based gels (containing an high percentage of emollients substances), if available. A liquid soap with triclosan can also be used, if the health-care workers compliance to hand washing increases, as expected in this explosive situation. On the basis of the results of some experimental data, the environmental disinfection may be effected with ethyl alcohol 70% in water. Disinfection of floors or larger surfaces may be obtained with chlorine compounds solutions, after an accurate pre-cleaning. When corrosion, bleaching or gas production have to be avoided, chlorine compounds may be substituted by phenolic detergent disinfectants.

positive: Stability of SARS-CoV-2 in different environmental conditions Stability of SARS-CoV-2 in different environmental conditions.

positive: Recreational waters – A potential transmission route for SARS-CoV-2 to humans? Coronavirus disease 2019 (COVID-19), the respiratory illness caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has lead to high morbidity and mortality rates worldwide, has been causing major public health concerns since first detected in late 2019. Following identification of novel pathogens, questions in relation to dissemination of the pathogen and transmission routes begin to emerge. This rapidly spreading SARS-CoV-2 virus has been detected in both faecal and wastewater samples across the globe, highlighting the potential for faecal-oral transmission of the virus. As a result, concerns regarding the transmission of the virus in the environment and the risk associated with contracting the virus in recreational waters, particularly where inadequately treated wastewater is discharged, have been emerging in recent weeks. This paper highlights the need for further research to be carried out to investigate the presence, infectivity and viability of this newly identified SARS-CoV-2 virus in wastewater effluent and receiving recreational waters.

positive: Stability of SARS‐CoV‐2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: A review Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID‐19) and its causative aetiology [severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS‐CoV‐2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS‐CoV‐2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS‐CoV‐2 has been suggested. SARS‐CoV‐2 and other human and animal CoVs have remarkably short persistence on copper, latex and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass and highly porous fabrics. It has also been reported that SARS‐CoV‐2 is associated with diarrhoea and that it is shed in the faeces of COVID‐19 patients. Some CoVs show persistence in human excrement, sewage and waters for a few days. These findings suggest a possible risk of faecal–oral, foodborne and waterborne transmission of SARS‐CoV‐2 in developing countries that often use sewage‐polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID‐19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.

positive: Environmental contamination of the SARS-CoV-2 in healthcare premises: An urgent call for protection for healthcare workers Importance A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. Objective To investigate the extent to which SARS-CoV-2 contaminates healthcare settings, including to identify function zones of the hospital with the highest contamination levels and to identify the most contaminated objects, and personal protection equipment (PPE) in Wuhan, China. Design A field investigation was conducted to collect the surface swabs in various environments in the hospital and a laboratory experiment was conducted to examine the presence of the SARS-CoV-2 RNA. Setting Six hundred twenty-six surface samples were collected within the Zhongnan Medical Center in Wuhan, China in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Participants Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major personal protection equipment (PPE). The SARS-CoV-2 RNAs were detected by reverse transcription-PCR (RT-PCR). Main Outcomes and Measures SARS-CoV-2 RNAs Results The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects are self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were most contaminated PPE. Conclusions and Relevance Many surfaces were contaminated with SARS-CoV-2 across the hospital in various patient care areas, commonly used objects, medical equipment, and PPE. The 13 hospital function zones were classified into four contamination levels. These findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention precautions among HCWs during the outbreak of COVID-19. The findings may have important implications for modifying and developing urgently needed policy to better protect healthcare workers during this ongoing pandemic of SARS-CoV-2.

positive: Consideration of the Aerosol Transmission for COVID‐19 and Public Health This article analyzes the available evidence to address airborne, aerosol transmission of the SARS‐CoV‐2. We review and present three lines of evidence: case reports of transmission for asymptomatic individuals in association with studies that show that normal breathing and talking produce predominantly small droplets of the size that are subject to aerosol transport; limited empirical data that have recorded aerosolized SARS‐CoV‐2 particles that remain suspended in the air for hours and are subject to transport over distances including outside of rooms and intrabuilding, and the broader literature that further supports the importance of aerosol transmission of infectious diseases. The weight of the available evidence warrants immediate attention to address the significance of aerosols and implications for public health protection.

positive: International Committee of the Red Cross (ICRC): General guidance for the management of the dead related to COVID-19 Abstract Based on its forensic capacity and experience gained worldwide from the management of the dead in emergencies, including epidemics, the International Committee of the Red Cross has been asked by the authorities and other relevant stakeholders in some of its operational contexts to advise on the management of the dead from COVID-19 infection, for which it has prepared the following guidance. This includes advice on the handling of COVID-19 fatalities and a set of considerations for managers faced with the need to plan for adequately responding to a possible surge in fatalities caused by COVID-19.

positive: Potential Fecal Transmission of SARS-CoV-2: Current Evidence and Implications for Public Health Abstract Coronavirus disease 2019 (COVID-19) emerged in Hubei Province, China in December 2019 and has since become a global pandemic, with hundreds of thousands of cases and over 165 affected countries. Primary routes of transmission of the causative virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are through respiratory droplets and close person-to-person contact. While information about other potential modes of transmission are relatively sparse, evidence supporting the possibility of a fecally-mediated mode of transmission has been accumulating. Here, current knowledge on the potential for fecal transmission is briefly reviewed and the possible implications are discussed from a public health perspective.

positive: Short term change in relative humidity during the festival of Diwali in India Abstract The changes in humidity levels during the Diwali festivities have been examined over a period of 13 years at three Indian metro cities: Ahmedabad, New Delhi and Kolkata. A small short term increase in relative humidity even in the absence of transport of humid air from Arabian Sea and Bay of Bengal has been observed. The relative humidity levels were found to be exceeding the ambient levels during night and lying below the ambient levels during morning hours, indicating an increase in the survival rates of viruses responsible for the transmission of viral infections, as well as triggering immune-mediated illnesses such as asthma during Diwali.

positive: Comprehensive review of coronavirus disease 2019 (COVID-19) Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 in Wuhan, the capital of China's Hubei province and has rapidly spread all over the world. The World Health Organization (WHO) declared the outbreak to be a Public Health Emergency of International Concern on 30 January 2020 and recognized it as a pandemic on 11 March 2020. The number of people diagnosed with COVID-19 worldwide crossed the one million mark on April 2, 2020; two million mark on April 15, 2020; three million mark on April 27,2020 and the four million mark on May 9,2020. Despite containment efforts, more than 187 countries have been affected with more than 4, 178,346 cases in the world with maximum being in USA (1, 347,936) followed by 227,436 in Spain and 224, 422 in United Kingdom as of May, 2020. COVID-19 is the latest threat to face mankind cutting across geographical barriers in a rapidly changing landscape. This review provides an update on a rapidly evolving global pandemic. As we face the threat of emerging and re-emerging infectious diseases, this is a stark reminder to invest in population health, climate change countermeasures, a global health surveillance system and effective research into identifying pathogens, their treatment and prevention and effective health delivery systems.

positive: Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing.

positive: Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy The practice of social distancing and wearing masks has been popular worldwide in combating the contraction of COVID-19. Undeniably, although such practices help control the COVID-19 pandemic to a greater extent, the complete control of viral-laden droplet and aerosol transmission by such practices is poorly understood. This review paper intends to outline the literature concerning the transmission of viral-laden droplets and aerosols in different environmental settings and demonstrates the behavior of droplets and aerosols resulted from a cough-jet of an infected person in various confined spaces. The case studies that have come out in different countries have, with prima facie evidence, manifested that the airborne transmission plays a profound role in contracting susceptible hosts. Interestingly, the nosocomial transmission by airborne SARS-CoV-2 viral-laden aerosols in healthcare facilities may be plausible. Hence, clearly defined, science-based administrative, clinical, and physical measures are of paramount importance to eradicate the COVID-19 pandemic from the world.

positive: Role of viral bioaerosols in nosocomial infections and measures for prevention and control Abstract The presence of patients with diverse pathologies in hospitals results in an environment that can be rich in various microorganisms including respiratory and enteric viruses, leading to outbreaks in hospitals or spillover infections to the community. All hospital patients are at risk of nosocomial viral infections, but vulnerable groups such as older adults, children and immuno-compromised/-suppressed patients are at particular risk of severe outcomes including prolonged hospitalization or death. These pathogens could transmit through direct or indirect physical contact, droplets or aerosols, with increasing evidence suggesting the importance of aerosol transmission in nosocomial infections of respiratory and enteric viruses. Factors affecting the propensity to transmit and the severity of disease transmitted via the aerosol route include the biological characteristics affecting infectivity of the viruses and susceptibility of the host, the physical properties of aerosol particles, and the environmental stresses that alter these properties such as temperature and humidity. Non-specific systematic and individual-based interventions designed to mitigate the aerosol route are available although empirical evidence of their effectiveness in controlling transmission of respiratory and enteric viruses in healthcare settings are sparse. The relative importance of aerosol transmission in healthcare setting is still an on-going debate, with particular challenge being the recovery of infectious viral bioaerosols from real-life settings and the difficulty in delineating transmission events that may also be a result of other modes of transmission. For the prevention and control of nosocomial infections via the aerosol route, more research is needed on identifying settings, medical procedures or equipment that may be associated with an increased risk of aerosol transmission, including defining which procedures are aerosol-generating; and on the effectiveness of systematic interventions on aerosol transmission of respiratory and enteric viruses in healthcare settings.

positive: Biological and social aspects of Coronavirus Disease 2019 (COVID-19) related to oral health. The expansion of coronavirus disease 2019 (COVID-19) throughout the world has alarmed all health professionals. Especially in dentistry, there is a growing concern due to it's high virulence and routes of transmission through saliva aerosols. The virus keeps viable on air for at least 3 hours and on plastic and stainless-steel surfaces up to 72 hours. In this sense, dental offices, both in the public and private sectors, are high-risk settings of cross infection among patients, dentists and health professionals in the clinical environment (including hospital's intensive dental care facilities). This manuscript aims to compile current available evidence on prevention strategies for dental professionals. Besides, we briefly describe promising treatment strategies recognized until this moment. The purpose is to clarify dental practitioners about the virus history and microbiology, besides guiding on how to proceed during emergency consultations based on international documents. Dentists should consider that a substantial number of individuals (including children) who do not show any signs and symptoms of COVID-19 may be infected and can disseminate the virus. Currently, there is no effective treatment and fast diagnosis is still a challenge. All elective dental treatments and non-essential procedures should be postponed, keeping only urgent and emergency visits to the dental office. The use of teledentistry (phone calls, text messages) is a very promising tool to keep contact with the patient without being at risk of infection.

positive: Routes of transmission of influenza A H1N1, SARS CoV, and norovirus in air cabin: Comparative analyses Identifying the exact transmission route(s) of infectious diseases in indoor environments is a crucial step in developing effective intervention strategies. In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in‐flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. The simulation results seemed to suggest that the close contact route was probably the most significant route (contributes 70%, 95% confidence interval [CI]: 67%‐72%) in the in‐flight transmission of influenza A H1N1 transmission; as a result, passengers within 2 rows of the index case had a significantly higher infection risk than others in the outbreak (relative risk [RR]: 13.4, 95% CI: 1.5‐121.2, P = .019). For SARS CoV, the airborne, close contact, and fomite routes contributed 21% (95% CI: 19%‐23%), 29% (95% CI: 27%‐31%), and 50% (95% CI: 48%‐53%), respectively. For norovirus, the simulation results suggested that the fomite route played the dominant role (contributes 85%, 95% CI: 83%‐87%) in most cases; as a result, passengers in aisle seats had a significantly higher infection risk than others (RR: 9.5, 95% CI: 1.2‐77.4, P = .022). This work highlighted a method for using observed outbreak data to analyze the roles of different infection transmission routes.

positive: SARS-CoV-2 is transmitted via contact and via the air between ferrets SARS-CoV-2, a coronavirus that newly emerged in China in late 2019 1,2 and spread rapidly worldwide, caused the first witnessed pandemic sparked by a coronavirus. As the pandemic progresses, information about the modes of transmission of SARS-CoV-2 among humans is critical to apply appropriate infection control measures and to slow its spread. Here we show that SARS-CoV-2 is transmitted efficiently via direct contact and via the air (via respiratory droplets and/or aerosols) between ferrets. Intranasal inoculation of donor ferrets resulted in a productive upper respiratory tract infection and long-term shedding, up to 11 to 19 days post-inoculation. SARS-CoV-2 transmitted to four out of four direct contact ferrets between 1 and 3 days after exposure and via the air to three out of four independent indirect recipient ferrets between 3 and 7 days after exposure. The pattern of virus shedding in the direct contact and indirect recipient ferrets was similar to that of the inoculated ferrets and infectious virus was isolated from all positive animals, showing that ferrets were productively infected via either route. This study provides experimental evidence of robust transmission of SARS-CoV-2 via the air, supporting the implementation of community-level social distancing measures currently applied in many countries in the world and informing decisions on infection control measures in healthcare settings 3.

positive: COVID-19: A promising cure for the global panic Abstract The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is the causative agent of a potentially fatal disease that is of great global public health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to inadequate risk assessment regarding the urgency of the situation. The COVID-19 pandemic has entered a dangerous new phase. When compared with SARS and MERS, COVID-19 has spread more rapidly, due to increased globalization and adaptation of the virus in every environment. Slowing the spread of the COVID-19 cases will significantly reduce the strain on the healthcare system of the country by limiting the number of people who are severely sick by COVID-19 and need hospital care. Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind the infection and its immune response. Further, the current treatment options, drugs available, ongoing trials and recent diagnostics for COVID-19 have been discussed. We suggest traditional Indian medicinal plants as possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways.

positive: An overview of coronaviruses including the SARS-2 coronavirus - Molecular biology, epidemiology and clinical implications Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.

positive: The role of environmental factors to transmission of SARS-CoV-2 (COVID-19) The current outbreak of the novel coronavirus disease 2019 (COVID-19) in more than 250 countries has become a serious threat to the health of people around the world. Human-to-human transmission of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs most often when people are in the incubation stage of the disease or are carriers and have no symptoms. Therefore, in this study, was discussed the role of environmental factors and conditions such as temperature, humidity, wind speed as well as food, water and sewage, air, insects, inanimate surfaces, and hands in COVID-19 transmission. The results of studies on the stability of the SARS-CoV-2 on different levels showed that the resistance of this virus on smooth surfaces was higher than others. Temperature increase and sunlight can facilitate the destruction of SARS-COV-2 and the stability of it on surfaces. When the minimum ambient air temperature increases by 1 °C, the cumulative number of cases decreases by 0.86%. According to the latest evidence, the presence of coronavirus in the sewer has been confirmed, but there is no evidence that it is transmitted through sewage or contaminated drinking water. Also, SARS-COV-2 transmission through food, food packages, and food handlers has not been identified as a risk factor for the disease. According to the latest studies, the possibility of transmitting SARS-COV-2 bioaerosol through the air has been reported in the internal environment of ophthalmology. The results additionally show that infectious bio-aerosols can move up to 6 feet. There have been no reports of SARS-COV-2 transmission by blood-feeding arthropods such as mosquitoes.

positive: Environmental concern regarding the effect of humidity and temperature on 2019-nCoV survival: fact or fiction The new coronavirus, called 2019-nCoV, is a new type of virus that was first identified in Wuhan, China, in December 2019. Environmental conditions necessary for survival and spread of 2019-nCoV are somewhat transparent but unlike animal coronaviruses. We are poorly aware of their survival in environment and precise factors of their transmission. Countries located in east and west of globe did not have a significant impact on prevalence of disease among communities, and on the other hand, north and south have provided a model for relative prediction of disease outbreaks. The 2019-nCoV can survive for up to 9 days at 25 °C, and if this temperature rises to 30 °C, its lifespan will be shorter. The 2019-nCoV is sensitive to humidity, and lifespan of viruses in 50% humidity is longer than that of 30%. Also, temperature and humidity are important factors influencing the COVID-19 mortality rate and may facilitate 2019-nCoV transmission. Thus, considering the available and recent evidence, it seems that low temperatures, as well as dry and unventilated air, may affect stability and transmissibility of 2019-nCoV.

positive: Viral air load due to sedimenting and evaporating droplets produced by speaking The effect of evaporation on droplet sedimentation times is crucial for estimating the risk of infection from virus-containing airborne droplets. For droplet radii in the range 100 nm<R<60 {\mu}m, evaporation can be described in the stagnant-flow approximation and is diffusion limited. Analytical equations are presented for the droplet evaporation rate, the time-dependent droplet size and the sedimentation time, including the significant effect of evaporation cooling. Evaporation makes the time for large droplets to sediment much longer and thus significantly increases the viral air load. Using recent estimates for SARS-CoV-2 concentrations in sputum and droplet production rates while speaking, a single infected person that constantly speaks without a mouth cover produces a total air load of more than 10^4 virions. In a mid-size closed room, this leads to a viral inhalation frequency of at least 2.5 per minute. Low relative humidity, as encountered inside buildings in winter and in airliners, speeds evaporation and thus keeps initially larger droplets suspended in air.

positive: 6.08 Indoor Microbiome and Airborne Pathogens Abstract Individuals spend a majority of their time in indoor or built environments (BEs), where they are exposed to a diverse community of co-existing microorganisms. These microorganisms constitute the BE microbiome. While predominantly consisting of commensal microorganisms, the BE microbiome also contains pathogens that may be transmitted to and between indoor occupants. Therefore, characterization of the BE microbiome and understanding how different factors affect the BE microbiome will enable building scientists to assess health risks associated with indoor microbial exposure and manipulate BE conditions to maximize the health and well-being of occupants. We provide an overview of various aspects of the BE microbiome, including the importance of understanding the indoor microbiome from ecological and clinical perspectives, the history behind BE microbiome research, current laboratory, statistical, and bioinformatic methodologies and considerations in BE microbiome research, the different BE microbiome components and factors that shape this microbiome, the risks of pathogen transmission within BEs, and future directions in BE microbiome research. Some of the most recent and cutting-edge research works are described here, with the aim of providing a comprehensive and up-to-date account of the key findings within the field of indoor microbiology.

positive: The coronavirus pandemic and aerosols: Does COVID-19 transmit via expiratory particles?

positive: Textile Masks and Surface Covers - A 'Universal Droplet Reduction Model' Against Respiratory Pandemics The main form of COVID-19 transmission is via oral-respiratory droplet contamination (droplet; very small drop of liquid) produced when individuals talk, sneeze or cough. In hospitals, health-care workers wear facemasks as a minimum medical droplet precaution to protect themselves. Due to the shortage of masks during the pandemic, priority is given to hospitals for their distribution. As a result, the availability/use of medical masks is discouraged for the public. However, given that asymptomatic individuals, not wearing masks within the public, can be highly contagious for COVID-19, prevention of environmental droplet contamination (EnDC) from coughing/sneezing/speech is fundamental to reducing transmission. As an immediate solution to promote public droplet safety, we assessed household textiles to quantify their potential as effective environmental droplet barriers (EDBs). The synchronized implementation of a universal community droplet reduction solution is discussed as a model against COVID-19. Using a bacterial-suspension spray simulation model of droplet ejection (mimicking a sneeze), we quantified the extent by which widely available clothing fabrics reduce the dispersion of droplets onto surfaces within 1.8m, the minimum distance recommended for COVID-19 social distancing. All textiles reduced the number of droplets reaching surfaces, restricting their dispersion to <30cm, when used as single layers. When used as double-layers, textiles were as effective as medical mask/surgical-cloth materials, reducing droplet dispersion to <10cm, and the area of circumferential contamination to ~0.3%. The synchronized implementation of EDBs as a community droplet reduction solution (i.e., face covers/scarfs/masks & surface covers) could reduce EnDC and the risk of transmitting or acquiring infectious respiratory pathogens, including COVID-19.

positive: Environmental and Decontamination Issues for Human Coronaviruses and Their Potential Surrogates Pandemic COVID-19 gives ample reason to generally review coronavirus (CoV) containment. For establishing some preliminary views on decontamination and disinfection, surrogate CoVs have commonly been assessed. This review serves to examine the existing science in regards to CoV containment generically and then to translate these findings into timely applications for COVID-19. There is widespread dissemination of CoVs in the immediate patient environment, and CoVs can potentially be spread via respiratory secretions, urine, and stool. Interpretations of the spread however must consider whether studies examine for viral RNA, virus viability by culture, or both. Pre-symptomatic, asymptomatic, and post-fourteen day virus excretion from patients may complicate the epidemiology. Whereas droplet spread is accepted, there continues to be controversy over the extent of possible airborne spread and especially now for SARS-CoV-2. CoVs are stable in body secretions and sewage at reduced temperatures. In addition to temperature, dryness or relative humidity, initial viral burden, concomitant presence of bioburden, and the type of surface can all affect stability. Generalizing, CoVs can be susceptible to radiation, temperature extremes, pH extremes, peroxides, halogens, aldehydes, many solvents, and several alcohols. Whereas detergent surfactants can have some direct activity, these agents are better used as complements to a complex disinfectant solution. Disinfectants with multiple agents and adverse pH are more likely to be best active at higher water temperatures. Real-life assessments should be encouraged with working dilutions. The use of decontamination and disinfection should be balanced with considerations of patient and caregiver safety. Processes should also be balanced with considerations for other potential pathogens that must be targeted. Given some CoV differences and given that surrogate testing provides experimental correlates at best, direct assessments with SARS-CoV, MERS-CoV, and SARS-CoV-2 are required. This article is protected by copyright. All rights reserved.

positive: Taiwan's traffic control bundle and the elimination of nosocomial severe acute respiratory syndrome among healthcare workers Summary The traffic control bundle consists of procedures designed to help prevent epidemic nosocomial infection. We retrospectively studied the serial infection control measures to determine factors most effective in preventing nosocomial infections of healthcare workers (HCWs) during the 2003 Taiwanese severe acute respiratory syndrome (SARS) epidemic. Fever screening stations, triage of fever patients, separating SARS patients from other patients, separation of entrances and passageways between patients and HCWs, and increasing hand-washing facilities all demonstrated a protective effect for HCWs (univariate analysis; P <0.05). By multiple logistic regression: (i) checkpoint alcohol dispensers for glove-on hand rubbing between zones of risk, and (ii) fever screening at the fever screen station outside the emergency department, were the significant methods effectively minimising nosocomial SARS infection of HCWs (P <0.05). The traffic control bundle should be implemented in future epidemics as a tool to achieve strict infection control measures.

positive: Effects of air temperature and relative humidity on coronavirus survival on surfaces. Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4 degrees C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20 degrees C than at 4 degrees C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40 degrees C than at 20 degrees C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.

positive: Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonosis that causes death in 35·7% of cases. As of Feb 28, 2018, 2182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide, with most being reported in Saudi Arabia (1807 cases with 705 deaths). MERS-CoV features prominently in the WHO blueprint list of priority pathogens that threaten global health security. Although primary transmission of MERS-CoV to human beings is linked to exposure to dromedary camels (Camelus dromedarius), the exact mode by which MERS-CoV infection is acquired remains undefined. Up to 50% of MERS-CoV cases in Saudi Arabia have been classified as secondary, occurring from human-to-human transmission through contact with asymptomatic or symptomatic individuals infected with MERS-CoV. Hospital outbreaks of MERS-CoV are a hallmark of MERS-CoV infection. The clinical features associated with MERS-CoV infection are not MERS-specific and are similar to other respiratory tract infections. Thus, the diagnosis of MERS can easily be missed, unless the doctor or health-care worker has a high degree of clinical awareness and the patient undergoes specific testing for MERS-CoV. The largest outbreak of MERS-CoV outside the Arabian Peninsula occurred in South Korea in May, 2015, resulting in 186 cases with 38 deaths. This outbreak was caused by a traveller with undiagnosed MERS-CoV infection who became ill after returning to Seoul from a trip to the Middle East. The traveller visited several health facilities in South Korea, transmitting the virus to many other individuals long before a diagnosis was made. With 10 million pilgrims visiting Saudi Arabia each year from 182 countries, watchful surveillance by public health systems, and a high degree of clinical awareness of the possibility of MERS-CoV infection is essential. In this Review, we provide a comprehensive update and synthesis of the latest available data on the epidemiology, determinants, and risk factors of primary, household, and nosocomial transmission of MERS-CoV, and suggest measures to reduce risk of transmission.

positive: Detection of SARS-CoV-2 in Exhaled Breath from COVID-19 Patients Ready for Hospital Discharge The COVID-19 pandemic has brought an unprecedented crisis to the global health sector1. When recovering COVID-19 patients are discharged in accordance with throat or nasal swab protocols using reverse transcription polymerase chain reaction (RT-PCR), the potential risk of re-introducing the infection source to humans and the environment must be resolved 2,3,4. Here we show that 20% of COVID-19 patients, who were ready for a hospital discharge based on current guidelines, had SARS-CoV-2 in their exhaled breath (~105 RNA copies/m3). They were estimated to emit about 1400 RNA copies into the air per minute. Although fewer surface swabs (1.3%, N=318) tested positive, medical equipment frequently contacted by healthcare workers and the work shift floor were contaminated by SARS-CoV-2 in four hospitals in Wuhan. All air samples (N=44) appeared negative likely due to the dilution or inactivation through natural ventilation (1.6-3.3 m/s) and applied disinfection. Despite the low risk of cross environmental contamination in the studied hospitals, there is a critical need for strengthening the hospital discharge standards in preventing re-emergence of COVID-19 spread.

positive: Resistance of Enteric Viruses on Fomites Human enteric viruses are associated with several clinical features, especially gastroenteritis. Large amounts of these viruses can be released in the environment and spread to people. Enteric viruses are nonenveloped viruses and have displayed good survival in the environment. They can be significantly resistant in food and water but also on fomites, and this is thought to play a role in transmission, leading to sporadic cases or outbreaks. The survival of enteric viruses on fomites relies on many factors including the virus itself, fomite properties, and extrinsic environmental factors such as temperature or relative humidity. Several reports in the literature have found an association with gastroenteritis cases or outbreaks and fomites naturally contaminated by enteric viruses. However, the study of virus survival following natural contamination is challenging, and most published studies are laboratory based, using experimental contamination. In addition, recent and detailed data on the resistance of each of the main enteric viruses on fomites are scarce. Many approaches, both physical and chemical, can be used to inactivate enteric viruses, the efficacy of which depends on the virus and the disinfection conditions.

positive: Disinfection effect of pulsed xenon ultraviolet irradiation on SARS-CoV-2 and implications for environmental risk of COVID-19 transmission Prolonged survival of SARS-CoV-2 on environmental surfaces and personal protective equipment (PPE) may lead to these surfaces transmitting disease to others. This article reports the effectiveness of a pulsed xenon ultraviolet (PX-UV) disinfection system in reducing the load of SARS-CoV-2 on hard surfaces and N95 respirators. Chamber slides and N95 respirator material were directly inoculated with SARS-CoV-2 and exposed to different durations of PX-UV disinfection. For hard surfaces, disinfection for 1, 2, and 5 minutes resulted in 3.53 Log10, >4.54 Log10, and >4.12 Log10 reductions in viral load, respectively. For N95 respirators, disinfection for 5 minutes resulted in >4.79 Log10 reduction in viral load. We found that PX-UV significantly reduces SARS-CoV-2 on hard surfaces and N95 respirators. With the potential to rapidly disinfectant environmental surfaces and N95 respirators, PX-UV devices are a promising technology for the reduction of environmental and PPE bioburden and to enhance both HCW and patient safety by reducing the risk of exposure to SARS-CoV-2.

positive: Considerations in performing endoscopy during the COVID-19 pandemic

positive: Experimental aerosol survival of SARS-CoV-2 in artificial saliva and tissue culture media at medium and high humidity SARS-CoV-2, the causative agent of the COVID-19 pandemic, may be transmitted via airborne droplets or contact with surfaces onto which droplets have deposited. In this study, the ability of SARS-CoV-2 to survive in the dark, at two different relative humidity values and within artificial saliva, a clinically relevant matrix, was investigated. SARS-CoV-2 was found to be stable, in the dark, in a dynamic small particle aerosol under the four experimental conditions we tested and viable virus could still be detected after 90 minutes. The decay rate and half-life was determined and decay rates ranged from 0.4 to 2.27 % per minute and the half lives ranged from 30 to 177 minutes for the different conditions. This information can be used for advice and modelling and potential mitigation strategies.

positive: Environmental Contamination of SARS-CoV-2 in Healthcare Premises Abstract Objectives A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. Methods We collected 626 surface swabs within the Zhongnan Medical Center in Wuhan in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major PPE. The SARS-CoV-2 RNAs were detected by reverse transcription-PCR. Results The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects were self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were the most contaminated PPE. Conclusion Our findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention among HCWs during the outbreak of COVID-19.

positive: COVID-19: Effects of weather conditions on the propagation of respiratory droplets As the number of confirmed cases of Coronavirus disease 2019 (COVID-19) continues to increase, there has been a rising concern regarding the effect of weather conditions, especially over the upcoming summer, on the transmission of this disease. In this study, we assess the transmission of COVID-19 under different weather conditions by investigating the propagation of infectious respiratory droplets. A comprehensive mathematical model is established to explore their evaporation, heat transfer and kinematics under different temperature, humidity and ventilation conditions. The transmitting pathway of COVID-19 through respiratory droplets is divided into short-range droplet contacts and long-range aerosol exposure. We show that the effect of weather conditions is not monotonic: low temperature and high humidity facilitate droplet contact transmission, while high temperature and low humidity promote the formation of aerosol particles and accumulation of particles with a diameter of 2.5 m or less (PM2.5). Our model suggests that the 6 ft of social distance recommended by the Center for Disease Control and Prevention (CDC) may be insufficient in certain environmental conditions, as the droplet spreading distance can be as long as 6 m (19.7 ft) in cold and humid weather. The results of this study suggest that the current pandemic may not ebb in the summer of the northern hemisphere without proper intervention, as there is an increasing chance of aerosol transmission. We also emphasize that the meticulous design of building ventilation systems is critical in containing both the droplet contact infections and aerosol exposures.

positive: COVID‐19 dentistry‐related aspects: a literature overview A new coronavirus (Sars‐CoV‐2) was detected in China at the end of 2019 and has since caused a worldwide pandemic. This virus is responsible for an acute respiratory syndrome (COVID‐19), distinguished by a potentially lethal interstitial bilateral pneumonia. Because Sars‐CoV‐2 is highly infective through airborne contamination, the high infection risk in the dental environment is a serious problem for both professional practitioners and patients. This literature overview provides a description of the clinical aspects of COVID‐19 and its transmission, while supplying valuable information regarding protection and prevention measures.

positive: An Imperative Need for Research on the Role of Environmental Factors in Transmission of Novel Coronavirus (COVID-19)

positive: Association between ambient temperature and COVID-19 infection in 122 cities from China Abstract Background Coronavirus disease 2019 (COVID-19) has become a severe public health problem globally. Both epidemiological and laboratory studies have shown that ambient temperature could affect the transmission and survival of coronaviruses. This study aimed to determine whether the temperature is an essential factor in the infection caused by this novel coronavirus. Methods Daily confirmed cases and meteorological factors in 122 cities were collected between January 23, 2020, to February 29, 2020. A generalized additive model (GAM) was applied to explore the nonlinear relationship between mean temperature and COVID-19 confirmed cases. We also used a piecewise linear regression to determine the relationship in detail. Results The exposure-response curves suggested that the relationship between mean temperature and COVID-19 confirmed cases was approximately linear in the range of <3 °C and became flat above 3 °C. When mean temperature (lag0–14) was below 3 °C, each 1 °C rise was associated with a 4.861% (95% CI: 3.209–6.513) increase in the daily number of COVID-19 confirmed cases. These findings were robust in our sensitivity analyses. Conclusions Our results indicate that mean temperature has a positive linear relationship with the number of COVID-19 cases with a threshold of 3 °C. There is no evidence supporting that case counts of COVID-19 could decline when the weather becomes warmer, which provides useful implications for policymakers and the public.

positive: How Should the Rehabilitation Community Prepare for 2019-nCoV? Abstract With the 2019-nCoV pandemic spreading quickly in USA and the world, it is urgent that the rehabilitation community quickly understands the epidemiology of the virus and what we can and must do to face this microbial adversary at the early stages of this likely long global pandemic. The 2019-nCoV is a novel virus so the majority of world’s population does not have prior immunity to it. It is more infectious and fatal than seasonal influenza, and definitive treatment and a vaccine are months away. Our arsenal against it are currently mainly social distancing and infection control measures.

positive: A physicist view of the airborne infection Naturally produced droplets from humans (such as those produced by breathing, talking, sneezing, and coughing) include several types of cells (e.g., epithelial cells and cells of the immune system), physiological electrolytes contained in mucous and saliva (e.g. Na+, K+, Cl-), as well as, potentially, several infectious agents (e.g. bacteria, fungi, and viruses). In response to the novel coronavirus SARS-CoV-2 epidemic, which has become a major public health issue worldwide, we provide a didactic overview of airborne germ transmission as seen from a physics perspective. We also provide a recommendation that could help to slow down the spread of the virus.

positive: Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China Data concerning the transmission of SARS-CoV-2 in asymptomatic and paucisymptomatic patients are lacking. We report a three-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight (53%) of 15 members from three families were confirmed with SARS-CoV-2 infection. Of eight patients, three were asymptomatic and one was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his three-month-old daughter. SARS-CoV-2 was detected in the environment of one household. The complete genomes of SARS-CoV-2 from the patients were >99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.

positive: Shell disorder analysis predicts greater resilience of the SARS-CoV-2 (COVID-19) outside the body and in body fluids The coronavirus (CoV) family consists of viruses that infects a variety of animals including humans with various levels of respiratory and fecal-oral transmission levels depending on the behavior of the viruses' natural hosts and optimal viral fitness. A model to classify and predict the levels of respective respiratory and fecal-oral transmission potentials of the various viruses was built before the outbreak of MERS-CoV using AI and empirically-based molecular tools to predict the disorder level of proteins. Using the percentages of intrinsic disorder (PID) of the nucleocapsid (N) and membrane (M) proteins of CoV, the model easily clustered the viruses into three groups with the SARS-CoV (M PID = 8%, N PID = 50%) falling into Category B, in which viruses have intermediate levels of both respiratory and fecal-oral transmission potentials. Later, MERS-CoV (M PID = 9%, N PID = 44%) was found to be in Category C, which consists of viruses with lower respiratory transmission potential but with higher fecal-oral transmission capabilities. Based on the peculiarities of disorder distribution, the SARS-CoV-2 (M PID = 6%, N PID = 48%) has to be placed in Category B. Our data show however, that the SARS-CoV-2 is very strange with one of the hardest protective outer shell, (M PID = 6%) among coronaviruses. This means that it might be expected to be highly resilient in saliva or other body fluids and outside the body. An infected body is likelier to shed greater numbers of viral particles since the latter is more resistant to antimicrobial enzymes in body fluids. These particles are also likelier to remain active longer. These factors could account for the greater contagiousness of the SARS-CoV-2 and have implications for efforts to prevent its spread.

positive: A Guide to COVID-19: a global pandemic caused by the novel coronavirus SARS-CoV-2 The emergence of the SARS-CoV-2 strain of the human coronavirus has thrown the world into the midst of a new pandemic. In the human body, the virus causes COVID-19, a disease characterized by shortness of breath, fever, and pneumonia, which can be fatal in vulnerable individuals. SARS-CoV-2 has characteristics of past human coronaviruses, with close genomic similarities to SARS-CoV, the virus that causes the disease SARS. Like these related coronaviruses, SARS-CoV-2 is transmitted through the inhalation of droplets and interaction with contaminated surfaces. Across the world, laboratories are developing candidate vaccines for the virus - with vaccine trials underway in the United States and the United Kingdom - and considering various drugs for possible treatments and prophylaxis. Here, we provide an overview of SARS-CoV-2 by analyzing its virology, epidemiology, and modes of transmission while examining the current progress of testing procedures and possible treatments through drugs and vaccines.

positive: Protective measures for COVID-19 for healthcare providers and laboratory personnel In the COVID-19 pandemic, which affects the whole world, healthcare professionals (HCP) are at high risk of transmission due to their direct contact with patients with COVID-19. Therefore, how to ensure the triage of the patient with acute respiratory symptoms should be determined in advance, the contact distance should be arranged to be at least 2 m, COVID-19 suspect or diagnosed patient should be instructed to wear a surgical mask. During the care of these patients, HCP should wear their personal protective equipment (PPE) in accordance with the procedure and should not neglect hand hygiene. The samples of the patient with known or suspected COVID-19, patient should also be known to be risky in terms of contamination, and a risk assessment should be performed for the procedures to be performed in laboratories. The PPE should be used in accordance with the procedure to be performed. The protection of the HCP, who sacrifice at the risk of life, is possible only by complying with infection control and precautions.

positive: No time for dilemma: mass gatherings must be suspended

positive: SARS-CoV-2 in environmental samples of quarantined households The role of environmental transmission of SARS-CoV-2 remains unclear. Particularly the close contact of persons living together or cohabitating in domestic quarantine could result in high risk for exposure to the virus within the households. Therefore, the aim of this study was to investigate the whereabouts of the virus and whether useful precautions to prevent the dissemination can be given. 21 households under quarantine conditions were randomly selected for this study. All persons living in each household were recorded in terms of age, sex and time of household quarantine. Throat swabs for analysis were obtained from all adult individuals and most of the children. Air, wastewater samples and surface swabs (commodities) were obtained and analysed by RT-PCR. Positive swabs were cultivated to analyse for viral infectivity. 26 of all 43 tested adults (60.47 %) tested positive by RT-PCR. All 15 air samples were PCR-negative. 10 of 66 wastewater samples were positive for SARS-CoV-2 (15.15 %) as well as 4 of 119 object samples (3.36 %). No statistically significant correlation between PCR-positive environmental samples and the extent of infection spread inside the household could be observed. No infectious virus could be isolated under cell culture conditions. As we cannot rule out transmission through surfaces, hygienic behavioural measures are important in the households of SARS-CoV-2 infected individuals to avoid potential transmission through surfaces. The role of the domestic environment, in particular the wastewater load in washbasins and showers, in the transmission of SARS CoV-2 should be further clarified.

positive: Conceptual Design of a Body Bag for Preventing Infections and Safe Disposal of Deceased from COVID-19 Virus The Covid-19 virus pandemic is leading to a large number of deaths. There are forecasts that there will be an exponential increase in the number of such deaths across the globe because of this deadly virus. To arrest the spread of the virus in this situation, the supply of medical materials including PPE and body bags (also known as human remains pouch or cadaver bag) should be designed to stop the spread of the Covid-19 virus. Conventional body bags have shortcomings, which need to be addressed by a refined redesigning and use of appropriate materials to adequately match the requirements in the current Covid-19 situation. Current designs of the body bags do not allow the family member’s sentiments towards the deceased and to cater to the desire of the family members to view the face of the deceased without exposing them to a strong possibility of infection from the cadaver. This is, therefore, a very traumatic experience to the family and in many cases, the cadaver is not handled with respect due to the unavailability of safe design body bags, which also exposes health workers to avoidable risk from the infections. Technopark@iitk has proposed an integrated 5-layer body bag to tackle this situation for Covid-19 deceased such that it is (1) leak-proof, (2) impermeable/water-proof, (3) strong enough for the purpose, (4) ergonomically designed, and (5) has provision to view the face of the dead body for family viewing before cremation/burial. This new design would keep the handling of the deceased body to a minimum during transportation from the hospital/site of death to a mortuary, and then to the home of the deceased/burial ground/crematorium, where it may be disposed-off along with the body in it, in a respectable manner, without putting people involved to the risk of infection.

positive: Personal protective equipment and possible routes of airborne spread during the COVID‐19 pandemic We welcomed Professor Cook's article clarifying the use of personal protective equipment (PPE) in protecting staff during the current COVID-19 pandemic [1]. There remains considerable debate about the extent to which airborne spread of SARS-CoV-2 occurs. Small droplets (< 5µm) are thought to remain suspended in the air and could theoretically be inhaled into the lungs causing infection [2]. Loose fitting "surgical" masks will not prevent such inhalation and only a tight-fitting filtering mask is adequate. Conversely larger (> 5µm) particles do not remain suspended in the air [2] and can only cause infection if they are immediately inhaled, or after contact with a surface they land on.

positive: A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19) Coronavirus disease 2019 (COVID-19) is a declared global pandemic. There are multiple parameters of the clinical course and management of the COVID-19 that need optimization. A hindrance to this development is the vast amount of misinformation present due to scarcely sourced manuscript preprints and social media. This literature review aims to presents accredited and the most current studies pertaining to the basic sciences of SARS-CoV-2, clinical presentation and disease course of COVID-19, public health interventions, and current epidemiological developments. The review on basic sciences aims to clarify the jargon in virology, describe the virion structure of SARS-CoV-2 and present pertinent details relevant to clinical practice. Another component discussed is the brief history on the series of experiments used to explore the origins and evolution of the phylogeny of the viral genome of SARS-CoV-2. Additionally, the clinical and epidemiological differences between COVID-19 and other infections causing outbreaks (SARS, MERS, H1N1) are elucidated. Emphasis is placed on evidence-based medicine to evaluate the frequency of presentation of various symptoms to create a stratification system of the most important epidemiological risk factors for COVID-19. These can be used to triage and expedite risk assessment. Furthermore, the limitations and statistical strength of the diagnostic tools currently in clinical practice are evaluated. Criteria on rapid screening, discharge from hospital and discontinuation of self-quarantine are clarified. Epidemiological factors influencing the rapid rate of spread of the SARS-CoV-2 virus are described. Accurate information pertinent to improving prevention strategies is also discussed. The penultimate portion of the review aims to explain the involvement of micronutrients such as vitamin C and vitamin D in COVID19 treatment and prophylaxis. Furthermore, the biochemistry of the major candidates for novel therapies is briefly reviewed and a summary of their current status in the clinical trials is presented. Lastly, the current scientific data and status of governing bodies such as the Center of Disease Control (CDC) and the WHO on the usage of controversial therapies such as angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen), and corticosteroids usage in COVID-19 are discussed. The composite collection of accredited studies on each of these subtopics of COVID-19 within this review will enable clarification and focus on the current status and direction in the planning of the management of this global pandemic.

positive: Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40°N latitude at sea level on a clear day. Significant inactivation also occurred, albeit at a slower rate, under lower simulated sunlight levels. The present study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments. Additionally, these data indicate that natural sunlight may be effective as a disinfectant for contaminated nonporous materials.

positive: What do we know about the SARS-CoV-2 coronavirus in the environment? Abstract In view of the current situation regarding the Covid-19 disease, a discussion is proposed on the need for research focusing on the presence and evolution of the SARS-CoV-2 virus in water, soils and other environmental compartments, reached through wastewater and sewage sludge spreading. Also, the evaluation of current treatments for wastewater and sewage sludge, as well as the eventual development of new specific techniques, based on sorption, nanotechnology, etc., would be of great interest for controlling the environmental dissemination of these viruses in the current and eventual future outbreaks.

positive: COVID-19 Patients: Are Current Isolation Guidelines Effective Enough?

positive: Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations Summary As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill.

positive: Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 °C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.

positive: Asymptomatic COVID-19 Infection in a Child with Nasal Foreign Body Abstract While children, particularly infants, are susceptible to severe and critical COVID-19 disease, over 55% of pediatric cases are present in asymptomatic or mildly symptomatic children. Aerosolized SARS-CoV-2 viral particles remain viable for up to 3 hours, raising concern about risk to healthcare workers during aerosol generating procedures (APGs) in the airway and nasopharynx. Herein we describe the first case of a nasal foreign body in an asymptomatic child with SARS-CoV-2 infection. We discuss management of this child and highlight the importance of considering asymptomatic infection and preoperative testing when planning procedures of the airway in the COVID-19 era.

positive: Detection of Airborne Severe Acute Respiratory Syndrome (SARS) Coronavirus and Environmental Contamination in SARS Outbreak Units Severe acute respiratory syndrome (SARS) is characterized by a risk of nosocomial transmission; however, the risk of airborne transmission of SARS is unknown. During the Toronto outbreaks of SARS, we investigated environmental contamination in SARS units, by employing novel air sampling and conventional surface swabbing. Two polymerase chain reaction (PCR)–positive air samples were obtained from a room occupied by a patient with SARS, indicating the presence of the virus in the air of the room. In addition, several PCR-positive swab samples were recovered from frequently touched surfaces in rooms occupied by patients with SARS (a bed table and a television remote control) and in a nurses’ station used by staff (a medication refrigerator door). These data provide the first experimental confirmation of viral aerosol generation by a patient with SARS, indicating the possibility of airborne droplet transmission, which emphasizes the need for adequate respiratory protection, as well as for strict surface hygiene practices

positive: Effects of temperature and humidity on the spread of COVID-19: A systematic review. Background: Faced with the global pandemic of COVID-19, declared by World Health Organization (WHO) on March 11th 2020, and the need to better understand the seasonal behavior of the virus, our team conducted this systematic review to describe current knowledge about the emergence and replicability of the virus and its correlation with different weather factors such as temperature and relative humidity. Methods: The review was registered with the PROSPERO database. The electronic databases PubMed, Scopus, Web of Science, Cochrane Library, LILACS, OpenGrey and Google Scholar were examined with the searches restricted to the years 2019 and 2020. Risk of bias assessment was performed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist tool. The GRADE tool was used to assess the quality of the evidence. Results: The initial screening identified 517 articles. After examination of the full texts, seventeen studies met the review's eligibility criteria. Great homogeneity was observed in the findings regarding the effect of temperature and humidity on the seasonal viability and transmissibility of COVID-19. Cold and dry conditions were potentiating factors on the spread of the virus. After quality assessment, four studies had a high risk of bias and thirteen studies were scored as moderate risk of bias. The certainty of evidence was graded as low for both outcomes evaluated. Conclusion: Considering the existing scientific evidence, warm and wet climates seem to reduce the spread of COVID-19. The certainty of the evidence generated was graded as low. However, these variables alone could not explain most of the variability in disease transmission.

positive: Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

positive: Survival on uncommon fomites of feline calicivirus, a surrogate of noroviruses BACKGROUND: Norovirus (NoV) transmission occurs mainly through food and fomites. Contaminated human fingers can transfer the virus to inanimate objects, which may then spread the virus to susceptible persons. However, no information is available on the survival of NoVs on fomites, which may be of importance in the transmission of NoVs in institutional settings such as hospitals and nursing homes. METHODS: In the absence of any in vitro cultivation system for NoVs, feline calicivirus (FCV) was used as a surrogate. Several fomites such as computer mouse, keyboard keys, telephone wire, telephone receiver, telephone buttons, and brass disks representing faucets and door handle surfaces were artificially contaminated with known amounts of FCV. Samples were taken at regular time intervals, and virus was titrated in feline kidney cells to determine its survival on these surfaces. RESULTS: Survivability of FCV varied with fomite type. The virus survived for up to 3 days on telephone buttons and receivers, for 1 or 2 days on computer mouse, and for 8 to 12 hours on keyboard keys and brass. The time for 90% virus reduction was <4 hours on computer keys, mouse, brass, and telephone wire; 4 to 8 hours on telephone receiver; and 12 to 24 hours on telephone buttons. CONCLUSION: The results of this study confirm that FCV (and perhaps NoV) can survive on fomites such as computers, telephones, and faucets and may be transmitted to humans using these contaminated materials. This may necessitate regular cleaning or disinfection of these items, especially in hospitals and nursing homes and after known outbreaks of NoVs.

positive: Influence of wind and relative humidity on the social distancing effectiveness to prevent COVID-19 airborne transmission: A numerical study It has been confirmed that the coronavirus disease 2019 (COVID-19) can transmit through droplets created when an infected human coughs or sneezes. Accordingly, 1.83-m (6-feet) social distancing is advised to reduce the spread of the disease among humans. This is based on the assumption that no air circulation exists around people. However, it is not well investigated whether the ambient wind and relative humidity (RH) will cause SARS-CoV-2 laden droplets to transport farther in the air, making the current social distancing policy insufficient. To provide evidence and insight into the “social distancing” guidelines, a validated computational fluid-particle dynamics (CFPD) model was employed to simulate the transient transport, condensation/evaporation, and deposition of SARS-CoV-2 laden droplets emitted by coughs, with different environmental wind velocities and RHs. Initial droplet diameters range from 2 to 2000 μm, and the wind velocities range from 0 to 16 km/h, representing different wind forces from calm air to moderate breeze. The comparison between a steady-state wind and a gust with a constant frequency has also been performed. Ambient RHs are 40% and 99.5%. The distances between the two virtual humans are 1.83 m and 3.05 m (6 feet and 10 feet). The facial covering effect on reducing the airborne transmission of the cough droplets has also been evaluated. Numerical results indicate that the ambient wind will enhance the complexity of the secondary flows with recirculation between the two virtual humans. Microdroplets follow the airflow streamlines well and deposit on both human bodies and head regions, even with the 3.05-m (10-feet) separation distance. The rest of the microdroplets can transport in the air farther than 3.05 m (10 feet) due to wind convection, causing a potential health risk to nearby people. High RH will increase the droplet sizes due to the hygroscopic growth effect, which increases the deposition fractions on both humans and the ground. With the complex environmental wind and RH conditions, the 6-feet social distancing policy may not be sufficient to protect the inter-person aerosol transmission, since the suspending micro-droplets were influenced by convection effects and can be transported from the human coughs/sneezes to the other human in less than 5 s. Thus, due to the complex real-world environmental ventilation conditions, a social distance longer than 6 feet needs to be considered. Wearing masks should also be recommended for both infected and healthy humans to reduce the airborne cough droplet numbers.

positive: Detection of Air and Surface Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Hospital Rooms of Infected Patients Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. We aimed to detect SARS-CoV-2 surface and air contamination and study associated patient-level factors. 245 surface samples were collected from 30 airborne infection isolation rooms of COVID-19 patients, and air sampling was conducted in 3 rooms. Air sampling detected SARS-CoV-2 PCR-positive particles of sizes >4 μm and 1-4 μm in two rooms, which warrants further study of the airborne transmission potential of SARS-CoV-2. 56.7% of rooms had at least one environmental surface contaminated. High touch surface contamination was shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01).

positive: Environmental Contamination and Viral Shedding in MERS Patients During MERS-CoV Outbreak in South Korea Background. Although Middle East Respiratory Syndrome coronavirus (MERS-CoV) is characterized by a risk of nosocomial transmission, the detailed mode of transmission and period of virus shedding from infected patients are poorly understood. The aims of this study were to investigate the potential role of environmental contamination by MERS-CoV in healthcare settings and to define the period of viable virus shedding from MERS patients. Methods. We investigated environmental contamination from 4 patients in MERS-CoV units of 2 hospitals. MERS-CoV was detected by reverse transcription polymerase chain reaction (PCR) and viable virus was isolated by cultures. Results. Many environmental surfaces of MERS patient rooms, including points frequently touched by patients or healthcare workers, were contaminated by MERS-CoV. Viral RNA was detected up to five days from environmental surfaces following the last positive PCR from patients’ respiratory specimens. MERS-CoV RNA was detected in samples from anterooms, medical devices, and air-ventilating equipment. In addition, MERS-CoV was isolated from environmental objects such as bed sheets, bedrails, IV fluid hangers, and X-ray devices. During the late clinical phase of MERS, viable virus could be isolated in 3 of the 4 enrolled patients on day 18 to day 25 after symptom onset. Conclusions. Most of touchable surfaces in MERS units were contaminated by patients and health care workers and the viable virus could shed through respiratory secretion from clinically fully recovered patients. These results emphasize the need for strict environmental surface hygiene practices, and sufficient isolation period based on laboratory results rather than solely on clinical symptoms.

positive: Risk of COVID-19 Transmission During Gastrointestinal Endoscopy COVID-19 is a viral illness caused by a novel severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). It is highly contagious virus with human-to-human transmission being primarily attributed to direct contact or air droplets. It is highly infectious and contagious due to high-viable viral loads in the upper respiratory tract secretions of infected patients and also similar viral load being detected in both asymptomatic and symptomatic patients. The virus stability characteristics and modes of transmission via fomites and air droplets make gastrointestinal (GI) endoscopy a high-risk procedure for COVID-19 transmission. This review discusses the currently available literature on risk of transmission of SARS-CoV-2 during GI endoscopy.

positive: Influence of wind and relative humidity on the social distancing effectiveness to prevent COVID-19 airborne transmission: A numerical study It has been confirmed that the coronavirus disease 2019 (COVID-19) can transmit through droplets created when an infected human coughs or sneezes. Accordingly, 1.83-m (6-feet) social distancing is advised to reduce the spread of the disease among humans. This is based on the assumption that no air circulation exists around people. However, it is not well investigated whether the ambient wind and relative humidity (RH) will cause SARS-CoV-2 laden droplets to transport farther in the air, making the current social distancing policy insufficient. To provide evidence and insight into the "social distancing" guidelines, a validated computational fluid-particle dynamics (CFPD) model was employed to simulate the transient transport, condensation/evaporation, and deposition of SARS-CoV-2 laden droplets emitted by coughs, with different environmental wind velocities and RHs. Initial droplet diameters range from 2 to 2000â¯µm, and the wind velocities range from 0 to 16â¯km/h, representing different wind forces from calm air to moderate breeze. The comparison between a steady-state wind and a gust with a constant frequency has also been performed. Ambient RHs are 40% and 99.5%. The distances between the two virtual humans are 1.83â¯m and 3.05â¯m (6 feet and 10 feet). The facial covering effect on reducing the airborne transmission of the cough droplets has also been evaluated. Numerical results indicate that the ambient wind will enhance the complexity of the secondary flows with recirculation between the two virtual humans. Microdroplets follow the airflow streamlines well and deposit on both human bodies and head regions, even with the 3.05-m (10-feet) separation distance. The rest of the microdroplets can transport in the air farther than 3.05â¯m (10 feet) due to wind convection, causing a potential health risk to nearby people. High RH will increase the droplet sizes due to the hygroscopic growth effect, which increases the deposition fractions on both humans and the ground. With the complex environmental wind and RH conditions, the 6-feet social distancing policy may not be sufficient to protect the inter-person aerosol transmission, since the suspending micro-droplets were influenced by convection effects and can be transported from the human coughs/sneezes to the other human in less than 5â¯s. Thus, due to the complex real-world environmental ventilation conditions, a social distance longer than 6 feet needs to be considered. Wearing masks should also be recommended for both infected and healthy humans to reduce the airborne cough droplet numbers.

positive: The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22–25°C and relative humidity of 40–50%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38°C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.

positive: Current emerging SARS-CoV-2 pandemic: potential direct/indirect negative impacts of virus persistence and related therapeutic drugs on the aquatic compartments The purpose of the present work is to provide a complete overview of possible direct/indirect implications on the quality of aquatic compartments due to the recent SARS-CoV-2 outbreak. With this aim, the environmental impacts are mainly related to i) the virus persistence in sewage and wastewaters, and ii) possible fate in aquatic compartments of drugs tested and administered to SARS-CoV-2 infected patients. Because SARS-CoV-2 spread is very recent, and there is a lack of specific studies on this strain, the virus persistence in wastewaters, the parameters influencing the persistence, as well as the detection methodologies are referenced to the general coronaviruses group. However, the present detailed report of up-to-date knowledge on this topic can provide a useful source for further studies focusing on more deepened investigations of SARS-CoV-2 behaviour in the environment. Such a perspective is significant not only for the control of virus diffusion but also represents a crucial point for the identification of produced alteration to the environmental quality.

positive: Fomite transmission and disinfection strategies for SARS-CoV-2 and related viruses Contaminated objects or surfaces, referred to as fomites, play a critical role in the spread of viruses, including SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The long persistence of viruses (hours to days) on surfaces calls for an urgent need for surface disinfection strategies to intercept virus transmission and the spread of the disease. Elucidating the physicochemical processes and surface science underlying the adsorption and transfer of virus between surfaces, as well as their inactivation, are important in understanding how the disease is transmitted, and in developing effective interception strategies. This review aims to summarize the current knowledge and underlying physicochemical processes of virus transmission, in particular via fomites, and common disinfection approaches. Gaps in knowledge and needs for further research are also identified. The review focuses on SARS-CoV-2, but will supplement the discussions with related viruses.

positive: Saliva is a non‐negligible factor in the spread of COVID‐19 SARS‐CoV‐2, a novel emerging coronavirus, has caused severe disease (COVID‐19), and rapidly spread worldwide since the beginning of 2020. SARS‐CoV‐2 mainly spreads by coughing, sneezing, droplet inhalation, and contact. SARS‐CoV‐2 has been detected in saliva samples, making saliva a potential transmission route for COVID‐19. The participants in dental practice confront a particular risk of SARS‐CoV‐2 infection due to close contact with the patients and potential exposure to saliva‐contaminated droplets and aerosols generated during dental procedures. In addition, saliva‐contaminated surfaces could lead to potential cross‐infection. Hence, the control of saliva‐related transmission in the dental clinic is critical, particularly in the epidemic period of COVID‐19. Based on our experience of the COVID‐19 epidemic, some protective measures that can help reduce the risk of saliva‐related transmission are suggested, in order to avoid the potential spread of SARS‐CoV‐2 among patients, visitors, and dental practitioners.

positive: Assessing the relationship between surface levels of PM2.5 and PM10 particulate matter impact on COVID-19 in Milan, Italy Abstract The novel coronavirus disease (COVID-19) is a highly pathogenic, transmittable and invasive pneumococcal disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which emerged in December 2019 and January 2020 in Wuhan city, Hubei province, China and fast spread later on the middle of February 2020 in the Northern part of Italy and Europe. This study investigates the correlation between the degree of accelerated diffusion and lethality of COVID-19 and the surface air pollution in Milan metropolitan area, Lombardy region, Italy. Daily average concentrations of inhalable particulate matter (PM) in two size fractions PM2.5, PM10 and maxima PM10 ground level atmospheric pollutants together air quality and climate variables (daily average temperature, relative humidity, wind speed, atmospheric pressure field and Planetary Boundary Layer-PBL height) collected during 1 January–30 April 2020 were analyzed. In spite of being considered primarily transmitted by indoor bioaerosols droplets and infected surfaces, or direct human-to-human personal contacts, it seems that high levels of urban air pollution, weather and specific climate conditions have a significant impact on the increased rates of confirmed COVID-19 Total number, Daily New and Total Deaths cases, possible attributed not only to indoor but also to outdoor airborne bioaerosols distribution. Our analysis demonstrates the strong influence of daily averaged ground levels of particulate matter concentrations, positively associated with average surface air temperature and inversely related to air relative humidity on COVID-19 cases outbreak in Milan. Being a novel pandemic coronavirus (SARS-CoV-2) version, COVID-19 might be ongoing during summer conditions associated with higher temperatures and low humidity levels. Presently is not clear if this protein “spike” of the new coronavirus COVID-19 is involved through attachment mechanisms on indoor or outdoor airborne aerosols in the infectious agent transmission from a reservoir to a susceptible host in some agglomerated urban areas like Milan is.

positive: Environmental contamination of SARS-CoV-2 during the COVID-19 outbreak in South Korea OBJECTIVES: Although contact precaution is generally recommended in situations where coronavirus disease 2019 (COVID-19) is suspected, there is limited evidence on environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we conducted environmental surveillance on SARS-CoV-2 contamination in 2 different healthcare settings. METHODS: Viral contamination was investigated on the environment of 2 hospitals that had admitted 13 COVID-19 patients. In hospital A, 5 patients with pneumonia occupied negative pressure rooms. In hospital B, 8 asymptomatic patients shared 2 common 4-bed rooms. Most rooms were poorly cleaned or disinfected. Environmental swab were collected from inside and outside the rooms and were tested using real-time RT-PCR for the detection of SARS-CoV-2. RESULTS: In hospital A, SARS-CoV-2 was detected in 10 of 57 (17.5%) samples from inside the rooms including the Ambu bag and infusion pump. Two samples obtained at more than 2 meters from the patients showed positive results. In hospital B, 3 of 22 (13.6%) samples from inside the rooms were positive. Areas outside the rooms, such as the anteroom, corridor, and nursing station, were all negative in both hospitals. CONCLUSIONS: Hospital surfaces surrounding patients were contaminated by SARS-CoV-2. Our findings support the value of strict contact precaution, routine cleaning and disinfection in the management of COVID-19 patients.

positive: Factors Involved in Aerosol Transmission of Infection and Control of Ventilation in Healthcare Experience with the recent viral pandemics has generated a renewed interest in the study of the transmission modes of respiratory pathogens. It not only provides better understanding of the pathogenesis of the disease but also of the rational design of infectious-control strategies. Hospital-acquired infections still account for many hospitalizations and deaths around the world, with many of these infections being transmitted via aerosolized microorganisms to patients and healthcare workers (HCWs).

positive: Optimal temperature zone for the dispersal of COVID-19 Abstract It is essential to know the environmental parameters within which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive to understand its global dispersal pattern. We found that 60.0% of the confirmed cases of coronavirus disease 2019 (COVID-19) occurred in places where the air temperature ranged from 5 °C to 15 °C, with a peak in cases at 11.54 °C. Moreover, approximately 73.8% of the confirmed cases were concentrated in regions with absolute humidity of 3 g/m3 to 10 g/m3. SARS-CoV-2 appears to be spreading toward higher latitudes. Our findings suggest that there is an optimal climatic zone in which the concentration of SARS-CoV-2 markedly increases in the ambient environment (including the surfaces of objects). These results strongly imply that the COVID-19 pandemic may spread cyclically and outbreaks may recur in large cities in the mid-latitudes in autumn 2020.

positive: Environmental sampling for respiratory pathogens in Jeddah airport during the 2013 Hajj season BACKGROUND: Respiratory tract infections (RTIs) are common during the Hajj season and are caused by a variety of organisms, which can be transmitted via the air or contaminated surfaces. We conducted a study aimed at sampling the environment in the King Abdul Aziz International (KAAI) Airport, Pilgrims City, Jeddah, during Hajj season to detect respiratory pathogens. METHODS: Active air sampling was conducted using air biosamplers, and swabs were used to sample frequently touched surfaces. A respiratory multiplex array was used to detect bacterial and viral respiratory pathogens. RESULTS: Of the 58 environmental samples, 8 were positive for at least 1 pathogen. One air sample (1 of 18 samples, 5.5%) tested positive for influenza B virus. Of the 40 surface samples, 7 (17.5%) were positive for pathogens. These were human adenovirus (3 out of 7, 42.8%), human coronavirus OC43/HKU1 (3 out of 7, 42.8%), Haemophilus influenzae (1 out of 7, 14.2%), and Moraxella catarrhalis (1 out of 7, 14.2%). Chair handles were the most commonly contaminated surfaces. The handles of 1 chair were cocontaminated with coronavirus OC43/HKU1 and H influenzae. CONCLUSION: Respiratory pathogens were detected in the air and on surfaces in the KAAI Airport in Pilgrims City. Larger-scale studies based on our study are warranted to determine the role of the environment in transmission of respiratory pathogens during mass gathering events (eg, Hajj) such that public health preventative measures might be better targeted.

positive: Transmission Potential of SARS-CoV-2 in Viral Shedding Observed at the University of Nebraska Medical Center Lack of evidence on SARS-CoV-2 transmission dynamics has led to shifting isolation guidelines between airborne and droplet isolation precautions. During the initial isolation of 13 individuals confirmed positive with COVID-19 infection, air and surface samples were collected in eleven isolation rooms to examine viral shedding from isolated individuals. While all individuals were confirmed positive for SARS-CoV-2, symptoms and viral shedding to the environment varied considerably. Many commonly used items, toilet facilities, and air samples had evidence of viral contamination, indicating that SARS-CoV-2 is shed to the environment as expired particles, during toileting, and through contact with fomites. Disease spread through both direct (droplet and person-to-person) as well as indirect contact (contaminated objects and airborne transmission) are indicated, supporting the use of airborne isolation precautions.

positive: Virus Transfer at the Skin-Liquid Interface. Understanding virus transfer between liquid and skin is necessary to estimate transmission during water-related activities. Here, we modeled virus transfer from liquid-to-skin and skin-to-liquid. We performed human subject studies using three bacteriophages as pathogenic virus surrogates: nonenveloped MS2 and Qβ and enveloped Φ6. Our study shows that transfer from liquid-to-skin is describable by a single model based on (1) virus concentration and (2) volume of liquid remaining on skin. Contact times (0.1-30 min), and virus species had little-to-no influence on virus transfer. Likewise, liquid conditions (pH 6-9, ionic strength 10-550 mM) had no influence on transfer as shown for MS2. The model accounts for both, virus adsorbed onto the skin, and virus in the liquid retained on skin. In comparison, virus transfer from skin-to-liquid was influenced by the wetness of the skin and by liquid type (water, saliva). 90 ± 19% of the virus inoculated on the skin are transferred to the water when the skin remains wet compared to 30 ± 17% when the skin is dry. The transfer from skin-to-liquid was 41% higher when the recipient liquid was water as compared with saliva. This study quantifies virus transfer between liquid and skin and guides risk assessments of water-related activities.

positive: SARS: Epidemiology, Clinical Presentation, Management, and Infection Control Measures Severe acute respiratory syndrome (SARS) is a recently recognized febrile respiratory illness that first appeared in southern China in November 2002, has since spread to several countries, and has resulted in more than 8000 cases and more than 750 deaths. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus. It appears to be spread primarily by large droplet transmission. There is no specific therapy, and management consists of supportive care. This article summarizes currently available information regarding the epidemiology, clinical features, etiologic agent, and modes of transmission of the disease, as well as infection control measures appropriate to contain SARS.

positive: Evaluating the virucidal efficacy of hydrogen peroxide vapour Summary Background Surface contamination has been implicated in the transmission of certain viruses, and surface disinfection can be an effective measure to interrupt the spread of these agents. Aim To evaluate the in-vitro efficacy of hydrogen peroxide vapour (HPV), a vapour-phase disinfection method, for the inactivation of a number of structurally distinct viruses of importance in the healthcare, veterinary and public sectors. The viruses studied were: feline calicivirus (FCV, a norovirus surrogate); human adenovirus type 1; transmissible gastroenteritis coronavirus of pigs (TGEV, a severe acute respiratory syndrome coronavirus [SARS-CoV] surrogate); avian influenza virus (AIV); and swine influenza virus (SwIV). Methods The viruses were dried on stainless steel discs in 20- or 40-μL aliquots and exposed to HPV produced by a Clarus L generator (Bioquell, Horsham, PA, USA) in a 0.2-m3 environmental chamber. Three vaporized volumes of hydrogen peroxide were tested in triplicate for each virus: 25, 27 and 33mL. Findings No viable viruses were identified after HPV exposure at any of the vaporized volumes tested. HPV was virucidal (>4-log reduction) against FCV, adenovirus, TGEV and AIV at the lowest vaporized volume tested (25mL). For SwIV, due to low virus titre on the control discs, >3.8-log reduction was shown for the 25-mL vaporized volume and >4-log reduction was shown for the 27-mL and 33-mL vaporized volumes. Conclusion HPV was virucidal for structurally distinct viruses dried on surfaces, suggesting that HPV can be considered for the disinfection of virus-contaminated surfaces.

positive: Prevention and control of COVID-19 in nursing homes, orphanages, and prisons As the number of Coronavirus Disease (2019) (COVID-19) cases increase globally, countries are taking more aggressive preventive measures against this pandemic. Transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) include droplet and contact transmissions. There are also evidence of transmission through aerosol generating procedures (AGP) in specific circumstances and settings. Institutionalized populations without mobility and living in close proximity with unavoidable contact are especially vulnerable to higher risks of COVID-19 infection, such as the elderly in nursing homes, children in orphanages, and inmates in prisons. In these places, higher prevention and control measures are needed. In this study, we proposed prevention and control strategies for these facilities and provided practical guidance for general measures, health management, personal protection measures, and prevention measures in nursing homes, orphanages, and prisons, respectively.

positive: Risk of SARS-CoV-2 infection from contaminated water systems Following the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in China, airborne water droplets (aerosols) have been identified as the main transmission route, although other transmission routes are likely to exist. We quantify SARS-CoV-2 virus survivability within water and the risk of infection posed by faecal contaminated water within 39 countries. We identify that the virus can remain stable within water for up to 25 days, and country specific relative risk of infection posed by faecal contaminated water is related to the environment. Faecal contaminated rivers, waterways and water systems within countries with high infection rates can provide infectious doses >100 copies within 100 ml of water. The implications for freshwater systems, the coastal marine environment and virus resurgence are discussed.

positive: Potential for Introduction of Bat-Borne Zoonotic Viruses into the EU: A Review Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. To date, significant human outbreaks of such viruses have not been reported in the European Union (EU). However, EU countries have strong historical links with many of the countries where NiV and MARV are present and a corresponding high volume of commercial trade and human travel, which poses a potential risk of introduction of these viruses into the EU. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. In this paper, we review the current scientific knowledge of all these factors, in relation to the introduction of NiV and MARV into the EU.

positive: Effects of temperature on COVID-19 transmission Coronavirus disease 2019 (COVID19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV2), it was first identified in 2019 in Wuhan, China and has resulted in the 2019-20 coronavirus pandemic. As of March 1, 2020, 79,968 patients in China and 7169 outside of China had tested positive for COVID19 and a mortality rate of 3.6% has been observed amongst Chinese patients. Its primary mode of transmission is via respiratory droplets from coughs and sneezes. The virus can remain viable for up to three days on plastic and stainless steel or in aerosols for upto 3 hours and is relatively more stable than the known human coronaviruses. It is stable in faeces at room temperature for at least 1-2 days and can be stable in infected patients for up to 4 days. Heat at 56 degree Celsius kills the SARS coronavirus at around 10000 units per 15 minutes. Thus, temperature is an important factor in survival of COVID19 virus and this article focuses on understanding the relationship between temperature and COVID19 transmission from the data available between January-March 2020.

positive: Impact of building ventilation systems and habitual indoor incense burning on SARS-CoV-2 virus transmissions in Middle Eastern countries Abstract Majority of countries across the globe have employed improving building ventilation, quarantine, social distancing, and disinfections as a general measure of preventing SARS-CoV-2 virus transmissions. However, arid Middle Eastern countries with hot climate (elevated outdoor temperature and humidity levels) are experiencing a different situation. Unfortunately, these harsh ambient climatic conditions in Middle Eastern countries make it impossible for most buildings to utilize natural/mechanical ventilation systems. Besides, indoor air temperatures of most buildings are very low due to overconsumption of air conditioning, thereby, it can be a potential factor of virus spread in most residential homes and public buildings. Most importantly, habitual indoor burning of incense which is the major source of coarse (PM10; aerodynamic diameter <10 μm) and fine (PM2.5; aerodynamic diameter <2.5 μm) particulate matters (PM) could facilitate the transmission of SARS-CoV-2 virus droplets and particles in indoor environments. In fact, it increases the spread of the virus via inhalation in these countries, especially where the wearing of masks is not regulated in public, commercial and residential buildings. It is therefore highly recommended for the relevant public health agencies to critically assess the role of poor indoor environmental conditions including the burning of incense on virus transmissions, which may help to develop control measures for the future viral outbreak effectively.

positive: Preparing for the Perpetual Challenges of Pandemics of Coronavirus Infections with Special Focus on SARS-CoV-2 COVID-19, arising from novel, zoonotic coronavirus-2, has gripped the world in a pandemic. The present chapter discusses the current internationally implemented pandemic preparedness strategies succeeding/recommended to curb the COVID-19 threat to humankind. The updated phase-wise categorization of a pandemic as recommended by the WHO is described, and associated innovations in surveillance, response, and medical measures/advisory in practice across the globe are elaborated. From a bird’s eye view, the COVID-19 pandemic management relies on revolutionizing the disease surveillance by incorporating artificial intelligence and data analytics, boosting the response strategies—extensive testing, case isolation, contact tracing, and social distancing—and promoting awareness and access to pharmaceutical and non-pharmaceutical interventions, which are discussed in the present chapter. We also preview the economic bearing of the COVID-19 pandemic.

positive: Inactivation of surrogate coronaviruses on hard surfaces by health care germicides BACKGROUND: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. METHODS: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). RESULTS: After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. CONCLUSION: Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.

positive: Is SARS-CoV-2 Also an Enteric Pathogen With Potential Fecal-Oral Transmission? A COVID-19 Virological and Clinical Review In as few as 3 months, coronavirus disease 2019 (COVID-19) has spread and ravaged the world at an unprecedented speed in modern history, rivaling the 1918 flu pandemic. Severe acute respiratory syndrome coronavirus-2, the culprit virus, is highly contagious and stable in the environment and transmits predominantly among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that severe acute respiratory syndrome coronavirus-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.

positive: Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ(2) test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1–4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.

positive: Methods for air cleaning and protection of building occupants from airborne pathogens Abstract This article aims to draw the attention of the scientific community towards the elevated risks of airborne transmission of diseases and the associated risks of epidemics or pandemics. The complexity of the problem and the need for multidisciplinary research is highlighted. The airborne route of transmission, i.e. the generation of pathogen laden droplets originating in the respiratory tract of an infected individual, the survivability of the pathogens, their dispersal indoors and their transfer to a healthy person are reviewed. The advantages and the drawbacks of air dilution, filtration, ultraviolet germicidal irradiation (UVGI), photocatalytic oxidation (PCO), plasmacluster ions and other technologies for air disinfection and purification from pathogens are analyzed with respect to currently used air distribution principles. The importance of indoor air characteristics, such as temperature, relative humidity and velocity for the efficiency of each method is analyzed, taking into consideration the nature of the pathogens themselves. The applicability of the cleaning methods to the different types of total volume air distribution used at present indoors, i.e. mixing, displacement and underfloor ventilation, as well as advanced air distribution techniques (such as personalized ventilation) is discussed.

positive: Stability of SARS-CoV-2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: a review Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID-19) and its causative etiology [Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS-CoV-2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS-CoV-2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS-CoV-2 has been suggested. SARS-CoV-2 and other human and animal CoVs have remarkably short persistence on copper, latex, and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass, and highly porous fabrics. It has also been reported that SARS-CoV-2 is associated with diarrhea and that it is shed in the feces of COVID-19 patients. Some CoVs show persistence in human excrement, sewage, and waters for a few days. These findings suggest a possible risk of fecal-oral, foodborne, and waterborne transmission of SARS-CoV-2 in developing countries that often use sewage-polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID-19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.

positive: Survival of the Enveloped Virus Phi6 in Droplets as a Function of Relative Humidity, Absolute Humidity, and Temperature Infectious diseases caused by enveloped viruses, such as influenza, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), cause thousands of deaths and billions of dollars of economic losses per year. Studies have found a relationship among temperature, humidity, and influenza virus incidence, transmission, or survival; however, there are contradictory claims about whether absolute humidity (AH) or relative humidity (RH) is most important in mediating virus infectivity. Using the enveloped bacteriophage Phi6, which has been suggested as a surrogate for influenza viruses and coronaviruses, we designed a study to discern whether AH, RH, or temperature is a better predictor of virus survival in droplets. Our results show that Phi6 survived best at high (>85%) and low (<60%) RHs, with a significant decrease in infectivity at mid-range RHs (∼60 to 85%). At an AH of less than 22 g · m(−3), the loss in infectivity was less than 2 orders of magnitude; however, when the AH was greater than 22 g · m(−3), the loss in infectivity was typically greater than 6 orders of magnitude. At a fixed RH of 75%, infectivity was very sensitive to temperature, decreasing two orders of magnitude between 19°C and 25°C. We used random forest modeling to identify the best environmental predictors for modulating virus infectivity. The model explained 83% of variation in Phi6 infectivity and suggested that RH is the most important factor in controlling virus infectivity in droplets. This research provides novel information about the complex interplay between temperature, humidity, and the survival of viruses in droplets. IMPORTANCE Enveloped viruses are responsible for a number of infectious diseases resulting in thousands of deaths and billions of dollars of economic losses per year in the United States. There has been a lively debate in the literature over whether absolute humidity (AH) or relative humidity (RH) modulates virus infectivity. We designed a controlled study and used advanced statistical modeling techniques specifically to address this question. By providing an improved understanding of the relationship between environmental conditions and virus infectivity, our work will ultimately lead to improved strategies for predicting and controlling disease transmission.

positive: Consideration of the Aerosol Transmission for COVID-19 and Public Health This article analyzes the available evidence to address airborne, aerosol transmission of the SARS-CoV-2. We review and present three lines of evidence: case reports of transmission for asymptomatic individuals in association with studies that show that normal breathing and talking produce predominantly small droplets of the size that are subject to aerosol transport; limited empirical data that have recorded aerosolized SARS-CoV-2 particles that remain suspended in the air for hours and are subject to transport over distances including outside of rooms and intrabuilding, and the broader literature that further supports the importance of aerosol transmission of infectious diseases. The weight of the available evidence warrants immediate attention to address the significance of aerosols and implications for public health protection.

positive: Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 × 10(4) to 1.7 × 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans.

positive: A framework for nosocomial transmission of emerging coronaviruses

positive: Microbes, Transmission Routes and Survival Outside the Body Microbes like bacteria, virus, parasites and fungi may naturally colonize skin and mucous membranes without any sign of illness, for a longer or shorter period, in all humans, animals, fish, parasites, plants and all other living beings. Some types may be more invasive in human tissue than others. Many microbes are free-living in the environment—in water, soil and air and on equipment—as a part of the normal microbial flora on the Earth. Most of them are not dangerous and live in peaceful symbiosis with other living beings and may also be transferred between living species, from man to animal or man to plants and environment—and vice versa. New and old human pathogenic microbes are increasing all over the world. Some agents, like drug-resistant bacteria and highly pathogenic viruses, are more dangerous than others, and some microbes may cause chronic devastating diseases. Transmission routes depend on the robustness of the microbe in the environment, virulence, infectious dose, anatomical site in the body, etc. Pathogenic microbes are spread by contact, air, water, food, beverages, contaminated equipment and environment and are more seldom vector-borne, by insects or animals. The following chapter is focused on the most frequent pathogenic microbes, their preselected localization in the body, transmission routes and survival in the environment.

positive: Severe Acute Respiratory Syndrome: What Have We Learned

positive: The role of absolute humidity on transmission rates of the COVID-19 outbreak A novel coronavirus (COVID-19) was identified in Wuhan, Hubei Province, China, in December 2019 and has caused over 40,000 cases worldwide to date. Previous studies have supported an epidemiological hypothesis that cold and dry (low absolute humidity) environments facilitate the survival and spread of droplet-mediated viral diseases, and warm and humid (high absolute humidity) environments see attenuated viral transmission (i.e., influenza). However, the role of absolute humidity in transmission of COVID-19 has not yet been established. Here, we examine province-level variability of the basic reproductive numbers of COVID-19 across China and find that changes in weather alone (i.e., increase of temperature and humidity as spring and summer months arrive in the North Hemisphere) will not necessarily lead to declines in COVID-19 case counts without the implementation of extensive public health interventions.

negative: The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? OBJECTIVES: To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China. METHODS: Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and COVID-19. Comparisons between the viruses were made. RESULTS: Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally. CONCLUSIONS: We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.

negative: Association between climate variables and global transmission oF SARS-CoV-2 Abstract In this study, we aimed at analyzing the associations between transmission of and deaths caused by SARS-CoV-2 and meteorological variables, such as average temperature, minimum temperature, maximum temperature, and precipitation. Two outcome measures were considered, with the first aiming to study SARS-CoV-2 infections and the second aiming to study COVID-19 mortality. Daily data as well as data on SARS-CoV-2 infections and COVID-19 mortality obtained between December 1, 2019 and March 28, 2020 were collected from weather stations around the world. The country's population density and time of exposure to the disease were used as control variables. Finally, a month dummy variable was added. Daily data by country were analyzed using the panel data model. An increase in the average daily temperature by one degree Fahrenheit reduced the number of cases by approximately 6.4 cases/day. There was a negative correlation between the average temperature per country and the number of cases of SARS-CoV-2 infections. This association remained strong even with the incorporation of additional variables and controls (maximum temperature, average temperature, minimum temperature, and precipitation) and fixed country effects. There was a positive correlation between precipitation and SARS-CoV-2 transmission. Countries with higher rainfall measurements showed an increase in disease transmission. For each average inch/day, there was an increase of 56.01 cases/day. COVID-19 mortality showed no significant association with temperature.

negative: CHAPTER 12 MICE AND RATS Publisher Summary This chapter focuses on mice and rats, and provides detailed information that may be useful for veterinarians treating these animals. Mice are continuous, polyestrous rodents that should be bred in polygamous or monogamous setups because of the males' aggressive territoriality behavior. When breeding mice that have been housed in a polygamous ratio, there may be one male with two to six females. Females are removed from a polygamous cage before parturition, whereas the monogamous pair is maintained together with the young until weaning. Mice are maintained in environments that are similar to other small rodents but require a thorough cleaning of their cage more often because of their malodorous urine. Ventilation is essential for small rodent housing to prevent irritation of the respiratory tract from ammonia vapors generated by urine. Quarantining is important when a new animal is being introduced into a setting in which there is an established group. As with other animals, a 30-day quarantine period is recommended, along with a physical examination and fecal parasite check. To maintain oversight of breeding animals' health and reduce the exposure of young animals to infectious disease and parasites, routine screening of representative animals within the colony is recommended. In very large colonies, special caging, food, and water may be necessary to prevent exposure to disease organisms.

negative: An outbreak of COVID‐19 caused by a new coronavirus: what we know so far

negative: Comparison of electrocardiographic parameters and serum electrolytes and microelements between single infection of rotavirus and coronavirus and concurrent infection of Cryptosporidium parvum with rotavirus and coronavirus in diarrheic dairy calves To study the effects of concurrent infection of Cryptosporidium parvum with rotavirus and coronavirus in comparison to single infection of rotavirus and coronavirus, electrocardiographic parameters and serum electrolytes and microelements are compared between eight calves with concurrent infection and ten calves with single infection. Calves with single infections had higher serum concentrations of sodium and calcium, and less potassium, copper, and iron, which was not statistically significant. They also had significantly shorter P and QRS wave amplitudes and longer T wave duration in electrocardiogram patterns.

negative: COVID-19: Review of Epidemiology and Potential Treatments Against 2019 Novel Coronavirus An epidemic of extreme respiratory deterrence, pneumonia and shortness of breath, the SARS-CoV-2 viral infection began in Wuhan, Hubei Province, China in December 2019, and rapidly spread across China and beyond, with human to human transmission. On February 12, 2020, World Health Organization officially named the new coronavirus disease as coronavirus disease 19 (COVID-19). Most COVID-19 patients were diagnosed with pneumonia and many were treated using Chinese medicines and other secondary therapies. As of April 22, 2020, the total figure of infected patients has crossed 2.6 million people worldwide with over 180,000 deaths and 700,000 patients that have recovered. Preliminary reports suggest that certain drugs, such as chloroquine and antiviral nucleotide analogues such as remdesivir, which inhibit viral replication, can target the new coronavirus, although their usefulness in the clinic is still under debate. An expert US committee developed the US NIH guidelines for COVID-19 treatment, which was just released and will be regularly updated. This manuscript reviews the epidemiology, etiology, mortality, COVID-19 clinical symptoms, and potential therapeutic drugs, while highlighting the seriousness and damage-induced by SARS-CoV-2.

negative: The molecular tweezer CLR01 inhibits Ebola and Zika virus infection Abstract Ebola (EBOV) and Zika viruses (ZIKV) are responsible for recent global health threats. As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. This small molecule has previously been shown to inactivate HIV-1 and herpes viruses through a selective interaction with lipid-raft-rich regions in the viral envelope, which results in membrane disruption and loss of infectivity. We found that CLR01 indeed blocked infection of EBOV and ZIKV in a dose-dependent manner. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Our findings show that CLR01 is a broad-spectrum inhibitor of enveloped viruses with prospects as a preventative microbicide or antiviral agent.

negative: Networks in a World Unknown: Public WhatsApp Groups in the Venezuelan Refugee Crisis By early March 2020, five million Venezuelans had fled their home country after its complete economic and institutional collapse, and over 1.6 million have migrated to Colombia. Migrants struggle to start their lives over in Colombia, having arrived with few economic resources, and often no legal documentation, in cities with little to offer them. Venezuelan migrants, however, rely heavily on mobile phones and social media networks as lifelines for information, opportunities, and resources -- making WhatsApp both a critical tool for migrants' settlement and integration, as well as an invaluable source of data through which we can better understand migrant experiences. This thesis explores the dynamics of public WhatsApp groups used by Venezuelan migrants to Colombia, and what they can tell us about how migrants use and share information. We center our research on information spread and trust, especially as they intersect with concentration and geographic heterogeneity within groups. We analyze messages and memberships broadly, then explore interaction within groups, fake news and economic scams, and effects of the coronavirus pandemic. Our results have a range of policy implications, from reflections on Colombia's decision to shut its borders amidst the coronavirus pandemic, to understandings of how aid organizations can effectively share information over social media channels.

negative: Emergency trauma care during the outbreak of corona virus disease 2019 (COVID-19) in China BACKGROUND: A novel coronavirus pneumonia outbreak began in Wuhan, Hubei Province, in December 2019; the outbreak was caused by a novel coronavirus previously never observed in humans. China has imposed the strictest quarantine and closed management measures in history to control the spread of the disease. However, a high level of evidence to support the surgical management of potential trauma patients during the novel coronavirus outbreak is still lacking. To regulate the emergency treatment of trauma patients during the outbreak, we drafted this paper from a trauma surgeon perspective according to practical experience in Wuhan. MAIN BODY: The article illustrates the general principles for the triage and evaluation of trauma patients during the outbreak of COVID-19, indications for emergency surgery, and infection prevention and control for medical personnel, providing a practical algorithm for trauma care providers during the outbreak period. CONCLUSIONS: The measures of emergency trauma care that we have provided can protect the medical personnel involved in emergency care and ensure the timeliness of effective interventions during the outbreak of COVID-19.

negative: Simple Economical Solution for Personal Protection Equipment (Face Mask/Shield) for Health Care Staff During COVID 19 Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. It has taken a toll of lots of lives since its outbreak. Infection prevention at present is an appropriate control measure in addition to other measure like hand hygiene and personal protective equipment (PPE). In our country with a large population, supplying PPE to all the health care workers of all hospitals definitely is an economic burden. Hence we have come up with an economic and simple solution for face mask. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12070-020-01863-4) contains supplementary material, which is available to authorized users.

negative: ACE 2 Coding Variants: A Potential X-linked Risk Factor for COVID-19 Disease Viral genetic variants are widely known to influence disease progression among infected humans. Given the recent and rapid emergence of pandemic SARS-CoV-2 infection, the cause of COVID-19 disease, viral protein variants have attracted research interest. However, little has yet been written about genetic risk factors among human hosts. Human genetic variation has proven to affect disease progression and outcome for important diseases such as HIV infection and malaria infestation. The fact that the human ACE2 protein is encoded on the X chromosome means that males who carry rare ACE2 coding variants will express those variants in all ACE2-expressing cells, whereas females will typically express those variants in a mosaic distribution determined by early X-inactivation events. This sex-based difference in ACE2 expression has unique implications for epidemiological studies designed to assess host genetic factors influencing progression from asymptomatic SARS-coV-2 infection to COVID-19. Here we present theoretical modelling of rare ACE2 coding variants documented to occur naturally in several human superpopulations and subpopulations, and show that rare variants predicted to affect the binding of ACE2 to the SARS-CoV-2 spike protein exist in people. Though the rs4646116 (p.Lys26Arg) allele is found in 1 in 70 Ashkenazi Jewish males, and in 1 in 172 non-Finnish European males, this allele is found at higher frequencies in females. Furthermore, the class of missense ACE2 alleles predicted to affect SARS-CoV-2 binding are found in aggregate among 1.43% and 2.16% of Ashkenazi males and females, respectively, as well as in 0.58% and 1.24% of European males and females outside of Finland. These alleles are rarer in other population groups, and almost absent from East Asians genotyped to date. Though we are aware that full genome-wide and exome-wide sequencing studies may ultimately be required to assess human genetic susceptibility to SARS-CoV-2 fully, we argue on the basis of strong prior probabilities that genotyping of this class of alleles is justified in cases of atypical SARS-CoV-2 diseases, such as asymptomatic super-spreaders (if any are identified), and in neonatal/paediatric-onset COVID-19 disease. Even relatively rare susceptibility factors (1% or fewer carriers) may become quantitatively important in the context of hundreds of thousands of infections. A small number of asymptomatic carriers, or a small number of super-spreaders, or a small segment of the population that is disproportionately likely to require intensive care, can magnify the medical, social and economic impacts of a pandemic of this size. The speed of the pandemic and the large number of affected cases worldwide justify efforts to identify all possible risk factors for adverse outcomes, including efforts to identify genetic susceptibility factors in human hosts.

negative: Virome genomics: a tool for defining the human virome High throughput, deep sequencing assays are powerful tools for gaining insights into virus–host interactions. Sequencing assays can discover novel viruses and describe the genomes of novel and known viruses. Genomic information can predict viral proteins that can be characterized, describe important genes in the host that control infections, and evaluate gene expression of viruses and hosts during infection. Sequencing can also describe variation and evolution of viruses during replication and transmission. This review recounts some of the major advances in the studies of virus–host interactions from the last two years, and discusses the uses of sequencing technologies relating to these studies.

negative: A novel human coronavirus: Middle East respiratory syndrome human coronavirus In 2012, a novel coronavirus, initially named as human coronavirus EMC (HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus (MERS-CoV), was identified in patients who suffered severe acute respiratory infection and subsequent renal failure that resulted in death. Ongoing epidemiological investigations together with retrospective studies have found 61 laboratory-confirmed cases of infection with this novel coronavirus, including 34 deaths to date. This novel coronavirus is culturable and two complete genome sequences are now available. Furthermore, molecular detection and indirect immunofluorescence assay have been developed. The present paper summarises the limited recent advances of this novel human coronavirus, including its discovery, genomic characterisation and detection.

negative: Negligible Risk of the COVID-19 Resurgence Caused by Work Resuming in China (outside Hubei): a Statistical Probability Study The COVID-19 outbreak in China appears to reach the late stage since late February 2020, and a stepwise restoration of economic operations is implemented. Risk assessment for such economic restoration is of significance. Here we estimated the probability of COVID-19 resurgence caused by work resuming in typical provinces/cities, and found that such probability is very limited (<5% for all the regions except Beijing). Our work may inform provincial governments to make risk level-based, differentiated control measures.

negative: A Review of SARS-CoV-2 and the Ongoing Clinical Trials The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.

negative: Understanding the emerging coronavirus: what it means for health security and infection prevention

negative: An immunoelectron microscopic and immunofluorescent study on the antigenic relationship between the coronavirus-like agent, CV 777, and several coronaviruses A possible antigenic relationship between the porcine enteropathogenic coronavirus-like agent (CVLA) and 6 known coronaviruses was examined by immunoelectron microscopy (IEM) and by immunofluorescence (IF). CVLA did not show cross reactivity with infectious bronchitis virus, transmissible gastroenteritis virus (TGEV), canine coronavirus (CCV) hemagglutinating encephalomyelitis virus (HEV), neonatal calf diarrhea coronavirus (NCDCV) or feline infectious peritonitis virus (FIPV). Antigenic relationship was detected by IEM between TGEV and CCV, NCDCV and HEV and by IF between TGEV and CCV, TGEV and FIPV, HEV and NCDCV.

negative: The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding Many pathogens take advantage of the dependence of the host on the interaction of hundreds of extracellular proteins with the glycosaminoglycans heparan sulfate to regulate homeostasis and use heparan sulfate as a means to adhere and gain access to cells. Moreover, mucosal epithelia such as that of the respiratory tract are protected by a layer of mucin polysaccharides, which are usually sulfated. Consequently, the polydisperse, natural products of heparan sulfate and the allied polysaccharide, heparin have been found to be involved and prevent infection by a range of viruses including S-associated coronavirus strain HSR1. Here we use surface plasmon resonance and circular dichroism to measure the interaction between the SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) and heparin. The data demonstrate an interaction between the recombinant surface receptor binding domain and the polysaccharide. This has implications for the rapid development of a first-line therapeutic by repurposing heparin and for next-generation, tailor-made, GAG-based antivirals.

negative: SRSF7 maintains its homeostasis through the expression of Split-ORFs and nuclear body assembly SRSF7 is an essential RNA-binding protein whose misexpression promotes cancer. Here, we describe how SRSF7 maintains its protein homeostasis in murine P19 cells using an intricate negative feedback mechanism. SRSF7 binding to its premessenger RNA promotes inclusion of a poison cassette exon and transcript degradation via nonsense-mediated decay (NMD). However, elevated SRSF7 levels inhibit NMD and promote translation of two protein halves, termed Split-ORFs, from the bicistronic SRSF7-PCE transcript. The first half acts as dominant-negative isoform suppressing poison cassette exon inclusion and instead promoting the retention of flanking introns containing repeated SRSF7 binding sites. Massive SRSF7 binding to these sites and its oligomerization promote the assembly of large nuclear bodies, which sequester SRSF7 transcripts at their transcription site, preventing their export and restoring normal SRSF7 protein levels. We further show that hundreds of human and mouse NMD targets, especially RNA-binding proteins, encode potential Split-ORFs, some of which are expressed under specific cellular conditions.

negative: How the SARS coronavirus causes disease: host or organism? The previous epidemic of severe acute respiratory syndrome (SARS) has ended. However, many questions concerning how the aetiological agent, the novel SARS coronavirus (CoV), causes illness in humans remain unanswered. The pathology of fatal cases of SARS is dominated by diffuse alveolar damage. Specific histological changes are not detected in other organs. These contrast remarkably with the clinical picture, in which there are apparent manifestations in multiple organs. Both pathogen and host factors are important in the pathogenesis of SARS. The choice of specific receptors and the unique genome of the SARS‐CoV are important elements in understanding the biology of the pathogen. For the host cells, the outcome of SARS‐CoV infection, whether there are cytopathic effects or not, depends on the cell types that are infected. At the whole‐body level, immune‐mediated damage, due to activation of cytokines and/or chemokines and, perhaps, autoimmunity, may play key roles in the clinical and pathological features of SARS. Continued research is still required to determine the pathogenetic mechanisms involved and to combat this new emerging human infectious disease. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

negative: 2019-nCoV transmission through the ocular surface must not be ignored

negative: Precautions are Needed for COVID-19 Patients with Coinfection of Common Respiratory Pathogens Background: With the ongoing outbreak of Coronavirus Disease 2019 (COVID-19), infected patients within and beyond the epidemic area, Wuhan, China, showed different epidemiological and clinical characteristics. There is a paucity of data concerning coinfection with other common respiratory pathogens in COVID-19 patients outside of Wuhan. Methods: We conducted a double-centre study recruiting 68 patients with severe acute respiratory coronavirus 2 (SARS-CoV-2) infection confirmed by nucleic acid testing in Qingdao and Wuhan from January 17 to February 16, 2020. Indirect immunofluorescence was performed to detect the specific IgM antibody against common respiratory pathogens in collected acute phase serum. Results: Of the 68 patients with SARS-CoV-2 infection, 30 (44.12%) were from Qingdao. The median age of Qingdao and Wuhan patients were 50 (IQR: 37-59) and 31 (IQR: 28-38) years, respectively, and the majority of patients were female in Qingdao (60.00%) and Wuhan (55.26%). Among COVID-19 patients in Qingdao, 24 (80.00%) of them had IgM antibodies against at least one respiratory pathogen, whereas only one (2.63%) of the patients in Wuhan had positive results for serum IgM antibody detection (P<0.0001). The most common respiratory pathogens detected in Qingdao COVID-19 patients were influenza virus A (60.00%) and influenza virus B (53.33%), followed by mycoplasma pneumoniae (23.33%) and legionella pneumophila (20.00%). While the pattern for coinfection in patients with community-acquired pneumonia in Qingdao was quite different, with a positive rate of only 20.90%. Interpretation: We reported a large proportion of COVID-19 patients with coinfection of seasonal respiratory pathogens in Qingdao, northeast China, which differed greatly from the patients in Wuhan, central China. Precautions are needed when dealing with COVID-19 patients beyond the epidemic centre who have coinfection with other respiratory pathogens. We highly recommend adding SARS-CoV-2 to routine diagnostic testing in capable hospitals to prevent misdetection of the virus.

negative: Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics At the time of writing this commentary (February 2020), the coronavirus COVID‐19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS‐CoV‐2 virus may take many months. Moreover, vaccines based on viral‐encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS‐CoV‐2 virus infections. This idea is based on observations that the angiotensin‐converting enzyme 2 (ACE2) very likely serves as the binding site for SARS‐CoV‐2, the strain implicated in the current COVID‐19 epidemic, similarly to strain SARS‐CoV implicated in the 2002–2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS‐CoV‐2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.

negative: A Guide to COVID‐19: a global pandemic caused by the novel coronavirus SARS‐CoV‐2 The emergence of the SARS‐CoV‐2 strain of the human coronavirus has thrown the world into the midst of a new pandemic. In the human body, the virus causes COVID‐19, a disease characterized by shortness of breath, fever, and pneumonia, which can be fatal in vulnerable individuals. SARS‐CoV‐2 has characteristics of past human coronaviruses, with close genomic similarities to SARS‐CoV, the virus that causes the disease SARS. Like these related coronaviruses, SARS‐CoV‐2 is transmitted through the inhalation of droplets and interaction with contaminated surfaces. Across the world, laboratories are developing candidate vaccines for the virus – with vaccine trials underway in the US and the United Kingdom ‐ and considering various drugs for possible treatments and prophylaxis. Here, we provide an overview of SARS‐CoV‐2 by analyzing its virology, epidemiology, and modes of transmission while examining the current progress of testing procedures and possible treatments through drugs and vaccines.

negative: Swine Diseases and Disorders Abstract Swine diseases and disorders that are significant in modern, commercial swine production systems are organized by body system; the reader will need to know basic anatomy and physiology. The industry significance, etiology, epidemiology, pathogenesis, clinical signs, postmortem and histpathologic lesions, diagnostic testing, and generic treatment, control, and prevention are described. Diseases of a particular system are summarized in a differential diagnosis table.

negative: Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. Coronavirus, which can cause respiratory syndrome, to date has affected over seventeen thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical compounds including histamine and protease; while late activation provokes the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.

negative: Nanoparticles for transcutaneous vaccination The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation can elicit a strong humoral and cellular immune response as well as mucosal immunity. Therefore, the skin is a very attractive site for vaccination, and an intradermal application of antigen may be much more effective than a subcutaneous or intramuscular injection. However, the stratum corneum (SC) is a most effective barrier against the invasion of topically applied vaccines. Products which have reached the stage of clinical testing, avoid this problem by injecting the nano‐vaccine intradermally or by employing a barrier disrupting method and applying the vaccine to a relatively large skin area. Needle‐free vaccination is desirable from a number of aspects: ease of application, improved patient acceptance and less risk of infection among them. Nanocarriers can be designed in a way that they can overcome the SC. Also incorporation into nanocarriers protects instable antigen from degradation, improves uptake and processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release systems may build a depot in the tissue gradually releasing antigen which may avoid booster doses. Therefore, nanoformulations of vaccines for transcutaneous immunization are currently a very dynamic field of research. Among the huge variety of nanocarrier systems that are investigated hopes lie on ultra‐flexible liposomes, superfine rigid nanoparticles and nanocarriers, which are taken up by hair follicles. The potential and pitfalls associated with these three classes of carriers will be discussed.

negative: Genetic diversity and evolution of SARS-CoV-2 Abstract COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.

negative: Towards effective COVID-19 vaccines: Updates, perspectives and challenges (Review) In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS-COV-2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID-19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.

negative: Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19 Our surrounding environment, especially often-touched contaminated surfaces, plays an important role in the transmission of pathogens in society. The shortage of effective sanitizing fluids, however, became a global challenge quickly after the coronavirus disease-19 (COVID-19) outbreak in December 2019. In this study, we present the effect of surfactants on coronavirus (SARS-CoV-2) virucidal efficiency in sanitizing fluids. Sodium dodecylbenzenesulfonate (SDBS), sodium laureth sulfate (SLS), and two commercial dish soap and liquid hand soap were studied with the goal of evaporation rate reduction in sanitizing liquids to maximize surface contact time. Twelve fluids with different recipes composed of ethanol, isopropanol, SDBS, SLS, glycerin, and water of standardized hardness (WSH) were tested for their evaporation time and virucidal efficiency. Evaporation time increased by 17-63% when surfactant agents were added to the liquid. In addition, surfactant incorporation enhanced the virucidal efficiency between 15-27% according to the 4-field test in the EN 16615:2015 European Standard method. Most importantly, however, we found that surfactant addition provides a synergistic effect with alcohols to inactivate the SARS-CoV-2 virus. This study provides a simple, yet effective solution to improve the virucidal efficiency of commonly used sanitizers.

negative: Association of national Bacille Calmette-Guerin vaccination policy with COVID-19 epidemiology: an ecological study in 78 countries A possible association between national Bacille Calmette-Guerin (BCG) vaccination policy and lower COVID-19 incidence has been suggested in some preprint papers. Using publicly accessible databases, I explored associations of national BCG vaccination policy with COVID-19 epidemiology in 78 countries. Data collection was conducted from April 25 to May 5, 2020. I compared countries that have a current universal BCG vaccination policy (BCG countries), with countries that currently lack such a policy (non-BCG countries). The mixed effect model revealed national BCG policy decreases in the country-specific risk of death by COVID-19, correspond to odds ratio of 0.446 (95% confidence intervals 0.323 - 0.614, P =1x10-5). In BCG countries, the case increase rate was attenuated marginally by 25.4% (95% CI 3.0 to 42.7, P=0.029) as compared with those of the non-BCG countries. Although the protective mechanism of BCG vaccination against COVID-19 remains unknown, further laboratory and clinical research should be warranted.

negative: Authors’ response: Plenty of coronaviruses but no SARS-CoV-2

negative: General Information Many bacteria, viruses, parasites, fungi and prions may cause serious infections and lead to the isolation of those who are infected from those who are susceptible. Isolation may be done in single rooms or in special isolation units. A modern isolate for patients with infections comprises (1) a sluice with a good space for dressing and undressing of personal protective equipment (PPE) and for hand hygiene, (2) a large patient room and (3) a bathroom/disinfection room with own decontaminator or autoclave and with separate entrance from the patient’s room. Isolates for airborne and droplet-transmitted infections have in addition a defined negative air pressure and hepafiltered exhaust. In all isolates, doors must be closed in such a way that contaminants do not escape the isolate. A modern isolate for patients with impaired immune defence is similar to the infection isolates, with following exceptions: usually no need for decontaminator, hepafiltered clean air into the room and with a defined positive air pressure. A positive pressure isolate should never be used for patients with infections, and a negative pressure isolate should never be used for patients with impaired immune defence, except if the patient also has an infection that needs isolation.

negative: Diseases of the Liver and Hepatobiliary System

negative: Correlation between the Spread of COVID-19 and the Interest in Personal Protective Measures in Poland and Portugal. The pandemic of the coronavirus disease 2019 (COVID-19), has gained extensive coverage in public media and global news, generated international and national communication campaigns to educate the communities worldwide and raised the attention of everyone. The coronavirus has caused viral pneumonia in tens of thousands of people around the world, and the COVID-19 outbreak changed most countries' routines and concerns and transformed social behaviour. This study explores the potential use of Google Trends (GT) in monitoring interest in the COVID-19 outbreak and, specifically, in personal protective equipment and hand hygiene, since these have been promoted by official health care bodies as two of the most protective measures. GT was chosen as a source of reverse engineering data, given the interest in the topic and the novelty of the research. Current data on COVID-19 are retrieved from GT using keywords in two languages-Portuguese and Polish. The geographical settings for GT are two countries: Poland and Portugal. The period under analysis is 20 January 2020, when the first cases outside China were known, to 15 June 2020. The results show that there is a correlation between the spread of COVID-19 and the search for personal protective equipment and hand hygiene and that GT can help, to a certain extent, understand people's concerns, behaviour and reactions to sanitary problems and protection recommendations.

negative: Seasonality and uncertainty in COVID-19 growth rates The virus causing COVID-19 has spread rapidly worldwide and threatens millions of lives. It remains unknown if summer weather will reduce its continued spread, thereby alleviating strains on hospitals and providing time for vaccine development. Early insights from laboratory studies of related coronaviruses predicted that COVID-19 would decline at higher temperatures, humidity, and ultraviolet light. Using current, fine-scaled weather data and global reports of infection we developed a model that explained 36% of variation in early growth rates before intervention, with 17% based on weather or demography and 19% based on country-specific effects. We found that ultraviolet light was most strongly associated with lower COVID-19 growth rates. Projections suggest that, in the absence of intervention, COVID-19 will decrease temporarily during summer, rebound by autumn, and peak next winter. However, uncertainty remains high and the probability of a weekly doubling rate remained >20% throughout the summer in the absence of control. Consequently, aggressive policy interventions will likely be needed in spite of seasonal trends.

negative: Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of SARS-CoV-2 entry Background Leading to a sustained epidemic spread with >2,000,000 confirmed human infections, including >100,000 deaths, COVID-19 was caused by SARS-CoV-2 and resulted in acute respiratory distress syndrome (ARDS) and sepsis, which brought more challenges to the patient’s treatment. The S-glycoprotein, which recognized as the key factor for the entry of SARS-CoV-2 into the cell, contains two functional domains: an ACE2 receptor binding domain and a second domain necessary for fusion of the coronavirus and cell membranes. FURIN activity, exposes the binding and fusion domains, is essential for the zoonotic transmission of SARS-CoV-2. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, FURIN enzyme and ACE2 receptor were expressed in airway epithelia, cardiac tissue, and enteric canals, which considered as the potential target organ of the virus. However, report about the expression of FURIN and ACE2 in oral tissues was limited. Methods In order to investigate the potential infective channel of new coronavirus in oral cavity, we analyze the expression of ACE2 and FURIN that mediate the new coronavirus entry into host cells in oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemical staining experiment was performed to confirm the expression of ACE2 and FURIN in the protein level. Results The bioinformatics results indicated the differential expression of ACE2 and FURIN on epithelial cells of different oral mucosal tissues and the proportion of FURIN-positive cells was obviously higher than that of ACE2-positive cells. IHC experiments revealed that both the ACE2-positive and FURIN-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, which further confirm the bioinformatics results. Conclusions Based on these findings, we speculated that SARS-CoV-2 could effectively invade oral mucosal cells though two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by FURIN protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2, which provides valuable information for virus-prevention strategy in clinical care as well as daily life.

negative: Ebola Virus Stability on Surfaces and in Fluids in Simulated Outbreak Environments. We evaluated the stability of Ebola virus on surfaces and in fluids under simulated environmental conditions for the climate of West Africa and for climate-controlled hospitals. This virus remains viable for a longer duration on surfaces in hospital conditions than in African conditions and in liquid than in dried blood.

negative: Investigation into SARS-CoV-2 Resistance of Compounds in Garlic Essential Oil [Image: see text] Eighteen active substances, including 17 organosulfur compounds found in garlic essential oil (T), were identified by GC–MS analysis. For the first time, using the molecular docking technique, we report the inhibitory effect of the considered compounds on the host receptor angiotensin-converting enzyme 2 (ACE2) protein in the human body that leads to a crucial foundation about coronavirus resistance of individual compounds on the main protease (PDB6LU7) protein of SARS-CoV-2. The results show that the 17 organosulfur compounds, accounting for 99.4% contents of the garlic essential oil, have strong interactions with the amino acids of the ACE2 protein and the main protease PDB6LU7 of SARS-CoV-2. The strongest anticoronavirus activity is expressed in allyl disulfide and allyl trisulfide, which account for the highest content in the garlic essential oil (51.3%). Interestingly, docking results indicate the synergistic interactions of the 17 substances, which exhibit good inhibition of the ACE2 and PDB6LU7 proteins. The results suggest that the garlic essential oil is a valuable natural antivirus source, which contributes to preventing the invasion of coronavirus into the human body.

negative: Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu(TM) database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.

negative: Long-term Co-existence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) with Antibody Response in Non-severe Coronavirus Disease 2019 (COVID-19) Patients Severe acute respiratory syndrome coronavirus 2 infection causing coronavirus disease 2019 has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms and no cases of severe symptoms were found among these patients. A striking feature of some patients is that SARS-CoV-2 could exist in patients who have virus-specific IgG antibodies for a very long period, with one case for up to 36 days. One COVID-19 patient who did not produce any SARS-CoV-2-bound IgG successfully cleared SARS-CoV-2 after 46 days of illness, revealing that without antibody-mediated adaptive immunity, innate immunity may still be powerful enough to eliminate SARS-CoV-2. Overall, this report may provide a basis for further analysis of both innate and adaptive immunity in SARS-CoV-2 clearance, especially in non-severe cases. This study also has implications for understanding the pathogenesis and treatment of SARS-CoV-2.

negative: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study BACKGROUND: Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. METHODS: We retrospectively retrieved data for paediatric patients (aged 0-16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. FINDINGS: From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5-38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir-ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. INTERPRETATION: Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. FUNDING: Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.

negative: A close-up on COVID-19 and cardiovascular diseases Abstract Aims To analyze the potential mechanism of cardiovascular dysfunctions induced by Coronavirus Disease 2019 (COVID-19) and to evaluate more effective therapeutic pathways for patients with cardiovascular diseases. Data Synthesis COVID-19 mainly invades the lungs, causing its serious damage. Studies found that COVID-19 induced the renin-angiotensin system imbalance, inflammatory storm, hypoxemia and stress response et al, all contributed to hypertension and serious myocardial damage in the process of virus pathogenesis, even increasing mortality in COVID-19 patients. Conclusions In the process of management of COVID-19 infections, close attention should be paid on both lung and cardiovascular damage, especially on those with only symptoms of cardiovascular diseases. Early identification, timely and effective treatments, maintenance of hemodynamics and electrophysiological stability are of great significance on effective treatment and long-term prognosis. The pandemic of COVID-19 has been taking lives worldwide. It caused by a novel coronavirus which human being are lack of defensive function in whole population. It targets human’s lung and causes serious damage of lungs. Based on early reports, for people with underlying heart issues, the concerns are serious. It appears people over 65 with coronary heart diseases or hypertension is more likely to be infected and to develop more severe symptoms. In addition, some of hospitalized COVID-19 patients had cardiovascular diseases in China. As characteristic analysis of COVID-19 patients, hypertension and severe myocardial damage contribute to severity [1] and mortality of COVID-19 patients [2]. Therefore, to better understand the development of COVID-19 and the impacts of cardiovascular diseases will add valuable measures to the management of COVID-19 patients.

negative: Temperature significantly changes COVID-19 transmission in (sub)tropical cities of Brazil Abstract The coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue. The novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus. Several studies have robustly identified a relationship between temperature and the number of cases. However, there is no specific study for a tropical climate such as Brazil. This work aims to determine the relationship of temperature to COVID-19 infection for the state capital cities of Brazil. Cumulative data with the daily number of confirmed cases was collected from February 27 to April 1, 2020, for all 27 state capital cities of Brazil affected by COVID-19. A generalized additive model (GAM) was applied to explore the linear and nonlinear relationship between annual average temperature compensation and confirmed cases. Also, a polynomial linear regression model was proposed to represent the behavior of the growth curve of COVID-19 in the capital cities of Brazil. The GAM dose-response curve suggested a negative linear relationship between temperatures and daily cumulative confirmed cases of COVID-19 in the range from 16.8 °C to 27.4 °C. Each 1 °C rise of temperature was associated with a −4.8951% (t = −2.29, p = 0.0226) decrease in the number of daily cumulative confirmed cases of COVID-19. A sensitivity analysis assessed the robustness of the results of the model. The predicted R-squared of the polynomial linear regression model was 0.81053. In this study, which features the tropical temperatures of Brazil, the variation in annual average temperatures ranged from 16.8 °C to 27.4 °C. Results indicated that temperatures had a negative linear relationship with the number of confirmed cases. The curve flattened at a threshold of 25.8 °C. There is no evidence supporting that the curve declined for temperatures above 25.8 °C. The study had the goal of supporting governance for healthcare policymakers.

negative: A Drone-based Networked System and Methods for Combating Coronavirus Disease (COVID-19) Pandemic Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. It is similar to influenza viruses and raises concerns through alarming levels of spread and severity resulting in an ongoing pandemic world-wide. Within five months (by May 2020), it infected 5.89 million persons world-wide and over 357 thousand have died. Drones or Unmanned Aerial Vehicles (UAVs) are very helpful in handling the COVID-19 pandemic. This work investigates the drone-based systems, COVID-19 pandemic situations, and proposes architecture for handling pandemic situations in different scenarios using real-time and simulation-based case studies. The proposed architecture uses wearable sensors to record the observations in Body Area Networks (BANs) in a push-pull data fetching mechanism. The proposed architecture is found to be useful in remote and highly congested pandemic areas where either the wireless or Internet connectivity is a major issue or chances of COVID-19 spreading are high. It collects and stores the substantial amount of data in a stipulated period and helps to take appropriate action as and when required. In real-time drone-based healthcare system implementation for COVID-19 operations, it is observed that a large area can be covered for sanitization, thermal image collection, patient identification etc. within a short period (2 KMs within 10 minutes approx.) through aerial route. In the simulation, the same statistics are observed with an addition of collision-resistant strategies working successfully for indoor and outdoor healthcare operations.

negative: Identification of a coronavirus transcription enhancer. Coronavirus (CoV) transcription includes a discontinuous mechanism during the synthesis of sub-genome-length minus-strand RNAs leading to a collection of mRNAs in which the 5' terminal leader sequence is fused to contiguous genome sequences. It has been previously shown that transcription-regulating sequences (TRSs) preceding each gene regulate transcription. Base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) in the nascent RNA is a determinant factor during CoV transcription. In fact, in transmissible gastroenteritis CoV, a good correlation has been observed between subgenomic mRNA (sg mRNA) levels and the free energy (DeltaG) of TRS-L and cTRS-B duplex formation. The only exception was sg mRNA N, the most abundant sg mRNA during viral infection in spite of its minimum DeltaG associated with duplex formation. We postulated that additional factors should regulate transcription of sg mRNA N. In this report, we have described a novel transcription regulation mechanism operating in CoV by which a 9-nucleotide (nt) sequence located 449 nt upstream of the N gene TRS core sequence (CS-N) interacts with a complementary sequence just upstream of CS-N, specifically increasing the accumulation of sg mRNA N. Alteration of this complementarity in mutant replicon genomes showed a correlation between the predicted stability of the base pairing between 9-nt sequences and the accumulation of sg mRNA N. This interaction is exclusively conserved in group 1a CoVs, the only CoV subgroup in which the N gene is not the most 3' gene in the viral genome. This is the first time that a long-distance RNA-RNA interaction regulating transcriptional activity specifically enhancing the transcription of one gene has been described to occur in CoVs.

negative: Protease Inhibitors: Candidate Drugs to Inhibit Severe Acute Respiratory Syndrome Coronavirus 2 Replication. The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 μg/mL) or nafamostat (0.01-1 μg/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.

negative: A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence Abstract The pneumonia caused by novel coronavirus (SARS-CoV-2) in Wuhan, China in December 2019 is a highly contagious disease. The World Health Organization (WHO) has declared the ongoing outbreak as a global public health emergency. Currently, the research on novel coronavirus is still in the primary stage. Based on the current published evidence, we systematically summarizes the epidemiology, clinical characteristics, diagnosis, treatment and prevention of knowledge surrounding COVID-19. This review in the hope of helping the public effectively recognize and deal with the 2019 novel coronavirus (SARS-CoV-2), and providing a reference for future studies.

negative: Bronchiolitis: lingering questions about its definition and the potential role of vitamin D.

negative: Follow-Up Information About the Four Pregnant Patients With Coronavirus Disease (COVID-19) Pneumonia Who Were Still in the Hospital at the End of Our Study

negative: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response Abstract Background and aim As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. Method We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. Results We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. Conclusion In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.

negative: A structural analysis of M protein in coronavirus assembly and morphology The M protein of coronavirus plays a central role in virus assembly, turning cellular membranes into workshops where virus and host factors come together to make new virus particles. We investigated how M structure and organization is related to virus shape and size using cryo-electron microscopy, tomography and statistical analysis. We present evidence that suggests M can adopt two conformations and that membrane curvature is regulated by one M conformer. Elongated M protein is associated with rigidity, clusters of spikes and a relatively narrow range of membrane curvature. In contrast, compact M protein is associated with flexibility and low spike density. Analysis of several types of virus-like particles and virions revealed that S protein, N protein and genomic RNA each help to regulate virion size and variation, presumably through interactions with M. These findings provide insight into how M protein functions to promote virus assembly.

negative: Still puzzling questions in immunology (infection and immunity)

negative: ‘The economy’ as if people mattered: revisiting critiques of economic growth in a time of crisis Coronavirus (COVID-19) policy shut down the world economy with a range of government actions unprecedented outside of wartime. In this paper, economic systems dominated by a capital accumulating growth imperative are shown to have had their structural weaknesses exposed, revealing numerous problems including unstable supply chains, unjust social provisioning of essentials, profiteering, precarious employment, inequities and pollution. Such phenomena must be understood in the context of long standing critiques relating to the limits of economic systems, their consumerist values and divorce from biophysical reality. Critical reflection on the Coronavirus pandemic is combined with a review of how economists have defended economic growth as sustainable, Green and inclusive regardless of systemic limits and multiple crises–climate emergency, economic crash and pandemic. Instead of rebuilding the old flawed political economy again, what the world needs now is a more robust, just, ethical and equitable social-ecological economy.

negative: Analysis clinical features of COVID-19 infection in secondary epidemic area and report potential biomarkers in evaluation Objective: Based on the clinical characteristics of infected patients with novel coronavirus in secondary epidemic areas,we aimed to identify potential biomarkers for the evaluation of novel coronavirus-infected patients,guide the diagnosis and treatment of this disease in secondary epidemic areas and provide a reference for the clinical prevention and control of this epidemic situation. Methods: The clinical data of 33 patients with respiratory symptoms caused by the novel coronavirus in Wenzhou city from January 15 to February 12,2020,were thoroughly reviewed. At the onset of the disease,we found that the primary symptoms were fever,cough,fatigue,chest tightness,chest pain and specific blood test results. According to the patients'histories,the patients were divided into two groups: those who spent time in the main epidemic area and those who did not spend time in the main epidemic area. The differences in the clinical manifestations between these two groups were analyzed. Results: The main clinical symptoms of patients infected with novel coronavirus in the secondary epidemic area were respiratory tract ailments and systemic symptoms. After grouping patients based on the presence or absence of residency in or travel history to the main epidemic area, there was no significant difference between the baseline data of these two groups, and there were no significant differences in symptoms and signs between the two groups (P>0.05). Some patients had abnormally increased serum amyloid protein A (SAA). There were statistically significant differences in the leukocyte count/C-reactive protein,monocyte ratio/C-reactive protein,neutrophil count/C-reactive protein,monocyte count/C-reactive protein and hemoglobin/C-reactive protein values between the two groups (P < 0.05). Conclusion: Respiratory tract ailments and systemic symptoms were the primary symptoms of novel coronavirus infection in the secondary epidemic area; these symptoms are not typical. The abnormal increase in serum amyloid protein (SAA) may be used as an auxiliary index for diagnosis and treatment. CRP changes before other blood parameters and thus may be an effective evaluation index for patients with COVID-19 infection.

negative: Research and application of physical protection technology and equipment against biological contamination in mainland of China Biological contamination is considered to be great hazardous and related to national security, it is very important to strengthen physical protection against biological contamination accordingly. Key technologies of physical protection against biological contamination were described in terms of isolation, positive/negative pressure, air filtration, antibacterial material and disinfection. Present situation of research and development about Chinese physical protection equipment against biological contamination were presented involving individual protection, collective protection, disinfections, quality control and ergonomics. Finally, Chinese and overseas status about physical protection equipment against biological contamination were analyzed and compared in the areas of administration, research and market. It was concluded that Chinese physical protection equipment against biological contamination fell behind in administration, research and industrialization. As a result, some suggestions with Chinese characteristics were presented to promote development of Chinese physical protection equipment against biological contamination.

negative: Survival of Hendra Virus in the Environment: Modelling the Effect of Temperature Hendra virus (HeV), a highly pathogenic zoonotic paramyxovirus recently emerged from bats, is a major concern to the horse industry in Australia. Previous research has shown that higher temperatures led to lower virus survival rates in the laboratory. We develop a model of survival of HeV in the environment as influenced by temperature. We used 20 years of daily temperature at six locations spanning the geographic range of reported HeV incidents to simulate the temporal and spatial impacts of temperature on HeV survival. At any location, simulated virus survival was greater in winter than in summer, and in any month of the year, survival was higher in higher latitudes. At any location, year-to-year variation in virus survival 24 h post-excretion was substantial and was as large as the difference between locations. Survival was higher in microhabitats with lower than ambient temperature, and when environmental exposure was shorter. The within-year pattern of virus survival mirrored the cumulative within-year occurrence of reported HeV cases, although there were no overall differences in survival in HeV case years and non-case years. The model examines the effect of temperature in isolation; actual virus survivability will reflect the effect of additional environmental factors.

negative: Metronomic oral vinorelbine and lung cancer therapy during the COVID 19 pandemic: a single-center experience • Intravenous vinorelbine is a standard treatment for advanced NSCLC; • Oral vinorelbine is equally effective as compared to intravenous vinorelbine; • Metronomic oral formulation of vinorelbine is a safe and active treatment for advanced NSCLC; • No established treatment is a “gold standard” during COVID19 era; • Metronomic oral vinorelbine permitted to carry on active treatment during COVID Emergency; • Metronomic oral vinorelbine reduce side effects and hospital visits to lung cancer patients; • Management of lung cancer patients may be improved by metronomic oral vinorelbine.

negative: Chapter 3 Basic Concepts A Step-by-Step Guide to Viral Infection Abstract Viral pathogenesis seeks to understand how a virus interacts with its host at multiple levels. Key questions include the source (an infected human, animal, or insect vector), the transmission mechanism, and how the virus is shed and transmitted. Following transmission, pathogenesis is governed by the initial site of replication, whether the virus disseminates within the host, and its tropism for specific tissues and organs. In turn, these steps are dictated by the structure and replication strategy of the virus. In addition to utilizing selected synthetic biochemical pathways in the host cell, viruses frequently reprogram host cells by inducing intracellular signaling pathways that render the cell more permissive. Host–virus interactions also control whether the infection is acute, chronic, latent, or transforming; how the virus interacts with the immune system; and the consequent pathophysiological response of the host. This chapter provides an overview of these basic concepts of viral pathogenesis, with emphasis on the interactions of viruses with their host cells and organisms.

negative: Inside-Out versus Outside-In models for virus induced demyelination: axonal damage triggering demyelination The primary target in multiple sclerosis (MS) is believed to be either myelin itself (myelinopathy) or the myelin-forming cell, the oligodendrocyte (oligodendrogliopathy). Although axonal injury occurs in MS, it is regarded as a secondary event to the myelin damage. Here, the lesion develops from myelin (outside) to the axon (inside) (Outside-In model). Recently, gray matter lesions and axonal injury in normal-appearing white matter have also been reported in MS. This raises two questions. 1) Is axonal injury exclusively secondary to myelin damage or from a direct insult to the axon or neurons (axonopathy)? (2) Is the injured axon regarded as only an end result of pathology or disease, or can axonal injury contribute to the spread of secondary damage, including demyelination? The former is raised from the fact that axonal damage has been reported in several virus infections, including human immunodeficiency virus, human T-lymphotropic virus 1, herpes simplex virus and coronavirus, which also cause demyelination. The latter possibility where axonal injury leads to other changes is raised from the rather unexpected similarity between spinal cord injury (SCI) and MS where axonal injury, oligodendrocyte apoptosis and demyelination are all present. In SCI, transection of axons leads to delayed oligodendrocyte apoptosis with secondary demyelination. Neurofilament immunostaining of spinal cord sections demonstrates that axonal injury with oligodendrocyte apoptosis also precedes demyelination in an animal model for MS, Theiler’s murine encephalomyelitis virus infection. This implies that axonal injury could trigger demyelination. In this instance, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).

negative: COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. In the current review, we summarize and comparatively analyze the emergence and pathogenicity of COVID-19 infection and previous human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). We also discuss the approaches for developing effective vaccines and therapeutic combinations to cope with this viral outbreak.

negative: Chapter 19 Membrane Transport Abstract Life depends on a membrane's ability to precisely control the level of solutes in the aqueous compartments, inside and outside, bathing the membrane. The membrane determines what solutes enter and leave a cell. Transmembrane transport is controlled by complex interactions between membrane lipids, proteins, and carbohydrates. How the membrane accomplishes these tasks is the topic of this chapter.

negative: Prediction of New Coronavirus Infection Based on a Modified SEIR Model BACKGROUND The outbreak of the new coronavirus infection in Wuhan City, Hubei Province in December 2019, poses a huge threat to China and even global public health security. Respiratory droplets and contact transmission are the main routes of transmission of new coronaviruses. Compared with SARS and Ebola viruses, new coronavirus infections are infectious during the incubation period. Traditional SEIR (susceptibility-exposure-infection-Removal) There are some differences in conditions for the prediction of the epidemic trend of new coronavirus infection. The outbreak of the new coronavirus infection coincided with the Spring Festival before and after the Chinese Spring Festival.It is necessary to make appropriate optimization and amendments to the traditional model to meet the actual evolution of the epidemic situation. METHODS The traditional SEIR model assumes that the virus-infected person is not infectious during the incubation period and that the infected person did not take isolation measures during the illness. The transmission of the new coronavirus no longer meets the basic assumptions of the classical kinetic system. Therefore, this article first establishes a modified SEIR model. Predict and analyze the changing trend of the epidemic situation, then estimate the parameters involved in the infection dynamics model, and then use Matlab to simulate the established dynamic equations based on public data and analyze the results. Recommendations for universal prevention and control of infectious diseases. RESULTS The first case of new coronavirus infection was confirmed in Wuhan on December 8, 2019. When Wuhan City took no action, assuming the average daily number of contacts per infected person k = 5, the number of infected persons will reach about 2,384,803 people; If wuhan adopts the measures of sealing the city on January 22, 2020, under the premise of k=2, the number of infected people decreases by 19,773 compared with that on January 23, and there is no significant change in the time when the number of infected people reaches the peak. Under the premise of k = 1, the number of infected persons was reduced by 14,330 compared with the closure on January 23, and the time to reach the peak of the number of infected persons was reduced by 2 days. If Wuhan City is closed for one day, the number of infected persons will increase from 106,145 to 130,626 under the premise of k = 2; the number of infected persons will increase from 74,369 to 92,010 under the premise of k = 1. CONCLUSIONS Comparing the number of confirmed diagnoses actually notified by the department with the number of infected people obtained from the simulation of the model, it can be seen that the city closure measures adopted by the Wuhan Municipal Government on January 23 and the first-level response measures adopted by the country are effective for the epidemic Prevention and control play a vital role. Wearing a mask when going out and avoiding close contact with people can effectively reduce the infection rate.

negative: Precaution and prevention of coronavirus disease 2019 infection in the eye Although current studies suggested that conjunctivitis is not a common presentation of coronavirus disease 2019 (COVID-19), several studies have reported the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ocular secretions. Coronavirus had not yet been successfully cultured from tears or conjunctival swabs in humans, neither SARS-CoV-2 nor SARS-CoV. However, live feline coronavirus has been isolated from conjunctival swabs. In addition, infection of COVID-19 through unprotected eye exposure had been suspected in several articles. Reports of ophthalmologists and otolaryngologists died of COVID-19 also raised concern on ocular transmission. As a result, we strongly suggest that personal protective equipment (PPE) should cover the mouth, nose, and eyes of ophthalmologists, especially when conjunctivitis caused by SARS-CoV-2 is clinically indistinguishable from other viral follicular conjunctivitis.

negative: Coronavirus disease-2019: is fever an adequate screening for the returning travelers? On Thursday, 30 January 2020, World Health Organization declared Coronavirus disease-2019 (COVID-2019) a Public Health Emergency of International Concern. Since its identification in late December 2019 in Wuhan, Hubei Province, People’s Republic of China, the number of cases imported into other countries is increasing, and the epidemiological map is changing rapidly. On the other hand, body temperature screening (fever) is the major test performed at points of entry, i.e., airports, in the returning travelers in most of the countries with limited resources. However, the recent report on asymptomatic contact transmission of COVID-19 and travelers who passed the symptoms-based screening and tested positive for COVID-19 using reverse transcription polymerase chain reaction (RT-PCR) challenges this approach as body temperature screening may miss travelers incubating the disease or travelers concealing fever during travel. On this note, travel restrictions to and from high risk areas and/or 14 days quarantine of travelers coming from high risk areas are recommended to prevent possible importation of COVID-19. Currently, RT-PCR is a reliable test in detecting both symptomatic and asymptomatic COVID-19.

negative: COVID-19 coronavirus: recommended personal protective equipment for the orthopaedic and trauma surgeon PURPOSE: With the COVID-19 crisis, recommendations for personal protective equipment (PPE) are necessary for protection in orthopaedics and traumatology. The primary purpose of this study is to review and present current evidence and recommendations for personal protective equipment and safety recommendations for orthopaedic surgeons and trauma surgeons. METHODS: A systematic review of the available literature was performed using the keyword terms "COVID-19", "Coronavirus", "surgeon", "health-care workers", "protection", "masks", "gloves", "gowns", "helmets", and "aerosol" in several combinations. The following databases were assessed: Pubmed, Cochrane Reviews, Google Scholar. Due to the paucity of available data, it was decided to present it in a narrative manner. In addition, participating doctors were asked to provide their guidelines for PPE in their countries (Austria, Luxembourg, Switzerland, Germany, UK) for consideration in the presented practice recommendations. RESULTS: World Health Organization guidance for respiratory aerosol-generating procedures (AGPs) such as intubation in a COVID19 environment was clear and included the use of an FFP3 (filtering face piece level 3) mask and face protection. However, the recommendation for surgical AGPs, such as the use of high-speed power tools in the operating theatre, was not clear until the UK Public Health England (PHE) guidance of 27 March 2020. This guidance included FFP3 masks and face protection, which UK surgeons quickly adopted. The recommended PPE for orthopaedic surgeons, working in a COVID19 environment, should consist of level 4 surgical gowns, face shields or goggles, double gloves, FFP2-3 or N95-99 respirator masks. An alternative to the mask, face shield and goggles is a powered air-purifying respirator, particularly if the surgeons fail the mask fit test or are required to undertake a long procedure. However, there is a high cost and limited availabilty of these devices at present. Currently available surgical helmets and toga systems may not be the solution due to a permeable top for air intake. During the current COVID-19 crisis, it appeared that telemedicine can be considered as an electronic personal protective equipment by reducing the number of physical contacts and risk contamination. CONCLUSION: Orthopaedic and trauma surgery using power tools, pulsatile lavage and electrocautery are surgical aerosol-generating procedures and all body fluids contain virus particles. Raising awareness of these issues will help avoid occupational transmission of COVID-19 to the surgical team by aerosolization of blood or other body fluids and hence adequate PPE should be available and used during orthopaedic surgery. In addition, efforts have to be made to improve the current evidence in this regard. LEVEL OF EVIDENCE: IV.

negative: Audience readings of media messages about MRSA Summary This paper explores whether, and to what extent, national newspaper messages tally with public perceptions about meticillin-resistant Staphylococcus aureus (MRSA). It compares research on media messages about MRSA with interview data gathered from a demographically diverse sample of 60 people interviewed from the Greater London area. Across the interview sample there was a shared consensus that most people associated MRSA not with the history of antibiotic use, but with dirty and poorly managed hospitals. Some media messages, such as blaming MRSA on the alleged ‘management culture’ of the NHS, seemed to capture the Zeitgeist, whereas others, in particular the ‘celebrity victims’ of MRSA, did not seem to resonate with the audience. This study also found that ideas based on scientific understandings about germ theory and the immune system were held alongside folklore such as miasmic theory. The comparison of media and mind thus points to the existence of pre-scientific understandings of germs, contagion and blame in parallel with the biomedical story in the minds of the public. The findings contribute to our understanding of the public and patients' views of this infection.

negative: Study of Non-Pharmacological Interventions on COVID-19 Spread COVID-19 disease has emerged as one of the life threatening threat to the society. It is caused by a novel beta coronavirus. It began as unidentified pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. No vaccine has been produced till now. Mathematical models are used to study impact of different measures used to decrease pandemic. Mathematical models have been designed to estimate the numbers of spreaders in different scenarios in the present manuscript. In the present manuscript, three different mathematical models have been proposed with different scenarios such as screening, quarantine and NPIs for estimating number of virus spreaders. the analysis shows that the numbers of COVID-19 patients will be more without screening the peoples coming from other countries. Since, every people suffering with COVID-19 disease are spreaders. The screening and quarantine with NPIs have been implemented to study their impact on the spreaders. It has been found that NPI measures are able to reduce number of spreaders. The NPI measures reduces the growth of the spread function and providing decision makers more time to prepare with in dealing of the disease.

negative: Genetic characteristics and polymorphisms in the chicken interferon-induced transmembrane protein (IFITM3) gene The interferon-induced transmembrane protein 3 (IFITM3) gene is classified as a small interferon-stimulated gene and is associated with a broad spectrum of antiviral functions against several fatal enveloped viruses, including influenza A viruses (IAVs). The rs12252 single nucleotide polymorphism (SNP) of the IFITM3 gene in humans was associated with susceptibility to H1N1 influenza in a 2009 pandemic. In addition, overexpression of the IFITM3 protein potently inhibits the highly pathogenic avian influenza H5N1 virus in ducks and chickens. Although chickens are a major host of influenza viruses and the IFITM3 gene participates in the host antiviral system, studies on chicken IFITM3 gene are very rare. To investigate the genetic characteristics of the chicken IFITM3 gene, we performed direct sequencing and alignment in 108 Dekalb White and 72 Ross breeds. We also investigated the genotype and haplotype frequencies and linkage disequilibrium of the IFITM3 gene polymorphisms and evaluated whether the non-synonymous SNPs are deleterious. We found significantly different genotype, allele and haplotypes frequencies between two chicken breeds, Dekalb White and Ross. Furthermore, we compared and analyzed the promoter structure of the chicken IFITM3 gene with that of several species. We found that birds have a long C-terminal domain and inverted topology of the IFITM3 protein compared to mammals. We also identified fourteen genetic polymorphisms in the chicken IFITM3 gene. L100 M and N125H were predicted as ‘probably damaging’ and L100 M can alter the length of its conserved intracellular loop (CIL). Furthermore, chickens, but not mammals, contain CpG islands (CGIs) in this promoter region.

negative: Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as ‘Public Health Emergency of International Concern’ on January 30(th), 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.

negative: Large-scale evolutionary surveillance of the 2009 H1N1 influenza A virus using resequencing arrays In April 2009, a new influenza A (H1N1 2009) virus emerged that rapidly spread around the world. While current variants of this virus have caused widespread disease, particularly in vulnerable groups, there remains the possibility that future variants may cause increased virulence, drug resistance or vaccine escape. Early detection of these virus variants may offer the chance for increased containment and potentially prevention of the virus spread. We have developed and field-tested a resequencing kit that is capable of interrogating all eight segments of the 2009 influenza A(H1N1) virus genome and its variants, with added focus on critical regions such as drug-binding sites, structural components and mutation hotspots. The accompanying base-calling software (EvolSTAR) introduces novel methods that utilize neighbourhood hybridization intensity profiles and substitution bias of probes on the microarray for mutation confirmation and recovery of ambiguous base queries. Our results demonstrate that EvolSTAR is highly accurate and has a much improved call rate. The high throughput and short turn-around time from sample to sequence and analysis results (30 h for 24 samples) makes this kit an efficient large-scale evolutionary biosurveillance tool.

negative: Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS‐CoV‐2 From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS‐CoV‐2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID‐19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID‐19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS‐CoV‐2 is spreading among the public and causing substantial burden due to its human‐to‐human transmission. However, the intermediate host of SARS‐CoV‐2 is still unclear. Finding the possible intermediate host of SARS‐CoV‐2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor‐binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin‐converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS‐CoV‐2 to humans.

negative: Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response. The rat coronavirus sialodacryoadenitis virus (SDAV) causes respiratory infection and provides a system for investigating respiratory coronaviruses in a natural host. A viral suspension in the form of a microspray aerosol was delivered by intratracheal instillation into the distal lung of 6-8-week-old Fischer 344 rats. SDAV inoculation produced a 7 % body weight loss over a 5 day period that was followed by recovery over the next 7 days. SDAV caused focal lesions in the lung, which were most severe on day 4 post-inoculation (p.i.). Immunofluorescent staining showed that four cell types supported SDAV virus replication in the lower respiratory tract, namely Clara cells, ciliated cells in the bronchial airway and alveolar type I and type II cells in the lung parenchyma. In bronchial alveolar lavage fluid (BALF) a neutrophil influx increased the population of neutrophils to 45 % compared with 6 % of the cells in control samples on day 2 after mock inoculation. Virus infection induced an increase in surfactant protein SP-D levels in BALF of infected rats on days 4 and 8 p.i. that subsided by day 12. The concentrations of chemokines MCP-1, LIX and CINC-1 in BALF increased on day 4 p.i., but returned to control levels by day 8. Intratracheal instillation of rats with SDAV coronavirus caused an acute, self-limited infection that is a useful model for studying the early events of the innate immune response to respiratory coronavirus infections in lungs of the natural virus host.

negative: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response BACKGROUND AND AIM: As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. METHOD: We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. RESULTS: We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. CONCLUSION: In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.

negative: A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease Live-attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3′-5′ exonuclease activity (ExoN) that likely functions in RNA proofreading. In this study, we demonstrate that engineered inactivation of SARS-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged, and immunocompromised mouse models of human SARS. The ExoN inactivation genotype and mutator phenotype are stable and do not revert to virulence, even after serial passage or long-term persistent infection in vivo. Our approach represents a strategy with potential for broad applications for the stable attenuation of coronaviruses and possibly other RNA viruses.

negative: Deposition of respiratory virus pathogens on frequently touched surfaces at airports BACKGROUND: International and national travelling has made the rapid spread of infectious diseases possible. Little information is available on the role of major traffic hubs, such as airports, in the transmission of respiratory infections, including seasonal influenza and a pandemic threat. We investigated the presence of respiratory viruses in the passenger environment of a major airport in order to identify risk points and guide measures to minimize transmission. METHODS: Surface and air samples were collected weekly at three different time points during the peak period of seasonal influenza in 2015–16 in Finland. Swabs from surface samples, and air samples were tested by real-time PCR for influenza A and B viruses, respiratory syncytial virus, adenovirus, rhinovirus and coronaviruses (229E, HKU1, NL63 and OC43). RESULTS: Nucleic acid of at least one respiratory virus was detected in 9 out of 90 (10%) surface samples, including: a plastic toy dog in the children’s playground (2/3 swabs, 67%); hand-carried luggage trays at the security check area (4/8, 50%); the buttons of the payment terminal at the pharmacy (1/2, 50%); the handrails of stairs (1/7, 14%); and the passenger side desk and divider glass at a passport control point (1/3, 33%). Among the 10 respiratory virus findings at various sites, the viruses identified were: rhinovirus (4/10, 40%, from surfaces); coronavirus (3/10, 30%, from surfaces); adenovirus (2/10, 20%, 1 air sample, 1 surface sample); influenza A (1/10, 10%, surface sample). CONCLUSIONS: Detection of pathogen viral nucleic acids indicates respiratory viral surface contamination at multiple sites associated with high touch rates, and suggests a potential risk in the identified airport sites. Of the surfaces tested, plastic security screening trays appeared to pose the highest potential risk, and handling these is almost inevitable for all embarking passengers.

negative: Fate of Manure‐Borne Pathogens during Anaerobic Digestion and Solids Separation Anaerobic digestion can inactivate zoonotic pathogens present in cattle manure, which reduces transmission of these pathogens from farms to humans through the environment. However, the variability of inactivation across farms and over time is unknown because most studies have examined pathogen inactivation under ideal laboratory conditions or have focused on only one or two full‐scale digesters at a time. In contrast, we sampled seven full‐scale digesters treating cattle manure in Wisconsin for 9 mo on a biweekly basis (n = 118 pairs of influent and effluent samples) and used real‐time quantitative polymerase chain reaction to analyze these samples for 19 different microbial genetic markers. Overall, inactivation of pathogens and fecal indicators was highly variable. When aggregated across digester and season, log‐removal values for several representative microorganisms—bovine Bacteroides, Bacteroidales‐like CowM3, and bovine polyomavirus—were 0.78 ± 0.34, 0.70 ± 0.50, and 0.53 ± 0.58, respectively (mean ± SD). These log‐removal values were up to two times lower than expected based on the scientific literature. Thus, our study indicates that full‐scale anaerobic digestion of cattle manure requires optimization with regard to pathogen inactivation. Future studies should focus on identifying the potential causes of this suboptimal performance (e.g., overloading, poor mixing, poor temperature control). Our study also examined the fate of pathogens during manure separation and found that the majority of microbes we detected ended up in the liquid fraction of separated manure. This finding has important implications for the transmission of zoonotic pathogens through the environment to humans. CORE IDEAS: Pathogen inactivation is highly variable among full‐scale anaerobic digesters. Pathogen inactivation by full‐scale digesters on cattle farms needs optimization. Most microbes end up in the liquid fraction during solids separation of manure.

negative: Hunting coronavirus severe acute respiratory syndrome coronavirus 2 (2019 novel coronavirus): From laboratory testing back to basic research The rapid spread of coronavirus disease 2019 (COVID-19) in many countries causes citizens of daily inconvenience and even life-threat for elderly population. The invasion of the main pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; 2019 novel coronavirus [2019-nCoV]), into human body causes different levels of impact to various patients. One of the most important issues for COVID-19 is how to defend this virus with the ability to foresee the infected targets. Thus, we maintain the quarantined essentially as for as others saved from COVID-19. So far, the routine laboratory test to confirm whether infected by SARS-CoV-2/2019-nCoV or not is through real-time reverse transcription polymerase chain reaction (rRT-PCR; quantitative polymerase chain reaction [qPCR]) with certain sequence regions that recognize SARS-CoV-2/2019-nCoV RNA genome. The heavy loading of rRT-PCR (qPCR) machine and handling labor have tight-packed the instruments as well as the manpower almost in every country. Therefore, the alternative approaches are eagerly waiting to be developed. In this review article, we sort out some state-of-the-art novel approaches that might be applied for a fast, sensitive, and precise detection of SARS-CoV-2/2019-nCoV not only to help the routine laboratory testing but also to improve effective quarantine.

negative: Investigation of effective climatology parameters on COVID-19 outbreak in Iran Abstract SARS CoV-2 (COVID-19) Coronavirus cases are confirmed throughout the world and millions of people are being put into quarantine. A better understanding of the effective parameters in infection spreading can bring about a logical measurement toward COVID-19. The effect of climatic factors on spreading of COVID-19 can play an important role in the new Coronavirus outbreak. In this study, the main parameters, including the number of infected people with COVID-19, population density, intra-provincial movement, and infection days to end of the study period, average temperature, average precipitation, humidity, wind speed, and average solar radiation investigated to understand how can these parameters effects on COVID-19 spreading in Iran? The Partial correlation coefficient (PCC) and Sobol’-Jansen methods are used for analyzing the effect and correlation of variables with the COVID-19 spreading rate. The result of sensitivity analysis shows that the population density, intra-provincial movement have a direct relationship with the infection outbreak. Conversely, areas with low values of wind speed, humidity, and solar radiation exposure to a high rate of infection that support the virus's survival. The provinces such as Tehran, Mazandaran, Alborz, Gilan, and Qom are more susceptible to infection because of high population density, intra-provincial movements and high humidity rate in comparison with Southern provinces.

negative: Early clinical manifestations and pulmonary imaging analysis of patients with Novel coronavirus pneumonia/ 中华急诊医学杂志 Objective To investigate the early clinical characteristics and radiographic changes in confirmed Novel coronavirus pneumonia (NCP) and excluded NCP patients. Methods Twenty-four patients with suspected NCP admitted to Shanghai Jiao Tong University Affiliated Sixth People’s Hospital and Jinshan Branch Hospital between January and February, 2020 were chosen as our research subjects. Early clinical features and radiographic changes were analyzed in 10 patients of confirmed NCP and 14 patients of excluded NCP. Results In the early stage, all 24 suspected patients were mild, and had normal blood gas analysis. Of 10 diagnosed patients, 50% were male. All the 10 patients had fever and fatigue, with body temperature between 37.5℃ and 38.5℃. Only 1 patient had dry cough. 2 patients had no clear epidemiological exposure history, the other 8 had a clear epidemiological exposure, with a possible incubation period of 1-10 days. From CT imaging, lesions were characterized as ground glass shadow ( n =9), which could be unilateral ( n =1) or bilateral ( n =9), and were mainly close to the pleura ( n =9), with nodule shadow ( n =1) and without focal necrosis, and could combined with pleural effusion ( n =1. Among patients excluded NCP, all 14 patients had a clear history of epidemic exposure, with an onset time of 1 to 13 days. 12 patients had fever , including 4 with temperature > 38.5°C, 8 with temperature 37.3-38.5°C, and 2 without fever. All patients had fatigue , 7 patients had dry cough and 2 patients had chest pain. From CT imaging, ground glass shadow appeared in 4 patients , lesions were unilateral in 10 patients and bilateral in 4 patients , and the lesions were relatively sporadic, without necrosis or pleural effusion. Conclusion 1．Not all patients with NCP have a direct history of epidemiology exposure, some patients may be infected unknowingly. 2. According to CT imaging, NCP seems to have no special manifestations different from other viral pneumonia. 3. NCP is more common among middle-aged people.

negative: Infections and foreign bodies in ENT Abstract Infections of the ear, nose and throat are common. The majority of these infections are managed by the primary care physicians and they settle with conservative and medical management. However, a small group can progress to become troublesome and develop complications to the extent that they may require surgical intervention. Some of the infections can lead to life-threatening complications therefore awareness and correct diagnosis along with appropriate management is paramount. Foreign bodies in the ear, nose and throat are commonly encountered. The location and type of foreign body can have an implication on the urgency of action and the possible complications. In this article the common ENT infections and foreign bodies and their management are discussed.

negative: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Emergence, History, Basic and Clinical Aspects Abstract In late December 2019, the world woke to a reality of a pandemic of Coronavirus Disease (COVID-19), elicited by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which belongs to a group of β-coronavirus. The potential to cause life-threatening respiratory failure and rapid transmission puts COVID-19 in the list of Public Health Emergency of International Concern (PHEIC). In the last two decades, this is the 3rd deadliest Coronavirus pandemic, following SARS which lasted between 2002 and 2003 and Middle East Respiratory Syndrome (MERS) from 2012 till date. Globally and as of April 1st 2020, COVID-19 has affected 924,688 individuals in over 200 countries, causing 46,368 fatalities. While the SARS-CoV-2 originated in China with over 82,724 confirmed cases and more than 3000 deaths as at the time of writing this review, the rapid transmission of SARS-CoV-2 has resulted in exponential increase in the number of cases outside of China to about 10 times the report case and death in mainland China. SARS-CoV-2 is suspected to be zoonotic in nature as genetic studies have shown sequence similarity to viruses originating from bats. Extreme precautionary measures, such as curfew, shutting of borders and quarantining of individuals suspected to be infected have been instituted with immediate effect; however, due to individuals that are asymptomatic, uncontrolled human-to-human transmission has resulted in exponential infection rate and numerous loss of lives even with this lockdown measures. This review article summarizes the developing situation surrounding the SARS-CoV-2 pandemic with respect to its epidemiology, unique genomic structure, possible origins, transmission, pathogenesis, comparison with other deadly species of Coronaviruses (CoV) and emerging treatment strategies built on informed literature.

negative: Understanding SARS-CoV-2: Genetic Diversity, Transmission and Cure in Human As the SARS-CoV-2 virus race around the world across the different population, there needs to be a consolidated effort to understand the divergence of demographically distributed strains. The emerging trends in SARS-CoV-2 genome data show specific mutation and genetic diversity, which could provide the basis to develop a cocktail of vaccine and may also be used to develop the region-specific diagnostic tool, thus decreasing the chances of testing failures in fields. Since the transmission of SARS-CoV-2 is subject to the extent of human interaction, the insights from the correlation of genetic diversity with epidemiological parameter would give paramount information to tackle this transmission. Previously, studies have also correlated the epidemiological data with gut microbiome and its role in immunomodulation for maintaining health status, and such information could be generated from recovered individuals from different demographic regions. It will help in designing a probiotic-based diet for modulation of the gut microbiome, and that could be another plausible prophylactic treatment option. The genomics data suggest that a specific variant of SARS-CoV-2 gets enriched with the specific demographic region. Overall, demographic data suggests that host influences mutation and expression of the virus. Hence, the experiences from the clinical intervention for that region should be considered in control and treatment strategies.

negative: Global rheumatology in the time of COVID-19

negative: Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors (VDR; GATA5; SFTPC; HIF1a) and activators (HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website.

negative: Cryo-EM structures of HKU2 and SADS-CoV spike glycoproteins and insights into coronavirus evolution A new porcine coronavirus SADS-CoV was recently identified from suckling piglets with severe diarrhea in southern China and its genome sequence is most identical (~95% identity) to that of bat α-coronavirus HKU2. It again indicates bats are the natural reservoir of many coronaviruses that have great potential for cross-species transmission to animals and humans by recombination and/or mutation. Here we report the cryo-EM structures of HKU2 and SADS-CoV spike glycoprotein trimers at 2.38 Å and 2.83 Å resolution, respectively. HKU2 and SADS-CoV spikes exhibit very high structural similarity, with subtle differences mainly distributed in the NTD and CTD of the S1 subunit responsible for cell attachment and receptor binding. We systematically analyzed and compared the NTD, CTD, SD1 and SD2 domains of the S1 subunit and the S2 subunit of HKU2 spike with those of α-, β-, γ-, and δ-coronavirus spikes. The results show that the NTD and CTD of HKU2/SADS-CoV are probably the most ancestral in the evolution of spike. Although the S2 subunit mediating membrane fusion is highly conserved, the connecting region after fusion peptide in HKU2/SADS-CoV S2 subunit also adopts a conformation distinct from other coronaviruses. These results structurally demonstrate a close evolutionary relationship between HKU2 /SADS-CoV and β-coronavirus spikes and provide new insights into the evolution and cross-species transmission of coronaviruses.

negative: Structural analysis of SARS-CoV-2 and prediction of the human interactome Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of>2500 coronaviruses and computed>100000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the 3 and 5 prime ends are the most structured elements in the viral genome and the 5 prime end has the strongest propensity to associate with human proteins. The domain encompassing nucleotides 23000-24000 is highly conserved both at the sequence and structural level, while the region upstream varies significantly. These two sequences code for a domain of the viral protein Spike S that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) and has the potential to bind sialic acids. Our predictions indicate that the first 1000 nucleotides in the 5 prime end can interact with proteins involved in viral RNA processing such as double-stranded RNA specific editases and ATP-dependent RNA-helicases, in addition to other high-confidence candidate partners. These interactions, previously reported to be also implicated in HIV, reveal important information on host-virus interactions. The list of transcriptional and post-transcriptional elements recruited by SARS-CoV-2 genome provides clues on the biological pathways associated with gene expression changes in human cells.

negative: [Extra-pulmonary clinical manifestations of novel coronavirus pneumonia]. COVID-19 has been prevalent in many countries and regions of the world since the end of December 2019. Studies have shown that SARS-CoV-2 infects the human body and replicates effectively through angiotensin-converting enzyme II (ACE2). ACE2 is widely distributed in various tissues and organs of the human body, such as intestinal epithelial cells, cardiomyocytes, renal tubular epithelial cells, and testicular stromal cells, etc. This could be one of the reasons for the diversity of clinical manifestations of COVID-19, or it may be the cause of accelerated disease progression and multi-system damage. This article reviews the clinical manifestations of COVID-19 related to the extrapulmonary system such as digestive, circulatory, urogenital, hematopoietic and nervous.

negative: Factors associated with prolonged viral RNA shedding in patients with COVID-19 BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from two hospitals outside Wuhan. RESULTS: The median duration of SARS-CoV-2 RNA detection was 17 days (Interquartile Range [IQR], 13–22 days) as measured from illness onset. When comparing patients with early (<15 days) and late viral RNA clearance (≥15 days after illness onset), prolonged SARS-CoV-2 RNA shedding was associated with male sex (p=0.009), old age (p=0.033), concomitated with hypertension (p=0.009), delayed admission to hospital after illness onset (p=0.001), severe illness at admission (p=0.049), invasive mechanical ventilation (p=0.006), and corticosteroid treatment (p=0.025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (p<0.001) and focal absorption on radiograph images (p<0.001) than patients with early SARS-CoV-2 RNA clearance. Male sex (odds ratio [OR], 3.24 [95% CI, 1.31–8.02]), delayed hospital admission (OR, 1.30 [95% CI, 1.10–1.54]), and invasive mechanical ventilation (OR, 9.88 [95% CI, 1.11–88.02]) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

negative: Psychological responses, behavioral changes and public perceptions during the early phase of the COVID-19 outbreak in China: a population based cross-sectional survey Objective: To investigate psychological and behavioral responses to the threat of SARS-CoV-2 infections and their associations with public perceptions in China Design: Cross sectional population-based telephone survey via random digital dialing between 1 and 10 February, 2020 Setting: Wuhan (the epicentre and quarantined city), and Shanghai (a typical major city with close transportation link with Wuhan) Participants: Random sample of 510 residents in Wuhan and 501 residents in Shanghai aged above 18 Main outcome measures: Anxiety (measured by the 7-item generalized anxiety disorder [GAD-7] scale), recommended and avoidance behaviors (engaged in all six behaviors such as increasing surface cleaning and reducing going out). Results: The prevalence rates of moderate or severe anxiety (score ≥10 on GAD-7) were 32.7% (n=167) among Wuhan participants and 20.4% (n=102) among Shanghai participants. 78.6% (n=401) of Wuhan participants and 63.9% (n=320) of Shanghai participants had carried out all six precautionary behaviors. For both measures, Wuhan participants were more responsive to the outbreak (p<0.001). Controlling for personal characteristics, logistic regression results suggested that risks of moderate or severe anxiety were positively associated with perceived susceptibility (odds ratio 1.6, 95% confidence interval 1.3-1.8) and severity of the disease (1.6, 1.4-1.9) and confusion about information reliability (1.6, 1.5-1.9). Having confidence in taking measures to protect oneself against the disease was associated with a lower risk (0.6, 0.5-0.7). The strongest predictor of behavioral change was perceived severity (1.2, 1.1-1.4), followed by confusion about information reliability (1.1, 1.0-1.3). Conclusions: Psychological and behavioral responses to COVID-19 have been dramatic during the rising phase of the outbreak. Our results support efforts for timely dissemination of accurate and reliable information to address the high anxiety level.

negative: The rippled newsvendor: A new inventory framework for modelling supply chain risk severity in the presence of risk propagation How should managers take into account the propagation of supply chain disruptions and risks (i.e. the ripple effect) when they design their inventory policies? For over 60 years, various extensions and applications to the popular newsvendor model have been suggested, where cost/profit are often the focal objective. We propose a new version of the traditional single-period newsvendor model - the ”Rippled Newsvendor” - with supply chain severity (i.e. risk propagation) as the primary objective while taking into account network structure. Our model considers exogenous and endogenous risk(s) of disruption while exploring the tension between under-supply and ”wear-and-tear” (i.e system breakdown). To model the intricacies of this trade-off whilst minimizing the potential spread of risk, we leverage a Bayesian Network whereby the conditional probability distributions are functions of the inventory ordering decisions. We use a simulation study to understand the nature of our objective function as well as to gain insight into the potential optimal ordering policies of this new model. Furthermore, the simulation seeks to understand how the various factors in our system impact total risk severity, and if they do so in different ways. Our simulations indicate that local exogenous risk is of greater importance than non-local exogenous risk. Furthermore, we show that the type of risk, as well as the structural characteristics of the supply chain and inventory system, impact risk severity differently.

negative: Randomised trial comparing forced-air warming to the upper or lower body to prevent hypothermia during thoracoscopic surgery in the lateral decubitus position. BACKGROUND In the supine position, forced-air warming is more effective on the lower body than on the upper body to prevent intraoperative hypothermia. However, it is unknown in the lateral decubitus position. We thus compared forced-air warming on the upper and lower bodies in the lateral position. METHODS Patients (n=123) were randomised to receive forced-air warming on the upper body or lower body during thoracoscopic surgery in the lateral position. We measured the nasopharyngeal temperature at 0, 30, 60, 90, and 120 min after lateral positioning during surgery and the infrared tympanic membrane temperature at 0, 30, 60, 90, and 120 min after surgery. Patients received both upper and lower body warming at a temperature of <35.5°C. The primary outcome was the incidence of intraoperative hypothermia with a temperature of <36.0°C. RESULTS Intraoperative hypothermia was less frequent with the upper body warming than with the lower body warming {21/62 vs 35/61, risk ratio [95% confidence interval (CI)] 0.6 (0.4-0.9), P=0.011}. The intraoperative temperature was higher with the upper body warming than with the lower body warming at 30 (P=0.002), 60 (P<0.001), and 90 (P<0.001) min after lateral positioning, and the postoperative temperature was higher at 0 (P<0.001) and 30 (P=0.001) min after surgery. Fewer patients received both upper and lower body warming in the upper body warming group than in the lower body warming group during surgery (1 vs 7, P=0.032). CONCLUSIONS Forced-air warming was more effective on the upper body than on the lower body to prevent hypothermia during thoracoscopic surgery in the lateral decubitus position. CLINICAL TRIAL REGISTRATION NCT02993666.

negative: Transmission of pathogen-laden expiratory droplets in a coach bus Droplet dispersion carrying viruses/bacteria in enclosed/crowded buses may induce transmissions of respiratory infectious diseases, but the influencing mechanisms have been rarely investigated. By conducting high-resolution CFD simulations, this paper investigates the evaporation and transport of solid-liquid mixed droplets (initial diameter 10 µm and 50 µm, solid to liquid ratio is 1:9) exhaled in a coach bus with 14 thermal manikins. Five air-conditioning supply directions and ambient relative humidity (RH = 35 % and 95 %) are considered. Results show that ventilation effectiveness, RH and initial droplet size significantly influence droplet transmissions in coach bus. 50 µm droplets tend to evaporate completely within 1.8 s and 7 s as RH = 35 % and 95 % respectively, while 0.2 s or less for 10 µm droplets. Thus 10 µm droplets diffuse farther with wider range than 50 µm droplets which tend to deposit more on surfaces. Droplet dispersion pattern differs due to various interactions of gravity, ventilation flows and the upward thermal body plume. The fractions of droplets suspended in air, deposited on wall surfaces are quantified. This study implies high RH, backward supply direction and passengers sitting at nonadjacent seats can effectively reduce infection risk of droplet transmission in buses. Besides taking masks, regular cleaning is also recommended since 85 %-100 % of droplets deposit on object surfaces.

negative: Facing the COVID‐19 outbreak: What should we know and what could we do? A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei Province in China in December 2019 and caused a serious type of pneumonia called coronavirus disease 2019 or COVID-19. This epidemic quickly spread across China and extended to more than 20 other countries. This commentary discusses the reasons for the fast spread of SARS-CoV-2 in three aspects: the infectious sources, including the biological nature of the virus; the susceptible population; and the transmission routes. The current situations and suggestions regarding the control of the disease are summarized. This article is protected by copyright. All rights reserved.

negative: Assessing the plausibility of subcritical transmission of 2019-nCoV in the United States Abstract: The 2019-nCoV outbreak has raised concern of global spread. While person-to-person transmission within the Wuhan district has led to a large outbreak, the transmission potential outside of the region remains unclear. Here we present a simple approach for determining whether the upper limit of the confidence interval for the reproduction number exceeds one for transmission in the United States, which would allow endemic transmission. As of February 7, 2020, the number of cases in the United states support subcritical transmission, rather than ongoing transmission. However, this conclusion can change if pre-symptomatic cases resulting from human-to-human transmission have not yet been identified.

negative: A Systems Approach to Assess Transport and Diffusion of Hazardous Airborne Particles in a Large Surgical Suite: Potential Impacts on Viral Airborne Transmission Airborne transmission of viruses, such as the coronavirus 2 (SARS-CoV-2), in hospital systems are under debate: it has been shown that transmission of SARS-CoV-2 virus goes beyond droplet dynamics that is limited to 3-6 feet, but it is unclear if the airborne viral load is significant enough to ensure transmission of the disease. Surgical smoke can act as a carrier for tissue particles, viruses, and bacteria. To quantify airborne transmission from a physical point of view, we consider surgical smoke produced by thermal destruction of tissue during the use of electrosurgical instruments as a marker of airborne particle diffusion-transportation. Surgical smoke plumes are also known to be dangerous for human health, especially to surgical staff who receive long-term exposure over the years. There are limited quantified metrics reported on long-term effects of surgical smoke on staff's health. The purpose of this paper is to provide a mathematical framework and experimental protocol to assess the transport and diffusion of hazardous airborne particles in every large operating room suite. Measurements from a network of air quality sensors gathered during a clinical study provide validation for the main part of the model. Overall, the model estimates staff exposure to airborne contamination from surgical smoke and biological material. To address the clinical implication over a long period of time, the systems approach is built upon previous work on multi-scale modeling of surgical flow in a large operating room suite and takes into account human behavior factors.

negative: The Malnutritional Status of the Host as a Virulence Factor for New Coronavirus SARS-CoV-2

negative: Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).

negative: Potential Factors Influencing Repeated SARS Outbreaks in China Within last 17 years two widespread epidemics of severe acute respiratory syndrome (SARS) occurred in China, which were caused by related coronaviruses (CoVs): SARS-CoV and SARS-CoV-2. Although the origin(s) of these viruses are still unknown and their occurrences in nature are mysterious, some general patterns of their pathogenesis and epidemics are noticeable. Both viruses utilize the same receptor-angiotensin-converting enzyme 2 (ACE2)-for invading human bodies. Both epidemics occurred in cold dry winter seasons celebrated with major holidays, and started in regions where dietary consumption of wildlife is a fashion. Thus, if bats were the natural hosts of SARS-CoVs, cold temperature and low humidity in these times might provide conducive environmental conditions for prolonged viral survival in these regions concentrated with bats. The widespread existence of these bat-carried or -released viruses might have an easier time in breaking through human defenses when harsh winter makes human bodies more vulnerable. Once succeeding in making some initial human infections, spreading of the disease was made convenient with increased social gathering and holiday travel. These natural and social factors influenced the general progression and trajectory of the SARS epidemiology. However, some unique factors might also contribute to the origination of SARS in Wuhan. These factors are discussed in different scenarios in order to promote more research for achieving final validation.

negative: Technologies to Optimize the Care of Severe Coronavirus Disease 2019 Patients for Health Care Providers Challenged by Limited Resources Health care systems are belligerently responding to the new Coronavirus Disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a specific condition, whose distinctive features are severe hypoxemia associated with (>50% of cases) normal respiratory system compliance.(1) When a patient requires intubation and invasive ventilation, the outcome is poor,(2–4) and the length of stay in the intensive care unit (ICU) is usually 2or 3 weeks.(2) In this article, theauthors review several technological devices, which could support health care providers at the bedside to optimizethe care for COVID-19 patients who are sedated, paralyzed, and ventilated. Particular attention is provided to the use of videolaryngoscopes (VL) because these can assist anesthetists to perform a successful intubation outside the ICU while protecting health care providers from this viral infection. Authors will also review processed electroencephalographic (EEG) monitors which are used to better titrate sedation and the train-of-four monitors which are utilizedto better titrate neuromuscular blocking agents in the view of sparing limited pharmacological resources. COVID-19 can rapidly exhaust human and technological resources too within the ICU. This review features a series of technological advancements that can significantly improve the care of patients requiring isolation. The working conditions in isolation could cause gaps or barriers in communication, fatigue, and poor documentation of provided care. The available technology has several advantages including (a) facilitating appropriate paperless documentation and communication between all health care givers working in isolation rooms or large isolation areas; (b) testing patients and staff at the bedside using smart point-of-care diagnostics (SPOCD) to confirm COVID-19 infection; (c) allowing diagnostics and treatment at the bedside through point-of-care ultrasound (POCUS) and thromboelastography(TEG); (d) adapting the use of anesthetic machines and the use of volatile anesthetics. Implementing technologies for safeguarding health care providers as well as monitoring the limited pharmacological resources are paramount. Only by leveraging new technologies, it will be possible to sustain and support health care systems during the expected long course of this pandemic.

negative: Review on Machine and Deep Learning Models for the Detection and Prediction of Coronavirus The novel Coronavirus disease has increased rapidly in the Wuhan city of China in December 2019. This fatal virus has spread across the whole world like a fire in different stages and affecting millions of population and thousands of deaths worldwide. Therefore, it is essential to classify the infected people, so that they can take the precaution in the earlier stages. Also, due to the increasing cases spread of Coronavirus, there are only limited numbers of polymerase change reaction kits available in the hospitals for testing Coronavirus patients. That why it is extremely important to develop artificial intelligence-based automatic diagnostic tools to classify the Coronavirus outbreak. The objective of this paper is to know the novel disease epidemiology, major prevention from spreading of Coronavirus Severe Acute Respiratory Syndrome, and to assess the machine and deep learning-based architectures performance that is proposed in the present year for classification of Coronavirus images such as, X-Ray and computed tomography. Specifically, advanced deep learning-based algorithms known as the Convolutional neural network, which plays a great effect on extracting highly essential features, mostly in terms of medical images. This technique, with using CT and X-Ray image scans, has been adopted in most of the recently published articles on the Coronavirus with remarkable results. Furthermore, according to this paper, this can be noted and said that deep learning technology has potential clinical applications.

negative: Health and growth of Finnish beef calves and the relation to acute phase response Abstract Healthy, thriving calves are essential for beef calf production. We studied the health status and factors associated with the growth of beef calves in six cow-calf herds during the first month of the calves’ lives and at weaning age (200 days). The six herds were visited three times, when calves were approximately 3 days, 16 days and 30 days of age. On each visit calves (n=37) were clinically examined, weighed or measured, blood samples were collected, faecal samples obtained and deep nasopharyngeal swabs were taken. Each blood sample was analysed for acute phase proteins (haptoglobin, serum amyloid-A, fibrinogen), total proteins and albumin, the faecal sample for intestinal tract pathogens (rotavirus, bovine coronavirus, enterotoxigenic Escherichia coli and Salmonella, oocysts of Eimeria coccidia and Cryptosporidium, and nematode eggs), and the nasopharyngeal swab for respiratory tract pathogens (bovine coronavirus (BCV), respiratory syncytial virus (RSV), bacteria and mycoplasma). Clinical diagnosis of respiratory tract disease, diarrhoea or umbilical disease was set at 15.0% for all the three consecutive examinations combined (n=107), but only few pathogens were detected from the samples. The increased levels of acute phase proteins were neither associated with any of the diseases nor with the pathogens. Random intercept linear models were used to explore factors affecting early (3–30 days) and long-term (3–200 days) growth, showing that calves with elevated serum amyloid-A concentrations at the age of 16 days had lower long-term growth. Increased albumin concentration at 30 days of age and higher parity of the dam increased early-term growth. The lack of association between a disease and the acute phase protein may stem from the low disease prevalence in the beef calves examined. The measurement of acute phase proteins of a young calf can help identify animals with possible future growth deficiencies, although the mechanisms through which the association between acute phase proteins and growth has yet to be explained.

negative: Human Coronavirus (HCoV) Infection Among Adults in Cleveland, Ohio: An Increasingly Recognized Respiratory Pathogen BACKGROUND: Human Coronaviruses (CoV) have been long recognized as a common cause of respiratory tract disease including severe respiratory tract illness, yet there are few recent studies characterizing disease among adults in the United States. Here, we describe CoV infections and clinical characteristics among adults (>18 years) presenting with respiratory illness in Cleveland, Ohio. METHODS: Between February 1, 2016 and April 30, 2017, 2949 nasopharyngeal swab specimens were analyzed by NxTAG Respiratory Pathogen Panel in adults presenting with respiratory illness at MetroHealth Medical Center. Clinical data were collected on adults whose samples screened positive for CoV-HKU1, CoV-OC43, CoV-229E or CoV-NL63. RESULTS: Coronaviruses were detected in 192 (6.5%) adults including 105 (3.5%) OC43, 67 (2.3%) 229E, 13 (0.4%) HKU1 and 7 (0.2%) NL63. The majority of adults with coronavirus infection were females (66.2%) with a median age of 53 years. Common comorbidities included smoking (40.0%), asthma (38.0%), COPD (35.4%), and inhaled corticosteroid use (28.6%). Eighty-five (46.4%) required admission to the hospital. Common presenting symptoms included shortness of breath (42.7%) and cough (31.0%) whereas fever was uncommon (12.5%). Gastrointestinal symptoms were more common in HKU1 and NL63 infected adults. Seventy-three percent of coronavirus disease occurred between the months of January and March. Despite the recognition of coronavirus infection, 70 (36.5%) received antibiotics for their disease. CONCLUSION: This study provides needed insight into clinical characteristics and severity associated with coronavirus infection in adults. Coronavirus infection should be considered in differential diagnosis of respiratory tract illness in adults including those that require hospitalization, have a history of smoking and have pulmonary comorbidities. DISCLOSURES: All authors: No reported disclosures.

negative: How lethal is the novel coronavirus, and how many undetected cases there are? The importance of being tested. There is big concern for estimating the lethality and the extent of undetected infections associated with the novel coronavirus SARS-CoV2 outbreak. While detailed epidemiological models are certainly needed, I suggest here an orthogonal approach based on a minimum number of parameters robustly fitted from the cumulative data easily accessible for all countries at the John Hopkins University database that became the worldwide reference for the pandemics. I show that, after few days from the beginning of the outbreak, the apparent death rate can be extrapolated to infinite time through regularized regression such as rescaled ridge regression. The variation from country to country of these extrapolated death rates appears to depend almost only (r^2=0.91) on the ratio between performed tests and detected cases even when the instantaneous apparent lethality rates are as different as 9% in Italy and 0.4% in Germany. Extrapolating to the limit of infinite number of tests, I obtain a death rate of 0.012+/- 0.012, in agreement with other estimates. The inverse relationship between the extrapolated death rate and the intensity tests allows estimating that more than 50% of cases were undetected in most countries, with more than 90% undetected cases in countries severely hit by the epidemics such as Italy. Finally, I propose to adopt the ratio between the cumulative number of recovered and deceased persons as an indicator that can anticipate the halting of the epidemics.

negative: Recombination in large RNA viruses: Coronaviruses Abstract Coronaviruses contain a very large RNA genome, which undergoes recombination at a very high frequency of nearly 25% for the entire genome. Recombination has been demonstrated to occur between viral genomes and between defective-interfering (DI) RNAs and viral RNA. It provides an evolutionary tool for both viral RNAs and DI RNA and may account for the diversity in the genomic structure of coronaviruses. The capacity of coronaviruses to undergo recombination may be related to its mRNA transcription mechanism, which involves discontinuous RNA synthesis, suggesting the nonprocessive nature of the viral polymerase. Recombination is used as a tool for the mutagenesis of viral genomic RNA.

negative: SARS-CoV-2 mortality in blacks and temperature-sensitivity to an angiotensin-2 receptor blocker Tropical climates provoke adaptations in skin pigmentation and in mechanisms controlling the volume, salt-content and pressure of body fluids. For many whose distant ancestors moved to temperate climes, these adaptations proved harmful: pigmentation decreased by natural selection and susceptibility to hypertension emerged. Now an added risk is lung inflammation from coronavirus that may be furthered by innate immune differences. Hypertension and coronavirus have in common angiotensin converting enzyme 2 (ACE2), which decreases blood pressure and mediates virus entry. In keeping with less detailed studies, a long-term case-report shows that decreased blood pressure induced by blocking a primary angiotensin receptor is supplemented, above critical blocker dosage, by a further temperature-dependent fall, likely mediated by ACE2 and secondary angiotensin receptors. Temperature-dependence suggests a linkage with tropical heritage and an influence of blockers on the progress of coronavirus infections. Positive therapeutic results should result from negation of host pro-inflammatory effects mediated by the primary angiotensin receptor and concomitant promotion of countervailing anti-inflammatory effects mediated by ACE2 through other receptors. These effects may involve components of the lectin complement pathway. Black vulnerability, more likely based on physiological than on socioeconomic differences, provides an important clue that may guide treatments.

negative: Understanding of COVID‐19 based on current evidence Since December 2019, a series of unexplained pneumonia cases have been reported in Wuhan, China. On 12 January 2020, the World Health Organization (WHO) temporarily named this new virus as the 2019 novel coronavirus (2019‐nCoV). On 11 February 2020, the WHO officially named the disease caused by the 2019‐nCoV as coronavirus disease (COVID‐19). The COVID‐19 epidemic is spreading all over the world, especially in China. Based on the published evidence, we systematically discuss the characteristics of COVID‐19 in the hope of providing a reference for future studies and help for the prevention and control of the COVID‐19 epidemic.

negative: Potential interventions for novel coronavirus in China: A systematic review An outbreak of a novel coronavirus (COVID‐19 or 2019‐CoV) infection has posed significant threats to international health and the economy. In the absence of treatment for this virus, there is an urgent need to find alternative methods to control the spread of disease. Here, we have conducted an online search for all treatment options related to coronavirus infections as well as some RNA‐virus infection and we have found that general treatments, coronavirus‐specific treatments, and antiviral treatments should be useful in fighting COVID‐19. We suggest that the nutritional status of each infected patient should be evaluated before the administration of general treatments and the current children's RNA‐virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers. In addition, convalescent plasma should be given to COVID‐19 patients if it is available. In conclusion, we suggest that all the potential interventions be implemented to control the emerging COVID‐19 if the infection is uncontrollable.

negative: Incorporating polymerase chain reaction-based identification, population characterization, and quantification of microorganisms into aerosol science: A review Abstract The quantity, identity, and distribution of biomass in indoor and outdoor aerosols are poorly described. This is not consistent with the current understanding of atmospheric chemistry or the microbiological characterization of aquatic and terrestrial environments. This knowledge gap is due to both difficulties in applying contemporary microbiological techniques to the low biomass concentrations present in aerosols, and the traditional reliance of aerosol researchers on culture-based techniques—the quantitative limitations and ecological biases of which have been well-documented and are now avoided in other environmental matrices. This article reviews the emergence of the polymerase chain reaction (PCR) as a nonculture-based method to determine the identity, distribution, and abundance of airborne microorganisms. To encourage the use of PCR-based techniques by a broad spectrum of aerosol researchers, emphasis is given to the critical, aerosol specific method issues of sample processing, DNA extraction, and PCR inhibition removal. These methods are synthesized into a generalized procedure for the PCR-based study of microbial aerosols—equally applicable to both indoor and outdoor aerosol environments.

negative: Estimating number of global importations of COVID-19 from Wuhan, risk of transmission outside mainland China and COVID-19 introduction index between countries outside mainland China Background The emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China in early December 2019 has caused widespread transmission within the country, with over 1,000 deaths reported to date. Other countries have since reported coronavirus disease 2019 (COVID-19) importation from China, with some experiencing local transmission and even case importation from countries outside China. We aim to estimate the number of cases imported from Wuhan to each country or territory outside mainland China, and with these estimates assess the risk of onward local transmission and the relative potential of case importation between countries outside China. Methods We used the reported number of cases imported from Wuhan and flight data to generate an uncertainty distribution for the estimated number of imported cases from Wuhan to each location outside mainland China. This uncertainty was propagated to quantify the local outbreak risk using a branching process model. A COVID-19 introduction index was derived for each pair of donor and recipient countries, accounting for the local outbreak risk in the donor country and the between-country connectivity. Results We identified 13 countries or territories outside mainland China that may have under-detected COVID-19 importation from Wuhan, such as Thailand and Indonesia. In addition, 16 countries had a local outbreak risk estimate exceeding 50%, including four outside Asia. The COVID-19 introduction index highlights potential locations outside mainland China from which cases may be imported to each recipient country. Conclusions As SARS-CoV-2 continues to spread globally, more epicentres may emerge outside China. Hence, it is important for countries to remain alert for the possibilities of viral introduction from other countries outside China, even before local transmission in a source country becomes known.

negative: A Rapid Fatal Evolution of Coronavirus Disease-19 in a Patient With Advanced Lung Cancer With a Long-Time Response to Nivolumab

negative: Effectiveness of airport screening at detecting travellers infected with 2019-nCoV As the number of novel coronavirus cases grows both inside and outside of China, public health authorities require evidence on the effectiveness of control measures such as thermal screening of arrivals at airports. We evaluated the effectiveness of exit and entry screening for 2019-nCoV infection. In our baseline scenario, we estimated that 46.5% (95%CI: 35.9 to 57.7) of infected travellers would not be detected, depending on the incubation period, sensitivity of exit and entry screening, and the proportion of cases which are asymptomatic. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers. We developed an online tool so that results can be updated as new information becomes available.

negative: Cordyceps industry in China Cordyceps, as a general term, describes a group of ascomycetous fungi growing on arthropods and other related fungi. Some cordyceps have been used in traditional Chinese medicine for centuries and cordyceps-derived products are currently a big industry in China. A number of medicinal and health products have been developed and extensively commercialized from natural Chinese cordyceps, its anamorphic fungus (Hirsutella sinensis), and other fungi known as Chinese cordyceps. The lack of a defined classification system for medicinal cordyceps fungi is a source of confusion in the industry and the public, and even among pharmaceutical scientists. This review summarizes the cordyceps fungi currently used in the industry in China with a special reference to clarify Chinese cordyceps and associated fungi. Cordyceps militaris, Cordyceps guangdongensis and Isaria cicadae are well recognized and commercialized cordyceps fungi in China. Except the natural Chinese cordyceps and its anamorphic fungus, Paecilomyces hepiali, Mortierella hepiali, Cephalosporium sinensis and Clonostachys rosea isolated from natural Chinese cordyceps are classified as Chinese cordyceps–associated fungi. P. hepiali is a cordyceps fungus based on current phylogenetic analysis of Hypocreales, while M. hepiali is a fungus in the Zygomycetes and should only be treated as associated fungus of Chinese cordyceps. C. sinensis and C. rosea belong to the Hypocreales and their relationship to cordyceps fungi should be further studied. The exploitation of the resources of cordyceps fungi and their quality control in the industry should be major topics for future studies. Cooperation between the industry and the research community will enhance the whole cordyceps industry.

negative: Why Challenge Trials of SARS‐CoV‐2 Vaccines Could Be Ethical Despite Risk of Severe Adverse Events Human challenge trials to test the efficacy of vaccine candidates against SARS‐CoV‐2, the novel coronavirus behind Covid‐19, could save considerable time and many lives. But they may initially seem unethical because they expose healthy volunteers to a live virus that is killing many people and for which no cure exists. This article argues that this is not the correct test of their ethics. The correct test is comparative. And in the special circumstances of the Covid‐19 pandemic, human challenge trials meet the correct test better than standard efficacy testing would.

negative: Molecular Diagnosis of Severe Acute Respiratory Syndrome : The State of the Art Severe acute respiratory syndrome (SARS) first appeared in Guangdong Province, China, in November 2002. Although virus isolation and serology were useful early in the SARS outbreak for diagnosing new cases, these tests are not generally useful because virus culture requires a BSL-3 laboratory and seroconversion is often delayed until 2 to 3 weeks after infection. The first qualitative reverse transcriptase-polymerase chain reaction tests for SARS-coronavirus (CoV) were sensitive and capable of detecting 1 to 10 genome equivalents. These assays were quickly supplemented with quantitative real-time assays that helped elucidate the natural history of SARS, particularly the initial presence of low viral loads in the upper respiratory tract and high viral loads in the lower respiratory tract. The unique natural history of SARS-CoV infection dictates the testing of both respiratory and nonrespiratory specimens, the testing of multiple specimens from the same patient, and sending out positives to be confirmed by a reference laboratory. Commercially available reverse transcriptase-polymerase chain reaction tests for SARS have recently appeared; however, meaningful evaluations of these assays have not yet been performed and their true performance has not been determined. These and other issues related to diagnosis of SARS-CoV infection are discussed in this review.

negative: Application of a portable instrument for rapid and reliable detection of SARS-CoV-2 infection in any environment The ongoing outbreak of the novel coronavirus (SARS-CoV-2) infection is creating serious challenges for health laboratories that seek to identify viral infections as early as possible, optimally at the earliest appearance of symptom. Indeed, there is urgent need to develop and deploy robust diagnostic methodologies not only to use in health laboratory environments but also directly in places where humans circulate and spread the virus such as airports, trains, boats, and any public aggregation places. The success of a reliable and sensitive asymptomatic diagnosis relies on the identification and measurement of informative biomarkers from human host and virus in a rapid, sensitive, and inexpensive manner. The objective of this article is to describe an innovative multidisciplinary approach to develop an efficient, inexpensive, and easy-to-use portable instrument (bCUBE® by Hyris Ltd) that can be employed as a surveillance system for the emergency caused by SARS-CoV-2. A solution for Coronavirus testing, compliant with CDC guidelines, is scheduled to be released in the next weeks. In addition, we will describe a workflow and path of an integrated multi-omic approach that will lead to host and pathogen biomarker discovery in order to train the instrument to provide reliable results based on a specific biomarker's fingerprint of SARS-CoV-2 infection.

negative: Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1–31 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4(th) quantile being the highest risk and 1(st) quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4(th) quantile of the risk index, two in the 3(rd) quantile, one in the 2(nd) quantile and none in the 1(st) quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to naïve countries.

negative: How Behaviour and the Environment Influence Transmission in Mobile Groups The movement of individuals living in groups leads to the formation of physical interaction networks over which signals such as information or disease can be transmitted. Direct contacts represent the most obvious opportunities for a signal to be transmitted. However, because signals that persist after being deposited into the environment may later be acquired by other group members, indirect environmentally-mediated transmission is also possible. To date, studies of signal transmission within groups have focused on direct physical interactions and ignored the role of indirect pathways. Here, we use an agent-based model to study how the movement of individuals and characteristics of the signal being transmitted modulate transmission. By analysing the dynamic interaction networks generated from these simulations, we show that the addition of indirect pathways speeds up signal transmission, while the addition of physically-realistic collisions between individuals in densely packed environments hampers it. Furthermore, the inclusion of spatial biases that induce the formation of individual territories, reveals the existence of a trade-off such that optimal signal transmission at the group level is only achieved when territories are of intermediate sizes. Our findings provide insight into the selective pressures guiding the evolution of behavioural traits in natural groups, and offer a means by which multi-agent systems can be engineered to achieve desired transmission capabilities.

negative: Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study BACKGROUND: Since Dec 31, 2019, the Chinese city of Wuhan has reported an outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV). Cases have been exported to other Chinese cities, as well as internationally, threatening to trigger a global outbreak. Here, we provide an estimate of the size of the epidemic in Wuhan on the basis of the number of cases exported from Wuhan to cities outside mainland China and forecast the extent of the domestic and global public health risks of epidemics, accounting for social and non-pharmaceutical prevention interventions. METHODS: We used data from Dec 31, 2019, to Jan 28, 2020, on the number of cases exported from Wuhan internationally (known days of symptom onset from Dec 25, 2019, to Jan 19, 2020) to infer the number of infections in Wuhan from Dec 1, 2019, to Jan 25, 2020. Cases exported domestically were then estimated. We forecasted the national and global spread of 2019-nCoV, accounting for the effect of the metropolitan-wide quarantine of Wuhan and surrounding cities, which began Jan 23–24, 2020. We used data on monthly flight bookings from the Official Aviation Guide and data on human mobility across more than 300 prefecture-level cities in mainland China from the Tencent database. Data on confirmed cases were obtained from the reports published by the Chinese Center for Disease Control and Prevention. Serial interval estimates were based on previous studies of severe acute respiratory syndrome coronavirus (SARS-CoV). A susceptible-exposed-infectious-recovered metapopulation model was used to simulate the epidemics across all major cities in China. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credibile interval (CrI). FINDINGS: In our baseline scenario, we estimated that the basic reproductive number for 2019-nCoV was 2·68 (95% CrI 2·47–2·86) and that 75 815 individuals (95% CrI 37 304–130 330) have been infected in Wuhan as of Jan 25, 2020. The epidemic doubling time was 6·4 days (95% CrI 5·8–7·1). We estimated that in the baseline scenario, Chongqing, Beijing, Shanghai, Guangzhou, and Shenzhen had imported 461 (95% CrI 227–805), 113 (57–193), 98 (49–168), 111 (56–191), and 80 (40–139) infections from Wuhan, respectively. If the transmissibility of 2019-nCoV were similar everywhere domestically and over time, we inferred that epidemics are already growing exponentially in multiple major cities of China with a lag time behind the Wuhan outbreak of about 1–2 weeks. INTERPRETATION: Given that 2019-nCoV is no longer contained within Wuhan, other major Chinese cities are probably sustaining localised outbreaks. Large cities overseas with close transport links to China could also become outbreak epicentres, unless substantial public health interventions at both the population and personal levels are implemented immediately. Independent self-sustaining outbreaks in major cities globally could become inevitable because of substantial exportation of presymptomatic cases and in the absence of large-scale public health interventions. Preparedness plans and mitigation interventions should be readied for quick deployment globally. FUNDING: Health and Medical Research Fund (Hong Kong, China).

negative: Development of an Aerosol Model of Cryptococcus Reveals Humidity as an Important Factor Affecting the Viability of Cryptococcus during Aerosolization Cryptococcus is an emerging global health threat that is annually responsible for over 1,000,000 infections and one third of all AIDS patient deaths. There is an ongoing outbreak of cryptococcosis in the western United States and Canada. Cryptococcosis is a disease resulting from the inhalation of the infectious propagules from the environment. The current and most frequently used animal infection models initiate infection via liquid suspension through intranasal instillation or intravenous injection. These models do not replicate the typically dry nature of aerosol exposure and may hinder our ability to decipher the initial events that lead to clearance or the establishment of infection. We have established a standardized aerosol model of murine infection for the human fungal pathogen Cryptococcus. Aerosolized cells were generated utilizing a Collison nebulizer in a whole-body Madison Chamber at different humidity conditions. The aerosols inside the chamber were sampled using a BioSampler to determine viable aerosol concentration and spray factor (ratio of viable aerosol concentration to total inoculum concentration). We have effectively delivered yeast and yeast-spore mixtures to the lungs of mice and observed the establishment of disease. We observed that growth conditions prior to exposure and humidity within the Madison Chamber during exposure can alter Cryptococcus survival and dose retained in mice.

negative: Middle East Respiratory Syndrome Coronavirus and the One Health concept Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is one of the major threats to the healthcare systems in some countries, especially in the Arabian Peninsula. MERS-CoV is considered an ideal example of the One Health concept. This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. However, there is some debate regarding the origin of MERS-CoV either from bats or other unknown reservoirs. The dromedary camel is the only identified animal reservoir to date. These animals play important roles in sustaining the virus in certain communities and may act as an amplifier of the virus by secreting it in their body fluids, especially in nasal and rectal discharges. MERS-CoV has been detected in the nasal and rectal secretions of infected camels, and MERS-CoV of this origin has full capacity to infect human airway epithelium in both in vitro and in vivo models. Other evidence confirms the direct transmission of MERS-CoV from camels to humans, though the role of camel meat and milk products has yet to be well studied. Human-to-human transmission is well documented through contact with an active infected patient or some silently infected persons. Furthermore, there are some significant risk factors of individuals in close contact with a positive MERS-CoV patient, including sleeping in the same patient room, removing patient waste (urine, stool, and sputum), and touching respiratory secretions from the index case. Outbreaks within family clusters have been reported, whereby some blood relative patients were infected through their wives in the same house were not infected. Some predisposing genetic factors favor MERS-CoV infection in some patients, which is worth investigating in the near future. The presence of other comorbidities may be another factor. Overall, there are many unknown/confirmed aspects of the virus/human/animal network. Here, the most recent advances in this context are discussed, and the possible reasons behind the emergence and sustainability of MERS-CoV in certain regions are presented. Identification of the exact mechanism of transmission of MERS-CoV from camels to humans and searching for new reservoir/s are of high priority. This will reduce the shedding of the virus into the environment, and thus the risk of human infection can be mitigated.

negative: Containing 2019-nCoV (Wuhan) coronavirus The novel coronavirus 2019-nCoV first appeared in December 2019 in Wuhan, China. While most of the initial cases were linked to the Huanan Seafood Wholesale Market, person-to-person transmission has been verified. Given that a vaccine cannot be developed and deployed for at least a year, preventing further transmission relies upon standard principles of containment, two of which are the isolation of known cases and the quarantine of persons believed at high risk of exposure. This note presents probability models for assessing the effectiveness of case isolation and quarantine within a community during the initial phase of an outbreak with illustrations based on early observations from Wuhan.

negative: Improving the collection efficiency of the liquid impinger for ultrafine particles and viral aerosols by applying granular bed filtration Abstract Liquid impingers are utilized to collect bioaerosols for many advantages, such as avoiding dehydration of biological agents. However, many previous studies have reported that the liquid impingers are surprisingly inefficient for the collection of ultrafine bioaerosols, with collection efficiencies <30%. In the present work, we have successfully improved the collection efficiency of the liquid impinger (AGI30) to as high as 99% for particles in the size range of 20–400nm with the aid of packed glass beads. We also systematically investigated the effects of influential factors on the collection efficiency. These factors include the volume of the sampling liquid (0, 20 and 30mL), depth (0, 7 and 10cm) of packed glass beads and sampling flow rate (4, 6 and 8 liter per min, lpm). According to our experimental results, increasing the depth of packed glass beads and the volume of sampling liquid can enhance the collection efficiency. Also, decreasing the sampling flow rate can increase the collection efficiency and reduce the loss of sampling liquid. For the sampling of viable MS2 phages, the collection efficiency of AGI30 sampler with packed glass beads is much higher than that without packed glass beads. Conclusively, this study validates that the granular bed filtration can enhance the collection efficiency of liquid impingers for submicron and ultrafine particles and viral aerosols.

negative: Collection of Viable Aerosolized Influenza Virus and Other Respiratory Viruses in a Student Health Care Center through Water-Based Condensation Growth The dynamics and significance of aerosol transmission of respiratory viruses are still controversial, for the major reasons that virus aerosols are inefficiently collected by commonly used air samplers and that the collected viruses are inactivated by the collection method. Without knowledge of virus viability, infection risk analyses lack accuracy. This pilot study was performed to (i) determine whether infectious (viable) respiratory viruses in aerosols could be collected from air in a real world environment by the viable virus aerosol sampler (VIVAS), (ii) compare and contrast the efficacy of the standard bioaerosol sampler, the BioSampler, with that of the VIVAS for the collection of airborne viruses in a real world environment, and (iii) gain insights for the use of the VIVAS for respiratory virus sampling. The VIVAS operates via a water vapor condensation process to enlarge aerosolized virus particles to facilitate their capture. A variety of viable human respiratory viruses, including influenza A H1N1 and H3N2 viruses and influenza B viruses, were collected by the VIVAS located at least 2 m from seated patients, during a late-onset 2016 influenza virus outbreak. Whereas the BioSampler when operated following our optimized parameters also collected virus aerosols, it was nevertheless overall less successful based on a lower frequency of virus isolation in most cases. This side-by-side comparison highlights some limitations of past studies based on impingement-based sampling, which may have generated false-negative results due to either poor collection efficiency and/or virus inactivation due to the collection process. IMPORTANCE The significance of virus aerosols in the natural transmission of respiratory diseases has been a contentious issue, primarily because it is difficult to collect or sample virus aerosols using currently available air sampling devices. We tested a new air sampler based on water vapor condensation for efficient sampling of viable airborne respiratory viruses in a student health care center as a model of a real world environment. The new sampler outperformed the industry standard device (the SKC BioSampler) in the collection of natural virus aerosols and in maintaining virus viability. These results using the VIVAS indicate that respiratory virus aerosols are more prevalent and potentially pose a greater inhalation biohazard than previously thought. The VIVAS thus appears to be a useful apparatus for microbiology air quality tests related to the detection of viable airborne viruses.

negative: Infrastructure and Contamination of the Physical Environment in Three Bangladeshi Hospitals: Putting Infection Control into Context OBJECTIVE: This paper describes the physical structure and environmental contamination in selected hospital wards in three government hospitals in Bangladesh. METHODS: The qualitative research team conducted 48 hours of observation in six wards from three Bangladeshi tertiary hospitals in 2007. They recorded environmental contamination with body secretions and excretions and medical waste and observed ward occupant handwashing and use of personal protective equipment. They recorded number of persons, number of open doors and windows, and use of fans. They measured the ward area and informally observed waste disposal outside the wards. They conducted nine focus group discussions with doctors, nurses and support staff. RESULTS: A median of 3.7 persons were present per 10 m(2) of floor space in the wards. A median of 4.9 uncovered coughs or sneezes were recorded per 10 m(2) per hour per ward. Floors in the wards were soiled with saliva, spit, mucous, vomitus, feces and blood 125 times in 48 hours. Only two of the 12 patient handwashing stations had running water and none had soap. No disinfection was observed before or after using medical instruments. Used medical supplies were often discarded in open containers under the beds. Handwashing with soap was observed in only 32 of 3,373 handwashing opportunities noted during 48 hours. Mosquitoes and feral cats were commonly observed in the wards. CONCLUSIONS: The physical structure and environment of our study hospitals are conducive to the spread of infection to people in the wards. Low-cost interventions on hand hygiene and cleaning procedures for rooms and medical equipment should be developed and evaluated for their practicality and effectiveness.

negative: Air care: an 'aerography' of breath, buildings and bugs in the cystic fibrosis clinic. With significant relevance to the Covid-19 pandemic, this paper contributes to emerging 'aerographic' research on the socio-materialities of air and breath, based on an in-depth empirical study of three hospital-based lung infection clinics treating people with cystic fibrosis. We begin by outlining the changing place of atmosphere in hospital design from the pre-antibiotic period and into the present. We then turn to the first of three aerographic themes where air becomes a matter of grasping and visualising otherwise invisible airborne infections. This includes imagining patients located within bodily spheres or 'cloud bodies', conceptually anchored in Irigaray's thoughts on the 'forgetting of the air' and Sloterdijk's immunitary 'spherology' of the body. Our second theme explores the material politics of air, air conditioning, window design and the way competing 'air regimes' come into conflict with each other at the interface of buildings, bodies and the biotic. Our final theme attends to the 'cost of air', the aero-economic problem of atmospheric scarcity within modern high-rise, deep-density healthcare architectures.

negative: Mutagenic analysis of the coronavirus intergenic consensus sequence. Previously, a system in which an intergenic region from mouse hepatitis virus (MHV) inserted into an MHV defective interfering (DI) RNA led to transcription of a subgenomic DI RNA in helper virus-infected cells was established. In the present study, a DI cDNA containing one UCUAAAC consensus sequence in the middle of the 0.3-kb-long intergenic region located between genes 6 and 7 was constructed. From this DI cDNA clone, 21 mutant DI RNAs were constructed so that each of the seven consensus sequence nucleotides was changed individually to the three alternative bases. These mutants were used to define how changes in the integrity of MHV transcription consensus sequence UCUAAAC affected mRNA transcription. Except for two mutants with the sequences UGUAAAC and UCGAAAC, all of the mutants supported efficient subgenomic DI RNA transcription. This indicated that MHV transcription regulation was sufficiently flexible to recognize altered consensus sequences. Next, these and other mutants were used to examine the leader-body fusion site on the subgenomic DI RNAs. Sequence analysis demonstrated that all subgenomic DI RNAs analyzed contained two pentanucleotide sequences; the first sequence seemed to be contributed by the leader, and the leader-body fusion most likely took place at either the first or the second nucleotide of the second sequence. This observation was not consistent with the proposed coronavirus transcription model (S. C. Baker and M. M. C. Lai, EMBO J. 9:4173-4179, 1990) which states that nucleotide mismatch can be corrected by RNA polymerase proofreading activity.

negative: Infectivity of human coronavirus in the brain A new strain of human coronaviruses (hCoVs), Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been identified to be responsible for the current outbreak of the coronavirus disease 2019 (COVID-19). Though major symptoms are primarily generated from the respiratory system, neurological symptoms are being reported in some of the confirmed cases, raising concerns of its potential for intracranial invasion and neurological manifestations, both in the acute phase and in the long-term. At present, it remains unclear the extent to which SARS-CoV-2 is present in the brain, and if so, its pathogenic role in the central nervous system (CNS). Evidence for neuroinvasion and neurovirulence of hCoVs has been recognised in animal and human studies. Given that SARS-CoV-2 belongs to the same family and shares characteristics in terms of receptor binding properties, it is worthwhile exploring its potential CNS manifestations. This review summarises previous findings from hCoVs in relation to the CNS, and compares these with the new strain, aiming to provide a better understanding of the effects of SARS-CoV-2 on the CNS.

negative: The One Health Concept: 10 Years Old and a Long Road Ahead Over the past decade, a significant increase in the circulation of infectious agents was observed. With the spread and emergence of epizootics, zoonoses, and epidemics, the risks of pandemics became more and more critical. Human and animal health has also been threatened by antimicrobial resistance, environmental pollution, and the development of multifactorial and chronic diseases. This highlighted the increasing globalization of health risks and the importance of the human–animal–ecosystem interface in the evolution and emergence of pathogens. A better knowledge of causes and consequences of certain human activities, lifestyles, and behaviors in ecosystems is crucial for a rigorous interpretation of disease dynamics and to drive public policies. As a global good, health security must be understood on a global scale and from a global and crosscutting perspective, integrating human health, animal health, plant health, ecosystems health, and biodiversity. In this study, we discuss how crucial it is to consider ecological, evolutionary, and environmental sciences in understanding the emergence and re-emergence of infectious diseases and in facing the challenges of antimicrobial resistance. We also discuss the application of the “One Health” concept to non-communicable chronic diseases linked to exposure to multiple stresses, including toxic stress, and new lifestyles. Finally, we draw up a list of barriers that need removing and the ambitions that we must nurture for the effective application of the “One Health” concept. We conclude that the success of this One Health concept now requires breaking down the interdisciplinary barriers that still separate human and veterinary medicine from ecological, evolutionary, and environmental sciences. The development of integrative approaches should be promoted by linking the study of factors underlying stress responses to their consequences on ecosystem functioning and evolution. This knowledge is required for the development of novel control strategies inspired by environmental mechanisms leading to desired equilibrium and dynamics in healthy ecosystems and must provide in the near future a framework for more integrated operational initiatives.

negative: Novel Coronavirus COVID-19: Current Evidence and Evolving Strategies COVID-19 is a global pandemic that has currently infected >300,000 globally. Fever and cough are the most common symptoms of the disease, and it is important to remember that the virus can even be transmitted by individuals who test positive for the disease but do not have any symptoms. Currently reported mortality rates vary because of the rapid spread of the disease and different approaches to calculating this estimate, but it is clear that the risk of death is associated with age and the presence of underlying conditions. Risk mitigation techniques (i.e., hand washing, social distancing, and self-isolation) have already been emphasized across major news outlets. It is essential that we continue these practices, as the outbreak is currently expected to last for many more months and we must be mindful of the lessons learned from past pandemics to prevent a second wave from occurring.

negative: Standard and AEGIS nicking molecular beacons detect amplicons from the Middle East respiratory syndrome coronavirus Abstract This paper combines two advances to detect MERS-CoV, the causative agent of Middle East Respiratory Syndrome, that have emerged over the past few years from the new field of “synthetic biology”. Both are based on an older concept, where molecular beacons are used as the downstream detection of viral RNA in biological mixtures followed by reverse transcription PCR amplification. The first advance exploits the artificially expanded genetic information systems (AEGIS). AEGIS adds nucleotides to the four found in standard DNA and RNA (xNA); AEGIS nucleotides pair orthogonally to the A:T and G:C pairs. Placing AEGIS components in the stems of molecular beacons is shown to lower noise by preventing unwanted stem invasion by adventitious natural xNA. This should improve the signal-to-noise ratio of molecular beacons operating in complex biological mixtures. The second advance introduces a nicking enzyme that allows a single target molecule to activate more than one beacon, allowing “signal amplification”. Combining these technologies in primers with components of a self-avoiding molecular recognition system (SAMRS), we detect 50 copies of MERS-CoV RNA in a multiplexed respiratory virus panel by generating fluorescence signal visible to human eye and/or camera.

negative: Infectious diseases: a call for manuscripts in an interdisciplinary era

negative: Coronavirus Contact Tracing: Evaluating The Potential Of Using Bluetooth Received Signal Strength For Proximity Detection We report on measurements of Bluetooth Low Energy (LE) received signal strength taken on mobile handsets in a variety of common, real-world settings. We note that a key difficulty is obtaining the ground truth as to when people are in close proximity to one another. Knowledge of this ground truth is important for accurately evaluating the accuracy with which contact events are detected by Bluetooth LE. We approach this by adopting a scenario-based approach. In summary, we find that the Bluetooth LE received signal strength can vary substantially depending on the relative orientation of handsets, on absorption by the human body, reflection/absorption of radio signals in buildings and trains. Indeed we observe that the received signal strength need not decrease with increasing distance. This suggests that the development of accurate methods for proximity detection based on Bluetooth LE received signal strength is likely to be challenging. Our measurements also suggest that combining use of Bluetooth LE contact tracing apps with adoption of new social protocols may yield benefits but this requires further investigation. For example, placing phones on the table during meetings is likely to simplify proximity detection using received signal strength. Similarly, carrying handbags with phones placed close to the outside surface. In locations where the complexity of signal propagation makes proximity detection using received signal strength problematic entry/exit from the location might instead be logged in an app by e.g. scanning a time-varying QR code or the like.

negative: Risk estimation and prediction by modeling the transmission of the novel coronavirus (COVID-19) in mainland China excluding Hubei province Background: In December 2019, an outbreak of coronavirus disease (COVID-19)was identified in Wuhan, China and, later on, detected in other parts of China. Our aim is to evaluate the effectiveness of the evolution of interventions and self-protection measures, estimate the risk of partial lifting control measures and predict the epidemic trend of the virus in mainland China excluding Hubei province based on the published data and a novel mathematical model. Methods: A novel COVID-19 transmission dynamic model incorporating the intervention measures implemented in China is proposed. We parameterize the model by using the Markov Chain Monte Carlo (MCMC) method and estimate the control reproduction number Rc, as well as the effective daily reproduction ratio Re(t), of the disease transmission in mainland China excluding Hubei province. Results: The estimation outcomes indicate that the control reproduction number is 3.36 (95% CI 3.20-3.64) and Re(t) has dropped below 1 since January 31st, 2020, which implies that the containment strategies implemented by the Chinese government in mainland China excluding Hubei province are indeed effective and magnificently suppressed COVID-19 transmission. Moreover, our results show that relieving personal protection too early may lead to the spread of disease for a longer time and more people would be infected, and may even cause epidemic or outbreak again. By calculating the effective reproduction ratio, we proved that the contact rate should be kept at least less than 30% of the normal level by April, 2020. Conclusions: To ensure the epidemic ending rapidly, it is necessary to maintain the current integrated restrict interventions and self-protection measures, including travel restriction, quarantine of entry, contact tracing followed by quarantine and isolation and reduction of contact, like wearing masks, etc. People should be fully aware of the real-time epidemic situation and keep sufficient personal protection until April. If all the above conditions are met, the outbreak is expected to be ended by April in mainland China apart from Hubei province.

negative: Transmission dynamics of 2019 novel coronavirus (2019-nCoV) Background Since December 29, 2019, pneumonia infection with 2019-nCoV has rapidly spread out from Wuhan, Hubei Province, China to most others provinces and other counties. However, the transmission dynamics of 2019-nCoV remain unclear. Methods Data of confirmed 2019-nCoV cases before January 23, 2020 were collected from medical records, epidemiological investigations or official websites. Data of severe acute respiratory syndrome (SARS) cases in Guangdong Province during 2002-2003 were obtained from Guangdong Provincial Center for Disease Control and Prevention (GDCDC). Exponential Growth (EG) and maximum likelihood estimation (ML) were applied to estimate the reproductive number (R) of 2019-nCoV and SARS. Findings As of January 23, 2020, a total of 830 confirmed 2019-nCoV cases were identified across China, and 9 cases were reported overseas. The average incubation duration of 2019-nCoV infection was 4.8days. The average period from onset of symptoms to isolation of 2019-nCoV and SARS cases were 2.9 and 4.2 days, respectively. The R values of 2019-nCoV were 2.90 (95%CI: 2.32-3.63) and 2.92 (95%CI: 2.28-3.67) estimated using EG and ML respectively, while the corresponding R values of SARS-CoV were 1.77 (95%CI: 1.37-2.27) and 1.85 (95%CI: 1.32-2.49). We observe a decreasing trend of the period from onset to isolation and R values of both 2019-nCoV and SARS-CoV. Interpretation The 2019-nCoV may have a higher pandemic risk than SARS broken out in 2003. The implemented public-health efforts have significantly decreased the pandemic risk of 2019-nCoV. However, more rigorous control and prevention strategies and measures to contain its further spread. Funding National Key Research and Development Program of China, Science and Technology Program of Guangdong Province, and Guangzhou Science and technology Plan Project.

negative: Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.

negative: Watch the coronavirus’ rampage through the body Science’s COVID-19 reporting is supported by the Pulitzer Center SARS-CoV-2, the virus that causes COVID-19, can severely damage lungs, but in serious cases it doesn’t stop there—clinicians have observed bodywide damage because of the coronavirus As researchers begin to better understand the pathology of the disease, new treatments can be deployed to help save lives Clinicians see a range of impacts from COVID-19—from pulmonary embolisms to kidney damage

negative: Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0–62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0–11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0–16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0–4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R(2) = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools (t = −2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

negative: Diagnostic Investigation of Emerging Viruses of Companion Animals In this article, the authors are specifically concerned with the timely and accurate detection of emerging diseases of small animals that are viral in origin. Veterinarians are bound to encounter emerging viruses in their practice. The problem is unavoidable, because viruses are highly mutagenic. Even the immune response dictates the nature of virus that evolves in a host. If the clinical signs and diagnostic methods fail to correlate, the veterinarian should work with the diagnostic laboratory to solve the diagnostic puzzle.

negative: Coronavirus disease 2019: achieving good mental health during social isolation The coronavirus disease 2019 pandemic has led to unprecedented disruption to the normal way of life for people around the globe. Social distancing, self-isolation or shielding have been strongly advised or mandated in most countries. We suggest evidence-based ways that people can maintain or even strengthen their mental health during this crisis.

negative: Functional long-range RNA–RNA interactions in positive-strand RNA viruses Positive-strand RNA viruses are important human, animal and plant pathogens that are defined by their single-stranded positive-sense RNA genomes. In recent years, it has become increasingly evident that interactions that occur between distantly positioned RNA sequences within these genomes can mediate important viral activities. These long-range intragenomic RNA–RNA interactions involve direct nucleotide base pairing and can span distances of thousands of nucleotides. In this Review, we discuss recent insights into the structure and function of these intriguing genomic features and highlight their diverse roles in the gene expression and genome replication of positive-strand RNA viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro3288) contains supplementary material, which is available to authorized users.

negative: Platelet-Derived Inhibitors of Platelet Activation Negative regulators of platelet activation are a relatively unexplored aspect of platelet physiology yet have an important role in tempering thrombus development by contributing much needed negative regulation to a process that is amplified by several positive feedback mechanisms. Some negative regulators, such as RASA3 and JAM-A, act as gatekeepers that modulate key mediators of activation and provide barriers that must be deactivated to permit full activation and stable thrombus formation. Other negative regulators, such as PECAM-1 and other proteins that signal through ITIMs, come into play once platelets are activated and provide restraining, negative feedback for activatory pathways. Many platelet-derived inhibitors have been identified but not fully characterised and so questions remain regarding the mechanisms that underlie the effects on platelet activity following their activation, inhibition or genetic disruption. However, dysregulation of inhibitory signals is believed to contribute to enhanced risk of thrombosis in diseases such as diabetes and other pathological conditions. In this chapter we have described platelet-derived inhibitors of platelet function that are secreted by or expressed within platelets themselves to provide inhibition or negative regulation to the processes that underpin activation.

negative: Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26 The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans(1,2), representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV(3). CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV(4). The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus–cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 β-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein–protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among betacoronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature12328) contains supplementary material, which is available to authorized users.

negative: In vivo and in vitro models of demyelinating diseases XV. Differentiation influences the regulation of coronavirus infection in primary explants of mouse CNS Abstract Mouse oligodendrocytes and astrocytes, in primary cerebral explant cultures, were infected with JHMV and MHV3 coronaviruses. Contrary to previous findings with neural cells from the rat (S. Beushausen and S. Dales, 1985, Virology 141, 89–101), these agents show no discrimination in the tropism and have the ability to replicate in either type of murine glial cell. Effects of the differentiation inducer dbcAMP on levels of the myelin-specific enzyme 2′:3′-cyclic nucleotide-3′-phosphohydrolase (CNPase) activity and virus replication were determined. In the mouse system there was a gradual, continuous elevation of CNPase beyond 30 days whereas in comparable rat cell cultures maximum CNPase enhancement is elicited within 21 days (F. A. McMorris,1983, J. Neurochem. 41, 506–515). After dbcAMP treatment replication of both coronaviruses was profoundly suppressed in murine oligodendrocytes, consistent with our findings on JHMV replication in treated rat oligodendrocytes. By contrast the replication of JHMV and MHV3 in dbcAMP-treated murine astrocytes was influenced only marginally. These findings provide further support for the hypothesis that susceptibility of rodents to CNS infection by coronaviruses is determined, in part, by the age-related maturation process of oligodendrocytes.

negative: Estimating human-to-human transmissibility of hepatitis A virus in an outbreak at an elementary school in China, 2011 Hepatitis A is caused by hepatitis A virus and occurs worldwide. Estimating the transmissibility, which is usually characterized by the basic reproductive number R(0), the mean number of secondary infectious cases generated by a single primary infectious case introduced into a totally susceptible population, provides crucial information for the effort required to stop infection spreading. Hepatitis A virus is usually transmitted indirectly through contaminated food and environment. An outbreak from March to June 2011 was reported to have occurred at an elementary school of 698 pupils in China and it was found that the outbreak was due to direct transmission between school children. Based on the symptom onset date and the social contact network of the children, in this study we estimate the serial interval (i.e. the gap in symptom onset between an infectee and its infector) and use different statistical methods to estimate R(0). Combining with the positivity of IgG antibodies tests, we develop a compartmental transmission dynamics model which includes both asymptomatic and symptomatic infections to estimate the overall R(0). Our analysis suggests a serial interval of mean = 23.9 days and standard deviation = 20.9 days. The different statistical methods suggest estimates for R(0) in the outbreak varying from 2.1 to 2.8, and the estimates from the transmission dynamics model are consistent with this range. Our estimates are in agreement with that from one study in England but are higher than that from one study in the United States. Our transmission dynamics model suggests that the proportion of symptomatic infections is about 9%, implying that there were about 344 asymptomatic infections along with the 32 observed symptomatic cases. Furthermore, it is shown that the inclusion of asymptomatic infection in the epidemic process increases the estimate of R(0) but does not do so greatly provided that the proportion of symptomatic infections is constant over the outbreak and there is no difference in transmissibility between symptomatic and asymptomatic infections.

negative: Longitudinal study of age-specific pattern of coronavirus infection in Lyle’s flying fox (Pteropus lylei) in Thailand BACKGROUND: Bats are natural reservoirs for several highly pathogenic and novel viruses including coronaviruses (CoVs) (mainly Alphacoronavirus and Betacoronavirus). Lyle’s flying fox (Pteropus lylei)‘s roosts and foraging sites are usually in the proximity to humans and animals. Knowledge about age-specific pattern of CoV infection in P. lylei, prevalence, and viral shedding at roosts and foraging sites may have an impact on infection-age-structure model to control CoV outbreak. METHODS: P. lylei bats were captured monthly during January–December 2012 for detection of CoV at three areas in Chonburi province; two human dwellings, S1 and S2, where few fruit trees were located with an open pig farm, 0.6 km and 5.5 km away from the bat roost, S3. Nested RT-PCR of RNA-dependent RNA polymerase (RdRp) gene from rectal swabs was used for CoV detection. The strain of CoV was confirmed by sequencing and phylogenetic analysis. RESULTS: CoV infection was found in both juveniles and adult bats between May and October (January, in adults only and April, in juveniles only). Of total rectal swab positives (68/367, 18.5%), ratio was higher in bats captured at S1 (11/44, 25.0%) and S2 (35/99, 35.4%) foraging sites than at roost (S3) (22/224, 9.8%). Juveniles (forearm length ≤ 136 mm) were found with more CoV infection than adults at all three sites; S1 (9/24, 37.5% vs 2/20, 10%), S2 (22/49, 44.9% vs 13/50, 26.0%), and S3 (10/30, 33.3% vs 12/194, 6.2%). The average BCI of CoV infected bats was significantly lower than uninfected bats. No gender difference related to infection was found at the sites. Phylogenetic analysis of conserved RdRp gene revealed that the detected CoVs belonged to group D betacoronavirus (n = 64) and alphacoronavirus (n = 4). CONCLUSIONS: The fact that CoV infection and shedding was found in more juvenile than adult bats may suggest transmission from mother during peripartum period. Whether viral reactivation during parturition period or stress is responsible in maintaining transmission in the bat colony needs to be explored.

negative: Towards a socially just model: balancing hunger and response to the COVID-19 pandemic in Bangladesh

negative: Potential impact of seasonal forcing on a SARS-CoV-2 pandemic A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 80,000 confirmed infections and 2,700 fatalities (as of Feb 27, 2020). Imported cases and transmission clusters of various sizes have been reported globally suggesting a pandemic is likely. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterize our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.

negative: Pathology of infectious diseases: new agents, opportunistic, neglectable, emergent, reemergent diseases and why not super resistant nosocomial bacteria?

negative: Prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019 Abstract Objective To determine the dynamic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory and fecal specimens in children with coronavirus disease 2019 (COVID-19). Methods From January 17, 2020 to February 23, 2020, three paediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data were collected. Patients were followed up to March 10, 2020, and dynamic profiles of nucleic acid testing results in throat swabs and fecal specimens were closely monitored. Results Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained detectable in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days. Conclusions SARS-CoV-2 may exist in children's gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children raises the possibility that the virus might be transmitted through contaminated fomites. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.

negative: Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1 [Image: see text] As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, the careful analysis of its transmission and cellular mechanisms is sorely needed. In this Communication, we first analyzed two recent studies that concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions share a unique similarity to HIV-1. However, the reimplementation of the analyses, built on larger scale data sets using state-of-the-art bioinformatics methods and databases, presents clear evidence that rebuts these conclusions. Next, using metagenomic samples from Manis javanica, we assembled a draft genome of the 2019-nCoV-like coronavirus, which shows 73% coverage and 91% sequence identity to the 2019-nCoV genome. In particular, the alignments of the spike surface glycoprotein receptor binding domain revealed four times more variations in the bat coronavirus RaTG13 than in the Manis coronavirus compared with 2019-nCoV, suggesting the pangolin as a missing link in the transmission of 2019-nCoV from bats to human.

negative: A Tale of Two Communities: Characterizing Reddit Response to COVID-19 through /r/China_Flu and /r/Coronavirus The COVID-19 pandemic has deeply impacted people's lives around the globe. During the extended lockdowns caused by the pandemic, online communities are crucial for people to access information and share experiences. In particular, two"new"communities have emerged on Reddit: /r/China_flu and /r/Coronavirus. By studying activities and users in these two communities, we provide a characterization of people's responses to COVID-19 on Reddit. First, we find that user activity peaks around March 17, when the World Health Organization (WHO) announced COVID-19 as a pandemic. Shortly after that, the activity levels of both communities have been declining week by week. We further illustrate the central role of these two communities in the emergence of COVID-related communities. Second, we study the differences between these two communities. /r/Coronavirus is recommended as the official community for COVID-19 on Reddit, while /r/China_flu adopts a loose moderation practice. As a result, we observe that these two communities are gradually growing apart and more extremism is being found in /r/China_flu. Finally, we examine the spillover effect of the COVID-19 pandemic on user activity across the entire Reddit platform. Our results show significant changes in user activities outside COVID-related communities. In subreddits related to finance, food, and countries/cities, user activity is recovering to the pre-pandemic level in late April and May as countries reopen, but subreddits related to travel and sports remain highly impacted and show lower activity levels than the pre-pandemic period. Our work highlights the strength of Reddit as a source for understanding public reactions to COVID-19 and the importance of content moderation on the Internet during a pandemic.

negative: Qualitative and quantitative analysis of glucosinolates and nucleosides in Radix Isatidis by HPLC and liquid chromatography tandem mass spectrometry Abstract Multi-component fingerprinting and quantitation of the glucosinolates and nucleosides in samples of Radix Isatidis have been carried out using high-performance liquid chromatography with diode-array detection and electrospray ionization tandem mass spectrometry (HPLC–DAD–ESI/MS). Five nucleosides together with one glucosinolate were identified by comparing retention times, ultraviolet spectra, mass spectra and/or empirical molecular formulae of reference compounds. Quantitation of these six compounds was carried out simultaneously by HPLC on a Phenomenex Luna C18 column using gradient elution with methanol and water and detection at 254nm. All calibration curves were linear (r>0.9994) within test ranges. Limits of detection and quantitation were 0.33ng and 2.50ng on column, respectively. Intra- and inter-day precision (as relative standard deviation) for all analytes was <2.19% with recoveries in the range 99.6%–101.8% at three concentration levels. The validated method was successfully applied to fingerprinting and assay of 25 batches of Radix Isatidis sourced from different geographical regions of China. The method is simple and reliable and has potential value in the quality control of Radix Isatidis.

negative: Roles of meteorological conditions in COVID-19 transmission on a worldwide scale The novel coronavirus (SARS-CoV-2/ 2019-nCoV) identified in Wuhan, China, in December 2019 has caused great damage to public health and economy worldwide with over 140,000 infected cases up to date. Previous research has suggested an involvement of meteorological conditions in the spread of droplet-mediated viral diseases, such as influenza. However, as for the recent novel coronavirus, few studies have discussed systematically about the role of daily weather in the epidemic transmission of the virus. Here, we examine the relationships of meteorological variables with the severity of the outbreak on a worldwide scale. The confirmed case counts, which indicates the severity of COVID-19 spread, and four meteorological variables, i.e., air temperature, relative humidity, wind speed, and visibility, were collected daily between January 20 and March 11 (52 days) for 430 cities and districts all over China, 21 cities/ provinces in Italy, 21 cities/ provinces in Japan, and 51 other countries around the world. Four different time delays of weather (on the day, 3 days ago, 7 days ago, and 14 days ago) as to the epidemic situation were taken for modeling and we finally chose the weather two weeks ago to model against the daily epidemic situation as its correlated with the outbreak best. Taken Chinese cities as a discovery dataset, it was suggested that temperature, wind speed, and relative humidity combined together could best predict the epidemic situation. The meteorological model could well predict the outbreak around the world with a high correlation (r2>0.6) with the real data. Using this model, we further predicted the possible epidemic situation in the future 12 days in several high-latitude cities with potential outbreak. This model could provide more information for government's future decisions on COVID-19 outbreak control.

negative: Combination attenuation offers strategy for live-attenuated coronavirus vaccines With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live-attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2’O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the SARS-CoV mouse model, a NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2’O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2’O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live-attenuated coronavirus vaccines. Significance Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations like the aged and immune-compromised. This study illustrates that despite success in young models, the NSP16 mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the NSP16 mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for NSP16 attenuation as a major component of future live-attenuated coronavirus vaccines.

negative: Mouse (Mus musculus) stocks derived from tropical islands: new models for genetic analysis of life‐history traits Founder effects, together with access to unoccupied ecological niches, may allow rodent populations on isolated islands to evolve constellations of life‐history traits that distinguish them from their mainland relatives, for example in body size, litter size, and longevity. In particular, low intrinsic mortality risks on islands with reduced predator numbers and not subject to harsh winter climates may in principle support the development of stocks with extended longevity. Conversely, the conditions under which laboratory rodents are typically bred are thought to select for genotypes that produce large, rapidly maturing races with high early reproductive rates but diminished longevity. To test these ideas, and to generate new mouse stocks suitable for genetic and molecular analysis of the processes that time life‐history events, we have developed specific pathogen‐free stocks from mice trapped from three distinct populations: the U.S. mainland (Idaho) and the tropical Pacific islands Majuro and Pohnpei. Mice from all three locations were found to be shorter and lighter, to have smaller litters, and to have higher faecal corticosterone levels than mice of a genetically heterogeneous stock derived from four common laboratory inbred strains. Among the wild‐derived stocks, mice from Pohnpei and Majuro were significantly lighter and shorter than Idaho‐derived animals, even in populations kept from birth under identical housing conditions. Litter size and reproductive success rates did not differ significantly among the three wild‐derived stocks. Although further work will be needed to see if, as predicted, the wild‐derived stocks differ from one another and from laboratory mice in longevity, these stocks provide useful tools for genetic dissection of factors that regulate body size and reproductive success.

negative: Artificial intelligence finds drugs that could fight the new coronavirus Two independent groups last week reported that they had used artificial intelligence in different ways to find possible treatments for the novel coronavirus, named 2019-nCoV On Feb 4, researchers from the AI drug discovery company BenevolentAI and Imperial College London reported that they had used AI software to find an already-approved drug that might limit the virus’s ability to infect people (Lancet 2020, DOI: 10 1016/S0140-6736(20)30304-4) On Feb 6, Insilico Medicine announced that its AI algorithms had designed new molecules that could stop the virus from replicating in people’s bodies The company says it submitted a paper to the bioRxiv server, but the preprint had not been posted there as of press time BenevolentAI’s algorithms connect molecular structure data to biomedical information about relevant receptors and diseases to find potential drug targets The group adapted its search to newly available information about 2019-nCoV and focused on the enzyme adaptor-associated protein kinase

negative: Perioperative Management of Patients Infected with the Novel Coronavirus: Recommendation from the Joint Task Force of the Chinese Society of Anesthesiology and the Chinese Association of Anesthesiologists The outbreak of the new Coronavirus disease, COVID-19, has been involved in 77,262 cases in China as well as in 27 other countries as of February 24, 2020. Because the virus is novel to human beings, and there is no vaccine yet available, every individual is susceptible and can become infected. Healthcare workers are at high risk, and unfortunately, more than 3,000 healthcare workers in China have been infected. Anesthesiologists are among healthcare workers who are at an even higher risk of becoming infected because of their close contact with infected patients and high potential of exposure to respiratory droplets or aerosol from their patients’ airways. In order to provide healthcare workers with updated recommendations on the management of patients in the perioperative setting as well as for emergency airway management outside of the operating room, the two largest anesthesia societies, the Chinese Society of Anesthesiology (CSA) and the Chinese Association of Anesthesiologists (CAA) have formed a task force to produce the recommendations. The task force hopes to help healthcare workers, particularly anesthesiologists, optimize the care of their patients and protect patients, healthcare workers, and the public from becoming infected. The recommendations were created mainly based on the practice and experience of anesthesiologists who provide care to patients in China. Therefore, adoption of these recommendations outside of China must be done with caution, and the local environment, culture, uniqueness of the healthcare system, and patients’ needs should be considered. The task force will continuously update the recommendations and incorporate new information in future versions.

negative: An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus A new SARS animal model was established by inoculating SARS coronavirus (SARS‐CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5–60 after virus inoculation. All eight animals showed a transient fever 2–3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS‐CoV‐specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS‐CoV RNA could be detected in pharyngeal swab samples using nested RT‐PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS‐CoV‐related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

negative: Analysis of epidemiological characteristics of coronavirus 2019 infection and preventive measures in Shenzhen China: a heavy population city Coronavirus 2019 infection (COVID-19) outbroke in Wuhan, Hubei and spread to all provinces in China and other countries. Shenzhen ranked the top cities outside Wuhan with reported 416 confirmed cases by February 20, 2020. Here, we analyzed the epidemiological characteristics of COVID-19 in Shenzhen and potential link to the preventive strategies for the whole city and inside hospitals. Based on the daily new cases, the epidemic of COVID-19 in Shenzhen can be classified into three phases: the slow increase phase from January 19 to January 28, the rapid increase and plateau phase from January 29 to February 5 and the decline phase since February 6. In the three phases, the number of patients from Hubei decreased, and the number of familial clustering cases increased. The newly diagnosed COVID-19 cases reached its peak around January 31, which was 7 days after the peak date of cases arrival at Shenzhen. A series of early preventive strategies were implemented since January 19, which included detection of body temperature at all entrances of main traffic and buildings, outpatients service specially for patients with fever in all main hospitals in Shenzhen. All the patients with fever were screened with nasal or throat swab PCR detection of coronavirus 2019, Chest CT and blood lymphocyte counting in order to find out early case of COVID-19. Observation wards were established in every main hospital and a designated hospital was responsible for admission and medical care of all confirmed cases. Protection procedure was established for all medical staff involved in the screening and care of suspected and confirmed cases. 14 days isolated observation of all subjects arrived at Shenzhen from Hubei was implemented in February 2. After the implementation of all these strategies and measures, the COVID-19 cases started to decline since February 6. There were almost no community transmission and nosocomial infection occurred in Shenzhen. In conclusion, in situation of major outbreak of respiratory infectious disease, such as COVID-19, in nearby province of Hubei, Shenzhen, a high population density, high proportion of external population and high mobility city, has to face the imported cases and risk of spreading the outbreak into Shenzhen city. The implementation of early preventive strategies and measures in Shenzhen were successful in early identification of COVID-19 cases and prevented major outbreak occurred in Shenzhen. Early identification of imported cases, prevention of family clustering transmission, preventive measures in the public area and very strict infection control procedure in hospital setting are crucial for the successful control of outbreak in Shenzhen.

negative: Ionic liquid-based enzyme-assisted extraction of chlorogenic acid from Flos Lonicera Japonicae BACKGROUND: In recent years, ionic liquids and enzymes have been widely used in the separation and extraction processes of natural products. Chlorogenic acid (CGA) has important biological and pharmacological activities. It is significant to develop a green and efficient method to extract GCA from Flos Lonicera japonica (FLJ) by integrating the advantages of the ionic liquids and enzymes. RESULTS: The optimal type of enzyme and ionic liquid was screened. Pectinase in [C6mim] Br aqueous phase was demonstrated to be an ideal combination. The parameters including extraction time, extraction temperature, pH, enzyme amount, and IL concentration were optimized systematically. Scanning electronic microscopy of FLJ samples demonstrated that pectinase and ionic liquid disposal both obviously facilitated the extraction process by destroying the structure of cell wall. Circular dichroism spectroscopy showed that ionic liquid enhanced the activity of the pectinase by altering its secondary structure. CONCLUSIONS: Compared with previous reported methods, ionic liquid-based enzyme-assisted extraction of GCA from FLJ was proved to be efficient and practical, offering a higher yield in a shorter time. A novel process was proposed for the extraction of active component from natural resources. [Image: see text]

negative: Curation of viral genomes: challenges, applications and the way forward BACKGROUND: Whole genome sequence data is a step towards generating the 'parts list' of life to understand the underlying principles of Biocomplexity. Genome sequencing initiatives of human and model organisms are targeted efforts towards understanding principles of evolution with an application envisaged to improve human health. These efforts culminated in the development of dedicated resources. Whereas a large number of viral genomes have been sequenced by groups or individuals with an interest to study antigenic variation amongst strains and species. These independent efforts enabled viruses to attain the status of 'best-represented taxa' with the highest number of genomes. However, due to lack of concerted efforts, viral genomic sequences merely remained as entries in the public repositories until recently. RESULTS: VirGen is a curated resource of viral genomes and their analyses. Since its first release, it has grown both in terms of coverage of viral families and development of new modules for annotation and analysis. The current release (2.0) includes data for twenty-five families with broad host range as against eight in the first release. The taxonomic description of viruses in VirGen is in accordance with the ICTV nomenclature. A well-characterised strain is identified as a 'representative entry' for every viral species. This non-redundant dataset is used for subsequent annotation and analyses using sequenced-based Bioinformatics approaches. VirGen archives precomputed data on genome and proteome comparisons. A new data module that provides structures of viral proteins available in PDB has been incorporated recently. One of the unique features of VirGen is predicted conformational and sequential epitopes of known antigenic proteins using in-house developed algorithms, a step towards reverse vaccinology. CONCLUSION: Structured organization of genomic data facilitates use of data mining tools, which provides opportunities for knowledge discovery. One of the approaches to achieve this goal is to carry out functional annotations using comparative genomics. VirGen, a comprehensive viral genome resource that serves as an annotation and analysis pipeline has been developed for the curation of public domain viral genome data . Various steps in the curation and annotation of the genomic data and applications of the value-added derived data are substantiated with case studies.

negative: A comprehensive Chinese experience against SARS-CoV-2 in ophthalmology The 2019 novel coronavirus disease (COVID-19) has now swept through the continents and poses a global threat to public health. Several investigations have been conducted to identify whether COVID-19 can be transmitted through the ocular route, and the conclusion is that it is a potential route but remains uncertain. Due to the face-to-face communication with patients, frequent exposure to tears and ocular discharge, and the unavoidable use of equipment which requires close proximity, ophthalmologists carry a high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on 33 articles published by Chinese scholars, guidelines and clinical practice experience in domestic hospitals, we have summarized the Chinese experience through the lens of ophthalmology, hoping to make a contribution to protecting ophthalmologists and patients around the world.

negative: A previously undescribed coronavirus associated with respiratory disease in humans. The etiology of acute respiratory tract illnesses is sometimes unclear due to limitations of diagnostic tests or the existence of as-yet-unidentified pathogens. Here we describe the identification and characterization of a not previously recognized coronavirus obtained from an 8-mo-old boy suffering from pneumonia. This coronavirus replicated efficiently in tertiary monkey kidney cells and Vero cells, in contrast to human coronaviruses (HCoV) 229E and OC43. The entire cDNA genome sequence of the previously undescribed coronavirus was determined, revealing that it is most closely related to porcine epidemic diarrhea virus and HCoV 229E. The maximum amino acid sequence identity between ORFs of the newly discovered coronavirus and related group 1 coronaviruses ranged from 43% to 67%. Real-time RT-PCR assays were designed to test for the prevalence of the previously undescribed coronavirus in humans. Using these tests, the virus was detected in four of 139 individuals (3%) who were suffering from respiratory illness with unknown etiology. All four patients suffered from fever, runny nose, and dry cough, and all four had underlying or additional morbidity. Our data will enable the development of diagnostic tests to study the prevalence and clinical impact of this virus in humans in more detail. Moreover, it will be important to discriminate this previously undescribed coronavirus from HCoV 229E and OC43 and the severe acute respiratory syndrome coronavirus.

negative: Chapter 15 Viral Diseases of Common Marmosets Abstract Common marmosets are highly susceptible to several viral pathogens that exist as latent or subclinical infections in their natural reservoir hosts but cause severe disease or death when interspecies transmission occurs. Examples of such viruses in marmosets are herpes simplex virus infections, parainfluenza virus 1 infections, and measles acquired from humans, Saimiriine herpesvirus 1 infection after transmission from squirrel monkeys, and infections with lymphocytic choriomeningitis virus originating from mice. Other relevant viral infections causing spontaneous disease in common marmoset colonies include cowpox virus infections and paramyxovirus saguinus infections. Callitrichine herpesvirus 3 is a newly recognized lymphocryptovirus that is associated with the development of intestinal lymphoproliferative disease in common marmosets. Most viral pathogens causing disease in common marmosets are potential zoonotic agents, and protective measures should be implemented when handling these small New World monkeys.

negative: The current understanding and potential therapeutic options to combat COVID-19 Abstract The ongoing wreaking global outbreak of the novel human beta coronavirus (CoV) pathogen was presumed to be from a seafood wholesale market in Wuhan, China, belongs to the Coronaviridae family in the Nidovirales order. The virus is highly contagious with potential human-human transmission which was named as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread across six continents and emerged as a global pandemic in short span with alarming levels of spread and severity. This virus associated symptoms and infectious respiratory illness is designated as coronavirus disease 19 (COVID-19). The SARS-CoV-2 possesses enveloped club-like spike protein projections with positive-sense large RNA genome and has a unique replication strategy. This virus was believed to have zoonotic origin with genetical identity to bat and pangolin CoV. In the current review, we introduce a general overview about the human CoVs and the associated diseases, the origin, structure, replication and key clinical events that occur in the COVID-19 pathogenicity. Furthermore, we focused on possible therapeutic options such as repurposing drugs including antimalarials, antivirals, antiparasitic drugs, and anti-HIV drugs, as well as monoclonal antibodies, vaccines as potential treatment options. Also we have summarized the latest research progress on the usage of stem cell therapy, human convalescent serum, interferon's, in the treatment of COVID-19.

negative: Recombinant live attenuated avian coronavirus vaccines with deletions in the accessory genes 3ab and/or 5ab protect against infectious bronchitis in chickens Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens, causing severe economic losses in poultry industry worldwide. Live attenuated viruses are widely used in both the broiler and layer industry because of their efficacy and ability to be mass applied. Recently, we established a novel reverse genetics system based on targeted RNA recombination to manipulate the genome of IBV strain H52. Here we explore the possibilities to attenuate IBV in a rational way in order to generate safe and effective vaccines against virulent IBV (van Beurden et al., 2017). To this end, we deleted the nonessential group-specific accessory genes 3 and/or 5 in the IBV genome by targeted RNA recombination and selected the recombinant viruses in embryonated eggs. The resulting recombinant (r) rIBV-Δ3ab, rIBV-Δ5ab, and rIBV-Δ3ab5ab could be rescued and grew to the same virus titer as recombinant and wild type IBV strain H52. Thus, genes 3ab and 5ab are not essential for replication in ovo. When administered to one-day-old chickens, rIBV-Δ3ab, rIBV-Δ5ab, and rIBV-Δ3ab5ab showed reduced ciliostasis as compared to rIBV H52 and wild type H52, indicating that the accessory genes contribute to the pathogenicity of IBV. After homologous challenge with the virulent IBV strain M41, all vaccinated chickens were protected against disease based on reduced loss of ciliary movement in the trachea compared to the non-vaccinated but challenged controls. Taken together, deletion of accessory genes 3ab and/or 5ab in IBV resulted in mutant viruses with an attenuated phenotype and the ability to induce protection in chickens. Hence, targeted RNA recombination based on virulent IBV provides opportunities for the development of a next generation of rationally designed live attenuated IBV vaccines.

negative: Risk assessment and prediction of severe or critical illness of COVID-19 in the elderly Background: This study aims to investigate the clinical characteristics and risk prediction of severe or critical events of COVID-19 in the elderly patients in China. Methods: The clinical data of COVID-19 in the elderly patients admitted to the Shanghai Public Health Clinical Center during the period of January 20, 2020 to March 16, 2020 were collected. A retrospective cohort study design was conducted to screen out independent factors through Cox univariable regression analysis and multivariable regression analysis, and the efficacy of risk prediction of severe or critical illness was examined through the receiver operating characteristic (ROC) curve. Results: A total of 110 elderly patients with COVID-19 were enrolled. 52 (47.3%) were males and 21 (19.1%) had severe or critical illness. Multivariable regression analysis showed that CD4 cells and D-dimer were independent risk factors. D-dimer, CD4 cells, and D-dimer/CD cells ratios with cut off values of 0.65 (mg/L), 268 (cell/ul) and 431 were in the prediction of severe or critical illness of the elderly COVID-19. The AUC value of D-dimer, CD4 cells, CD4 cells/D-dimer ratio, the tandem group and the parallel group were 0.703, 0.804, 0.794, 0.812 and 0.694, respectively. Conclusions: D-dimer, CD4 cells and their combination have risk assessment value in predicting severe or critical illness of COVID-19 in the elderly.

negative: Understanding novel COVID-19: its impact on organ failure and risk assessment for diabetic and cancer patients Abstract The current pandemic outbreak of COVID-19 originated from Wuhan, China. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant mortality and morbidity rate. The severe risk factors are commonly detected in patients of older age and with medical comorbidities like cancer and diabetes. Scientists and doctors have scrambled to gain knowledge about the novel virus and its pathophysiology in order to discover possible therapeutic regimens and vaccines for COVID-19. The therapeutic strategies like targeting the viral genome emphasize the promising approach to target COVID-19. Additionally, blocking the receptor, ACE2 via the neutralizing antibodies for viral escape that prevents it from entering into the cells provides another therapeutic regimen. In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. Based on the data available from the scientific literature and ongoing clinical trials, we have focused on therapeutic strategies. We hope that we would fill the gaps that puzzled the researchers and clinicians with the best of our knowledge collected for the betterment of the patients for the coming future.

negative: Coronavirus, as a source of pandemic pathogens The coronavirus and the influenza virus have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence Summary The genome data of coronavirus were compared to influenza virus, to investigate its spreading mechanism and future status. Coronavirus would repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics.

negative: Emergence of deadly severe acute respiratory syndrome coronavirus-2 during 2019–2020 Wuhan, the city in Hubei province in China is in the focus of global community due to the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), formerly known as 2019-nCoV. The virus emerged in humans from Wuhan seafood market probably via zoonotic transmission. Within a few days the virus spread its tentacles rapidly to neighboring cities in China and to different geographical regions through travelers and to some extent by human to human transmission leading to significant disease burden globally. More than 2,00,000 people (including more than 8000 deaths) have been infected with this respiratory illness across 167 countries and territories worldwide leading to a pandemic. The present review provides an outline about emergence and spread of SARS-CoV-2 from Wuhan, China in 2019–2020. We have also provided information about the classification, genome, proteins, clinical presentation of COVID-19, type of clinical specimens to be collected and diagnostic methods adopted to identify the respiratory illness. In addition we have also provided information about transmission dynamics, prevention measures and treatment options that are available at the present. Subsequently, we have given a comprehensive overview of the spread of this infection from China to the other parts of the globe. Management of the ongoing outbreak of SARS-CoV-2 encompassing surveillance, clinical, immunological, genetic and evolutionary investigations are likely to provide the desired results. Joint efforts of global scientific community are needed at this hour in terms of enhancement of research on development of accurate diagnostics, antiviral therapeutics and finally into formation of an effective vaccine against the emerging novel coronavirus.

negative: Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis, and viral infection The DEAD-box RNA helicase DDX3 is a multifunctional protein involved in all aspects of RNA metabolism, including transcription, splicing, mRNA nuclear export, translation, RNA decay and ribosome biogenesis. In addition, DDX3 is also implicated in cell cycle regulation, apoptosis, Wnt-β-catenin signaling, tumorigenesis, and viral infection. Notably, recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. Indeed, DDX3 contributes to enhance the induction of anti-viral mediators, interferon (IFN) regulatory factor 3 and type I IFN. However, DDX3 seems to be an important target for several viruses, such as human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV), and poxvirus. DDX3 interacts with HIV-1 Rev or HCV Core protein and modulates its function. At least, DDX3 is required for both HIV-1 and HCV replication. Therefore, DDX3 could be a novel therapeutic target for the development of drug against HIV-1 and HCV.

negative: Recommendations for anesthesia in patients suspected of COVID-19 Coronavirus infection

negative: Infectome: A platform to trace infectious triggers of autoimmunity Abstract The “exposome” is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases. Environmental triggers are largely subdivided into infectious and non-infectious agents. In this review, we introduce the concept of the “infectome”, which is the part of the exposome referring to the collection of an individual's exposures to infectious agents. The infectome directly relates to geoepidemiological, serological and molecular evidence of the co-occurrence of several infectious agents associated with autoimmune diseases that may provide hints for the triggering factors responsible for the pathogenesis of autoimmunity. We discuss the implications that the investigation of the infectome may have for the understanding of microbial/host interactions in autoimmune diseases with long, pre-clinical phases. It may also contribute to the concept of the human body as a superorganism where the microbiome is part of the whole organism, as can be seen with mitochondria which existed as microbes prior to becoming organelles in eukaryotic cells of multicellular organisms over time. A similar argument can now be made in regard to normal intestinal flora, living in symbiosis within the host. We also provide practical examples as to how we can characterise and measure the totality of a disease-specific infectome, based on the experimental approaches employed from the “immunome” and “microbiome” projects.

negative: Protecting Health Care Workers: Use of a Body Covering Transparent Sheet During and After Intubation of Patients With COVID-19

negative: Changes of CT findings in a 2019 novel coronavirus (2019-nCoV) pneumonia patient

negative: Evolutionary insights into host–pathogen interactions from mammalian sequence data Infections are one of the major selective pressures acting on humans, and host-pathogen interactions contribute to shaping the genetic diversity of both organisms. Evolutionary genomic studies take advantage of experiments that natural selection has been performing over millennia. In particular, inter-species comparative genomic analyses can highlight the genetic determinants of infection susceptibility or severity. Recent examples show how evolution-guided approaches can provide new insights into host–pathogen interactions, ultimately clarifying the basis of host range and explaining the emergence of different diseases. We describe the latest developments in comparative immunology and evolutionary genetics, showing their relevance for understanding the molecular determinants of infection susceptibility in mammals. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrg3905) contains supplementary material, which is available to authorized users.

negative: COVID-19: is there a role for immunonutrition, particularly in the over 65s? In late December 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, Hubei, China, resulting in the potentially fatal COVID-19. It went on to be officially recognised as a pandemic by the World Health Organisation on 11 March 2020. While many public health strategies have evolved, there has been little mention of the immune system and how this could be strengthened to help protect against viral infections such as SARS-CoV-2. The present paper evaluates the current evidence base relating to immunonutrition, with a particular focus on respiratory viruses. Within the nutrition sector a promising body of evidence studying inter-relationships between certain nutrients and immune competence already exists. This could potentially be an important player in helping the body to deal with the coronavirus, especially among elders. Evidence for vitamins C, D and zinc and their roles in preventing pneumonia and respiratory infections (vitamins C and D) and reinforcing immunity (zinc) appears to look particularly promising. Ongoing research within this important field is urgently needed.

negative: A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features We first described the 2019 novel coronavirus infection in 10 children occurring in areas other than Wuhan. The coronavirus diseases in children are usually mild and epidemiological exposure is a key clue to recognize pediatric case. Prolonged virus shedding is observed in respiratory tract and feces at the convalescent stage.

negative: HOW LONG WILL MY MOUSE LIVE? MACHINE LEARNING APPROACHES FOR PREDICTION OF MOUSE LIFESPAN Prediction of individual lifespan based upon characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict lifespan in a stock of genetically heterogeneous mice. Lifespan-prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before two years of age, we show that the lifespan quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (± 0.10%). This result provides a new benchmark for the development of lifespan-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity.

negative: Bioaerosols Over the Indo-Gangetic Plain: Influence of Biomass Burning Emission and Ambient Meteorology Bioaerosols (particles of biological origin) can be produced from living or dead plants and animals. They can potentially serve as the cloud condensation and ice nuclei (CCN and IN). Their role in global carbon cycle further highlights importance of studying their variability to link up with climate relevance parameters. Focusing on tropical region reveals that it holds wealthy number of human population and has massive vegetation cover-area. From Indian region, production estimates of bioaerosols from human population (current: ~1.25 billion; of which over 45% resides in Indo-Gangetic Plain: IGP) and Wildlife Sanctuaries and National Parks (100 in numbers, situated from north to south and east to west) is not known. Most of the forest fires in India occur during March–June (hot and drier season). The detailed information on chemical composition, fingerprinting and radiative forcing from regional forest fires is also lacking. Unlike natural sources (forest cover and fires), the seasonal variability of pollutants emission characteristic and chemical, optical and radiative forcing are relatively well studied from anthropogenic biomass (post-harvest paddy- and wheat-residue and biofuels) burning emission in India. However, the abundance of bioaerosols and their variability over a large stretch of IGP (north-west to north-east) was not well documented. Towards this, we have undertaken a year-long campaign to study and document (first-attempt) bioaerosols variability over a complete annual cycle from central IGP. We observed a parallel enhancement in concentrations of fine-particulate matter (PM(2.5) in October–November: 158 ± 89 µg m(−3) as compared to June–September months: 40 ± 18 µg m(−3); two-tailed t = 8.2, p < 0.05) and bioaerosols (particularly Gram-negative bacteria: GNB, a source of endotoxin in ambient air; 186 ± 87 CFU/m(3) during October-November as compared to 114 ± 58 CFU/m(3); t = 4.0, p < 0.05) with the biomass burning emissions intensification period. The abundance of bioaerosols exhibits influence of ambient meteorology, for example GNB exhibited negative correlations with T, wind speed and heavy (>4 mm daily) precipitation, whereas it showed positive correlations with RH and low precipitation amount (<4 mm). Studying bioaerosols and establishing its linkage to health and climate appear to be of utmost importance.

negative: A focus on CORONA VIRUS (COVID-19) The coronavirus episode is a worldwide concern. As time passes, the circumstance appears to change for the most noticeably terrible. An ever-increasing number of individuals are affirmed as contaminated, the death rate goes up somewhat with each deadly case and the infection is advancing outside the Chinese outskirts. The news outlets are everywhere throughout the point, giving day by day or even hourly updates to the inexorably critical circumstance. Be that as it may, most articles and reports appear to concentrate more on instigating alarm and making disarray as opposed to giving an account of log-ical realities or advancing avoidance measures Along these lines, for this arti-cle, how about we leave the frenzy aside and see where that brings us. The Wuhan infection is the main significant wellbeing danger of 2020, yet it’s a long way from being the first or the most noticeably awful wellbeing emergency that humankind confronted. Before we had the Ebola infection, Avian flu and SARS, with the keep goisecng on this rundown, really being a kind of coro-navirus. All were profoundly infectious and possibly savage, yet none caused such an instinctive response from the populace. Regardless of whether we dis-miss those, we have the basic influenza infection that causes a large number of passing right off the bat, and we don’t hear much about that in the news, isn’t that right?.

negative: Reflecting upon vulnerable and dependent bodies during the COVID‐19 crisis This paper is a short narrative on how feminism helped me find a balance in my life and how this balance has been disrupted with the Covid‐19 crisis. I reflect on how this crisis is showing our vulnerabilities as human beings. This crisis reflects how our bodies depend on each other, moving away from the dominant patriarchal ontology that perceives bodies as being independent (Butler, 2016). I reflect on how this crisis is letting the most vulnerable in situations of survival because the infrastructures (Butler, 2016) that support our bodies are not functioning. At the same time, this crisis is providing visibility to certain occupations that are dominated by issues of race, class and gender. These occupations are being at least temporarily rehabilitated to their central position in society. We are living a time where we could show, through our teaching, possible resistance to the neoliberal ontology that captured humanity.

negative: Assessing the welfare of kennelled dogs—A review of animal-based measures Abstract Hundreds of thousands of dogs are housed in kennels worldwide, yet there are no standard protocols for assessing the welfare of dogs in these environments. Animal science is focusing increasingly on the importance of animal-based measures for determining welfare states, and those measures that have been used with kennelled dogs are reviewed in this paper with particular focus on their validity and practicality. From a physiological standpoint, studies using cortisol, heart rate and heart rate variability, temperature changes, and immune function are discussed. Behavioural measures are also of great relevance when addressing canine welfare, thus studies on fear and anxiety behaviours, abnormal behaviours like stereotypies, as well as responses to strangers and novel objects are reviewed. Finally, a limited number of studies attempting to use cognitive bias and learning ability are also mentioned as cognitive measures. The literature to date provides a strong background for which measures may be useful in determining the welfare of kennelled canines, however more research is needed to further assess the value of using these methods, particularly in regard to the large degree of individual differences that exist between dogs.

negative: Expert consensus on protocol of rehabilitation for COVID‐19 patients using framework and approaches of WHO International Family Classifications Coronavirus disease 2019 (COVID‐19) has widely spread all over the world and the numbers of patients and deaths are increasing. According to the epidemiology, virology, and clinical practice, there are varying degrees of changes in patients, involving the human body structure and function and the activity and participation. Based on the World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) and its biopsychosocial model of functioning, we use the WHO Family of International Classifications (WHO‐FICs) framework to form an expert consensus on the COVID‐19 rehabilitation program, focusing on the diagnosis and evaluation of disease and functioning, and service delivery of rehabilitation, and to establish a standard rehabilitation framework, terminology system, and evaluation and intervention systems based the WHO‐FICs.

negative: Indomethacin has a potent antiviral activity against SARS coronavirus. UNLABELLED Severe acute respiratory syndrome (SARS) is a newly emerging, highly transmissible and fatal disease caused by a previously unknown coronavirus (SARS-CoV). Existing in non-identified animal reservoirs, SARS-CoV continues to represent a threat to humans because there is no effective specific antiviral therapy for coronavirus infections. OBJECTIVES Starting from the observation that cyclopentenone cyclooxygenase (COX) metabolites are active against several RNA viruses, we investigated the effect of the COX inhibitor indomethacin on coronavirus replication. METHODS Work involving infectious SARS-CoV was performed in biosafety level 3 facilities. SARS-CoV was grown in monkey VERO cells and human lung epithelial A549 cells, while canine coronavirus (CCoV) was grown in A72 canine cells. Antiviral activity was analysed by determining infective virus titres by TCID50, viral RNA synthesis by Northern blot analysis and real-time RT-PCR, and viral protein synthesis by SDS-PAGE analysis after 35S-methionine-labelling. Antiviral efficacy in vivo was determined by evaluating virus titres in CCoV-infected dogs treated orally with 1 mg/kg body weight indomethacin (INDO). RESULTS Unexpectedly, we found that INDO has a potent direct antiviral activity against the coronaviruses SARS-CoV and CCoV. INDO does not affect coronavirus binding or entry into host cells, but acts by blocking viral RNA synthesis at cytoprotective doses. This effect is independent of cyclooxygenase inhibition. INDO's potent antiviral activity (>1,000-fold reduction in virus yield) was confirmed in vivo in CCoV-infected dogs. CONCLUSIONS The results identify INDO as a potent inhibitor of coronavirus replication and suggest that, having both anti-inflammatory and antiviral activity, INDO could be beneficial in SARS therapy.

negative: COVID-19 Outbreak in Italy: Protecting Worker Health and the Response of the Italian Industrial Hygienists Association The number of people infected with severe acute respiratory syndrome—coronavirus 2 (SARS-CoV-2), i.e. the virus causing coronavirus disease (COVID-19), is dramatically increasing worldwide to the size of a pandemic. At the time of writing Italy is ranking first among countries both in terms of number of COVID-19 confirmed cases and in terms of number of deaths. Such a wide spread of COVID-19 has led to concern among workers who are facing the risk of becoming infected during the execution of their duties. We believe it is useful to remark on the need for professional expertise in the field of Occupational Hygiene in this emergency context, in which the indications provided by national and international bodies, the available scientific literature and the legal provisions are constantly and rapidly evolving. It is of fundamental importance that there is an effective analysis of expert inputs, to provide essential guidance to Health, Safety and Environmental managers and other prevention managers in workplaces. In this regard, not only a constant update of the regulatory framework is needed, but also a development and circulation of operational guidance to all the stakeholders to translate general indications into clear operating procedures and implementation tools to be adopted in the workplaces. We believe that the scientific associations in the field of Occupational Hygiene play a crucial role in guiding and assisting prevention professionals. There is considerable expertise in the occupational hygiene and exposure science communities that can help employers and workers to contain and delay the spread of COVID-19. For this reason, the Italian Association of Industrial Hygienists (AIDII—Associazione Italiana degli Igienisti Industriali) published documents containing operational guidelines to provide correct and constantly updated information for: (i) workers employed in essential activities (with low and medium risk of contagion), (ii) health workers and other workers at high or very high risk of contagion, and (iii) for the correct use and handling of personal protective equipment for workers and for the population in general. It is worth pointing out that the documents produced are not intended to replace those produced by authoritative bodies, but to comply with and complete them by reporting an effective summary and further indications about the measures that should be taken in practice under the light of the Italian legislation. At present, the challenge is to produce scientifically sound knowledge, appropriate tools, and effective methodologies, by coordinating the initiatives of different scientific associations, with the final aim to effectively transfer them to employers and workers.

negative: Two False Negative Test Results in a Symptomatic Patient with a Confirmed Case of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Suspected Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) The recent outbreak of COVID-19 has put significant strain on the current health system and has exposed dangers previously overlooked. The pathogen known as severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), is notable for attacking the pulmonary system causing acute respiratory distress, but it can also severely affect other systems in at-risk individuals including cardiovascular compromise, gastrointestinal distress, acute kidney injury, coagulopathies, cutaneous manifestations, and ultimately death from multi-organ failure. Unfortunately, the reliability of negative test results is questionable and the high infectious burden of the virus calls for extended safety precautions, especially in symptomatic patients. We present a confirmed COVID-19 case that was transferred to our burn center for concern of Steven Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) overlap syndrome after having two negative confirmatory COVID-19 tests at an outside hospital. A 58-year-old female with a history of morbid obesity, HTN, gout, CML managed with imatinib, and chronic kidney disease presented as a transfer from a community hospital to our burn center. The patient was admitted to her community hospital with febrile, acute respiratory distress. Imaging and clinical presentation was consistent with COVID-19 and lab tests for the pathogen were ordered. During observation, while waiting for results, she was placed under patient under investigation (PUI) protocol. Once negative results were obtained, the PUI protocol was abandoned despite ongoing symptoms. Subsequently, dermatological symptoms developed and transfer to our burn center was initiated. After a second negative test result, the symptomatic patient was transferred to our burn center for expert wound management. Given the lack of resolve of respiratory symptoms and concern for the burn patient population, the patient was placed in PUI protocol and an internal COVID-19 was ordered. The patient’s initial exam under standard COVID-19 airborne precautions revealed 5% total body surface area of loss of epidermis affecting bilateral thighs, bilateral arms, and face. A dermatopathological biopsy suggested a bullous drug reaction with an erythema multiform-like reaction pattern versus SJS/TEN. Moreover, the internal COVID-19 test returned positive. The delayed positive test results and complicated hospital course with our patient required us to scale back and notify every patient and staff member whom they came in contact with, across multiple institutions. We suggest that whenever a suspected COVID-19 patient is transferred to a specialized center, they should be isolated and re-checked before joining the new patient population for treatment of the unique condition.

negative: Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response. This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity, allergenicity and physiochemical parameters. To enhance the stability of vaccine protein, disulfide engineering was performed in a region of high mobility. Codon adaptation and in silico cloning was also performed to ensure the higher expression of designed subunit vaccine in E. coli K12 expression system. Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability. Moreover, the designed subunit vaccine was found to induce anti-salivary immunity which may have the ability to prevent the entry of Plasmodium sporozoites into the human host.

negative: Outbreak of Marburg Hemorrhagic Fever in Angola: A Review of the History of the Disease and its Biological Aspects Transmission of a dangerous infectious disease threatens not merely a local population but the world at large as the result of immigration and increased and faster travel. Any outbreak elicits considerable concern and demands that various precautionary methods be instituted and that the disease be contained as quickly as possible. Recently, an old disease, one that may have been present for centuries and was identified decades ago, reared its ugly head, killing more than 200 people before it was contained. Fortunately, the disease, Marburg hemorrhagic fever, was limited to a small geographic area, but the devastation of lives was much greater than that of many epidemics and was a warning of the numerous factors, including fear, lack of understanding, and deception, that can exacerbate the spread of disease and hinder implementation of restraints. This article reviews the history of the disease caused by Marburg virus and its biological components.

negative: Modulation of angiotensin II signaling in the prevention of fibrosis Over the last decade, it has become clear that the role of angiotensin II extends far beyond recognized renal and cardiovascular effects. The presence of an autologous renin-angiotensin system has been demonstrated in almost all tissues of the body. It is now known that angiotensin II acts both independently and in synergy with TGF-beta to induce fibrosis via the angiotensin type 1 receptor (AT(1)) in a multitude of tissues outside of the cardiovascular and renal systems, including pulmonary fibrosis, intra-abdominal fibrosis, and systemic sclerosis. Interestingly, recent studies have described a paradoxically regenerative effect of the angiotensin system via stimulation of the angiotensin type 2 receptor (AT(2)). Activation of AT(2) has been shown to ameliorate fibrosis in animal models of skeletal muscle, gastrointestinal, and neurologic diseases. Clinical reports suggest a beneficial role for modulation of angiotensin II signaling in cutaneous scarring. This article reviews current knowledge on the role that angiotensin II plays in tissue fibrosis, as well as current and potential therapies targeting this system.

negative: Sudden Death from Pulmonary Causes This chapter seeks to survey many of the common pathological entities identified in the lungs at autopsy and the potential role of pulmonary disease in formulating an opinion regarding the cause of death. Appreciation of pulmonary pathology in the medicolegal context is important as it frequently contributes to the immediate or underlying mechanisms of death. The primacy of the lungs in breathing and their coordinated function with the cardiovascular system means that pulmonary failure can rapidly compromise tissue oxygenation and body chemistry, leading to an alteration in blood pH, hypoxic damage to downstream tissues and ultimately multiorgan failure and death. Moreover, given that the lungs have direct contact with the environment through inhalation and receive approximately 50% of the cardiac output with each beat of the heart, they may be adversely affected by hazardous agents from the outside world or other pathologic processes not primarily located in the lungs. The range of topics discussed herein is limited by design to deaths due to disease and largely foregoes discussion of more forensically relevant issues relating to toxicology or trauma. Furthermore, the content and format of this chapter is not intended to be encyclopedic, but rather attempts to highlight selected issues regarding pulmonary disease of potential relevance to surgical or forensic pathologists who perform medicolegal postmortem examinations.

negative: Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.

negative: Do we know when to end isolation of persons affected with COVID-19?

negative: Preparedness and vulnerability of African countries against introductions of 2019-nCoV The novel coronavirus (2019-nCoV) epidemic has spread to 23 countries from China. Local cycles of transmission already occurred in 7 countries following case importation. No African country has reported cases yet. The management and control of 2019-nCoV introductions heavily relies on the public health capacity of a country. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of 2019-nCoV. We used data on air travel volumes departing from airports in the infected provinces in China and directed to Africa to estimate the risk of introduction per country. We determined the countries capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulation Monitoring and Evaluation Framework; and vulnerability, with the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing the most to their risk. Findings: Countries at the highest importation risk (Egypt, Algeria, Republic of South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, Kenya) have variable capacity and high vulnerability. Three clusters of countries are identified that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and Beijing, respectively. Interpretation: Several countries in Africa are stepping up their preparedness to detect and cope with 2019-nCoV importations. Resources and intensified surveillance and capacity capacity should be urgently prioritized towards countries at moderate risk that may be ill-prepared to face the importation and to limit onward transmission.

negative: Unknown unknowns – COVID-19 and potential global mortality COVID-19 (SARS-CoV-2) is currently a global pandemic. This paper will attempt to estimate global infection rates and potential resultant mortality in the absence of effective treatment and/or vaccination. Calculations are based on World Health Organisation data from Wuhan in China: 14% of infected cases are severe, 5% require intensive care and 4% die. Estimated infection rates and mortality rates at the level of continents and some individual countries (when these are of sufficient size) are tabulated. This pandemic may cause close to half a billion deaths, i.e. 6% of the global population – and potentially more. At the risk of sounding sensational, but with a sober sense of realism, healthcare risks being plunged into the Middle-Ages if the public do not do their part. Infection cannot occur in the absence of contact. The only way to mitigate these numbers is to apply social distancing and take the standard precautions so frequently reiterated by Public Health: hand washing, avoid touching the face and so on. These measures are crucial as the human cost is going to be unthinkable even in the best-case scenarios that epidemiologists are modelling.

negative: A study of the probable transmission routes of MERS‐CoV during the first hospital outbreak in the Republic of Korea Infections caused by the Middle East respiratory syndrome coronavirus (MERS‐CoV) are a serious health issue due to their prevalence and associated mortality. However, the transmission routes of the virus remain unclear, and thus, the current recommended control strategies are not evidence based. In this study, we investigated the transmission routes of MERS‐CoV during the first nosocomial outbreak in the Republic of Korea in May 2015 using a multi‐agent modeling framework. We identified seven hypothesized transmission modes based on the three main transmission routes (long‐range airborne, close contact, and fomite). The infection risks for each hypothesis were estimated using the multi‐agent modeling framework. Least‐squares fitting was conducted to compare the distribution of the predicted infection risk in the various scenarios with that of the reported attack rates and to identify the hypotheses with the best fit. In the scenarios in which the index patient was a super‐spreader, our model simulations suggested that MERS‐CoV probably spread via the long‐range airborne route. However, it is possible that the index patient shed an average viral load comparable to the loads reported in the literature, and that transmission occurred via a combined long‐range airborne and close contact route.

negative: Ultrastructure of human nasal epithelium during an episode of coronavirus infection The nasal epithelium from a young girl was examined by electron microscopy and found to be infected by coronavirus. Virions are seen within and outside the ciliated cells, but not outside or within the goblet cells or other cells of the nasal mucosa. Some virions are located near the microvilli, others in pockets in the apical cell membrane. The cytoplasm contains many small vesicles with a single virion, large apical vesicles containing hundreds of virions, and lysosome-like cytosomes with a moderate number of virions. Some viruslike particles devoid of an electron-dense interior are seen both in the cytosomes and extracellularly. Virus budding was observed in the Golgi apparatus but nowhere else in the cell. The ciliated cells seem not to be destroyed by the viruses, although in many cases the cilia are withdrawn into the cell body. The loss of cilia is likely to cause rhinorrhoea.

negative: Informational needs assessment of non‐Hodgkin lymphoma survivors and their physicians

negative: Coronavirus entry and release in polarized epithelial cells: a review Most coronaviruses cause respiratory or intestinal infections in their animal or human host. Hence, their interaction with polarized epithelial cells plays a critical role in the onset and outcome of infection. In this paper, we review the knowledge regarding the entry and release of coronaviruses, with particular emphasis on the severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. As these viruses approach the epithelial surfaces from the apical side, it is not surprising that coronavirus cell receptors are exposed primarily on the apical domain of polarized epithelial cells. With respect to release, all possibilities appear to occur. Thus, most coronaviruses exit through the apical surface, several through the basolateral one, although the Middle East respiratory syndrome coronavirus appears to use both sides. These observations help us understand the local or systematic spread of the infection within its host as well as the spread of the virus within the host population. Copyright © 2014 John Wiley & Sons, Ltd.

negative: Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases Exosomes are 40–100 nm membrane vesicles secreted into the extracellular space by numerous cell types. These structures can be isolated from body fluids including urine and plasma. Exosomes contain proteins, mRNAs, miRNAs, and signaling molecules that reflect the physiological state of their cells of origin and consequently provide a rich source of potential biomarker molecules. Aside from diagnostic uses, exosome-mediated transfer of proteins, mRNAs, miRNAs, and signaling molecules offer the promise that they may be used for therapeutic purposes. In this review, we integrate new knowledge about exosomes from outside the field of nephrology with recent progress by renal researchers in order to provide a basis for speculation about how the study of exosomes may impact the fields of nephrology and renal physiology in the next few years.

negative: Impacts of social and economic factors on the transmission of coronavirus disease 2019 (COVID-19) in China This study models local and cross-city transmissions of the novel coronavirus in China between January 19 and February 29, 2020. We examine the role of various socioeconomic mediating factors, including public health measures that encourage social distancing in local communities. Weather characteristics 2 weeks prior are used as instrumental variables for causal inference. Stringent quarantines, city lockdowns, and local public health measures imposed in late January significantly decreased the virus transmission rate. The virus spread was contained by the middle of February. Population outflow from the outbreak source region posed a higher risk to the destination regions than other factors, including geographic proximity and similarity in economic conditions. We quantify the effects of different public health measures in reducing the number of infections through counterfactual analyses. Over 1.4 million infections and 56,000 deaths may have been avoided as a result of the national and provincial public health measures imposed in late January in China.

negative: The RNA Virus Database http://virus.zoo.ox.ac.uk/rnavirusdb; http://hivweb.sanbi.ac.za/rnavirusdb; http://bioinf.cs.auckland.ac.nz/rnavirusdb; http://tree.bio.ed.ac.uk/rnavirusdb.

negative: Coronavirus: Update Related to the Current Outbreak of COVID-19 In December 2019, some cases of viral pneumonia were epidemiologically related to a new coronavirus in the province of Hubei, China. Subsequently, there has been an increase in infections attributable to this virus throughout China and worldwide. The World Health Organization (WHO) has officially named the infection coronavirus disease 2019 (COVID-19), and the virus has been classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This appears to be a virus from Rhinolophus bats, but the intermediate host has not yet been identified. The mechanism of infection of SARS-CoV-2 is not yet known; it appears to have affinity for cells located in the lower airways, where it replicates. The interhuman transmission of coronaviruses mainly occurs through saliva droplets and direct and indirect contact via surfaces. As of March 10, 2020, the number of cases worldwide was 113,702. Along with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), COVID-19 appears to cause a severe clinical picture in humans, ranging from mild malaise to death by sepsis/acute respiratory distress syndrome. The prognosis is worse in elderly patients with comorbidities. To date, there is no specific therapy for COVID-19. Prevention of SARS-CoV-2 infection implies strategies that limit the spread of the virus. WHO and other international and national bodies have developed continuously updated strategic objectives and provisions to contain the spread of the virus and infection.

negative: Risk of nosocomial transmission of coronavirus disease 2019: an experience in a general ward setting in Hong Kong BACKGROUND: Coronavirus disease 2019 (COVID-19) was first reported in Wuhan in December 2019 and has rapidly spread across different cities within and outside China. Hong Kong started to prepare for COVID-19 on 31(st) December 2019 and infection control measures in public hospitals were tightened to limit nosocomial transmission within healthcare facilities. However, the recommendations on the transmission-based precautions required for COVID-19 in hospital settings vary from droplet and contact precautions, to contact and airborne precautions with placement of patients in airborne infection isolation rooms. AIM: To describe an outbreak investigation of a patient with COVID-19 who was nursed in an open cubicle of a general ward before the diagnosis was made. METHOD: Contacts were identified and risk categorized as ‘close’ or ‘casual’ for decisions on quarantine and/or medical surveillance. Respiratory specimens were collected from contacts who developed fever, and/or respiratory symptoms during the surveillance period and were tested for SARS-CoV-2. FINDINGS: A total of 71 staff and 49 patients were identified from contact tracing, seven staff and 10 patients fulfilled the criteria of ‘close contact’. At the end of 28-day surveillance, 76 tests were performed on 52 contacts and all were negative, including all patient close contacts and six of the seven staff close contacts. The remaining contacts were asymptomatic throughout the surveillance period. CONCLUSION: Our findings suggest that SARS-CoV-2 is not spread by an airborne route, and nosocomial transmissions can be prevented through vigilant basic infection control measures, including wearing of surgical masks, hand and environmental hygiene.

negative: MERS-CoV as an emerging respiratory illness: A review of prevention methods Abstract Introduction Middle East Respiratory Coronavirus Virus (MERS-CoV) first emerged from Saudi Arabia in 2012 and has since been recognized as a significant human respiratory pathogen on a global level. Methods In this narrative review, we focus on the prevention of MERS-CoV. We searched PubMed, Embase, Cochrane, Scopus, and Google Scholar, using the following terms: ‘MERS’, ‘MERS-CoV’, ‘Middle East respiratory syndrome’ in combination with ‘prevention’ or ‘infection control’. We also reviewed the references of each article to further include other studies or reports not identified by the search. Results As of Nov 2019, a total of 2468 laboratory-confirmed cases of MERS-CoV were diagnosed mostly from Middle Eastern regions with a mortality rate of at least 35%. A major outbreak that occurred outside the Middle East (in South Korea) and infections reported from 27 countries. MERS-CoV has gained recognition as a pathogen of global significance. Prevention of MERS-CoV infection is a global public health priority. Healthcare facility transmission and by extension community transmission, the main amplifier of persistent outbreaks, can be prevented through early identification and isolation of infected humans. While MERS-CoV vaccine studies were initially hindered by multiple challenges, recent vaccine development for MERS-CoV is showing promise. Conclusions The main factors leading to sustainability of MERS-CoV infection in high risk courtiers is healthcare facility transmission. MERS-CoV transmission in healthcare facility mainly results from laps in infection control measures and late isolation of suspected cases. Preventive measures for MERS-CoV include disease control in camels, prevention of camel to human transmission.

negative: The Mighty World of Microbes: An Overview The world of microbes on our planet is vast and diverse. This includes the normal bacterial flora present on the skin and mucous membranes of humans. The human microbiome project (HMP) was launched by NIH in 2007 as a part of a road map for medical research. The HMP serves as a template for researchers who are studying more than 1,000 microbial genomes with a focus on their role in health and disease. The study samples have been derived from five human body regions that are known to be inhabited by microbial flora. These include the gastrointestinal tract, female urogenital tract, mouth, nose, and skin. The techniques being used include finger printing, sequencing, dynamic range, and comparison of multiple samples. It is now well accepted that there are more microbial cells than human cells in the human body. Just the gastrointestinal tract harbors more than tenfold microbial cells than the number of human cells in the entire body. The understanding of the relationship between microbes and humans is at best rudimentary at this point in time. Similarly, the relationship between humans and microbes in the environment and environmental surfaces is poorly understood except for a few pathogenic microbes.

negative: New evidence of SARS-CoV-2 transmission through the ocular surface

negative: Clinical findings of patients with coronavirus disease 2019 in Jiangsu province, China: A retrospective, multi-center study Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0–54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m(2) (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P<0.001) and a known history of type 2 diabetes (OR, 4.326; 95% CI, 1.059 to 17.668; P = 0.041). In this case series in Jiangsu Province, COVID-19 patients had less severe symptoms and had better outcomes than the initial COVID-19 patients in Wuhan. The BMI ≥ 28 kg/m(2) and a known history of type 2 diabetes were independent risk factors of severe illness in patients with COVID-19.

negative: A Murine and a Porcine Coronavirus Are Released from Opposite Surfaces of the Same Epithelial Cells Abstract Epithelial cells are important target cells for coronavirus infection. Earlier we have shown that transmissible gastroenteritis coronavirus (TGEV) and mouse hepatitis coronavirus (MHV) are released from different sides of porcine and murine epithelial cells, respectively. To study the release of these viruses from the same cells, we constructed a porcine LLC-PK1 cell line stably expressing the recombinant MHV receptor cDNA (LMR cells). The MHV and TGEV receptor glycoproteins were shown by immunofluorescence to appear at the surface of the cells and to be functional so that the cells were susceptible to both MHV and TGEV infection. Both coronaviruses entered polarized LMR cells only through the apical surface. Remarkably, while the cells remained susceptible to TGEV for long periods, infectability by MHV decreased with time after plating of the cells onto filters. This was not due to a lack of expression of the MHV receptor, since this glycoprotein was still abundant on the apical surface of these cells. TGEV and MHV appeared to exit LMR cells from opposite sides. Whereas TGEV was released preferentially at the apical membrane, MHV was released preferentially at the basolateral surface. These results show that vesicles containing the two coronaviruses are targeted differently in LMR cells. We propose that the viruses are sorted at the Golgi complex into different transport vesicles that carry information directing them to one of the two surface domains. The apical release of TGEV and the basolateral release of MHV might be factors contributing to the difference in virus spread found between TGEV and MHV in their respective natural hosts, the former causing mainly a localized enteric infection, the latter spreading through the body to other organs.

negative: COVID-19 and the role of chronic inflammation in patients with obesity Coronavirus disease 2019 (COVID-19) and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a particular risk to people living with preexisting conditions that impair immune response or amplify pro-inflammatory response. Low-grade chronic systemic inflammation, common in people with obesity, is associated with the development of atherosclerosis, type 2 diabetes, and hypertension, well known comorbidities that adversely affect the outcomes of patients with COVID-19. Risk stratification based on the Edmonton Obesity Staging System (EOSS), which classifies obesity based on the presence of medical, mental, and/or functional complications rather than on body mass index (BMI), has been shown to be a better predictor of all-cause mortality and it may well be that EOSS stages may better describe the risk of hyperinflammation in patients with COVID-19 infection. Analyzing a group of metabolic ill patients with obesity (EOSS 2 and 3), we found an increased interleukin-6 and linear regression analysis showed a positive correlation with C-reactive protein (CRP) (p = 0.014) and waist-to-hip-ratio (WHR) (p = 0.031). Physicians should be aware of these findings in patients with COVID-19 infection. Early identification of possible hyperinflammation could be fundamental and should guide decision making regarding hospitalization, early respiratory support, and therapy with immunosuppression to improve mortality.

negative: SARS-CoV-2 in the ocular surface of COVID-19 patients The 2019 novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, while the routes of transmission of this virus are still controversial. We enrolled 33 patients, without any ocular manifestation, with their ocular surface swabs collected for virus detection. RNA was detected strong positive in samples of both eyes from two patients. Therefore, SARS-CoV-2 may exist in the normal ocular surface of COVID-19 patients, suggesting that this virus might be spread through conjunctival contact.

negative: International Course on Emerging Viruses in the Amazon Region

negative: Impact of school closures for COVID-19 on the US health-care workforce and net mortality: a modelling study BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is leading to social (physical) distancing policies worldwide, including in the USA. Some of the first actions taken by governments are the closing of schools. The evidence that mandatory school closures reduce the number of cases and, ultimately, mortality comes from experience with influenza or from models that do not include the effect of school closure on the health-care labour force. The potential benefits from school closures need to be weighed against costs of health-care worker absenteeism associated with additional child-care obligations. In this study, we aimed to measure child-care obligations for US health-care workers arising from school closures when these are used as a social distancing measure. We then assessed how important the contribution of health-care workers would have to be in reducing mortality for their absenteeism due to child-care obligations to undo the benefits of school closures in reducing the number of cases. METHODS: For this modelling analysis, we used data from the monthly releases of the US Current Population Survey to characterise the family structure and probable within-household child-care options of US health-care workers. We accounted for the occupation within the health-care sector, state, and household structure to identify the segments of the health-care workforce that are most exposed to child-care obligations from school closures. We used these estimates to identify the critical level at which the importance of health-care labour supply in increasing the survival probability of a patient with COVID-19 would undo the benefits of school closures and ultimately increase cumulative mortality. FINDINGS: Between January, 2018, and January, 2020, the US Current Population Survey included information on more than 3·1 million individuals across 1·3 million households. We found that the US health-care sector has some of the highest child-care obligations in the USA, with 28·8% (95% CI 28·5–29·1) of the health-care workforce needing to provide care for children aged 3–12 years. Assuming non-working adults or a sibling aged 13 years or older can provide child care, 15·0% (14·8–15·2) of the health-care workforce would still be in need of child care during a school closure. We observed substantial variation within the health-care system. We estimated that, combined with reasonable parameters for COVID-19 such as a 15·0% case reduction from school closings and 2·0% baseline mortality rate, a 15·0% decrease in the health-care labour force would need to decrease the survival probability per percent health-care worker lost by 17·6% for a school closure to increase cumulative mortality. Our model estimates that if the infection mortality rate of COVID-19 increases from 2·00% to 2·35% when the health-care workforce declines by 15·0%, school closures could lead to a greater number of deaths than they prevent. INTERPRETATION: School closures come with many trade-offs, and can create unintended child-care obligations. Our results suggest that the potential contagion prevention from school closures needs to be carefully weighted with the potential loss of health-care workers from the standpoint of reducing cumulative mortality due to COVID-19, in the absence of mitigating measures. FUNDING: None.

negative: A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells The respiratory syndrome caused by a new type of coronavirus has been emerging from China and caused more than 1000 death globally since December 2019. This new virus, called 2019 novel coronavirus (2019-nCoV) uses the same receptor called Angiotensinconverting enzyme 2 (ACE2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (SARS) seventeen years ago. Both viruses recognize ACE2 through the spike proteins (S-protein) on their surfaces. It was found that the S-protein from the SARS coronavirus (SARS-CoV) bind stronger to ACE2 than 2019-nCoV. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 and the S-protein from 2019-nCoV, so that the rate of their association can be estimated and compared with the binding of S-protein from SARS-CoV by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that the new disease by far spread much faster than SARS.

negative: An Experimental Model for Myocarditis and Congestive Heart Failure after Rabbit Coronavirus Infection In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2–5) and subacute (days 6–12) phases on the basis of day of death and pathologic findings. During the acute phase, the principal histologic lesions were degeneration and necrosis of myocytes, myocytolysis, interstitial edema, and hemorrhage. The severity of these changes increased in the subacute phase. Pleural effusion and congestion of the lungs and liver were also present at this time. Myocarditis was detected by day 9 and peaked by day 12. Heart weights and heart weight-to-body weight ratios were increased, and dilation of the right ventricular cavity became prominent early in infection and persisted. In contrast, dilation of the left ventricle occurred late in the subacute stage. Virus was isolated from infected hearts between days 2 and 12. These data suggest that rabbit coronavirus infection progresses to myocarditis and congestive heart failure.

negative: Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease BACKGROUND: Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aims to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia. METHODS: Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression. RESULTS: Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ(2) = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ(2) = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ(2) = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628–44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577–25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036–78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942–40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098–50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224−34.701, P = 0.028) were risk factors for disease progression. CONCLUSIONS: Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.

negative: Impact of Severe Acute Respiratory Syndrome (SARS) on Blood Services and Blood in Hong Kong in 2003 The current global pandemic of COVID‐19 due to the novel coronavirus SARS‐CoV‐2 is causing considerable loss of life and enormous social and economic disruption. Here, we describe the response of the blood service, the impact on blood donation and the effects on the blood supply in Hong Kong posed by the earlier SARS epidemic in 2002 and 2003. The infection, like SARS‐CoV‐2 was highly contagious through droplet transmission. In the 2003 SARS epidemic in Hong Kong, donor and staff safety was secured by using stringent infection control measures to protect both donors and staff from contacting the virus. All the donors were requested to wear face masks within the donation venue and use an alcohol‐based hand rinse. The donors' body temperature was checked before donation and staff's body temperatures were checked daily. The safety of the blood supply was secured by a donor deferral policy for 4 weeks following contact with a confirmed or suspected case of and a post‐donation call‐back system. Despite scheduling mobile donation sessions and a decrease in donors attending blood donor centers, the blood supply was maintained as there was a 12.8% reduction of the demand of blood and only a 16.9% reduction in the blood donation. Lessons learnt during the epidemic may help preparation for future epidemics and provide a basis for understanding the pathogenesis, laboratory diagnosis and role of coronaviruses in transfusion medicine. These are continuing problems as coronavirus epidemics may recur with future impact on blood collection and blood donation screening. This article is protected by copyright. All rights reserved.

negative: Epidemiological parameters of coronavirus disease 2019: a pooled analysis of publicly reported individual data of 1155 cases from seven countries Background The outbreak of coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization, while several key epidemiological parameters of the disease remain to be clarified. This study aimed to obtain robust estimates of the incubation period, upper limit of latent period (interval between exposure of infector and infectee), serial interval, time point of exposure and basic reproduction number (R0) of COVID-19. Methods Between late February and early March of 2020, the individual data of laboratory confirmed cases of COVID-19 were retrieved from 10728 publicly available reports released by the health authorities of and outside China and from 1790 publications identified in PubMed and CNKI. To be eligible, a report had to contain the data that allowed for estimation of at least one parameter. As relevant data mainly came from clustering cases, the clusters for which no evidence was available to establish transmission order were all excluded to ensure accuracy of estimates. Additionally, only the cases with an exposure period spanning 3 days or less were included in the estimation of parameters involving exposure date, and a simple method for determining exposure date was adopted to ensure the error of estimates be small (< 0.3 day). Depending on specific parameters, three or four of normal, lognormal, Weibull, and gamma distributions were fitted to the datasets and the results from appropriate models were presented. Findings In total, 1155 cases from China, Japan, Singapore, South Korea, Vietnam, Germany and Malaysia were included for the final analysis. The mean and standard deviation were 7.44 days and 4.39 days for incubation period, 2.52 days and 3.95 days for the upper limit of latent period, 6.70 days and 5.20 days for serial interval, and -0.19 day (i.e., 0.19 day before symptom onset of infector) and 3.32 days for time point of exposure. R0 was estimated to be 1.70 and 1.78 based on two different formulas. For 39 (6.64%) cases, the incubation periods were longer than 14 days. In 102 (43.78%) infector-infectee pairs, transmission occurred before the symptom onsets of infectors. In 27 (3.92%) infector-infectee pairs, symptom onsets of infectees occurred before those of infectors. Stratified analysis showed that incubation period and serial interval were consistently longer for those with less severe disease and for those whose primary cases had less severe disease. Asymptomatic transmission was also observed. Interpretation This study obtained robust estimates of several key epidemiological parameters of COVID-19. The findings support current practice of 14-day quarantine of persons with potential exposure, but also suggest that longer monitoring periods might be needed for selected groups. The estimates of serial interval, time point of exposure and latent period provide consistent evidence on pre-symptomatic transmission. This together with asymptomatic transmission and the generally longer incubation and serial interval of less severe cases suggests a high risk of long-term epidemic in the absence of appropriate control measures.

negative: Targeting Inflammatory Demyelinating Lesions to Sites of Wallerian Degeneration In Theiler’s murine encephalomyelitis virus (TMEV) infection, an animal model for multiple sclerosis (MS), axonal injury precedes inflammatory demyelinating lesions, and the distribution of axonal damage present during the early phase of infection corresponds to regions where subsequent demyelination occurs during the chronic phase. We hypothesized that axonal damage recruits inflammatory cells to sites of Wallerian degeneration, leading to demyelination. Three weeks after TMEV infection, axonal degeneration was induced in the posterior funiculus of mice by injecting the toxic lectin Ricinus communis agglutinin (RCA) I into the sciatic nerve. Neuropathology was examined 1 week after lectin injection. Control mice, infected with TMEV but receiving no RCA I, had inflammatory demyelinating lesions in the anterior/lateral funiculi. Other control mice that received RCA I alone did not develop inflammatory lesions. In contrast, RCA I injection into TMEV-infected mice induced lesions in the posterior funiculus in addition to the anterior/lateral funiculi. We found no differences in lymphoproliferative responses or antibody titers against TMEV among the groups. This suggests that axonal degeneration contributes to the recruitment of inflammatory cells into the central nervous system by altering the local microenvironment. In this scenario, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).

negative: Infection Virus infection of higher organisms is the cumulative result of all the processes of replication and gene expression described in the previous chapters. Together, these determine the overall course of each infection. Infections range in complexity and duration from a very brief, superficial interaction between the virus and its host to infections that may span the entire life of the host organism, from before birth to its eventual death. A common misconception is that virus infection inevitably results in disease. In reality, the reverse is true—only a small minority of virus infections gives rise to any disease symptoms. This chapter provides an overview of the numerous patterns of virus infection and forms an introduction to the discussion of virus pathogenesis in Chapter 7. Unlike previous and subsequent chapters, this chapter deals primarily with the interaction of viruses with intact organisms rather than with the molecular biologist’s usual concern about the interaction between a virus and the cell.

negative: Assessing the Tendency of 2019-nCoV (COVID-19) Outbreak in China Since December 8, 2019, the spread of COVID-19 is increasing every day. It is particularly important to predict the trend of the epidemic for the timely adjustment of the economy and industries. We proposed a Flow-SEHIR model in this paper, based on which we further analyzed the trends of 2019-nCoV (COVID-19) in China. The results show that the basic reproductive numbers R0 of COVID-19 is 3.56 (95% CI: 2.31-4.81). The number of daily confirmed new cases reaches the inflection point on Feb. 6-10 outside Hubei. For the maximum of infected cases number, the predicted peak value in China except Hubei was estimated to be 13806 (95% CI: 11926-15845). The peak arrival time is on March 3-9. The temporal number of patients in most areas of China outside Hubei will peak from March 12 to March 15. The peak values of more than 73.5% provinces or regions in China will be controlled within 1000. According to Flow-SEHIR model and estimations from the data of evacuation of nationals from Wuhan, the peak cumulative number of patients in Hubei was estimated to be 403481 (95% CI: 143284-1166936).

negative: Maintaining Places of Social Inclusion: Ebola and the Emergency Department We introduce the concept of places of social inclusion—institutions endowed by a society or a community with material resources, meaning, and values at geographic sites where citizens can access services for specific needs—as taken-for-granted, essential, and inherently precarious. Based on our study of an emergency department that was disrupted by the threat of the Ebola virus in 2014, we develop a process model to explain how a place of social inclusion can be maintained by custodians. We show how these custodians—in our fieldsite, doctors and nurses—experience and engage in institutional work to manage different levels of tension between the value of inclusion and the reality of finite resources, as well as tension between inclusion and the desire for safety. We also demonstrate how the interplay of custodians’ emotions is integral to maintaining the place of social inclusion. The primary contribution of our study is to shine light on places of social inclusion as important institutions in democratic society. We also reveal the theoretical and practical importance of places as institutions, deepen understanding of custodians and custodianship as a form of institutional work, and offer new insight into the dynamic processes that connect emotions and institutional work.

negative: Body temperature of free-ranging koalas (Phascolarctos cinereus) in south-east Queensland. The distribution of the koala (Phascolarctos cinereus) in Queensland is predicted to contract as a result of climate change, driven by the frequency, intensity and duration of heatwaves and drought. However, little is known about the physiological responses of this species to environmental extremes under field conditions. This study aimed to establish the efficacy of surgically implanted thermal radio transmitters and data loggers to measure the body temperature of free-ranging koalas across a range of environmental conditions and ambient temperatures. Five free-ranging koalas in southeast Queensland were implanted with thermal transmitters and data loggers waxed together as a single package. Body temperatures were recorded for variable periods ranging from 3 to 12 months. Diurnal rhythms in body temperature were detected irrespective of season. The long-term diurnal body temperature peak for all koalas occurred between 16:00 and 17:00 h and body temperature was 36.7-36.9 °C, the long-term nadir occurred between 07:00 and 08:00 h and body temperature was 35.4-35.7 °C. Koala body temperatures as low as 34.2 °C and as high as 39.0 °C were recorded. Thermolability became apparent when ambient temperatures were outside the deduced thermal neutral zone for koalas (14.5-24.5 °C): heat was accumulated during the day and dissipated during the cool of the night. While this study is the first to report on body temperature of free-ranging koalas in their normal behavioural context, further investigations are necessary to determine the physiological boundaries of the thermal niche for this species, in order to better equip models that will more accurately predict the impacts of climate change on koalas.

negative: [Management strategies for patients with gynecological malignancies during the outbreak of COVID19]. Objective: To explore the management strategies for patients with gynecological malignant tumors during the outbreak and transmission of COVID19. Methods: We retrospectively analyzed the clinical characteristics, treatment, and disease outcomes of three patients with gynecological malignancies associated with COVID19 in Renmin Hospital of Wuhan University in January 2020, and proposed management strategies for patients with gynecological tumors under risk of COVID19. Results: Three patients were treated COVID19 based on the national diagnosis and treatment protocol as well as research progress. Meanwhile, these patients were appropriately adjusted the treatment plan in accordance with the clinical guidelines for gynecological tumors. Pneumonia was cured in 2 patients, and one patient died of COVID-19. Conclusions: Patients with gynecological malignant tumors are high-risk groups prone to COVID-19 infection, and gynecological oncologists need to carry out education, prevention, control and treatment according to specific conditions. While actively preventing and controlling COVID-19, the diagnosis and treatment of gynecological malignant tumors should be carried out in an orderly and safe manner.

negative: Viral Sepsis Viruses are the smallest infective agents currently known to affect humans and animals. The virus has a centrally situated nucleic acid, which is encased within a capsid consisting of a protein core. Viruses are obligatory intracellular microorganisms that live inside cells, using components of the nucleic acid and protein generating system of the host to replicate and trigger cell destruction leading to diseases. Alternatively, the host’s defense mechanisms lead to cell destruction in an attempt to clear cells infected by the viruses. The nucleic acid is RNA or DNA, which may be single-stranded or double-stranded [1]. The pathophysiology of viral infections may be attributed to the degeneration and cellular necrosis of the infected cells, leading to local and systemic inflammatory responses. The body’s defense mechanisms include phagocytosis, humoral and cell-mediated responses and the production of interferons [2]. Interferons prevent the local spread of viruses, whereas antibodies prevent viremia, ensure long-term immunity and sensitize infected cells to be destroyed by T-cells and macrophages [3, 4]. Cell-mediated immunity leads to an increase in cytotoxic cells that then release lymphokines, including interferon.

negative: The phenotypic changes of Î³Î´ T cells in COVID-19 patients A novel pneumonia-associated respiratory syndrome named coronavirus disease-2019 (COVID-19), which caused by SARS-CoV-2 and broken in Wuhan, China in the end of 2019. Unfortunately, there is no specific antiviral agent or vaccine available to treat SARS-CoV-2 infections. Also, information regarding the immunological characteristics in COVID-19 patients remains limited. Here we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes in {gamma}{delta} T cells. In comparison to HD, the {gamma}{delta} T cells percentage was decreased. {gamma}{delta} T cells are able to immediately respond to SARS-CoV-2 infection and upregulate the activation marker CD25. In addition, the increased expression of CD4 in {gamma}{delta} T cells may serve as a biomarker for the assessment of SARS-CoV-2 infection.

negative: Translation from the 5' untranslated region (UTR) of mRNA 1 is repressed, but that from the 5' UTR of mRNA 7 is stimulated in coronavirus-infected cells. Viral gene products are generally required in widely differing amounts for successful virus growth and assembly. For coronaviruses, regulation of transcription is a major contributor to these differences, but regulation of translation may also be important. Here, we examine the possibility that the 5' untranslated regions (UTRs), unique for each of the nine species of mRNA in the bovine coronavirus and ranging in length from 70 nucleotides (nt) to 210 nt (inclusive of the common 5'-terminal 65-nt leader), can differentially affect the rate of protein accumulation. When the natural 77-nt 5' UTR on synthetic transcripts of mRNA 7 (mRNA for N and I proteins) was replaced with the 210-nt 5' UTR from mRNA 1 (genomic RNA, mRNA for viral polymerase), approximately twofold-less N, or (N) CAT fusion reporter protein, was made in vitro. Twofold less was also made in vivo in uninfected cells when a T7 RNA polymerase-driven transient-transfection system was used. In coronavirus-infected cells, this difference surprisingly became 12-fold as the result of both a stimulated translation from the 77-nt 5' UTR and a repression of translation from the 210-nt 5' UTR. These results reveal that a differential 5' UTR-directed regulation of translation can occur in coronavirus-infected cells and lead us to postulate that the direction and degree of regulation is carried out by viral or virally induced cellular factors acting in trans on cis-acting elements within the 5' UTR.

negative: The emergence of enterovirus D68 in a Dutch University Medical Center and the necessity for routinely screening for respiratory viruses Abstract Background Since August 2014, an increase in infections caused by enterovirus D68 (EV-D68) was reported in the USA and Canada, for the most part in children presenting with severe respiratory symptoms. Objectives To determine whether an increase in severe EV-D68 respiratory infections was observed in our region. Study design Samples from patients with respiratory symptoms were screened for viral pathogens, including rhinovirus and enterovirus. Subsequently, samples positive for rhinovirus and enterovirus were routinely sequenced for phylogenetic analysis. Furthermore, an additional method was used to detect EV-D68 specifically. Results During the first three quarters of the year 2014, 1896 respiratory samples were analyzed; 39 (2%) of them tested positive for enterovirus. Eighteen samples tested positive for EV-D68, obtained from 16 different patients admitted to our hospital. Eleven were children below the age of 18, of whom five children needed intensive care treatment. The remaining five samples were from adults, who all had an underlying disease; three were transplant patients (heart, lung and renal transplantation), the other two had an underlying lung condition (COPD, asthma). Phylogenetic analysis showed a close relationship with the strains circulating currently in the USA, all belonging to the known EV-D68 genetic subtypes. Conclusions We observed an increase of EV-D68 infections in our population, both in children as well as in adult. In 2014 there have been 16 cases so far, compared to none in 2011 and 2013 and a single case in 2012. Phylogenetic analysis identified two similar clusters as shown in the USA and Canada.

negative: Pyogranulomatous panophthalmitis in a ferret

negative: Comprehensive quantitative analysis of Shuang-Huang-Lian oral liquid using UHPLC–Q-TOF-MS and HPLC-ELSD Abstract Shuang-Huang-Lian oral liquid (SHL) is a well-known Chinese patent drug containing three herbal medicines: Radix Scutellariae, Flos Lonicerae Japonicae and Fructus Forsythiae. It is usually used to treat acute upper respiratory tract infection caused by virus or bacteria. Although the licensing of botanical drug Veregen approved by FDA has indicated the importance of quantitative analysis in quality control of herbal medicines, quantitative evaluation of a Chinese patent drug like SHL remains a challenge due to the complex chemical profile. In this study, 15 small molecular components of SHL (four flavonoids, six quinic acid derivatives, three saponins and two phenylethanoid glycosides) were simultaneously determined using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC–Q-TOF-MS). The contents of the three major saccharides, namely fructose, glucose and sucrose were quantified using high performance liquid chromatography-evaporative light scattering detector on an amino column (HPLC-ELSD). The macromolecules were quantified by precipitating in 80% ethanol, drying the precipitate, and then weighing. The established methods were validated in terms of linearity, sensitivity, precision, accuracy and stability and then successfully applied to analyze 12 batches of commercial products of SHL produced by four different manufacturers. The results indicated that 57.52–78.11% (w/w) of SHL could be quantitatively determined (non-saccharide small molecules: 1.77–3.75%, monosaccharides: 0.93–20.93%, macromolecules: 2.63–5.76% and sucrose: 49.20–65.94%). This study may provide a useful way to comprehensively evaluate the quality of SHL.

negative: Evolutionary Trajectory for the Emergence of Novel Coronavirus SARS-CoV-2 Over the last two decades, the world experienced three outbreaks of coronaviruses with elevated morbidity rates. Currently, the global community is facing emerging virus SARS-CoV-2 belonging to Betacoronavirus, which appears to be more transmissible but less deadly than SARS-CoV. The current study aimed to track the evolutionary ancestors and different evolutionary strategies that were genetically adapted by SARS-CoV-2. Our whole-genome analysis revealed that SARS-CoV-2 was the descendant of Bat SARS/SARS-like CoVs and bats served as a natural reservoir. SARS-CoV-2 used mutations and recombination as crucial strategies in different genomic regions including the envelop, membrane, nucleocapsid, and spike glycoproteins to become a novel infectious agent. We confirmed that mutations in different genomic regions of SARS-CoV-2 have specific influence on virus reproductive adaptability, allowing for genotype adjustment and adaptations in rapidly changing environments. Moreover, for the first time we identified nine putative recombination patterns in SARS-CoV-2, which encompass spike glycoprotein, RdRp, helicase and ORF3a. Six recombination regions were spotted in the S gene and are undoubtedly important for evolutionary survival, meanwhile this permitted the virus to modify superficial antigenicity to find a way from immune reconnaissance in animals and adapt to a human host. With these combined natural selected strategies, SARS-CoV-2 emerged as a novel virus in human society.

negative: A method for the improved detection of aerosolized influenza viruses and the male-specific (F+) RNA coliphage MS2 Abstract The detection of aerosolized viruses can serve as an important surveillance and control tool in agriculture, human health, and environmental settings. Here, we adapted an anion exchange resin-based method, initially developed to concentrate negatively charged viruses from water, to liquid impingement-based bioaerosol sampling. In this method, aerosolized viruses are collected in a 20ml liquid sample contained within widely used impingers, BioSamplers (SKC Inc., Eighty Four, PA), and further concentrated via adsorption to an anion exchange resin that is suspended within this liquid. Viral nucleic acids are then extracted from the resin to facilitate molecular analyses through a reduction in the effective sample volume. For this study, various quantities of two negatively charged viruses, type A and type B influenza viruses (FluMist Quadrivalent vaccine) and the male-specific (F+) RNA coliphage MS2 (MS2), were nebulized into a custom-built bioaerosolization chamber, and sampled using BioSamplers with and without anion exchange resin. Compared to direct testing of the BioSampler liquid, detection was improved by 6.77× and 3.33× for type A and type B influenza viruses, respectively, by using the anion exchange resin. For MS2, the anion exchange resin method allowed for an average improvement in detection of 8.26×.

negative: Host Immune Responses to SARS Coronavirus in Humans The severe acute respiratory syndrome (SARS) is a newly identified infectious disease caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. The risk of SARS reemergence in humans remains high due to the large animal reservoirs of SARS-CoV-like coronavirus and the genome instability of RNA coronaviruses. An epidemic in 2003 affected more than 8,000 patients in 29 countries, with 10% mortality. SARS infection is transmitted by air droplets. Clinical and laboratory manifestations include fever, chills, rigor, myalgia, malaise, diarrhea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase, alanine aminotransferase, and creatine kinase activities. Health care workers are a high-risk group, and advanced age is strongly associated with disease severity. Treatment has been empirical, and there is no licensed SARS vaccine for humans so far. However, presence of long-lived neutralizing antibodies and memory T- and B-lymphocytes in convalescent SARS patients raises hope for active immunization. Furthermore, results from preclinical SARS vaccines expressing spike protein to elicit neutralizing antibodies and cellular responses that are protective in mouse and nonhuman primate models are encouraging. Very little is known of the early events in viral clearance and the onset of innate and inflammatory responses during the SARS infection. Regulation of the innate immune response is associated with the development of adaptive immunity and disease severity in SARS infection. Notably, SARS-CoV has evolved evasive strategies to suppress antiviral type I interferon responses in infected cells. In addition, inflammatory responses are characterized by upregulation of proinflammatory cytokines/chemokines such as IL-6, IP-10, and MCP-1 in tissues and serum, and massive infiltrations of inflammatory cells such as macrophages in infected tissues. Due to the lack of animal models that mimic the clinical manifestations of human SARS infection for mechanistic study and vaccine evaluation, development of a safe prophylactic SARS vaccine for human use remains a huge challenge. This chapter is written to summarize and highlight the latest clinical, serological, and immunological parameters relevant to the pathogenesis and protective immunity of SARS infection in humans.

negative: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial Abstract Background Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. Patients and methods French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Results Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Conclusion Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

negative: COVID-19 outbreak: Migration, effects on society, global environment and prevention Abstract The COVID-19 pandemic is considered as the most crucial global health calamity of the century and the greatest challenge that the humankind faced since the 2nd World War. In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China and was named by the World Health Organization as COVID-19 (coronavirus disease 2019). A new class of corona virus, known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been found to be responsible for occurrence of this disease. As far as the history of human civilization is concerned there are instances of severe outbreaks of diseases caused by a number of viruses. According to the report of the World Health Organization (WHO as of April 18 2020), the current outbreak of COVID-19, has affected over 2164111 people and killed more than 146,198 people in more than 200 countries throughout the world. Till now there is no report of any clinically approved antiviral drugs or vaccines that are effective against COVID-19. It has rapidly spread around the world, posing enormous health, economic, environmental and social challenges to the entire human population. The coronavirus outbreak is severely disrupting the global economy. Almost all the nations are struggling to slow down the transmission of the disease by testing & treating patients, quarantining suspected persons through contact tracing, restricting large gatherings, maintaining complete or partial lock down etc. This paper describes the impact of COVID-19 on society and global environment, and the possible ways in which the disease can be controlled has also been discussed therein.

negative: Clinical Characteristics of Hospitalized Patients with SARS-CoV-2 and Hepatitis B virus Co-infection Background & Aims The coronavirus disease 2019 (COIVD-19) caused by SARS-CoV-2 has been characterized as a pandemic, which causes a serious public health challenge in the world. A very large group of patients infected by HBV has been reported worldwide, especially in China. In order to answer whether specific treatment strategy on the patients coinfected with HBV and SARS-CoV-2, it requires profound understanding of the clinical characteristics on those patients. However, the impacts of SARS-CoV-2 infection on HBV patients remain largely unknown. Approach & Results In this retrospective investigation, we included 123 COVID-19 patients admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from January 5 to March 7, 2020. All enrolled patients are the laboratory confirmed COVID-19 pneumonia cases according to the criteria reported previously. A total of 123 patients were analyzed for their Clinical records, laboratory results including the diagnosis of HBV infection and liver function. Among 123 confirmed COVID-19 patients, the mean age was 51 years old and 59.3% were females (73/123). Fifteen were previously HBV infected patients, 66.7% of them were males (10/15), patients with HBV infection appeared to have a higher incidence of liver cirrhosis and an increased level of total bilirubin. Seven (46.7%) patients with HBV infection were defined as severe cases, while the severity rate was 24.1% for the patients without HBV infection (26/108). The mortality of patients with HBV infection was 13.3% (2/15) compared to 2.8% (3/108) for the patients without HBV infection. Conclusions SARS-CoV-2 infection may cause liver function damage in COVID-19 cases and the patients with HBV infection are likely to have more severe disease outcome.

negative: Recombinant M protein-based ELISA test for detection of antibodies to canine coronavirus Abstract The membrane (M) protein of canine coronavirus (CCoV) was cloned and expressed in E. coli. The purified recombinant protein was then evaluated for its antigenicity and reliability in an enzyme-linked immunosorbent assay (ELISA) for detection of CCoV antibodies in dog sera. Fifty serum samples, screened previously by whole virus ELISA and Western blotting, were tested. When the performance of the new test was compared with those of whole virus ELISA and Western blotting, an excellent correlation was found with the latter two assays. The ELISA based on recombinant M protein represents an alternative and valid test for detection of antibodies to CCoV in dog sera.

negative: Characteristics of Microbes Most Likely to Cause Pandemics and Global Catastrophes Predicting which pathogen will confer the highest global catastrophic biological risk (GCBR) of a pandemic is a difficult task. Many approaches are retrospective and premised on prior pandemics; however, such an approach may fail to appreciate novel threats that do not have exact historical precedent. In this paper, based on a study and project we undertook, a new paradigm for pandemic preparedness is presented. This paradigm seeks to root pandemic risk in actual attributes possessed by specific classes of microbial organisms and leads to specific recommendations to augment preparedness activities.

negative: Real-time monitoring the transmission potential of COVID-19 in Singapore, March 2020 BACKGROUND: As of March 31, 2020, the ongoing COVID-19 epidemic that started in China in December 2019 is now generating local transmission around the world. The geographic heterogeneity and associated intervention strategies highlight the need to monitor in real time the transmission potential of COVID-19. Singapore provides a unique case example for monitoring transmission, as there have been multiple disease clusters, yet transmission remains relatively continued. METHODS: Here we estimate the effective reproduction number, R(t), of COVID-19 in Singapore from the publicly available daily case series of imported and autochthonous cases by date of symptoms onset, after adjusting the local cases for reporting delays as of March 17, 2020. We also derive the reproduction number from the distribution of cluster sizes using a branching process analysis that accounts for truncation of case counts. RESULTS: The local incidence curve displays sub-exponential growth dynamics, with the reproduction number following a declining trend and reaching an estimate at 0.7 (95% CI 0.3, 1.0) during the first transmission wave by February 14, 2020, while the overall R based on the cluster size distribution as of March 17, 2020, was estimated at 0.6 (95% CI 0.4, 1.02). The overall mean reporting delay was estimated at 6.4 days (95% CI 5.8, 6.9), but it was shorter among imported cases compared to local cases (mean 4.3 vs. 7.6 days, Wilcoxon test, p < 0.001). CONCLUSION: The trajectory of the reproduction number in Singapore underscores the significant effects of successful containment efforts in Singapore, but it also suggests the need to sustain social distancing and active case finding efforts to stomp out all active chains of transmission.

negative: Human aminopeptidase N is a receptor for human coronavirus 229E HUMAN coronaviruses (HCV) in two serogroups represented by HCV-229E and HCV-OC43 are an important cause of upper respiratory tract infections(1). Here we report that human aminopeptidase N, a cell-surface metalloprotease on intestinal, lung and kidney epithelial cells(2–5), is a receptor for human coronavirus strain HCV-229E, but not for HCV-OC43. A monoclonal antibody, RBS, blocked HCV-229E virus infection of human lung fibroblasts, immunoprecipitated aminopeptidase N and inhibited its enzymatic activity. HCV-229E-resistant murine fibroblasts became susceptible after transfection with complementary DNA encoding human aminopeptidase N. By contrast, infection of human cells with HCV-OC43 was not inhibited by antibody RBS and expression of aminopeptidase N did not enhance HCV-OC43 replication in mouse cells. A mutant aminopeptidase lacking the catalytic site of the enzyme did not bind HCV-229E or RBS and did not render murine cells susceptible to HCV-229E infection, suggesting that the virus-binding site may lie at or near the active site of the human aminopeptidase molecule.

negative: Generation and Characterization of Eptesicus fuscus (Big brown bat) kidney cell lines immortalized using the Myotis polyomavirus large T-antigen Abstract It is speculated that bats are important reservoir hosts for numerous viruses, with 27 viral families reportedly detected in bats. Majority of these viruses have not been isolated and there is little information regarding their biology in bats. Establishing a well-characterized bat cell line supporting the replication of bat-borne viruses would facilitate the analysis of virus-host interactions in an in vitro model. Currently, few bat cell lines have been developed and only Tb1-Lu, derived from Tadarida brasiliensis is commercially available. Here we describe a method to establish and immortalize big brown bat (Eptesicus fuscus) kidney (Efk3) cells using the Myotis polyomavirus T-antigen. Subclones of this cell line expressed both epithelial and fibroblast markers to varying extents. Cell clones expressed interferon beta in response to poly(I:C) stimulation and supported the replication of four different viruses, namely, vesicular stomatitis virus (VSV), porcine epidemic diarrhea coronavirus (PED-CoV), Middle-East respiratory syndrome coronavirus (MERS-CoV) and herpes simplex virus (HSV). To our knowledge, this is the first bat cell line from a northern latitude insectivorous bat developed using a novel technology. The cell line has the potential to be used for isolation of bat viruses and for studying virus-bat interactions in culture.

negative: A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus—A possible reference for coronavirus disease‐19 treatment option In the past few decades, coronaviruses have risen as a global threat to public health. Currently, the outbreak of coronavirus disease‐19 (COVID‐19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID‐19. However, there are agents that were used during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID‐19.

negative: Occupational and Environmental Exposures to Waterborne Microbial Diseases

negative: Prolonged social isolation of the elderly during COVID-19: between benefit and damage

negative: Will novel virus go pandemic or be contained?

negative: [Guidance for routine pathology practice during the prevention and control period of novel coronavirus pneumonia].

negative: Weaponized Interdependence: China's Economic Statecraft and Social Penetration against Taiwan

negative: Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). DESIGN: Retrospective case series. SETTING: Seven hospitals in Zhejiang province, China. PARTICIPANTS: 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020. MAIN OUTCOME MEASURES: Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification. RESULTS: Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days. CONCLUSION: As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.

negative: The SARS Coronavirus: Rapid Diagnostics in the Limelight

negative: Mitigating the Effects of a Pandemic: Facilitating Improved Nursing Home Care Delivery Through Technology The coronavirus disease (COVID-19) pandemic has been particularly challenging for nursing home staff and residents. Centers for Medicare & Medicaid Services regulation waivers are burdening staff and affecting how care is delivered. Residents are experiencing social isolation, which can result in physical and behavioral health issues, particularly for persons with dementia. These challenges can be addressed in part through technology adaptations. Full integration of electronic health record systems can improve workflow and care quality. Telehealth can improve access to outside providers, provide remote monitoring, and improve social connectedness. Electronic and audiovisual programs can be used for end-of-life planning and information sharing between nursing home staff and families. Online learning systems and other online resources provide flexible options for staff education and training. Investing in and adapting technology can help mitigate workforce stress and improve the quality of nursing home care during and after the COVID-19 crisis.

negative: Prediction of Intrinsic Disorder in MERS-CoV/HCoV-EMC Supports a High Oral-Fecal Transmission A novel coronavirus, MERS-CoV (NCoV, HCoV-EMC/2012), originating from the Middle-East, has been discovered. Incoming data reveal that the virus is highly virulent to humans. A model that categorizes coronaviuses according to the hardness of their shells was developed before the discovery of MERS-CoV. Using protein intrinsic disorder prediction, coronaviruses were categorized into three groups that can be linked to the levels of oral-fecal and respiratory transmission regardless of genetic proximity. Using this model, MERS-CoV is placed into disorder group C, which consists of coronaviruses that have relatively hard inner and outer shells. The members of this group are likely to persist in the environment for a longer period of time and possess the highest oral-fecal components but relatively low respiratory transmission components. Oral-urine and saliva transmission are also highly possible since both require harder protective shells. Results show that disorder prediction can be used as a tool that suggests clues to look for in further epidemiological investigations.

negative: Becoming bovine: Mechanics and metamorphosis in Hokkaido's animal-human-machine Abstract The fieldwork for my doctoral degree was carried out over nineteen months, a year of which was spent working on an industrial dairy farm in Hokkaido, Japan's northernmost Island. As in much of the industrialised world, dairy farming in Japan is rapidly changing. Many farmers are forced by neo-liberal agricultural policies to shift from small family operated farms to high-tech, high-speed, and high overhead industrial operations. This paper focuses on the history of dairy farming in the Tokachi region; more specifically one farm and the shift over a generation to a rotary parlour milking system. It addresses the linkages this mode of production has cultivated amongst humans, dairy cows and industrialized space. The parlour system at Great Hopes Farm allows five workers (aided by three more stall staff) to milk over 1000 cows, fifty at a time, three times a day. The impetus behind moving to parlour technology is that it increases productivity through mechanically enhanced observation and control. However this recent mechanical separation of human and cow during the milking process has led to affectively shared interspecies and inter-human alienation. The technology of the parlour system sets daily rhythms for bovine and human alike, and separates both from a process formerly dependent upon, specialized knowledge, affective empathy, and embodied knowledge. Human and bovine experience the systemic violence of the machine and what remains is a complex bio-politics of interspecies affect and the separation of “bare” and “political” life.

negative: Relative survival of Bacillus subtilis spores loaded on filtering facepiece respirators after five decontamination methods This study determines the relative survival (RS) of Bacillus subtilis spores loaded on an N95 filtering facepiece respirator (FFR) after decontamination by five methods under worst‐case conditions. Relative survival was obtained by testing after decontamination and after storing the FFRs at 37°C and 95% relative humidity for 24 hours. The decontamination methods involved ethanol, bleach, ultraviolet irradiation (UVA 365 nm, UVC 254 nm), an autoclave, and a traditional electric rice cooker (TERC) that was made in Taiwan. Without decontamination, 59 ± 8% of the loaded spores survived for 24 hours. When 70% ethanol was added to the N95 FFR at a packing density of 0.23, the RS was 73 ± 5% initially and decayed to 22 ± 8% in 24 hours. Relative survival remained above 20% after 20 minutes of UVA irradiation. The other four decontamination measures achieved 99%‐100% biocidal efficacy, as measured immediately after the methods were applied to the test FFRs. Relative survival is a useful parameter for measuring sterilization or degree of disinfection. Bleach, UVC, an autoclave, and a TERC provide better biocidal efficacy than ethanol and UVA. Not only a higher filter quality but also a lower value of RS produced the most decontaminated FFR.

negative: Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China Cases of coronavirus disease 2019 (COVID-19) emigrating from Wuhan escalated the risk of spreading the disease in other cities. This report focused on outside-Wuhan patients to assess the transmission and clinical characteristics of this illness. Contact investigation was conducted on each patient who was admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from 22 January to 23 February 2020. Cases were confirmed by the polymerase chain reaction test. Demographic, clinical, and outcomes were collected and analyzed. Of the 104 patients, 48 (46.15%) were cases who immigrated from Wuhan; 93 (89.42%) had a definite contact history with infection. Family clusters were the major body of patients. Transmission along the chain of three "generations" was observed. Five asymptomatic infected cases were found and two of them infected their relatives. Mean age was 43 (range, 8-84) years, and 49 (47.12%) were male. The median incubation period was 6 (range, 1-32) days, which of 8 patients ranged from 18 to 32 days, 96 (92.31%) were discharged, and 1 (0.96%) died. The average hospital stay was 10 (range, 8-14) days. Family but not community transmission became the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown worked well. Asymptomatic transmission demonstrated here warned us that it may lead to the widespread of COVID-19. A 14-day quarantine may need to be prolonged.

negative: Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against coronavirus disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the treatment of this disease, and several approved drugs such as lopinavir have been evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication of SARS-CoV-2. The effective concentrations for 50% and 90% inhibition (EC50 and EC90) of nelfinavir were 1.13 µM and 1.76 µM respectively, the lowest of the nine HIV-1 protease inhibitors including lopinavir. The trough and peak serum concentrations of nelfinavir were three to six times higher than EC50 of this drug. These results suggest that nelfinavir is a potential candidate drug for the treatment of COVID-19 and should be assessed in patients with COVID-19.

negative: Recognition of Functional Sites in Protein Structures Abstract Recognition of regions on the surface of one protein, that are similar to a binding site of another is crucial for the prediction of molecular interactions and for functional classifications. We first describe a novel method, SiteEngine, that assumes no sequence or fold similarities and is able to recognize proteins that have similar binding sites and may perform similar functions. We achieve high efficiency and speed by introducing a low-resolution surface representation via chemically important surface points, by hashing triangles of physico-chemical properties and by application of hierarchical scoring schemes for a thorough exploration of global and local similarities. We proceed to rigorously apply this method to functional site recognition in three possible ways: first, we search a given functional site on a large set of complete protein structures. Second, a potential functional site on a protein of interest is compared with known binding sites, to recognize similar features. Third, a complete protein structure is searched for the presence of an a priori unknown functional site, similar to known sites. Our method is robust and efficient enough to allow computationally demanding applications such as the first and the third. From the biological standpoint, the first application may identify secondary binding sites of drugs that may lead to side-effects. The third application finds new potential sites on the protein that may provide targets for drug design. Each of the three applications may aid in assigning a function and in classification of binding patterns. We highlight the advantages and disadvantages of each type of search, provide examples of large-scale searches of the entire Protein Data Base and make functional predictions.

negative: Lack of Antiviral Activity of Darunavir against SARS-CoV-2 Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. DRV showed no activity against SARS-CoV-2 at clinically relevant concentrations (EC50 >100 μM). Remdesivir, used as a positive control, showed potent antiviral activity (EC50 = 0.38 μM). Overall, the data do not support the use of DRV for treatment of COVID-19.

negative: PC-FACS May 2020 for July 2020 Issue PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care) provides hospice and palliative care clinicians with concise summaries of the most important findings from more than 100 medical and scientific journals. If you have colleagues who would benefit from receiving PCFACS, please encourage them to join the AAHPM at aahpm.org. Comments from readers are welcomed at pcfacs@aahpm.org.

negative: Central nervous system myelin: structure, function, and pathology Multiple sclerosis (MS) and a number of related distinctive diseases are characterized by the active degradation of central nervous system (CNS) myelin, an axonal sheath comprised essentially of proteins and lipids. These demyelinating diseases appear to arise from complex interactions of genetic, immunological, infective, and biochemical mechanisms. While circumstances of MS etiology remain hypothetical, one persistent theme involves recognition by the immune system of myelin-specific antigens derived from myelin basic protein (MBP), the most abundant extrinsic myelin membrane protein, and/or another equally susceptible myelin protein or lipid component. Knowledge of the biochemical and physical—chemical properties of myelin proteins and lipids, particularly their composition, organization, structure, and accessibility with respect to the compacted myelin multilayers, thus becomes central to the understanding of how and why these antigens become selected during the development of MS. This review focuses on current understanding of the molecular basis underlying demyelinating disease as it may relate to the impact of the various protein and lipid components on myelin morphology; the precise molecular architecture of this membrane as dictated by protein—lipid and lipid—lipid interactions; and the relationship, if any, between the protein/lipid components and the destruction of myelin in pathological situations.

negative: Converting Home Spaces Into Food Gardens At the Time of Covid-19 Quarantine: All the Benefits of Plants in This Difficult and Unprecedented Period People are facing uncertain and difficult times in the face of the Covid-19 pandemic. The benefits of plants (psychological, health, economic, productive) in this period of forced isolation can be of key importance. If many of us have to self-isolate in urban or suburban environments, we need something to do to keep our bodies and minds active and fed. In such a challenging scenario, a vegetable garden in home spaces can bring recreational, health, economic and environmental benefits. Regardless of the Covid-19 pandemic, there is untapped potential for this kind of garden to impact environmental outcomes, public awareness, and market trends. Home vegetable gardens could provide a small-scale approach to the sustainable use of natural resources, leading towards self-sufficiency, self-regulation, sustainability, and environmental protection.

negative: Evolution of large-scale flow structures and traces of marked fluid particles within a single-aisle cabin mock-up Over the past several decades, rapidly growing popularity of airline transportation has pushed many passengers and crew to focus on potential risk of contaminant transmission during commercial air travel. Understanding airflow dynamics and transport property within an aircraft cabin is critical to creating a healthy cabin environment and improving control of epidemics. This work reveals the temporal and spatial evolution process of large-scale flow structures around the aisle region and evaluates impact of airflow’s large-scale flow structures (swing motion around the aisle region and large-scale vortices) on transport property by calculating traces of marked fluid particles (MFPs) passing through passengers’ exhalation area within a Boeing 737-200 cabin mock-up. The Peixoto theorem has been used to interpret temporal and spatial evolution process of large-scale flow structures around the aisle region. Transport property within this single-aisle aircraft cabin is a mixed effect of the airflow’s swing motion, large-scale vortices and longitudinal airflow. Airflow’s swing motion around the aisle region tends to carry MFPs nearby across the aisle region and invade the large-scale vortex in the opposite side. The large-scale vortices try to control MFPs in its each separated zone. The airflow’s swing motion and large-scale vortices dominate MFPs’ latitudinal transmission, while longitudinal airflow dominates MFPs’ longitudinal transmission.

negative: COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics The novel coronavirus infection (COVID-19 or Coronavirus disease 2019) that emerged from Wuhan, Hubei province of China has spread to many countries worldwide. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS in the past decades. However, to date, no licensed antiviral treatment or vaccine exists for MERS and SARS. Most of the efforts for developing CoV vaccines and drugs target the spike glycoprotein or S protein, the major inducer of neutralizing antibodies. Although a few candidates have shown efficacy in in vitro studies, not many have progressed to randomized animal or human trials, hence may have limited use to counter COVID-19 infection. This article highlights ongoing advances in designing vaccines and therapeutics to counter COVID-19 while also focusing on such experiences and advances as made with earlier SARS- and MERS-CoVs, which together could enable efforts to halt this emerging virus infection.

negative: [Chlamydia-like and coronavirus-like agents found in dead cases of atypical pneumonia by electron microscopy]. OBJECTIVE To explore the causative agents of the atypical pneumonia (also SARS) occurred recently in some regions of our country. METHOD Organ samples of 7 dead cases of SARS were collected from Guangdong, Shanxi, Sichuan Provinces and Beijing for electron microscopic examination. 293 cell line was inoculated with the materials derived from the lungs to isolate causative agent(s). The agents in the organs and cell cultures were revealed by immunoassay. RESULTS Both Chlamydia-like and coronavirus-like particles were found in EM. Inclusion bodies containing elementary bodies, reticulate antibodies and intermediate bodies of Chlamydia-like agent were visualized in multiple organs from the 7 dead cases, including lungs (7 cases), spleens (2 cases), livers (2 cases), kidneys (3 cases) and lymph nodes (1 cases), by ultrathin section electron microscopy (EM). In some few sections, coronavirus-like particles were concurrently seen. A coronavirus RNA- polymerase segment (440 bp) was amplified from the lung tissues of two cases of the SARS. After inoculated with materials from the lung samples, the similar Chlamydia-like particles were also found in the inoculated 293 cells. Since the Chlamydia-like agents visualized in both organs and cell cultures could not react with the genus specific antibodies against Chlamydia and monoclonal antibodies against C. pneumoniae and C. psittaci, the results might well be suggestive of a novel Chlamydia-like agent. CONCLUSION Since the novel Chlamydia-like agent was found co-existing with a coronavirus-like agent in the dead cases of SARS, it looks most likely that both the agents play some roles in the disease. At the present time, however, one can hardly determining how did these agents interact each other synergetically, or one follows another, need further study.

negative: Effects of temperature variation and humidity on the death of COVID-19 in Wuhan, China Abstract Meteorological parameters are the important factors influencing the infectious diseases such as severe acute respiratory syndrome (SARS) and influenza. This study aims to explore the association between Corona Virus Disease 2019 (COVID-19) deaths and weather parameters. In this study, we collected the daily death numbers of COVID-19, meteorological parameters and air pollutant data from 20 January 2020 to 29 February 2020 in Wuhan, China. Generalized additive model was applied to explore the effect of temperature, humidity and diurnal temperature range on the daily death counts of COVID-19. There were 2299 COVID-19 death counts in Wuhan during the study period. A positive association with COVID-19 daily death counts was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = −0.32). In addition, one unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 deaths in lag 3. However, both 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 death in lag 3 and lag 5, with the greatest decrease both in lag 3 [−7.50% (95% CI: −10.99%, −3.88%) and −11.41% (95% CI: −19.68%, −2.29%)]. In summary, this study suggests the temperature variation and humidity may also be important factors affecting the COVID-19 mortality.

negative: Optimization of the extraction of total flavonoids from Scutellaria baicalensis Georgi using the response surface methodology The response surface methodology (RSM) was used to optimize the conditions for total flavonoid extraction from Scutellaria baicalensis Georgi. The influences of the ethanol concentration, extraction time, temperature, and the liquid–solid ratio on flavonoid yield were investigated. Based on ANOVA results, a second-order quadratic polynomial model could be applied to characterize the extraction process. The following optimal extraction conditions were identified: ethanol concentration, 52.98 %; extraction time, 2.12 h; extraction temperature, 62.46 °C; and liquid–solid ratio, 35.23. The predicted extraction yield was 19.437 mg/g when these optimal conditions were used. The proposed method was successfully employed to extract flavonoids from S. baicalensis.

negative: Biosafety Level 3 Laboratory for Autopsies of Patients with Severe Acute Respiratory Syndrome: Principles, Practices, and Prospects Background. During the outbreak of the emergent severe acute respiratory syndrome (SARS) infection, >30% of the ∼8000 infected persons were health care workers. The highly infectious nature of SARS coronavirus (SARS-CoV) compelled our pathologists to consider biosafety issues in the autopsy room and for tissue processing procedures. Methods. A specially designed biosafety level 3 (BSL-3) autopsy laboratory was constructed and divided into a clean area, a semicontaminated area, a contaminated area, and 2 buffer zones. High-efficiency particulate air filters were placed in the air supply and exhaust systems. Laminar air flow was from the clean areas to the less clean areas. The negative pressures of the contaminated, semicontaminated, and clean areas were approximately -50 pa, -25 pa, and -5 pa, respectively. Personal protective equipment, including gas mask, impermeable protective clothing, and 3 layers of gloves worn during autopsies; the equipment was decontaminated before it was allowed to exit the facility. Strict BSL-3 practices were followed. Results. When a given concentration of particulate sarin simulant was introduced into the contaminated area, it could not be detected in either the semicontaminated area or clean area, and particles >0.3 μm in size were not detected in the exhaust air. A total of 16 complete postmortem examinations for probable and suspected SARS were performed during a 2-month period. Of these, 7 reported confirmed cases of SARS. None of the 23 pathologists and technicians who participated in these autopsies was infected with SARS-CoV. Conclusions. Our experience suggests that BSL-3 laboratory operating principles should be among the special requirements for performing autopsies of contaminated bodies and that they can safeguard the clinicians and the environment involved in these procedures.

negative: Potential Factors Influencing Repeated SARS Outbreaks in China Within last 17 years two widespread epidemics of severe acute respiratory syndrome (SARS) occurred in China, which were caused by related coronaviruses (CoVs): SARS-CoV and SARS-CoV-2. Although the origin(s) of these viruses are still unknown and their occurrences in nature are mysterious, some general patterns of their pathogenesis and epidemics are noticeable. Both viruses utilize the same receptor—angiotensin-converting enzyme 2 (ACE2)—for invading human bodies. Both epidemics occurred in cold dry winter seasons celebrated with major holidays, and started in regions where dietary consumption of wildlife is a fashion. Thus, if bats were the natural hosts of SARS-CoVs, cold temperature and low humidity in these times might provide conducive environmental conditions for prolonged viral survival in these regions concentrated with bats. The widespread existence of these bat-carried or -released viruses might have an easier time in breaking through human defenses when harsh winter makes human bodies more vulnerable. Once succeeding in making some initial human infections, spreading of the disease was made convenient with increased social gathering and holiday travel. These natural and social factors influenced the general progression and trajectory of the SARS epidemiology. However, some unique factors might also contribute to the origination of SARS in Wuhan. These factors are discussed in different scenarios in order to promote more research for achieving final validation.

negative: Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status Abstract Coronaviruses are a large group of viruses known to cause illnesses that vary between the common cold and more severe diseases to include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A novel coronavirus was identified in December 2019 in Wuhan city, Hubei province, China. This virus represents a new strain that has not been previously identified in humans. The virus is now known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting disease is called coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) declared the novel coronavirus outbreak a global pandemic in March 2020. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with more than 1,948,617 laboratory-confirmed cases and over 121,846 deaths worldwide. Currently, no specific medication is recommended to treat COVID-19 patients. However, governments and pharmaceutical companies are struggling to quickly find an effective drug to defeat the coronavirus. In the current review, we summarize the existing state of knowledge about COVID-19, available medications, and treatment options. Favilavir is an antiviral drug that is approved in Japan for common influenza treatment and is now approved to treat symptoms of COVID-19 in China. Moreover, Chloroquine and hydroxychloroquine, drugs used to treat malaria and arthritis, respectively, were recommended by the National Health Commission of the People's Republic of China for treatment of COVID-19. Presently, chloroquine and hydroxychloroquine are under investigation by the US Food and Drug Administration (FDA) as a treatment for COVID-19. The first COVID-19 vaccine is not expected to be ready for clinical trials before the end of the year.

negative: UV-C irradiation is able to inactivate pathogens found in commercially collected porcine plasma as demonstrated by swine bioassay Abstract Liquid porcine plasma is an animal origin raw material for the manufacturing process of spray-dried porcine plasma that is used in pig nutrition worldwide. In previous studies we found that the application of ultraviolet light C (UV-C) in liquid plasma that was inoculated with a variety of bacteria or viruses of importance in the swine industry can be considered as redundant safety steps because in general achieve around 4 logs reduction for most of these pathogens. However, the final validation of the UV-C light as safety feature should be conducted with commercial liquid plasma and using the pig bioassay model. As a first objective, the potential infectivity of a raw liquid plasma product collected from an abattoir was tested by means of a swine bioassay. We used Porcine circovirus 2 (PCV-2), a ubiquitous virus that has been systematically detected by PCR in porcine plasma at abattoirs as selection criteria for commercial liquid plasma lot. As a second aim of the study, the effects of different doses of UV-C irradiation on the selected raw liquid plasma were assayed in the animal bioassay. Moreover, other swine infecting agents, including Porcine reproductive and respiratory syndrome virus (PRRSV), were also determined in the original plasma and monitored in the inoculated animals. Pigs negative for PCV-2 and PRRSV genome and antibodies were allotted to one of five groups (6 to 8 pigs/ group) and injected intra-peritoneally with 10 mL of their assigned inoculum at 50 d of age. Negative control pigs (group 1) were injected with PBS. Positive control pigs (group 5) were injected with a PCV-2 inoculum. Groups 2, 3 and 4 were injected with liquid porcine plasma that had been subjected to 0 (raw plasma), 3000 or 9000 J/L UV-C irradiation, respectively. Group 2 pigs (0 J/L UV-C) got infection by PRRSV but no PCV-2 infection or seroconversion. However, one pig from group 2 seroconverted to Rotavirus A (RVA) and Hepatitis E virus (HEV) and three group 2 pigs seroconverted to Porcine parvovirus (PPV). Groups 1, 3 and 4 pigs showed no evidence of infection or seroconversion associated with the tested viruses or any other pathogens found in the liquid plasma before UV-C irradiation. Group 5 pigs developed PCV-2 infectivity as expected. UV-C irradiation of liquid plasma at 3000 and 9000 J/L was effective in preventing PRRSV and other pathogens transmission. Moreover, raw liquid plasma was non-infectious for PCV-2 in naïve pigs.

negative: Repurposing Antiviral Protease Inhibitors Using Extracellular Vesicles for Potential Therapy of COVID-19 In January 2020, Chinese health agencies reported an outbreak of a novel coronavirus-2 (CoV-2) which can lead to severe acute respiratory syndrome (SARS). The virus, which belongs to the coronavirus family (SARS-CoV-2), was named coronavirus disease 2019 (COVID-19) and declared a pandemic by the World Health Organization (WHO). Full-length genome sequences of SARS-CoV-2 showed 79.6% sequence identity to SARS-CoV, with 96% identity to a bat coronavirus at the whole-genome level. COVID-19 has caused over 133,000 deaths and there are over 2 million total confirmed cases as of 15 April 2020. Current treatment plans are still under investigation due to a lack of understanding of COVID-19. One potential mechanism to slow disease progression is the use of antiviral drugs to either block the entry of the virus or interfere with viral replication and maturation. Currently, antiviral drugs, including chloroquine/hydroxychloroquine, remdesivir, and lopinavir/ritonavir, have shown effective inhibition of SARS-CoV-2 in vitro. Due to the high dose needed and narrow therapeutic window, many patients are experiencing severe side effects with the above drugs. Hence, repurposing these drugs with a proper formulation is needed to improve the safety and efficacy for COVID-19 treatment. Extracellular vesicles (EVs) are a family of natural carriers in the human body. They play a critical role in cell-to-cell communications. EVs can be used as unique drug carriers to deliver protease inhibitors to treat COVID-19. EVs may provide targeted delivery of protease inhibitors, with fewer systemic side effects. More importantly, EVs are eligible for major aseptic processing and can be upscaled for mass production. Currently, the FDA is facilitating applications to treat COVID-19, which provides a very good chance to use EVs to contribute in this combat.

negative: Investigation into the causes of canine infectious respiratory disease: antibody responses to canine respiratory coronavirus and canine herpesvirus in two kennelled dog populations Two training centres for working dogs were monitored for one year to determine the presence of viruses and viral antibodies and their association with canine infectious respiratory disease (CIRD). Tonsillar swabs and serum were obtained from dogs on entry into the kennels and in regular intervals thereafter. Additional samples were collected during outbreaks of CIRD. The swabs were examined by virus culture and PCR for canine parainfluenza virus, canine adenovirus, canine herpesvirus (CHV) and canine respiratory coronavirus (CRCoV). Furthermore the prevalence of antibodies to CHV and CRCoV was determined. During this study CIRD was reported mainly in one of the two kennels investigated. In that kennel antibody responses to CRCoV indicated a seasonal occurrence of the virus, which coincided with two outbreaks of respiratory disease. CHV antibody responses were detected throughout the year. In the other kennel, which reported few cases of CIRD a high prevalence of antibodies to CRCoV was detected on entry but only sporadic seroconversions to CRCoV or CHV. By PCR three dogs were found positive for CRCoV in one kennel whereas all PCR tests for other viruses were negative for both kennels. Virus culture failed to detect any viruses in either kennel.

negative: Preparing for the Unthinkable: Emergency Preparedness for the Hematopoietic Cell Transplant Program Abstract Emergencies come at the most inopportune times. Some are totally unexpected, others come with short warnings. Although rare, an emergency comes with the potential to wreak disaster and pose serious risk to the services provided to hematopoietic cell transplant (HCT) patients. Yet, the consequences of an emergency can be mitigated by thinking the unthinkable and having a plan for emergency preparedness in place. Each HCT center should develop a plan containing steps of mitigation, preparedness, response and recovery. This report provides the framework for a HCT-specific emergency preparedness plan that can be used by individual centers to develop customized guidelines on preparing for, responding to, and recovering from an emergency.

negative: The effect of immunosuppression on protective immunity of turkey poults against infection with turkey coronavirus Abstract The objective of the present study was to evaluate the protective effect of humoral and cellular immunities on turkeys infected with turkey coronavirus (TCV). Two trials were conducted with two separate hatches of turkey poults. Turkeys were experimentally immunosuppressed with cyclosporin A (CsA) or cyclophosphamide (CY) and infected with TCV. Prior to infection, treatment with CsA selectively suppressed T cell activity as revealed by 2–3 fold decreased (p<0.1) lymphocyte proliferation responses to a T cell mitogen, concanavalin A (Con A). Treatment with CY mainly induced B cell deficiency as indicated by significant reductions (p<0.05) in antibody responses to sheep erythrocytes 7 days after injection. Body weight gain of turkeys treated with CY was significantly lower (p<0.05) than that of untreated turkeys at 9 days post-infection (PI). Turkeys treated with CY had 1–2 fold higher immunofluorescent antibody assay (IFA) scores for TCV antigens (p<0.05) in the intestine than untreated turkeys at 9 or 14 days PI. These results suggested that humoral immunity against TCV infection may be important in turkeys.

negative: New Method to Reduce COVID-19 Transmission - The Need for Medical Air Disinfection is Now

negative: Identification of a new human coronavirus Three human coronaviruses are known to exist: human coronavirus 229E (HCoV-229E), HCoV-OC43 and severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV). Here we report the identification of a fourth human coronavirus, HCoV-NL63, using a new method of virus discovery. The virus was isolated from a 7-month-old child suffering from bronchiolitis and conjunctivitis. The complete genome sequence indicates that this virus is not a recombinant, but rather a new group 1 coronavirus. The in vitro host cell range of HCoV-NL63 is notable because it replicates on tertiary monkey kidney cells and the monkey kidney LLC-MK2 cell line. The viral genome contains distinctive features, including a unique N-terminal fragment within the spike protein. Screening of clinical specimens from individuals suffering from respiratory illness identified seven additional HCoV-NL63-infected individuals, indicating that the virus was widely spread within the human population. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1024) contains supplementary material, which is available to authorized users.

negative: Middle East respiratory syndrome coronavirus: transmission and phylogenetic evolution The Middle East respiratory syndrome coronavirus (MERS-CoV) was first described in 2012 and, subsequently, many cases were reported with a lower case fatality rate than initial cases. Humans can become infected within their communities and transmission can then be amplified in the healthcare setting. Contact investigation among cases shows a variable amount of spread among family members and healthcare workers. So far, circulating virus strains remain similar under continuous monitoring, with no genetic changes. Here, we discuss the transmission pattern, phylogenetic evolution, and pathogenesis of MERS-CoV infection.

negative: Kallikrein 13: a new player in coronaviral infections Human coronavirus HKU1 (HCoV-HKU1) is associated with respiratory disease and is prevalent worldwide, but in vitro model for virus replication is lacking. Interaction between the coronaviral spike (S) protein and its receptor is the major determinant of virus tissue and host specificity, but virus entry is a complex process requiring a concerted action of multiple cellular elements. Here, we show that KLK13 is required for the infection of the human respiratory epithelium and is sufficient to mediate the entry of HCoV-HKU1 to non-permissive RD cells. We also demonstrated HCoV-HKU1 S protein cleavage by KLK13 in the S1/S2 region, proving that KLK13 is the priming enzyme for this virus. Summarizing, we show for the first time that protease distribution and specificity predetermines the tissue and cell specificity of the virus and may also regulate interspecies transmission. It is also of importance that presented data may be relevant for the emerging coronaviruses, including SARS-CoV-2 and may help to understand the differences in their zoonotic potential.

negative: Correction for Dietz et al., “2019 Novel Coronavirus (COVID-19) Pandemic: Built Environment Considerations To Reduce Transmission”

negative: Searching therapeutic strategy of new coronavirus pneumonia from angiotensin-converting enzyme 2: the target of COVID-19 and SARS-CoV Since December 2019, the infection of the new coronavirus (COVID-19) caused an outbreak of new coronavirus pneumonia in Wuhan, China, and caused great public concern. Both COVID-19 and SARS-CoV belong to the coronavirus family and both invade target cells through ACE2. An in-depth understanding of ACE2 and a series of physiological and physiological changes caused by the virus invading the human body may help to discover and explain the corresponding clinical phenomena and then deal with them timely. In addition, ACE2 is a potential therapeutic target. This article will summarize the role of ACE2 in multiple organ damage caused by COVID-19 and SARS-CoV, targeted blocking drugs against ACE2, and drugs that inhibit inflammation in order to provide the basis for subsequent related research, diagnosis and treatment, and drug development.

negative: Facemask shortage and the coronavirus disease (COVID-19) outbreak: Reflection on public health measures To the best of our knowledge, this is the first study to investigate the facemask shortage during the novel coronavirus pneumonia (COVID-19) outbreak in China. We have summarized in detail the management strategies implemented by the Chinese governments during the outbreaks. By considering three scenarios for the outbreak development, we simulated the facemasks availability from late-December 2019 to late-April 2020 and estimated the duration of sufficient facemask supplies. Our findings showed that if the COVID-19 outbreak occurred only in Wuhan city or Hubei province, facemask shortage would not appear with the existing public health measures. However, if the outbreak occurred in the whole of China, a shortage of facemask could be substantial assuming no alternative public health measures. Supplies of facemasks in the whole of China would have been sufficient for both healthcare workers and the general population if the COVID-19 outbreak only occurred in Wuhan city or Hubei province. However, if the outbreak occurred in the whole of China, facemask supplies in China could last for 5 days if under the existing public health measures and a shortage of 853 million facemasks is expected by 30 Apr 2020. Assuming a gradually decreased import volume, we estimated that dramatic increase in productivity (42.7 times of the usual level) is needed to mitigate the facemask crisis by the end of April. In light of the COVID-19 outbreak in China, a shortage of facemasks and other medical resources can considerably compromise the efficacy of public health measures. Effective public health measures should also consider the adequacy and affordability of medical resources. Global collaboration should be strengthened to prevent the development of a global pandemic from a regional epidemic via easing the medical resources crisis in the affected countries.

negative: Does form meet function in the coronavirus replicative organelle? If we use the analogy of a virus as a living entity, then the replicative organelle is the part of the body where its metabolic and reproductive activities are concentrated. Recent studies have illuminated the intricately complex replicative organelles of coronaviruses, a group that includes the largest known RNA virus genomes. This review takes a virus-centric look at the coronavirus replication transcription complex organelle in the context of the wider world of positive sense RNA viruses, examining how the mechanisms of protein expression and function act to produce the factories that power the viral replication cycle.

negative: Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6 Abstract Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells.

negative: The effect of environmental parameters on the survival of airborne infectious agents. The successful transmission of infection via the airborne route relies on several factors, including the survival of the airborne pathogen in the environment as it travels between susceptible hosts. This review summarizes the various environmental factors (particularly temperature and relative humidity) that may affect the airborne survival of viruses, bacteria and fungi, with the aim of highlighting specific aspects of environmental control that may eventually enhance the aerosol or airborne infection control of infectious disease transmission within hospitals.

negative: Overcoming regulatory gaps in biological materials oversight by enhancing IBC protocol review In the United States, several regulations and federal policies govern the use of potentially biohazardous materials in research and industry. Part of this oversight is assigned by mandate to Institutional Biosafety Committees (IBCs). However, most research entities give additional responsibilities to their IBC to take advantage of a standing body with significant expertise in review and oversight of biohazardous research. Two case studies are provided to highlight functions of the IBC which are not mandated, yet are critical for safe and responsible research. There are also types of biohazardous work that are currently unregulated and receive no review from an IBC or other group of subject matter experts, leaving a gap in safety oversight. To mitigate the hazard of working with potentially hazardous unregulated biological material, the necessity of performing a risk assessment and of performing a hazard review by subject matter experts, such as those on an IBC, is of paramount importance.

negative: Rethinking the Renin-Angiotensin System and Its Role in Cardiovascular Regulation Angiotensin-converting enzyme (ACE) plays a pivotal role in the renin-angiotensin system (RAS) and ACE-inhibitors are widely used in several clinical conditions, including hypertension and heart failure. Recently, a homologue of ACE, ACE(2) has been discovered. Both ACE and ACE(2) are emerging as key enzymes of the RAS, where ACE(2) may play a role as negative regulator of ACE. Moreover, ACE(2) appears to be an important enzyme outside the classical RAS, as it hydrolyzes apelins, dynorphin A 1-13, des-Arg-bradykinin and other peptide substrates. The precise interplay between tissue ACE, ACE(2), and their substrates and by-products are presently still unclear. ACE-inhibitors reduce angiotensin II formation and bradykinin degradation, but do not inhibit ACE(2) activity. Moreover, ACE-inhibitors differ in their affinity for tissue ACE, and it has been suggested that tissue ACE affinity might be responsible for some of the beneficial properties of these drugs. ACE-inhibitors also increase nitric oxide availability, and activate several kinases that may regulate protein synthesis by interacting with the nucleus of the cells (outside-in signaling). The outside-in signaling may also be activated by bradykinin itself. Although, the precise significance of the outside-in signaling is still unclear, this new role of ACE-inhibitors may represent a discriminant factor versus angiotensin II receptors antagonists. This mini review will summarize some new aspects concerning the recently discovered biological functions of RAS and in particular of ACE, ACE(2) and ACE-inhibitors in cardiovascular system.

negative: Middle East respiratory syndrome: An emerging coronavirus infection tracked by the crowd Abstract In 2012 in Jordan, infection by a novel coronavirus (CoV) caused the first known cases of Middle East respiratory syndrome (MERS). MERS-CoV sequences have since been found in a bat and the virus appears to be enzootic among dromedary camels across the Arabian Peninsula and in parts of Africa. The majority of human cases have occurred in the Kingdom of Saudi Arabia (KSA). In humans, the etiologic agent, MERS-CoV, has been detected in severe, mild and influenza-like illness and in those without any obvious signs or symptoms of disease. MERS is often a lower respiratory tract disease associated with fever, cough, breathing difficulties, pneumonia that can progress to acute respiratory distress syndrome, multiorgan failure and death among more than a third of those infected. Severe disease is usually found in older males and comorbidities are frequently present in cases of MERS. Compared to SARS, MERS progresses more rapidly to respiratory failure and acute kidney injury, is more often observed as severe disease in patients with underlying illnesses and is more often fatal. MERS-CoV has a broader tropism than SARS-CoV, rapidly triggers cellular damage, employs a different receptor and induces a delayed proinflammatory response in cells. Most human cases have been linked to lapses in infection prevention and control in healthcare settings, with a fifth of virus detections reported among healthcare workers. This review sets out what is currently known about MERS and the MERS-CoV, summarises the new phenomenon of crowd-sourced epidemiology and lists some of the many questions that remain unanswered, nearly three years after the first reported case.

negative: While Stability Lasts: A Stochastic Model of Stablecoins The `Black Thursday' crisis in cryptocurrency markets demonstrated deleveraging risks in over-collateralized lending and stablecoins. We develop a stochastic model of over-collateralized stablecoins that helps explain such crises. In our model, the stablecoin supply is decided by speculators who optimize the profitability of a leveraged position while incorporating the forward-looking cost of collateral liquidations, which involves the endogenous price of the stablecoin. We formally characterize stable and unstable domains for the stablecoin. We prove bounds on the probabilities of large deviations and quadratic variation in the stable domain and distinctly greater price variance in the unstable domain. The unstable domain can be triggered by large deviations, collapsed expectations, and liquidity problems from deleveraging. We formally characterize a deflationary deleveraging spiral as a submartingale that can cause such liquidity problems in a crisis. We also demonstrate `perfect' stability results in idealized settings and discuss mechanisms which could bring realistic settings closer to the idealized stable settings.

negative: Limited adaptation of chimeric H9N2 viruses containing internal genes from bat influenza viruses in chickens Abstract Influenza virus-like sequences of H17N10 and H18N11 were identified in bats, despite there has been no live virus isolated. The genetic analysis indicated that they have distinct but relatively close evolutionary relationships to known influenza A viruses. However, the infectivity and adaptation of bat influenza viruses in avian species remain unclear. In this study, two modified bat influenza viruses cH9cN2/H17 and cH9cN2/H18 containing HA and NA coding regions replaced with those of H9N2 influenza A virus were generated in the background of the H17N10 or H18N11 viruses. These two modified viruses replicated less efficiently than wild type H9N2 virus in cultured chicken cells. The mini-genome assay showed that viral ribonucleoproteins (vRNPs) of H9N2 has significantly higher polymerase activity than that of bat influenza viruses in avian cells. In chicken study, compared with H9N2 virus, which replicated and transmitted efficiently in chickens, the cH9cN2/H17 and cH9cN2/H18 viruses only replicated in chicken tracheas with lower titers. Pathological examination showed that the H9N2 caused severer lesions in lung and trachea than the modified bat influenza viruses. Notably, the cH9cN2/H18 transmitted among chickens, but not cH9cN2/H17, and chicken IFN-β antagonism results showed that H18N11 NS1 protein inhibited chicken IFN-β response more efficiently than H17N10 NS1 protein in avian cells. Taken together, our data indicated that the internal genes of bat influenza viruses adapted poorly to chickens, while the internal genes of H18N11 seemed to adapt to chickens better than H17N10.

negative: Airborne Infectious Microorganisms☆ Abstract Inhalation exposes the upper and lower respiratory tracts of humans to a variety of airborne particles and vapors. Airborne transmission of pathogenic microorganisms to humans from the environment, animals, or other humans can result in disease. Inhalation is an important route of exposure as the lung is more susceptible to infection than the gastrointestinal tract. Ingested microorganisms must pass through the acidic environment of the stomach before they can colonize tissue while inhaled microorganisms are deposited directly on the moist surfaces of the respiratory tract. Inhalation of microbial aerosols can elicit adverse human health effects including infection, allergic reaction, inflammation, and respiratory disease. Following inhalation, infectious viruses, bacteria, and fungi can establish in host cells of the respiratory tract. Some are translocated and infect the gastrointestinal tract and other tissues. This article discusses human viral, bacterial, and fungal diseases transmitted via aerosols. Viral diseases presented are influenza, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), enteric viruses related infections, hantavirus disease, measles, and varicella. Bacterial diseases are Legionnaires’ disease, tuberculosis, and nontubercule mycobacterial disease. Exposure to some Gram-negative and Gram-positive bacteria, endotoxin, and actinomycetes when dispersed through the air can result in disease following inhalation. Fungal diseases included are histoplasmosis, coccidiomycosis, blastomycosis, cryptococcosis, and aspergillosis. The threat of bioterrorism with airborne infectious agents is also briefly presented.

negative: Highly infectious SARS-CoV pseudotyped virus reveals the cell tropism and its correlation with receptor expression Abstract Studies of SARS coronavirus (SARS-CoV)—the causative agent of severe acute respiratory syndrome (SARS)—have been hampered by its high transmission rate and the pathogenicity of this virus. To permit analysis of the host range and entry mechanism of SARS-CoV, we incorporated the humanized SARS-CoV spike (S) glycoprotein into HIV particles to generate a highly infectious SARS-CoV pseudotyped virus. The infection on Vero E6—a permissive cell line to SARS-CoV—could be neutralized by sera from convalescent SARS patients, and the entry was a pH-dependent process. With these highly infectious SARS-CoV pseudotypes, several cell lines derived from various tissues were revealed as susceptible to SARS-CoV, which were highly corresponding to the expression pattern of virus’s receptor angiotensin-converting enzyme 2 (ACE2). In addition, we also demonstrated angiotensin 1 converting enzyme (ACE)—the homologue of ACE2 could not function as a receptor for SARS-CoV.

negative: School-Based Interventions in Low Socioeconomic Settings to Reduce Obesity Outcomes among Preschoolers: A Scoping Review. Pediatric obesity continues to grow globally, specifically in low-socioeconomic rural areas. Strategies that combat pediatric obesity have not yet been fully determined. While the implementation of some interventions in preschool (ages 2-5) populations have demonstrated successful results, others have proven to be inconclusive and less have focused specifically on low socioeconomic populations. This scoping review aims to examine the literature to study the effectiveness of the school-based interventions in low socioeconomic settings on adiposity-related outcomes among preschoolers. PubMed/MEDLINE and EBSCO (ERIC (Education Resource Information Center) and Food Science Source) were used to conduct the search strategy. A total of 15 studies were assessed that met the inclusion criteria: Studies that included school-based interventions; reported adiposity-related data; targeting preschoolers (2 to 5 years old) in rural/low socioeconomic/underserved/areas. Interventions were then described as successful or inconclusive based on the primary outcome. Nine out of the fifteen studies were labeled as successful, which had a reduction in adiposity-related outcomes (BMI (body mass index), BMI z-score, waist circumference, skinfold, percent body fat). Current evidence, although scarce, suggest that obesity outcomes can be targeted in low socioeconomic settings through school interventions with a multicomponent approach (nutrition and physical activity) and the inclusion of parents. Further research is needed to determine effective interventions, their efficacy, and their long-term outcomes.

negative: Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.

negative: Viruses In the past, viruses were considered nonliving infectious particles, little more than genetic material wrapped in a protein capsid. Today, virologists are beginning to think of viruses as living organisms that can be classified phylogenetically into defined species, much like any other living organism. The primary reasons for this shift in attitude can be partially attributed to the discovery of giant viruses, having large genomes and complex regulatory systems. Aside from that, it has become obvious that viruses lead complex lives; they evolve, speciate, and participate in the evolution of all classes of living organisms. In this chapter, we will discuss the early attempts to classify viruses, and review the biologic properties of the classes of virus that contain human pathogens.

negative: SARS‐associated viral hepatitis caused by a novel coronavirus: Report of three cases Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse‐transcriptase polymerase chain reaction (RT‐PCR) using enhanced real‐time PCR was applied to look for evidence of SARS‐associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki‐67. RT‐PCR showed evidence of SARS‐associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro‐ or macro‐vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS‐associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course. (Hepatology 2004;39:302–310.)

negative: Characterization of a coronavirus II. Glycoproteins of the viral envelope: Tryptic peptide analysis Abstract Two species of membrane-associated glycoproteins have been identified in the coronavirus virion. They are readily distinguished on the basis of size, radiolabeling characteristics, and location in relation to the lipid bilayer. The larger glycoprotein is highly labeled by both radiolabeled fucose and glucosamine. This species is found in two forms, GP180 and GP90, with apparent molecular weights of 180,000 and 90,000. GP180 can be converted to GP90 in vitro by treatment of virions with trypsin. Analysis of tryptic digests of GP90 and GP180 give identical peptide patterns. Based on pronase and bromelain sensitivities, GP180/90 is the only protein which is located entirely external to the viral envelope. It appears to comprise the characteristic long, petal-shaped peplomers of the virion. The smaller glycoprotein, GP23, has an apparent molecular weight of 23,000 and is labeled by radiolabeled glucosamine but not by fucose. The level of glucosamine-labeling of GP23 is about 1/10 that of GP180/90. GP23 appears to possess two distinct domains: a smaller, carbohydrate containing region which is found outside the viral envelope, and a larger portion, highly labeled by methionine, which is integrally associated with the viral membrane. A new nomenclature is proposed for the three major coronavirus structural proteins. The two envelope glycoproteins, GP23 and GP180/90 are designated E1 and E2, respectively; the inner core protein, VP50, is designated N.

negative: Full genome characterization of two novel Alpha-coronavirus species from Italian bats Abstract Coronaviruses (CoVs) have been detected worldwide in several bat species, which are considered the main reservoir. The attention to the high diversity of CoVs hosted by bats has increased during the last decade due to the high number of human infections caused by two zoonotic Beta-CoVs, SARS-CoV and MERS-CoV, that cause several respiratory diseases. Among coronaviruses, two Alpha-CoV strains (HuCoV-229E and HuCoV-NL63) cause mild respiratory disease that can change to severe disease in children, elderly and individuals affected by illnesses. Phylogenetic analysis conducted on bat Alpha-CoV strains revealed their evolutive correlation to human strains, suggesting their origin in bats. The genome of CoVs is characterized by a high frequency of mutations and recombination events, increasing their ability to switch hosts and their zoonotic potential. In this study, three strains of Alpha-CoV genera detected in Italian bats (Pipistrellus kuhlii) were fully sequenced by Next Generation Sequencing (NGS) and characterized. The complete genome analysis showed the correlation of the Italians strains with a Chinese strain detected in 2013 and, based on CoV molecular species demarcation, two new Alpha-CoV species were established. The analysis of a fragment of the RNA-dependent RNA polymerase (RdRp) showed the correlation of the Italian strains with CoVs that was only detected in the bat Pipistrellus genera (Pipistrellus kuhlii and Pipistrellus Pipistrellus) in European countries.

negative: From SARS to MERS, Thrusting Coronaviruses into the Spotlight Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders. In this review, we focus on our current understanding of the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, as well as provides details on the pivotal structure and function of the spike proteins (S proteins) on the surface of each of these viruses. For building up more suitable animal models, we compare the current animal models recapitulating pathogenesis and summarize the potential role of host receptors contributing to diverse host affinity in various species. We outline the research still needed to fully elucidate the pathogenic mechanism of these viruses, to construct reproducible animal models, and ultimately develop countermeasures to conquer not only SARS-CoV and MERS-CoV, but also these emerging coronaviral diseases.

negative: Necessitating repeated chest CT in COVID-19 pneumonia

negative: Transmission Dynamics of 2019-nCoV in Malaysia This paper focuses on the formulation of a deterministic 2019-nCov transmission model by considering the exposed and recovered populations with immunity. The scenario of the simulation is depicted based on the patient zero in Malaysia. The transmission model is found to be able to predict the next confirmed case given a single case introduced in a fully susceptible population. The mathematical model is developed based on the SEIR model which has susceptible, exposed, infectious and recovered populations. The system of equations which were obtained were solved numerically and the simulation results were analyzed. The analysis includes the impact of the disease if no control is taken.

negative: Risk estimation of the SARS-CoV-2 acute respiratory disease outbreak outside China BACKGROUND: On December 31, 2019, the World Health Organization was alerted to the occurrence of cases of pneumonia in Wuhan, Hubei Province, China, that were caused by an unknown virus, which was later identified as a coronavirus and named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to estimate the reproductive number of SARS-CoV-2 in the Hubei Province and evaluate the risk of an acute respiratory coronavirus disease (COVID-19) outbreak outside China by using a mathematical model and stochastic simulations. RESULTS: We constructed a mathematical model of SARS-CoV-2 transmission dynamics, estimated the rate of transmission, and calculated the reproductive number in Hubei Province by using case-report data from January 11 to February 6, 2020. The possible number of secondary cases outside China was estimated by stochastic simulations in various scenarios of reductions in the duration to quarantine and rate of transmission. The rate of transmission was estimated as 0.8238 (95% confidence interval [CI] 0.8095-0.8382), and the basic reproductive number as 4.1192 (95% CI 4.0473-4.1912). Assuming the same rate of transmission as in Hubei Province, the possibility of no local transmission is 54.9% with a 24-h quarantine strategy, and the possibility of more than 20 local transmission cases is 7% outside of China. CONCLUSION: The reproductive number for SARS-CoV-2 transmission dynamics is significantly higher compared to that of the previous SARS epidemic in China. This implies that human-to-human transmission is a significant factor for contagion in Hubei Province. Results of the stochastic simulation emphasize the role of quarantine implementation, which is critical to prevent and control the SARS-CoV-2 outbreak outside China.

negative: Estimation of airborne viral emission: quanta emission rate of SARS-CoV-2 for infection risk assessment Airborne transmission is a pathway of contagion that is still not sufficiently investigated despite the evidence in the scientific literature of the role it can play in the context of an epidemic. While the medical research area dedicates efforts to find cures and remedies to counteract the effects of a virus, the engineering area is involved in providing risk assessments in indoor environments by simulating the airborne transmission of the virus during an epidemic. To this end, virus air emission data are needed. Unfortunately, this information is usually available only after the outbreak, based on specific reverse engineering cases. In this work, a novel approach to estimate the viral load emitted by a contagious subject on the basis of the viral load in the mouth, the type of respiratory activity (e.g. breathing, speaking), respiratory physiological parameters (e.g. inhalation rate), and activity level (e.g. resting, standing, light exercise) is proposed. The estimates of the proposed approach are in good agreement with values of viral loads of well-known diseases from the literature. The quanta emission rates of an asymptomatic SARS-CoV-2 infected subject, with a viral load in the mouth of 108 copies mL-1, were 10.5 quanta h-1 and 320 quanta h-1 for breathing and speaking respiratory activities, respectively, at rest. In the case of light activity, the values would increase to 33.9 quanta h-1 and 1.03×103 quanta h-1, respectively. The findings in terms of quanta emission rates were then adopted in infection risk models to demonstrate its application by evaluating the number of people infected by an asymptomatic SARS-CoV-2 subject in Italian indoor microenvironments before and after the introduction of virus containment measures. The results obtained from the simulations clearly highlight that a key role is played by proper ventilation in containment of the virus in indoor environments.

negative: A review of studies on animal reservoirs of the SARS coronavirus Abstract In this review, we summarize the researches on animal reservoirs of the SARS coronavirus (SARS-CoV). Masked palm civets were suspected as the origin of the SARS outbreak in 2003 and was confirmed as the direct origin of SARS cases with mild symptom in 2004. Sequence analysis of the SARS-CoV-like virus in masked palm civets indicated that they were highly homologous to human SARS-CoV with nt identity over 99.6%, indicating the virus has not been circulating in the population of masked palm civets for a very long time. Alignment of 10 complete viral genome sequences from masked palm civets with those of human SARS-CoVs revealed 26 conserved single-nucleotide variations (SNVs) in the viruses from masked palm civets. These conserved SNVs were gradually lost from the genomes of viruses isolated from the early phase to late phase human patients of the 2003 SARS epidemic. In 2005, horseshoe bats were identified as the natural reservoir of a group of coronaviruses that are distantly related to SARS-CoV. The genome sequences of bat SARS-like coronavirus had about 88–92% nt identity with that of the SARS-CoV. The prevalence of antibodies and viral RNA in different bat species and the characteristics of the bat SARS-like coronavirus were elucidated. Apart from masked palm civets and bats, 29 other animal species had been tested for the SARS-CoV, and the results are summarized in this paper.

negative: Searching for the cause of Kawasaki disease — cytoplasmic inclusion bodies provide new insight Kawasaki disease (KD) has emerged as the most common cause of acquired heart disease in children in the developed world. The cause of KD remains unknown, although an as-yet unidentified infectious agent might be responsible. By determining the causative agent, we can improve diagnosis, therapy and prevention of KD. Recently, identification of an antigen-driven IgA response that was directed at cytoplasmic inclusion bodies in KD tissues has provided new insights that could unlock the mysteries of KD.

negative: Polyphyletic origin of MERS coronaviruses and isolation of a novel clade A strain from dromedary camels in the United Arab Emirates Little is known regarding the molecular epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) circulating in dromedaries outside Saudi Arabia. To address this knowledge gap, we sequenced 10 complete genomes of MERS-CoVs isolated from 2 live and 8 dead dromedaries from different regions in the United Arab Emirates (UAE). Phylogenetic analysis revealed one novel clade A strain, the first detected in the UAE, and nine clade B strains. Strain D998/15 had a distinct phylogenetic position within clade A, being more closely related to the dromedary isolate NRCE-HKU205 from Egypt than to the human isolates EMC/2012 and Jordan-N3/2012. A comparison of predicted protein sequences also demonstrated the existence of two clade A lineages with unique amino acid substitutions, A1 (EMC/2012 and Jordan-N3/2012) and A2 (D998/15 and NRCE-HKU205), circulating in humans and camels, respectively. The nine clade B isolates belong to three distinct lineages: B1, B3 and B5. Two B3 strains, D1271/15 and D1189.1/15, showed evidence of recombination between lineages B4 and B5 in ORF1ab. Molecular clock analysis dated the time of the most recent common ancestor (tMRCA) of clade A to March 2011 and that of clade B to November 2011. Our data support a polyphyletic origin of MERS-CoV in dromedaries and the co-circulation of diverse MERS-CoVs including recombinant strains in the UAE.

negative: A case of COVID-19 with long duration of viral shedding

negative: Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study BACKGROUND: The novel coronavirus disease 2019 (COVID-19) epidemic has spread from China to 25 countries. Local cycles of transmission have already occurred in 12 countries after case importation. In Africa, Egypt has so far confirmed one case. The management and control of COVID-19 importations heavily rely on a country's health capacity. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of COVID-19. METHODS: We used data on the volume of air travel departing from airports in the infected provinces in China and directed to Africa to estimate the risk of importation per country. We determined the country's capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulations Monitoring and Evaluation Framework; and vulnerability, using the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing most to their risk. FINDINGS: Countries with the highest importation risk (ie, Egypt, Algeria, and South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (ie, Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya) have variable capacity and high vulnerability. We identified three clusters of countries that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and the city of Beijing, respectively. INTERPRETATION: Many countries in Africa are stepping up their preparedness to detect and cope with COVID-19 importations. Resources, intensified surveillance, and capacity building should be urgently prioritised in countries with moderate risk that might be ill-prepared to detect imported cases and to limit onward transmission. FUNDING: EU Framework Programme for Research and Innovation Horizon 2020, Agence Nationale de la Recherche.

negative: The impact of the SARS‐CoV‐2 outbreak on the safety and availability of blood transfusions in Italy Coronaviruses are enveloped single-stranded RNA viruses belonging to the family of Coronaviridae. While initial research focused on their ability to cause enzootic infections, infections which have emerged in the past two decades demonstrate their ability to cross the species barrier and infect humans [1,2]. The ensuing epidemics have included Severe Acute Respiratory Syndrome (SARS) in 2002 and the more recent Middle East Respiratory Syndrome (MERS) in 2012, and have resulted in severe disease burden, mortality and economic disruption [3]. A novel flu-like coronavirus, emerging towards the end of 2019 and subsequently named SARS-CoV-2, has been associated with an epidemic initially focused in Wuhan, China.

negative: Robot assisted surgery during the COVID-19 pandemic, especially for gynecological cancer: a statement of the Society of European Robotic Gynaecological Surgery (SERGS) All surgery performed in an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, irrespective of the known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status of the patient, should be regarded as high risk and protection of the surgical team at the bedside should be at the highest level. Robot assisted surgery (RAS) may help to reduce hospital stay for patients that urgently need complex-oncological-surgery, thus making room for COVID-19 patients. In comparison to open or conventional laparoscopic surgery, RAS potentially reduces not only contamination with body fluids and surgical gasses of the surgical area but also the number of directly exposed medical staff. A prerequisite is that general surgical precautions under COVID-19 circumstances must be taken, with the addition of prevention of gas leakage: • Use highest protection level III for bedside assistant, but level II for console surgeon. • Reduce the number of staff at the operation room. • Ensure safe and effective gas evacuation. • Reduce the intra-abdominal pressure to 8 mmHg or below. • Minimize electrocautery power and avoid use of ultrasonic sealing devices. • Surgeons should avoid contact outside theater (both in and out of the hospital).

negative: Pandemic Influenza Planning for the Mental Health Security of Survivors of Mass Deaths Influenza A pandemics have been documented to occur at 10- to 50-year intervals—an average of three events per century, dating back from the 16th century. Each recorded pandemic has resulted in an increase in annual mortality rates in the infected population, with mass deaths in one pandemic wave equalling fatalities sustained over six months of an epidemic season. This chapter aims to rectify the oversight in pandemic preparedness plans by presenting a compendium of guidelines and recommendations by international health organisations, pandemic fatality experts, and experienced mass death management professionals. Its objective is to have available a mass fatality framework to complement the WHO Pandemic Influenza Preparedness and Response (2009) guideline, from which individual national pandemic preparedness plans are based. It is written in a format that incorporates WHO’s emphasis on finding the ethical balance between human rights and successful plan implementation; the assimilation of national pandemic plans with existing national emergency measures; and the ‘whole group’ system of engaging individuals, families, localities, and business establishments in the process. This chapter is also written such that it can be made applicable to analogous infectious disease outbreaks such as SARS and Ebola, as well as comparable mass fatality events.

negative: Indomethacin has a potent antiviral activity against SARS CoV-2 in vitro and canine coronavirus in vivo Background The outbreak of SARS CoV-2 has caused ever-increasing attention and public panic all over the world. Currently, there is no specific treatment against the SARS CoV-2. Therefore, identifying effective antiviral agents to combat the disease is urgently needed. Previous studies found that indomethacin has the ability to inhibit the replication of several unrelated DNA and RNA viruses, including SARS-CoV. Methods SARS CoV-2 pseudovirus-infected African green monkey kidney VERO E6 cells treated with different concentrations of indomethacin or aspirin at 48 hours post infection (p.i). The level of cell infection was determined by luciferase activity. Anti-coronavirus efficacy in vivo was confirmed by evaluating the time of recovery in canine coronavirus (CCV) infected dogs treated orally with 1mg/kg body weight indomethacin. Results We found that indomethacin has a directly and potently antiviral activity against the SARS CoV-2 pseudovirus (reduce relative light unit to zero). In CCV-infected dogs, recovery occurred significantly sooner with symptomatic treatment + oral indomethacin (1 mg/kg body weight) daily treatments than with symptomatic treatment + ribavirin (10-15 mg/kg body weight) daily treatments (P =0.0031), but was not significantly different from that with symptomatic treatment + anti-canine coronavirus serum + canine hemoglobin + canine blood immunoglobulin + interferon treatments (P =0.7784). Conclusion The results identify indomethacin as a potent inhibitor of SARS CoV-2.

negative: Coronavirus questions that will not go away: interrogating urban and socio-spatial implications of COVID-19 measures The highly contagious coronavirus and the rapid spread of COVID-19 disease have generated a global public health crisis, which is being addressed at various local and global scales through social distancing measures and guidelines. This is coupled with debates about the nature of living and working patterns through intensive utilisation of information and telecommunication technologies, leading to the social and institutional acceptability of these patterns as the ‘new normal.’ The primary objective of this article is to instigate a discourse about the potential contribution of architecture and urban design and planning in generating knowledge that responds to pressing questions about future considerations of post pandemic architecture and urbanism. Methodologically, the discussion is based on a trans-disciplinary framework, which is utilised for conceptual analysis and is operationalized by identifying and discoursing design and planning implications. The article underscores relevant factors; originates insights for areas where future research will be critically needed, through key areas: a) Issues related to urban dynamics are delineated from the perspective of urban and human geography, urban design and planning, and transportation engineering; b) Questions that pertain to socio-spatial implications and urban space/ urban life dialectics stem from the field of environmental psychology; and c) Deliberations about new environments that accommodate new living/working styles supervene from ethnographical and anthropological perspectives. The article concludes with an outlook that captures key aspects of the needed synergy between architectural and urban education, research, and practice and public health in a post pandemic virtual and global world.

negative: Sustained fecal-oral human-to-human transmission following a zoonotic event Bacterial, viral and parasitic zoonotic pathogens that transmit via the fecal-oral route have a major impact on global health. However, the mechanisms underlying the emergence of such pathogens from the animal reservoir and their persistence in the human population are poorly understood. Here, we present a framework of human-to-human transmission of zoonotic pathogens that considers the factors relevant for fecal-oral human-to-human transmission route at the levels of host, pathogen, and environment. We discuss current data gaps and propose future research directions.

negative: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers Abstract Background and aims COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). Methods We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. Results From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. Conclusion Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.

negative: Spinal anaesthesia for patients with coronavirus disease 2019 and possible transmission rates in anaesthetists: retrospective, single-centre, observational cohort study BACKGROUND: The safety of performing spinal anaesthesia for both patients and anaesthetists alike in the presence of active infection with the novel coronavirus disease 2019 (COVID-19) is unclear. Here, we report the clinical characteristics and outcomes for both patients with COVID-19 and the anaesthetists who provided their spinal anaesthesia. METHODS: Forty-nine patients with radiologically confirmed COVID-19 for Caesarean section or lower-limb surgery undergoing spinal anaesthesia in Zhongnan Hospital, Wuhan, China participated in this retrospective study. Clinical characteristics and perioperative outcomes were recorded. For anaesthesiologists exposed to patients with COVID-19 by providing spinal anaesthesia, the level of personal protective equipment (PPE) used, clinical outcomes (pulmonary CT scans), and confirmed COVID-19 transmission rates (polymerase chain reaction [PCR]) were reviewed. RESULTS: Forty-nine patients with COVID-19 requiring supplementary oxygen before surgery had spinal anaesthesia (ropivacaine 0.75%), chiefly for Caesarean section (45/49 [91%]). Spinal anaesthesia was not associated with cardiorespiratory compromise intraoperatively. No patients subsequently developed severe pneumonia. Of 44 anaesthetists, 37 (84.1%) provided spinal anaesthesia using Level 3 PPE. Coronavirus disease 2019 infection was subsequently confirmed by PCR in 5/44 (11.4%) anaesthetists. One (2.7%) of 37 anaesthetists who wore Level 3 PPE developed PCR-confirmed COVID-19 compared with 4/7 (57.1%) anaesthetists who had Level 1 protection in the operating theatre (relative risk reduction: 95.3% [95% confidence intervals: 63.7–99.4]; P<0.01). CONCLUSIONS: Spinal anaesthesia was delivered safely in patients with active COVID-19 infection, the majority of whom had Caesarean sections. Level 3 PPE appears to reduce the risk of transmission to anaesthetists who are exposed to mildly symptomatic surgical patients.

negative: How to Handle a COVID-19 Patient in the Angiographic Suite This is a single-center report on coordination of staff and handling of patients during the outbreak of the COVID-19 (coronavirus disease 2019) in a region with high incidence and prevalence of disease. The selection of procedures for interventional radiology (IR), preparation of staff and interventional suite before the arrival of patients, the facility ventilation systems and intra- and post-procedural workflow optimization are described. The control measures described may increase the cost of the equipment, prolong procedural times and increase technical difficulties. However, these precautions may help control the spread of COVID-19 within the healthcare facility.

negative: The stability of the duplex between sense and antisense transcription-regulating sequences is a crucial factor in arterivirus subgenomic mRNA synthesis. Subgenomic mRNAs of nidoviruses (arteriviruses and coronaviruses) are composed of a common leader sequence and a "body" part of variable size, which are derived from the 5'- and 3'-proximal part of the genome, respectively. Leader-to-body joining has been proposed to occur during minus-strand RNA synthesis and to involve transfer of the nascent RNA strand from one site in the template to another. This discontinuous step in subgenomic RNA synthesis is guided by short transcription-regulating sequences (TRSs) that are present at both these template sites (leader TRS and body TRS). Sense-antisense base pairing between the leader TRS in the plus strand and the body TRS complement in the minus strand is crucial for strand transfer. Here we show that extending the leader TRS-body TRS duplex beyond its wild-type length dramatically enhanced the subgenomic mRNA synthesis of the arterivirus Equine arteritis virus (EAV). Generally, the relative amount of a subgenomic mRNA correlated with the calculated stability of the corresponding leader TRS-body TRS duplex. In addition, various leader TRS mutations induced the generation of minor subgenomic RNA species that were not detected upon infection with wild-type EAV. The synthesis of these RNA species involved leader-body junction events at sites that bear only limited resemblance to the canonical TRS. However, with the mutant leader TRS, but not with the wild-type leader TRS, these sequences could form a duplex that was stable enough to direct subgenomic RNA synthesis, again demonstrating that the stability of the leader TRS-body TRS duplex is a crucial factor in arterivirus subgenomic mRNA synthesis.

negative: COVID-19 Epidemic Outside China: 34 Founders and Exponential Growth Background: In December 2019, pneumonia infected with a novel coronavirus burst in Wuhan, China. Now the situation is almost controlled in China but is worse outside China. We aimed to build a mathematical model to capture the global trend of epidemics outside China. Methods: In this retrospective, outside-China diagnosis number reported from Jan 21 to Feb 28, 2020 was downloaded from WHO website. We develop a simple regression model on these numbers: log10 (Nt+34)=0.0515*t+2.075 where Nt is the total diagnosed patient till the ith day, t=1 at Feb 1. Findings: Based on this model, we estimate that there have been about 34 unobserved founder patients at the beginning of spread outside China. The global trend is approximately exponential, with the rate of 10 folds every 19 days.

negative: South Korea’s COVID-19 Infection Status: From the Perspective of Re-positive Test Results After Viral Clearance Evidenced by Negative Test Results Coronavirus disease (COVID-19) started to occur in South Korea by means of inflow of the virus from abroad, when a case from Wuhan, China, was first confirmed on January 19, 2020. Although South Korea has drastically reduced the number of new confirmed cases and is stabilizing the situation with its exemplary disease prevention policies, there remains a problem. These are cases that had shown negative results to polymerase chain reaction (PCR) (gene amplification) tests as the COVID-19 virus had become undetectable but turned re-positive after a short period. The Central Clinical Committee determined that these re-positive cases after COVID-19 viral clearance are due to the limits of the test method; it is considered that the genetic material of the “dead virus” remaining in a recovered patient’s body is amplified during the test process. Comprehending the above evidence, re-positive cases of COVID-19 are not infectious; the virus is not even reactivated. However, further research is required as we lack research results on this subject. Until we can be sure, social distancing and other such policies should be maintained.

negative: Mechanism for noncompetitive inhibition by novel GluN2C/D N-methyl-D-aspartate receptor subunit-selective modulators. The compound 4-(5-(4-bromophenyl)-3-(6-methyl-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid (DQP-1105) is a representative member of a new class of N-methyl-d-aspartate (NMDA) receptor antagonists. DQP-1105 inhibited GluN2C- and GluN2D-containing receptors with IC(50) values that were at least 50-fold lower than those for recombinant GluN2A-, GluN2B-, GluA1-, or GluK2-containing receptors. Inhibition was voltage-independent and could not be surmounted by increasing concentrations of either coagonist, glutamate or glycine, consistent with a noncompetitive mechanism of action. DQP-1105 inhibited single-channel currents in excised outside-out patches without significantly changing mean open time or single-channel conductance, suggesting that DQP inhibits a pregating step without changing the stability of the open pore conformation and thus channel closing rate. Evaluation of DQP-1105 inhibition of chimeric NMDA receptors identified two key residues in the lower lobe of the GluN2 agonist binding domain that control the selectivity of DQP-1105. These data suggest a mechanism for this new class of inhibitors and demonstrate that ligands can access, in a subunit-selective manner, a new site located in the lower, membrane-proximal portion of the agonist-binding domain.

negative: Feeding behavior during sialodacryoadenitis viral infection in rats Abstract Sialodacryoadenitis (SDA) is a highly contagious common viral infection in rats, akin to mumps in humans. Anorexia occurs during such viral infection. But the pattern of the decrease in food intake (a decrease in either meal size and meal number or both) during spontaneous viral infection has not been previously characterized. We observed the onset of anorexia and an abnormal feeding pattern during an opportunistic SDA viral infection in our rat colony. We thus studied seven male rats. Before the viral infection there was a positive association between food intake and meal number (P<.05). After infection food intake decreased by 68%. This occurred via a significant decrease in meal size (by 69%) (P<.05); and a nonsignificant decrease in meal number (P=.71). This pattern of decreased food intake is similar to that occurring during indomethacin-induced ulcerative ileitis, where we previously measured an increase in plasma tumor-necrosis factor (TNF)-α. Anorexia in response to bacterial lipopolysaccharide administration, which is also linked to plasma TNF-α, is however, caused only via a decrease in meal number. The differences in the decrease in the feeding pattern between the SDA viral and a bacterial infection suggest that factors other than TNF-α alone play a significant role in the mechanism of anorexia during a viral infection.

negative: The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19 Wuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus.

negative: Novel coronavirus (COVID-19) infection: What a doctor on the frontline needs to know Coronavirus disease 2019 (COVID-19) is a zoonotic respiratory infection originating from Wuhan, China. Rapidly spreading from Wuhan to all inhabited continents of the world, the World Health Organisation declared COVID-19 a pandemic on March 11, 2019. Infected patients present with fever and cough; radiological features include bilateral infiltrates on chest x-ray and computed tomography scanning. Management is supportive with oxygen supplementation, broad-spectrum antibiotics as well as careful fluid balancing. A number of drugs, both new and old, are currently in clinical trials and being used on an experimental basis in clinical practice. The COVID-19 pandemic is the greatest worldwide public health crisis of a generation, and has led to seismic political, economic and social changes. This review provides an overview of COVID-19 for junior doctors who find themselves on a new frontline of healthcare.

negative: Cough aerosol in healthy participants: fundamental knowledge to optimize droplet-spread infectious respiratory disease management BACKGROUND: The Influenza A H1N1 virus can be transmitted via direct, indirect, and airborne route to non-infected subjects when an infected patient coughs, which expels a number of different sized droplets to the surrounding environment as an aerosol. The objective of the current study was to characterize the human cough aerosol pattern with the aim of developing a standard human cough bioaerosol model for Influenza Pandemic control. METHOD: 45 healthy non-smokers participated in the open bench study by giving their best effort cough. A laser diffraction system was used to obtain accurate, time-dependent, quantitative measurements of the size and number of droplets expelled by the cough aerosol. RESULTS: Voluntary coughs generated droplets ranging from 0.1 - 900 microns in size. Droplets of less than one-micron size represent 97% of the total number of measured droplets contained in the cough aerosol. Age, sex, weight, height and corporal mass have no statistically significant effect on the aerosol composition in terms of size and number of droplets. CONCLUSIONS: We have developed a standard human cough aerosol model. We have quantitatively characterized the pattern, size, and number of droplets present in the most important mode of person-to-person transmission of IRD: the cough bioaerosol. Small size droplets (< 1 μm) predominated the total number of droplets expelled when coughing. The cough aerosol is the single source of direct, indirect and/or airborne transmission of respiratory infections like the Influenza A H1N1 virus. STUDY DESIGN: Open bench, Observational, Cough, Aerosol study

negative: Behavioral Welfare Economics A growing body of normative work explores whether and how deference to people’s choices might be reconciled with behavioral findings about human error. This work has strong implications for economic analysis of law, cost–benefit analysis, and regulatory policy. In light of behavioral findings, regulators should adopt a working presumption in favor of respect for people’s self-regarding choices, but only if those choices are adequately informed and sufficiently free from behavioral biases. The working presumption should itself be rebuttable on welfare grounds, with an understanding that the ends that people choose might make their lives go less well. For example, people might die prematurely or suffer from serious illness, and what they receive in return might not (on any plausible account of welfare) be nearly enough. The underlying reason might involve a lack of information or a behavioral bias, identifiable or not, in which case intervention can fit with the working presumption, but the real problem might involve philosophical questions about the proper understanding of welfare, and about what it means for people to have a good life.

negative: Method for contamination of filtering facepiece respirators by deposition of MS2 viral aerosols Abstract A droplet/aerosol loading chamber was designed to deliver uniform droplets/aerosols onto substrates. An ultrasonic nebulizer was used to produce virus-containing droplets from artificial saliva to emulate those from coughing and sneezing. The operating conditions were determined by adjusting various parameters to achieve loading density and uniformity requirements. The count median diameter and mass median diameter were 0.5–2 and 3–4μm, respectively, around the loading location when 35% relative humidity was applied. The average loading density was ∼2×103 plaque-forming units/cm2 for 5-min loading time with a virus titer of 107 plaque-forming units/mL. Six different filtering facepiece respirators from commercial sources were loaded to evaluate uniform distribution. For each of the six FFRs, the virus loading uniformity within a sample and across numerous samples was 19.21% and 12.20%, respectively. This system supports a standard method for loading viable bioaerosols onto specimen surfaces when different decontamination techniques are to be compared.

negative: Revisiting the dangers of the coronavirus in the ophthalmology practice

negative: Environmental contamination of SARS-CoV-2 during the COVID-19 outbreak in South Korea OBJECTIVES: Although contact precaution is generally recommended in situations where coronavirus disease 2019 (COVID-19) is suspected, there is limited evidence on environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we conducted environmental surveillance on SARS-CoV-2 contamination in 2 different healthcare settings. METHODS: Viral contamination was investigated on the environment of 2 hospitals that had admitted 13 COVID-19 patients. In hospital A, 5 patients with pneumonia occupied negative pressure rooms. In hospital B, 8 asymptomatic patients shared 2 common 4-bed rooms. Most rooms were poorly cleaned or disinfected. Environmental swab were collected from inside and outside the rooms and were tested using real-time RT-PCR for the detection of SARS-CoV-2. RESULTS: In hospital A, SARS-CoV-2 was detected in 10 of 57 (17.5%) samples from inside the rooms including the Ambu bag and infusion pump. Two samples obtained at more than 2 m from the patients showed positive results. In hospital B, 3 of 22 (13.6%) samples from inside the rooms were positive. Areas outside the rooms, such as the anteroom, corridor, and nursing station, were all negative in both hospitals. CONCLUSIONS: Hospital surfaces surrounding patients were contaminated by SARS-CoV-2. Our findings support the value of strict contact precaution, routine cleaning, and disinfection in the management of COVID-19 patients.

negative: Structural basis to design multi-epitope vaccines against Novel Coronavirus 19 (COVID19) infection, the ongoing pandemic emergency: an in silico approach The 2019 novel coronavirus (COVID19 / Wuhan coronavirus), officially named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a positive-sense single-stranded RNA coronavirus. SARS-CoV-2 causes the contagious COVID19 disease also known as 2019-nCoV acute respiratory disease and has led to the ongoing 2019–20 pandemic COVID19 outbreak. The effective counter measures against SARS-CoV-2 infection require the design and development of specific and effective vaccine candidate. In the present study, we have screened and shortlisted 38 CTL, 33 HTL and 12 B cell epitopes from the eleven Protein sequences of SARS-CoV-2 by utilizing different in silico tools. The screened epitopes were further validated for their binding with their respective HLA allele binders and TAP (Transporter associated with antigen processing) molecule by molecular docking. The shortlisted screened epitopes were further utilized to design novel two multi-epitope vaccines (MEVs) composed of CTL, HTL and B cell epitopes overlaps with potential to elicit humoral as well as cellular immune response against SARS-CoV-2. To enhance the immune response for our vaccine design, truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has been utilized as an adjuvant at N terminal of both the MEVs. Further molecular models for both the MEVs were prepared and validated for their stable molecular interactions with Toll-Like Receptor 3 (TLR 3). The codon-optimized cDNA of both the MEVs were further analyzed for their potential of high level of expression in a human cell line. The present study is very significant in terms of molecular designing of prospective CTL and HTL vaccine against SARS-CoV-2 infection with the potential to elicit cellular as well as humoral immune response. (SARS-CoV-2), Coronavirus, Human Transporter associated with antigen processing (TAP), Toll-Like Receptor (TLR), Epitope, Immunoinformatics, Molecular Docking, Molecular dynamics simulation, Multi-epitope Vaccine Graphical abstract The designed CTL (Cytotoxic T lymphocyte) and HTL (Helper T lymphocyte) multi-epitope vaccines (MEV) against COVID19 infection. Both the CTL and HTL MEV models show a very stable and well fit conformational complex formation tendency with the Toll like receptor 3. CTL and HTL MEVs: ribbon; Toll like receptor 3: gray cartoon; Adjuvant [truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1]: orange ribbon regions; Epitopes: cyan ribbons regions; 6xHis Tag: magenta ribbon regions.

negative: Political Intrusions into the International Health Regulations Treaty and Its Impact on Management of Rapidly Emerging Zoonotic Pandemics: What History Tells Us For a large number of health care providers world-wide, the coronavirus disease 2019 (COVID-19) pandemic is their first experience in population-based care. In past decades, lower population densities, infectious disease outbreaks, epidemics, and pandemics were rare and driven almost exclusively by natural disasters, predatory animals, and war. In the early 1900s, Sir William Osler first advanced the knowledge of zoonotic diseases that are spread from reservoir animals to human animals. Once rare, they now make up 71% or more of new diseases. Globally, zoonotic spread occurs for many reasons. Because the human population has grown in numbers and density, the spread of these diseases accelerated though rapid unsustainable urbanization, biodiversity loss, and climate change. Furthermore, they are exacerbated by an increasing number of vulnerable populations suffering from chronic deficiencies in food, water, and energy. The World Health Organization (WHO) and its International Health Regulation (IHR) Treaty, organized to manage population-based diseases such as Influenza, severe acute respiratory syndrome (SARS), H1N1, Middle East respiratory syndrome (MERS), HIV, and Ebola, have failed to meet population-based expectations. In part, this is due to influence from powerful political donors, which has become most evident in the current COVID-19 pandemic. The global community can no longer tolerate an ineffectual and passive international response system, nor tolerate the self-serving political interference that authoritarian regimes and others have exercised over the WHO. In a highly integrated globalized world, both the WHO with its IHR Treaty have the potential to become one of the most effective mechanisms for crisis response and risk reduction world-wide. Practitioners and health decision-makers must break their silence and advocate for a stronger treaty, a return of the WHO’s singular global authority, and support highly coordinated population-based management. As Osler recognized, his concept of “one medicine, one health” defines what global public health is today.

negative: Severe Acute Respiratory Syndrome Coronavirus 2 from Patient with Coronavirus Disease, United States The etiologic agent of an outbreak of pneumonia in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 in January 2020. A patient in the United States was given a diagnosis of infection with this virus by the state of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens from this patient and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into 2 virus repositories, making it broadly available to the public health and research communities. We hope that open access to this reagent will expedite development of medical countermeasures.

negative: Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity? Insights from All-Atom Simulations [Image: see text] The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic is setting the global health crisis of our time, causing a devastating societal and economic burden. An idiosyncratic trait of coronaviruses is the presence of spike glycoproteins on the viral envelope, which mediate the virus binding to specific host receptor, enabling its entry into the human cells. In spite of the high sequence identity of SARS-CoV-2 with its closely related SARS-CoV emerged in 2002, the atomic-level determinants underlining the molecular recognition of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor and, thus, the rapid virus spread into human body, remain unresolved. Here, multi-microsecond-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 toward ACE2 as compared to SARS-CoV. This supplies a minute per-residue contact map underlining its stunningly high infectivity. Harnessing this knowledge is pivotal for urgently developing effective medical countermeasures to face the ongoing global health crisis.

negative: Development of methods to study the survival of airborne viruses Abstract A number of viruses have been shown to be transmitted by the airborne route. It is the ability of these viruses to retain their infectivity for living hosts which play a key role in their aerial dissemination. Data generated by a number of workers on the airborne survival of viruses varies considerably because laboratory techniques have not been standardized. About 5 yr ago we started studies on the airborne survival of a number of animal and human viruses. This paper describes the methodology developed to study the aerobiology of these viruses. These methods should be useful in the aerobiological work of other viruses.

negative: Chapter 8 Forensic public health epidemiological and microbiological investigations for biosecurity Abstract Deliberate dissemination of a biological agent via several different routes presents the latest challenge to global public health security. Novel pathogens and transmission methods can easily be exploited to cause disease outbreaks. Advancements in molecular biology that make it possible to genetically modify, edit, or disrupt the genome of pathogens increase the disease risk of an accidental or intentional release of pathogens with pandemic potential. The occurrence of a disease at more than an endemic level may stimulate an investigation to determine the source of the disease, who has the disease, when it occurred, and how it spreads. When intentional release of pathogens is suspected, investigators have the additional task of attributing the outbreak not only to a pathogen but also to a human source. The deliberate nature of such dissemination may be obvious. However, some forms of bioterrorism may be more covert, requiring molecular methods to uncover. The field of microbial forensics emerged following the anthrax attack in the United States in 2001 to extend epidemiologic principles to aid in the investigation of bioterrorism incidents. Microbial forensics combines epidemiology with genomic and microbiologic methods, to identify, characterize, and ascribe the cause of an incident resulting from the intentional or unintentional release of a harmful pathogen. Unlike routine epidemiologic investigations, microbial forensic investigations are undertaken when there is a potential crime due to the release of a pathogen with disease-causing potential. The investigation is conducted to attribute cause to a source based on indisputable evidence and is used to support criminal charges against the perpetrator(s). However, because bioterrorism may be unannounced, the initial investigation will start the same as to any public health incident of concern. This chapter discusses how epidemiology integrated with laboratory science can be used to identify the source of diseases caused by microorganisms or toxins—especially for attribution purposes.

negative: Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV’s capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV. IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.

negative: Characterizations of Coronaviruscis-Acting RNA Elements and the Transcription Step Affecting Its Transcription Efficiency Abstract Seven to eight species of viral subgenomic mRNAs are produced in coronavirus-infected cells. These mRNAs are produced in different quantities, and their molar ratios remain constant during viral replication. We studied RNA elements that affect coronavirus transcription efficiency by characterizing a series of cloned coronavirus mouse hepatitis virus (MHV) defective interfering (DI) RNAs containing an inserted intergenic sequence, from which subgenomic DI RNA is transcribed in MHV-infected cells. Certain combinations of upstream and downstream flanking sequences of the intergenic sequence suppressed subgenomic DI RNA transcription, yet changing one of the flanking sequences to a different sequence eliminated transcription suppression. The suppressive effect of certain combinations of flanking sequences, but not all combinations, could be counteracted by altering the intergenic sequence. Thus, the combination of intergenic sequence and flanking sequence affected transcription efficiency. We also characterized another set of DI RNAs designed to clarify which transcription step determines the relative molar ratios of coronavirus mRNAs. Our study indicated that if subgenomic mRNAs were exclusively synthesized from negative-strand genomic RNA, then the relative molar ratios of coronavirus mRNAs were most likely determined after synthesis of the genomic-sized template RNA. If negative-strand subgenomic RNAs were templates for subgenomic mRNAs, then the relative molar ratios of coronavirus mRNAs probably were determined after synthesis of the genomic-sized template RNA used for subgenomic-sized RNA transcription but prior to the completion of the synthesis of subgenomic-sized RNAs containing the leader sequence. The relative molar ratios of coronavirus mRNAs, therefore, seem to have been established prior to a putative replicon-type amplification of subgenomic mRNAs.

negative: Comparison of Epidemiological Variations in COVID-19 Patients Inside and Outside of China—A Meta-Analysis The objective of this study is to compare the epidemiological variations in COVID-19 patients reported in studies from inside and outside of China. We selected COVID-19 observational studies from eight countries, including, China, Italy, Australia, Canada, Korea, Taiwan, Singapore, and the USA, comprising a total of 13 studies and performed a meta-analysis for age, gender, fatality rate, and clinical symptoms of fever, cough, shortness of breath, and diarrhea. The meta-analysis shows that there are differences in symptoms and other characteristics reported by the patients of COVID-19 inside and outside China. Patients in China have a higher proportion of fever, cough, and shortness of breath as compared to patients outside of China. However, we found the opposite results for the gastrointestinal symptoms such as Diarrhea. Patients outside of China have a significantly higher proportion of Diarrhea as compared to patients within China. We also observed gender disparity among our studies, with the male population being more susceptible than the female population. Moreover, the analysis suggests that the fatality rate in China is relatively lower as compared to the fatality rate in other countries. These findings also suggest that the clinical symptoms of COVID-19 should not be generalized to fever, shortness of breath, and cough only but other symptoms such as diarrhea are also prevalent in patients with COVID-19.

negative: Overview of Covid-19; its prevention and management in the light of Unani medicine Abstract Since December 2019, a respiratory pandemic, named as coronavirus disease 2019 (Covid-19) caused by a new coronavirus named as SARS-CoV-2, has taken the world by storm. The symptoms are fever, malaise, and cough which resolve in a few days in most cases; but may progress to respiratory distress and organ failure. Transmission is through droplet infection or fomites, but other modes such as airborne transmission and oro-fecal transmission is also speculated. Research is underway to develop effective vaccines and medicines for the disease. In such a scenario, we present the measures described in Unani system of medicine for health protection during epidemics. Unani is a traditional system of medicine developed during the middle ages, which employs natural drugs of herbal, animal and mineral origin for treatment. In Unani medicine, during an epidemic, apart from isolation and quarantine, three measures are of utmost importance, (i) purification of surroundings using certain herbal drugs as fumigants or sprays, (ii) health promotion and immune-modulation, and (iii) use of health-protecting drugs and symptom-specific drugs. Drugs such as loban (Styrax benzoides W. G. Craib), sandroos (Hymenaea verrucosa Gaertn.) za'fran (Crocus sativus L.), vinegar etc. are prescribed in various forms. Scientific researches on these drugs reveal the presence of a number of pharmacologically active substances, which may provide a new insight into the management of infections and epidemics.

negative: A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses World Health Organization has declared the ongoing outbreak of coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern. The virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. Human infection with SARS-CoV-2 leads to a wide range of clinical manifestations ranging from asymptomatic, mild, moderate to severe. The severe cases present with pneumonia, which can progress to acute respiratory distress syndrome. The outbreak provides an opportunity for real-time tracking of an animal coronavirus that has just crossed species barrier to infect humans. The outcome of SARS-CoV-2 infection is largely determined by virus-host interaction. Here, we review the discovery, zoonotic origin, animal hosts, transmissibility and pathogenicity of SARS-CoV-2 in relation to its interplay with host antiviral defense. A comparison with SARS-CoV, Middle East respiratory syndrome coronavirus, community-acquired human coronaviruses and other pathogenic viruses including human immunodeficiency viruses is made. We summarize current understanding of the induction of a proinflammatory cytokine storm by other highly pathogenic human coronaviruses, their adaptation to humans and their usurpation of the cell death programmes. Important questions concerning the interaction between SARS-CoV-2 and host antiviral defence, including asymptomatic and presymptomatic virus shedding, are also discussed.

negative: Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2 Background COVID-19 has become a worldwide pandemic. It is caused by a novel coronavirus named SARS-CoV-2 with elusive origin. SARS-CoV-2 infects mammalian cells by binding to ACE2, a transmembrane protein. Therefore, the conservation of ACE2 and its expression pattern across mammalian species, which are yet to be comprehensively investigated, may provide valuable insights into tracing potential hosts of SARS-CoV-2. Methods We analyzed gene conservation of ACE2 across mammals and collected more than 140 transcriptome datasets from human and common mammalian species, including presumed hosts of SARS-CoV-2 and other animals in close contact with humans. In order to enable comparisons across species and tissues, we used a unified pipeline to quantify and normalize ACE2 expression levels. Results We first found high conservation of ACE2 genes among common mammals at both DNA and peptide levels, suggesting that a broad range of mammalian species can potentially be the hosts of SARS-CoV-2. Next, we showed that high level of ACE2 expression in certain human tissues is consistent with clinical symptoms of COVID-19 patients. Furthermore, we observed that ACE2 expressed in a species-specific manner in the mammals examined. Notably, high expression in skin and eyes in cat and dog suggested that these animals may play roles in transmitting SARS-CoV-2 to humans. Conclusions Through building the first atlas of ACE2 expression in pets and livestock, we identified species and tissues susceptible to SARS-CoV-2 infection, yielding novel insights into the viral transmission.

negative: COVID-19 and pets: When pandemic meets panic Abstract As the novel coronavirus outbreak spreads globally with devastating effects on human health, pets are also becoming unnecessary victims amidst the pandemic panic. Many have been reluctantly left home alone by owners who have been forced to temporarily evacuate their homes. And, although no evidence exists to indicate that they can either transmit the virus or develop its associated coronavirus disease 2019 (COVID-19), fear among the public that pets might play a role in spreading COVID-19 has resulted in pets being abandoned or even killed. This article outlines some of the ways in which the current pandemic has negatively impacted the welfare of pets. It also highlights the relationships between animal, human, and environmental health, as well as the importance of taking a collaborative transdisciplinary One Health approach to help prevent future COVID-19 outbreaks.

negative: The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. OBJECTIVE: To estimate the length of the incubation period of COVID-19 and describe its public health implications. DESIGN: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. SETTING: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. PARTICIPANTS: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. MEASUREMENTS: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. RESULTS: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. LIMITATION: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. CONCLUSION: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. PRIMARY FUNDING SOURCE: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.

negative: Detecting fake news for the new coronavirus by reasoning on the Covid-19 ontology In the context of the Covid-19 pandemic, many were quick to spread deceptive information. I investigate here how reasoning in Description Logics (DLs) can detect inconsistencies between trusted medical sources and not trusted ones. The not-trusted information comes in natural language (e.g."Covid-19 affects only the elderly"). To automatically convert into DLs, I used the FRED converter. Reasoning in Description Logics is then performed with the Racer tool.

negative: News Chinese scientists released genetic information on the coronavirus causing an outbreak of SARS-like illness in Wuhan, China The Vaccine Research Institute at the US National Institutes of Health (NIH) immediately began development of a new vaccine After the 2003 SARS outbreak, it took 20 months from the release of the viral genome to get a vaccine ready for human trials The zika virus took six months Now, the NIH is pushing to have a vaccine ready for testing in three to six months The race is on The NIH team took the template for a SARS vaccine and swapped enough code from the new virus to start a new vaccine Researchers, having experience with SARS, already knew which part of the virus to choose for the vaccine’s antigen, a sort of red flag for the immune system This synthetic antigen will prod the body to make antibodies

negative: Trend and forecasting of the COVID-19 outbreak in China By using the public data from Jan. 20 to Feb. 11, 2020, we perform data-driven analysis and forecasting on the COVID-19 epidemic in mainland China, especially Hubei province. Our results show that the turning points of the daily infections are predicted to be Feb. 6 and Feb. 1, 2020, for Hubei and China other than Hubei, respectively. The epidemic in China is predicted to end up after Mar. 10, 2020, and the number of the total infections are predicted to be 51600. The data trends reveal that quick and active strategies taken by China to reduce human exposure have already had a good impact on the control of the epidemic.

negative: Predicting the impacts of epidemic outbreaks on global supply chains: A simulation-based analysis on the coronavirus outbreak (COVID-19/SARS-CoV-2) case Abstract Epidemic outbreaks are a special case of supply chain (SC) risks which is distinctively characterized by a long-term disruption existence, disruption propagations (i.e., the ripple effect), and high uncertainty. We present the results of a simulation study that opens some new research tensions on the impact of COVID-19 (SARS-CoV-2) on the global SCs. First, we articulate the specific features that frame epidemic outbreaks as a unique type of SC disruption risks. Second, we demonstrate how simulation-based methodology can be used to examine and predict the impacts of epidemic outbreaks on the SC performance using the example of coronavirus COVID-19 and anyLogistix simulation and optimization software. We offer an analysis for observing and predicting both short-term and long-term impacts of epidemic outbreaks on the SCs along with managerial insights. A set of sensitivity experiments for different scenarios allows illustrating the model’s behavior and its value for decision-makers. The major observation from the simulation experiments is that the timing of the closing and opening of the facilities at different echelons might become a major factor that determines the epidemic outbreak impact on the SC performance rather than an upstream disruption duration or the speed of epidemic propagation. Other important factors are lead-time, speed of epidemic propagation, and the upstream and downstream disruption durations in the SC. The outcomes of this research can be used by decision-makers to predict the operative and long-term impacts of epidemic outbreaks on the SCs and develop pandemic SC plans. Our approach can also help to identify the successful and wrong elements of risk mitigation/preparedness and recovery policies in case of epidemic outbreaks. The paper is concluded by summarizing the most important insights and outlining future research agenda.

negative: Phylogenetic network analysis of SARS-CoV-2 genomes In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide.

negative: Differential Gene Expression in Coiled versus Flow-Diverter-Treated Aneurysms: RNA Sequencing Analysis in a Rabbit Aneurysm Model. BACKGROUND AND PURPOSE The biologic mechanisms leading to aneurysm healing or rare complications such as delayed aneurysm ruptures after flow-diverter placement remain poorly understood. We used RNA sequencing following implantation of coils or flow diverters in elastase aneurysms in rabbits to identify genes and pathways of potential interest. MATERIALS AND METHODS Aneurysms were treated with coils (n = 5) or flow diverters (n = 4) or were left untreated for controls (n = 6). Messenger RNA was isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed by using RNA-sequencing technology and were analyzed by using the Ingenuity Pathway Analysis tool. RESULTS With RNA sequencing for coiled versus untreated aneurysms, 464/9990 genes (4.6%) were differentially expressed (58 down-regulated, 406 up-regulated). When we compared flow-diverter versus untreated aneurysms, 177/10,041 (1.8%) genes were differentially expressed (8 down-regulated, 169 up-regulated). When we compared flow-diverter versus coiled aneurysms, 13/9982 (0.13%) genes were differentially expressed (8 down-regulated, 5 up-regulated). Keratin 8 was overexpressed in flow diverters versus coils. This molecule may potentially play a critical role in delayed ruptures due to plasmin production. We identified overregulation of apelin in flow diverters, supporting the preponderance of endothelialization, whereas we found overexpression of molecules implicated in wound healing (dectin 1 and hedgehog interacting protein) for coiled aneurysms. Furthermore, we identified metallopeptidases 1, 12, and 13 as overexpressed in coiled versus untreated aneurysms. CONCLUSIONS We observed different physiopathologic responses after endovascular treatment with various devices. Flow diverters promote endothelialization but express molecules that could potentially explain the rare delayed ruptures. Coils promote wound healing and express genes potentially implicated in the recurrence of coiled aneurysms.

negative: Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020 Data concerning the transmission of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) in paucisymptomatic patients are lacking. We report an Italian paucisymptomatic case of coronavirus disease 2019 with multiple biological samples positive for SARS-CoV-2. This case was detected using the World Health Organization protocol on cases and contact investigation. Current discharge criteria and the impact of extra-pulmonary SARS-CoV-2 samples are discussed.

negative: A highly conserved WDYPKCDRA epitope in the RNA directed RNA polymerase of human coronaviruses can be used as epitope-based universal vaccine design BACKGROUND: Coronaviruses are the diverse group of RNA virus. From 1960, six strains of human coronaviruses have emerged that includes SARS-CoV and the recent infection by deadly MERS-CoV which is now going to cause another outbreak. Prevention of these viruses is urgent and a universal vaccine for all strain could be a promising solution in this circumstance. In this study we aimed to design an epitope based vaccine against all strain of human coronavirus. RESULTS: Multiple sequence alignment (MSA) approach was employed among spike (S), membrane (M), enveloped (E) and nucleocapsid (N) protein and replicase polyprotein 1ab to identify which one is highly conserve in all coronaviruses strains. Next, we use various in silico tools to predict consensus immunogenic and conserved peptide. We found that conserved region is present only in the RNA directed RNA polymerase protein. In this protein we identified one epitope WDYPKCDRA is highly immunogenic and 100% conserved among all available human coronavirus strains. CONCLUSIONS: Here we suggest in vivo study of our identified novel peptide antigen in RNA directed RNA polymerase protein for universal vaccine – which may be the way to prevent all human coronavirus disease.

negative: Follow-up studies in COVID-19 recovered patients - is it mandatory? Abstract The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.

negative: The Coronavirus Nucleocapsid Is a Multifunctional Protein The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. Recent studies have confirmed that N is a multifunctional protein. The aim of this review is to highlight the properties and functions of the N protein, with specific reference to (i) the topology; (ii) the intracellular localization and (iii) the functions of the protein.

negative: Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson’s leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.

negative: Middle East respiratory syndrome coronavirus: current situation and travel-associated concerns The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. More than 1500 MERS-CoV cases were recorded in 42 months with a case fatality rate (CFR) of 40%. Meanwhile, 8000 cases of SARS-CoV were confirmed in six months with a CFR of 10%. The clinical presentation of MERS-CoV ranges from mild and non-specific presentation to progressive and severe pneumonia. No predictive signs or symptoms exist to differentiate MERS-CoV from community-acquired pneumonia in hospitalized patients. An apparent heterogeneity was observed in transmission. Most MERS-CoV cases were secondary to large outbreaks in healthcare settings. These cases were secondary to community-acquired cases, which may also cause family outbreaks. Travel-associated MERS infection remains low. However, the virus exhibited a clear tendency to cause large outbreaks outside the Arabian Peninsula as exemplified by the outbreak in the Republic of Korea. In this review, we summarize the current knowledge about MERS-CoV and highlight travel-related issues.

negative: 2792. Association of Body Mass Index with Rates of Hospitalization in Patients with Respiratory Viral Infections—Puerto Rico, 2012–2018 BACKGROUND: Obesity is a serious public health problem in Puerto Rico, where 31% of the population is obese. Multiple studies have suggested that adults with influenza who are underweight, overweight, or obese have increased risk of hospitalization compared with those of normal weight. We sought to determine whether risk of hospitalization among patients infected with influenza or other respiratory viruses differs by BMI among patients in Puerto Rico. METHODS: We analyzed data from patients enrolled in the Sentinel Enhanced Dengue Surveillance System (SEDSS), a prospective study of patients with acute febrile illness (AFI), from May 2012 to September 2018. We evaluated those older than 24 months, who had height, weight, and clinical disposition recorded, and tested positive by RT–PCR for infection with influenza A (n = 1253), influenza B (n = 844), adenovirus (n = 435), respiratory syncytial virus (n = 289), parainfluenza virus (n = 361), metapneumovirus (n = 247), or coronavirus (n = 15). BMI categories were determined using standard cutoffs in adults and BMI-for-age percentiles for children and adolescents. Risk of hospitalization by BMI category was calculated using multivariate Poisson regression. RESULTS: Among the 3,388 patients included, 675 (20%) were overweight, 926 (27%) were obese, 405 (12%) were underweight, and 1382 (41%) were normal weight. Median age was 13.4 (range: 2–100 years), and 50% were male. Risk of hospitalization was not significantly different in children and adult patients infected with a respiratory virus who were overweight relative to those that had normal BMI; however, once hospitalized, obese individuals of any age had a mean length of hospital stay 1.7 days longer than normal weight persons (95% CI: 0.27–3.17 days). Among adult patients, underweight patients were nearly 3 times more likely to be hospitalized compared with normal weight patients (relative risk 2.8, 95% CI: 1.4–5.9). Underweight children were not at increased risk of hospitalization. CONCLUSION: Among patients infected with a respiratory virus, risk of hospitalization was higher among underweight adult patients, and obese patients had a longer mean length of stay once hospitalized. Body mass index should be considered when evaluating risk and managing these patients. DISCLOSURES: All authors: No reported disclosures.

negative: Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study Summary Background The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. Methods A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. Results Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16–23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation-period was 2 days (range, 1–4). The median serial-interval was 1 day (range, 0–4). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. Conclusions SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.

negative: Discovering drugs to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.

negative: The World of Clinical Trial Development Post-Covid-19: Lessons Learned from a Global Pandemic. The novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health threat.1 Cancer patients are one of the most vulnerable populations. During this pandemic clinical trial accrual to NCI studies has fallen dramatically. Investigators quickly turned to regulatory bodies to simplify treatment schedules, facilitate telemedicine and to decrease required data collection Going forward the oncology research community must use the lessons learned to focus on redesigning studies to ensure that the critical scientific questions are answered safely while expanding access and increasing partnerships with community physicians. These changes will accelerate clinical progress while protecting our patients.

negative: COVID-19 Outbreak in Italy: Protecting Worker Health and the Response of the Italian Industrial Hygienists Association The number of people infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), i.e. the virus causing coronavirus disease (COVID-19), is dramatically increasing worldwide to the size of a pandemic. At the time of writing Italy is ranking first among countries both in terms of number of COVID-19 confirmed cases and in terms of number of deaths. Such a wide spread of COVID-19 has led to concern among workers who are facing the risk of becoming infected during the execution of their duties. We believe it is useful to remark on the need for professional expertise in the field of Occupational Hygiene in this emergency context, in which the indications provided by national and international bodies, the available scientific literature and the legal provisions are constantly and rapidly evolving. It is of fundamental importance that there is an effective analysis of expert inputs, to provide essential guidance to Health, Safety and Environmental managers and other prevention managers in workplaces. In this regard, not only a constant update of the regulatory framework is needed, but also a development and circulation of operational guidance to all the stakeholders to translate general indications into clear operating procedures and implementation tools to be adopted in the workplaces. We believe that the scientific associations in the field of Occupational Hygiene play a crucial role in guiding and assisting prevention professionals. There is considerable expertise in the occupational hygiene and exposure science communities that can help employers and workers to contain and delay the spread of COVID-19. For this reason, the Italian Association of Industrial Hygienists (AIDII-Associazione Italiana degli Igienisti Industriali) published documents containing operational guidelines to provide correct and constantly updated information for: (i) workers employed in essential activities (with low and medium risk of contagion), (ii) health workers and other workers at high or very high risk of contagion, and (iii) for the correct use and handling of personal protective equipment for workers and for the population in general. It is worth pointing out that the documents produced are not intended to replace those produced by authoritative bodies, but to comply with and complete them by reporting an effective summary and further indications about the measures that should be taken in practice under the light of the Italian legislation. At present, the challenge is to produce scientifically sound knowledge, appropriate tools, and effective methodologies, by coordinating the initiatives of different scientific associations, with the final aim to effectively transfer them to employers and workers.

negative: Clinical findings of patients with coronavirus disease 2019 in Jiangsu province, China: A retrospective, multi-center study Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0-54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m2 (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P<0.001) and a known history of type 2 diabetes (OR, 4.326; 95% CI, 1.059 to 17.668; P = 0.041). In this case series in Jiangsu Province, COVID-19 patients had less severe symptoms and had better outcomes than the initial COVID-19 patients in Wuhan. The BMI ≥ 28 kg/m2 and a known history of type 2 diabetes were independent risk factors of severe illness in patients with COVID-19.

negative: SARS-CoV-2 strategically mimics proteolytic activation of human ENaC Molecular mimicry is an evolutionary strategy adopted by viruses to exploit the host cellular machinery. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site, absent in any previous coronavirus sequenced, resulting in the striking mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic alteration of ENaC-α causes aldosterone dysregulation in patients, highlighting that the FURIN site is critical for activation of ENaC. Single cell RNA-seq from 66 studies shows significant overlap between expression of ENaC-α and the viral receptor ACE2 in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular characterization with cleavage signatures of 178 proteases highlights proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. Evolution of SARS-CoV-2 into a global pandemic may be driven in part by its targeted mimicry of ENaC-α, a protein critical for the homeostasis of airway surface liquid, whose misregulation is associated with respiratory conditions.

negative: Discovery of a novel accessory protein NS7a encoded by porcine deltacoronavirus Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Bioinformatics predicts that PDCoV encodes two accessory proteins (NS6 and NS7), the species-specific proteins for coronavirus. In this study, four mAbs against the predicted NS7 were prepared by using the purified recombinant NS7 protein. Indirect immunofluorescence assay demonstrated that all mAbs recognized cells transfected with an NS7 expression construct or infected with PDCoV. Western blot showed that NS7-specific mAbs recognized an additional protein band of about 12 kDa from PDCoV-infected cell lysates but not from cells with the ectopic expression of NS7. Detailed analysis suggested that this additional protein band represented a novel accessory protein, termed NS7a, a 100 amino acid polypeptide identical to the 3′ end of NS7. Moreover, NS7a is encoded by a separate subgenomic mRNA with a non-canonical transcription regulatory sequence. In summary, our results identified a third accessory protein encoded by PDCoV, which will enhance our understanding of PDCoV.

negative: [Epidemiological study of the transmission chain of a severe acute respiratory syndrome outbreak]. OBJECTIVE To investigate the process of SARS transmission and to evaluate infectivity of SARS patients in different periods of disease development. METHODS A case of SARS outbreak beginning from a male, 74-year-old patient in Beijing. Two hundred and seventy five primary, secondary and tertiary contacts, including family members relatives, colleagues, and others exposed to him, were traced by field investigation and telephone interview using a standardized questionnaire. The transmission process and infectivity of disease were analyzed with transmission chain diagram and contact history diagram. RESULTS Among the 275 contacts of the index case, 41 fell ill of SARS with an attack rate of 14.9% and 5 deaths with a fatality rate of 12.2%. The transmission chain of this outbreak could be clearly delineated, and all the 41 cases had close contacts with their infectors, SARS cases of the previous generation within the symptomatic period thereof. All of the 114 contacts that contacted their infectors, SARS cases of the previous generation during the incubation period thereof remained healthy. The incubation period of 27 cases that had contacted their infectors only once was 1 - 10 days with a median of 3 days. The highest risk of being infected was caring the patients unprotectedly, followed by living together with patient, visiting patient, and handling patient without protection. CONCLUSION All the secondary cases have the history of close contact with their symptomatic infectors of previous generation. It cannot be proved at all that SARS is infective during the incubation period. The infectivity of SARS is related to the degree of closeness of contact with the patient.

negative: Chapter 1 Mechanisms and Morphology of Cellular Injury, Adaptation, and Death 1 1 For a glossary of abbreviations and terms used in this chapter see E-Glossary 1-1.

negative: How to prevent outbreak of a hospital-affiliated dementia day-care facility in the pandemic COVID-19 infection in Taiwan

negative: Coronavirus 2019-nCoV: A brief perspective from the front line Abstract A novel coronavirus, designated as 2019-nCoV, hit the central Chinese city of Wuhan in late December 2019, and subsequently spread rapidly to all provinces of China and multiple countries. As of 0:00 am February 9, 2020, a total of 37,287 cases have been confirmed infection of 2019-nCoV in China mainland, and 302 cases have also been cumulatively reported from 24 countries. According to the latest data, a total of 813 deaths occurred in China mainland, with the mortality reaching approximately 2.2%. At present, there is no vaccine or specific drugs for the human coronavirus. Therefore, it is critical to understand the nature of the virus and its clinical characteristics, in order to respond to the 2019-nCoV outbreak. Thus, the present study briefly but comprehensively summarizes the not much but timely reports on the 2019-nCoV.

negative: Novel human coronavirus (SARS-CoV-2): A lesson from animal coronaviruses Abstract The recent pandemic caused by the novel human coronavirus, referrred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), not only is having a great impact on the health care systems and economies in all continents but it is also causing radical changes of common habits and life styles. The novel coronavirus (CoV) recognises, with high probability, a zoonotic origin but the role of animals in the SARS-CoV-2 epidemiology is still largely unknown. However, CoVs have been known in animals since several decades, so that veterinary coronavirologists have a great expertise on how to face CoV infections in animals, which could represent a model for SARS-CoV-2 infection in humans. In the present paper, we provide an up-to-date review of the literature currently available on animal CoVs, focusing on the molecular mechanisms that are responsible for the emergence of novel CoV strains with different antigenic, biologic and/or pathogenetic features. A full comprehension of the mechanisms driving the evolution of animal CoVs will help better understand the emergence, spreading, and evolution of SARS-CoV-2.

negative: The relationship of severe acute respiratory syndrome coronavirus with avian and other coronaviruses. In February 2003, a severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in humans in Guangdong Province, China, and caused an epidemic that had severe impact on public health, travel, and economic trade. Coronaviruses are worldwide in distribution, highly infectious, and extremely difficult to control because they have extensive genetic diversity, a short generation time, and a high mutation rate. They can cause respiratory, enteric, and in some cases hepatic and neurological diseases in a wide variety of animals and humans. An enormous, previously unrecognized reservoir of coronaviruses exists among animals. Because coronaviruses have been shown, both experimentally and in nature, to undergo genetic mutations and recombination at a rate similar to that of influenza viruses, it is not surprising that zoonosis and host switching that leads to epidemic diseases have occurred among coronaviruses. Analysis of coronavirus genomic sequence data indicates that SARS-CoV emerged from an animal reservoir. Scientists examining coronavirus isolates from a variety of animals in and around Guangdong Province reported that SARS-CoV has similarities with many different coronaviruses including avian coronaviruses and SARS-CoV-like viruses from a variety of mammals found in live-animal markets. Although a SARS-like coronavirus isolated from a bat is thought to be the progenitor of SARS-CoV, a lack of genomic sequences for the animal coronaviruses has prevented elucidation of the true origin of SARS-CoV. Sequence analysis of SARS-CoV shows that the 5' polymerase gene has a mammalian ancestry; whereas the 3' end structural genes (excluding the spike glycoprotein) have an avian origin. Spike glycoprotein, the host cell attachment viral surface protein, was shown to be a mosaic of feline coronavirus and avian coronavirus sequences resulting from a recombination event. Based on phylogenetic analysis designed to elucidate evolutionary links among viruses, SARS-CoV is believed to have branched from the modern Group 2 coronaviruses, suggesting that it evolved relatively rapidly. This is significant because SARS-CoV is likely still circulating in an animal reservoir (or reservoirs) and has the potential to quickly emerge and cause a new epidemic.

negative: SARS-CoV-2 nucleocapsid protein undergoes liquid-liquid phase separation stimulated by RNA and partitions into phases of human ribonucleoproteins. Tightly packed complexes of nucleocapsid protein and genomic RNA form the core of viruses and may assemble within viral factories, dynamic compartments formed within the host cells. Here, we examine the possibility that the multivalent RNA-binding nucleocapsid protein (N) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) compacts RNA via protein-RNA liquid-liquid phase separation (LLPS) and that N interactions with host RNA-binding proteins are mediated by phase separation. To this end, we created a construct expressing recombinant N fused to a N-terminal maltose binding protein tag which helps keep the oligomeric N soluble for purification. Using in vitro phase separation assays, we find that N is assembly-prone and phase separates avidly. Phase separation is modulated by addition of RNA and changes in pH and is disfavored at high concentrations of salt. Furthermore, N enters into in vitro phase separated condensates of full-length human hnRNPs (TDP-43, FUS, and hnRNPA2) and their low complexity domains (LCs). However, N partitioning into the LC of FUS, but not TDP-43 or hnRNPA2, requires cleavage of the solubilizing MBP fusion. Hence, LLPS may be an essential mechanism used for SARS-CoV-2 and other RNA viral genome packing and host protein co-opting, functions necessary for viral replication and hence infectivity.

negative: Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants BACKGROUND: Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. METHODS AND FINDINGS: Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318–510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. CONCLUSIONS: The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection.

negative: A cluster of pneumonia associated with the SARS-Cov-2 outside of Wuhan related to a house-warming banquet

negative: Ethics in Transplantation: Allotransplantation and Xenotransplantation

negative: Detection of a group 2 coronavirus in dogs with canine infectious respiratory disease Abstract An investigation into the causes of canine infectious respiratory disease was carried out in a large rehoming kennel. Tissue samples taken from the respiratory tract of diseased dogs were tested for the presence of coronaviruses using RT–PCR with conserved primers for the polymerase gene. Sequence analysis of four positive samples showed the presence of a coronavirus with high similarity to both bovine and human coronavirus (strain OC43) in their polymerase and spike genes, whereas there was a low similarity to comparable genes in the enteric canine coronavirus. This canine respiratory coronavirus (CRCV) was detected by RT–PCR in 32/119 tracheal and 20/119 lung samples, with the highest prevalence being detected in dogs with mild clinical symptoms. Serological analysis showed that the presence of antibodies against CRCV on the day of entry into the kennel decreased the risk of developing respiratory disease.

negative: Body Mass Index, Weight Discrimination, and Psychological, Behavioral, and Interpersonal Responses to the Coronavirus Pandemic OBJECTIVE: To examine whether body mass index (BMI) and weight discrimination are associated with psychological, behavioral, and interpersonal responses to the coronavirus pandemic. METHODS: Using a prospective design, participants (N=2,094) were first assessed in early February 2020 before the coronavirus crisis in the United States and again in mid‐March 2020 during the President’s 15 Days to Slow the Spread guidelines. Weight, height, and weight discrimination were assessed in the February survey. Psychological, behavioral, and interpersonal responses to the coronavirus were assessed in the March survey. RESULTS: Pre‐pandemic experiences with weight discrimination were associated with greater concerns about the virus, engaging in more preventative behaviors, less trust in people and institutions to manage the outbreak, and greater perceived declines in connection to one’s community. BMI tended to be unrelated to these responses. CONCLUSIONS: Despite the risks of complications of COVID‐19 associated with obesity, individuals with higher BMI were neither more concerned about the virus nor taking more behavioral precautions than individuals in other weight categories. Weight discrimination, in contrast, may heighten vigilance to threat, which may have contributed to both positive (greater concern, more precautionary behavior) and negative (less trust, declines community connection) responses to the pandemic.

negative: Novel coronavirus disease (COVID-19): a pandemic (epidemiology, pathogenesis and potential therapeutics) The coronavirus disease (COVID-19) is highly pathogenic viral infection caused by SARS-CoV-2. Currently, COVID-19 has caused global health concern. It is assumed that COVID-19 has zoonotic origin based on the large number of infected people who were exposed to the wet market in Wuhan City, China. The phylogenetic analysis has revealed that SARS-CoV-2 has significant sequence similarity with severe acute respiratory syndrome-like (SARS-like) bat viruses, thus bats could be primary possible reservoir. The intermediate host and there subsequent transfer is not known yet, although human to human transfer is widely confirmed. The transmission of COVID-19 infection from one person to another resulted in the isolation of patients who were subsequently given a variety of treatments. To monitor the current outbreak, robust steps have been taken around the globe to reduce the transmission of COVID-19 infection particularly banning international and domestic flights, inducting lockdowns in vulnerable areas, social distancing etc. No clinically approved antiviral drug or vaccine against COVID-19 is reported yet. However, in clinical trials, few broad-spectrum antiviral drugs were evaluated against COVID-19 infection which resulted in clinical recovery. In this article emergence and pathogenicity of COVID-19 infection along with potential therapeutic strategies are analyzed to combat the COVID-19 pandemic.

negative: Do COVID-19 and SARS Gene Complexities and Variations Help Overcome the Knowledge Gap? A whole new pathogen, to which humans have virtually no pre-existing immunity, has caused fear all over the world. Severe acute respiratory syndrome coronavirus (SARS CoV-2) is one of the types of human novel-coronavirus of the family coronavirus. The nature of transmission of the virus makes it one of the most infectious pathogenic diseases that has ever existed. Though the human coronaviruses have existed since the discovery of the human coronavirus 229E (HCoV-229E) and human coronavirus OC43 (HCoV-OC43) in 1960, it has been a challenge to develop an effective cure as well as vaccine for the diseases associated with coronaviruses. Commonly, human coronaviruses cause illnesses such as intestinal and respiratory tract illnesses. Nevertheless, the symptoms reflected after infection from the coronaviruses take some time before being identified. Thus, viruses can replicate and cause more harm to the human body before being detected. Moreover, research continues to explain why some gene variations in some individuals increase the risk of some infectious diseases, while others are not affected. Looking at gene variations in people infected with Coronavirus Disease 2019 (COVID-19) and studying how genes influence people's response to infection will help to develop a vaccine that will help strengthen the immune system. Knowing how the human genes respond to the virus COVID-19 will help to cure people more effectively.

negative: Key to successful treatment of COVID-19: accurate identification of severe risks and early intervention of disease progression Abstract Background COVID-19 is a new and highly contagious respiratory disease that has caused global spread, high case fatality rate in severe patients, and a huge medical burden due to invasive mechanical ventilation. The current diagnosis and treatment guidelines are still need to be improved, and more excellent clinical experience is needed to provide reference. Methods We analyzed and summarized clinical data of 97 confirmed COVID-19 adult patients (including 26 severe cases) admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, 2020 to March 10, 2020,included laboratory examination results, imaging findings, treatment effect, prognosis , etc, in order to put forward prediction index of severe COVID-19 patients, principles of early intervention and methylprednisolone usages in COVID-19 patients. Results 1.Hypoxemia, hyperlactic acid, hypoproteinemia, and hypokalemia were prevalent in COVID-19 patients.The significant low lymphocyte count, hypoproteinemia, hypokalemia, the persistent or worsen high CRP, high D-dimer, and high BNP, and the occurrence of hemoptysis and novel coronavirus (SARS-CoV-2) viremia were important indicators for early diagnosis and prediction of severe disease progression. 2.Characteristic images of lung CT had a clear change in COVID - 19, Ground-glass opacity (GGO) and high-density linear combinations may indicate different pathological changes. Rapid lobular progression of GGO suggests the possibility of severe disease. 3.Basic principles of early intervention treatment of COVID-19: on the premise of no effective antiviral drugs, treatment is based on supportive and symptomatic therapy (albumin supplementation, supplement of potassium, supplement blood plasma, etc.) in order to maintain the stability of the intracellular environment and adequately reactivate body immunity to clean up SARS-CoV-2 . 4. According to severity, oxygenation index, body weight, age, underlying diseases, appropriate amount methylprednisolone application on severe/critical COVID-19 patients on demand, improved blood oxygen and reduced the utilization rate of invasive mechanical ventilation, case fatality rate and medical burden significantly. The most common indications for invasive mechanical ventilation should be strictly control in critical COVID-19 patients. Conclusions: 1.Accurate and timely identification of clinical features in severe risks, and early and appropriate intervention can block disease progression. 2.Appropriate dose of methylprednisolone can effectively avoid invasive mechanical ventilation and reduce case fatality rate in critical COVID-19 patients.

negative: Why the SARS‐Cov‐2 has prolonged spreading time in children?

negative: Respiratory viral infections are not uncommon in neonatal intensive care units

negative: Epidemiology, genome, and clinical features of the pandemic SARS-CoV-2: a recent view Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, the number of globally confirmed cases according to World Health Organization statistics reached 292 124 in 189 countries by 22 March 2020. The number of deaths reached 12 784, with estimated case-fatality rates ranging from 0.5% to 5.7%. Children population seems to be the least affected by the disease, while the highest rate of death is among the elderly and people with comorbidities. Most infected individuals are asymptomatic or only exhibit mild symptoms. After the incubation period, the most common symptoms are fever, cough and fatigue. Asymptomatic carrier state is of paramount importance because of carriers' ability to spread the infection and to shed the virus into the air and surroundings. Although much is still unknown about SARS-CoV-2, the scientific research is moving at an unprecedented pace towards understanding the nature, effective control, prevention and treatment of SARS-CoV-2. Various reports have suggested an in vivo evolution of the virus, which may explain the rapid spread and changing epidemiology of SARS-CoV-2, but further evidence is needed. Unfortunately, no effective treatment or therapeutic drug is available for the disease; only supportive treatment and classical intervention measures are available for confronting the SARS-CoV-2 pandemic.

negative: Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly discovered enteric coronavirus, is the aetiological agent that causes severe clinical diarrhea and intestinal pathological damage in piglets. To understand the effect of SADS-CoV on host cells, we characterized the apoptotic pathways and elucidated mechanisms underlying the process of apoptotic cell death after SADS-CoV infection. SADS-CoV-infected cells showed evidence of apoptosis in vitro and in vivo. The use of a pan-caspase inhibitor resulted in the inhibition of SADS-CoV-induced apoptosis and reduction in SADS-CoV replication, suggestive of the association of a caspase-dependent pathway. Furthermore, SADS-CoV infection activated the initiators caspase-8 and -9 and upregulated FasL and Bid cleavage, demonstrating a crosstalk between the extrinsic and intrinsic pathways. However, the proapoptotic proteins Bax and Cytochrome c (Cyt c) relocalized to the mitochondria and cytoplasm, respectively, after infection by SADS-CoV. Moreover, Vero E6 and IPI-2I cells treated with cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPTP) opening, were completely protected from SADS-CoV-induced apoptosis and viral replication, suggesting the involvement of cyclophilin D (CypD) in these processes. Altogether, our results indicate that caspase-dependent FasL (extrinsic)- and mitochondria (intrinsic)- mediated apoptotic pathways play a central role in SADS-CoV-induced apoptosis that facilitates viral replication. In summary, these findings demonstrate mechanisms by which SADS-CoV induces apoptosis and improve our understanding of SADS-CoV pathogenesis.

negative: Animal coronavirus vaccines: lessons for SARS. Severe acute respiratory syndrome (SARS) emerged in China and spread globally as a human pandemic. It is caused by a new coronavirus (CoV) of suspect animal origin. The emergence of SARS stunned medical scientists, but veterinary virologists had previously recognized CoVs as causing fatal respiratory or enteric disease in animals with interspecies transmission and wildlife reservoirs. Because of its public health impact, major efforts are focused on development of SARS vaccines. Occurrence of CoV disease at mucosal surfaces necessitates the stimulation of local immunity, having an impact on the vaccine type, delivery and adjuvant needed to achieve mucosal immunity. Such immunity is often short-lived, requires frequent boosting and may not prevent re-infection, all factors complicating CoV vaccine design. SARS vaccine efforts should be enhanced by understanding the correlates of protection and reasons for the success or failure of animal CoV vaccines. This review will focus on studies of immunity and protection in swine to the enteric CoV, transmissible gastroenteritis (TGEV) versus the respiratory variant, porcine respiratory CoV (PRCV), comparing live, inactivated and subunit vaccines, various vaccine vectors, routes and adjuvants. In addition avian infectious bronchitis CoV (IBV) vaccines targeted for protection of the upper respiratory tract of chickens are discussed. Unfortunately, despite long-term efforts, effective vaccines to prevent enteric CoV infections remain elusive, and generally live, but not killed vaccines, have induced the most consistent protection against animal CoVs. Confirmation of the pathogenesis of SARS in humans or animals models that mimic SARS may further aid in vaccine design and evaluation.

negative: Chapter 1 Discovery and Classification Abstract The virus was first described 120 years ago as a filterable, transmissible agent that causes disease in plants and animals. A virus is a “submicroscopic and intracellular parasite” that can propagate only inside a living cell. The obligatory nature of a virus brought a debate on whether it is living or nonliving. Virology, as a discipline that studies the diverse aspects of viral infection of host cells and its consequence, became established during the early 20th century. Viruses are found in almost all living organisms on earth, ranging from bacteria, fungi, and amoeba, to plants and animals. Viruses are classified into seven groups, according to genomic features. This molecular classification, also called the “Baltimore classification,” allows us to predict precisely the mode of viral genome replication.

negative: SARS Severe acute respiratory syndrome (SARS) is an acute respiratory tract infectious disease induced by SARS-CoV and mainly transmitted through the short-distance air droplets and close contact. Its main clinical characteristics is abrupt onset of the disease and the initial symptom is fever accompanied with systematic symptoms of headache, soreness and fatigue, and respiratory tract symptoms such as cough, chest dullness, and dyspnea. A few cases may progress to acute respiratory distress syndrome (ARDS). Due to its self-limiting feature, the prognosis is predominantly good but may be poor in severe cases, with mortality about 9.3 %. Some patients may develop such complications such as lung fibrosis and necrosis of the head of femur. On April 8, 2003, SARS was defined as a legal infectious disease by the Ministry of Heath of China.

negative: Infectious Diseases: The Role of the Forensic Physician Infections have plagued doctors for centuries, in both the diagnosis of the specific diseases and the identification and subsequent management of the causative agents. There is a constant need for information as new organisms emerge, existing ones develop resistance to current drugs or vaccines, and changes in epidemiology and prevalence occur. In the 21st century, obtaining this information has never been more important. Population migration and the relatively low cost of flying means that unfamiliar infectious diseases may be brought into industrialized countries. An example of this was an outbreak of severe acute respiratory syndrome (SARS), which was first recognized in 2003. Despite modern technology and a huge input of money, it took months for the agent to be identified, a diagnostic test to be produced, and a strategy for disease reporting and isolation to be established. There is no doubt that other new and fascinating diseases will continue to emerge.

negative: Surveillance and Control of Communicable Disease in Conflicts and Disasters

negative: Employing Live Microbes for Vaccine Delivery The employment of live attenuated vaccines has a long-standing record in human and veterinary medicine. Most of the vaccines in current use were empirically developed during the last century. Today, due to the great advances in fields such as immunology and bioengineering, the rational development of live attenuated vaccines becomes increasingly feasible. Moreover, live vaccines can be used as carrier systems for heterologous antigens or therapeutic factors. In each case, the development of a recombinant live attenuated vaccine is a complex task where properties such as targeting specificity, antigen synthesis, antigen release, and safety aspects have to be integrated. A range of such recombinant vaccine candidates have successfully been tested in the clinics, but very few have been approved so far. In many cases, further optimization of such vaccines is necessary with regard to their efficacy and safety profiles. In the present chapter, we focus on current strategies which are employed for the development of new and the optimization of first generation recombinant live vaccines based on bacteria and viruses.

negative: Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan

negative: Nucleocapsid Phosphorylation and RNA Helicase DDX1 Recruitment Enables Coronavirus Transition from Discontinuous to Continuous Transcription Coronaviruses contain a positive-sense single-stranded genomic (g) RNA, which encodes nonstructural proteins. Several subgenomic mRNAs (sgmRNAs) encoding structural proteins are generated by template switching from the body transcription regulatory sequence (TRS) to the leader TRS. The process preferentially generates shorter sgmRNA. Appropriate readthrough of body TRSs is required to produce longer sgmRNAs and full-length gRNA. We find that phosphorylation of the viral nucleocapsid (N) by host glycogen synthase kinase-3 (GSK-3) is required for template switching. GSK-3 inhibition selectively reduces the generation of gRNA and longer sgmRNAs, but not shorter sgmRNAs. N phosphorylation allows recruitment of the RNA helicase DDX1 to the phosphorylated-N-containing complex, which facilitates template readthrough and enables longer sgmRNA synthesis. DDX1 knockdown or loss of helicase activity markedly reduces the levels of longer sgmRNAs. Thus, coronaviruses employ a unique strategy for the transition from discontinuous to continuous transcription to ensure balanced sgmRNAs and full-length gRNA synthesis.

negative: The Chinese governance system: Its strengths and weaknesses in a comparative development perspective Abstract This is an overview paper focusing on the organizational aspects of the Chinese governance system and their relation to development. Compared to other developing countries like India, it has special positive features of career incentives promoting growth at the local level, the ability to take long-term decisions relatively quickly, and a unique blend of political centralization and decentralization of economic power and responsibility, that is conducive to central guidance and local business development. On the other hand, with a lack of sufficient downward (as opposed to upward) accountability and absence of institutionalized systems of scrutiny and challenge from below, mistakes or abuse of power are more difficult to check and correct quickly, political loyalty may often get a premium over performance at the upper levels, and there are insufficient checks on collusion between business and officials. The over-all organizational system is prone to over-reaction in times of crisis and thus only weakly resilient compared to systems where information flows from below are less controlled or choked.

negative: Comparison of laparoendoscopic single-site (LESS) surgery and conventional multiport laparoscopic (CMPL) surgery for hysterectomy: long-term outcomes of abdominal incisional scar. There is scarcity of data about the long-term results such as port-site hernia, body image scale and cosmesis scale outcomes between laparoendoscopic single-site (LESS) surgery and conventional multiport laparoscopy (CMPL) for hysterectomy. Eighty women, who underwent total hysterectomy by the LESS (n = 40) and CMPL (n = 40) technique due to benign and malign gynecological disorders, were evaluated with a cosmesis and body image questionnaire in an age-matched cohort study. Median follow-up time was 25 (6-30) months in both groups. The mean age of the patients was 49.3 ± 6.3 years. The mean body image scale scores were 5.3 ± 0.6 and 5.5 ± 1.2 in the LESS and CMPL groups, respectively (p = 0.268). The mean cosmesis and scar scale scores were significantly higher in the LESS group compared to the CMPL group (p = .011 and p < .001, respectively). Port-site hernia was detected in two patients in the LESS group, but not in the CMPL group. There was no cuff dehiscence in the LESS nor in the CMPL group. The LESS technique provides better cosmesis when compared with the CMPL technique. The body image perceptions in the two groups were similar. Women who wish to undergo the LESS surgery should be informed about the risk of incisional hernia. Impact statement What is already known on this subject? Short-term results of LESS hysterectomy such as complication rates, additional port requirement, conversion to CMPL or laparotomy, pain score and analgesic use were evaluated in various studies. Several studies have been published on the safety and efficacy of single-port laparoscopic hysterectomy (LH); however, it has been unclear whether single-port LH offers benefits over multiport LH regarding long-term patient satisfaction and cosmetic satisfaction. What do the results of this study add? In this prospective cohort study, we aimed to compare long-term results (at least six months) of abdominal incisional scar between LESS and CMPL surgery for hysterectomy. The LESS technique provides better cosmesis when compared with the CMPL technique, although, the body image perceptions in the two groups were similar. What are the implications of these findings for clinical practice and/or further research? LESS technique can be offered as an option for hysterectomy since it provides better long-term cosmesis compared to CMPL.

negative: Considerations of coronavirus (COVID-19) impact and the management of the dead in Brazil Abstract During a pandemic such as COVID-19, the forensic community plays a key role in the management of the crisis, both nationally and internationally. Much has been written and disseminated regarding protocols for death investigation, infection mitigation and risks, and management of dead. However, in many contexts, the ability of forensic practitioners to follow best-practice procedures is limited by the resources available to them. This article examines some of the impact of the novel coronavirus (COVID-19) in Brazil, with emphasis on management of the dead and challenges faced by medicolegal services.

negative: Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2 Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic.

negative: Isolation of a coronavirus during studies on puffinosis, a disease of the Manx shearwater(Puffinus puffinus) A virus was isolated from 2 day-old mice inoculated with homogenates of either the lungs or blood of 2 different shearwaters affected by puffinosis. Examination of infected suckling mouse brain and infected NCTC-1469 (mouse liver) cell cultures, by electron microscopy, revealed virus particles and inclusion bodies characteristic of a coronavirus. Neutralization, complement fixation and fluorescent antibody tests showed that the virus was related to mouse hepatitis virus. The virus was not isolated from 445 control, uninfected mice. Neutralising antibodies were not detected in 39 sera from diseased shearwaters and 2 sera from apparently healthy birds. Two shearwaters inoculated with the virus did not develop clinical signs of infection. The question of whether the virus was isolated from shearwaters or from laboratory mice is discussed.

negative: sOptimizing screening strategies for coronavirus disease 2019: A study from Middle China Abstract Background Coronavirus disease 2019 (COVID-19) has been highly epidemic in China since January 2020. Rapid detection of the causative agent, severe acute respiratory coronavirus-2 (SARS-CoV-2), is very important due to its high rate of infectivity. This study aimed to clarify the epidemiology and clinical characteristics of COVID-19 outside of Hubei province, China, and to optimize screening strategies for COVID-19 in attempts to contain spread of the virus. Methods This retrospective study included all confirmed cases of COVID-19 in Hunan Provincial People's Hospital (Changsha, China) between January 22 and February 15, 2020. All cases were detected using a real-time reverse transcription polymerase chain reaction assay. The epidemiology and clinical characteristic of these cases were investigated according to outcome in attempts to optimize screening strategies for COVID-19. Results There were 24 confirmed cases of COVID-19 in the fever outpatient department of Hunan Provincial People's Hospital. Three patients were asymptomatic, and 3 exhibited mild and 3 moderate disease. There was a family cluster phenomenon. Conclusion Individuals with COVID-19 can be asymptomatic or exhibit mild manifestations of disease. Close monitoring and an optimized screening strategy for COVID-19 could help deter spread of the virus.

negative: The genetic sequence, origin, and diagnosis of SARS-CoV-2 Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease that first emerged in Hubei province, China, in December 2019, which was found to be associated with a large seafood and animal market in Wuhan. Airway epithelial cells from infected patients were used to isolate a novel coronavirus, named the SARS-CoV-2, on January 12, 2020, which is the seventh member of the coronavirus family to infect humans. Phylogenetic analysis of full-length genome sequences obtained from infected patients showed that SARS-CoV-2 is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV. The possible person-to-person disease rapidly spread to many provinces in China as well as other countries. Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against novel Coronavirus. In this review, we introduced current diagnostic methods and criteria for the SARS-CoV-2 in China and discuss the advantages and limitations of the current diagnostic methods, including chest imaging and laboratory detection.

negative: Beyond RGD: virus interactions with integrins Viruses successfully infect host cells by initially binding to the surfaces of the cells, followed by an intricate entry process. As multifunctional heterodimeric cell-surface receptor molecules, integrins have been shown to usefully serve as entry receptors for a plethora of viruses. However, the exact role(s) of integrins in viral pathogen internalization has yet to be elaborately described. Notably, several viruses harbor integrin-recognition motifs displayed on viral envelope/capsid-associated proteins. The most common of these motifs is the minimal peptide sequence for binding integrins, RGD (Arg-Gly-Asp), which is known for its role in virus infection via its ability to interact with over half of the more than 20 known integrins. Not all virus-integrin interactions are RGD-dependent, however. Non-RGD-binding integrins have also been shown to effectively promote virus entry and infection as well. Such virus-integrin binding is shown to facilitate adhesion, cytoskeleton rearrangement, integrin activation, and increased intracellular signaling. Also, we have attempted to discuss the role of carbohydrate moieties in virus interactions with receptor-like host cell surface integrins that drive the process of internalization. As much as possible, this article examines the published literature regarding the role of integrins in terms of virus infection and virus-encoded glycosylated proteins that mediate interactions with integrins, and it explores the idea of targeting these receptors as a therapeutic treatment option.

negative: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Publisher Summary Severe acute respiratory syndrome (SARS) is caused by a coronavirus (CoV), SARSCoV. SARS-CoV belongs to the family Coronaviridae, which are enveloped RNA viruses in the order Nidovirales. Global research efforts are continuing to increase the understanding of the virus, the pathogenesis of the disease it causes (SARS), and the “heterogeneity of individual infectiousness” as well as shedding light on how to prepare for other emerging viral diseases. Promising drugs and vaccines have been identified. The milestones achieved have resulted from a truly international effort. Molecular studies dissected the adaptation of this virus as it jumped from an intermediary animal, the civet, to humans, thus providing valuable insights into processes of molecular emergence.

negative: SCHOOL Model and New Targeting Strategies Protein-protein interactions play a central role in biological processes and thus are an appealing target for innovative drug design and development. They can be targeted by small molecule inhibitors, peptides and peptidomimetics, which represent an alternative to protein therapeutics that carry many disadvantages. In this chapter, I describe specific protein-protein interactions suggested by a novel model of immune signaling, the Signaling Chain HOmoO Ligomerization (SCHOOL) model, to be critical for cell activation mediated by multichain immune recognition receptors (MIRRs) expressed on different cells of the hematopoietic system. Unraveling a long-standing mystery of MIRR triggering and transmembrane signaling, the SCHOOL model reveals the intrareceptor transmembrane interactions and interreceptor cytoplasmic homointeractions as universal therapeutic targets for a diverse variety of disorders mediated by immune cells. Further, assuming that the general principles underlying MIRR-mediated transmembrane signaling mechanisms are similar, the SCHOOL model can be applied to any particular receptor of the MIRR family. Thus, an important application of the SCHOOL model is that global therapeutic strategies targeting key protein-protein interactions involved in MIRR triggering and transmembrane signal transduction may be used to treat a diverse set of immune-mediated diseases. This assumes that clinical knowledge and therapeutic strategies can be transferred between seemingly disparate disorders, such as T-cell-mediated skin diseases and platelet disorders, or combined to develop novel pharmacological approaches. Intriguingly, the SCHOOL model unravels the molecular mechanisms underlying ability of different human viruses such as human immunodeficiency virus, cytomegalovirus and severe acute respiratory syndrome coronavirus to modulate and/or escape the host immune response. It also demonstrates how the lessons learned from viral pathogenesis can be used practically for rational drug design. Application of this model to platelet collagen receptor signaling has already led to the development of a novel concept of platelet inhibition and the invention of new platelet inhibitors, thus proving the suggested hypothesis and highlighting the importance and broad perspectives of the SCHOOL model in the development of new targeting strategies.

negative: The Neglected Role of Physical Education Participation on Suicidal Ideation and Stress in High School Adolescents from South Korea Adolescents are at high risk of suicidal ideation and stress. This study aimed to investigate how physical education participation predicts suicidal ideation and stress in South Korean high school students. Data from the Twelfth Korea Youth Risk Behaviour Web-Based Survey 2016 (KYRBS) were used for analyses. Two multiple logistic regressions were performed to determine the influence of selected factors on suicidal ideation and stress (model 1: subjective health, social support, body mass index, academic achievement, perceived economic status of family, and physical education participation; model 2: adjusting for school type and year). Model 2 revealed negative associations between subjective health, academic achievement, perceived economic status of family, social support, physical education participation (≥2 times/weekly), and suicidal ideation for male students. Female students exhibited negative associations between subjective health, social support, and academic achievement, along with a positive association between body mass index and suicidal ideation. For both genders, stress was negatively associated with subjective health, social support, academic achievement, perceived economic status of family, and physical education participation (≥2 times/weekly). These findings suggest that participating in physical education can mitigate the risk of suicidal ideation and stress among high school students.

negative: The Coronavirus Disease 2019 (COVID-19) Pandemic. The present study provides an overview of the coronavirus disease 2019 (COVID-19) outbreak which has rapidly extended globally within a short period. COVID-19 is a highly infectious respiratory disease caused by a new coronavirus known as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2). SARS-CoV-2 is different from usual coronaviruses responsible for mild sickness such as common cold among human beings. It is crucial to understand the impact and outcome of this pandemic. We therefore overview the changes in the curves of COVID-19 confirmed cases and fatality rate in China and outside of China from 31st of December 2019 to 25th of March 2020. We also aimed to assess the temporal developments and death rate of COVID-19 in China and worldwide. More than 414,179 confirmed cases of COVID-19 have been reported in 197 countries, including 81,848 cases in China and 332,331 outside of China. Furthermore, 18,440 infected patients died from COVID-19 infection; 3,287 cases were from China and 15,153 fatalities were reported worldwide. Among the worldwide infected cases, 113,802 patients have been recovered and discharged from different hospitals. Effective prevention and control measures should be taken to control the disease. The presented Chinese model (protocol) of disease prevention and control could be utilized in order to curb the pandemic situation.

negative: Development of antiviral therapy for severe acute respiratory syndrome Abstract A new disease, the severe acute respiratory distress syndrome (SARS), caused by the SARS coronavirus (SARS-CoV), emerged at the beginning of 2003 and rapidly spread throughout the world. Although the disease had disappeared in June 2003 its re-emergence cannot be excluded. The development of vaccines against SARS-CoV may take years. Therefore, the availability of effective antiviral drugs against SARS-CoV may be crucial for the control of future SARS outbreaks. In this review, experimental and clinical data about potential anti-SARS drugs is summarised and discussed. Animal model studies will be needed to help to determine which interventions warrant controlled clinical testing.

negative: Covid-19 Pandemic and Current Medical Interventions Abstract First humanoid coronavirus was discovered in the middle of 1960s, the class of viruses are considered to be a huge threat. The first onset of human coronavirus, SARS (SARS-CoV) appeared in 2003 which spanned five continents having lethal effects on human population accompanied by The Middle East Respiratory Syndrome Coronavirus in 2012 with a death rate of 35%. The viruses remain a threat till date and are of serious concern since no vaccine or specified drug therapy has been approbated for treating human coronaviruses. The viruses became a pandemic worldwide with the emergence of Wuhan coronavirus (2019-nCoV). SARS-CoV2 viral manifestation poses a serious human life risk by causing acute lung injury and various respiratory outcomes and has become a global concern. High pathogenicity and transmission rate of the viral strain has become the spotlight of research community throughout the world. With the ongoing studies on viral structure and host interactions, the intricacy of the viral proteome structure and replication cycle proposes a need to explore our understanding of host factors playing role in viral multiplication cycle. This review provides insight into our prevalent perception of coronavirus-host interactions, structure of SARS-CoV2, receptor mediated entry of virus inside the human cells, ongoing clinical trials and drug therapies and treatments that are being used to combat COVID-19 targeting viral fusion, replication and its multiplication.

negative: Likelihood of survival of coronavirus disease 2019

negative: Mathematical Modeling of Epidemic Diseases; A Case Study of the COVID-19 Coronavirus The outbreak of the Coronavirus COVID-19 has taken the lives of several thousands worldwide and locked-out many countries and regions, with yet unpredictable global consequences. In this research we study the epidemic patterns of this virus, from a mathematical modeling perspective. The study is based on an extensions of the well-known susceptible-infected-recovered (SIR) family of compartmental models. It is shown how social measures such as distancing, regional lockdowns, quarantine and global public health vigilance, influence the model parameters, which can eventually change the mortality rates and active contaminated cases over time, in the real world. As with all mathematical models, the predictive ability of the model is limited by the accuracy of the available data and to the so-called level of abstraction used for modeling the problem. In order to provide the broader audience of researchers a better understanding of spreading patterns of epidemic diseases, a short introduction on biological systems modeling is also presented and the Matlab source codes for the simulations are provided online.

negative: Infectivity of human coronavirus strain 229E. The replication of human coronavirus strain 229E was observed by using indirect immunofluorescence in infected monolayers of MRC continuous cells. By 8 h after infection, bright cytoplasmic fluorescence was detected in cells infected with human coronavirus 229E. Discrete foci of infection were observed from 8 to 16 h after infection in cells infected with high dilutions of human coronavirus 229E; each fluorescent focus corresponded to a single virus infection. A fluorescent focus assay is described, using indirect immunofluorescence, which is more sensitive than the established techniques of tube titration and plaque assay. Particle/infectivity ratios for unpurified and purified virus preparations revealed a considerable drop in infectivity on purification.

negative: Continuous temperature monitoring by a wearable device for early detection of febrile events in the SARS-CoV-2 outbreak in Taiwan, 2020

negative: Inactivation of murine norovirus on a range of copper alloy surfaces is accompanied by loss of capsid integrity. Norovirus is one of the most common causes of acute viral gastroenteritis. The virus is spread via the fecal-oral route, most commonly from infected food and water, but several outbreaks have originated from contamination of surfaces with infectious virus. In this study, a close surrogate of human norovirus causing gastrointestinal disease in mice, murine norovirus type 1 (MNV-1), retained infectivity for more than 2 weeks following contact with a range of surface materials, including Teflon (polytetrafluoroethylene [PTFE]), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. Persistence was slightly prolonged on ceramic surfaces. A previous study in our laboratory observed that dry copper and copper alloy surfaces rapidly inactivated MNV-1 and destroyed the viral genome. In this new study, we have observed that a relatively small change in the percentage of copper, between 70 and 80% in copper nickels and 60 and 70% in brasses, had a significant influence on the ability of the alloy to inactivate norovirus. Nickel alone did not affect virus, but zinc did have some antiviral effect, which was synergistic with copper and resulted in an increased efficacy of brasses with lower percentages of copper. Electron microscopy of purified MNV-1 that had been exposed to copper and stainless steel surfaces suggested that a massive breakdown of the viral capsid had occurred on copper. In addition, MNV-1 that had been exposed to copper and treated with RNase demonstrated a reduction in viral gene copy number. This suggests that capsid integrity is compromised upon contact with copper, allowing copper ion access to the viral genome.

negative: Analysis of the evolution of the Sars-Cov-2 in Italy, the role of the asymptomatics and the success of Logistic model In this letter we study the temporal evolution of the Sars-Cov-2 in Italy. The time window of the real data is between February 24 and March 25. After we upgrade the data until April 1.We perform the analysis with 4 different model and we think that the best candidate to describe correctly the italian situation is a generalized Logistic equation. We use two coupled differential equations that describe the evolution of the severe infected and the deaths. We have done this choice, because in Italy the pharyngeal swabs are made only to severe infected and so we have no information about asymptomatic people. An important observation is that the virus spreads between Regions with some delay; so we suggest that a different analysis region by region would be more sensible than that on the whole Italy. In particular the region Lombardia has a behaviour very fast with respect to the other ones. We show the behaviour of the total deaths and the total severe infected for Italy and five regions: Lombardia, Emilia Romagna, Veneto, Piemonte, Toscana. Finally we do an analysis of the peak and an estimation of how many lifes have been saved with the LockDown.

negative: CHAPTER 17 GUINEA PIGS Publisher Summary This chapter deals with the health and medical care issues of guinea pigs. Guinea pigs have wide bodies with short limbs. They have a short, flat nose, laterally placed eyes, and hairless external pinnae. The dentition of the guinea pig is described as aradicular hypsodont. Guinea pigs are best housed in well-ventilated, wire-sided cages with solid bottoms. If housed indoors, guinea pig enclosures do not require a cover, as these animals do not typically jump or climb. Heavy food containers are recommended to make dumping of the receptacle more difficult. All food containers should be easy to disinfect and should be cleaned regularly, because guinea pigs have a habit of soiling their food bowls. These animals, native to the Andes Mountains, are very susceptible to hyperthermia and should never be housed in temperatures greater than 80°F. High humidity can also exacerbate a guinea pig's sensitivity to elevated temperatures by increasing the heat index. Guinea pigs often do not exhibit clinical signs early in a disease process. Therefore, a thorough physical examination can be extremely useful in determining the overall health status of the animal.

negative: H1N1 Is Not a Chinese Virus: the Racialization of People and Viruses in Post-SARS China In this article, I trace how the race-making of people, viruses, and the places they share became a powerful means by which Chinese public health professionals made sense of two major infectious outbreaks that threatened to stall or interrupt China’s development: the SARS outbreak of 2003 and the H1N1 influenza pandemic of 2009. By inscribing geographical stability onto infected bodies in motion through the languages of race and genetics, Chinese public health professionals sought to constrain the mobility of infection and, in doing so, to contain the symbolic and material threats to China’s modernity and development that flu-like infections, and the people who carried and spread them, had come to represent. While SARS in this imaginary became a “Chinese” or “Cantonese” disease, H1N1 became a EuroAmerican disease that, when it reached inside China, adhered more easily to those Chinese who did not quite belong. In constructing this imaginary, public health professionals’ racialization of certain groups thought to be infectious joined with the racialization of the infections themselves. H1N1 could not easily infect most Chinese because both the virus and its hosts were racially alien.

negative: Review of bioaerosols in indoor environment with special reference to sampling, analysis and control mechanisms Abstract Several tiny organisms of various size ranges present in air are called airborne particles or bioaerosol which mainly includes live or dead fungi and bacteria, their secondary metabolites, viruses, pollens, etc. which have been related to health issues of human beings and other life stocks. Bio-terror attacks in 2001 as well as pandemic outbreak of flue due to influenza A H1N1 virus in 2009 have alarmed us about the importance of bioaerosol research. Hence characterization i.e. identification and quantification of different airborne microorganisms in various indoor environments is necessary to identify the associated risks and to establish exposure threshold. Along with the bioaerosol sampling and their analytical techniques, various literatures revealing the concentration levels of bioaerosol have been mentioned in this review thereby contributing to the knowledge of identification and quantification of bioaerosols and their different constituents in various indoor environments (both occupational and non-occupational sections). Apart from recognition of bioaerosol, developments of their control mechanisms also play an important role. Hence several control methods have also been briefly reviewed. However, several individual levels of efforts such as periodic cleaning operations, maintenance activities and proper ventilation system also serve in their best way to improve indoor air quality.

negative: Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain Previous results suggested that, after intranasal inoculation, mouse hepatitis virus (MHV), a neurotropic coronavirus, entered the central nervous system (CNS) via the olfactory and trigeminal nerves. To prove this hypothesis, the effect of interruption of the olfactory pathway on spread of the virus was studied using in situ hybridization. Unilateral surgical ablation of this pathway prevented spread of the virus via the olfactory tract on the side of the lesion. MHV RNA could be detected, however, at distal sites on the operated side, indicating that the virus spread via well-described circuits involving the anterior commissure from the control (intact) side of the brain. Viral transport via the trigeminal nerve was not affected by removal of the olfactory bulb, showing that the surgical procedure was specific for the olfactory pathway. These results prove conclusively that MHV gains entry to the CNS via a transneuronal route, and spreads to additional sites in the brain via known neuroanatomic pathways.

negative: Caution of coronavirus transmission through ocular surface/ 国际眼科杂志(Guoji Yanke Zazhi) @#At present, the new coronavirus(COVID-19)epidemic is spreading rapidly in Wuhan city Hubei province of China, and has aroused great attention of the international community. There have been clues that the conjunctiva may be one of the entries for the new coronavirus(SARS-CoV-2). In the absence of clinical evidence on ocular infection with SARS-CoV-2. Therefore, understanding the mechanism and cell receptors of coronavirus transmission through ocular surface and the transmission characteristics of homologous coronavirus can provide some suggestions for appropriately ocular protection and identify COVID-19 coexisting with ocular signs for ophthalmologists during this epidemic disease.

negative: Severe Acute Respiratory Syndrome (SARS) Severe acute respiratory syndrome (SARS) is a new human disease caused by an animal coronavirus that adapted to efficient human-to-human transmission. The disease first emerged in November 2002 in Guangdong Province, China and spread globally within months. The SARS coronavirus (SARS CoV) affects multiple organ systems with severe viral pneumonia as its main clinical manifestation but with diarrhea, lymphopenia, and mild liver dysfunction being common extra-pulmonary manifestations. Increasing age and the presence of underlying respiratory diseases worsens the prognosis. Unlike other respiratory viral infections, transmission of SARS was less frequent in the first 5days of illness and correlated with low viral load in the upper respiratory tract at this stage of the illness. This fortuitous feature of the disease allowed the public health measures of case detection and patient isolation to interrupt virus transmission in the community and abort the SARS outbreak. Bats are a reservoir of a virus closely related to SARS CoV and this may be the likely precursor from which the human-adapted SARS CoV emerged. Small mammals such as ‘civet-cats’ (Paguma larvata) within live animal markets in southern China serve as amplifiers of infection and these markets were the likely interface where zoonotic transmission occurred. The viral spike protein is necessary and sufficient for inducing protective antibody responses and has been a key target in the development of candidate vaccines.

negative: [Standardized diagnosis and treatment of colorectal cancer during the outbreak of novel coronavirus pneumonia in Renji hospital]. Novel coronavirus pneumonia (NCP) is currently raging in China. It has been proven that NCP can be transmitted from human to human and cause hospital infection, which seriously threatens surgical staffs and inpatients. Although colorectal surgery is not a front-line subject in the fight against the epidemic, but in this special situation, now it is a difficult task that with the premise of how to maximize the protection for patients and their families, health of medical staff, and the safety of wards and hospitals, we can provide the highest quality medical services to ensure the orderly development of previous clinical work. Referring to the "Diagnosis and Treatment Scheme for NCP (Trial Version 4 and 5)" and combining the actual practice situation in our hospital with the "Summary of New Coronavirus Files of Shanghai Renji Hospital", we summarize how to carry out the clinical practice of colorectal surgery under the situation of the prevention and control of the NCP epidemiology, meanwhile under such situation aiming the procedure of diagnose and treatment for emergency patients with colorectal tumor, we share the experiences of the diagnosis of colorectal tumor, the management of patients with colorectal cancer who are scheduled to be admitted for surgery, the protection of wards, the perioperative management. More importantly, we introduce in detail the operative management and perioperative management of colorectal surgery patients suspected or diagnosed with new coronary pneumonia, including prevention and control measures for medical staff, operating rooms and surgical instruments. The main points are as follows: (1) Multidisciplinary team (MDT) must be run through the diagnosis and treatment of colorectal cancer. The members include not only routine departments, but also respiratory department and infectious department. (2) Colonoscopy examination may cause cross infection of NCP to patients and doctors. Therefore, it is prior to examine the emergency cases and life-threatening patients (bleeding, obstruction, gastrointestinal foreign bodies, etc.). If the emergent patients (intestinal obstruction) with suspected or confirmed NCP, the surgeons must perform emergency surgery, and intestinal decompressive tube through colonoscopy is not recommended. (3) The colorectal cancer patients with suspected or confirmed NCP should be placed in the isolated room with separate medical devices, and the operative room with negative pressure (under-5 Pa) must be separated. All disposable medical items, body fluids and feces of the patients in perioperative periods must be unified disposed according to the medical waste standard. (4) The surgical medical workers who process colorectal cancer patients with NCP must be protected by three-level. After operation, the medical workers must receive medical observation and be isolated for 14 days. We hope our "Renji experience" will be beneficial to colleagues.

negative: Coronaviruses pandemics: Can neutralizing antibodies help? For the first time in Homo sapiens history, possibly, most of human activities is stopped by coronavirus disease 2019 (COVID-19). Nearly eight billion people of this world are facing a great challenge, maybe not "to be or not to be" yet, but unpredictable. What happens to other major pandemics in the past, and how human beings went through these hurdles? The human body is equipped with the immune system that can recognize, respond and fight against pathogens such as viruses. Following the innate response, immune system processes the adaptive response by which each pathogen is encoded and recorded in memory system. The humoral reaction containing cytokines and antibodies is expected to activate when the pathogens come back. Exploiting this nature of body protection, neutralizing antibodies have been investigated. Learning from past, in parallel to SARS-CoV-2, other coronaviruses SARS-CoV and MERS-CoV who caused previous pandemics, are recalled in this review. We here propose insights of origin and characteristics and perspective for the future of antibodies development.

negative: Diagnosis and treatment of novel coronavirus pneumonia based on the theory of traditional Chinese medicine Abstract Since the outbreak of novel coronavirus pneumonia (coronavirus disease 2019, COVID-19) in December 2019, it has rapidly spread to 187 countries, causing serious harm to the health of people and a huge social burden. However, currently, drugs specifically approved for clinical use are not available, except for vaccines against COVID-19 that are being evaluated. Traditional Chinese medicine (TCM) is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients, and has a better ability of epidemic prevention and control. The authors comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM, and discussed its syndrome differentiation, treatment and prevention measures so as to provide strategies and reference for the prevention and treatment with TCM.

negative: Current efforts and challenges facing responses to 2019-nCoV in Africa The novel coronavirus is a pandemic that has started to creep into Africa thus making the virus a truly global, health security threat. The number of new 2019-nCoV cases has been rising in Africa, though currently lower than the cases reported outside the region. African countries have activated their Emergency Operations Centres to coordinate responses and preparedness activities to the pandemic. A series of measures such as restricting travel, case detection and contact tracing, mandatory quarantine, guidance and information to the public among other efforts are being implemented across Africa. However, the presence of porous borders, the double burden of communicable and non-communicable diseases, poverty, poor health literacy, infodemic and family clustering, and most of all, weak health systems, may make containment challenging. It is important for African countries to continue to intensify efforts and address the challenges to effectively respond to the uncertainty the pandemic poses.

negative: How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes On rounds in a 20-bed intensive care unit (ICU) one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure and others whose kidneys were on a dangerous downhill slide Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped All shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine “They are all COVID positive ” As the number of confirmed cases of COVID-19 surges past 2 2 million globally and deaths surpass 150,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body They are realizing that although the lungs are ground zero, its reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain

negative: Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington BACKGROUND: Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel among facilities in a region. METHODS: After identification on February 28, 2020, of a confirmed case of Covid-19 in a skilled nursing facility in King County, Washington, Public Health–Seattle and King County, aided by the Centers for Disease Control and Prevention, launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control. RESULTS: As of March 18, a total of 167 confirmed cases of Covid-19 affecting 101 residents, 50 health care personnel, and 16 visitors were found to be epidemiologically linked to the facility. Most cases among residents included respiratory illness consistent with Covid-19; however, in 7 residents no symptoms were documented. Hospitalization rates for facility residents, visitors, and staff were 54.5%, 50.0%, and 6.0%, respectively. The case fatality rate for residents was 33.7% (34 of 101). As of March 18, a total of 30 long-term care facilities with at least one confirmed case of Covid-19 had been identified in King County. CONCLUSIONS: In the context of rapidly escalating Covid-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of Covid-19.

negative: A Hybrid Model for Disease Spread and an Application to the SARS Pandemic Pandemics can cause immense disruption and damage to communities and societies. Thus far, modeling of pandemics has focused on either large-scale difference equation models like the SIR and the SEIR models, or detailed micro-level simulations, which are harder to apply at a global scale. This paper introduces a hybrid model for pandemics considering both global and local spread of infections. We hypothesize that the spread of an infectious disease between regions is significantly influenced by global traffic patterns and the spread within a region is influenced by local conditions. Thus we model the spread of pandemics considering the connections between regions for the global spread of infection and population density based on the SEIR model for the local spread of infection. We validate our hybrid model by carrying out a simulation study for the spread of SARS pandemic of 2002-2003 using available data on population, population density, and traffic networks between different regions. While it is well-known that international relationships and global traffic patterns significantly influence the spread of pandemics, our results show that integrating these factors into relatively simple models can greatly improve the results of modeling disease spread.

negative: Maintenance of pluripotency in mouse embryonic stem cells persistently infected with murine coronavirus. A persistently coronavirus-infected embryonic stem (ES) cell line A3/MHV was established by infecting an ES cell line, A3-1, with mouse hepatitis virus type-2. Although almost all A3/MHV cells were found infected, both A3/MHV and A3-1 cells expressed comparable levels of cell surface differentiation markers. In addition, A3/MHV cells retained the ability to form embryoid bodies. These results suggest that persistent coronavirus infection does not affect the differentiation of ES cells.

negative: Is thermal scanner losing its bite in mass screening of fever due to SARS? Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a coronavirus. Screening to detect a potential SARS infected person plays an important role in preventing the spread of SARS. The use of infrared thermal imaging cameras has been proposed as a noninvasive, speedy, cost effective and fairly accurate means for mass blind screening of potential SARS infected persons. Infrared thermography provides a digital image showing temperature patterns. This has been previously utilized in the detection of inflammation and nerve dysfunctions. It is believed that IR cameras can potentially be used to detect subjects with fever, the cardinal symptom of SARS, and avian influenza. The accuracy of the infrared system can, however, be affected by human, environmental, and equipment variables. It is also limited by the fact that the thermal imager measures the skin temperature and not the core body temperature. As known, the body determines a temperature as its so‐called “set point” at any one time during the body temperature regulation. Fever happens if the hypothalamus detects pyrogens and then raises the set point. The time course of a typical fever can be divided into three stages. When the fever initiates, the body attempts to raise its temperature but vasoconstriction occurs to prevent heat loss through the skin. With this reason, some individuals at this stage of fever (at the rising slope and immediately after fever begins or falling slope after the fever breaks) will not be detected by the scanner if it is not designed to detect subject at the plateau of the fever (with her/his high core temperature) in particular. This paper aims to study the effectiveness of infrared systems for its application in mass blind screening to detect subjects with elevated body temperature. For this application, it is critical for thermal imagers to be able to identify febrile from normal subjects accurately. Minimizing the number of false positive and false negative cases, improves the efficiency of the screening stations. False negative results should be avoided at all costs, as letting a SARS infected person through the screening process may result in potentially catastrophic results. Various statistical methods such as linear regression, Receiver Operating Characteristics analysis, and neural networks based classification were used to analyze the temperature data collected from various sites on the face on both the frontal and side profiles. Two important conclusions were drawn from the analysis: the best region on the face to obtain temperature readings and the optimal preset threshold temperature for the thermal imager. To conclude, the current research application will remain an interest and useful for reference by both local and overseas manufacturers of thermal scanners, users, and various government and private establishments. As elevation of body temperature is a common presenting symptom for many illnesses including infectious diseases, thermal imagers are useful tools for mass screening of body temperature not only for SARS but also during other public health crisis where widespread transmission of infection is a concern.

negative: Coronavirus (COVID-19): A Review of Clinical Features, Diagnosis, and Treatment Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. A total of six species have been identified to cause disease in humans. They are known to infect the neurological, respiratory, enteric, and hepatic systems. The past few decades have seen endemic outbreaks in the form of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome related coronavirus (SARS-CoV). Yet again, we see the emergence of another outbreak due to a new strain called the SARS-CoV-2 virus. The most recent outbreak initially presented as pneumonia of unknown etiology in a cluster of patients in Wuhan, China. The epicenter of infection was linked to seafood and exotic animal wholesale markets in the city. SARS-CoV-2 is highly contagious and has resulted in a rapid pandemic of COVID-19. As the number of cases continues to rise, it is clear that these viruses pose a threat to public health. This review will introduce a general overview of coronavirus and describe the clinical features, evaluation, and treatment of COVID-19 patients. It will also provide a means to raise awareness among primary and secondary healthcare providers during the current pandemic. Furthermore, our review focuses on the most up-to-date clinical information for the effective management, prevention, and counseling of patients worldwide.

negative: Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome Severe acute respiratory syndrome (SARS) is thought to be caused by a novel coronavirus, SARS-associated coronavirus. We studied viral shedding of SARS coronavirus to improve diagnosis and infection control. Reverse-transcriptase PCR was done on 2134 specimens of different types. 355 (45%) specimens of nasopharyngeal aspirates and 150 (28%) of faeces were positive for SARS coronavirus RNA. Positive rates peaked at 6–11 days after onset of illness for nasopharyngeal aspirates (87 of 149 [58%], to 37 of 62 [60%]), and 9–14 days for faeces (15 of 22 [68%], to 26 of 37 [70%]). Overall, peak viral loads were reached at 12–14 days of illness when patients were probably in hospital care, which would explain why hospital workers were prone to infection. Low rate of viral shedding in the first few days of illness meant that early isolation measures would probably be effective.

negative: Environmental Conditions Affect Exhalation of H3N2 Seasonal and Variant Influenza Viruses and Respiratory Droplet Transmission in Ferrets The seasonality of influenza virus infections in temperate climates and the role of environmental conditions like temperature and humidity in the transmission of influenza virus through the air are not well understood. Using ferrets housed at four different environmental conditions, we evaluated the respiratory droplet transmission of two influenza viruses (a seasonal H3N2 virus and an H3N2 variant virus, the etiologic virus of a swine to human summertime infection) and concurrently characterized the aerosol shedding profiles of infected animals. Comparisons were made among the different temperature and humidity conditions and between the two viruses to determine if the H3N2 variant virus exhibited enhanced capabilities that may have contributed to the infections occurring in the summer. We report here that although increased levels of H3N2 variant virus were found in ferret nasal wash and exhaled aerosol samples compared to the seasonal H3N2 virus, enhanced respiratory droplet transmission was not observed under any of the environmental settings. However, overall environmental conditions were shown to modulate the frequency of influenza virus transmission through the air. Transmission occurred most frequently at 23°C/30%RH, while the levels of infectious virus in aerosols exhaled by infected ferrets agree with these results. Improving our understanding of how environmental conditions affect influenza virus infectivity and transmission may reveal ways to better protect the public against influenza virus infections.

negative: Astrovirology, Astrobiology, Artificial Intelligence: Extra-Solar System Investigations This chapter attempts to encompass and tackle a large problem in Astrovirology and Astrobiology. There is a huge anthropomorphic prejudice that although life is unlikely, the just-right Goldilocks terrestrial conditions mean that the just-right balance of minerals and basic small molecules inevitably result in life as we know it throughout our solar system, galaxy, and the rest of the universe. Moreover, when such conditions on planets such as ours may not be quite right for the origin of life, it is popularly opined that asteroids and comets magically produce life or at the very least, the important, if not crucial components of terrestrial life so that life then blooms, when their fragments cruise the solar system, stars, and galaxies, and plummet onto appropriately bedecked planets and moons. It is no longer extraordinary to detect extraterrestrial solar systems. Moreover, since extra-solar system space exploration has commenced, this provides the problem of detecting life with enhanced achievability. Small organisms, which replicate outside of a living cell or host, would not be catalogued as viruses. How about viruses that cohabit with life? On the Earth, viruses are a major, if underestimated, condition of life – will that be the case elsewhere? Detection of extra-solar system viruses, if they exist, requires finding life, since viruses necessitate life to replicate. (It should be noted, though, that viruses could be detected through various types of portable ultra-microscopes, including Electron Microscopes (EM) (scanning and transmission) as well as Atomic Force Microscopes (AFM).) However, extra-solar system detection of life does not oblige that viruses exist ubiquitously. Viruses are important potential components of biospheres because of their multiple interactions and influence on evolution, although viruses are small and obligatory parasitic. In addition, nanotechnology – living or replicating nano-synthetic machine organisms might also be present out there, and require consideration as well. An imposing caveat is that, if found, could some extraterrestrial viruses and synthetic nanotechnological microorganisms infect humans? Possibly, intelligence and cognition may at times be contemporaneous with life. Concomitantly, life and viruses that may be detected, could well be impacted upon by intelligences existing on such exoplanets (and vice versa). Coming to an understanding of the plurality of extraterrestrial intelligence is an optimal objective, in order to avoid causing harm on exoplanets, as well as avoiding conflict and possible human devastation. This is especially the case if we encounter greatly advanced galactic-level civilizations, compared to terrestrial civilizations. Their machine and bionic technologies on the Dyson engineering civilization scale may be prominently superior to ours; their biological expertise may be similarly critically radical. For example, they may use viruses for purposes for which we are barely aware, and which could be utterly deadly for humans. A series of steps is being taken in space exploration. Scientists hypothesize and claim that types of life may be near the Earth, in the solar system, and outside the solar system, similar to ours in the sense that only such conditions, Goldilocks conditions, are key sine qua non requirements, based on our terrestrial chemistry and biochemistry. If detected within the solar system, will life or its remnants resemble terrestrial life? Outside the solar system a similar chauvinism exists, although the likelihood for life, in any event, remains probably low, according to more cautious approaches to the problem. The study of our solar system includes planets, asteroids, comets, and other planetesimals that have been in overall contiguity during several billion years; anthropomorphisms claims life consequently has been developing along terrestrial-type mechanisms. However, a non-anthropomorphic view would surmise, probably not, especially for extra-solar system locales. The prime warning and admonition in all these deliberations is the contamination and damage, which current and past practice and procedures has caused and continues, due to insufficient biocontainment concepts and technology to date. Advances in the development of robotics, artificial intelligence (AI), and high capacity ultrafast quantum computers (QC) greatly enhance the sophisticated control and logical development of extra-solar system studies. Consequently, future long-range manned space exploration seems unwarranted. Clearly, reduced dangers to human health and safety, will result from the use of intelligent machine-based investigations and besides, with increased cost-effectiveness. Space exploration comes at great cost to humanity as a whole and utilizes global resources. Consequently, appropriate organizational measures and planning/cooperation need to be in place. Moreover, the bottom line is that despite all the slogans and claims, there have been next to no financial benefits to our planet as a whole. Such financial and heedless difficulties need to be addressed, the sooner the better. In addition, prior to exposure to exoplanetary life, deep understanding of the problems of infectious diseases and immune dysfunction risks are needed. In addition, global efforts should avoid serendipity and stochasticity as this work should be directed with long-term organization, commitment, scientific, and technological methodology. This chapter briefly reviews such questions assuming a new paradigm for oversight of extrasolar system viral investigations including intelligence and life. Finances are included as an essential adjunct.

negative: The effect of two closely inserted transcription consensus sequences on coronavirus transcription. Insertion of an intergenic region from the murine coronavirus mouse hepatitis virus into a mouse hepatitis virus defective interfering (DI) RNA led to transcription of subgenomic DI RNA in helper virus-infected cells. Using this system, we studied how two intergenic regions in close proximity affected subgenomic RNA synthesis. When two intergenic regions were separated by more than 100 nucleotides, slightly less of the larger subgenomic DI RNA (synthesized from the upstream intergenic region) was made; this difference was significant when the intergenic region separation was less than about 35 nucleotides. Deletion of sequences flanking the two intergenic regions inserted in close proximity did not affect transcription. No significant change in the ratio of the two subgenomic DI RNAs was observed when the sequence between the two intergenic regions was altered. Removal of the downstream intergenic region restored transcription of the larger subgenomic DI RNA. The UCUAAAC consensus sequence was needed for efficient suppression of the larger subgenomic DI RNA synthesis. These results demonstrated that the downstream intergenic sequence was suppressing subgenomic DI RNA synthesis from the upstream intergenic region. We discuss possible mechanisms to account for the regulation of this suppression of subgenomic DI RNA synthesis and the ways in which they relate to the general regulation of coronavirus transcription.

negative: Pay attention to situation of SARS-CoV-2 and TCM advantages in treatment of novel coronavirus infection Since the outbreak of the new coronavirus epidemic, novel coronavirus has infected nearly 100,000 people in more than 110 countries. How to face this new coronavirus epidemic outbreak is an important issue. Basic reproduction number (R0) is an important parameter in epidemiology; The basic reproduction number of an infection can be thought of as the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection. Epidemiology dynamics is a mathematical model based on a susceptibility-infection-recovery epidemic model. Researchers analyzed the epidemiological benefits of different transmission rates for the establishment of effective strategy in prevention and control strategies for epidemic infectious diseases. In this review, the early use of TCM for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have wide application in treating infectious and non-infectious diseases. The TCM theoretical system of treating epidemic diseases with TCM and the treatment scheme of integrated Chinese and Western medicine have proved their effectiveness in clinical practice. TCM can cure COVID-19 pneumonia, and also shows that the role of TCM in blocking the progress of COVID-19 pneumonia.

negative: EMERGING RESPIRATORY DISEASE - CORONAVIRUSES

negative: Keeping the Country Positive during the COVID 19 Pandemic: Evidence from India

negative: COVID-19 (Novel Coronavirus 2019) - recent trends. The World Health Organization (WHO) has issued a warning that, although the 2019 novel coronavirus (COVID-19) from Wuhan City (China), is not pandemic, it should be contained to prevent the global spread. The COVID-19 virus was known earlier as 2019-nCoV. As of 12 February 2020, WHO reported 45,171 cases and 1115 deaths related to COVID-19. COVID-19 is similar to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) virus in its pathogenicity, clinical spectrum, and epidemiology. Comparison of the genome sequences of COVID-19, SARS-CoV, and Middle East Respiratory Syndrome coronavirus (MERS-CoV) showed that COVID-19 has a better sequence identity with SARS-CoV compared to MERS CoV. However, the amino acid sequence of COVID-19 differs from other coronaviruses specifically in the regions of 1ab polyprotein and surface glycoprotein or S-protein. Although several animals have been speculated to be a reservoir for COVID-19, no animal reservoir has been already confirmed. COVID-19 causes COVID-19 disease that has similar symptoms as SARS-CoV. Studies suggest that the human receptor for COVID-19 may be angiotensin-converting enzyme 2 (ACE2) receptor similar to that of SARS-CoV. The nucleocapsid (N) protein of COVID-19 has nearly 90% amino acid sequence identity with SARS-CoV. The N protein antibodies of SARS-CoV may cross react with COVID-19 but may not provide cross-immunity. In a similar fashion to SARS-CoV, the N protein of COVID-19 may play an important role in suppressing the RNA interference (RNAi) to overcome the host defense. This mini-review aims at investigating the most recent trend of COVID-19.

negative: Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review INTRODUCTION: Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies. METHODS: We searched five general, three Chinese and four coronavirus disease (COVID-19)-specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments. RESULTS: We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps. CONCLUSION: While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.

negative: Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number [Formula: see text]). We found that in countries with low connectivity to China but with relatively high [Formula: see text] , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low [Formula: see text] benefit the most from policies that further reduce [Formula: see text]. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.

negative: Are We from Outer Space?: A Critical Review of the Panspermia Hypothesis The biological record suggests that life on Earth arose as soon as conditions were favorable, which indicates that life either originated quickly, or arrived from elsewhere to seed Earth. Experimental research under the theme of “astrobiology” has produced data that some view as strong evidence for the second possibility, known as the panspermia hypothesis. While it is not unreasonable to consider the possibility that Earth’s life originated elsewhere and potentially much earlier, we conclude that the current literature offers no definitive evidence to support this hypothesis. Chladni’s view, that they fall from the skies, pronounced in 1795, was ridiculed by the learned men of the times. (Rachel, 1881) Evidence of life on Mars, even if only in the distant past, would finally answer the age-old question of whether living beings on Earth are alone in the universe. The magnitude of such a discovery is illustrated by President Bill Clinton’s appearance at a 1996 press conference to announce that proof had been found at last. A meteorite chipped from the surface of the Red Planet some 15 million years ago appeared to contain the fossil remains of tiny life-forms that indicated life had once existed on Mars. (Young and Martel, 2010)

negative: SARS‐CoV‐2: Structural diversity, phylogeny, and potential animal host identification of spike glycoprotein To investigate the evolutionary history of the current pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a total of 137 genomes of coronavirus strains with release dates between January 2019 and 25 March 2020, were analyzed. To investigate the potential intermediate host of the SARS‐CoV‐2, we analyzed spike glycoprotein sequences from different animals, with particular emphasis on bats. We performed phylogenetic analysis and structural reconstruction of the spike glycoproteins with subsequent alignment and comparison. Our phylogenetic results revealed that SARS‐CoV‐2 was more similar to the bats' betacoronavirus isolates: HKU5‐related from Pipistrellus abramus and HKU4‐related from Tylonycteris pachypus. We also identified a yak betacoronavirus strain, YAK/HY24/CH/2017, as the closest match in the comparison of the structural models of spike glycoproteins. Interestingly, a set of unique features has been described for this particular strain of the yak betacoronavirus. Therefore, our results suggest that the human SARS‐CoV‐2, responsible for the current outbreak of COVID‐19, could also come from yak as an intermediate host.

negative: Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell–cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.

negative: Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2 Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen A [HLA-A], -B, and -C genes) may affect susceptibility to and severity of the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We performed a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA-A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explored the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome was successfully sampled and was represented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting that individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (M. Lin, H.-T. Tseng, J. A. Trejaut, H.-L. Lee, et al., BMC Med Genet 4:9, 2003, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting that it could enable cross-protective T-cell-based immunity. Finally, we reported global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic. IMPORTANCE Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.

negative: The Emerging Threat of Ebola Ebola is one of the deadliest infectious disease of the modern era. Over 50% of those infected die. Prior to 1976, the disease was unknown. No one knows exactly where it came from, but it is postulated that a mutation in an animal virus allowed it to jump species and infect humans. In 1976 simultaneous outbreaks of Ebola occurred in what is now South Sudan and the Democratic Republic of the Congo (DRC). For 20 years, only sporadic cases were seen, but in 1995 a new outbreak occurred killing hundreds in the DRC. Since that time the frequency of these outbreaks has been increasing. It is uncertain why this is occurring, but many associate it with increasing human encroachment into forested areas bringing people and animals into more intimate contact and increased mobility of previously remote population. This chapter will navigate Ebola in the context of global health and security. There are multiple objectives of this chapter. First is to provide a basic understanding of Ebola disease processes and outbreak patterns. Second, is to explore the interplay between social determinants of health and Ebola. The role of technology in spreading Ebola outbreaks will be explained as will Ebola’s potential as a bioweapon. Readers will gain understanding of the link between environmental degradation and Ebola outbreaks. This chapter will be divided into five main sections. These are (1) a case study; (2) Ebola Disease process; (3) Social determinants of health and Ebola; (4) Ebola in the modern era, and (5) the link between Ebola and environmental degradation.

negative: Household transmissions of SARS-CoV-2 in the time of unprecedented travel lockdown in China IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, China, in December 2019 and then spread globally. Limited information is available for characterizing epidemiological features and transmission patterns in the regions outside of Hubei Province. Detailed data on transmission at the individual level could be an asset to understand the transmission mechanisms and respective patterns in different settings. OBJECTIVE: To reconstruct infection events and transmission clusters of SARS-CoV-2 for estimating epidemiological characteristics at household and non-household settings, including super-spreading events, serial intervals, age- and gender-stratified risks of infection in China outside of Hubei Province. DESIGN, SETTING, AND PARTICIPANTS: 9,120 confirmed cases reported online by 264 Chinese urban Health Commissions in 27 provinces from January 20 to February 19, 2020. A line-list database is established with detailed information on demographic, social and epidemiological characteristics. The infection events are categorized into the household and non-household settings. EXPOSURES: Confirmed cases of SARS-CoV-2 infections. MAIN OUTCOMES AND MEASURES: Information about demographic characteristics, social relationships, travel history, timelines of potential exposure, symptom onset, confirmation, and hospitalization were extracted from online public reports. 1,407 infection events formed 643 transmission clusters were reconstructed. RESULTS: In total 34 primary cases were identified as super spreaders, and 5 household super-spreading events were observed. The mean serial interval is estimated to be 4.95 days (standard deviation: 5.24 days) and 5.19 days (standard deviation: 5.28 days) for households and non-household transmissions, respectively. The risk of being infected outside of households is higher for age groups between 18 and 64 years, whereas the hazard of being infected within households is higher for age groups of young (<18) and elderly (>65) people. CONCLUSIONS AND RELEVANCE: The identification of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of age between 18 and 64 indicate a significant barrier to the case identification and management, which calls for intensive non-pharmaceutical interventions (e.g. cancellation of public gathering, limited access of public services) as the potential mitigation strategies.

negative: Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV) The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.

negative: Current status and progress of 2019 novel coronavirus pneumonia/ 中华危重病急救医学 Recently, the 2019 novel coronavirus (2019-nCoV) pneumonia outbroke in Wuhan and rapidly spread to all over China and even the world. Because of the strong infectivity and various clinical symptoms, it has brought certain difficulties to the epidemic prevention and control. Currently there is no specific drug for 2019-nCoV. Previous drugs used to treat other coronaviruses may be effective, but further clinical trials remain needed. We reviewed literature on the epidemiology, etiology, clinical manifestations, imaging manifestations, laboratory examination, diagnosis, complications, treatment and outcome of 2019-nCoV pneumonia.

negative: Can biowarfare agents be defeated with light? Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious and profoundly virulent diseases may be caused in combat personnel or in civilian populations by the appropriate dissemination of viruses, bacteria, spores, fungi, or toxins. Dissemination may be airborne, waterborne, or by contamination of food or surfaces. Countermeasures may be directed toward destroying or neutralizing the agents outside the body before infection has taken place, by destroying the agents once they have entered the body before the disease has fully developed, or by immunizing susceptible populations against the effects. A range of light-based technologies may have a role to play in biodefense countermeasures. Germicidal UV (UVC) is exceptionally active in destroying a wide range of viruses and microbial cells, and recent data suggests that UVC has high selectivity over host mammalian cells and tissues. Two UVA mediated approaches may also have roles to play; one where UVA is combined with titanium dioxide nanoparticles in a process called photocatalysis, and a second where UVA is combined with psoralens (PUVA) to produce “killed but metabolically active” microbial cells that may be particularly suitable for vaccines. Many microbial cells are surprisingly sensitive to blue light alone, and blue light can effectively destroy bacteria, fungi, and Bacillus spores and can treat wound infections. The combination of photosensitizing dyes such as porphyrins or phenothiaziniums and red light is called photodynamic therapy (PDT) or photoinactivation, and this approach cannot only kill bacteria, spores, and fungi, but also inactivate viruses and toxins. Many reports have highlighted the ability of PDT to treat infections and stimulate the host immune system. Finally pulsed (femtosecond) high power lasers have been used to inactivate pathogens with some degree of selectivity. We have pointed to some of the ways light-based technology may be used to defeat biological warfare in the future.

negative: From the frontlines of COVID-19 - How prepared are we as obstetricians: a commentary. The World Health Organization (WHO) has declared the outbreak of novel coronavirus (2019-nCoV) - now known as Coronavirus Disease (COVID-19)1 - as a global health emergency. Singapore currently stands as the country with the highest number of reported cases of COVID-19 outside of China2 , excluding patients on a cruise ship offshore of Japan.

negative: Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Last decade witnessed the outbreak of many life-threatening human pathogens including Nipah, Ebola, Chikungunya, Zika, Middle East respiratory syndrome coronavirus (MERS-CoV), Severe Acute respiratory syndrome coronavirus (SARS-CoV) and more recently novel coronavirus (2019-nCoV or SARS-CoV-2). The disease condition associated with novel coronavirus, referred to as Coronavirus disease (COVID-19). The emergence of novel coronavirus in 2019 in Wuhan, China marked the third highly pathogenic coronavirus infecting humans in the 21st century. The continuing emergence of coronaviruses at regular intervals poses a significant threat to human health and economy. Ironically, even after a decade of research on coronavirus, still there are no licensed vaccines or therapeutic agents to treat coronavirus infection which highlights an urgent need to develop effective vaccines or post-exposure prophylaxis to prevent future epidemics. Several clinical, genetic and epidemiological features of COVID-19 resemble SARS-CoV infection. Hence, the research advancements on SARS-CoV treatment might help scientific community in quick understanding of this virus pathogenesis and develop effective therapeutic/prophylactic agents to treat and prevent this infection. Monoclonal antibodies represent the major class of biotherapeutics for passive immunotherapy to fight against viral infection. The therapeutic potential of monoclonal antibodies has been well recognized in the treatment of many diseases. Here, we summarize the potential monoclonal antibody based therapeutic intervention for COVID-19 by considering the existing knowledge on the neutralizing monoclonal antibodies against similar coronaviruses SARS-CoV and MERS-CoV. Further research on COVID-19 pathogenesis could identify appropriate therapeutic targets to develop specific anti-virals against this newly emerging pathogen.

negative: PhEVER: a database for the global exploration of virus–host evolutionary relationships Fast viral adaptation and the implication of this rapid evolution in the emergence of several new infectious diseases have turned this issue into a major challenge for various research domains. Indeed, viruses are involved in the development of a wide range of pathologies and understanding how viruses and host cells interact in the context of adaptation remains an open question. In order to provide insights into the complex interactions between viruses and their host organisms and namely in the acquisition of novel functions through exchanges of genetic material, we developed the PhEVER database. This database aims at providing accurate evolutionary and phylogenetic information to analyse the nature of virus–virus and virus–host lateral gene transfers. PhEVER (http://pbil.univ-lyon1.fr/databases/phever) is a unique database of homologous families both (i) between sequences from different viruses and (ii) between viral sequences and sequences from cellular organisms. PhEVER integrates extensive data from up-to-date completely sequenced genomes (2426 non-redundant viral genomes, 1007 non-redundant prokaryotic genomes, 43 eukaryotic genomes ranging from plants to vertebrates) and offers a clustering of proteins into homologous families containing at least one viral sequences, as well as alignments and phylogenies for each of these families. Public access to PhEVER is available through its webpage and through all dedicated ACNUC retrieval systems.

negative: Negligible risk of the COVID-19 resurgence caused by work resuming in China (outside Hubei): a statistical probability study The COVID-19 outbreak in China appears to reach the late stage since late March 2020, and a stepwise restoration of economic operations is implemented. Risk assessment for such economic restoration is of significance. Here, we estimated the probability of COVID-19 resurgence caused by work resuming in typical provinces/cities and found that such probability is very limited (<5% for all the regions except Beijing). Our work may inform provincial governments to make risk level-based, differentiated control measures.

negative: A Stakeholder Survey on Live Bird Market Closures Policy for Controlling Highly Pathogenic Avian Influenza in Vietnam Extensive research in Vietnam and elsewhere has shown that live bird markets (LBMs) play a significant role in the ecology and zoonotic transmission of avian influenzas (AIs) including H5N1 and H7N9. Vietnam has a large number of LBMs reflecting the consumer preferences for live poultry. Under pressure to mitigate risks for H7N9 and other zoonotic AIs, Vietnam is considering, among other mitigation measures, temporary closures of LBMs as a policy to reduce risk of AI outbreaks. However, the efficacy of market closure is debated, particularly because little is known about how poultry traders may react, and whether trading may emerge outside formal marketplaces. Combining efforts of anthropologists, economists, sociologists, and veterinarians can be useful to elucidate the drivers behind poultry traders’ reactions and better understanding the barriers to implementing risk mitigation measures. In this paper, we present results from a stakeholder survey of LBM stakeholders in Vietnam. Our qualitative data show that trading outside formal markets is very likely to occur in the event of a temporary LBM market closure. Our data show that the poultry value chain in Vietnam remains highly flexible, with traders willing and able to trade poultry in many possible locations. Our results indicate that simplification of the poultry value chain along with strict enforcement, engagement of stakeholders, and adequate communication would be a necessary prerequisite before market closure could be an effective policy.

negative: Report from the World Health Organization’s third Product Development for Vaccines Advisory Committee (PDVAC) meeting, Geneva, 8–10th June 2016 The third meeting of WHO’s Product Development for Vaccines Advisory Committee (PDVAC) was held in June 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. Since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase III trials of a respiratory syncytial virus (RSV) vaccine candidate has started in the elderly and pregnant women. In addition, PDVAC has also supported vaccine development efforts against important emerging pathogens, including Middle Eastern Coronavirus (MERS CoV) and Zika virus. Trials of HIV and tuberculosis vaccine candidates are steadily progressing towards pivotal data points, and the leading norovirus vaccine candidate has entered a phase IIb efficacy study. WHO’s Immunization, Vaccine and Biologicals (IVB) department is actively working in several pathogen areas on the recommendation of PDVAC, as well as continuing horizon scanning for advances in the development of vaccines that may benefit low and middle income countries (LMICs), such as the recent licensure of the enterovirus 71 (EV71) vaccine in China. Following on from discussions with WHO’s Strategic Advisory Group of Experts (SAGE) on Immunization, PDVAC will also look beyond licensure and consider data needs for vaccine recommendation and implementation to reduce the delay between vaccine approval and vaccine impact.

negative: Chapter 17 Family Coronaviridae Abstract Members of the family Coronaviridae are large, enveloped, single-stranded RNA viruses. They are the largest known RNA viruses, with genomes ranging from 25 to 32kb and virions of 118–140nm in diameter. The family is divided into two subfamilies, the Coronavirinae and the Torovirinae. They can be distinguished on the basis of their nucleocapsids as the toroviruses have unique doughnut-shaped nucleocapsids. Virions are roughly spherical and are notable for the large spike (S) glycoprotein that extends from the virus envelope. Current taxonomy places the family in the order Nidovirales. Within the subfamily Coronavirinae are four genera, the alpha-, beta-, gamma-, and deltacoronaviruses. All family members share the same unique strategy for mRNA synthesis whereby the polymerase complex jumps or moves from one region of the template to a more distant region. The need for the polymerase complex to dissociate from the template may explain the high rate of RNA recombination that occurs during genome replication. Both the coronaviruses and toroviruses are enteric and respiratory tract pathogens, usually associated with only mild disease (or inapparent infection). However the human severe acute respiratory syndrome (SARS) coronavirus and the Middle East respiratory syndrome (MERS) coronavirus cause severe respiratory diseases.

negative: Dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a Coronavirus Disease 2019 patient Abstract We report the dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a COVID-19 patient: from successive negative results to successive single positive nucleocapsid gene, to two positive target genes (orf1ab and nucleocapsid) by RT-PCR testing of SARS-Cov-2, and describe the diagnosis, clinical course, and management of the case. In this case, negative results of RT-PCR testing was not excluded to diagnose a suspected COVID-19 patient, clinical signs and symptoms, other laboratory findings, and chest CT images should be taken into account for the absence of enough positive evidence. This case highlights the importance of successive sampling and testing SARS-Cov-2 by RT-PCR as well as the increased value of single positive target gene from pending to positive in two specimens to diagnose laboratory-confirmed COVID-19.

negative: Infectious Diseases of the Gastrointestinal Tract

negative: Infection respiratoire nosocomiale par le coronavirus dars une unité de réanimation néonatále: évaluation prospective

negative: An outbreak of feline infectious peritonitis in a Taiwanese shelter: epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV) infection. FCoV can be divided into serotypes I and II. The virus that causes FIP (FIPV) is believed to occur sporadically and spread infrequently from cat to cat. Recently, an FIP outbreak from an animal shelter was confirmed in Taiwan. FCoV from all the cats in this shelter were analyzed to determine the epidemiology of this outbreak. Thirteen of 46 (28.2%) cats with typical signs of FIP were identified. Among them, seven cats were confirmed by necropsy and/or histopathological examinations. Despite the fact that more than one FCoV was identified in this multi-cat environment, the eight FIP cats were invariably found to be infected with a type II FCoV. Sequence analysis revealed that the type II FIPV detected from fecal samples, body effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene. Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene. Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death. Taken together, our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment.

negative: Excess cases of Influenza like illnesses in France synchronous with COVID19 invasion. Several French regions where COVID19 has been reported currently show a renewed increase in ILI cases in the general practice based Sentinelles network. Here we computed the number of excess cases by region and found correlation with the number of reported COVID19 cases so far. These data suggest larger circulation of SARS-CoV-2 in the French population than apparent from confirmed cases.

negative: In vitro inhibition of transmissible gastroenteritis coronavirus replication in swine testicular cells by short hairpin RNAs targeting the ORF 7 gene BACKGROUND: Transmissible gastroenteritis (TGE) is a highly contagious viral disease of swine, characterized by severe vomiting, diarrhea, and high mortality. Currently, the vaccines for it are only partially effective and no specific drug is available for treatment of TGE virus (TGEV) infection. RNA interference has been confirmed as a new approach for controlling viral infections. In this study, the inhibitory effect of short hairpin RNAs (shRNAs) targeting the ORF 7 gene of TGEV on virus replication was examined. RESULTS: Four theoretically effective sequences of TGEV ORF 7 gene were designed and selected for construction of shRNA expression plasmids. In the reporter assays, three of four shRNA expression plasmids were able to inhibit significantly the expression of ORF 7 gene and replication of TGEV, as shown by real-time quantitative RT-PCR analysis of viral ORF 7 and N genes and detection of virus titers (TCID(50)/ml). Stable swine testicular (ST) cells expressing the shRNAs were established. Observation of the cytopathic effect and apoptosis, as well as a cell proliferation assay demonstrated that the three shRNAs were capable of protecting ST cells against TGEV destruction, with high specificity and efficiency. CONCLUSIONS: Our results indicated that plasmid-transcribed shRNAs targeting the ORF 7 gene in the TGEV genome effectively inhibited expression of the viral target gene and viral replication in vitro. These findings provide evidence that the shRNAs have potential therapeutic application for treatment of TGE.

negative: The modelling of COVID19 pathways sheds light on mechanisms, opportunities and on controversial interpretations of medical treatments. v2 The new coronavirus (2019-nCoV or SARS-CoV2), inducing the current pandemic disease (COVID-19) and causing pneumoniae in humans, is dramatically increasing in epidemic scale since its first appearance in Wuhan, China, in December 2019. The first infection from epidemic coronaviruses in 2003 fostered the spread of an overwhelming amount of related scientific efforts. The manifold aspects that have been raised, as well as their redundancy offer precious information that has been underexploited and needs to be critically re-evaluated, appropriately used and offered to the whole community, from scientists, to medical doctors, stakeholders and common people. These efforts will favour a holistic view on the comprehension, prevention and development of strategies (pharmacological, clinical etc) as well as common intervention against the new coronavirus spreading. Here we describe a model that emerged from our analysis that was focused on the Renin Angiotensin System (RAS) and the possible routes linking it to the viral infection. because the infection is mediated by the viral receptor on human cell membranes Angiotensin Converting Enzyme (ACE2), which is a key component in RAS signalling. The model depicts the main pathways determining the disease and the molecular framework for its establishment, and can help to shed light on mechanisms involved in the infection. It promptly gives an answer to some of the controversial, and still open, issues concerning predisposing conditions and medical treatments that protect from or favour the severity of the disease (such as the use of ACE inhibitors or ARBs/sartans), or to the sex related biases in the affected population. The model highlights novel opportunities for further investigations, diagnosis and appropriate intervention to understand and fight COVID19.

negative: The effects of injection of bovine vaccine into a human digit: a case report BACKGROUND: The incidence of needlestick injuries in farmers and veterinary surgeons is significant and the consequences of such an injection can be serious. CASE PRESENTATION: We report accidental injection of bovine vaccine into the base of the little finger. This resulted in increased pressure in the flexor sheath causing signs and symptoms of ischemia. Amputation of the digit was required despite repeated surgical debridement and decompression. CONCLUSION: There have been previous reports of injection of oil-based vaccines into the human hand resulting in granulomatous inflammation or sterile abscess and causing morbidity and tissue loss. Self-injection with veterinary vaccines is an occupational hazard for farmers and veterinary surgeons. Injection of vaccine into a closed compartment such as the human finger can have serious sequelae including loss of the injected digit. These injuries are not to be underestimated. Early debridement and irrigation of the injected area with decompression is likely to give the best outcome. Frequent review is necessary after the first procedure because repeat operations may be required.

negative: Aerodrome Security The airport is the frontier between the outside world and the State in which the airline passenger lands. It is also the final point at which a person can be checked before embarking on a flight. Moreover, the aerodrome is where cargo is loaded into an aircraft before takeoff. Therefore, security at the airport carries multiple dimensions, from border control to body scanning; from cargo security to security of the aircraft and its passengers.

negative: Early Spread of SARS-Cov-2 in the Icelandic Population BACKGROUND Limited data exist on how SARS-CoV-2 enters and spreads in the general population. METHODS We used two strategies for SARS-CoV-2 testing: targeted testing of high-risk individuals (n=4,551) and a population screening (n=5,502). We sequenced SARS-CoV-2 from 340 individuals. RESULTS On March 22 2020, 528 had tested positive for SARS-CoV-2 in the targeted testing (11.6%) and 50 in the population screening (0.9%); approximately 0.2% of the Icelandic population. Large fractions of positives had travelled outside Iceland (38.4% and 34.0%). Fewer under 10 years old were positive than those older: 2.8% vs. 12.3% for targeted testing (P=1.6e-9) and 0.0% vs. 1.0% for population screening (P=0.031). Fewer females were positive in the targeted testing than males (9.5% vs. 14.6%, P=6.8e-9). SARS-CoV-2 came from eight clades, seven A clades and one B clade. The clade composition differed between the testing groups and changed with time. In the early targeted testing, 65.0% of clades were A2a1 and A2a2 derived from Italian and Austrian skiing areas, but in the later targeted testing went down to 30.6% and were overtaken by A1a and A2a, the most common clades in the population screening. CONCLUSION SARS-CoV-2 has spread widely in Iceland outside of the high-risk groups. Several strains cause these infections and their relative contribution changed rapidly. Children and females are less vulnerable than adults and males. To contain the pandemic we must increase the scope of the testing.

negative: Chapter 6 Cubic Membranes The Missing Dimension of Cell Membrane Organization Abstract Biological membranes are among the most fascinating assemblies of biomolecules: a bilayer less than 10 nm thick, composed of rather small lipid molecules that are held together simply by noncovalent forces, defines the cell and discriminates between “inside” and “outside”, survival, and death. Intracellular compartmentalization—governed by biomembranes as well—is a characteristic feature of eukaryotic cells, which allows them to fulfill multiple and highly specialized anabolic and catabolic functions in strictly controlled environments. Although cellular membranes are generally visualized as flat sheets or closely folded isolated objects, multiple observations also demonstrate that membranes may fold into “unusual”, highly organized structures with 2D or 3D periodicity. The obvious correlation of highly convoluted membrane organizations with pathological cellular states, for example, as a consequence of viral infection, deserves close consideration. However, knowledge about formation and function of these highly organized 3D periodic membrane structures is scarce, primarily due to the lack of appropriate techniques for their analysis in vivo. Currently, the only direct way to characterize cellular membrane architecture is by transmission electron microscopy (TEM). However, deciphering the spatial architecture solely based on two-dimensionally projected TEM images is a challenging task and prone to artifacts. In this review, we will provide an update on the current progress in identifying and analyzing 3D membrane architectures in biological systems, with a special focus on membranes with cubic symmetry, and their potential role in physiological and pathophysiological conditions. Proteomics and lipidomics approaches in defined experimental cell systems may prove instrumental to understand formation and function of 3D membrane morphologies.

negative: Comparison of real-time reverse transcriptase polymerase chain reaction of peripheral blood mononuclear cells, serum and cell-free body cavity effusion for the diagnosis of feline infectious peritonitis. Objectives Diagnosis of feline infectious peritonitis (FIP) remains challenging, especially in cats without effusions. The objective of this study was to evaluate the sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction (RT-PCR) detecting feline coronavirus (FCoV) RNA in peripheral blood mononuclear cells (PBMCs) and serum in comparison with the same real-time RT-PCR in cell-free body cavity effusion. Methods This prospective case-control study included 92 cats. Forty-three cats had a definitive diagnosis of FIP, established either by histopathological examination (n = 28) or by positive immunofluorescence staining of FCoV antigen in macrophages of effusions (n = 11), or by both methods (n = 4). Forty-nine control cats had other diseases but similar clinical signs. Real-time RT-PCR was performed on PBMCs of 37 cats (21 cats with FIP, 16 controls), on serum of 51 cats (26 cats with FIP, 25 controls) and on cell-free body cavity effusion of 69 cats (36 cats with FIP, 33 controls). Sensitivity, specificity, positive and negative predictive value, including 95% confidence intervals (CI), were calculated. Results Real-time RT-PCR of PBMCs, serum and cell-free body cavity effusion showed a specificity of 100% (95% CI 79.4-100% in PBMCs, 86.3-100% in serum, 89.4-100% in cell-free body cavity effusion) and a sensitivity of 28.6% (95% CI 11.3-52.2%) in PBMCs, 15.4% (95% CI 4.4-34.9%) in serum and 88.9% (95% CI 73.9-96.9%) in cell-free body cavity effusion to diagnose FIP. Conclusions and relevance Although it is known that RT-PCR can often provide false-positive results in healthy cats, this real-time RT-PCR was shown to be a specific tool for the diagnosis of FIP when applied in a clinical setting. Sensitivity in cell-free body cavity effusion was high but low in PBMCs and serum. PBMC samples showed a higher sensitivity than serum samples, and are therefore a better choice if no effusion is present.

negative: Moving-average based index to timely evaluate the current epidemic situation after COVID-19 outbreak A pneumonia outbreak caused by a novel coronavirus (COVID-19) occurred in Wuhan, China at the end of 2019 and then spread rapidly to the whole country. A total of 81,021 laboratory-confirmed cases, including 3,194 deaths (3.9%) had been reported in China by March 14, 2020, meanwhile, 61,518 laboratory-confirmed cases and 2,199 deaths were reported outside China. Common symptoms of COVID-19 pneumonia included fever, fatigue and dry cough. Faced with such a sudden outbreak of new infectious diseases, we have no history to learn from and no evidence to count on. Traditional models often predict inconsistent results. Aiming at estimate the epidemic trend timely after the outbreak, we mainly used 7-day moving average of log-transformed daily new cases (LMA) to establish a new index named "epidemic trend index", which will be used to predict the evolutionary trend of the epidemic situation and support epidemic control decision making processes. We used SARS epidemic data from Hong Kong in 2003 to verify the practicability of the new index, which shows that the index is acceptable. The epidemic trend index was then applied to the COVID-19 epidemic analysis in China. The results show that during the epidemic, the trend direction of different districts of China changed on different date. In the whole country and in Hubei Province alone, the epidemic reached the peak on February 9. While the peak appeared earlier, i.e. on February 5 in other provinces. It indicated that decisive outbreak control measures of the Chinese government are effective. While local governments should adjust management measures based on local risk level of epidemic. Although the epidemic has eased since late February, continued efforts in epidemic control are still needed to accelerate the end of the epidemic in China. However, the global COVID-19 epidemic outside China continues to expand as indicated by the epidemic trend index we proposed. In order to cope with the novel coronavirus pandemic, people all over the world should work together and governments of all countries should take efficient measures in the light of China's experience and according to national circumstances and local conditions.

negative: Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus BACKGROUND: Severe Acute Respiratory Syndrome (SARS) emerged as a human disease in 2002 and detailed phylogenetic analysis and epidemiological studies have suggested that the SARS-Coronavirus (SARS-CoV) originated from animals. The Spike (S) glycoprotein has been identified as a major target of protective immunity and contains at least three regions that are targeted by neutralizing antibodies in the S1 and S2 domains. We previously characterized a panel of neutralizing human monoclonal antibodies (MAbs) but the majority of epitopes recognized by the MAbs remained unknown. METHODS: In this study we generated neutralization escape mutants and studied the effect of these neutralization escape mutations on human and animal receptor usage as well as in vitro and in vivo fitness. RESULTS: Distinct but partially overlapping sets of amino acids were identified that are critical to the binding of MAbs with differential neutralization profiles. We also identified possible interactions between the S1 and S2 domains of the SARS-CoV S glycoprotein. Finally, we showed that escape from neutralization usually attenuates SARS-CoV infection. CONCLUSIONS: These data provide a mechanism to overcome neutralization escape by using broadly cross reactive cocktails of cross-neutralizing MAbs that recognize residues within the receptor binding domain, critical for virus replication and virulence.

negative: Preliminary prediction of the basic reproduction number of the Wuhan novel coronavirus 2019‐nCoV OBJECTIVES: To estimate the basic reproduction number of the Wuhan novel coronavirus (2019‐nCoV). METHODS: Based on the susceptible‐exposed‐infected‐removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurred before 26 January, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019‐nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome (SARS). RESULTS: The basic reproduction number fall between 2.8 and 3.3 by using the real‐time reports on the number of 2019‐nCoV‐infected cases from People's Daily in China and fall between 3.2 and 3.9 on the basis of the predicted number of infected cases from international colleagues. CONCLUSIONS: The early transmission ability of 2019‐nCoV is close to or slightly higher than SARS. It is a controllable disease with moderate to high transmissibility. Timely and effective control measures are needed to prevent the further transmissions.

negative: COVID-19, a worldwide public health emergency Abstract A new coronavirus outbreak emerged on the 31st of December 2019 in Wuhan, China, causing commotion among the medical community and the rest of the world. This new species of coronavirus has been termed 2019-nCoV and has caused a considerable number of cases of infection and deaths in China and, to a growing degree, beyond China, becoming a worldwide public health emergency. 2019-nCoV has high homology to other pathogenic coronaviruses, such as those originating from bat-related zoonosis (SARS-CoV), which caused approximately 646 deaths in China at the start of the decade. The mortality rate for 2019-nCoV is not as high (approximately 2–3%), but its rapid propagation has resulted in the activation of protocols to stop its spread. This pathogen has the potential to become a pandemic. It is therefore vital to follow the personal care recommendations issued by the World Health Organization.

negative: Society of General Internal Medicine: 28th Annual Meeting New Orleans, LA May 11–14, 2005: Out of Chaos: The Critical Role of Generalists, ABSTRACTS OF SUBMISSIONS ACCEPTED FOR PRESENTATIOIN

negative: A Comprehensive Review of Manifestations of Novel Coronaviruses in the Context of Deadly COVID-19 Global Pandemic Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths [1]. COVID-19 causes a severe pneumonia characterized by fever, cough, and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extra-pulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis, and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multi-organ manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What's more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV, and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.

negative: What's trending in the infection prevention and control literature? From HIS 2012 to HIS 2014, and beyond Summary This is an informal review of some of the trends in the infection prevention and control literature since the last Healthcare Infection Society (HIS) conference in late 2012. Google Trends was used to investigate how the volume of interest in various infection control topics had changed over time. Ebola trumped all the others in Google searches, reflecting a surge of publications in the literature. Aside from Ebola, other trends in the infection prevention and control literature covered in this article include Middle East Respiratory Syndrome (MERS) coronavirus, universal versus targeted interventions, faecal microbiota transplantation, whole genome sequencing, carbapenem-resistant Enterobacteriaceae, and some aspects of environmental science. The review ends with an attempt to predict some of the trends in the infection prevention and control literature between now and the next HIS conference in 2016.

negative: Immune Response in COVID-19: A Review The immune system protects us from viruses and diseases. It produces an antibody to kill pathogen. This review shows a brief picture about the immune system to protect us from COVID-19. It illustrates the process of the immune system, how it works, and mechanism of the immune system to fight virus. It also provides information on recent COVID-19 treatment and experimental data. Various types of potential challenges are also discussed for the immunes system. At the end, some foods have been suggested and some are discouraged. Physical exercise is also encouraged. This article can be used as a state of the art at this critical moment to the globe for a promising alternative solutions related to the survival of people from coronavirus.

negative: Demyelination, and remyelination by Schwann cells and oligodendrocytes after kainate-induced neuronal depletion in the central nervous system Abstract Excitotoxins are thought to kill neurons while sparing afferent fibers and axons of passage. The validity of this classical conclusion has recently been questioned by the demonstration of axonal demyelination. In addition, axons are submitted to a profound alteration of their glial environment. This work was, therefore, undertaken to reassess axonoglial interactions over time after an excitotoxic lesion in the rat. Ultrastructural studies were carried out in the ventrobasal thalamus two days to 18 months after neuronal depletion by in situ injections of kainic acid. In some cases, lemniscal afferents were identified by using anterograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase from the dorsal column nuclei. Two and four days after kainate injection, numerous dying axons displaying typical signs of Wallerian degeneration were observed in a neuropile characterized by the loss of neuronal somata and dendrites, an increase in number of microglia/macrophages and the disappearance of astrocytes. Ten and 12 days after kainate injection, degenerating axons were no longer observed although myelin degeneration of otherwise unaltered axons was ongoing with an accumulation of myelin remnants in the neuropile. At 16 and 20 days, the demyelination process was apparently complete and axons of different diameters were sometimes packed together. One and two months after kainate injection, the axonal environment changed again: remyelination of large-caliber axons occurred at the same time as reactive astrocytes, oligodendrocytes and numerous Schwann cells appeared in the tissue. Schwann cell processes surrounded aggregates of axons of diverse calibers, ensheathed small ones and myelinated larger ones. Axons were also remyelinated by oligodendrocytes. Horseradish peroxidase-labeled lemniscal afferents could be myelinated by either of the two cell types. After three months, the neuropile exhibited an increase in number of hypertrophied astrocytes and the progressive loss of any other cellular or axonal element. At this stage, remaining Schwann cells were surrounded by a glia limitans formed by astrocytic processes. These data indicate that although excitotoxins are sparing the axons, they are having a profound and complex effect on the axonal environment. Demyelination occurs over the first weeks, accompanying the loss of astrocytes and oligodendrocytes. Axonal ensheathment and remyelination takes place in a second period, associated with the reappearance of oligodendrocytes and recruitment of numerous Schwann cells, while reactive astrocytes appear in the tissue at a slightly later time. Over the following months, astrocytes occupy a greater proportion of the neuron-depleted territory and other elements decrease in number. These successive stages in alteration of axonoglial interactions seem to evolve in parallel to the changes in density and terminal morphology that we described earlier for myelinated afferent fibers to the excitotoxic lesion.

negative: Chapter 15 Biology and Diseases of Ruminants (Sheep, Goats, and Cattle) Ruminants continue to be important in their traditional role in agricultural research and teaching. They are now also extensively used for studies in molecular biology; genetic engineering; and biotechnology for basic science, agricultural and clinical applications. Concern and interest for the welfare for these species and improved understanding of their biology and behavior have continued and are reflected in changing husbandry and management systems. This chapter addresses at high levels basic biology, husbandry, and the more common or important diseases of the three ruminant species used most commonly in the laboratory, namely sheep, goats and cattle.

negative: Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission

negative: Animal models of mechanisms of SARS‐CoV‐2 infection and COVID‐19 pathology The coronavirus disease 2019 (COVID‐19) pandemic caused by SARS‐CoV‐2 infections has led to substantial unmet need for treatments, many of which will require testing in appropriate animal models of this disease. Vaccine trials are already underway, but there remains an urgent need to find other therapeutic approaches to either target SARS‐CoV‐2 or the complications arising from viral infection, particularly the dysregulated immune response and systemic complications which have been associated with progression to severe COVID‐19. At the time of writing, in vivo studies of SARS‐CoV‐2 infection have been described using macaques, cats, ferrets, hamsters, and transgenic mice expressing human angiotensin I converting enzyme 2 (ACE2). These infection models have already been useful for studies of transmission and immunity, but to date only partially model the mechanisms implicated in human severe COVID‐19. There is therefore an urgent need for development of animal models for improved evaluation of efficacy of drugs identified as having potential in the treatment of severe COVID‐19. These models need to recapitulate key mechanisms of COVID‐19 severe acute respiratory distress syndrome and reproduce the immunopathology and systemic sequelae associated with this disease. Here, we review the current models of SARS‐CoV‐2 infection and COVID‐19‐related disease mechanisms and suggest ways in which animal models can be adapted to increase their usefulness in research into COVID‐19 pathogenesis and for assessing potential treatments.

negative: Numerical investigation of airborne contaminant transport under different vortex structures in the aircraft cabin Abstract Airborne contaminants such as pathogens, odors and CO2 released from an individual passenger could spread via air flow in an aircraft cabin and make other passengers unhealthy and uncomfortable. In this study, we introduced the airflow vortex structure to analyze how airflow patterns affected contaminant transport in an aircraft cabin. Experimental data regarding airflow patterns were used to validate a computational fluid dynamics (CFD) model. Using the validated CFD model, we investigated the effects of the airflow vortex structure on contaminant transmission based on quantitative analysis. It was found that the contaminant source located in a vorticity-dominated region was more likely to be “locked” in the vortex, resulting in higher 62% higher average concentration and 14% longer residual time than that when the source was on a deformation dominated location. The contaminant concentrations also differed between the front and rear parts of the cabin because of different airflow structures. Contaminant released close to the heated manikin face was likely to be transported backward according to its distribution mean position. Based on these results, the air flow patterns inside aircraft cabins can potentially be improved to better control the spread of airborne contaminant.

negative: Joint Guidance from SGEI, ISG and INASL for Gastroenterologists and Gastrointestinal Endoscopists on the Prevention, Care, and Management of Patients With COVID-19 Coronavirus disease 2019 (COVID-19), which started in December 2019 in China, has resulted in a pandemic leading to significant morbidity and mortality across the globe. Although it mainly causes respiratory symptoms, respiratory failure and death due to multiorgan failure, there is evolving evidence to suggest gastrointestinal (GI) and liver involvement by this virus. Owing to this, health-care professionals taking care of GI and liver diseases are also at an increased risk of getting exposed. Hence, there is a need for protocols to be prepared to guide the handling of COVID-19 patients by the GI and liver specialists, as well as to manage the pre-existing GI and liver diseases during the ongoing pandemic. We present here the guidelines prepared jointly by the three Indian professional bodies in the field of GI diseases, namely the Society of Gastrointestinal Endoscopy of India, Indian Society of Gastroenterology, and Indian National Association for the Study of the Liver.

negative: LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES Objective: To determine the long-term clinical problems in adult survivors of coronavirus (CoV) infection [Coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)] after hospitalisation or Intensive Care Unit (ICU) admission. Design: Systematic review and meta-analysis of the literature. Data sources: Ovid MEDLINE, EMBASE, CINAHL Plus and PsycINFO were searched using the strategy: (Coronavirus OR Coronavirus Infections OR COVID OR SARS virus OR Severe acute respiratory syndrome OR MERS OR Middle east respiratory syndrome) AND (Follow-up OR Follow-up studies OR Prevalence). Original studies reporting the clinical outcomes of adult survivors of coronavirus outbreaks two months after discharge or three months after admission were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 Level of Evidence Tool. Meta-analysis was conducted to derive pooled estimates of prevalence and severity for different outcomes at time points up to 6 months follow-up and beyond 6 months follow-up. Results: The search yielded 1169 studies of which 28 were included in this review. There were 15 Level 1b, 8 Level 2b, 2 Level 3b and 3 Level 4 studies by OCEBM grading. Pooled analysis of studies revealed that complications commonly observed were impaired diffusing capacity for carbon monoxide (DLCO) [prevalence of 27.26%, 95% CI 14.87 to 44.57] and reduced exercise capacity [(6-minute walking distance (6MWD) mean 461m, 95% CI 449.66 to 472.71] at 6 months with limited improvement beyond 6 months. Coronavirus survivors had considerable prevalence of psychological disorders such as post-traumatic stress disorder (PTSD) [38.80%, CI 30.93 to 47.31], depression [33.20%, CI 19.80 to 50.02] and anxiety [30.04%, CI 10.44 to 61.26) beyond 6 months. These complications were accompanied by low Short Form 36 (SF-36) scores at 6 months and beyond indicating reduced quality of life which is present long-term. Conclusions: The long term clinical problems in survivors of CoV infections (SARS and MERS) after hospitalisation or Intensive Care Unit (ICU) admission include respiratory dysfunction, reduced exercise capacity, psychological problems such as PTSD, depression and anxiety, and reduced quality of life. Critical care, rehabilitation and mental health services should anticipate a high prevalence of these problems following COVID-19 and ensure their adequate and timely management with the aim of restoring premorbid quality of life.

negative: Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2 The burgeoning epidemic caused by novel coronavirus 2019 (2019-nCoV) is currently a global concern. Angiotensin-converting enzyme-2 (ACE2) is a receptor of 2019-nCoV spike 1 protein (S1) and mediates viral entry into host cells. Despite the abundance of ACE2 in small intestine, few digestive symptoms are observed in patients infected by 2019-nCoV. Herein, we investigated the interactions between ACE2 and human defensins (HDs) specifically secreted by intestinal Paneth cells. The lectin-like HD5, rather than HD6, bound ACE2 with a high affinity of 39.3 nM and weakened the subsequent recruitment of 2019-nCoV S1. The cloak of HD5 on the ligand-binding domain of ACE2 was confirmed by molecular dynamic simulation. A remarkable dose-dependent preventive effect of HD5 on 2019-nCoV S1 binding to intestinal epithelial cells was further evidenced by in vitro experiments. Our findings unmasked the innate defense function of lectin-like intestinal defensin against 2019-nCoV, which may provide new insights into the prevention and treatment of 2019-nCoV infection.

negative: Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.

negative: Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors Summary Background Studies on the fusion-inhibitory peptides derived from the heptad repeat 1 and 2 (HR1 and HR2) regions of the HIV-1 envelope glycoprotein gp41 provided crucial information on the viral fusogenic mechanism. We used a similar approach to study the fusogenic mechanism of severe-acute-respiratory-syndrome-associated coronavirus (SARS-CoV). Methods We tested the inhibitory activity against infection of two sets of peptides corresponding to sequences of SARS-CoV spike protein HR1 and HR2 regions and investigated the interactions between the HR1 and HR2 peptides by surface plasmon resonance, sedimentation equilibration analysis, circular dichroism, native polyacrylamide-gel electrophoresis, size exclusion high-performance liquid chromatography, and computer-aided homology modelling and molecule docking analysis. Findings One peptide, CP-1, derived from the HR2 region, inhibited SARS-CoV infection in the micromolar range. CP-1 bound with high affinity to a peptide from the HR1 region, NP-1. CP-1 alone had low -helicity and self-associated to form a trimer in phosphate buffer (pH 7·2). CP-1 and NP-1 mixed in equimolar concentrations formed a six-helix bundle, similar to the fusogenic core structure of HIV-1 gp41. Interpretation After binding to the target cell, the transmembrane spike protein might change conformation by association between the HR1 and HR2 regions to form an oligomeric structure, leading to fusion between the viral and target-cell membranes. At the prefusion intermediate state, CP-1 could bind to the HR1 region and interfere with the conformational changes, resulting in inhibition of SARS-CoV fusion with the target cells. CP-1 might be modifiable to increase its anti-SARS-CoV activity and could be further developed as an antiviral agent for treatment or prophylaxis of SARS-CoV infection.

negative: Combining Clinical and Epidemiologic Features for Early Recognition of SARS Early recognition and rapid initiation of infection control precautions are currently the most important strategies for controlling severe acute respiratory syndrome (SARS). No rapid diagnostic tests currently exist that can rule out SARS among patients with febrile respiratory illnesses. Clinical features alone cannot with certainty distinguish SARS from other respiratory illnesses rapidly enough to inform early management decisions. A balanced approach to screening that allows early recognition of SARS without unnecessary isolation of patients with other respiratory illnesses will require clinicians not only to look for suggestive clinical features but also to routinely seek epidemiologic clues suggestive of SARS coronavirus exposure. Key epidemiologic risk factors include 1) exposure to settings where SARS activity is suspected or documented, or 2) in the absence of such exposure, epidemiologic linkage to other persons with pneumonia (i.e., pneumonia clusters), or 3) exposure to healthcare settings. When combined with clinical findings, these epidemiologic features provide a possible strategic framework for early recognition of SARS.

negative: Promising methods for detection of novel coronavirus SARS‐CoV‐2 A very recent outbreak of the novel coronavirus, COVID‐19, in the city of Wuhan, China, in December 2019 and its subsequent spread within and across China have resulted in several deaths and infections. Presently, nucleic acid amplification test is essential for the confirmation of COVID infection. In this report, we summarized the six promising methods, including whole‐genome sequencing, real‐time reverse transcription polymerase chain reaction, nanopore target sequencing, antibody‐based immunoassay techniques, use of paper‐based biomolecular sensors, and the clustered regularly interspaced short palindromic repeats‐Cas system‐based technology, which can also be deployed for the detection of SARS‐CoV‐2. We further introduced the principles of these methods, discussed the scope and practicability of application of the available products and methods, and highlighted the potential approaches to develop additional products and techniques for early diagnosis of COVID‐19.

negative: Current Vaccination Strategies in Puppies and Kittens Motivation in writing this article stems from many things: a lack of time spent in the veterinary curriculum discussing vaccines, a growing concern(by the general public and the veterinary community) regarding adverse reactions associated with vaccines, and a desire to prevent a recurrence of preventable infectious diseases resulting from a fear-driven cessation of vaccine administration. The objectives of this article are to present a basic review of immunology as related to vaccines, to discuss general guidelines for pediatric vaccines in canine and feline patients,and to offer suggestions as to how we can most positively influence our patients' health from the first visit.

negative: Three-Dimensional Reconstruction of the Nucleolus Using Meta-Confocal Microscopy in Cells Expressing the Coronavirus Nucleoprotein

negative: A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV BACKGROUND: Evidence points to the emergence of a novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), which causes a severe acute respiratory syndrome (SARS)-like disease. In response, the development of effective vaccines and therapeutics remains a clinical priority. To accomplish this, it is necessary to evaluate neutralizing antibodies and screen for MERS-CoV entry inhibitors. METHODS: In this study, we produced a pseudovirus bearing the full-length spike (S) protein of MERS-CoV in the Env-defective, luciferase-expressing HIV-1 backbone. We then established a pseudovirus-based inhibition assay to detect neutralizing antibodies and anti-MERS-CoV entry inhibitors. RESULTS: Our results demonstrated that the generated MERS-CoV pseudovirus allows for single-cycle infection of a variety of cells expressing dipeptidyl peptidase-4 (DPP4), the confirmed receptor for MERS-CoV. Consistent with the results from a live MERS-CoV-based inhibition assay, the antisera of mice vaccinated with a recombinant protein containing receptor-binding domain (RBD, residues 377–662) of MERS-CoV S fused with Fc of human IgG exhibited neutralizing antibody response against infection of MERS-CoV pseudovirus. Furthermore, one small molecule HIV entry inhibitor targeting gp41 (ADS-J1) and the 3-hydroxyphthalic anhydride-modified human serum albumin (HP-HSA) could significantly inhibit MERS-CoV pseudovirus infection. CONCLUSION: Taken together, the established MERS-CoV inhibition assay is a safe and convenient pseudovirus-based alternative to BSL-3 live-virus restrictions and can be used to rapidly screen MERS-CoV entry inhibitors, as well as evaluate vaccine-induced neutralizing antibodies against the highly pathogenic MERS-CoV.

negative: Coronavirus et COVID-19 : le point sur une pandémie galopante./ [Coronavirus and COVID-19 : focus on a galopping pandemic] The international community is currently facing a pandemic of acute respiratory syndrome caused by a new coronavirus, SARS-CoV-2. This syndrome has been named COVID-19 for CoronaVIrus Disease 2019 by the World Health Organization. The starting point of the epidemic is the city of Wuhan (China), where the virus is said to have been transmitted from animals to humans before inter-human transmission. This is the third epidemic caused by a coronavirus after those of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) started in 2012. COVID-19 has rapidly spread to China and is currently spreading all over the world. The infection mainly affects patients over 40 years of age and mortality is increased in the presence of comorbidities. Children are pauci- or asymptomatic. The diagnosis is most often based on the detection of the viral genome in the nasopharynx by molecular biology methods. In the absence of specific anti-viral molecules, treatment is currently mainly symptomatic. It is clear that the COVID-19 pandemic is more difficult to control than what the first data suggested. The key strategy to SARS-CoV-2 is to limit its transmission. Preventive measures are mainly based on the application of adequate hand hygiene measures and disinfection of the environment, as well as measures of social distance aimed at limiting contacts in the population and protecting populations at risk.

negative: Telehealth in the Context of COVID-19: Changing Perspectives in Australia, the United Kingdom, and the United States BACKGROUND: On March 12, 2020, the World Health Organization declared the coronavirus disease (COVID-19) outbreak a pandemic. On that date, there were 134,576 reported cases and 4981 deaths worldwide. By March 26, 2020, just 2 weeks later, reported cases had increased four-fold to 531,865, and deaths increased five-fold to 24,073. Older people are both major users of telehealth services and are more likely to die as a result of COVID-19. OBJECTIVE: This paper examines the extent that Australia, the United Kingdom, and the United States, during the 2 weeks following the pandemic announcement, sought to promote telehealth as a tool that could help identify COVID-19 among older people who may live alone, be frail, or be self-isolating, and give support to or facilitate the treatment of people who are or may be infected. METHODS: This paper reports, for the 2-week period previously mentioned and immediately prior, on activities and initiatives in the three countries taken by governments or their agencies (at national or state levels) together with publications or guidance issued by professional, trade, and charitable bodies. Different sources of information are drawn upon that point to the perceived likely benefits of telehealth in fighting the pandemic. It is not the purpose of this paper to draw together or analyze information that reflects growing knowledge about COVID-19, except where telehealth is seen as a component. RESULTS: The picture that emerges for the three countries, based on the sources identified, shows a number of differences. These differences center on the nature of their health services, the extent of attention given to older people (and the circumstances that can relate to them), the different geographies (notably concerned with rurality), and the changes to funding frameworks that could impact these. Common to all three countries is the value attributed to maintaining quality safeguards in the wider context of their health services but where such services are noted as sometimes having precluded significant telehealth use. CONCLUSIONS: The COVID-19 pandemic is forcing changes and may help to establish telehealth more firmly in its aftermath. Some of the changes may not be long-lasting. However, the momentum is such that telehealth will almost certainly find a stronger place within health service frameworks for each of the three countries and is likely to have increased acceptance among both patients and health care providers.

negative: Predicting the receptor-binding domain usage of the coronavirus based on kmer frequency on spike protein

negative: Regulating epidemic space: the nomos of global circulation After the Severe Acute Respiratory Syndrome (SARS) outbreak in 2002, legal theorist David Fidler diagnosed the arrival of the ‘first post-Westphalian pathogen’. The coinage indicates that the spread of infectious disease transforms the spatial coordinates of the modern political environment. This article analyses this transformation by asking how the legal regime, designed to prepare for the pandemic, envisions the globe as an object of government. It demonstrates that the WHO’s International Health Regulations (IHR) articulate a space of global circulation that exhibits two features. First, the infrastructures of microbial traffic become the primary matters of concern. The IHR do not focus on human life so much as they aim at securing transnational mobilities. Second, the IHR circumscribe a space that is fragmented by zones of intensified governmental control at transportational nodal points, such as airports and harbours. In these zones, technologies of screening and quarantine are applied to modulate the connectivity of people, organic matter and things. As a whole, the article investigates how processes of de- and re-territorialisation interact in the context of global health security. In analysing forms of legal worldmaking, it unearths a nomos of global circulation which applies its regulatory force to the post-human materialities of microbial traffic.

negative: Chapter 4 Method of Ending Disease and the Future Medical System Abstract The characteristics of disease changed with the arrival of the age of chronic diseases. Now, we observe a spectrum of diverse diseases that cannot be properly managed with a simple strategy developed in the age of infectious diseases. Because our living environment changes so quickly, the response of the human body, such as the genes or epigenetic program, cannot keep up with it if we continue the current strategy. We need to find a way to enable adaptation of the human body program to change. Medical education should also be changed to focus on the harmony and balance of complexly entangled systems. Addressing such a need for changes, “systems medicine” is a new approach to achieving breakthroughs in disease prevention and treatment by obtaining and using fairly comprehensive information, such as molecular-, gene-, and cell-level information, as well as lifestyle, clinical, physiological, and environmental information.

negative: Infection control challenge in setting up a temporary test centre at the international airport for rapid diagnosis of coronavirus disease 2019 (COVID-19) due to SARS-CoV-2

negative: Pushing beyond specifications: Evaluation of linearity and clinical performance of a fully automated SARS-CoV-2 RT-PCR assay for reliable quantification in blood and other materials outside recommendations Background: The ongoing SARS-CoV-2 pandemic presents a unique challenge to diagnostic laboratories. There are preliminary studies correlating qRT-PCR results from different materials to clinical outcomes, yet, comparability is limited due to the plethora of different assays used for diagnostics. In this study we evaluate clinical performance and linear range for the SARS-CoV-2 IVD (cobas6800/8800 system, a fully automated sample-to-result platform) in different clinically relevant matrix materials outside official specifications. Methods: Assay performance was assessed in human plasma, BAL/BL and transport medium following chemical inactivation. For analytical evaluation, respective matrix materials were spiked with SARS-CoV-2 RNA in ten-fold dilution series. The efficacy of chemical inactivation by guanidine hydrochloride solution was confirmed in cell culture infectivity experiments. For correlation, a total of 235 predetermined clinical samples including respiratory swabs, plasma and BAL/BL were subjected to the SARS-CoV-2 IVD test and results were compared. Results: The SARS-CoV-2 IVD showed excellent linearity over five to seven log steps depending on matrix material. Chemical inactivation resulted in a reduction in plaque forming units of at least 3.5 log steps, while having no significant impact on assay performance. Inter-run consistency from three different testing sites demonstrated excellent comparability of RT-PCR results (maximum deviation was 1.53 CT). Clinical evaluation for respiratory swabs showed very good agreement with the comparator assay (Positive agreement 95.7%, negative agreement 98.9%). Conclusion: The SARS-CoV-2 IVD test for the cobas6800/8800 systems offers excellent linear range and inter-run consistency for quantification of SARS-CoV-2 RNA in different matrices outside official specifications.

negative: Liver Disease Associated with Non-Hepatitis Viruses Abstract Hepatitis is commonly associated with certain viruses labeled as “Hepatitis” viruses. However, many other viral infections can also affect the liver ranging from mild asymptomatic elevations of aminotransferases to fulminant hepatic failure. This article will provide a brief overview on a variety of different viral infections that may be associated with significant liver pathology at least under certain conditions, for example, immunosuppression. This overview discusses key virological features, clinical presentation of associated liver disease and provides some information on diagnosis and an outline of treatment options. Thus, the overview can provide first orientation when infectious hepatitis is encountered in a patient that cannot be explained by the usual hepatitis viruses.

negative: Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV) that vary fundamentally in their virulence, but are indistinguishable by a number of diagnostic methods. This review focuses on all important steps every veterinary practitioner has to deal with and new diagnostic tests that can be considered when encountering a cat with suspected FIP with the aim to establish a definitive diagnosis. It gives an overview on all available direct and indirect diagnostic tests and their sensitivity and specificity reported in the literature in different sample material. By providing summarized data for sensitivity and specificity of each diagnostic test and each sample material, which can easily be accessed in tables, this review can help to facilitate the interpretation of different diagnostic tests and raise awareness of their advantages and limitations. Additionally, diagnostic trees depict recommended diagnostic steps that should be performed in cats suspected of having FIP based on their clinical signs or clinicopathologic abnormalities. These steps can easily be followed in clinical practice.

negative: Is Africa prepared for tackling the COVID-19 (SARS-CoV-2) epidemic. Lessons from past outbreaks, ongoing pan-African public health efforts, and implications for the future

negative: A review of feline infectious peritonitis virus infection: 1963–2008

negative: Effect of donor-recipient relatedness on the plasmid conjugation frequency: a meta-analysis. BACKGROUND Conjugation plays a major role in the transmission of plasmids encoding antibiotic resistance genes in both clinical and general settings. The conjugation efficiency is influenced by many biotic and abiotic factors, one of which is the taxonomic relatedness between donor and recipient bacteria. A comprehensive overview of the influence of donor-recipient relatedness on conjugation is still lacking, but such an overview is important to quantitatively assess the risk of plasmid transfer and the effect of interventions which limit the spread of antibiotic resistance, and to obtain parameter values for conjugation in mathematical models. Therefore, we performed a meta-analysis on reported conjugation frequencies from Escherichia coli donors to various recipient species. RESULTS Thirty-two studies reporting 313 conjugation frequencies for liquid broth matings and 270 conjugation frequencies for filter matings were included in our meta-analysis. The reported conjugation frequencies varied over 11 orders of magnitude. Decreasing taxonomic relatedness between donor and recipient bacteria, when adjusted for confounding factors, was associated with a lower conjugation frequency in liquid matings. The mean conjugation frequency for bacteria of the same order, the same class, and other classes was 10, 20, and 789 times lower than the mean conjugation frequency within the same species, respectively. This association between relatedness and conjugation frequency was not found for filter matings. The conjugation frequency was furthermore found to be influenced by temperature in both types of mating experiments, and in addition by plasmid incompatibility group in liquid matings, and by recipient origin and mating time in filter matings. CONCLUSIONS In our meta-analysis, taxonomic relatedness is limiting conjugation in liquid matings, but not in filter matings, suggesting that taxonomic relatedness is not a limiting factor for conjugation in environments where bacteria are fixed in space.

negative: Critical Differences between the Binding Features of the Spike Proteins of SARS-CoV-2 and SARS-CoV The COVID-19 caused by SARS-CoV-2 has spread globally and caused tremendous loss of lives and properties, and it is of utmost urgency to understand its propagation process and to find ways to slow down the epidemic. In this work, we used a coarse-grained model to calculate the binding free energy of SARS-CoV-2 or SARS-CoV to their human receptor ACE2. The investigation of the free energy contribution of the interacting residues indicates that the residues located outside the receptor binding domain are the source of the stronger binding of the novel virus. Thus, the current results suggest that the essential evolution of SARS-CoV-2 happens remotely from the binding domain at the spike protein trimeric body. Such evolution may facilitate the conformational change and the infection process that occurs after the virus is bound to ACE2. By studying the binding pattern between SARS-CoV antibody m396 and SARS-CoV-2, it is found that the remote energetic contribution is missing, which might explain the absence of cross-reactivity of such antibodies.

negative: National Governance of Public Health Responses in a Pandemic? The world is currently facing the worst pandemic in a century and we were caught unprepared. COVID-19 has proven highly contagious and with severe consequences that are still unfolding. As of 16 April 2020, there were over 2 million confirmed cases and over 136,000 related deaths reported worldwide. Over 1 million of those confirmed cases were in the preceding 14 days, with the USA accounting for nearly half of those. Furthermore, the International Monetary Fund (IMF) is now warning that the world is about to suffer the worst economic recession since the Great Depression in the 1920s.

negative: Comparison of risk factors for viral and nonviral asthma exacerbations

negative: Pharmaceutical Prescription in Canine Acute Diarrhoea: A Longitudinal Electronic Health Record Analysis of First Opinion Veterinary Practices Canine acute diarrhoea is frequently observed in first opinion practice, though little is known about commonly used diagnostic or therapeutic management plans, including use of antimicrobials. This retrospective observational study utilised electronic health records augmented with practitioner-completed questionnaires from 3,189 cases (3,159 dogs) collected from 179 volunteer veterinary practices between April 2014 and January 2017. We used multivariable analysis to explore factors potentially associated with pharmaceutical agent prescription, and resolution of clinical signs by 10 days post-initial presentation. Use of bacteriological and/or parasitological diagnostic tests were uncommon (3.2% of cases, 95% confidence interval, CI, 2.4–4.0), though systemic antimicrobials were the most commonly prescribed pharmaceutical agents (49.7% of cases, 95% CI 46.1–53.2). Such prescription was associated with haemorrhagic diarrhoea (odds ratio, OR, 4.1; 95% CI 3.4–5.0), body temperature in excess of 39.0°C, or moderate/severe cases (OR 1.3, 95% CI 1.1–1.7). Gastrointestinal agents (e.g., antacids) were prescribed to 37.7% of cases (95% CI 35.4–39.9), and were most frequently prescribed to vomiting dogs regardless of presence (OR 46.4, 95% CI 19.4–110.8) or absence of blood (OR 17.1, 95% CI 13.4–21.9). Endoparasiticides/endectocides were prescribed to 7.8% of cases (95% CI 6.8–9.0), such prescription being less frequent for moderate/severe cases (OR 0.5, 95% CI 0.4–0.7), though more frequent when weight loss was recorded (OR 3.4, 95% CI 1.3–9.0). Gastrointestinal nutraceuticals (e.g., probiotics) were dispensed to 60.8% of cases (95% CI 57.1–64.6), these cases less frequently presenting with moderate/severe clinical signs (OR 0.6, 95% CI 0.5–0.8). Nearly a quarter of cases were judged lost to follow-up (n=754). Insured (OR 0.7, 95% CI 0.5–0.9); neutered (OR 0.4, 95% CI 0.3–0.5), or vaccinated dogs (OR 0.3, 95% CI 0.3–0.4) were less commonly lost to follow-up. Of remaining dogs, clinical signs were deemed resolved in 95.4% of cases (95% CI 94.6–96.2). Provision of dietary modification advice and gastrointestinal nutraceuticals alone were positively associated with resolution (OR 2.8, 95% CI 1.3–6.1); no such associations were found for pharmaceutical agents, including antimicrobials. Hence, this study supports the view that antimicrobials are largely unnecessary for acute diarrhoea cases; this being of particular importance when considering the global threat posed by antimicrobial resistance.

negative: Pyogranulomatous panophthalmitis with systemic coronavirus disease in a domestic ferret (Mustela putorius furo) A 15‐month‐old spayed female ferret (Mustela putorius furo) presented for lethargy and weight loss of 2 weeks duration. Upon physical examination, a 2‐mm‐diameter focal area of opacity was noted in the left cornea. In addition, the ferret was quiet, in poor body condition, and dehydrated. A complete blood count and plasma biochemistry revealed a severe nonregenerative anemia, azotemia, hyperproteinemia, hypoalbuminemia, and mild hyperphosphatemia and hyperchloremia. Urinalysis revealed hyposthenuria. Whole body radiographs showed multifocal thoracic nodular disease, splenomegaly, and renomegaly. Abdominal ultrasonography confirmed bilaterally enlarged kidneys, hypoechoic liver and spleen, and a caudal abdominal hypoechoic mobile nodule. The ferret was humanely euthanized, and a postmortem examination with subsequent histopathology showed multifocal necrotizing pyogranulomas in the lung, spleen, kidneys, mesenteric lymph nodes, and serosa of the duodenum. Pyogranulomatous panophthalmitis was diagnosed in the left eye. The multisystemic granulomatous lesions were suggestive of ferret systemic coronavirus (FRSCV). The presence of coronavirus in the left eye was confirmed by positive immunohistochemistry. Reverse transcriptase polymerase chain reaction (RT‐PCR) on formalin fixed paraffin embedded tissue from the lung, spleen, and kidney was negative for FRSCV and positive for ferret enteric coronavirus (FRECV). Systemic coronavirus disease in ferrets closely resembles feline infectious peritonitis (FIP) in domestic cats, which can manifest with anterior uveitis, chorioretinitis, optic neuritis, and retinal detachment. To the authors’ knowledge, this is the first report of ocular lesions in a ferret with systemic coronavirus disease, suggesting that ferrets presented with similar ocular lesions should also be evaluated for evidence of coronavirus infection.

negative: Critical care management of adults with community-acquired severe respiratory viral infection With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17–53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05943-5) contains supplementary material, which is available to authorized users.

negative: Prevalence and clinical features of 2019 novel coronavirus disease (COVID-19) in the Fever Clinic of a teaching hospital in Beijing: a single-center, retrospective study Background With the spread of COVID-19 from Wuhan, Hubei Province to other areas of the country, medical staff in Fever Clinics faced the challenge of identifying suspected cases among patients with respiratory infections manifested with fever. We aimed to describe the prevalence and clinical features of COVID-19 as compared to pneumonias of other etiologies in a Fever Clinic in Beijing. Methods In this single-center, retrospective study, 342 cases of pneumonia were diagnosed in Fever Clinic in Peking University Third Hospital between January 21 to February 15, 2020. From these patients, 88 were reviewed by panel discussion as possible or probable cases of COVID-19, and received 2019-nCoV detection by RT-PCR. COVID-19 was confirmed by positive 2019-nCoV in 19 cases, and by epidemiological, clinical and CT features in 2 cases (the COVID-19 Group, n=21), while the remaining 67 cases served as the non-COVID-19 group. Demographic and epidemiological data, symptoms, laboratory and lung CT findings were collected, and compared between the two groups. Findings The prevalence of COVID-19 in all pneumonia patients during the study period was 6.14% (21/342). Compared with the non-COVID-19 group, more patients with COVID-19 had an identified epidemiological history (90.5% versus 32.8%, P<0.001). The COVID-19 group had lower WBC [5.19×10^9/L (±1.47) versus 7.21×10^9/L (±2.94), P<0.001] and neutrophil counts [3.39×10^9/L (±1.48) versus 5.38×10^9/L (±2.85), P<0.001] in peripheral blood. However, the percentage and count of lymphocytes were not different. On lung CT scans, involvement of 4 or more lobes was more common in the COVID-19 group (45% versus 16.4%, P=0.008). Interpretation In the period of COVID-19 epidemic outside Hubei Province, the prevalence of COVID-19 in patients with pneumonia visiting to our Fever Clinic in Beijing was 6.14%. Epidemiological evidence was important for prompt case finding, and lower blood WBC and neutrophil counts may be useful for differentiation from pneumonia of other etiologies.

negative: Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM Since December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.

negative: Heat sensitivity of a SARS‐associated coronavirus introduced into plasma products Background and Objectives Various measures to inactivate/remove viruses have been implemented for manufacturing plasma‐derived products. Here, we examined the heat inactivation ability of an agent of the severe acute respiratory syndrome (SARS), SARS coronavirus (CoV). Materials and Methods The Frankfurt‐1 strain of SARS‐CoV was incorporated in manufacturing processes of several products by using samples collected immediately before liquid heat treatment at 60 °C. Results SARS‐CoV was easily inactivated by this treatment for 60 min in all in‐process samples. However, the different composition of the tested samples affected the heat sensitivity of the virus strain: the infectivity of the virus in Antithrombin III preparation still remained after heating for 30 min at 60 °C. Conclusion If by rare chance SARS‐CoV contaminates source plasma, there should be no or only minor risk of this virus infection, due to sufficient inactivation by the 60 °C 10 h liquid heating step, although we must pay attention to the composition used for blood product preparation.

negative: COVID-19 coronavirus: recommended personal protective equipment for the orthopaedic and trauma surgeon PURPOSE: With the COVID-19 crisis, recommendations for personal protective equipment (PPE) are necessary for protection in orthopaedics and traumatology. The primary purpose of this study is to review and present current evidence and recommendations for personal protective equipment and safety recommendations for orthopaedic surgeons and trauma surgeons. METHODS: A systematic review of the available literature was performed using the keyword terms “COVID-19”, “Coronavirus”, “surgeon”, “health-care workers”, “protection”, “masks”, “gloves”, “gowns”, “helmets”, and “aerosol” in several combinations. The following databases were assessed: Pubmed, Cochrane Reviews, Google Scholar. Due to the paucity of available data, it was decided to present it in a narrative manner. In addition, participating doctors were asked to provide their guidelines for PPE in their countries (Austria, Luxembourg, Switzerland, Germany, UK) for consideration in the presented practice recommendations. RESULTS: World Health Organization guidance for respiratory aerosol-generating procedures (AGPs) such as intubation in a COVID19 environment was clear and included the use of an FFP3 (filtering face piece level 3) mask and face protection. However, the recommendation for surgical AGPs, such as the use of high-speed power tools in the operating theatre, was not clear until the UK Public Health England (PHE) guidance of 27 March 2020. This guidance included FFP3 masks and face protection, which UK surgeons quickly adopted. The recommended PPE for orthopaedic surgeons, working in a COVID19 environment, should consist of level 4 surgical gowns, face shields or goggles, double gloves, FFP2-3 or N95-99 respirator masks. An alternative to the mask, face shield and goggles is a powered air-purifying respirator, particularly if the surgeons fail the mask fit test or are required to undertake a long procedure. However, there is a high cost and limited availabilty of these devices at present. Currently available surgical helmets and toga systems may not be the solution due to a permeable top for air intake. During the current COVID-19 crisis, it appeared that telemedicine can be considered as an electronic personal protective equipment by reducing the number of physical contacts and risk contamination. CONCLUSION: Orthopaedic and trauma surgery using power tools, pulsatile lavage and electrocautery are surgical aerosol-generating procedures and all body fluids contain virus particles. Raising awareness of these issues will help avoid occupational transmission of COVID-19 to the surgical team by aerosolization of blood or other body fluids and hence adequate PPE should be available and used during orthopaedic surgery. In addition, efforts have to be made to improve the current evidence in this regard. LEVEL OF EVIDENCE: IV.

negative: An Internet-Based Epidemiological Investigation of the Outbreak of H7N9 Avian Influenza A in China Since Early 2013 BACKGROUND: In early 2013, a new type of avian influenza, H7N9, emerged in China. It quickly became an issue of great public concern and a widely discussed topic on the Internet. A considerable volume of relevant information was made publicly available on the Internet through various sources. OBJECTIVE: This study aimed to describe the outbreak of H7N9 in China based on data openly available on the Internet and to validate our investigation by comparing our findings with a well-conducted conventional field epidemiologic study. METHODS: We searched publicly accessible Internet data on the H7N9 outbreak primarily from government and major mass media websites in China up to February 10, 2014. Two researchers independently extracted, compared, and confirmed the information of each confirmed H7N9 case using a self-designed data extraction form. We summarized the epidemiological and clinical characteristics of confirmed H7N9 cases and compared them with those from the field study. RESULTS: According to our data updated until February 10, 2014, 334 confirmed H7N9 cases were identified. The median age was 58 years and 67.0% (219/327) were males. Cases were reported in 15 regions in China. Five family clusters were found. Of the 16.8% (56/334) of the cases with relevant data, 69.6% (39/56) reported a history of exposure to animals. Of the 1751 persons with a close contact with a confirmed case, 0.6% (11/1751) of them developed respiratory symptoms during the 7-day surveillance period. In the 97.9% (327/334) of the cases with relevant data, 21.7% (71/327) died, 20.8% (68/327) were discharged from a hospital, and 57.5% (188/327) were of uncertain status. We compared our findings before February 10, 2014 and those before December 1, 2013 with those from the conventional field study, which had the latter cutoff date of ours in data collection. Our study showed most epidemiological and clinical characteristics were similar to those in the field study, except for case fatality (71/327, 21.7% for our data before February 10; 45/138, 32.6% for our data before December 1; 47/139, 33.8% for the field study), time from illness onset to first medical care (4 days, 3 days, and 1 day), and time from illness onset to death (16.5 days, 17 days, and 21 days). CONCLUSIONS: Findings from our Internet-based investigation were similar to those from the conventional field study in most epidemiological and clinical aspects of the outbreak. Importantly, publicly available Internet data are open to any interested researchers and can thus greatly facilitate the investigation and control of such outbreaks. With improved efforts for Internet data provision, Internet-based investigation has a great potential to become a quick, economical, novel approach to investigating sudden issues of great public concern that involve a relatively small number of cases like this H7N9 outbreak.

negative: Coronavirus Infection Among Children and Adolescents Coronavirus infection is a global emergency. Over the past few months, there is a rapid increase in the number of cases and deaths due to coronavirus infection. It has been observed that elderly individuals and those with medical co-morbidities are maximally affected. In children and adolescents, coronavirus infection has low mortality as well as the severity of symptoms are less. Children and adolescents with immunocompromised state, malnutrition, medical co-morbidities and poor hygiene are at higher risk of contracting coronavirus infection. Minimizing this risk factors and adopting appropriate prevention measures will be helpful in limiting the spread of infection as there is no specific treatment and immunization available to date to address this serious issue. This chapter highlights the issues and challenges of coronavirus infection in children and adolescents.

negative: COVID‐19 – Looking beyond the immediate concerns

negative: Bat origin of human coronaviruses Bats have been recognized as the natural reservoirs of a large variety of viruses. Special attention has been paid to bat coronaviruses as the two emerging coronaviruses which have caused unexpected human disease outbreaks in the 21st century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), are suggested to be originated from bats. Various species of horseshoe bats in China have been found to harbor genetically diverse SARS-like coronaviruses. Some strains are highly similar to SARS-CoV even in the spike protein and are able to use the same receptor as SARS-CoV for cell entry. On the other hand, diverse coronaviruses phylogenetically related to MERS-CoV have been discovered worldwide in a wide range of bat species, some of which can be classified to the same coronavirus species as MERS-CoV. Coronaviruses genetically related to human coronavirus 229E and NL63 have been detected in bats as well. Moreover, intermediate hosts are believed to play an important role in the transmission and emergence of these coronaviruses from bats to humans. Understanding the bat origin of human coronaviruses is helpful for the prediction and prevention of another pandemic emergence in the future.

negative: Vitamin E and immune response in the aged: molecular mechanisms and clinical implications Summary: Nutritional status has been indicated as a contributing factor to age‐related dysregulation of the immune response. Vitamin E, a lipid‐soluble antioxidant vitamin, is important for normal function of the immune cells. The elderly are at a greater risk for vitamin E intake that is lower than recommended levels. Vitamin E supplementation above currently recommended levels has been shown to improve immune functions in the aged including delayed‐type hypersensitivity skin response and antibody production in response to vaccination, which was shown to be mediated through increased production of interleukin (IL)‐2, leading to enhanced proliferation of T cells, and through reduced production of prostaglandin E(2), a T‐cell suppressive factor, as a result of a decreased peroxynitrite formation. Vitamin E increased both cell‐dividing and IL‐producing capacities of naïve T cells, but not memory T cells. The vitamin E‐induced enhancement of immune functions in the aged was associated with significant improvement in resistance to influenza infection in aged mice and a reduced risk of acquiring upper respiratory infections in nursing home residents. Further studies are needed to determine the signaling mechanisms involved in the upregulation of naïve T‐cell function by vitamin E as well as the specific mechanisms involved in reduction of risk for upper respiratory infections.

negative: Social Dimensions of COVID-19 in South Africa: A Neglected Element of the Treatment Plan

negative: Bioinformatics in Design of Antiviral Vaccines Abstract Viral diseases and epidemics are occurring across the world with increasing frequency and with incidences of new and old viruses with renewed vigor. Traditional drugs and vaccines with their long developmental times, incidences of allergenic reactions, growth of resistant strains and other issues are proving inadequate to curb the menace. Advancements in computer science and technology, in genetics and immunology and the growth of the new science of bioinformatics are leading to a more focused approach in a new paradigm of vaccine design that challenges the traditional approach and promises to be more effective; lead times should get much shorter, preselection of peptide antivirals will be designed to preclude allergenic reactions, stability against mutational changes to viral strains will be much more assured, and coverage of immunological status will enable community-specific vaccines development. We outline in this article the basics of viruses, immune responses, and traditional vaccines and move on to describe the bioinformatics methods and development of new vaccines.

negative: Multifaceted Regulation of Translational Readthrough by RNA Replication Elements in a Tombusvirus Translational readthrough of stop codons by ribosomes is a recoding event used by a variety of viruses, including plus-strand RNA tombusviruses. Translation of the viral RNA-dependent RNA polymerase (RdRp) in tombusviruses is mediated using this strategy and we have investigated this process using a variety of in vitro and in vivo approaches. Our results indicate that readthrough generating the RdRp requires a novel long-range RNA-RNA interaction, spanning a distance of ∼3.5 kb, which occurs between a large RNA stem-loop located 3'-proximal to the stop codon and an RNA replication structure termed RIV at the 3'-end of the viral genome. Interestingly, this long-distance RNA-RNA interaction is modulated by mutually-exclusive RNA structures in RIV that represent a type of RNA switch. Moreover, a different long-range RNA-RNA interaction that was previously shown to be necessary for viral RNA replicase assembly was also required for efficient readthrough production of the RdRp. Accordingly, multiple replication-associated RNA elements are involved in modulating the readthrough event in tombusviruses and we propose an integrated mechanistic model to describe how this regulatory network could be advantageous by (i) providing a quality control system for culling truncated viral genomes at an early stage in the replication process, (ii) mediating cis-preferential replication of viral genomes, and (iii) coordinating translational readthrough of the RdRp with viral genome replication. Based on comparative sequence analysis and experimental data, basic elements of this regulatory model extend to other members of Tombusviridae, as well as to viruses outside of this family.

negative: Effect of thermal control of dry fomites on regulating the survival of human pathogenic bacteria responsible for nosocomial infections We monitored the survival of human pathogenic bacteria [Escherichia coli (ATCC), extended-spectrum β-lactamase-producing E. coli (Clinical isolate), New Delhi metallo-β-lactamase-producing E. coli (clinical isolate), Staphylococcus aureus (ATCC)] on dry materials (vinyl chloride, aluminum, plastic, stainless steel) at distinct temperatures (room temperature or 15°C–37°C). These bacteria favored a lower temperature for their prolonged survival on the dry fomites, regardless of the material type. Interestingly, when mixed with S. aureus, E. coli survived for a longer time at a lower temperature. Cardiolipin, which can promote the survival of S. aureus in harsh environments, had no effect on maintaining the survival of E. coli. Although the trends remained unchanged, adjusting the humidity from 40% to 60% affected the survival of bacteria on dry surfaces. Scanning electron microscopic analysis revealed no morphological differences in these bacteria immediately before or after one day of dry conditions. In addition, ATP assessment, a method used to visualize high-touch surfaces in hospitals, was not effective at monitoring bacterial dynamics. A specialized handrail device fitted with a heater, which was maintained at normal human body core temperature, successfully prohibited the prolonged survival of bacteria [Enterococcus faecalis (ATCC), E. coli (ATCC), Pseudomonas aeruginosa (ATCC), S. aureus (ATCC), Acinetobacter baumannii (clinical isolate), and Serratia marcescens (clinical isolate)], with the exception of spore-forming Bacillus subtilis (from our laboratory collection) and the yeast-like fungus Candida albicans (from our laboratory collection)] on dry surfaces. Taken together, we concluded that the tested bacteria favor lower temperatures for their survival in dry environments. Therefore, the thermal control of dry fomites has the potential to control bacterial survival on high-touch surfaces in hospitals.

negative: Virus-like particle vaccine containing hemagglutinin confers protection against 2009 H1N1 pandemic influenza. Immunization of the world population before an influenza pandemic such as the 2009 H1N1 virus spreads globally is not possible with current vaccine production platforms. New influenza vaccine technologies, such as virus-like-particles (VLPs), offer a promising alternative. Here, we tested the immunogenicity and protective efficacy of a VLP vaccine containing hemagglutinin (HA) and M1 from the 2009 pandemic H1N1 influenza virus (H1N1pdm) in ferrets and compared intramuscular (i.m.) and intranasal (i.n.) routes of immunization. Vaccination of ferrets with VLPs containing the M1 and HA proteins from A/California/04/2009 (H1N1pdm) induced high antibody titers and conferred significant protection against virus challenge. VLP-vaccinated animals lost less weight, shed less virus in nasal washes, and had markedly lower virus titers in all organs tested than naïve controls. A single dose of VLPs, either i.m. or i.n., induced higher levels of antibody than did two doses of commercial split vaccine. Ferrets vaccinated with split vaccine were incompletely protected against challenge; these animals had lower virus titers in olfactory bulbs, tonsils, and intestines, but lost weight and shed virus in nasal washes to a similar extent as naïve controls. Challenge with heterologous A/Brisbane/59/07 (H1N1) virus revealed that the VLPs conferred minimal cross-protection to heterologous infection, as revealed by the lack of reduction in nasal wash and lung virus titers and slightly higher weight loss relative to controls. In summary, these experiments demonstrate the strong immunogenicity and protective efficacy of VLPs compared to the split vaccine and show that i.n. vaccination with VLPs has the potential for highly efficacious vaccination against influenza.

negative: Emergence of a Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2: Biology and Therapeutic Options The new decade of the 21(st) century (2020) started with the emergence of a novel coronavirus known as SARS-CoV-2 that caused an epidemic of coronavirus disease (COVID-19) in Wuhan, China. It is the third highly pathogenic and transmissible coronavirus after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in humans. The source of origin, transmission to humans, and mechanisms associated with the pathogenicity of SARS-CoV-2 are not yet clear, however, its resemblance to SARS-CoV and several other bat coronaviruses was recently confirmed through genome sequencing-related studies. The development of therapeutic strategies is necessary in order to prevent further epidemics and cure infections. In this review, we summarize current information about the emergence, origin, diversity, and epidemiology of three pathogenic coronaviruses with a specific focus on the current outbreak in Wuhan, China. Furthermore, we discuss the clinical features and potential therapeutic options that may be effective against SARS-CoV-2.

negative: Graphene-Based Strategies in Liquid Biopsy and in Viral Diseases Diagnosis Graphene-based materials are intriguing nanomaterials with applications ranging from nanotechnology-related devices to drug delivery systems and biosensing. Multifunctional graphene platforms were proposed for the detection of several typical biomarkers (i.e., circulating tumor cells, exosomes, circulating nucleic acids, etc.) in liquid biopsy, and numerous methods, including optical, electrochemical, surface-enhanced Raman scattering (SERS), etc., have been developed for their detection. Due to the massive advancements in biology, material chemistry, and analytical technology, it is necessary to review the progress in this field from both medical and chemical sides. Liquid biopsy is considered a revolutionary technique that is opening unexpected perspectives in the early diagnosis and, in therapy monitoring, severe diseases, including cancer, metabolic syndrome, autoimmune, and neurodegenerative disorders. Although nanotechnology based on graphene has been poorly applied for the rapid diagnosis of viral diseases, the extraordinary properties of graphene (i.e., high electronic conductivity, large specific area, and surface functionalization) can be also exploited for the diagnosis of emerging viral diseases, such as the coronavirus disease 2019 (COVID-19). This review aimed to provide a comprehensive and in-depth summarization of the contribution of graphene-based nanomaterials in liquid biopsy, discussing the remaining challenges and the future trend; moreover, the paper gave the first look at the potentiality of graphene in COVID-19 diagnosis.

negative: Isolation of the subunits of the coronavirus envelope glycoprotein E2 by hydroxyapatite high-performance liquid chromatography Abstract The coronavirus glycoprotein E2, which is responsible for virus attachment to cell receptors and virus-induced cell fusion, was purified by solubilization of virions with Triton X-114 and phase fractionation. Native E2 and tryptic subunits of the glycoprotein were separated by size-exclusion high-performance liquid chromatography (HPLC). Two distinct 90 kD E2 subunits, which had identified elecrophoretic mobilities when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were separated by hydroxyapetite HPLC in the presence of sodium dodecyl sulfate.

negative: Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV

negative: Biological Warfare: Infectious Disease and Bioterrorism The term biological warfare typically conjures images of medieval warriors tossing dead cattle over city walls or clandestine government agents secretly releasing mysterious microbes into enemy territory. Of course, biological warfare does encompass such activity, but the vast majority of what constitutes biological warfare is far more mundane. Ever since life evolved on earth about 3.8 billion years ago, organisms have constantly devised new ways to kill each other. Any organism that makes use of toxins—from bacteria to snakes—is engaging in a form of biological warfare. Humans who engage in biological warfare do so by taking advantage of these toxin-producing organisms.

negative: Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.

negative: Chapter 21 Gnotobiotics and the Microbiome Abstract This chapter provides an overview of germfree (GF), gnotobiotic (GN), and defined flora (DF) laboratory rats, relating their history, traditional and modern derivation procedures, the anatomy and physiology, and their use in the study of mammalian host–microbiome relationships. Extensive literature on the nutrition and physiology of GF rats and the expanding library of immunological reagents have increased the research utility of GF, GN, or DF rats. Such rats have been extensively used in metabolic experiments as nucleus seed stocks for the production of disease-free animals and as tools for infectious disease studies, among others. The chapter also presents research applications of GF rats that are particularly suitable for testing candidate viral carcinogens since they are uniquely free of all known viruses, for pathology studies in the distinguishing of primary mediation lesions from those associated with infections, and the study of the biological effects of radiation.

negative: Fighting against the common enemy of COVID-19: a practice of building a community with a shared future for mankind The outbreak of coronavirus disease 2019 (COVID-19) has caused more than 80 813 confirmed cases in all provinces of China, and 21 110 cases reported in 93 countries of six continents as of 7 March 2020 since middle December 2019. Due to biological nature of the novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with faster spreading and unknown transmission pattern, it makes us in a difficulty position to contain the disease transmission globally. To date, we have found it is one of the greatest challenges to human beings in fighting against COVID-19 in the history, because SARS-CoV-2 is different from SARS-CoV and MERS-CoV in terms of biological features and transmissibility, and also found the containment strategies including the non-pharmaceutical public health measures implemented in China are effective and successful. In order to prevent a potential pandemic-level outbreak of COVID-19, we, as a community of shared future for mankind, recommend for all international leaders to support preparedness in low and middle income countries especially, take strong global interventions by using old approaches or new tools, mobilize global resources to equip hospital facilities and supplies to protect noisome infections and to provide personal protective tools such as facemask to general population, and quickly initiate research projects on drug and vaccine development. We also recommend for the international community to develop better coordination, cooperation, and strong solidarity in the joint efforts of fighting against COVID-19 spreading recommended by the joint mission report of the WHO-China experts, against violating the International Health Regulation (WHO, 2005), and against stigmatization, in order to eventually win the battle against our common enemy — COVID-19.

negative: Essentials of infection prevention in the pediatric population Application of infection prevention and control (IP&C) measures is synonymous with safety, quality, resource saving, and the rights of all patients, staff and visitors. An extensive literature review was undertaken to identify key IP&C measures that address pediatric-specific requirements, taking into account age-related factors, diseases that occur most frequently among pediatric populations, and the important role of the caregiver in prevention and disease transmission. IP&C initiatives that target and incorporate both human (intrinsic) and environmental (extrinsic) sources of infection are population specific and guide practices and provide safe caring environments when used appropriately. Categories of care specifically geared to the pediatric age-group (0–14 years) are divided into two categories: within-the-healthcare system and outside-of-the-healthcare setting. By taking into account the child's developmental age; physiological, psycho-social and immunological development; differing impacts on the body's natural defense mechanisms, including procedural, device type and length of utilization; and availability of specific technologies and disciplines, the caregiver IP&C strategies can be developed and tailored to address specific needs. Within-the-healthcare setting strategies focus on surveillance, standard and transmission-based precautions, the immune system, age-related factors, institutional regulations, the family and visitation. Outside the healthcare setting preventative and protective measures are vital for providing maximum and comprehensive care. Care provided within and outside the healthcare setting can either be independent of each other or work together to maximize the health and safety of the child. This review article highlights the importance of IP&C knowledge, need for strict adherence to approved standards, and need for auditing compliance to achieve the ultimate goal of providing safe, quality care as well as an infection-free environment.

negative: Infection of porcine precision cut intestinal slices by transmissible gastroenteritis coronavirus demonstrates the importance of the spike protein for enterotropism of different virus strains Abstract TGEV is a coronavirus that is still widely spread in pig farming. On molecular level this virus has been studied in detail. However, studying TGEV infection within the complexity of the porcine intestinal epithelium reveals difficulties due to limiting infection models. Here we established a new ex vivo model to analyze the enterotropism of TGEV in porcine intestinal tissue. Precision cut intestinal slices (PCIS) were produced and ATP level was measured to proof vitality of the slices. ATP measurements and HE staining revealed living tissue in culture for up to 24h. PCIS were infected with three different TGEV strains. TGEV PUR 46-MAD is a commonly used TGEV strain that is known to be attenuated. TGEV Miller was passaged in piglets several times to reveal high infection. Finally, TGEV GFP is a recombinant strain that obtained its main body from TGEV PUR 46-MAD, but its spike protein from TGEV PUR-C11 that showed high mortality in piglets in vivo. Our results were in complete consensus of these statements. TGEV Miller mildly and TGEV GFP extensively infected the cells in the jejunum based on the amount of positive stained epithelial cells. However, for TGEV PUR 46-MAD no nucleocapsid protein was detected in the epithelial cells of the tissue. This shows that differences in TGEV strains and their infectious potential are highly dependent on their S protein.

negative: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.

negative: Performing the nasopharyngeal and oropharyngeal swab for 2019‐novel coronavirus (SARS‐CoV‐2) safely: How to dress, undress, and technical notes BACKGROUND: To show how to safely perform nasopharyngeal and/or oropharyngeal swabs for 2019‐novel coronavirus. METHODS: The video describes in detail the dressing and undressing procedures of health personnel, with the appropriate personal protective equipment. Technical notes for the execution of the nasopharyngeal and oropharyngeal swab are also provided to avoid sampling errors. RESULTS: The undressing phase is the procedure with the highest risk of self‐contamination for the health worker. Following the various steps as shown in the video, there were no cases of contagion among the otolaryngology team appointed to perform the swabs for SARS‐CoV‐2 testing. CONCLUSIONS: This study demonstrates the technical feasibility of safely performing nasopharyngeal and/or oropharyngeal swabs for identification of SARS‐CoV‐2 viral RNA.

negative: Guidance for building a dedicated health facility to contain the spread of the 2019 novel coronavirus outbreak Preparedness for the ongoing coronavirus disease 2019 (COVID-19) and its spread in India calls for setting up of adequately equipped and dedicated health facilities to manage sick patients while protecting healthcare workers and the environment. In the wake of other emerging dangerous pathogens in recent times, such as Ebola, Nipah and Zika, it is important that such facilities are kept ready during the inter-epidemic period for training of health professionals and for managing cases of multi-drug resistant and difficult-to-treat pathogens. While endemic potential of such critically ill patients is not yet known, the health system should have surge capacity for such critical care units and preferably each tertiary government hospital should have at least one such facility. This article describes elements of design of such unit (e.g., space, infection control, waste disposal, safety of healthcare workers, partners to be involved in design and plan) which can be adapted to the context of either a new construction or makeshift construction on top of an existing structure. In view of a potential epidemic of COVID-19, specific requirements to handle it are also given.

negative: Effects of different sampling solutions on the survival of bacteriophages in bubbling aeration The present study focuses on the effects of three different sampling solutions, namely distilled water, phosphatic buffer solution, and suspension medium (SM), adding antifoam or not, on the survival probability of several different bacteriophages (EcP1,PhiX174,SM702, and F2) as surrogates for the mammalian viruses in the bubbling process. AGI-10 impinger was used as the representative for all the impingers which would bubble during operation. It was found that the survival probability of the same bacteriophage bubbling with different sampling solutions was different except that there was no significant difference observed for the bacteriophage F2. The use of SM as the collection fluid was relative to a high survival probability for the four bacteriophages. And the endurance or resistance of different kinds of bacteriophages in the same sampling solution was different. We conclude that SM is a promising sampling solution for liquid impingers in the process of sampling phages.

negative: Absencing/presencing risk: Rethinking proximity and the experience of living with major technological hazards Abstract There is now a substantial body of sociocultural research that has investigated the ways in which specific communities living in physical proximity with a variety of polluting or hazardous technological installations experience and respond to their exposure to the associated risk. Much of this research has sought to understand the apparent acceptance or acquiescence displayed by local populations towards established hazards of the kind that are typically resisted when the subject of siting proposals. However, recent theoretical contributions, produced largely outside the field of risk research, have problematised the objective distinction between proximity and distance. In this paper we explore the potential of some of these ideas for furthering our understanding of the relationship between place and the constitution of risk subjectivities. To do this we re-examine a number of existing sociocultural studies that are predicated on a localised approach and conceptualise the relationship of physically proximate sources of risk to everyday experience in terms of practices of ‘presencing’ and ‘absencing’. We conclude with some thoughts on the methodological and substantive implications of this reworking of proximity for future research into risk subjectivities.

negative: Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes—A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.

negative: Middle East respiratory syndrome coronavirus (MERS-CoV): Impact on Saudi Arabia, 2015 Middle East respiratory syndrome is the acute respiratory syndrome caused by betacoronavirus MERS-CoV. The first case of this disease was reported from Saudi Arabia in 2012. This virus is lethal and is a close relative of a severe acute respiratory syndrome (SARS), which is responsible for more than 3000 deaths in 2002–2003. According to Ministry of Health, Saudi Arabia. The number of new cases is 457 in 2015. Riyadh has the highest number of reports in comparison to the other cities. According to this report, males are more susceptible than female, especially after the age of 40. Because of the awareness and early diagnosis the incidence is falling gradually. The pre-existence of another disease like cancer or diabetic etc. boosts the infection. MERS is a zoonotic disease and human to human transmission is low. The MERS-CoV is a RNA virus with protein envelope. On the outer surface, virus has spike like glycoprotein which is responsible for the attachment and entrance inside host cells. There is no specific treatment for the MERS-CoV till now, but drugs are in pipeline which bind with the spike glycoprotein and inhibit its entrance host cells. MERS-CoV and SAR-CoV are from the same genus, so it was thought that the drugs which inhibit the growth of SARS-CoV can also inhibit the growth of MERS-CoV but those drugs are not completely inhibiting virus activity. Until we don’t have proper structure and the treatment of MERS-CoV, We should take precautions, especially the health care workers, Camel owners and Pilgrims during Hajj and Umrah, because they are at a higher risk of getting infected.

negative: COVID-19 related home confinement in adults: weight gain risks and opportunities As the global COVID-19 pandemic unfolds, over 90% of U.S. adult residents are confined to their homes, with restaurants, shops, schools, and workplaces shut down to prevent disease spread. While it is a priority to mitigate the immediate impact, one area of great concern is the long-term effects of this pandemic on weight management in adults. As evident from previous research, small changes in body weight in relatively short time periods can become permanent and lead to substantial weight gain over time(1). Considering that the current situation could last a total of several months, this extended home confinement could exacerbate the problem of obesity in adults by substantially contributing to or exceeding annual weight gain.

negative: Clinical features and sexual transmission potential of SARS-CoV-2 infected female patients: a descriptive study in Wuhan, China Background: As of March 2, 2020, SARS-CoV-2 has infected more than 80174 people and caused 2915 deaths in China. This virus rapidly spreads to 56 countries worldwide. Thus, in order to effectively block its transmission, it is urgent to uncover all the possible transmission routes of SARS-CoV-2. Methods: From January 28 to February 18, 2020, 35 female patients diagnosed with COVID-19 in Tongji Hospital were included in this descriptive study. The gynecologic history, clinical characteristics, laboratory findings and chest computed tomography (CT) of all patients were recorded in detail. To examine whether there is sexual transmission through vaginal from female to her partner, we employed real-time polymerase chain reaction testing (RT-PCR) to detect SARS-CoV-2 in vaginal environment (including vaginal discharge, cervical or vaginal residual exfoliated cells) and anal swab samples, and inquired recent sexual behaviors from the patients. Findings: The age range of the 35 patients with COVID-19 was 37-88 years. Over 50% patients infected with SARS-CoV-2 had chronic diseases. We tested the vaginal environment and anal swabs from the 35 female patients with COVID-19 and found that only an anal swab sample from one patient was positive for SARS-CoV-2. All the samples from vaginal environment were negative for SARS-CoV-2. The infection rate of the patients' sexual partner was 42.9%. Additionally, two female patients admitted having sex with their partners during a possible infection incubation period, while one patient's partner was uninfected and the other patient's partner was diagnosed with COVID-19 (after the diagnosis of the female patient). Conclusion: No positive RT-PCR result was found in the vaginal environment perhaps due to the lack of ACE2 expression, which is the receptor of SARS-CoV-2, in the vagina and cervix tissues (human protein atlas). The results from this study show no evidence of transmission of SARS-CoV-2 through vaginal sex from female to her partner. However, the risk of infection of non vaginal sex and other intimate contacts during vaginal sex should not be ignored.

negative: How the Double Spherules of Infectious Bronchitis Virus Impact Our Understanding of RNA Virus Replicative Organelles Powered by advances in electron tomography, recent studies have extended our understanding of how viruses construct “replication factories” inside infected cells. Their function, however, remains an area of speculation with important implications for human health. It is clear from these studies that whatever their purpose, organelle structure is dynamic (M. Ulasli, M. H. Verheije, C. A. de Haan, and F. Reggiori, Cell. Microbiol. 12:844-861, 2010) and intricate (K. Knoops, M. Kikkert, S. H. Worm, J. C. Zevenhoven-Dobbe, Y. van der Meer, et al., PLOS Biol. 6:e226, 2008). But by concentrating on medically important viruses, these studies have failed to take advantage of the genetic variation inherent in a family of viruses that is as diverse as the archaea, bacteria, and eukaryotes combined (C. Lauber, J. J. Goeman, M. del Carmen Parquet, P. T. Nga, E. J. Snijder, et al., PLOS Pathog. 9:e1003500, 2013). In this climate, Maier et al. (H. J. Maier, P. C. Hawes, E. M. Cottam, J. Mantell, P. Verkade, et al., mBio 4:e00801-13, 2013) explored the replicative structures formed by an avian coronavirus that appears to have diverged at an early point in coronavirus evolution and shed light on controversial aspects of viral biology.

negative: [Respiratory and Facial Protection: Current Perspectives in the Context of the COVID-19 Pandemic]. The new SARS-CoV-2 pandemic is an example of an international public health emergency, which is associated with considerable social and economic challenges. At the healthcare level there is the risk that nosocomial outbreaks can be local amplifiers. Adequate infection control practices are of critical importance, which include proper use of personal protective equipment. This equipment must be appropriate to the pathogen transmission route that, in the case of SARS-CoV-2, occurs through droplet and contact routes. The infected individual, when talking, coughing or sneezing, spreads droplets containing the virus, directly contaminating other individuals within one to two meters of distance, as well as the surrounding environment. Airborne transmission may occur when aerosol-generating procedures are performed. Concerning respiratory protection, there is currently weak evidence that the use of respirators provides better protection than surgical masks for SARS-CoV-2 or other viruses (with the exception of aerosol-generating procedures, in which case the use of a respirator is recommended). Eye protection should be guaranteed whenever there is a risk of splashes, droplets or aerosols. The use of different, or higher than necessary, level of personal protective equipment, for the transmission route of the agent, is a form of misuse and can affect its supply for situations when it is clearly indicated. The adequate provision of protective equipment, as well as training of healthcare professionals in its correct use, is highly recommended to ensure safety of care.

negative: AJN On the Web. SARS-CoV-2, the novel coronavirus causing coronavirus disease 2019 (COVID-19), is now a global pandemic Human-to-human transmission has been documented to occur through respiratory secretions, feces, aerosols, and contaminated environmental surfaces Pediatric patients present a unique challenge as they may have minimal symptoms and yet transmit disease Endoscopists face risk for infection with viruses like SARS-CoV-2, as the aerosol generating nature of endoscopy diffuses respiratory disease that can be spread via an airborne and droplet route We describe our center's methodology for pediatric patient risk stratification to facilitate responsible use of endoscopic resources during this crisis We also describe our recommendations for use of personal protective equipment by endoscopists, with the goal of ensuring the safety of ourselves, our anesthesiology and endoscopy staff, and our patients Address correspondence and reprint requests to Daphne S Say, MD, Assistant Clinical Professor, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, Davis, 2516 Stockton Boulevard, Ticon II, Sacramento, CA 95817 (e-mail: dsay@ucdavis edu) Received 26 March, 2020 Accepted 30 March, 2020 Conflict of Interest Disclosure: The authors have no conflicts of interest relevant to this article to disclose Funding Source: No funding was secured for this study Financial Disclosure: The authors have no financial relationships relevant to this article to disclose © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology

negative: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Summary Background Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. Methods We retrospectively retrieved data for paediatric patients (aged 0–16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. Findings From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5–38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir–ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Interpretation Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Funding Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.

negative: Recent Advances in AIV Biosensors Composed of Nanobio Hybrid Material Since the beginning of the 2000s, globalization has accelerated because of the development of transportation systems that allow for human and material exchanges throughout the world. However, this globalization has brought with it the rise of various pathogenic viral agents, such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus, and Dengue virus. In particular, avian influenza virus (AIV) is highly infectious and causes economic, health, ethnical, and social problems to human beings, which has necessitated the development of an ultrasensitive and selective rapid-detection system of AIV. To prevent the damage associated with the spread of AIV, early detection and adequate treatment of AIV is key. There are traditional techniques that have been used to detect AIV in chickens, ducks, humans, and other living organisms. However, the development of a technique that allows for the more rapid diagnosis of AIV is still necessary. To achieve this goal, the present article reviews the use of an AIV biosensor employing nanobio hybrid materials to enhance the sensitivity and selectivity of the technique while also reducing the detection time and high-throughput process time. This review mainly focused on four techniques: the electrochemical detection system, electrical detection method, optical detection methods based on localized surface plasmon resonance, and fluorescence.

negative: TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection Transmembrane serine protease TMPRSS2 activates the spike protein of highly pathogenic human coronaviruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV). In vitro, activation induces virus-cell membrane fusion at the cell surface. However, the roles of TMPRSS2 during coronavirus infection in vivo are unclear. Here, we used animal models of SARS-CoV and MERS-CoV infection to investigate the role of TMPRSS2. Th1-prone C57BL/6 mice and TMPRSS2-knockout (KO) mice were used for SARS-CoV infection, and transgenic mice expressing the human MERS-CoV receptor DPP4 (hDPP4-Tg mice) and TMPRSS2-KO hDPP4-Tg mice were used for MERS-CoV infection. After experimental infection, TMPRSS2-deficient mouse strains showed reduced body weight loss and viral kinetics in the lungs. Lack of TMPRSS2 affected the primary sites of infection and virus spread within the airway, accompanied by less severe immunopathology. However, TMPRSS2-KO mice showed weakened inflammatory chemokine and/or cytokine responses to intranasal stimulation with poly(I·C), a Toll-like receptor 3 agonist. In conclusion, TMPRSS2 plays a crucial role in viral spread within the airway of murine models infected by SARS-CoV and MERS-CoV and in the resulting immunopathology. IMPORTANCE Broad-spectrum antiviral drugs against highly pathogenic coronaviruses and other emerging viruses are desirable to enable a rapid response to pandemic threats. Transmembrane protease serine type 2 (TMPRSS2), a protease belonging to the type II transmembrane serine protease family, cleaves the coronavirus spike protein, making it a potential therapeutic target for coronavirus infections. Here, we examined the role of TMPRSS2 using animal models of SARS-CoV and MERS-CoV infection. The results suggest that lack of TMPRSS2 in the airways reduces the severity of lung pathology after infection by SARS-CoV and MERS-CoV. Taken together, the results will facilitate development of novel targets for coronavirus therapy.

negative: COVID‐19 epidemic: Disease characteristics in children In mid‐December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus‐2, which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease‐2019 (COVID‐19) has also increased significantly. Although information regarding the epidemiology of COVID‐19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID‐19 in children.

negative: Severe Respiratory Illness Outbreak Associated with Human Coronavirus NL63 in a Long-Term Care Facility We describe an outbreak of severe respiratory illness associated with human coronavirus NL63 in a long-term care facility in Louisiana in November 2017. Six of 20 case-patients were hospitalized with pneumonia, and 3 of 20 died. Clinicians should consider human coronavirus NL63 for patients in similar settings with respiratory disease.

negative: Preliminary evidence that higher temperatures are associated with lower incidence of COVID-19, for cases reported globally up to 29th February 2020 Seasonal variation in COVID-19 incidence could impact the trajectory of the pandemic. Using global line-list data on COVID-19 cases reported until 29th February 2020 and global gridded temperature data, and after adjusting for surveillance capacity and time since first imported case, higher average temperature was strongly associated with lower COVID-19 incidence for temperatures of 1°C and higher. However, temperature explained a relatively modest amount of the total variation in COVID-19 incidence. These preliminary findings support stringent containment efforts in Europe and elsewhere.

negative: COVID-19 will severely impact older people's lives, and in many more ways than you think!

negative: Serological evidence of coronavirus infections in native hamadryas baboons (Papio hamadryas hamadryas) of the Kingdom of Saudi Arabia The hamadryas baboon (Papio hamadryas hamadryas) is the only indigenous species of non-human primates (NHP) found in the Kingdom of Saudi Arabia (KSA). There are no peer-reviewed publications on viral infections of the baboons of KSA. Apart from camels, other animals are likely sources of the novel Middle East Respiratory Syndrome coronavirus (MERSCoV) for humans. We investigated evidence of highly pathogenic coronavirus infections including MERSCoV in a large group of commensal baboons accompanied by feral dogs, on the outskirts of Ta'if city, KSA, in February 2013. Fifty baboons (16 juveniles and 34 adults) were screened for serum antibodies to human coronaviruses (HCoV-043/-NL63/-229) and canine coronaviruses (CCoV-1-3) using direct Enzyme-linked Immunosorbent Assay (ELISA) technique and for MERSCoV antibodies using Serum Neutralization Test (SNT). Of the 50 sampled baboons, 22% (n = 11) were seropositive to HCoVs, 10% (n = 5) were seropositive to CCoVs, while none had detectable MERSCoV antibodies. These findings bear potentially significant implications for public health, canine health and baboon conservation efforts, necessitating follow-up investigations and preventive measures at locations where baboons frequent human habitations, or are regarded as tourist attractions, in KSA.

negative: SARS in Taiwan: an overview and lessons learned Summary Objectives: This report aims to describe the epidemiology of severe acute respiratory syndrome (SARS) in Taiwan between March and July 2003, and to examine the public health response. Methods: Surveillance for SARS was initiated on 14 March 2003. Response activities are described for the isolation of patients; contact tracing; quarantine of contact persons; fever screening for inbound and outbound passengers at the airport; and hospital infection control as assessed by mobile SARS containment teams. Results: Between 14 March and 30 July 2003 a total of 668 probable cases of SARS were reported. Of the 668 cases, 181 (27%) were fatal. Compared to the survivors, fatal cases were more likely to be older (p <0.001), male (p <0.05), exposed through hospital contact (p <0.001), and have a coexisting medical disorder (p <0.001). Between 28 March and 30 July a total of 151,270 persons were quarantined. Among them, 46 (3.0/10,000) were subsequently classified as being probable SARS cases. At the time of the mobile team assessments, 46 (53%) hospitals had implemented WHO infection control recommendations. Conclusions: In this outbreak, an emergency plan consisted of patient isolation and strict hospital infection control.

negative: Computational Prediction of the Comprehensive SARS-CoV-2 vs. Human Interactome to Guide the Design of Therapeutics Understanding the disease pathogenesis of the novel coronavirus, denoted SARS-CoV-2, is critical to the development of anti-SARS-CoV-2 therapeutics. The global propagation of the viral disease, denoted COVID-19 (“coronavirus disease 2019”), has unified the scientific community in searching for possible inhibitory small molecules or polypeptides. Given the known interaction between the human ACE2 (“Angiotensin-converting enzyme 2”) protein and the SARS-CoV virus (responsible for the coronavirus outbreak circa. 2003), considerable focus has been directed towards the putative interaction between the SARS-CoV-2 Spike protein and ACE2. However, a more holistic understanding of the SARS-CoV-2 vs. human inter-species interactome promises additional putative protein-protein interactions (PPI) that may be considered targets for the development of inhibitory therapeutics. To that end, we leverage two state-of-the-art, sequence-based PPI predictors (PIPE4 & SPRINT) capable of generating the comprehensive SARS-CoV-2 vs. human interactome, comprising approximately 285,000 pairwise predictions. Of these, we identify the high-scoring subset of human proteins predicted to interact with each of the 14 SARS-CoV-2 proteins by both methods, comprising 279 high-confidence putative interactions involving 225 human proteins. Notably, the Spike-ACE2 interaction was the highest ranked for both the PIPE4 and SPRINT predictors, corroborating existing evidence for this PPI. Furthermore, the PIPE-Sites algorithm was used to predict the putative subsequence that might mediate each interaction and thereby inform the design of inhibitory polypeptides intended to disrupt the corresponding host-pathogen interactions. We hereby publicly release the comprehensive set of PPI predictions and their corresponding PIPE-Sites landscapes in the following DataVerse repository: 10.5683/SP2/JZ77XA. All data and metadata are released under a CC-BY 4.0 licence. The information provided represents theoretical modeling only and caution should be exercised in its use. It is intended as a resource for the scientific community at large in furthering our understanding of SARS-CoV-2.

negative: Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies INTRODUCTION: Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown. OBJECTIVES: The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure. METHOD: Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression. RESULTS: Bacterial bronchopneumonia was present in 33.9% of the cases and cancer in 28.1%. The pulmonary histopathology showed diffuse alveolar damage in 40.7% (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/AIDS and liver cirrhosis. CONCLUSIONS: Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.

negative: Foreign Aid and Humanitarian Assistance Together the US and EU provide two-thirds of global humanitarian assistance for the alleviation of emergencies arising from natural and man-made disasters and 80% of global foreign aid for longer-term development assistance programs. It is therefore vital that they continue their close partnership to ensure their dollars and euros are spent as effectively as possible in an era of increasingly tight budgetary constraints. The outbreak of Ebola in West Africa in 2014 is a good example of how the US and the EU successfully addressed (albeit belatedly) a major health crisis that could have turned into a global pandemic. In many areas in Africa, they are collaborating closely on the foundation of shared priorities, including on food security, resilience, and electrification. They are also among the largest donors to the Global Fund to fight HIV/AIDS, tuberculosis, and malaria and to the Global Alliance for Vaccines and Immunisation.

negative: Risk estimation of the SARS-CoV-2 acute respiratory disease outbreak outside China BACKGROUND: On December 31, 2019, the World Health Organization was alerted to the occurrence of cases of pneumonia in Wuhan, Hubei Province, China, that were caused by an unknown virus, which was later identified as a coronavirus and named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to estimate the reproductive number of SARS-CoV-2 in the Hubei Province and evaluate the risk of an acute respiratory coronavirus disease (COVID-19) outbreak outside China by using a mathematical model and stochastic simulations. RESULTS: We constructed a mathematical model of SARS-CoV-2 transmission dynamics, estimated the rate of transmission, and calculated the reproductive number in Hubei Province by using case-report data from January 11 to February 6, 2020. The possible number of secondary cases outside China was estimated by stochastic simulations in various scenarios of reductions in the duration to quarantine and rate of transmission. The rate of transmission was estimated as 0.8238 (95% confidence interval [CI] 0.8095–0.8382), and the basic reproductive number as 4.1192 (95% CI 4.0473–4.1912). Assuming the same rate of transmission as in Hubei Province, the possibility of no local transmission is 54.9% with a 24-h quarantine strategy, and the possibility of more than 20 local transmission cases is 7% outside of China. CONCLUSION: The reproductive number for SARS-CoV-2 transmission dynamics is significantly higher compared to that of the previous SARS epidemic in China. This implies that human-to-human transmission is a significant factor for contagion in Hubei Province. Results of the stochastic simulation emphasize the role of quarantine implementation, which is critical to prevent and control the SARS-CoV-2 outbreak outside China.

negative: Bat Hunting and Bat-Human Interactions in Bangladeshi Villages: Implications for Zoonotic Disease Transmission and Bat Conservation Bats are an important reservoir for emerging zoonotic diseases. Close human-bat interactions, including the sharing of living spaces and hunting and butchering of bats for food and medicines, may lead to spillover of zoonotic disease into human populations. We used bat exposure and environmental data gathered from 207 Bangladeshi villages to characterize bat exposures and hunting in Bangladesh. Eleven percent of households reported having a bat roost near their homes, 65% reported seeing bats flying over their households at dusk, and 31% reported seeing bats inside their compounds or courtyard areas. Twenty percent of households reported that members had at least daily exposure to bats. Bat hunting occurred in 49% of the villages surveyed and was more likely to occur in households that reported nearby bat roosts (adjusted prevalence ratio [aPR] 2.3, 95% CI 1.1-4.9) and villages located in Northwest (aPR 7.5, 95% CI 2.5-23.0) and Southwest (aPR 6.8, 95% CI 2.1-21.6) regions. Our results suggest high exposure to bats and widespread hunting throughout Bangladesh. This has implications both for zoonotic disease spillover and bat conservation.

negative: Abstract Presentations from the AABB Annual Meeting Boston, MA, October 13–16, 2018

negative: Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats BACKGROUND AND OBJECTIVES: A drug repurposing strategy is an approach for identifying new therapeutic uses for approved or investigational drugs. Thanks to the moderate cost of repurposing a drug compared to bringing new chemical entity to the market, drug repurposing is rapidly gaining ground. The aim of this work is to study the anti-obesity effect of disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor approved by the Food and Drug Administration (FDA) to treat chronic alcoholism since 1951. METHODS: Thirty male Albino rats were randomly assigned to six groups. G1, the control group, was given a standard diet. G2, the positive control group, was given a high-fat diet (HFD). G3 was given an HFD, and DSF 50 mg/kg/day was administered orally from day one for six weeks. G4 was given an HFD, and DSF 200 mg/kg/day was administered orally from day one for six weeks. G5 was given an HFD for six weeks; then treatment started with 50 mg/kg/day DSF orally. G6 was given an HFD for six weeks; then treatment started with 200 mg/kg/day DSF orally for three weeks. The body weight, food consumption and blood glucose levels were monitored over the given time interval. RESULTS: Both doses of DSF significantly limited the body weight gain caused by an HFD for the treated animals. HF-fed rats received 50 and 200 mg/kg/day of DSF had their body weight increased by 51.93 ± 7.89% and 20.88 ± 15.05% respectively, whereas the body weight of control animals increased by 93.1 ± 20.04%. DSF also significantly decreased the body weight of obese animals. At 50 and 200 mg/kg/day of DSF, HF-fed rats lost 16.74 ± 8.61% and 23.9 ± 3.93% respectively, as their untreated counterparts had their body weight increased by 11.85 ± 3.79% after three weeks of treatment, thus restoring a body weight matching those who received a standard diet. CONCLUSION: FDA-approved disulfiram has a strong anti-obesity effect on HFD-fed rats.

negative: Coronavirus nixes conference, twilight zone beckons and a faded star brightens.

negative: The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China The novel coronavirus can be transmitted from person to person with infection ranging from mild disease to severe pneumonia and radiological abnormalities on chest CT for most patients improved after RT-PCR conversion.

negative: Severe acute respiratory syndrome: review and lessons of the 2003 outbreak

negative: Structural disorder in the proteome and interactome of Alkhurma virus (ALKV) Infection by the Alkhurma virus (ALKV) leading to the Alkhurma hemorrhagic fever is a common thread in Saudi Arabia, with no efficient treatment or prevention available as of yet. Although the rational drug design traditionally uses information on known 3D structures of viral proteins, intrinsically disordered proteins (i.e., functional proteins that do not possess unique 3D structures), with their multitude of disorder-dependent functions, are crucial for the biology of viruses. Here, viruses utilize disordered regions in their invasion of the host organisms and in hijacking and repurposing of different host systems. Furthermore, the ability of viruses to efficiently adjust and accommodate to their hostile habitats is also intrinsic disorder-dependent. However, little is currently known on the level of penetrance and functional utilization of intrinsic disorder in the ALKV proteome. To fill this gap, we used here multiple computational tools to evaluate the abundance of intrinsic disorder in the ALKV genome polyprotein. We also analyzed the peculiarities of intrinsic disorder predisposition of the individual viral proteins, as well as human proteins known to be engaged in interaction with the ALKV proteins. Special attention was paid to finding a correlation between protein functionality and structural disorder. To the best of our knowledge, this work represents the first systematic study of the intrinsic disorder status of ALKV proteome and interactome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-018-2968-8) contains supplementary material, which is available to authorized users.

negative: Coronavirus Disease (COVID-19) Pandemic: An Overview of Systematic Reviews Background: Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging and ongoing critical appraisal of this output is essential. We aimed to collate and summarize all published systematic reviews on the coronavirus disease (COVID-19). Methods: Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO's Global Research, LILACS and Epistemonikos) were searched from December 1, 2019 to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory and radiological findings) and quality assessment (AMSTAR 2). Meta-analysis on prevalence of clinical outcomes was performed. Results: Eighteen systematic reviews were included; one was empty. Using AMSTAR 2, confidence in the results of 13 reviews was rated as "critically low", one as "low", one as "moderate" and two as "high". Symptoms of COVID-19 were (range values of point estimates): fever (82-95%), cough with or without sputum (58-72%), dyspnea (26-59%), myalgia or muscle fatigue (29-51%), sore throat (10-13%), headache (8-12%) and gastrointestinal complaints (5-9%). Severe symptoms were more common in men. Elevated C-reactive protein (associated with lymphocytopenia) and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. Chest imaging described a frequent pattern of uni- or bilateral multilobar ground-glass opacity. Only one review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3% to 14%. Conclusions: Confidence in the results of most reviews was "critically low". Future studies and systematic reviews should adhere to established methodologies. The majority of included systematic reviews were hampered by imprecise search strategy and no previous protocol submission. Protocol registration: This is an extension of a PROSPERO protocol (CRD42020170623); protocol available on Open Science Framework (https://osf.io/6xtyw).

negative: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff BACKGROUND: In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES: To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA: We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS: Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants), people with a long gown had less contamination than those with a coverall, and coveralls were more difficult to doff (low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS: We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort, and may therefore even lead to more contamination. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.

negative: The China Syndrome: the impact of the SARS epidemic in Southeast Asia The war in Iraq, the threat of terrorism and the Severe Acute Respiratory Syndrome (SARS) epidemic have made international business activities increasingly difficult and risky. The worldwide economic downturn and slow growth in domestic markets are forcing companies to depend more than ever on overseas trade. SARS emerged in China in November 2002 and has spread to 26 countries. The SARS epidemic has caused the most severe economic crisis in Southeast Asia since the wave of bank failures and currency devaluations that swept the region five years ago. The SARS epidemic has prompted health officials to implement travel advisories and restrictions, in order to defer nonessential travel to regions of Asia with large numbers of SARS cases. They are enforcing quarantine and isolation measures in major cities to try and limit the spread of SARS. The President of the United States has signed an executive order adding SARS to the list of communicable diseases that can be quarantined. A major disruption in China could paralyze just‐in‐time supply chains and cause an economic crisis for retailers and other businesses worldwide. The SARS epidemic has caused many economists to drastically reduce their economic‐growth forecasts for Asia. New infectious diseases, such as SARS, can emerge and easily travel around the globe, infecting less‐resilient hosts and mutating because of the influence of viruses and bacteria in their new environment. Health officials are even more concerned about the pandemic disaster that hasn’t happened, but may still. However, the SARS epidemic has created positive economic benefits for some companies.

negative: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff. BACKGROUND In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants) coveralls were more difficult to doff than isolation gowns (very low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). According to three studies that tested more recently introduced full-body PPE ensembles, there may be no difference in contamination. Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.

negative: COVID-19 preclinical models: human angiotensin-converting enzyme 2 transgenic mice Coronavirus disease 2019 (COVID-19) is a declared pandemic that is spreading all over the world at a dreadfully fast rate. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen of COVID-19, infects the human body using angiotensin-converting enzyme 2 (ACE2) as a receptor identical to the severe acute respiratory syndrome (SARS) pandemic that occurred in 2002–2003. SARS-CoV-2 has a higher binding affinity to human ACE2 than to that of other species. Animal models that mimic the human disease are highly essential to develop therapeutics and vaccines against COVID-19. Here, we review transgenic mice that express human ACE2 in the airway and other epithelia and have shown to develop a rapidly lethal infection after intranasal inoculation with SARS-CoV, the pathogen of SARS. This literature review aims to present the importance of utilizing the human ACE2 transgenic mouse model to better understand the pathogenesis of COVID-19 and develop both therapeutics and vaccines.

negative: Studies on the survival of aerosolized bovine rotavirus (UK) and a murine rotavirus The effect of relative humidity (RH) and temperature on the survival of airborne bovine rotavirus UK isolate (BRV-UK) and a murine rotavirus (MRV) was studied. In any one experiment, the virus under test was suspended in tryptose phosphate broth (TPB) supplemented with uranine (physical tracer) and an antifoam, was aerosolized using a Collison nebulizer into the rotating drum with the RH at either low (30 ± 5%), medium (50 + 5%) or high (80 ± 5%) level at 20 ± 1°C. Following a 15-min period of viral aerosol stabilization, sequential samples of drum air were collected using an All-Glass Impinger (AGI) for 24 h post-aerosolization. Both of the rotavirus isolates were found to survive best at medium RH level and high RH was found least favorable for the survival of these aerosolized rotaviruses. The survival pattern of aerosolized MRV was found to be the best when compared with survival pattern of all animal and human rotavirus isolates studies performed under aerosolized conditions in our laboratory. The findings of these experiments confirm and extend our previous reports on the survival of other animal and human aerosolized rotaviruses and emphasize the fact that air may be one of the vehicles for their dissemination and could explain why it is difficult to control nosocomial outbreaks of rotavirus gastroenteritis and to keep animal colonies rotavirus-free.

negative: Old and new antirheumatic drugs for the treatment of COVID-19

negative: Chapter Two Fly foregut and transmission of microbes Abstract Two areas of research that have greatly increased in attention are: dipterans as vectors and the microbes they are capable of vectoring. Because it is the front-end of the fly that first encounters these microbes, this review focuses on the legs, mouthparts, and foregut, which includes the crop as major structures involved in dipteran vectoring ability. The legs and mouthparts are generally involved in mechanical transmission of microbes. However, the crop is involved in more than just mechanical transmission, for it is within the lumen of the crop that microbes are taken up with the meal of the fly, stored, and it is within the lumen that horizontal transmission of bacterial resistance has been demonstrated. In addition to storage of microbes, the crop is also involved in depositing the microbes via a process known as regurgitation. Various aspects of crop regulation are discussed and specific examples of crop involvement with microorganisms are discussed. The importance of biofilm and biofilm formation are presented, as well as, some physical parameters of the crop that might either facilitate or inhibit biofilm formation. Finally, there is a brief discussion of dipteran model systems for studying crop microbe interactions.

negative: A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease—COVID-19— within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronavirus’s surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 Å. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the “closed” prefusion S structure, but is accessible in “open” conformations. This first-ever resolution of a human antibody in complex with SARS-CoV-2 and the broad reactivity of this set of antibodies to a conserved betacoronavirus epitope will allow antigenic assessment of vaccine candidates, and provide a framework for accelerated vaccine, immunotherapeutic and diagnostic strategies against SARS-CoV-2 and related betacoronaviruses. HIGHLIGHTS High resolution structure of the SARS-CoV-2 Receptor-Binding-Domain (RBD). Recognition of the SARS-CoV-2 RBD by SARS-CoV antibodies. Structure of the SARS-COV-2 RBD in complex with antibody CR3022. Identification of a cryptic site of vulnerability on the SARS-CoV-2 Spike.

negative: Risk assessment of novel coronavirus COVID-19 outbreaks outside China We developed a computational tool to assess the risk of novel coronavirus outbreaks outside China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number Rloc). We found that in countries with low connectivity to China but with relatively high Rloc, the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low Rloc benefit the most from policies that further reduce Rloc. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia and Europe, and we investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.

negative: Data analytics for novel coronavirus disease This paper describes different aspects of novel coronavirus disease (COVID-19), presents visualization of the spread of the infection, and discusses the potential applications of data analytics on this viral infection. Firstly, a literature survey is done on COVID-19 highlighting a number of factors including its origin, its similarity with previous coronaviruses, its transmission capacity, its symptoms, etc. Secondly, data analytics is applied on a dataset of Johns Hopkins University to find out the spread of the viral infection. It is shown here that although the disease started in China in December 2019, the highest number of confirmed cases up to June 04, 2020 is in the USA. Thirdly, the worldwide increase in the number of confirmed cases over time is modelled here using a polynomial regression algorithm with degree 2. Fourthly, classification algorithms are applied on a dataset of 5644 samples provided by Hospital Israelita Albert Einstein of Brazil in order to diagnose COVID-19. It is shown here that multilayer perceptron (MLP), XGBoost and logistic regression can classify COVID-19 patients at an accuracy above 91%. Finally, a discussion is presented on the potential applications of data analytics in several important factors of COVID-19.

negative: The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins SARS-CoV-2 emerged in late 2019, leading to the COVID-19 pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as well as related coronaviruses circulating in bats, SARS-CoV-2 is thought to have originated in Chiroptera species in China. However, whether the virus spread directly to humans or through an intermediate host is currently unclear, as is the potential for this virus to infect companion animals, livestock and wildlife that could act as viral reservoirs. Using a combination of surrogate entry assays and live virus we demonstrate that, in addition to human ACE2, the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins. Of the twenty-two different hosts we investigated, ACE2 proteins from dog, cat and rabbit were the most permissive to SARS-CoV-2, while bat and bird ACE2 proteins were the least efficiently used receptors. The absence of a significant tropism for any of the three genetically distinct bat ACE2 proteins we examined indicates that SARS-CoV-2 receptor usage likely shifted during zoonotic transmission from bats into people, possibly in an intermediate reservoir. Interestingly, while SARS-CoV-2 pseudoparticle entry was inefficient in cells bearing the ACE2 receptor from bats or birds the live virus was still able to enter these cells, albeit with markedly lower efficiency. The apparently broad tropism of SARS-CoV-2 at the point of viral entry confirms the potential risk of infection to a wide range of companion animals, livestock and wildlife.

negative: Challenges in the interpretation and application of typical imaging features of COVID-19

negative: Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy.

negative: Stability of RNA sequences derived from the coronavirus genome in human cells Most viruses inhibit the innate immune system and/or the RNA degradation processes of host cells to construct an advantageous intracellular environment for their survival. Characteristic RNA sequences within RNA virus genomes or RNAs transcribed from DNA virus genomes contribute toward this inhibition. In this study, we developed a method called "Fate-seq" to comprehensively identify the RNA sequences derived from RNA and DNA viruses, contributing RNA stability in the cells. We examined the stabilization activity of 5,924 RNA fragments derived from 26 different viruses (16 RNA viruses and 10 DNA viruses) using next-generation sequencing of these RNAs fused 3' downstream of GFP reporter RNA. With the Fate-seq approach, we detected multiple virus-derived RNA sequences that stabilized GFP reporter RNA, including sequences derived from severe acute respiratory syndrome-related coronavirus (SARS-CoV). Comparative genomic analysis revealed that these RNA sequences and their predicted secondary structures are highly conserved between SARS-CoV and the novel coronavirus, SARS-CoV-2, which is responsible for the global outbreak of the coronavirus-associated disease that emerged in December 2019 (COVID-19). These sequences have the potential to enhance the stability of viral RNA genomes, thereby augmenting viral replication efficiency and virulence.

negative: The First 75 Days of Novel Coronavirus (SARS-CoV-2) Outbreak: Recent Advances, Prevention, and Treatment The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) outbreak has engulfed an unprepared world amidst a festive season. The zoonotic SARS-CoV-2, believed to have originated from infected bats, is the seventh member of enveloped RNA coronavirus. Specifically, the overall genome sequence of the SARS-CoV-2 is 96.2% identical to that of bat coronavirus termed BatCoV RaTG13. Although the current mortality rate of 2% is significantly lower than that of SARS (9.6%) and Middle East respiratory syndrome (MERS) (35%), SARS-CoV-2 is highly contagious and transmissible from human to human with an incubation period of up to 24 days. Some statistical studies have shown that, on average, one infected patient may lead to a subsequent 5.7 confirmed cases. Since the first reported case of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 on December 1, 2019, in Wuhan, China, there has been a total of 60,412 confirmed cases with 1370 fatalities reported in 25 different countries as of February 13, 2020. The outbreak has led to severe impacts on social health and the economy at various levels. This paper is a review of the significant, continuous global effort that was made to respond to the outbreak in the first 75 days. Although no vaccines have been discovered yet, a series of containment measures have been implemented by various governments, especially in China, in the effort to prevent further outbreak, whilst various medical treatment approaches have been used to successfully treat infected patients. On the basis of current studies, it would appear that the combined antiviral treatment has shown the highest success rate. This review aims to critically summarize the most recent advances in understanding the coronavirus, as well as the strategies in prevention and treatment.

negative: Chapter 16 Combustion, reactive hazard, and bioprocess safety Abstract Is bioprocess dangerous? How to maintain safety? What is reactive hazard? What is biohazard? Chemical or biotransformation means change. Any changes have irreversible consequences. Managing the changes can help us, while changes can also be harmful. The first-line of defense on any potential unwanted transformations is isolation or containment. WHO defines four-risk groups of biosafety levels. There are six key knowledge bases for biosafety. With chemical safety, substance identification is the first step. The global harmonized system (GHS) of classification and labeling is generally agreed by the world bodies. The hazards are divided into three categories—physical, health, and environmental hazards. Chemical reactivity hazard is a situation where an uncontrolled reaction could result directly or indirectly in serious harm to people, property, or equipment. Fire and explosion are common reactivity hazards. To safe guard processes and facility, one needs to first identify the threat, or screening for reactivity hazards. Combustion processes proceed with chain reactions and the reaction is highly exothermic. Combined with the high-activation energy, combustion leads to large-temperature dependence. The overall reaction products can also vary (partial oxidation versus total oxidation). Partial oxidation reactions are important in chemical industry. Pyrolysis and gasification of biomass, for example, are useful technologies in biomass conversion. An explosion is a fast, transient, exothermic reaction. Unintended and accidental explosions can occur due to (1) The accumulation of reactive chemicals (gas, liquid, or solid) in confined space; (2) Leakage of “significant amount” of reactive chemicals (gas, liquid, or solid) to atmosphere or environment; or (3) Reactor runaway. As a bioprocess engineer, you will be responsible for creating safe processes and protecting the lives and health of your colleagues.

negative: Guide to Understanding the 2019 Novel Coronavirus

negative: Novel Coronavirus Disease 2019 (COVID-19): An Emerging Infectious Disease in the 21st Century Background: At the beginning of the New Year 2020, China alerted the world health organization (WHO) to a cluster of unusual pneumonia cases in Wuhan After extensive speculation, eventually a new species of coronavirus introduced as the causative pathogen of the disease Coronavirus disease 2019 (COVID-19) is a name for the disease, and the virus that causes it is known SARS-CoV-2 The very rapid spread of the COVID-19 in China and in many other countries has caused fear among people across the world The novel coronavirus outbreak declared a Public Health Emergency of International Concern on 30 January 2020 Materials and Methods: Several databases such as PubMed, Scopus, Google scholar, and BioRxiv were searched for publications reporting on the novel coronavirus up to 29 February 2020 Literature searches were performed using keywords including “Coronavirus 2019”, “2019-nCoV”, “COVID-19”, and “SARS-CoV-2” Moreover, websites such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) were searched to retrieve updated data and statistics regarding the novel coronavirus We extracted data on the epidemiology, pathogenesis, virology, clinical manifestations, transmission routes, diagnosis, treatment, and prevention measures Results: From the 1416 articles identified in the initial search, 53 were remained after title and abstract screening After full-text review, 37 articles were eligible to include in our study Incubation period for COVID-19 is between 2-10 days, according to the World Health Organization (WHO) The case fatality rate in patients infected with SARC-CoV-2 is 4 3%, and the results indicate that the mortality is higher in elderly individuals and patients with chronic conditions including patients with coronary artery disease, diabetes, chronic pulmonary disease, and hypertension The mortality rate in healthy subjects is less than 1% Conclusion: The outbreak caused by the novel coronavirus is larger than the previous human coronaviruses, showing that the SARS-CoV-2 is an extremely contagious virus However, the mortality rate of COVID-19 is lower than that of other coronaviruses diseases such as SARS or MERS and other viruses like HIV and Ebola Currently, due to the lack of an effective treatment and vaccine, the best way to deal with the COVID-19 disease is to prevent transmission and spread of the virus and to execute personal protective measures

negative: Chapter Four Structural insights into coronavirus entry Abstract Coronaviruses (CoVs) have caused outbreaks of deadly pneumonia in humans since the beginning of the 21st century. The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and was responsible for an epidemic that spread to five continents with a fatality rate of 10% before being contained in 2003 (with additional cases reported in 2004). The Middle-East respiratory syndrome coronavirus (MERS-CoV) emerged in the Arabian Peninsula in 2012 and has caused recurrent outbreaks in humans with a fatality rate of 35%. SARS-CoV and MERS-CoV are zoonotic viruses that crossed the species barrier using bats/palm civets and dromedary camels, respectively. No specific treatments or vaccines have been approved against any of the six human coronaviruses, highlighting the need to investigate the principles governing viral entry and cross-species transmission as well as to prepare for zoonotic outbreaks which are likely to occur due to the large reservoir of CoVs found in mammals and birds. Here, we review our understanding of the infection mechanism used by coronaviruses derived from recent structural and biochemical studies.

negative: 9-[2-(R)-(Phosphonomethoxy)propyl]-2,6-diaminopurine (R)-PMPDAP and its prodrugs: Optimized preparation, including identification of by-products formed, and antiviral evaluation in vitro Abstract New large-scale synthetic approach to antiretroviral agent 9-[2-(R)-(phosphonomethoxy)propyl]-2,6-diaminopurine, (R)-PMPDAP, was developed. Reaction of (R)-propanediol carbonate with 2,6-diaminopurine afforded exclusively (R)-9-(2-hydroxypropyl)-2,6-diaminopurine which was subsequently used for introduction of a phosphonomethyl residue using TsOCH2P(O)(OiPr)2 or BrCH2P(O)(OiPr)2 followed by deprotection of ester groups. All minor ingredients and by-products formed during the process were identified and further studied. The final product was obtained in high yield and its high enantiomeric purity (>99%) was confirmed by chiral capillary electrophoretic analysis using β-cyclodextrin as a chiral selector. Antiretroviral activity data of (R)-PMPDAP and its diverse prodrugs against HIV and FIV were investigated. Akin to (R)-PMPDAP, both prodrugs inhibit FIV replication in a selective manner. Compared to the parent molecule, the amidate prodrug was 10-fold less active against FIV in cell culture, whereas the alkoxyalkyl ester prodrug was 200-fold more potent in inhibiting FIV replication in vitro.

negative: Evaluating the potential impact of targeted vaccination strategies against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks in the healthcare setting BACKGROUND: Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are two coronaviruses with demonstrated potential to generate significant nosocomial outbreaks. In particular, MERS continues to pose a significant threat in the Middle East since 2012. Currently, no licensed vaccine or drug treatment is available to treat patients infected with either coronavirus. However, there are some MERS vaccines in the preclinical stage of development. We sought to evaluate the potential impact of targeted vaccination strategies for mitigating SARS and MERS outbreaks in healthcare settings using simple mathematical models and detailed historic transmission trees describing the progression of past nosocomial outbreaks of SARS and MERS. RESULTS: Our findings suggest that vaccination strategies targeting patients and healthcare workers, which have been disproportionately affected during past outbreaks, and assuming two vaccination coverage levels at 50 and 75% have the potential to avert nearly 50% or more of MERS or SARS cases. CONCLUSION: Our modeling results informed by historic outbreak data for SARS and MERS suggest that vaccination strategies targeting patients could be an effective measure to mitigate and prevent outbreaks in the healthcare setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12976-019-0112-6) contains supplementary material, which is available to authorized users.

negative: Transmission potential of the novel coronavirus (COVID-19) onboard the Diamond Princess Cruises Ship, 2020 An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January-February 2020. Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak. Our estimate of the mean reproduction number in the confined setting reached values as high as ~11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1-7). Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control. Most recent estimates of Rt reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.

negative: Dangerous Viral Pathogens of Animal Origin: Risk and Biosecurity: Zoonotic Select Agents Most of emerging infectious diseases affecting humans are of animal origin and transmitted under natural circumstances from either, wild or domestic vertebrate animals giving the way of zoonotic infection or epidemics. Zoonotic diseases carry a common ancient history between human and animals as a result of pathogen exchanges involving transgression of the species barrier. Nowadays, several agents have been targeted for their potential to be a major risk for human and animal populations and, have been characterized by their potential to be highly pathogenic and/or transmissible, and lacking of any means of protection. Those agents have been listed as “Select Agents” having the potential to pose a severe threat to both human and animal health, as well as to animal and plant products. Several of the most dangerous agents responsible of viral hemorrhagic fever are review in this chapter including: Ebola virus, Marburg virus, Rift valley fever virus, Kyasanur forest virus, Omsk hemorrhagic fever virus, Alkhurma hemorrhagic fever virus.

negative: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future Abstract At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.

negative: A Mechanism of Virus-Induced Demyelination Myelin forms an insulating sheath surrounding axons in the central and peripheral nervous systems and is essential for rapid propagation of neuronal action potentials. Demyelination is an acquired disorder in which normally formed myelin degenerates, exposing axons to the extracellular environment. The result is dysfunction of normal neuron-to-neuron communication and in many cases, varying degrees of axonal degeneration. Numerous central nervous system demyelinating disorders exist, including multiple sclerosis. Although demyelination is the major manifestation of most of the demyelinating diseases, recent studies have clearly documented concomitant axonal loss to varying degrees resulting in long-term disability. Axonal injury may occur secondary to myelin damage (outside-in model) or myelin damage may occur secondary to axonal injury (inside-out model). Viral induced demyelination models, has provided unique imminent into the cellular mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). In this review we will discuss potential cellular and molecular mechanism of central nervous system axonal loss and demyelination in a viral induced mouse model of multiple sclerosis.

negative: Coronaviruses: Molecular Biology☆ Abstract Coronaviruses (CoVs) are enveloped, positive-strand RNA viruses with characteristic spike glycoproteins that project outward like the rays of the sun (corona – Latin for ‘crown’), when visualized by electron microscopy. CoV are classified, together with the toroviruses, in the family Coronaviridae and the order Nidovirales. All nidoviruses have a common genome organization and generate a nested set (nido – Latin for ‘nest’) of 3′ co-terminal mRNAs. CoVs have been isolated from a variety of species, including birds, livestock, domestic animals, and humans. CoV infections can cause respiratory, gastrointestinal, and neurologic disease, depending on the strain of the virus and the site of infection. Importantly, CoVs have been shown to cross species barriers and have emerged from animal reservoirs to infect humans and cause severe disease. The CoV responsible for an outbreak of severe acute respiratory disease (SARS-CoV) in 2002–03 likely originated as a bat coronavirus which, during replication in an intermediate host (such as the palm civet), evolved to be able to infect humans efficiently. SARS-CoV infected over 8000 people with approximately 10% mortality rate before it was controlled by public health measures of isolation of infected individuals and contacts. Middle East Respiratory Syndrome CoV (MERS-CoV), first reported in 2012, is likely transmitted from camels to humans with potentially fatal consequences. To date, there are no approved vaccines or direct acting antiviral drugs to combat coronavirus infections in humans. The emergence or re-emergence of CoVs from animal reservoirs is a potential concern for public health.

negative: Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution The Coronavirus Disease-2019 (COVID-19) that started in Wuhan, China in December 2019 has spread worldwide emerging as a global pandemic. The severe respiratory pneumonia caused by the novel SARS-CoV-2 has so far claimed more than 60,000 lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 displays high transmission rates, their underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries suggesting that the outbreak is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nsp13-16 (ORF1b polyprotein) and S-Protein within 10 viral isolates from the USA. These viral proteins are involved in RNA replication, indicating highly evolved viral strains circulating in the population of USA than other countries. Furthermore, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of the USA isolate (MT188341) leading to shift in amino acid frame from position 2540 onwards. Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. Thus, the replicative machinery of SARS-CoV-2 is fast evolving to evade host challenges which need to be considered for developing effective treatment strategies.

negative: Ecological dynamics of emerging bat virus spillover. Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.

negative: Recommendations on the clinical management of the COVID-19 infection by the «new coronavirus» SARS-CoV2. Spanish Paediatric Association working group Abstract On 31 December 2019, the Wuhan Municipal Committee of Health and Healthcare (Hubei Province, China) reported that there were 27 cases of pneumonia of unknown origin with symptoms starting on the 8 December. There were 7 serious cases with common exposure in market with shellfish, fish, and live animals, in the city of Wuhan. On 7 January 2020, the Chinese authorities identified that the agent causing the outbreak was a new type of virus of the Coronaviridae family, temporarily called «new coronavirus», 2019-nCoV. On January 30th, 2020, the World Health Organisation (WHO) declared the outbreak an International Emergency. On 11 February 2020 the WHO assigned it the name of SARS-CoV2 and COVID-19 (SARS-CoV2 and COVID-19). The Ministry of Health summoned the Specialties Societies to prepare a clinical protocol for the management of COVID-19. The Spanish Paediatric Association appointed a Working Group of the Societies of Paediatric Infectious Diseases and Paediatric Intensive Care to prepare the present recommendations with the evidence available at the time of preparing them.

negative: Are Powered Air Purifying Respirators a Solution for Protecting Healthcare Workers from Emerging Aerosol-Transmissible Diseases?

negative: Live bacterial vaccines – a review and identification of potential hazards The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development.

negative: Characteristics of a long term in vitro persistent infection with human coronavirus 229E.

negative: Experimental bovine coronavirus in turkey poults and young chickens. The DB2 calf strain of bovine coronavirus (BCV) was used to inoculate 1-day-old specific-pathogen-free (SPF) turkey poults in three trials. In all trials, the birds developed clinical signs of enteritis at 48-72 hr postinoculation. Birds euthanatized at 3, 5, and 7 days postinoculation (DPI) had flaccid, pale intestines with watery contents, and the ceca were markedly enlarged with frothy contents. Coronavirus particles were detected by immune electron microscopy with BCV antibodies from the intestinal contents of birds killed at 3, 5, 7, and 12 DPI. Body weights of inoculated poults killed at 3, 5, and 7 DPI were significantly reduced as compared with controls. Hemagglutinating antibodies were detected in sera of convalescent birds at 12 DPI. However, experimental inoculation of 1-day-old SPF chicks in two trials with the same virus resulted in no clinical signs or macroscopic or microscopic lesions. No coronaviruses were detected from intestinal contents, and there were no significant differences in body weights of inoculated and noninoculated control chicks.

negative: The Promise and Peril of Antibody Testing for COVID-19.

negative: Dynamics of the COVID-19 -- Comparison between the Theoretical Predictions and Real Data A new coronavirus disease, called COVID-19, appeared in the Chinese region of Wuhan at the end of last year; since then the virus spread to other countries, including most of Europe. We propose a differential equation governing the evolution of the COVID-19. This dynamic equation also describes the evolution of the number of infected people for 13 common respiratory viruses (including the SARS-CoV-2). We validate our theoretical predictions with experimental data for Italy, Belgium and Luxembourg, and compare them with the predictions of the logistic model. We find that our predictions are in good agreement with the real world since the beginning of the appearance of the COVID-19; this is not the case for the logistic model that only applies to the first days. The second part of the work is devoted to modelling the descending phase, i.e. the decrease of the number of people tested positive for COVID-19. Also in this case, we propose a new set of dynamic differential equations that we solved numerically. We use our differential equations parametrised with experimental data to make several predictions, such as the date when Italy, Belgium, and Luxembourg will reach a peak number of SARS-CoV-2 infected people. The descending curves provide valuable information such as the duration of the COVID-19 epidemic in a given Country and therefore when it will be possible to return to normal life.

negative: Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period There is an urgent need to project how transmission of the novel betacoronavirus SARS-CoV-2 will unfold in coming years. These dynamics will depend on seasonality, the duration of immunity, and the strength of cross-immunity to/from the other human coronaviruses. Using data from the United States, we measured how these factors affect transmission of human betacoronaviruses HCoV-OC43 and HCoV-HKU1. We then built a mathematical model to simulate transmission of SARS-CoV-2 through the year 2025. We project that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after an initial pandemic wave. We summarize the full range of plausible transmission scenarios and identify key data still needed to distinguish between them, most importantly longitudinal serological studies to determine the duration of immunity to SARS-CoV-2.

negative: Effects of temperature variation and humidity on the mortality of COVID-19 in Wuhan Object Meteorological parameters are the important factors influencing the infectious diseases like severe acute respiratory syndrome (SARS). This study aims to explore the association between coronavirus disease (COVID-19) death and weather parameters. Methods In this study, we collected the daily death number of COVID-19, meteorological and air pollutant data from 20 January, 2020 to 29 February, 2020 in Wuhan, China. Then, the generalized additive model was applied to explore the impact of temperature, humidity and diurnal temperature range on daily mortality of COVID-19. Results There were in total 2299 COVID-19 mortality counts in Wuhan. A positive association with COVID-19 mortality was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = -0.32). In addition, each 1 unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 mortality at lag 3. However, both per 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 mortality at lag 3 and lag 5, respectively. Conclusion In summary, this study suggests the temperature variation and humidity may be important factors affecting the COVID-19 mortality.

negative: Pandemic stricken cities on lockdown. Where are our planning and design professionals [now, then and into the future]? Chinese cities have been placed upon lockdown in early 2020 in an attempt to contain the novel coronavirus (COVID-19), as increasingly huge demands are being placed upon Chinese and international health professionals to address this pandemic. Surprisingly, planning and design professionals are absent in the discourses about existing and post−COVID-19 strategies and actions even though previous pandemics historically revealed major impacts on the urban fabric from social and economic perspectives. This paper is a call for action for international architectural and urban organisations to include pandemics and similar in their disaster management strategies. This need is very evident in their need to better design creative and relevant protocols in partnership with health discipine organisations, and so that their applied deployment in pandemic stricken cities can be effected integrated seamlessly within normal city environment planning activities and also in incident situations like containing the current COVID-19 pandemic.

negative: How to deal with 2019 novel coronavirus (COVID-19): Public health practices from the Centers for Disease Control and Prevention in Zhanggong District, Ganzhou City, China

negative: Using Mind–Body Modalities via Telemedicine during the COVID-19 Crisis: Cases in the Republic of Korea The coronavirus disease 2019 (COVID-19) pandemic affected the world, and its deleterious effects on human domestic life, society, economics, and especially on human mental health are expected to continue. Mental health experts highlighted health issues this pandemic may cause, such as depression, anxiety, obsessive compulsive disorder, and post-traumatic stress disorder. Mind–body intervention, such as mindfulness meditation, has accumulated sufficient empirical evidence supporting the efficacy in improving human mental health states and the use for this purpose has been increasing. Notably, some of these interventions have already been tried in the form of telemedicine or eHealth. Korea, located adjacent to China, was exposed to COVID-19 from a relatively early stage, and today it is evaluated to have been successful in controlling this disease. “The COVID-19 telemedicine center of Korean medicine” has treated more than 20% of the confirmed COVID-19 patients in Korea with telemedicine since 9 March 2020. The center used telemedicine and mind–body modalities (including mindfulness meditation) to improve the mental health of patients diagnosed with COVID-19. In this paper, the telemedicine manual is introduced to provide insights into the development of mental health interventions for COVID-19 and other large-scale disasters in the upcoming new-normal era.

negative: Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study Summary Background As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks. Methods In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time. Findings We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020. Interpretation News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions. Funding Fogarty International Center, US National Institutes of Health.

negative: Cluster analysis of epidemiological characteristic features of confirmed cases with the novel coronavirus (COVID-19) outside China: a descriptive study Background: Novel coronavirus COVID-19 has caused significant global outbreaks outside China. Many countries have closed their borders with China and performed obligate protective procedures, however, this disease was still rising worldwide. In this report, we aim to identify transmission patterns from China to other countries, along with describing the disease control situation of countries. Methods: We retrospectively collected information about infected cases with COVID-19 from WHO situation reports, official notification websites of health ministries and reliable local newspapers from each country. Descriptive and cluster analysis was performed to describe the transmission characteristics while the logistic regression test was used to estimate the risk factors for the occurrence of an infected individual with an unknown source. Results: A total of 446 infected cases were recorded from 24 countries outside China until 12 February 2020, with the number of reported infected cases were doubled every 3.08 days (range from 2.6 to 3.9). Besides the spread from China, the transmission was originated from sub-endemic countries (Japan, Thailand, Singapore, Malaysia, France, German). Out of 6 countries got occurrence of an infected individual with unknown source and possible potential factors contributed to this occurrence was a time of epidemic circulating, number of patients and number of clusters when the occurrence still has not happened, and notably, the unreported situation of Chinese tourists information. Conclusions: The situational reports of each country about COVID-19 should be more detailed mentioning the transmissions routes with keeping contact tracing of the unknown cases to increase the control of this disease.

negative: 17 Health constraints on the agricultural recycling of wastewater sludges

negative: Climate affects global patterns of COVID-19 early outbreak dynamics Environmental factors, including seasonal climatic variability, can strongly impact on spatio-temporal patterns of infectious disease outbreaks, but relationships between Covid-19 dynamics and climate remain controversial. We assessed the impact of temperature and humidity on the global patterns of Covid-19 early outbreak dynamics during January-March 2020. Here we show that Covid-19 growth rates peaked in temperate regions of the Northern Hemisphere with mean temperature of ~5 C, and specific humidity of 4-6 g/m3 during the outbreak period, while they were lower both in warmer/wetter and colder/dryer regions. Relationships between Covid-19 and climate were robust to the potential confounding effects of air pollution and socio-economic variables, including population size, density and health expenditure. The strong relationship between local climate and Covid-19 growth rates suggests the possibility of seasonal variation in the spatial pattern of outbreaks, with temperate regions of the Southern Hemisphere becoming at particular risk of severe outbreaks during the austral autumn-winter.

negative: Direct RNA nanopore sequencing of full-length coronavirus genomes provides novel insights into structural variants and enables modification analysis. Sequence analyses of RNA virus genomes remain challenging owing to the exceptional genetic plasticity of these viruses. Because of high mutation and recombination rates, genome replication by viral RNA-dependent RNA polymerases leads to populations of closely related viruses, so-called "quasispecies." Standard (short-read) sequencing technologies are ill-suited to reconstruct large numbers of full-length haplotypes of (1) RNA virus genomes and (2) subgenome-length (sg) RNAs composed of noncontiguous genome regions. Here, we used a full-length, direct RNA sequencing (DRS) approach based on nanopores to characterize viral RNAs produced in cells infected with a human coronavirus. By using DRS, we were able to map the longest (∼26-kb) contiguous read to the viral reference genome. By combining Illumina and Oxford Nanopore sequencing, we reconstructed a highly accurate consensus sequence of the human coronavirus (HCoV)-229E genome (27.3 kb). Furthermore, by using long reads that did not require an assembly step, we were able to identify, in infected cells, diverse and novel HCoV-229E sg RNAs that remain to be characterized. Also, the DRS approach, which circumvents reverse transcription and amplification of RNA, allowed us to detect methylation sites in viral RNAs. Our work paves the way for haplotype-based analyses of viral quasispecies by showing the feasibility of intra-sample haplotype separation. Even though several technical challenges remain to be addressed to exploit the potential of the nanopore technology fully, our work illustrates that DRS may significantly advance genomic studies of complex virus populations, including predictions on long-range interactions in individual full-length viral RNA haplotypes.

negative: Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus) have arguably been the most successful, and certainly the most widely used, of vaccines for diseases caused by coronaviruses, the others being against bovine, canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV), together with the genetically related coronaviruses of turkey (Meleagris gallopavo) and ring-necked pheasant (Phasianus colchicus), is a group 3 coronavirus, Severe acute respiratory syndrome (SARS) coronavirus being tentatively in group 4, the other known mammalian coronaviruses being in groups 1 and 2. IBV replicates not only in respiratory tissues (including the nose, trachea, lungs and airsacs, causing respiratory disease), but also in the kidney (associated with minor or major nephritis), oviduct, and in many parts of the alimentary tract—the oesophagus, proventriculus, duodenum, jejunum, bursa of Fabricius, caecal tonsils, rectum and cloaca, usually without clinical effects. The virus can persist, being re-excreted at the onset of egg laying (4 to 5 months of age), believed to be a consequence of the stress of coming into lay. Genetic lines of chickens differ in the extent to which IBV causes mortality in chicks, and in respect of clearance of the virus after the acute phase. Live attenuated (by passage in chicken embryonated eggs) IBV strains were introduced as vaccines in the 1950s, followed a couple of decades later by inactivated vaccines for boosting protection in egg-laying birds. Live vaccines are usually applied to meat-type chickens at 1 day of age. In experimental situations this can result in sterile immunity when challenged by virulent homologous virus. Although 100% of chickens may be protected (against clinical signs and loss of ciliary activity in trachea), sometimes 10% of vaccinated chicks may not respond with a protective immune response. Protection is short lived, the start of the decline being apparent 9 weeks after vaccination with vaccines based on highly attenuated strains. IBV exists as scores of serotypes (defined by the neutralization test), cross-protection often being poor. Consequently, chickens may be re-vaccinated, with the same or another serotype, two or three weeks later. Single applications of inactivated virus has generally led to protection of <50% of chickens. Two applications have led to 90 to 100% protection in some reports, but remaining below 50% in others. In practice in the field, inactivated vaccines are used in laying birds that have previously been primed with two or three live attenuated virus vaccinations. This increases protection of the laying birds against egg production losses and induces a sustained level of serum antibody, which is passed to progeny. The large spike glycoprotein (S) comprises a carboxy-terminal S2 subunit (approximately 625 amino acid residues), which anchors S in the virus envelope, and an amino-terminal S1 subunit (approximately 520 residues), believed to largely form the distal bulbous part of S. The S1 subunit (purified from IBV virus, expressed using baculovirus or expressed in birds from a fowlpoxvirus vector) induced virus neutralizing antibody. Although protective immune responses were induced, multiple inoculations were required and the percentage of protected chickens was too low (<50%) for commercial application. Remarkably, expression of S1 in birds using a non-pathogenic fowl adenovirus vector induced protection in 90% and 100% of chickens in two experiments. Differences of as little as 5% between the S1 sequences can result in poor cross-protection. Differences in S1 of 2 to 3% (10 to 15 amino acids) can change serotype, suggesting that a small number of epitopes are immunodominant with respect to neutralizing antibody. Initial studies of the role of the IBV nucleocapsid protein (N) in immunity suggested that immunization with bacterially expressed N, while not inducing protection directly, improved the induction of protection by a subsequent inoculation with inactivated IBV. In another study, two intramuscular immunizations of a plasmid expressing N induced protective immunity. The basis of immunity to IBV is not well understood. Serum antibody levels do not correlate with protection, although local antibody is believed to play a role. Adoptive transfer of IBV-infection-induced αβ T cells bearing CD8 antigen protected chicks from challenge infection. In conclusion, live attenuated IBV vaccines induce good, although short-lived, protection against homologous challenge, although a minority of individuals may respond poorly. Inactivated IBV vaccines are insufficiently efficacious when applied only once and in the absence of priming by live vaccine. Two applications of inactivated IBV are much more efficacious, although this is not a commercially viable proposition in the poultry industry. However, the cost and logistics of multiple application of a SARS inactivated vaccine would be more acceptable for the protection of human populations, especially if limited to targeted groups (e.g. health care workers and high-risk contacts). Application of a SARS vaccine is perhaps best limited to a minimal number of targeted individuals who can be monitored, as some vaccinated persons might, if infected by SARS coronavirus, become asymptomatic excretors of virus, thereby posing a risk to non-vaccinated people. Looking further into the future, the high efficacy of the fowl adenovirus vector expressing the IBV S1 subunit provides optimism for a live SARS vaccine, if that were deemed to be necessary, with the possibility of including the N protein gene.

negative: Modelling the spread of COVID-19 with new fractal-fractional operators: Can the lockdown save mankind before vaccination? Countries around the world are implementing lock-down measures in a bid to flatten the curve of the new deadly COVID-19 disease. Our paper does not claim to have found the cure for COVID-19, neither does it claim that the suggested model have taken into account all the complexities around the spread of the disease. Nonetheless, the fundamental question asked in this paper is to know if within the conditions taken into account in this suggested model, the integral lock-down is effective in saving human lives. To answer this question, a mathematical model was suggested taking into account the possibility of transmission of COVID-19 from dead bodies to humans and the effect of lock-down. Three cases were considered. The first case suggested that there is transmission from dead to the living (medical staffs as they perform postmortem procedures on corpses, and direct contacts with during burial ceremonies). This case has no equilibrium points except for disease free equilibrium, a clear indication that care must be taken when dealing with corpses due to corona-19. In the second case we removed the transmission rate from dead bodies. This case showed an equilibrium point, although the number of deaths, carriers and infected grew exponentially up to a certain stability level. In the last case, we incorporated a lock-down and social distancing effect, using the next generation matrix. We could achieve a zero reproduction number, with number of deaths, infected and carriers decaying very rapidly. This is a clear indication that if lock-down recommendations are observed the threat of COVID-19 can be reduced to zero in few months.While our mathematical model agrees with the effectiveness of the lock-down, it is important to mention damaging effects of inadequate testing. The long waiting period of few days before confirmation of status, can only lead to more infections. The asymptomatic tested person could be positive and spread the infection, or could contact the virus in days after testing and will spread the disease further, after being given a false result. Testing kit that with immediate results are needed for more efficient measures. We used Italy's Data to guide the construction of the mathematical model. To include non-locality into mathematical formulas, differential and integral operators were suggested. Properties and numerical approximations were presented in details. Finally, the suggested differential and integral operators were applied to the model.

negative: Virus–Platelet Associations Virus–platelet interplay is complex. Diverse virus types have been shown to associate with numerous distinct platelet receptors. This association can benefit the virus or the host, and thus the platelet is somewhat of a renegade. Evidence is accumulating to suggest that viruses are capable of entering platelets. For at least one type of RNA virus (dengue virus), the platelet has the necessary post-translational and packaging machinery required for production of replicative viral progeny. As a facilitator of immunity, the platelet also participates in eradicating the virus by direct and indirect mechanisms involving presentation of the pathogen to the innate and adaptive immune systems, thus enhancing inflammation by release of cytokines and other agonists. Virus-induced thrombocytopenia is caused by tangential imbalance of thrombopoeisis, autoimmunity, and loss of platelet function and integrity.

negative: COVID-19: a look into the modern age pandemic AIM: COVID-19 presents as a pandemic requiring the utmost attention from the world, especially the healthcare sector. This review intends to discuss the symptoms, prevention, and management carried out related to the coronavirus, while also providing the healthcare provider strategies used by different countries in combating the disease. SUBJECT AND METHODS: This study was conducted over a period of 2 weeks where different sources were used to assess the ongoing situation regarding COVID-19. The data used in this study was verified and collected from authentic sources only. RESULTS: Results show that there is at present no definite cure for the disease and that prevention is the best possible defense at our disposal at the moment. Data reviewed suggests that social distancing and isolation is the best possible option at the moment. CONCLUSION: This study provides an overview of the developments taking place in response to the pandemic. More research is required, especially in the treatment and prevention of the disease, so that we may progress towards finding a cure as well as creating a vaccine for the COVID-19.

negative: Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Coronaviruses and Ocular Implications in Humans and Animals In December 2019, a novel coronavirus (CoV) epidemic, caused by the severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2) emerged from China. This virus causes the coronavirus disease 2019 (COVID-19). Since then, there have been anecdotal reports of ocular infection. The ocular implications of human CoV infections have not been widely studied. However, CoVs have been known to cause various ocular infections in animals. Clinical entities such as conjunctivitis, anterior uveitis, retinitis, and optic neuritis have been documented in feline and murine models. In this article, the current evidence suggesting possible human CoV infection of ocular tissue is reviewed. The review article will also highlight animal CoVs and their associated ocular infections. We hope that this article will serve as a start for further research into the ocular implications of human CoV infections.

negative: Emerging viral infections in a rapidly changing world Abstract Emerging viral infections in both humans and animals have been reported with increased frequency in recent years. Recent advances have been made in our knowledge of some of these, including severe acute respiratory syndrome-associated coronavirus, influenza A virus, human metapneumovirus, West Nile virus and Ebola virus. Research efforts to mitigate their effects have concentrated on improved surveillance and diagnostic capabilities, as well as on the development of vaccines and antiviral agents. More attention needs to be given to the identification of the underlying causes for the emergence of infectious diseases, which are often related to anthropogenic social and environmental changes. Addressing these factors might help to decrease the rate of emergence of infectious diseases and allow the transition to a more sustainable society.

negative: SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain in the host population. In turn, the virus can never completely eliminate the host population, because evolutionarily such an event is a dead end for the virus as an obligate intracellular parasite. A certain existential balance exists in the virus-host relationship. Against this backdrop, viral epidemics and pandemics only become manifest and egregious to human beings when tens and hundreds of thousands of people die and the question emerges what caused the high mortality peaks on the death chart. The answer seems clear; the emerging strain of the virus is new to the host population, and new mutations of the virus and natural selection will lead to a survival of only genetically resistant individuals in a host population. The dangers inherent to a novel virus are due to new features generally inthe molecular structure of proteins, which enable the virus to infect the cells of the host organism more intensively, dramatically challenging host immunity, and thus be transmitted more readily in the host population. In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In fact, only two scenarios will occur simultaneously in the very near future: people who are genetically resistant to the virus will get sick, recover, and develop immunity, while people who are sensitive to the virus will need drugs and vaccines, which will have to be researched and developed if they are to recover. If the pandemic does not stop, in a few decades it is anticipated that SARS-CoV-2 will become as safe as the four non-severe acute respiratory syndrome human coronaviruses (HCoV-NL63, HCoV-HKU1, HCoV-OC43, and HCoV-229E) currently circulating but causing low mortality in the human population.

negative: Chapter 18 Molecular Basis of Pulmonary Disease Publisher Summary Pulmonary pathology includes a large spectrum of both neoplastic and non-neoplastic diseases that affect the lung. Many of these are a result of the unusual relationship of the lung with the outside world. Every breath that a human takes brings the outside world into the body in the form of infectious agents, organic and inorganic particles, and noxious agents of all types. Although the lung has many defense mechanisms to protect itself from these insults, these are not infallible; therefore, lung pathology arises. Damage to the lung is particularly important given the role of the lung in the survival of the organism. Any impairment of lung function has widespread effects throughout the body, since all organs depend on the lungs for the oxygen they need. Pulmonary pathology catalogs the changes in the lung tissues and the mechanisms through which these occur. This chapter presents a review of lung pathology and the current state of knowledge about the pathogenesis of each disease. It suggests that a clear understanding of both morphology and mechanism is required for the development of new therapies and preventive measures.

negative: Prediction and Evolution of B Cell Epitopes of Surface Protein in SARS-CoV-2 The discovery of epitopes is helpful to the development of SARS-CoV-2 vaccine. The sequences of the surface protein of SARS-CoV-2 and its proximal sequences were obtained by BLAST, the sequences of the whole genome of SARS-CoV-2 were obtained from the GenBank. Based on the NCBI Reference Sequence: NC_045512.2, the conformational and linear B cell epitopes of the surface protein were predicted separately by various prediction methods. Furthermore, the conservation of the epitopes, the adaptability and other evolutionary characteristics were also analyzed. 7 epitopes were predicted, including 5 linear epitopes and 2 conformational epitopes, one of the linear and one of the conformational were coincide. The epitope D mutated easily, but the other epitopes were very conservative and the epitope C was the most conservative. It is worth mentioning that all of the 6 dominated epitopes were absolutely conservative in nearly 1000 SARS-CoV-2 genomes, and they deserved further study. The findings would facilitate the vaccine development, had the potential to be directly applied on the treatment in this disease, but also have the potential to prevent the possible threats caused by other types of coronavirus.

negative: Infection prevention and control in paediatric office settings Transmission of infection in the paediatric office is an issue of increasing concern. This document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (e.g., hand hygiene; use of gloves, masks, eye protection, and gowns for specific procedures; adequate cleaning, disinfection, and sterilization of surfaces and equipment, including toys; and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies.

negative: Cytokine Storm Induced by SARS-CoV-2 A novel coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading globally, causing severe pneumonia and acute lung injury in many patients. Even worse, severe respiratory may develop into acute respiratory distress syndrome and multiple organ dysfunction syndrome in COVID-19. The cytokine storm caused by immune over-activation due to virus infection may be an important cause of death in the late period of progress, but the pathogenesis of cytokine storm is still unclear. This article reviews the mechanisms of SARS-CoV-2-induced cytokine storm in detail based on the current discovered researches, and put forward some valuable medication ideas for the targeted cytokines drug researches and treatment. The goal of this work will be helpful for reducing excessive immune response.

negative: [Health protection guideline of mobile cabin hospitals during Novel Coronavirus Pneumonia (NPC) outbreak]. This guideline is applicable to the health protection requirements of large indoor stadiums which are reconstructed as treatment sites for the Novel Coronavirus Pneumonia (NPC) patients with mild symptoms during the outbreak. Focusing on the health emergency scenario of severe virus infectious diseases and atypical places where NPC patients with mild symptom gather, from perspectives of functional zones, hygiene facilities, personal protection, and management system, health risk protection recommendations and countermeasures are comprehensively proposed to mainly protect staffs and surrounding environment. The implementation of this guideline will provide technique support for emergency requirements of indoor stadiums reconstructed as mobile cabin hospitals.

negative: Chemokine CXCL10 and Coronavirus-Induced Neurologic Disease. Chemokines (chemotactic cytokines) are involved in a wide variety of biological processes. Following microbial infection, there is often robust chemokine signaling elicited from infected cells, which contributes to both innate and adaptive immune responses that control growth of the invading pathogen. Infection of the central nervous system (CNS) by the neuroadapted John Howard Mueller (JHM) strain of mouse hepatitis virus (JHMV) provides an excellent example of how chemokines aid in host defense as well as contribute to disease. Intracranial inoculation of the CNS of susceptible mice with JHMV results in an acute encephalomyelitis characterized by widespread dissemination of virus throughout the parenchyma. Virus-specific T cells are recruited to the CNS, and control viral replication through release of antiviral cytokines and cytolytic activity. Sterile immunity is not acquired, and virus will persist primarily in white matter tracts leading to chronic neuroinflammation and demyelination. Chemokines are expressed and contribute to defense as well as chronic disease by attracting targeted populations of leukocytes to the CNS. The T cell chemoattractant chemokine CXCL10 (interferon-inducible protein 10 kDa, IP-10) is prominently expressed in both stages of disease, and serves to attract activated T and B lymphocytes expressing CXC chemokine receptor 3 (CXCR3), the receptor for CXCL10. Functional studies that have blocked expression of either CXCL10 or CXCR3 illuminate the important role of this signaling pathway in host defense and neurodegeneration in a model of viral-induced neurologic disease.

negative: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.

negative: Thermal effect of human body on cough droplets evaporation and dispersion in an enclosed space Abstract This study numerically investigated the thermal effect of human body on the time-dependent dispersion of cough droplets with evaporation process. The thermal flow of human body was imitated using a 3D thermal manikin with real body features, while a recent developed multi-component Eulerian-Lagrangian approach was used to address the effects of inhomogeneous temperature and humidity fields on droplet evaporation. By comparing the results yielded without and with the human body heat, the outcomes demonstrated strong impact of human body heat on the droplets mass fraction and local air velocity distributions. Inspirable droplets could potentially drop into respirable droplets by evaporation, although the evaporation rate was not significantly affected by body heat. The thermal effect of human body revealed its vital impacts on the time-dependent droplets dispersion. Due to the buoyancy driven thermal flow, both the vertical velocity and displacement of small droplets (≤20 μm) were completely reversed from descending to ascending, while the deposition time of large droplets (≥50 μm) were significantly delayed. With the reduced droplet size by evaporation and droplets lifted into breathing zone by human thermal effect, the inhalability and infection risks of cough droplets would be much higher in real occupied indoor spaces.

negative: Avoiding COVID-19: Aerosol Guidelines The COVID-19 pandemic has brought into sharp focus the need to understand respiratory virus transmission mechanisms. In preparation for an anticipated influenza pandemic, a substantial body of literature has developed over the last few decades showing that the short-range aerosol route is an important, though often neglected transmission path. We develop a simple mathematical model for COVID-19 transmission via aerosols, apply it to known outbreaks, and present quantitative guidelines for ventilation and occupancy in the workplace.

negative: Epidemiology reveals mask wearing by the public is crucial for COVID-19 control Abstract Objective The pandemic 2019 Coronavirus disease (COVID-19) is the greatest concern globally. Here we analyzed the epidemiological features of China, South Korea, Italy and Spain to find out the relationship of major public health events and epidemiological curves. Study design In this study we describe and analyze the epidemiological characteristics of COVID-19 in and outside China. We use GAM to generate the epidemiological curves and simulate infection curves with reported incubation period. Results The epidemiological curved derived from the GAM suggested that the infection curve can reflect the public health measurements sensitively. Under the massive actions token in China, the infection curve flattened at 23rd of January. While surprisingly, even before Wuhan lockdown and first level response of public emergency in Guangdong and Shanghai, those infection curve came to the reflection point both at 21st of January, which indicated the mask wearing by the public before 21st Jan were the key measure to cut off the transmission. In the countries outside China, infection curve also changed in response to measures, but its rate of decline was much smaller than the curve of China's. Conclusion The present analysis comparing the epidemiological curves in China, South Korea, Italy and Spain supports the importance of mask wearing by the public. Analysis of the infection curve helped to clarify the impact of important public health events, evaluate the efficiencies of prevention measures, and showed wearing masks in public resulted in significantly reduced daily infected cases.

negative: Knowledge-based repositioning of the anti-HCV direct antiviral agent Sofosbuvir as SARS-CoV-2 treatment The new human coronavirus named SARS-CoV-2 is a positive-sense RNA virus for which no specific drugs are currently available. A knowledge-based analysis strongly suggests a possible repositioning of the anti-HCV direct antiviral agent (DAA) Sofosbuvir as treatment for SARS-CoV-2. Indeed, the RNA-dependent RNA-polymerases (RdRp) of the two viruses show high sequence and structural homology, supporting the likelihood of binding the Sofosbuvir molecule with similar efficiency. Such a repositioning would allow the containment of the SARS-CoV-2 pandemic and limit the progression of disease to potentially deadly COVID19.

negative: Attenuated live vaccine usage affects accurate measures of virus diversity and mutation rates in avian coronavirus infectious bronchitis virus Abstract The full-length genomes of 11 infectious bronchitis virus (IBV) field isolates from three different types of the virus; Massachusetts (Mass), Connecticut (Conn) and California (CAL) isolated over a 41, 25 and 8 year period respectively, were sequenced and analyzed to determine the mutation rates and level of polymorphisms across the genome. Positive selection was not detected and mutation rates ranged from 10−4 to 10−6 substitutions/site/year for Mass and Conn IBV types where attenuated live vaccines are routinely used to control the disease. In contrast, for CAL type viruses, for which no vaccine exists, positive selection was detected and mutation rates were 10 fold higher ranging from 10−2 to 10−3 substitutions/site/year. Lower levels of genetic diversity among the Mass and Conn viruses as well as sequence similarities with vaccine virus genomes suggest that the origin of the Mass and all but one of the Conn viruses was likely vaccine virus that had been circulating in the field for an unknown but apparently short period of time. The genetic data also identified a recombinant IBV isolate with 7 breakpoints distributed across the entire genome suggesting that viruses within the same serotype can have a high degree of genetic variability outside of the spike gene. These data are important because inaccurate measures of genetic diversity and mutation rates could lead to underestimates of the ability of IBV to change and potentially emerge to cause disease.

negative: Epidemiology of 2019 novel coronavirus in Jiangsu Province, China after wartime control measures: A population-level retrospective study Abstract Background A novel coronavirus emerged in China in December 2019, and human-to-human transmission was previously identified. This study aimed to compare the epidemiological characteristics in Jiangsu Province and assess whether so-called wartime control measures changed the trend of coronavirus disease 2019 (COVID-19) in the province. Methods Epidemiological data were obtained from the websites of China's Bureau of Health and the People's Government of Jiangsu Province and informal online sources from January 22 to February 20, 2020. Results The cumulative number of patients in Jiangsu Province (over 79 million people) was 613. The number of daily confirmed new cases reached the inflection point on January 31 with the maximum of 39 cases. The temporal number of patients peaked from January 29 to February 9. The proportion of confirmed cases who were residents or travelers to Hubei Province was 100.0%–58.8% before January 31 and then gradually declined. The proportion of close contacts increased gradually from January 27 to February 17. The geographical distribution of COVID-2019 cases showed that all 13 cites reported confirmed new cases after only five days of the first confirmed new case in Suzhou. The cases were concentrated in Nanjing, Suzhou, and Xuzhou with a high population density (over eight million people). The epidemiological features of COVID-2019 cases in Wuxi, Jiangsu showed that seven confirmed cases were tourists from others areas beyond Hubei Province. The longest incubation period of COVID-2019 was 19 days based on the onset of laboratory-confirmed cases. Conclusion The number of daily confirmed new cases in Jiangsu Province peaked around January 31 and then declined. This result emphasized that wartime control measures, such as putting cities on lockdown to limit population mobility in Jiangsu Province, resulted in dramatic reductions in COVID-19 cases.

negative: Abortion at the edges: Politics, practices, performances This article provides a brief overview of the state of discourse, politics and provision of abortion in the Anglophone West, including developments in the wake of the COVID-19 pandemic. It then surveys three promising directions for feminist abortion scholarship. The first is work inspired by the Reproductive Justice Movement, that points to the intersectional axes of inequality that shape abortion discourse and position us in relation to reproductive choice and access issues. The second is work that examines the particularity of the constitution of the aborting body, reflecting the particularity of the pregnant body. This is a specific body, with a specific history; abortion discourse draws from and makes a significant contribution to the meaning and lived experience of this body. The third area of scholarship we highlight is that which seeks to amplify the meaning of abortion as a social good. Much abortion scholarship is attuned to a critique of negative aspects of abortion-from its representation in popular culture to restrictive law and access issues. This is critical work but/and the performative nature of abortion scholarship, like all discourse, means that it can amplify the association of negativity with abortion. The article concludes by introducing the articles contained in the special section of Women's Studies International Forum, 'Abortion at the edges: Politics, practices, performances'.

negative: Epidemiological and clinical features of 125 Hospitalized Patients with COVID-19 in Fuyang, Anhui, China Abstract Objective To investigate the epidemiological and clinical features of patients with COVID-19 in Anhui province of China. Method In this descriptive study, we obtained epidemiological, demographic, manifestations, laboratory data and radiological findings of patients confirmed by real-time RT-PCR in the NO.2 People’s Hospital of Fuyang City from Jan 20 to Feb 9, 2020. Clinical outcomes were followed up to Feb 18, 2020. Results Of 125 patients infected SARS-CoV-2, the mean age was 38.76 years (SD, 13.799) and 71(56.8%) were male. Common symptoms include fever [116 (92.8%)], cough [102(81.6%)], and shortness of breath [57(45.6%)]. Lymphocytopenia developed in 48(38.4%) patients. 100(80.0%) patients showed bilateral pneumonia, 26(20.8%) patients showed multiple mottling and ground-glass opacity. All patients were given antiviral therapy. 19(15.2%) patients were transferred to the intensive care unit. By February 18, 47(37.6%) patients were discharged and none of patients died. Among the discharged patients, the median time of length of stay was 14.8 days (SD 4.16). Conclusion In this single-center, retrospective, descriptive study, fever is the most common symptom. Old age, chronic underlying diseases and smoking history may be risk factors to worse condition. Certain laboratory inspection may contribute to the judgment of the severity of illness.

negative: Initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of Hubei, China With an increasing number of Coronavirus Disease 2019 (COVID‐19) cases outside of Hubei, emergency departments (EDs) and fever clinics are facing challenges posed by the large number of admissions of patients suspected to have COVID‐19. Therefore, it is of crucial importance to study the initial clinical features of patients, to better differentiate between infected and uninfected patients outside Hubei. A total of 116 patients suspected of having COVID‐19 who presented to two emergency departments in Anhui for the first time between 24 January 2020 and 20 February 2020 were enrolled in the study. The initial clinical data of these patients, such as epidemiological features, symptoms, laboratory results, and chest computed tomography (CT) findings were collected using a standard case report form on admission. Thirty‐two patients were diagnosed with COVID‐19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID‐19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and ground‐glass opacity (GGO) were present in 91% and 47% of the diagnosed patients. Thirty‐two patients were diagnosed with COVID‐19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID‐19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and GGO were present in 91% and 47% of the diagnosed patients.

negative: Powerful Sequence Similarity Search Methods and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently “Orphan” Viral Proteins The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as “genus specific” by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virions.

negative: Robust neutralization assay based on SARS-CoV-2 S-bearing vesicular stomatitis virus (VSV) pseudovirus and ACE2-overexpressed BHK21 cells The global pandemic of Coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable in vitro neutralization assay is very important for the development of neutralizing antibodies, vaccines and other inhibitors. In this study, G protein-deficient vesicular stomatitis virus (VSVdG) bearing full-length and truncated spike (S) protein of SARS-CoV-2 were evaluated. The virus packaging efficiency of VSV-SARS-CoV-2-Sdel18 (S with C-terminal 18 amino acid truncation) is much higher than VSV-SARS-CoV-2-S. A neutralization assay for antibody screening and serum neutralizing titer quantification was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and human angiotensin-converting enzyme 2 (ACE2) overexpressed BHK21 cell (BHK21-hACE2). The experimental results can be obtained by automatically counting EGFP positive cell number at 12 hours after infection, making the assay convenient and high-throughput. The serum neutralizing titer of COVID-19 convalescent patients measured by VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with live SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting receptor binding domain (RBD) of SARS-CoV-2-S were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.

negative: Chloroquine: Can it be a Novel Drug for COVID-19 Coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization. The United States Food and Drug Administration has not approved any drug or vaccine for the treatment of COVID-19; however, reports have emerged from different parts of the world about the potential therapeutic benefits of existing drugs. Chloroquine and phosphate hydroxychloroquine are the drugs currently in the limelight, and recently, the National Task Force for COVID-19 constituted by the Indian Council of Medical Research has recommended the use of antimalarial drug hydroxychloroquine for prophylaxis of severe acute respiratory syndrome-coronavirus 2 infection in selected high-risk individuals. This short write-up explores the potential efficacy and established safety of chloroquine in COVID-19.

negative: Chapter 5 Virus Transmission and Epidemiology Abstract For transmission of a virus to occur, a virus must enter a host through a portal of entry, replicate or disseminate within the host, and be transmitted to a new host through a portal of exit. Unless delivered directly into bodily tissues through a bite or needle, most viruses interact with the epithelium at the site of entry. Localized infections replicate at the initial site of infection, while systemic infections spread to additional areas of the body. Viruses are shed into the environment most often through the same route they entered the body. The stability of virions within the environment is dependent upon virion and environmental factors. Epidemiology is the study of how diseases are transmitted through a population. Epidemiologists perform descriptive or analytic studies to characterize the chain of viral infection throughout a population and design control measures to interrupt it.

negative: Phylogenetic analysis of a highly conserved region of the polymerase gene from 11 coronaviruses and development of a consensus polymerase chain reaction assay Abstract Viruses in the genus Coronavirus are currently placed in three groups based on antigenic cross-reactivity and sequence analysis of structural protein genes. Consensus polymerase chain reaction (PCR) primers were used to obtain cDNA, then cloned and sequenced a highly conserved 922 nucleotide region in open reading frame (ORF) 1b of the polymerase (pol) gene from eight coronaviruses. These sequences were compared with published sequences for three additional coronaviruses. In this comparison, it was found that nucleotide substitution frequencies (per 100 nucleotides) varied from 46.40 to 50.13 when viruses were compared among the traditional coronavirus groups and, with one exception (the human coronavirus (HCV) 229E), varied from 2.54 to 15.89 when compared within these groups. (The substitution frequency for 229E, as compared to other members of the same group, varied from 35.37 to 35.72.) Phylogenetic analysis of these pol gene sequences resulted in groupings which correspond closely with the previously described groupings, including recent data which places the two avian coronaviruses—infectious bronchitis virus (IBV) of chickens and turkey coronavirus (TCV)—in the same group [Guy, J.S., Barnes, H.J., Smith L.G., Breslin, J., 1997. Avian Dis. 41:583–590]. A single pair of degenerate primers was identified which amplify a 251 bp region from coronaviruses of all three groups using the same reaction conditions. This consensus PCR assay for the genus Coronavirus may be useful in identifying as yet unknown coronaviruses.

negative: Initial success in the identification and management of the coronavirus disease 2019 (COVID-19) indicates human-to-human transmission in Wuhan, China Coronavirus (CoV) has been one of the major pandemic threats to human health in the last two decades. The human coronavirus was first identified in 1960s. CoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV have caused numerous disasters or human deaths worldwide. Recently, an outbreak of the previously unknown deadly CoV disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome CoV 2 (SARS-CoV-2, early named 2019-nCoV) occurred in Wuhan, China, and it had caused 81238 cases of confirmed infection, including 3250 deaths until March 19, 2020. Its risks and pandemic potential have brought global consideration. We summarized epidemiology, virological characteristics, clinical symptoms, diagnostic methods, clinical treatments, and prevention methods for COVID-19 to present a reference for the future wave of probable CoV outbreaks.

negative: Coronavirus: Update Related to the Current Outbreak of COVID-19. In December 2019, some cases of viral pneumonia were epidemiologically related to a new coronavirus in the province of Hubei, China. Subsequently, there has been an increase in infections attributable to this virus throughout China and worldwide. The World Health Organization (WHO) has officially named the infection coronavirus disease 2019 (COVID-19), and the virus has been classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This appears to be a virus from Rhinolophus bats, but the intermediate host has not yet been identified. The mechanism of infection of SARS-CoV-2 is not yet known; it appears to have affinity for cells located in the lower airways, where it replicates. The interhuman transmission of coronaviruses mainly occurs through saliva droplets and direct and indirect contact via surfaces. As of March 10, 2020, the number of cases worldwide was 113,702. Along with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), COVID-19 appears to cause a severe clinical picture in humans, ranging from mild malaise to death by sepsis/acute respiratory distress syndrome. The prognosis is worse in elderly patients with comorbidities. To date, there is no specific therapy for COVID-19. Prevention of SARS-CoV-2 infection implies strategies that limit the spread of the virus. WHO and other international and national bodies have developed continuously updated strategic objectives and provisions to contain the spread of the virus and infection.

negative: Senegal faces the coronavirus disease −19 challenge

negative: The Ocular Surface and the Coronavirus Disease 2019: Does a Dual ‘Ocular Route’ Exist? Coronavirus disease 2019 (COVID-19) is an important health problem that was defined as a pandemic by the World Health Organization on 11 March 2020. Although great concern has been expressed about COVID-19 infection acquired through ocular transmission, its underlying mechanism has not currently been clarified. In the current work, we analyzed and elucidated the two main elements that should be taken into account to understand the “ocular route”, both from a clinical and molecular point of view. They are represented by the dynamism of the ocular surface system (e.g., the tear film turnover) and the distribution of ACE2 receptors and TMPRSS2 protein. Although it seems, at the moment, that there is a low risk of coronavirus spreading through tears, it may survive for a long time or replicate in the conjunctiva, even in absence of conjunctivitis signs, indicating that eye protection (e.g., protective goggles alone or in association with face shield) is advisable to prevent contamination from external droplets and aerosol.

negative: Chapter 45 Naked Mole Rat This chapter describes the use of the naked mole rat in the research laboratory setting giving details on its anatomy, natural habitat, reproductive behavior, and physiology followed by a detailed description of its organ systems. This is followed by sections on aging, husbandry of the naked mole rat, colony health, and finally the main models used in research.

negative: Subgenomic messenger RNAs: Mastering regulation of (+)-strand RNA virus life cycle Abstract Many (+)-strand RNA viruses use subgenomic (SG) RNAs as messengers for protein expression, or to regulate their viral life cycle. Three different mechanisms have been described for the synthesis of SG RNAs. The first mechanism involves internal initiation on a (−)-strand RNA template and requires an internal SGP promoter. The second mechanism makes a prematurely terminated (−)-strand RNA which is used as template to make the SG RNA. The third mechanism uses discontinuous RNA synthesis while making the (−)-strand RNA templates. Most SG RNAs are translated into structural proteins or proteins related to pathogenesis: however other SG RNAs regulate the transition between translation and replication, function as riboregulators of replication or translation, or support RNA–RNA recombination. In this review we discuss these functions of SG RNAs and how they influence viral replication, translation and recombination.

negative: Estimation of airborne viral emission: quanta emission rate of SARS-CoV-2 for infection risk assessment Airborne transmission is a pathway of contagion that is still not sufficiently investigated despite the evidence in the scientific literature of the role it can play in the context of an epidemic. While the medical research area dedicates efforts to find cures and remedies to counteract the effects of a virus, the engineering area is involved in providing risk assessments in indoor environments by simulating the airborne transmission of the virus during an epidemic. To this end, virus air emission data are needed. Unfortunately, this information is usually available only after the outbreak, based on specific reverse engineering cases. In this work, a novel approach to estimate the viral load emitted by a contagious subject on the basis of the viral load in the mouth, the type of respiratory activity (e.g. breathing, speaking, whispering), respiratory physiological parameters (e.g. inhalation rate), and activity level (e.g. resting, standing, light exercise) is proposed. The results showed that high quanta emission rates (>100 quanta h(-1)) can be reached by an asymptomatic infectious SARS-CoV-2 subject performing vocalization during light activities (i.e. walking slowly) whereas a symptomatic SARS-CoV-2 subject in resting conditions mostly has a low quanta emission rate (<1 quantum h(-1)). The findings in terms of quanta emission rates were then adopted in infection risk models to demonstrate its application by evaluating the number of people infected by an asymptomatic SARS-CoV-2 subject in Italian indoor microenvironments before and after the introduction of virus containment measures. The results obtained from the simulations clearly highlight that a key role is played by proper ventilation in containment of the virus in indoor environments.

negative: Bioaerosol sampling: sampling mechanisms, bioefficiency and field studies Summary Investigations into the suspected airborne transmission of pathogens in healthcare environments have posed a challenge to researchers for more than a century. With each pathogen demonstrating a unique response to environmental conditions and the mechanical stresses it experiences, the choice of sampling device is not obvious. Our aim was to review bioaerosol sampling, sampling equipment, and methodology. A comprehensive literature search was performed, using electronic databases to retrieve English language papers on bioaerosol sampling. The review describes the mechanisms of popular bioaerosol sampling devices such as impingers, cyclones, impactors, and filters, explaining both their strengths and weaknesses, and the consequences for microbial bioefficiency. Numerous successful studies are described that point to best practice in bioaerosol sampling, from the use of small personal samplers to monitor workers' pathogen exposure through to large static samplers collecting airborne microbes in various healthcare settings. Of primary importance is the requirement that studies should commence by determining the bioefficiency of the chosen sampler and the pathogen under investigation within laboratory conditions. From such foundations, sampling for bioaerosol material in the complexity of the field holds greater certainty of successful capture of low-concentration airborne pathogens. From the laboratory to use in the field, this review enables the investigator to make informed decisions about the choice of bioaerosol sampler and its application.

negative: The Food Systems in the Era of the Coronavirus (COVID-19) Pandemic Crisis The World Health Organization (WHO) declared the outbreak of coronavirus disease (COVID-19, broadly referred to as “coronavirus”) a global pandemic, while thousands of infections and deaths are reported daily. The current article explores the food systems in the era of the COVID-19 pandemic crisis. It provides insights about the properties of bioactive ingredients of foods and herbs for the support of the human immune system against infections before discussing the possibility of COVID-19 transmission through the food chain. It also highlights the global food security issues arising from the fact that one-third of the world’s population is on lockdown. Finally, it underlines the importance of sustainability in the food chain in order to avoid or reduce the frequency of relevant food and health crises in the future.

negative: Clinical progression of patients with COVID-19 in Shanghai, China Summary Background Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. Methods In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. Results Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2–7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12–20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8–11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10–12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. Conclusions The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.

negative: Mental health services in Shanghai during the COVID-19 outbreak

negative: One month of the novel coronavirus 2019 outbreak: Is it still a threat? The novel coronavirus 2019 disease (COVID-19) is now in an outbreak not only in China but also around the world, suspected to be originated from a wet market in Wuhan, Hubei province, China. The flare-up of COVID-19, it has already been infected 78,811 people with 2462 fatalities in 1 month window. The most alarming issue is the virus can transmit from host to host and still asymptomatic. Currently, 24 counties with 505 confirmed cases have been reported. Presently, there is no specific treatment or vaccine but physicians are battling with the use of antibiotics, steroid, anti-viral and anti-HIV drugs and some of the infected cases are testified improved. WHO and China National health Commission are cooperatively striving to come up with elucidation but it will take a minimum of 3 to 4 months at least to undergo a phase-1 trial. However, the soaring rates of spreading each day has become much stable which might even improve within the next few weeks in China but not for some other countries. Healthy peoples are instructed to avoid public gathering, always wearing the mask and frequently wash hands. Currently, China has able to hold up more than 97.7% infection within China but a scientific breakthrough is crucial before it’s too late.

negative: Technologies to optimize the care of severe COVID-19 patients for healthcare providers challenged by limited resources Healthcare systems are belligerently responding to the new Coronavirus Disease 2019 (COVID-19). The severe acute respiratory syndrome (SARS co-V2) is a specific condition, whose distinctive features are severe hypoxemia associated with (>50% of cases) normal respiratory system compliance. When a patient requires intubation and invasive ventilation the outcome is poor and the length of stay in the intensive care unit (ICU) is usually two or three weeks. In this manuscript, authors will review several technological devices, which could support healthcare providers at the bedside to optimise the care for COVID-19 patients who are sedated, paralysed and ventilated. Particular attention is provided to the use of video-laryngoscopes (VL) because these can assist anaesthetists to perform a successful intubation outside the ICU while protecting healthcare providers from this viral infection. Authors will also review processed electroencephalographic (EEG) monitors which are used to better titrate sedation and the train of four monitors which are utilised to better titrate neuromuscular blocking agents in the view of sparing limited pharmacological resources. COVID-19 can rapidly exhaust human and technological resources too within the ICU. This review features a series of technological advancements that can significantly improve the care of patients requiring isolation. The working conditions in isolation could cause gaps or barriers in communication, fatigue and poor documentation of provided care. The available technology has several advantages including: a) facilitating appropriate paperless documentation and communication between all healthcare givers working in isolation rooms or large isolation areas; b) testing patients and staff at the bedside using smart point of care diagnostics (SPOCD) to confirm COVID-19 infection; c) allowing diagnostics and treatment at the bedside through point of care ultrasound (POCUS) and Thromboelastography (TEG); d) adapting the use of anaesthetic machines and the use of volatile anaesthetics. Implementing technologies for safeguarding healthcare providers as well as monitoring the limited pharmacological resources is paramount. Only by leveraging new technologies it will be possible to sustain and support healthcare systems during the expected long course of this pandemic.

negative: Considerations for Postacute Rehabilitation for Survivors of COVID-19 Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question “What rehabilitation services do survivors of COVID-19 require?” The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.

negative: Macrotiter assay for coronavirus-neutralizing activity in cats using a canine continuous cell line (A-72). A heterologous neutralization assay for feline infectious peritonitis virus serology was developed using a single continuous cell line of canine origin, A-72, which is susceptible to cytopathic infection with both transmissible gastroenteritis virus of pigs and canine coronavirus. Of several coronavirus isolates tested, the 1-71 isolate of canine coronavirus demonstrated the most effective neutralization by serum and body fluids of cats with histopathologically confirmed feline infectious peritonitis.

negative: Search for Therapeutics Continues as SARS ‘Epidemic’ Abates

negative: Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.

negative: A hybrid multi-scale model of COVID-19 transmission dynamics to assess the potential of non-pharmaceutical interventions Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged in Wuhan, China in December 2019. It has caused a global outbreak which represents a major threat to global health. Public health resorted to non-pharmaceutical interventions such as social distancing and lockdown to slow down the spread of the pandemic. However, the effect of each of these measures remains hard to quantify. We design a multi-scale model that simulates the transmission dynamics of COVID-19. We describe the motion of individual agents using a social force model. Each agent can be either susceptible, infected, quarantined, immunized or deceased. The model considers both mechanisms of direct and indirect transmission. We parameterize the model to reproduce the early dynamics of disease spread in Italy. We show that panic situations increase the risk of infection transmission in crowds despite social distancing measures. Next, we reveal that pre-symptomatic transmission accelerates the onset of the exponential growth of cases. After that, we demonstrate that the persistence of SARS-CoV-2 on hard surfaces determines the number of cases reached during the peak of the epidemic. Then, we show that the restricted movement of the individuals flattens the epidemic curve. Finally, model predictions suggest that measures stricter than social distancing and lockdown were used to control the epidemic in Wuhan, China.

negative: Preventing Airborne Disease Transmission: Review of Methods for Ventilation Design in Health Care Facilities Health care facility ventilation design greatly affects disease transmission by aerosols. The desire to control infection in hospitals and at the same time to reduce their carbon footprint motivates the use of unconventional solutions for building design and associated control measures. This paper considers indoor sources and types of infectious aerosols, and pathogen viability and infectivity behaviors in response to environmental conditions. Aerosol dispersion, heat and mass transfer, deposition in the respiratory tract, and infection mechanisms are discussed, with an emphasis on experimental and modeling approaches. Key building design parameters are described that include types of ventilation systems (mixing, displacement, natural and hybrid), air exchange rate, temperature and relative humidity, air flow distribution structure, occupancy, engineered disinfection of air (filtration and UV radiation), and architectural programming (source and activity management) for health care facilities. The paper describes major findings and suggests future research needs in methods for ventilation design of health care facilities to prevent airborne infection risk.

negative: ESICM LIVES 2016: part one: Milan, Italy. 1-5 October 2016

negative: Analysing the combined health, social and economic impacts of the corovanvirus pandemic using agent-based social simulation During the COVID-19 crisis there have been many difficult decisions governments and other decision makers had to make. E.g. do we go for a total lock down or keep schools open? How many people and which people should be tested? Although there are many good models from e.g. epidemiologists on the spread of the virus under certain conditions, these models do not directly translate into the interventions that can be taken by government. Neither can these models contribute to understand the economic and/or social consequences of the interventions. However, effective and sustainable solutions need to take into account this combination of factors. In this paper, we propose an agent-based social simulation tool, ASSOCC, that supports decision makers understand possible consequences of policy interventions, bu exploring the combined social, health and economic consequences of these interventions.

negative: Day Level Forecasting for Coronavirus Disease (COVID-19) Spread: Analysis, Modeling and Recommendations In mid of March 2020, Coronaviruses such as COVID-19 is declared as an international epidemic. More than 125000 confirmed cases and 4,607 death cases have been recorded around more than 118 countries. Unfortunately, a coronavirus vaccine is expected to take at least 18 months if it works at all. Moreover, COVID -19 epidemics can mutate into a more aggressive form. Day level information about the COVID -19 spread is crucial to measure the behavior of this new virus globally. Therefore, this study presents a comparison of day level forecasting models on COVID-19 affected cases using time series models and mathematical formulation. The forecasting models and data strongly suggest that the number of coronavirus cases grows exponentially in countries that do not mandate quarantines, restrictions on travel and public gatherings, and closing of schools, universities, and workplaces (Social Distancing).

negative: What role do viruses play in nosocomial pneumonia? PURPOSE OF THE REVIEW Viruses are an increasingly recognized cause of community-acquired pneumonia (CAP), but their exact role in nosocomial pneumonia is still debated. This review focuses on the role of viruses as a cause of nosocomial pneumonia. RECENT FINDINGS Respiratory viruses may be responsible for healthcare-associated pneumonia, because affected patients and those with CAP have the same risk factors for viral disease. In mechanically ventilated patients, viruses belonging to the Herpesviridae family, namely herpes simplex virus (HSV) and cytomegalovirus, can be reactivated and cause bronchopneumonitis or ventilator-associated pneumonia, respectively. Recent results confirmed the high rate of HSV reactivation in the distal airways of mechanically ventilated patients, and that patients with high virus loads (>10(5) copies/ml of bronchoalveolar lavage fluid) have poorer outcomes than those with low or no virus load. However, the responsibility of mimivirus, initially described as a possible cause of pneumonia, was not confirmed for nosocomial pneumonia. SUMMARY Respiratory viruses are mainly responsible for CAP, but they may also cause healthcare-associated pneumonia. HSV bronchopneumonitis and cytomegalovirus pneumonia are not rare diseases, and patients with Herpesviridae lung infections have worse prognoses than those without. Whether or not those Herpesviridae infections are responsible for true morbidity or morbidity remains to be determined.

negative: Early dynamics of transmission and control of COVID-19: a mathematical modelling study Background: An outbreak of the novel coronavirus SARS-CoV-2 has led to 46,997 confirmed cases as of 13th February 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Methods: We combined a stochastic transmission model with data on cases of novel coronavirus disease (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January and February 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. Findings: We estimated that the median daily reproduction number, Rt , declined from 2.35 (95% CI: 1.15-4.77) one week before travel restrictions were introduced on 23rd January to 1.05 (95% CI: 0.413-2.39) one week after. Based on our estimates of Rt,we calculated that in locations with similar transmission potential as Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. Interpretation: Our results show that COVID-19 transmission likely declined in Wuhan during late January 2020, coinciding with the introduction of control measures. As more cases arrive in international locations with similar transmission potential to Wuhan pre-control, it is likely many chains of transmission will fail to establish initially, but may still cause new outbreaks eventually.

negative: Feminist Ethics and Women Leaders: From Difference to Intercorporeality This paper problematises the ways women’s leadership has been understood in relation to male leadership rather than on its own terms. Focusing specifically on ethical leadership, we challenge and politicise the symbolic status of women in leadership by considering the practice of New Zealand Prime Minister Jacinda Ardern. In so doing, we demonstrate how leadership ethics based on feminised ideals such as care and empathy are problematic in their typecasting of women as being simply the other to men. We apply different strategies of mimesis for developing feminist leadership ethics that does not derive from the masculine. This offers a radical vision for leadership that liberates the feminine and women’s subjectivities from the masculine order. It also offers a practical project for changing women’s working lives through relationality, intercorporeality, collective agency and ethical openness with the desire for fundamental political transformation in the ways in which women can lead.

negative: PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks virus attachment and infection of target cells. These findings suggest that PSGL-1 may potentially inhibit coronavirus replication in PSGL-1+ cells.

negative: Lysosomal Proteases Are a Determinant of Coronavirus Tropism. Cell entry by coronaviruses involves two principal steps, receptor binding and membrane fusion; the latter requires activation by host proteases, particularly lysosomal proteases. Despite the importance of lysosomal proteases in both coronavirus entry and cell metabolism, the correlation between lysosomal proteases and cell tropism of coronaviruses has not been established. Here, we examined the roles of lysosomal proteases in activating coronavirus surface spike proteins for membrane fusion, using the spike proteins from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) as the model system. To this end, we controlled the contributions from receptor binding and other host proteases, thereby attributing coronavirus entry solely or mainly to the efficiency of lysosomal proteases in activating coronavirus spike-mediated membrane fusion. Our results showed that lysosomal proteases from bat cells support coronavirus spike-mediated pseudovirus entry and cell-cell fusion more effectively than their counterparts from human cells. Moreover, purified lysosomal extracts from bat cells cleave cell surface-expressed coronavirus spikes more efficiently than their counterparts from human cells. Overall, our study suggests that different lysosomal protease activities from different host species and tissue cells are an important determinant of the species and tissue tropism of coronaviruses.IMPORTANCE Coronaviruses are capable of colonizing new species, as evidenced by the recent emergence of SARS and MERS coronaviruses; they can also infect multiple tissues in the same species. Lysosomal proteases play critical roles in coronavirus entry by cleaving coronavirus surface spike proteins and activating the fusion of host and viral membranes; they also play critical roles in cell physiology by processing cellular products. How do different lysosomal protease activities from different cells impact coronavirus entry? Here, we controlled the contributions from known factors that function in coronavirus entry so that lysosomal protease activities became the only or the main determinant of coronavirus entry. Using pseudovirus entry, cell-cell fusion, and biochemical assays, we showed that lysosomal proteases from bat cells activate coronavirus spike-mediated membrane fusion more efficiently than their counterparts from human cells. Our study provides the first direct evidence supporting lysosomal proteases as a determinant of the species and tissue tropisms of coronaviruses.

negative: A recombinant baculovirus-expressed S glycoprotein vaccine elicits high titers of SARS-associated coronavirus (SARS-CoV) neutralizing antibodies in mice A recombinant SARS-CoV spike (S) glycoprotein vaccine produced in insect cells in a pre-clinical development stage is described. A truncated version of S glycoprotein, containing only the ecto-domain, as well as a His-tagged full-length version were cloned and expressed in a serum-free insect cell line, ExpresSF+(®). The proteins, purified to apparent homogeneity by liquid column chromatography, were formulated without adjuvant at 3, 9, 27, and 50 μg per dose in phosphate saline and used to immunize mice. Both antigens in each formulation elicited a strong immune response after two or three vaccinations with the antigen. Neutralizing antibody titers correlated closely with standard ELISA reactivity against the S glycoprotein. The truncated S protein was also formulated with an adjuvant, aluminum hydroxide, at 1 μg per dose (±adjuvant), and 5 μg per dose (±adjuvant). Significantly enhanced immune responses, manifested by higher titers of serum ELISA and viral neutralizing antibodies, were achieved in adjuvanted groups with fewer doses and lower concentration of S glycoprotein. These findings indicate that the ecto-domain of SARS-CoV S glycoprotein vaccine, with or without adjuvant, is immunogenic and induces high titers of virus neutralizing antibodies to levels similar to those achieved with the full S glycoprotein vaccine.

negative: Viruses with Single-Stranded, Positive-Sense RNA Genomes Eight virus families whose members infect vertebrates are currently known to possess single-stranded, positive-sense RNA genomes: the families Picornaviridae, Caliciviridae and Hepeviridae have non-enveloped capsids, whereas the families Flaviviridae, Togaviridae, Arteriviridae and Coronaviridae are characterized by enveloped capsids. They all have in common the property of using their own genome as messenger RNA (mRNA), from which they synthesize one or several polyproteins that are subsequently cleaved into individual proteins by viral or cellular proteases. These viruses possess the genetic information for the synthesis of an RNA-dependent RNA polymerase. This enzyme transcribes the positive RNA strand as well as the complementary negative RNA strands, which arise as intermediate products of genome replication. In the course of this process, the new genomic RNA molecules are generated from the second transcription step. The classification into the different taxonomic families depends on the number, size, position and orientation of viral genes in the RNA molecule, the number of different polyproteins that are synthesized during viral infection and the existence of an envelope as a virion component.

negative: Investigation of the Impact of Infrared Sensors on Core Body Temperature Monitoring by Comparing Measurement Sites Many types of thermometers have been developed to measure body temperature. Infrared thermometers (IRT) are fast, convenient and ease to use. Two types of infrared thermometers are uses to measure body temperature: tympanic and forehead. With the spread of COVID-19 coronavirus, forehead temperature measurement is used widely to screen people for the illness. The performance of this type of device and the criteria for screening are worth studying. This study evaluated the performance of two types of tympanic infrared thermometers and an industrial infrared thermometer. The results showed that these infrared thermometers provide good precision. A fixed offset between tympanic and forehead temperature were found. The measurement values for wrist temperature show significant offsets with the tympanic temperature and cannot be used to screen fevers. The standard operating procedure (SOP) for the measurement of body temperature using an infrared thermometer was proposed. The suggestion threshold for the forehead temperature is 36 °C for screening of fever. The body temperature of a person who is possibly ill is then measured using a tympanic infrared thermometer for the purpose of a double check.

negative: Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development Novel Coronavirus (2019-nCoV) is an emerging pathogen that was first identified in Wuhan, China in late December 2019. This virus is responsible for the ongoing outbreak that causes severe respiratory illness and pneumonia-like infection in humans. Due to the increasing number of cases in China and outside China, the WHO declared coronavirus as a global health emergency. Nearly 35,000 cases were reported and at least 24 other countries or territories have reported coronavirus cases as early on as February. Inter-human transmission was reported in a few countries, including the United States. Neither an effective anti-viral nor a vaccine is currently available to treat this infection. As the virus is a newly emerging pathogen, many questions remain unanswered regarding the virus’s reservoirs, pathogenesis, transmissibility, and much more is unknown. The collaborative efforts of researchers are needed to fill the knowledge gaps about this new virus, to develop the proper diagnostic tools, and effective treatment to combat this infection. Recent advancements in plant biotechnology proved that plants have the ability to produce vaccines or biopharmaceuticals rapidly in a short time. In this review, the outbreak of 2019-nCoV in China, the need for rapid vaccine development, and the potential of a plant system for biopharmaceutical development are discussed.

negative: Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster Background: In coronavirus disease 2019 (COVID-19), current case definitions presume mainly lower respiratory tract infection. However, cases seen outside the epicenter of the epidemic may differ in their overall clinical appearance due to more sensitive case finding. Methods: We studied viral load courses by RT-PCR in oro- and nasopharyngeal swabs, sputum, stool, blood, and urine in nine hospitalized cases. Infectious virus was detected by cell culture. Active replication was demonstrated by analysis of viral subgenomic replicative intermediates. Serology including neutralization testing was done to characterize immune response. Results: Seven cases had upper respiratory tract disease. Lower respiratory tract symptoms seen in two cases were limited. Clinical sensitivity of RT-PCR on swabs taken on days 1-5 of symptoms was 100%, with no differences comparing swab and sputum samples taken simultaneously. Average viral load was 6.76x10E5 copies per swab during the first 5 days. Live virus isolates were obtained from swabs during the first week of illness. Proof of active viral replication in upper respiratory tract tissues was obtained by detection of subgenomic viral RNA. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after about one week. Conclusions: The present study shows that COVID-19 can often present as a common cold-like illness. SARS-CoV-2 can actively replicate in the upper respiratory tract, and is shed for a prolonged time after symptoms end, including in stool. These findings suggest adjustments of current case definitions and re-evaluation of the prospects of outbreak containment.

negative: Scientific Opinion on an update on the present knowledge on the occurrence and control of foodborne viruses A review of the biology, epidemiology, diagnosis and public health importance of foodborne viruses was performed. Data needs to support a risk assessment were also identified. In addition possible control options and their anticipated impact to prevent or reduce the number of foodborne viral human infections were identified, including the scientific reasons for and against the establishment of food safety criteria and process hygiene criteria for viruses for certain food categories. Food may be contaminated by virus during all stages of the food supply chain, and transmission can occur by consumption of food contaminated during the production process (primary production, or during further processing), or contaminated by infected food handlers. Transmission of zoonotic viruses (e.g. HEV) can also occur by consumption of products of animal origin. Viruses do not multiply in foods, but may persist for extended periods of time as infectious particles in the environment, or in foods. At the EU‐level it is unknown how much viral disease can be attributed to foodborne spread. The relative contribution of different sources (shellfish, fresh produce, food handler including asymptomatic shedders, food handling environment) to foodborne illness has not been determined. The Panel recommends focusing controls on preventive measures to avoid viral contamination rather than trying to remove/inactivate these viruses from food. Also, it is recommended to introduce a microbiological criteria for viruses in bivalve molluscs, unless they are labelled “to be cooked before consumption”. The criteria could be used by food business operators to validate their control options. Furthermore, it is recommended to refine the regulatory standards and monitoring approaches in order to improve public health protection. Introduction of virus microbiological criteria for classification of bivalve molluscs production areas should be considered. A virus monitoring programme for compliance with these criteria should be risk based according to the findings of a sanitary survey.

negative: Point-of-Care Microdevices for Blood Plasma Analysis in Viral Infectious Diseases Each year, outbreaks of viral infections cause illness, disability, death, and economic loss. As learned from past incidents, the detrimental impact grows exponentially without effective quarantine. Therefore, rapid on-site detection and analysis are highly desired. In addition, for high-risk areas of viral contamination, close monitoring should be provided during the potential disease incubation period. As the epidemic progresses, a response protocol needs tobe rapidly implemented and the virus evolution fully tracked. For these scenarios, point-of-care microdevices can provide sensitive, accurate, rapid and low-cost analysis for a large population, especially in handling complex patient samples, such as blood, urine and saliva. Blood plasma can be considered as a mine of information containing sources and clues of biomarkers, including nucleic acids, immunoglobulin and other proteins, as well as pathogens for clinical diagnosis. However, blood plasma is also the most complicated body fluid. For targeted plasma biomarker detection or untargeted plasma biomarker discovery, the challenges can be as difficult as identifying a needle in a haystack. A useful platform must not only pursue single performance characteristics, but also excel at multiple performance parameters, such as speed, accuracy, sensitivity, selectivity, cost, portability, reliability, and user friendliness. Throughout the decades, tremendous progress has been made in point-of-care microdevices for viral infectious diseases. In this paper, we review fully integrated lab-on-chip systems for blood analysis of viral infectious disease.

negative: Intubation outside of the operating room: new challenges and opportunities in COVID-19 era PURPOSE OF REVIEW: Airway management in patients outside the operating room is associated with increased difficulties and risks, and the setting of the COVID-19 global pandemic adds another layer of complexity. Therefore, endotracheal intubation (ETT) of a patient who is presumptive COVID-19 or COVID-19 positive presents an additional challenge to an anesthesiologist. The aim of this review is to summarize the important principles of airway management outside of the operating room during the COVID-19 pandemic. RECENT FINDINGS: Several professional societies have formulated guidelines on airway management COVID-19 suspect and proven patients. Additionally, anesthesiologists working in hospitals treating many infected patients have developed specialized teams responsible for airway management outside the operating room. These documents and protocols focus on the importance of wearing personal protective equipment and the skills of the providers responsible for securing the airway. Staff safety is always a priority when performing ETT outside operating room. SUMMARY: The COVID-19 pandemic redefined the management of patients requiring aerosol generating procedures (droplet and airborne precautions). ETT is one of them and anesthesiologists are experts in performing airway management. Although the operating room is a highly controlled environment, airway management outside of this setting is not always the easiest task.

negative: Epidemic update of COVID-19 in Hubei Province compared with other regions in China Abstract Aims & Background The COVID-19 outbreak spread in China and is a threat to the world. The aims of this study to help health workers better understand the epidemic of the COVID-19 and provide different control strategies toward Hubei Province and other regions in China. Methods A comprehensive search of the Chinese Center for Disease Control and Prevention official websites and announcements was performed between 20 Jan 2019 and 29 Feb 2020. The relevant data of the distribution of the infection on each reported day were obtained. Results& findings Up to 29 Feb 2020, 79,824 confirmed cases with the COVID-19 including 66,907 in Hubei Province and 12,377 in other administrative regions were reported. The SARS-COV-2 showed faster epidemic trends compared with the 2003-SARS-CoV. A total of 2,870 deaths have been reported nationwide among 79,824 confirmed cases, with a mortality of 3.6%. The mortality of the COVID-19 was significantly higher in Hubei Province than that in other regions(4.1% versus 0.84%). Since 1 Feb 2020 the number of discharged cases exceeded the number of the dead. By 29 Feb 2020, the number of discharged patients was 41,625, which exceeded the number of hospitalized patients, and the trend has further increased. Conclusions The infection of the SARS-COV-2 is spreading and increasing nationwide, and Hubei Province is the main epidemic area, with higher mortality. The outbreak is now under initial control especially in other regions outside of Hubei Province. Due to the different epidemic characteristics between Hubei Province and other regions, we should focus on different prevention and control strategies.

negative: Viral contamination of aerosol and surfaces through toilet use in health care and other settings BACKGROUND: The airborne spreading of enteric viruses can occur through the aerosol and droplets produced by toilet flushing. These can contaminate the surrounding environment, but few data exist to estimate the risk of exposure and infection. For this reason environmental monitoring of air and selected surfaces was carried out in 2 toilets of an office building and in 3 toilets of a hospital before and after cleaning operations. METHODS: To reveal the presence of norovirus, enterovirus, rhinovirus, human rotavirus, and Torque teno virus and to quantify human adenovirus and bacteria counts, molecular and cultural methods were used. RESULTS: On the whole, viruses were detected on 78% of surfaces and in 81% of aerosol. Among the researched viruses, only human adenovirus and Torque teno virus were found in both surface and air samples. In several cases the same adenovirus strain was concurrently found in all matrices. Bacterial counts were unrelated to viral presence and cleaning did not seem to substantially reduce contamination. CONCLUSIONS: The data collected in our study confirm that toilets are an important source of viral contamination, mainly in health care settings, where disinfection can have a crucial role in preventing virus spread.

negative: Cold Plasma, a New Hope in the Field of Virus Inactivation Viruses can infect all cell-based organisms, from bacteria to humans, animals, and plants. They are responsible for numerous cases of hospitalization, many deaths, and widespread crop destruction, all of which result in an enormous medical, economical, and biological burden. Each of the currently used decontamination methods has important drawbacks. Cold plasma (CP) has entered this field as a novel, efficient, and clean solution for virus inactivation. We present recent developments in this promising field of CP-mediated virus inactivation, and describe the applications and mechanisms of the inactivation. This is particularly relevant because viral pandemics, such as COVID-19, highlight the need for alternative virus inactivation methods to replace, complement, or upgrade existing procedures.

negative: The enlightenment from two cases of asymptomatic infection with SARS-CoV-2: is it safe after 14 days of isolation? Abstract From 78 laboratory-confirmed cases, we found 2 asymptomatic infections. One patient was discharged within 14 days after treatment. Another patient was discharged 25 days after treatment, and his TR-PCR test was still positive on the 15th day. We found that there may be virus carriers in asymptomatic population with epidemiological contact history. After 14 days of isolation, asymptomatic infection may still carry the virus, which means the risk of transmission and present a new challenge to home isolation.

negative: A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19 PURPOSE: COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19. METHODS: PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19. RESULTS: We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro. CONCLUSIONS: There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed.

negative: Unexplained Deaths and Critical Illnesses of Suspected Infectious Cause, Taiwan, 2000–2005 We report 5 years’ surveillance data from the Taiwan Centers for Disease Control on unexplained deaths and critical illnesses suspected of being caused by infection. A total of 130 cases were reported; the incidence rate was 0.12 per 100,000 person-years; and infectious causes were identified for 81 cases (62%).

negative: In memory of Patrick Manson, founding father of tropical medicine and the discovery of vector-borne infections Patrick Manson, a clinician-scientist serving in China (1866–1889), discovered that many tropical infectious diseases require a vector peculiar to warm climate for person to person transmission. He demonstrated the nocturnal periodicity of microfilariae in the blood of patients with elephantiasis. These microfilariae undergo metamorphosis when ingested by the mosquito acting as the vector for the completion of their life cycle. Furthermore, he demonstrated the linkage between the lung fluke and endemic haemoptysis by finding operculated eggs in patients' sputa. He predicted that the miracidium from hatched eggs uses crustaceans, such as fresh-water snails found at tropical conditions, as the intermediate hosts in the life cycle of many trematodes. His vector hypothesis leads to vector control which is now the cornerstone for the World Health Organization's programme for the elimination/control of lymphatic filariasis, dracunculiasis and malaria. Before leaving China, he established the Alice Memorial Hospital, the Hong Kong College of Medicine for Chinese (the forerunner of the University of Hong Kong), and the Hong Kong Medical Society for medical service and education. He also incepted the Hong Kong Dairy Farm for supplying hygienic milk affordable by pregnant women, children and patients.

negative: Bacterial survival in evaporating deposited droplets on a teflon-coated surface Understanding of bacterial survival in aerosols is crucial for controlling infection transmission via airborne aerosols and/or large droplets routes. The cell viability changes of four bacteria species (Escherichia coli K12 JM109; Acinetobacter sp. 5A5; Pseudomonas oleovorans X5; and Staphylococcus aureus X8), three Gram-negative and one Gram-positive, in a large evaporating droplet of size 1,800 μm in diameter on teflon-coated slides were measured using the LIVE/DEAD BacLight solution and a microscope. Droplets of three levels of salinity (0, 0.9, and 36% w/v) were tested. All four species survived well during the droplet evaporation process, but died mostly at the time when droplets were dried out at 40–45 min. The final bacteria survival rate after droplets were completely dried was dependent on bacteria species and the salinity of the suspension solution. Droplet evaporation over the first 35–40 min had no adverse effect on bacterial survival for the droplets tested. The lethal effect of desiccation was found to be the most important death mechanism.

negative: Bovine coronavirus hemagglutinin protein Abstract Treatment of purified bovine coronavirus (Mebus strain) with pronase destroyed the integrity of virion surface glycoproteins gp140, gp120, gp100, reduced the amount of gp26 and destroyed the hemagglutinating activity of the virus. Bromelain, on the other hand, destroyed the integrity of gp120, gp100 and gp26 but failed to remove gp140 and failed to destroy viral hemagglutinating activity. These experiments suggest that gp140 is the virion hemagglutinin. Immunoblotting studies using monospecific antiserum demonstrate that gp140 is a disulfide-linked dimeric structure reducible to monomers of 65 kDa.

negative: COVID-19 therapeutic options for patients with kidney disease

negative: [Analysis of variation and evolution of SARS-CoV-2 genome]. OBJECTIVE To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019. METHODS We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution. RESULTS The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of β Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic. CONCLUSIONS SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.

negative: Antiviral activity of carbohydrate-binding agents against Nidovirales in cell culture Abstract Coronaviruses are important human and animal pathogens, the relevance of which increased due to the emergence of new human coronaviruses like SARS-CoV, HKU1 and NL63. Together with toroviruses, arteriviruses, and roniviruses the coronaviruses belong to the order Nidovirales. So far antivirals are hardly available to combat infections with viruses of this order. Therefore, various antiviral strategies to counter nidoviral infections are under evaluation. Lectins, which bind to N-linked oligosaccharide elements of enveloped viruses, can be considered as a conceptionally new class of virus inhibitors. These agents were recently evaluated for their antiviral activity towards a variety of enveloped viruses and were shown in most cases to inhibit virus infection at low concentrations. However, limited knowledge is available for their efficacy towards nidoviruses. In this article the application of the plant lectins Hippeastrum hybrid agglutinin (HHA), Galanthus nivalis agglutinin (GNA), Cymbidium sp. agglutinin (CA) and Urtica dioica agglutinin (UDA) as well as non-plant derived pradimicin-A (PRM-A) and cyanovirin-N (CV-N) as potential antiviral agents was evaluated. Three antiviral tests were compared based on different evaluation principles: cell viability (MTT-based colorimetric assay), number of infected cells (immunoperoxidase assay) and amount of viral protein expression (luciferase-based assay). The presence of carbohydrate-binding agents strongly inhibited coronaviruses (transmissible gastroenteritis virus, infectious bronchitis virus, feline coronaviruses serotypes I and II, mouse hepatitis virus), arteriviruses (equine arteritis virus and porcine respiratory and reproductive syndrome virus) and torovirus (equine Berne virus). Remarkably, serotype II feline coronaviruses and arteriviruses were not inhibited by PRM-A, in contrast to the other viruses tested.

negative: Epigenetic Landscape during Coronavirus Infection Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus–host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype. Epigenetic modifications, such as histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs, function as important regulators that remodel host chromatin, altering host expression patterns and networks in a highly flexible manner. For most of the past two and a half decades, research has focused on the molecular mechanisms by which RNA viruses antagonize the signaling and sensing components that regulate induction of the host innate immune and antiviral defense programs upon infection. More recently, a growing body of evidence supports the hypothesis that viruses, even lytic RNA viruses that replicate in the cytoplasm, have developed intricate, highly evolved, and well-coordinated processes that are designed to regulate the host epigenome, and control host innate immune antiviral defense processes, thereby promoting robust virus replication and pathogenesis. In this article, we discuss the strategies that are used to evaluate the mechanisms by which viruses regulate the host epigenome, especially focusing on highly pathogenic respiratory RNA virus infections as a model. By combining measures of epigenome reorganization with RNA and proteomic datasets, we articulate a spatial-temporal data integration approach to identify regulatory genomic clusters and regions that play a crucial role in the host’s innate immune response, thereby defining a new viral antagonism mechanism following emerging coronavirus infection.

negative: Isolation and Morphology of the Internal Component of Human Coronavirus, Strain 229E Biochemical studies on human coronavirus, strain 229E, indicate that the RNA is present in the virion in association with protein as a ribonucleoprotein (RNP) complex. Morphological studies have revealed that this nucleocapsid is probably a continuous helical RNP.

negative: Physiology in Perspective: In a World of Social Distancing

negative: First respiratory transmitted food borne outbreak? Abstract The world is faced with a remarkable coronavirus outbreak with epicentre in Wuhan, China. Altogether 40554 cases have been confirmed globally with novel coronavirus (SARS-CoV-2) until February 10, 2020. Rigorous surveillance in other countries is required to prevent further global expansion of the outbreak, but resolving the exact mechanism of the initial transmission events is crucial. Most initial cases had visited Huanan South Seafood Market in Wuhan selling also various exotic live animals. Based on the limited initial human-to-human transmission and timely clustering of cases in Huanan market among elderly men, coupled with knowledge that coronaviruses are derived from animals and relationship of SARS-CoV-2 to bat coronavirus, zoonotic transmission in the first instance is probable. To target the actions, similar epidemiological actions to human cases are needed with animal or food exposures. According to current information, an exceptionally wide contamination of seafood market might explain the initiation of the SARS-CoV-2 outbreak. Seafood tanks, air contamination by live animals or rodents are possibilities, but sold animals normally come from various sources. The mode of transmission may become clearer in future: usually in outbreak investigations, hindsight is easy, but for now information about the initial source of this outbreak is limited.

negative: Half-Life of African Swine Fever Virus in Shipped Feed African swine fever virus is transmissible through animal consumption of contaminated feed. To determine virus survival during transoceanic shipping, we calculated the half-life of the virus in 9 feed ingredients exposed to 30-day shipment conditions. Half-lives ranged from 9.6 to 14.2 days, indicating that the feed matrix environment promotes virus stability.

negative: SARS-CoV-2 and COVID-19: The most important research questions Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.

negative: In vitro and ex vivo systems at the forefront of infection modeling and drug discovery Abstract Bacterial infections and antibiotic resistant bacteria have become a growing problem over the past decade. As a result, the Centers for Disease Control predict more deaths resulting from microorganisms than all cancers combined by 2050. Currently, many traditional models used to study bacterial infections fail to precisely replicate the in vivo bacterial environment. These models often fail to incorporate fluid flow, bio-mechanical cues, intercellular interactions, host-bacteria interactions, and even the simple inclusion of relevant physiological proteins in culture media. As a result of these inadequate models, there is often a poor correlation between in vitro and in vivo assays, limiting therapeutic potential. Thus, the urgency to establish in vitro and ex vivo systems to investigate the mechanisms underlying bacterial infections and to discover new-age therapeutics against bacterial infections is dire. In this review, we present an update of current in vitro and ex vivo models that are comprehensively changing the landscape of traditional microbiology assays. Further, we provide a comparative analysis of previous research on various established organ-disease models. Lastly, we provide insight on future techniques that may more accurately test new formulations to meet the growing demand of antibiotic resistant bacterial infections.

negative: Viral survival How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this? Douglas Fairchild, Two Harbors, Minnesota, US

negative: Nonproliferative and Proliferative Lesions of the Ratand Mouse Special Sense Organs(Ocular [eye and glands], Olfactory and Otic)

negative: SARS & the Health Care System: Exploring Your Questions About This New Infectious Disease

negative: What are we doing in the dermatology outpatient department amidst the raging of the 2019 novel coronavirus?

negative: Coronavirus just caused the American Physical Society to cancel its biggest meeting of the year ;Science ;AAAS Citing the growing threat of the coronavirus, the American Physical Society (APS), the 55,000 member professional society for physicists and researchers in associated fields, cancelled its largest meeting of the year just 34 hours before it was supposed to begin APS’s March Meeting was to be held this week at the Colorado Convention Center in Denver, and the society anticipated more than 10,000 people from all over the world would attend However, late yesterday, APS issued a statement abruptly calling off the meeting “The decision to cancel was based on the latest scientific data being reported, and the fact that a large number of attendees at this meeting are coming from outside the U S ,” including countries where the virus is circulating and for which the U S Centers for Disease Control and Prevention have advised people to avoid non-essential travel, the APS statement says “[T]his decision was made out of deep concern for the health and well-being of our registrants, staff, vendors, and the Denver community ”

negative: Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study OBJECTIVE: To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. DESIGN: Retrospective case series. SETTING: Tongji Hospital in Wuhan, China. PARTICIPANTS: Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. MAIN OUTCOME MEASURES: Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. RESULTS: The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

negative: Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV) Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.

negative: Clinical characteristics and reasons of different duration from onset to release from quarantine for patients with COVID-19 Outside Hubei province, China. Objective: To find out more characteristics and rules of COVID-19 by analyzing the clinical course of COVID-19 patients in a region outside Hubei province. Methods: 37 cases diagnosed adult COVID-19 cases of general characteristics, history of epidemiology, chronic underlying diseases,clinical symptoms and complications, chest CT, biochemical monitoring, severity assessment, treatment and outcome were retrospectively analyzed, and according to the duration from onset to release from quarantine were divided into 20-day group and > 20-day group, compare the similarities and differences between the two groups. Results: Among the 37 patients, 5 were mild, 30 were moderate, 1 was severe and 1 was critical. All the patients were released from quarantine without death. The average duration from onset to release from quarantine was 20.2±6.6 days, The average length of stay from onset to hospitalization was 4.1±3.7 days, and hospitalization duration average 16.1± 6.2 days. The average age was 44.3±1.67 years. 78.4% of cases were caused by exposure to a confirmed patient or the workplace of a confirmed patient. The main symptoms were cough (67.6%), fever( 62.2%), shortness of breath (32.4%), fatigue (24.3%), sore throat (21.6%,) vomiting or diarrhea (21.6%). The white blood cell count was decreased in 27.0% of the patients, and the lymphocyte count was decreased in 62.2% of the patients, of which 43.5% patients were <0.6 × 109/L. On admission, 86.5% of patients with chest CT showed pneumonia, including some asymptomatic patients. 68.8% of patients showed bilateral infiltration. In the > 20-day group, the average age was 49.9±1.38 years old, and the duration from onset to hospitalization was 5.5±3.9 days. Compared with the ≤20-day group, the age was older and and duration was longer, P < 0.05. All the 7 asymptomatic patients were ≤20-day group. When 37 patients were released from quarantine, the white blood cell count of 16.2% patients was <4.0 × 109/L, and the lymphocyte count of 59.5% patients was <1.1×109/L, and the absolute count of white blood cells and lymphocytes was 5.02 ± 1.34×109/L and 1.03± 0.34×109/L respectively , compared with those on admission, P >0.05. Conclusion: The majority of COVID-19 cases in the study area were mild and moderate, with good clinical outcomes. There were some special characteristics in the clinical process. The reasons of duration from onset to release from quarantine were complex. There was no significant change in the number of granulocytes at the time of release from quarantine compared to the time of admission.

negative: Epidemiologic analysis of respiratory viral infections among Singapore military servicemen in 2016 BACKGROUND: Respiratory illnesses have been identified as a significant factor leading to lost training time and morbidity among Singapore military recruits. A surveillance programme has been put in place to determine etiological agents responsible for febrile, as well as afebrile respiratory illnesses in a military camp. The goal of the study is to better understand the epidemiology of these diseases and identify potential countermeasures to protect military recruits against them. METHODS: From Jan 2016 - Jan 2017, a total of 2647 respiratory cases were enrolled into the surveillance programme. The cases were further stratified into Febrile Respiratory Illness (FRI, with body temperature > 37.5 °C) or Acute Respiratory Illness (ARI, with body temperature < 37.5 °C). Nasal washes were collected and tested by multiplex PCR to detect 26 different pathogens. RESULTS: One thousand ninety five cases (41% of total cases) met the criteria of FRI in which 932 cases (85% of FRI cases) were screened positive for at least one virus. The most common etiological agents for FRI mono-infection cases were Adenovirus E and Rhinovirus. Recruits infected with H3N2 influenza, Influenza B and Adenovirus E viruses were most likely presented as FRI cases. Notably, H3N2 influenza resulted in the greatest rise in body temperature. The remaining 1552 cases (59% of total cases) met the criteria of ARI in which 1198 cases (77% of ARI cases) were screened positive for at least one virus. The most common etiological agent for ARI mono-infection was Rhinovirus. The distribution pattern for dual infections was different for ARI and FRI cases. Maximum number of pathogens detected in a sample was five for both groups. CONCLUSION: Previous studies on respiratory diseases in military focused largely on FRI cases. With the expanded surveillance to ARI cases, this study allows unbiased evaluation of the impact of respiratory disease pathogens among recruits in a military environment. The results show that several pathogens have a much bigger role in causing respiratory diseases in this cohort. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3040-x) contains supplementary material, which is available to authorized users.

negative: Knowledge and Beliefs of General Public of India on COVID-19: A Web-based Cross-sectional Survey Context: Despite many awareness programs conducted by the governments and other agencies, there are certain false beliefs among the general public of India towards the transmission, prevention, and treatment of COVID-19. Aims: To assess the knowledge and beliefs of the general public of India on COVID-19. Materials and Methods: A web-based cross-sectional survey was conducted between 20th March and 15th April 2020. A 17-item questionnaire was developed, validated, and used for the study. The questionnaire was randomly distributed among the public using Google forms through social media networks. Descriptive analysis was performed to represent the study characteristics, Chi-square test for assessing the associations among the study variables, and logistic regression analysis for identifying the factors influencing the beliefs. Results: A total of 462 participants with a mean (SD) age of 30.66 (11.31) years were responded to the questionnaire. Study participants are having fairly good knowledge of the basic aspects of COVID-19. However, a considerable fraction of participants were having false beliefs towards the transmission of new coronavirus, and prevention & treatment of COVID-19. It was observed that the participants who were aged 31-60 years and >60 years, education level of intermediate or diploma and high school certificate, and occupation as the unskilled workers had more of false beliefs towards COVID-19 compared to their counterparts. Conclusion: Though the overall knowledge on COVID-19 was good enough among the general public of India, still there is a need for education to avoid false beliefs especially among the people who are elderly, having a low level of education, and non-professional workers.

negative: Feline Infectious Peritonitis: An Immune-Mediated Coronaviral Vasculitis Mainly through studies inducing experimental infection of susceptible cats, significant advances have recently been made in our understanding of the pathogenesis of FIP. Much of this knowledge should not presently be directly extrapolated to field cases of FIP, because the route of infection and challenge dose and strain of virus may be significantly different. Advances in the prevention and treatment of FIP will depend greatly on clarification of the exact nature of the several coronaviruses affecting cats and the role of cell-mediated immunity in resistance to FIPV.

negative: Chapter 12 Planning and Managing Health Systems Abstract Health systems are complex organizations. They are often the largest single employer in a country, with expenditures of public and private money of 4–17 percent of gross domestic product. Overall and individual facility management requires mission statements, objectives, targets, budgets, activities planning, human interaction, services delivery, and quality assurance. Health organization involves a vast complex of stakeholders and participants, suppliers and purchasers, regulators and direct providers, and individual patients, and their decision-making. These include pyramidal and network organizations and ethical decision-making based on public interest, resource allocations, priority selection, and assurance of certain codes of law and ethical conduct. This chapter discusses how complex organizations work, with potential for application in health, and the motivations of workers and of the population being served. Organization theory helps in devising methods to integrate relevant factors to become more effective in defining and achieving goals and missions.

negative: Arterivirus discontinuous mRNA transcription is guided by base pairing between sense and antisense transcription-regulating sequences. To generate an extensive set of subgenomic (sg) mRNAs, nidoviruses (arteriviruses and coronaviruses) use a mechanism of discontinuous transcription. During this process, mRNAs are generated that represent the genomic 5' sequence, the so-called leader RNA, fused at specific positions to different 3' regions of the genome. The fusion of the leader to the mRNA bodies occurs at a short, conserved sequence element, the transcription-regulating sequence (TRS), which precedes every transcription unit in the genome and is also present at the 3' end of the leader sequence. Here, we have used site-directed mutagenesis of the infectious cDNA clone of the arterivirus equine arteritis virus to show that sg mRNA synthesis requires a base-pairing interaction between the leader TRS and the complement of a body TRS in the viral negative strand. Mutagenesis of the body TRS of equine arteritis virus RNA7 reduced sg RNA7 transcription severely or abolished it completely. Mutations in the leader TRS dramatically influenced the synthesis of all sg mRNAs. The construction of double mutants in which a mutant leader TRS was combined with the corresponding mutant RNA7 body TRS resulted in the specific restoration of mRNA7 synthesis. The analysis of the mRNA leader-body junctions of a number of mutants with partial transcriptional activity provided support for a mechanism of discontinuous minus-strand transcription that resembles similarity-assisted, copy-choice RNA recombination.

negative: Virus RNA Persists within the Retina in Coronavirus-Induced Retinopathy Abstract The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. In the early phase, Day 1 to Day 7, a retinal vasculitis is noted which is associated with the presence of viral proteins and infectious virus. In the late phase, Day 10 to Day 140, a retinal degeneration is associated with the absence of viral proteins, infectious virus, and inflammatory cells. The purpose of this study was to determine if viral RNA persists within the retina during the retinal degenerative phase of the disease. BALB/c mice were inoculated by the intravitreal route with 104.0TCID50/5 μl of virus. The presence of viral RNA was detected byin situhybridization with a viral cDNA probe and viral proteins were identified by immunocytochemical staining. During the acute phase of the infection, viral RNA was found in the retina, RPE, ciliary body epithelium, and the iris epithelium. During the late phase of the infection, viral RNA was almost exclusively found within the retina and RPE and not in the anterior segment of the eye. Within the retina, viral RNA was detected in the ganglion cell layer, the inner retina, the outer retina, and the RPE cell. Immunocytochemical staining identified viral protein within the retina only from Day 1 to Day 8. This ocular disease was also associated with a persistent systemic infection. Both viral RNA and viral proteins were identified within the liver during the first 8 days. However, only viral RNA was detected in the liver from Day 8 to Day 60. These studies demonstrate that MHV established an acute infection (Day 1–8) where infectious virus and viral proteins were identified. This was followed by a persistent infection within the retina and liver where only viral RNA were detected byin situhybridization.

negative: Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. The spike protein (S) of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). A defined receptor-binding domain (RBD) on S mediates this interaction. The crystal structure at 2.9 angstrom resolution of the RBD bound with the peptidase domain of human ACE2 shows that the RBD presents a gently concave surface, which cradles the N-terminal lobe of the peptidase. The atomic details at the interface between the two proteins clarify the importance of residue changes that facilitate efficient cross-species infection and human-to-human transmission. The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.

negative: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version) In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

negative: Epidemiological, Clinical Characteristics and Outcome of Medical Staff Infected with COVID-19 in Wuhan, China: A Retrospective Case Series Analysis Backgrounds Since December 2019, a novel coronavirus epidemic has emerged in Wuhan city, China and then rapidly spread to other areas. As of 20 Feb 2020, a total of 2,055 medical staff confirmed with coronavirus disease 2019 (COVID-19) caused by SARS-Cov-2 in China had been reported. We sought to explore the epidemiological, clinical characteristics and prognosis of novel coronavirus-infected medical staff. Methods In this retrospective study, 64 confirmed cases of novel coronavirus-infected medical staff admitted to Union Hospital, Wuhan between 16 Jan, 2020 to 15 Feb, 2020 were included. Two groups concerned were extracted from the subjects based on duration of symptoms: group 1 (<= 10 days) and group 2 (>10 days). Epidemiological and clinical data were analyzed and compared across groups. The Kaplan-Meier plot was used to inspect the change in hospital discharge rate. The Cox regression model was utilized to identify factors associated with hospital discharge. Findings The median age of medical staff included was 35 years old. 64% were female and 67% were nurses. None had an exposure to Huanan seafood wholesale market or wildlife. A small proportion of the cohort had contact with specimens (5%) as well as patients in fever clinics (8%) and isolation wards (5%). Fever (67%) was the most common symptom, followed by cough (47%) and fatigue (34%). The median time interval between symptoms onset and admission was 8.5 days. On admission, 80% of medical staff showed abnormal IL-6 levels and 34% had lymphocytopenia. Chest CT mainly manifested as bilateral (61%), subpleural (80%) and ground-glass (52%) opacities. During the study period, no patients was transferred to intensive care unit or died, and 34 (53%) had been discharged. Higher body mass index (BMI) (HR 0.14; 95% CI 0.03-0.73), fever (HR 0.24; 95% CI 0.09-0.60) and higher levels of IL-6 on admission (HR 0.31; 95% CI 0.11-0.87) were unfavorable factors for discharge. Interpretation In this study, medical staff infected with COVID-19 have relatively milder symptoms and favorable clinical course, which may be partly due to their medical expertise, younger age and less underlying diseases. Smaller BMI, absence of fever symptoms and normal IL-6 levels on admission are favorable for discharge for medical staff. Further studies should be devoted to identifying the exact patterns of SARS-CoV-2 infection among medical staff.

negative: Bats and Viruses: complex relationships With more than 1 200 species, bats and flying foxes (Order Chiroptera) constitute the most important and diverse order of Mammals after Rodents. Many species of bats are insectivorous while others are frugivorous and few of them are hematophagous. Some of these animals fly during the night, others are crepuscular or diurnal. Some fly long distances during seasonal migrations. Many species are colonial cave-dwelling, living in a rather small home range while others are relatively solitary. However, in spite of the importance of bats for terrestrial biotic communities and ecosystem ecology, the diversity in their biology and lifestyles remain poorly known and underappreciated. More than sixty viruses have been detected or isolated in bats; these animals are therefore involved in the natural cycles of many of them. This is the case, for instance, of rabies virus and other Lyssavirus (Family Rhabdoviridae), Nipah and Hendra viruses (Paramyxoviridae), Ebola and Marburg viruses (Filoviridae), SARS-CoV and MERS-CoV (Coronaviridae). For these zoonotic viruses, a number of bat species are considered as important reservoir hosts, efficient disseminators or even directly responsible of the transmission. Some of these bat-borne viruses cause highly pathogenic diseases while others are of potential significance for humans and domestic or wild animals; so, bats are an important risk in human and animal public health. Moreover, some groups of viruses developed through different phylogenetic mechanisms of coevolution between viruses and bats. The fact that most of these viral infections are asymptomatic in bats has been observed since a long time but the mechanisms of the viral persistence are not clearly understood. The various bioecology of the different bat populations allows exchange of virus between migrating and non-migrating conspecific species. For a better understanding of the role of bats in the circulation of these viral zoonoses, epidemiologists must pay attention to some of their biologic properties which are not fully documented, like their extreme longevity, their diet, the population size and the particular densities observed in species with crowded roosting behavior, the population structure and migrations, the hibernation permitting overwintering of viruses, their particular innate and acquired immune response, probably related at least partially to their ability to fly, allowing persistent virus infections and preventing immunopathological consequences, etc. It is also necessary to get a better knowledge of the interactions between bats and ecologic changes induced by man and to attentively follow bat populations and their viruses through surveillance networks involving human and veterinary physicians, specialists of wild fauna, ecologists, etc. in order to understand the mechanisms of disease emergence, to try to foresee and, perhaps, to prevent viral emergences beforehand. Finally, a more fundamental research about immune mechanisms developed in viral infections is essential to reveal the reasons why Chiroptera are so efficient reservoir hosts. Clearly, a great deal of additional work is needed to document the roles of bats in the natural history of viruses.

negative: Why This Book? An Introduction For the sake of simplicity, let us start by naming an infectious agent a “germ.” There are countless germs that can infect human, animal, and plant hosts. Germs can be transmitted directly between hosts via respiratory air droplets or bodily fluids (e.g., saliva, blood, or secretions from sexual organs). Germs can also be transmitted indirectly through an intermediary source, for instance via mosquitoes, ticks, rodents, environmental particles (e.g., contaminated water and food) or contaminated blood products. Germs evolve and transform while new germs emerge regularly, implying their supply can be considered infinite. A broad distinction is often made between microscopically small germs with relatively short life spans, which replicate within their hosts (often called microparasites such as viruses, bacteria, and fungi), and much larger germs with relatively longer life spans (often called macroparasites such as parasitic worms). Many germs live inside or on the surface of their hosts’ bodies without causing illness or even discomfort.

negative: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff. BACKGROUND In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants), people with a long gown had less contamination than those with a coverall, and coveralls were more difficult to doff (low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort, and may therefore even lead to more contamination. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.

negative: Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. METHODS: We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level. FINDINGS: We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33-56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4·4 days (95% CI 0·0-14·0) for the period of Dec 24 to Jan 27, to 2·6 days (0·0-9·0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5·2 days (1·8-12·4) and the mean serial interval at 5·1 days (1·3-11·6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1·08 (95% CI 0·74-1·54) in Shenzhen city of Guangdong province and 1·71 (1·32-2·17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, <1) after Jan 30. INTERPRETATION: Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province. FUNDING: National Science Fund for Distinguished Young Scholars, National Institute of General Medical Sciences, and European Commission Horizon 2020.

negative: Infrared assessment of human facial temperature in the presence and absence of common cosmetics Using a sensitive research-grade infrared camera, we find that common facial cosmetics and lotions mask skin temperature in assays of the human forehead. We test a family of 10 commonly-used cosmetic products and find that volatile liquids and creams lower thermal skin temperature by at least 2 C for up to 5-10 min and at least 1 C for up to 20 min, respectively. Powder and cream that contains brightening agent lower indefinitely the skin temperature sensed by infrared camera. With the qualification that these experiments were performed in a controlled laboratory setting rather than the mass crowd screening environment where infrared temperature sensing of humans sees widespread use, our tests suggest that for human subjects whose face was treated with certain cosmetics and lotions, infrared-based screening for elevated facial temperature (fever) can be unreliable.

negative: Temporal relationship between outbound traffic from Wuhan and the 2019 coronavirus disease (COVID-19) incidence in China Background: The city of Wuhan is the epicenter of the 2019 coronavirus disease (COVID-19) outbreak and a central Chinese hub for transportation and industry. Mass migration prior to the Chinese New Year may have accelerated the spread of COVID-19 across China. This analysis investigated the temporal relationship between daily outbound traffic from Wuhan and the incidence of COVID-19 in 31 Chinese provinces during January-February 2020. Methods: We collected incidence of confirmed COVID-19 cases from National and Provincial Health Committee reports from January 10 to February 29, 2020. Volume of outbound traffic from Wuhan to other provinces was measured by Baidu Migration Index, a widely used metric that tracks migration based on cellphone location. We used cross-correlation function and autoregressive integrated moving average (ARIMA) model to examine time-lagged association between traffic volume and COVID-19 incidence by province. Contributors to the provincial variation in the temporal associations were investigated. Additionally, we estimated the reduction in cumulative incidence of COVID-19 cases following the travel ban for Wuhan. Results: Cross-correlation function analyses suggested that the volume of outbound traffic from Wuhan was positively associated with COVID-19 incidence in all provinces, with correlation coefficients between 0.22-0.78 (all P<0.05). Approximately 42% of provinces showed <1 week of lag between traffic volume and COVID-19 incidence, 39% with 1 week, and 19% with 2-3 weeks. Migration had more prolonged impacts in provinces closer to Wuhan and with more passenger influx from Wuhan, but affected economically advantaged provinces to a lesser extent. We further estimated that the travel ban may have prevented approximately 19,768 COVID-19 cases (95% CI: 13,589, 25,946) outside of Wuhan by February 29, 2020. Conclusions: Outflowing migration from Wuhan facilitated the COVID-19 transmission to other parts of China with varying time-lagged effects dependent on provincial characteristics. The travel ban led to a significant reduction in COVID-19 outside of Wuhan.

negative: Ventilation and laboratory confirmed acute respiratory infection (ARI) rates in college residence halls in College Park, Maryland Abstract Strategies to protect building occupants from the risk of acute respiratory infection (ARI) need to consider ventilation for its ability to dilute and remove indoor bioaerosols. Prior studies have described an association of increased self-reported colds and influenza-like symptoms with low ventilation but have not combined rigorous characterization of ventilation with assessment of laboratory confirmed infections. We report a study designed to fill this gap. We followed laboratory confirmed ARI rates and measured CO2 concentrations for four months during the winter-spring of 2018 in two campus residence halls: (1) a high ventilation building (HVB) with a dedicated outdoor air system that supplies 100% of outside air to each dormitory room, and (2) a low ventilation building (LVB) that relies on infiltration as ventilation. We enrolled 11 volunteers for a total of 522 person-days in the HVB and 109 volunteers for 6069 person-days in the LVB, and tested upper-respiratory swabs from symptomatic cases and their close contacts for the presence of 44 pathogens using a molecular assay. We observed one ARI case in the HVB (0.70/person-year) and 47 in the LVB (2.83/person-year). Simultaneously, 154 CO2 sensors distributed primarily in the dormitory rooms collected 668,390 useful data points from over 1 million recorded data points. Average and standard deviation of CO2 concentrations were 1230 ppm and 408 ppm in the HVB, and 1492 ppm and 837 ppm in the LVB, respectively. Importantly, this study developed and calibrated multi-zone models for the HVB with 229 zones and 983 airflow paths, and for the LVB with 529 zones and 1836 airflow paths by using a subset of CO2 data for model calibration. The models were used to calculate ventilation rates in the two buildings and potential for viral aerosol migration between rooms in the LVB. With doors and windows closed, the average ventilation rate was 12 L/s in the HVB dormitory rooms and 4 L/s in the LVB dormitory rooms. As a result, residents had on average 6.6 L/(s person) of outside air in the HVB and 2.3 L/(s person) in the LVB. LVB rooms located at the leeward side of the building had smaller average ventilation rates, as well as a somewhat higher ARI incidence rate and average CO2 concentrations when compared to those values in the rooms located at the windward side of the building. Average ventilation rates in twenty LVB dormitory rooms increased from 2.3 L/s to 7.5 L/s by opening windows, 3.6 L/s by opening doors, and 8.8 L/s by opening both windows and doors. Therefore, opening both windows and doors in the LVB dormitory rooms can increase ventilation rates to the levels comparable to those in the HVB. But it can also have a negative effect on thermal comfort due to low outdoor temperatures. Simulation results identified an aerobiologic pathway from a room occupied by an index case of influenza A to a room occupied by a possible secondary case.

negative: Impact of Hajj on Global Health Security With the human society transfers from scattered pieces to a society as a whole and the advent of the aviation era, the occurrence of infectious diseases and their diffusion have led to international health security issues. As the world’s largest and irrevocable annual transnational religious movement, the Hajj and its connection with health security concerns have caught attention since the ancient times, because a huge population from all over the world gathers in the holy city of Mecca, which has tropical arid climate. Currently, the international community and international organizations are implementing multilevel governance with respect to the health security issues of the Hajj. Relevant agencies include the World Health Organization and its regional branches, International Red Cross and Red Crescent Movement (ICRC), the Ministry of Hajj as well as the Ministry of Health of Saudi Arabia, and the public health sectors/agencies in various countries that are involved with Hajj activities. The international community has successfully held the Hajj events, even when facing the challenges brought by some viral respiratory diseases such as SARS and MERS. The Hajj has become a rare opportunity for all stakeholders to improve their capabilities in international health security governance.

negative: Chapter 9 Pathogenic agents Publisher Summary This chapter describes the pathogens of humans, animals, and plants that may be present in organic wastes. The recycling of biological wastes by aerobic or anaerobic biotechnological treatment is necessary to protect the environment and to save natural resources. The recycling process may be conducted either in large-scale plants operated mostly in urban industrial areas, or in small plants operated primarily in the rural environment to improve the farmer's income. A relatively large number of pathogens are found in solid and liquid organic wastes and the most prevalent are bacteria, viruses, fungi, and parasites. Fungi present in wastes and materials used for composting are mainly of interest from the point of view of occupational health and phytohygiene. The presence of parasites or their infective stages in wastes or residues of plant, animal, or human origin depends on the nature of the wastes and the level of pretreatment. Parasites are of veterinary and medical importance if the raw materials used for composting are generated in wastewater treatment facilities or in slaughterhouses. Plant pathogenic parasites must also be considered, even if some of them are highly specialized on certain plants, which limit their epidemiological importance. Cyst-forming nematodes are the most relevant because these cysts may survive in the soil for several years.

negative: Discontinuous and non-discontinuous subgenomic RNA transcription in a nidovirus Arteri-, corona-, toro- and roniviruses are evolutionarily related positive-strand RNA viruses, united in the order Nidovirales. The best studied nidoviruses, the corona- and arteriviruses, employ a unique transcription mechanism, which involves discontinuous RNA synthesis, a process resembling similarity-assisted copy-choice RNA recombination. During infection, multiple subgenomic (sg) mRNAs are transcribed from a mirror set of sg negative-strand RNA templates. The sg mRNAs all possess a short 5′ common leader sequence, derived from the 5′ end of the genomic RNA. The joining of the non-contiguous ‘leader’ and ‘body’ sequences presumably occurs during minus-strand synthesis. To study whether toroviruses use a similar transcription mechanism, we characterized the 5′ termini of the genome and the four sg mRNAs of Berne virus (BEV). We show that BEV mRNAs 3–5 lack a leader sequence. Surprisingly, however, RNA 2 does contain a leader, identical to the 5′-terminal 18 residues of the genome. Apparently, BEV combines discontinuous and non-discontinous RNA synthesis to produce its sg mRNAs. Our findings have important implications for the understanding of the mechanism and evolution of nidovirus transcription.

negative: Some One Health based control strategies for the Middle East respiratory syndrome coronavirus The Middle East respiratory syndrome coronavirus (MERS-CoV) presents an ideal example for developing One Health concepts. Dromedary camels are the principal reservoir for the virus. Infected camels shed the virus in body secretions, particularly nasal discharges. MERS-CoV has the potential to remain active in the environment for some time under optimum conditions of temperature and humidity. This shedding sustains the virus in endemic communities and thus contact with camels is considered a major risk factor for human infection. Reducing virus shedding from camels will have a great positive impact on reducing the human risk of infection. Our main objective is to highlight the potential aspects of reducing virus shedding from camels to the environment, thereby reducing the possibility of human infection. We will focus on the potential roles of camel markets, camel shows, importation, transportation and grazing in the amplification and shedding of the virus, providing some novel concepts for the control approaches for the MERS-CoV.

negative: COVID19-Tracker: A shiny app to produce comprehensive data visualization for SARS-CoV-2 epidemic in Spain Data visualization is an essential tool for exploring and communicating findings in medical research, and especially in epidemiological surveillance. The COVID19-Tracker web application systematically produces daily updated data visualization and analysis of the SARS-CoV-2 epidemic in Spain. It collects automatically daily data on COVID-19 diagnosed cases, intensive care unit admissions, and mortality, from February 24th, 2020 onwards. Two applications have already been developed; 1) to analyze data trends and estimating short-term projections; 2) to estimate the case fatality rate, and; 3) To assess the effect of the lockdown measures on the trends of incident data. The application may help for a better understanding of the SARS-CoV-2 epidemic data in Spain.

negative: COVID-19 transmission in Mainland China is associated with temperature and humidity: A time-series analysis Abstract COVID-19 has become a pandemic. The influence of meteorological factors on the transmission and spread of COVID-19 is of interest. This study sought to examine the associations of daily average temperature (AT) and relative humidity (ARH) with the daily count of COVID-19 cases in 30 Chinese provinces (in Hubei from December 1, 2019 to February 11, 2020 and in other provinces from January 20, 2020 to Februarys 11, 2020). A Generalized Additive Model (GAM) was fitted to quantify the province-specific associations between meteorological variables and the daily cases of COVID-19 during the study periods. In the model, the 14-day exponential moving averages (EMAs) of AT and ARH, and their interaction were included with time trend and health-seeking behavior adjusted. Their spatial distributions were visualized. AT and ARH showed significantly negative associations with COVID-19 with a significant interaction between them (0.04, 95% confidence interval: 0.004–0.07) in Hubei. Every 1 °C increase in the AT led to a decrease in the daily confirmed cases by 36% to 57% when ARH was in the range from 67% to 85.5%. Every 1% increase in ARH led to a decrease in the daily confirmed cases by 11% to 22% when AT was in the range from 5.04 °C to 8.2 °C. However, these associations were not consistent throughout Mainland China.

negative: Knowledge and Beliefs towards Universal Safety Precautions to flatten the curve during Novel Coronavirus Disease (nCOVID-19) Pandemic among general Public in India: Explorations from a National Perspective Background: The novel Coronavirus disease (COVID-19) is being considered as the most serious health threat that the world has never witnessed in the recent times and significantly affecting the daily routine of mankind by emerging as a global pandemic. Yet, as there is no treatment nor a vaccine that was approved so far, universal safety precautions (USPs) and mitigating strategies are the only way to deal with this emergency crisis. However, knowledge and beliefs towards USPs among the general public in countries such as India with a large population are lacking. Methods: A prospective, cross-sectional, web-based online survey was conducted among the general public in India during March 2020. A 20-items self-administered survey questionnaire was developed and randomly distributed among the public using google document forms through social media networks. Descriptive statistics were used in representing the study characteristics, and the Chi-square test was used in assessing the associations among the study variables with a p-value of < 0.05 was considered as statistically significant. Results: Of 1287 participants, 1117 have given their consent of willingness and completed the questionnaire with a response rate of 86.8%. The mean age of the study participants was 28.8 ± 10.9 years, where the majority of them belong to the age category <25 years, and sex was equally distributed. Based upon the socio-demographic information, the majority were post-graduates (32.9%), professional job holders (45%) and belonged to the upper-middle (40%) economic class. Overall, the knowledge and beliefs towards USPs and mitigating strategies among participants varied between moderate to high, with statistically significant associations with their socio-demographic characteristics. Conclusions: Although the knowledge and beliefs of the general public in India towards USPs are encouraging, there is a need for long-term educational interventions as the dynamics and severity of COVID-19 have been changing day-by-day rapidly. The findings of this study could guide the public health authorities in making and implementing decisions to combat this pandemic. Keywords: Coronavirus, COVID-19, outbreak, Pandemic, universal precautions, SARS-CoV-2.

negative: Differentiation of transmissible gastroenteritis virus from porcine respiratory coronavirus and other antigenically related coronaviruses by using cDNA probes specific for the 5' region of the S glycoprotein gene. Two cDNA clones prepared from the virulent Miller strain of transmissible gastroenteritis virus (TGEV) were identified, and their nucleotide sequences were determined. The clones were nonoverlapping and located in the 5' region of the S glycoprotein gene. Their nucleotide and predicted amino acid sequences were compared with published sequences of the attenuated Purdue strain of TGEV and feline infectious peritonitis virus (FIPV). TGEV clone pE21 contained 381 bp of the S glycoprotein gene and had greater than 98% nucleotide and amino acid sequence homology with Purdue TGEV and over 87% nucleotide and amino acid sequence homology with FIPV. TGEV clone pD24 contained 267 bp of the S glycoprotein gene. It had greater than 98% nucleotide and amino acid sequence homology with Purdue TGEV but only 54% nucleotide sequence homology and 24% amino acid sequence homology with FIPV. A probe prepared from pD24 could differentiate TGEV from porcine respiratory coronavirus and other antigenically related coronaviruses, FIPV, feline enteric coronavirus, and canine coronavirus in a dot blot hybridization assay.

negative: Critical Differences between the Binding Features of the Spike Proteins of SARS-CoV-2 and SARS-CoV [Image: see text] The COVID-19 caused by SARS-CoV-2 has spread globally and caused tremendous loss of lives and properties, and it is of utmost urgency to understand its propagation process and to find ways to slow down the epidemic. In this work, we used a coarse-grained model to calculate the binding free energy of SARS-CoV-2 or SARS-CoV to their human receptor ACE2. The investigation of the free energy contribution of the interacting residues indicates that the residues located outside the receptor binding domain are the source of the stronger binding of the novel virus. Thus, the current results suggest that the essential evolution of SARS-CoV-2 happens remotely from the binding domain at the spike protein trimeric body. Such evolution may facilitate the conformational change and the infection process that occurs after the virus is bound to ACE2. By studying the binding pattern between SARS-CoV antibody m396 and SARS-CoV-2, it is found that the remote energetic contribution is missing, which might explain the absence of cross-reactivity of such antibodies.

negative: ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection Purpose Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. Methods We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. Results Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. Conclusions Together, these results indicate that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.

negative: Does COVID-19 Spread Through Droplets Alone?

negative: The role of virtual support groups for patients with hidradenitis suppurativa during the COVID-19 pandemic

negative: An Opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory Syndrome Coronavirus The human coronaviruses (CoV) include HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, some of which have been known for decades. The severe acute respiratory syndrome (SARS) CoV briefly emerged into the human population but was controlled. In 2012, another novel severely human pathogenic CoV—the Middle East Respiratory Syndrome (MERS)-CoV—was identified in the Kingdom of Saudi Arabia; 80% of over 2000 human cases have been recorded over five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world’s surveillance and response capabilities, and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded, but it remains unclear whether there is any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation, and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.

negative: Homeless problems in Taiwan: Looking beyond legality toward social issues Abstract Encouraged by the public policy, citizens in Taiwan have traditionally enjoyed a high percentage of home ownership. Therefore, it has been perplexing and enigmatic to witness the growing homeless population sleeping outside in public areas in recent years. Public actions have been called for to deal with the problem. However, the approach of these public actions has depended on how the problem of homelessness has been defined. This paper presents a historical context of how homelessness has been presented in policy discourses. Further, on the basis of a survey conducted in 2004, this paper describes the profile of the homeless and discusses why the homeless began sleeping on the streets. Finally, an outreach worker narrates his story about working with the homeless in Taipei City, the capital of Taiwan. The paper also includes policy implications in terms of appropriate public actions to be taken in response to the homelessness problem in Taiwan.

negative: Le virus influenza, le SARS-CoV2 et les voies aériennes : mise au point pour l’Otorhinolaryngologiste Résumé Le virus influenza et le SARS-CoV2 provoquent des infections respiratoires hautes banales et basses sévères (Virus influenza 290 000 à 650 000 décès/an). Ces virus entrent en contact avec les voies aériennes soit par projection directe, soit par inhalation secondaire de gouttelettes en suspension dans l’air, soit par manuportage. L’objectif de cet article est de faire une mise au point sur les mécanismes de production et de pénétration des gouttelettes de sécrétions, émises lors de tous les phénomènes expiratoires, susceptibles de transporter ces virus et venir au contact de la muqueuse respiratoire. Les gouttelettes > 5 µm suivent les lois de la balistique, celles < 5 µm suivent le mouvement Brownien et restent en suspension dans l’air. Les aérosols de gouttelettes sont hétérogènes que le sujet soit sain ou malade. En période infectieuse, les gouttelettes ne contiennent pas toutes de l’ARN viral. Si ces ARNs sont détectables autour des patients, sur les surfaces et dans l’air ambiant à des distances variables selon les études (de 0,5 m jusqu’au-delà de la chambre du patient) cela ne préjuge pas du caractère infectieux (viabilité) du virus et de la dose minimale infectieuse. Il y a un décalage entre la période de contagiosité et celle de la détection de l’ARN. Enfin, si des gouttelettes sont inhalées, elles devront suivre les lois de la dynamique des fluides (filtration) pour se déposer dans l’arbre respiratoire. Tout ceci explique pour partie la contagiosité et l’expression clinique de ces virus de la fente olfactive aux alvéoles pulmonaires.

negative: Ebola virus disease: a highly fatal infectious disease reemerging in West Africa Abstract Ebolavirus can cause a highly fatal and panic-generating human disease which may jump from bats to other mammals and human. High viral loads in body fluids allow efficient transmission by contact. Lack of effective antivirals, vaccines and public health infrastructures in parts of Africa make it difficult to health workers to contain the outbreak.

negative: Gastroenteritis Acute gastroenteritis is an infectious disease of the alimentary tract that may be caused by one or more bacterial, viral, or protozoal pathogens producing damage, either structural or functional, of variable extent and severity to the mucosa. Acute gastroenteritis is a very common diagnosis in pediatric practices. It is usually a clinical diagnosis. Its most common symptoms are acute vomiting and diarrhea. The most important acute complication of gastroenteritis is dehydration, which occurs when the child's overall output of fluid exceeds input. Insensible water loss is the volume of fluid that leaves the body as a result of the difference in vapor pressure between the skin and lung surfaces and the surrounding atmosphere. The small intestine is the organ principally affected in most children by gastroenteritis but the stomach and colon may also be involved to a varying extent. Most often acute gastroenteritis is a self-limiting illness and may result in full recovery after 24 hours.

negative: Estimating the distribution of the incubation period of 2019 novel coronavirus (COVID-19) infection between travelers to Hubei, China and non-travelers Objectives: Amid the continuing spread of the novel coronavirus (COVID-19), the incubation period of COVID-19 should be regularly re-assessed as more information is available upon the increase in reported cases. The present work estimated the distribution of incubation periods of patients infected in and outside Hubei province of China. Methods: Clinical data were collected from the individual cases reported by the media as they were not fully available on the official pages of the Chinese health authorities. MLE was used to estimate the distributions of the incubation period. Results: It was found that the incubation period of patients with no travel history to Hubei was longer and more volatile. Conclusion: It is recommended that the duration of quarantine should be extended to at least 3 weeks.

negative: Low serum 25-hydroxyvitamin D levels are associated with increased risk of viral coinfections in wheezing children

negative: Application of a portable instrument for rapid and reliable detection of SARS‐CoV‐2 infection in any environment The ongoing outbreak of the novel coronavirus (SARS‐CoV‐2) infection is creating serious challenges for health laboratories that seek to identify viral infections as early as possible, optimally at the earliest appearance of symptom. Indeed, there is urgent need to develop and deploy robust diagnostic methodologies not only to use in health laboratory environments but also directly in places where humans circulate and spread the virus such as airports, trains, boats, and any public aggregation places. The success of a reliable and sensitive asymptomatic diagnosis relies on the identification and measurement of informative biomarkers from human host and virus in a rapid, sensitive, and inexpensive manner. The objective of this article is to describe an innovative multidisciplinary approach to develop an efficient, inexpensive, and easy‐to‐use portable instrument (bCUBE(®) by Hyris Ltd) that can be employed as a surveillance system for the emergency caused by SARS‐CoV‐2. A solution for Coronavirus testing, compliant with CDC guidelines, is scheduled to be released in the next weeks. In addition, we will describe a workflow and path of an integrated multi‐omic approach that will lead to host and pathogen biomarker discovery in order to train the instrument to provide reliable results based on a specific biomarker's fingerprint of SARS‐CoV‐2 infection.

negative: Genetic diversity of MERS-CoV spike protein gene in Saudi Arabia Abstract Background Middle East respiratory syndrome coronavirus (MERS-CoV) was primarily detected in 2012 and still causing disease in human and camel. Camel and bats have been identified as a potential source of virus for disease spread to human. Although, significant information related to MERS-CoV disease, spread, infection, epidemiology, clinical features have been published, A little information is available on the sequence diversity of Spike protein gene. The Spike protein gene plays a significant role in virus attachment to host cells. Recently, the information about recombinant MERS-CoV has been published. So, this work was designed to identify the emergence of any another recombinant virus in Jeddah, Saudi Arabia. Methods In this study samples were collected from both human and camels and the Spike protein gene was amplified and sequenced. The nucleotide and amino acid sequences of MERS-CoV Spike protein gene were used to analyze the recombination, genetic diversity and phylogenetic relationship with selected sequences from Saudi Arabia. Results The nucleotide sequence identity ranged from 65.7% to 99.8% among all the samples collected from human and camels from various locations in the Kingdom. The lowest similarity (65.7%) was observed in samples from Madinah and Dammam. The phylogenetic relationship formed different clusters with multiple isolates from various locations. The sample collected from human in Jeddah hospital formed a closed cluster with human samples collected from Buraydah, while camel sample formed a closed cluster with Hufuf isolates. The phylogenetic tree by using Aminoacid sequences formed closed cluster with Dammam, Makkah and Duba isolates. The amino acid sequences variations were observed in 28/35 samples and two unique amino acid sequences variations were observed in all samples analyzed while total 19 nucleotides sequences variations were observed in the Spike protein gene. The minor recombination events were identified in eight different sequences at various hotspots in both human and camel samples using recombination detection programme. Conclusion The generated information from this study is very valuable and it will be used to design and develop therapeutic compounds and vaccine to control the MERS-CoV disease spread in not only in the Kingdom but also globally.

negative: Documentary Research of Human Respiratory Droplet Characteristics() Respiratory droplet characteristics are key to determine the droplet-borne pathogen transmission, which provide scientific basis for formulating the disease prevention from droplet transmission and control measures. Through studying the data information from existing documents, this paper gives the respiratory droplet characteristics, like size, concentration, velocity, etc. Meanwhile, droplet evaporation, droplet-borne pathogen activity and their transmission are discussed. The droplet size is no significant difference with human health level, gender and age. The size of droplets produced by health people is between 0.1 and 10 μm, it produced by patients is between 0.05 and 10 μm, and the patients’ droplet concentration is higher. The coughed droplet concentrations change with the size into a peak rule. The velocity of the cough droplets is the biggest, the range of 10 to 25m/s, the transmission distance is more than 2m.

negative: 89 Severe Acute Respiratory Syndrome (SARS) Abstract Severe acute respiratory syndrome (SARS) first appeared in November 2002 and ultimately resulted in 8096 probable human infections and 774 deaths worldwide. By July 2003, the global outbreak was declared over. A new coronavirus, SARS-associated coronavirus (SARS-CoV), was identified as the causative agent; this virus appeared to have a zoonotic origin, as genetically similar coronaviruses have been identified in several animal species. The global response to the outbreak was extensive. Within a short period, the pathogen had been identified, new diagnostic tests were developed, surveillance systems were created, infection control and prevention measures were instituted, and transmission among humans stopped. It is unclear if and when person-to-person SARS-CoV transmission will reappear. However, procedures have been established by public health organizations, including the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), to help guide diagnosis, reporting, surveillance, and prevention.

negative: Sharing public health data and information across borders: lessons from Southeast Asia BACKGROUND: The importance of data and information sharing for the prevention and control of infectious diseases has long been recognised. In recent years, public health emergencies such as avian influenza, drug-resistant malaria, and Ebola have brought renewed attention to the need for effective communication channels between health authorities, particularly in regional contexts where neighbouring countries share common health threats. However, little empirical research has been conducted to date to explore the range of factors that may affect the transfer, exchange, and use of public health data and expertise across borders, especially in developing contexts. METHODS: To explore these issues, 60 interviews were conducted with domestic and international stakeholders in Cambodia and Vietnam, selected amongst those who were involved in regional public health programmes and networks. Data analysis was structured around three categories mapped across the dataset: (1) the nature of shared data and information; (2) the nature of communication channels; and (3) how information flow may be affected by the local, regional, and global system of rules and arrangements. RESULTS: There has been a great intensification in the circulation of data, information, and expertise across borders in Southeast Asia. However, findings from this study document ways in which the movement of data and information from production sites to other places can be challenging due to different standards and practices, language barriers, different national structures and rules that govern the circulation of health information inside and outside countries, imbalances in capacities and power, and sustainability of financing arrangements. CONCLUSIONS: Our study highlights the complex socio-technical nature of data and information sharing, suggesting that best practices require significant involvement of an independent third-party brokering organisation or office, which can redress imbalances between country partners at different levels in the data sharing process, create meaningful communication channels and make the most of shared information and data sets.

negative: Coronavirus envelope protein: current knowledge BACKGROUND: Coronaviruses (CoVs) primarily cause enzootic infections in birds and mammals but, in the last few decades, have shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. A renewed interest in coronaviral research has led to the discovery of several novel human CoVs and since then much progress has been made in understanding the CoV life cycle. The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis. Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins. MAIN BODY: This review aims to establish the current knowledge on CoV E by highlighting the recent progress that has been made and comparing it to previous knowledge. It also compares E to other viral proteins of a similar nature to speculate the relevance of these new findings. Good progress has been made but much still remains unknown and this review has identified some gaps in the current knowledge and made suggestions for consideration in future research. CONCLUSIONS: The most progress has been made on SARS-CoV E, highlighting specific structural requirements for its functions in the CoV life cycle as well as mechanisms behind its pathogenesis. Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates. The high mortality rate of certain CoVs, along with their ease of transmission, underpins the need for more research into CoV molecular biology which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.

negative: Some actions for behavior analyst licensing bodies to consider in response to the COVID‐19 pandemic The COVID‐19 global pandemic has had a significant impact on the practice of applied behavior analysis (ABA). Practitioners and caregivers have had to adapt quickly as physical distancing, stay‐at‐home orders, and shelter‐in‐place directives have become commonplace. As the field copes with the changes produced by the COVID‐19 outbreak, many behavior analytic practitioners are seeking guidance from regulatory bodies to ensure they are practicing legally and ethically. This article outlines some actions that the regulatory bodies that manage state behavior analyst licensure programs may consider to assist ABA practitioners and consumers during this unprecedented time. Additionally, suggestions are offered as to how state licensing bodies might prepare to support the practice of licensees during future events that present challenges similar to the current pandemic.

negative: Helping Couples in the Shadow of COVID‐19 The pandemic caused by the SARS‐CoV‐2 virus (coronavirus) and the associated illness, COVID‐19, has caused a level of worldwide upheaval unlike any most people now living have seen in their lifetimes. This crisis affects people in their most important, committed, and intimate relationships. Although this crisis has damaged the health and well‐being of individuals, crushed economies, and led to an extensive period of uncertainty about the future, there may also be positive outcomes in the motivation people have to protect their relationships. In this paper, we focus on strategies that therapists and relationship educators can use to help couples preserve and protect their relationships during such a time. We describe four foundations of safety that allow relationships to thrive: physical, emotional, commitment, and community. We then highlight three keys from our body of work that can help guide individuals and couples in protecting their relationships on a day‐to‐day and moment‐to‐moment basis: (1) decide, don’t slide; (2) make it safe to connect; (3) do your part.

negative: Surveillance of COVID-19 in the General Population Using an Online Questionnaire: Report From 18,161 Respondents in China BACKGROUND: The recent outbreak of the coronavirus disease (COVID-19) has become an international pandemic. So far, little is known about the role of an internet approach in COVID-19 participatory surveillance. OBJECTIVE: The aim of this study is to investigate whether an online survey can provide population-level information for observing prevalence trends during the early phase of an outbreak and identifying potential risk factors of COVID-19 infection. METHODS: A 10-item online questionnaire was developed according to medical guidelines and relevant publications. It was distributed between January 24 and February 17, 2020. The characteristics of respondents and temporal changes of various questionnaire-derived indicators were analyzed. RESULTS: A total of 18,161 questionnaires were returned, including 6.45% (n=1171) from Wuhan City. Geographical distributions of the respondents were consistent with the population per province (R(2)=0.61, P<.001). History of contact significantly decreased with time, both outside Wuhan City (R(2)=0.35, P=.002) and outside Hubei Province (R(2)=0.42, P<.001). The percentage of respondents reporting a fever peaked around February 8 (R(2)=0.57, P<.001) and increased with a history of contact in the areas outside Wuhan City (risk ratio 1.31, 95% CI 1.13-1.52, P<.001). Male sex, advanced age, and lung diseases were associated with a higher risk of fever in the general population with a history of contact. CONCLUSIONS: This study shows the usefulness of an online questionnaire for the surveillance of outbreaks like COVID-19 by providing information about trends of the disease and aiding the identification of potential risk factors.

negative: Assessing the Impact of Reduced Travel on Exportation Dynamics of Novel Coronavirus Infection (COVID-19) The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to estimate the impact of travel reduction on three epidemiological outcome measures: (i) the number of exported cases, (ii) the probability of a major epidemic, and (iii) the time delay to a major epidemic. From 28 January to 7 February 2020, we estimated that 226 exported cases (95% confidence interval: 86,449) were prevented, corresponding to a 70.4% reduction in incidence compared to the counterfactual scenario. The reduced probability of a major epidemic ranged from 7% to 20% in Japan, which resulted in a median time delay to a major epidemic of two days. Depending on the scenario, the estimated delay may be less than one day. As the delay is small, the decision to control travel volume through restrictions on freedom of movement should be balanced between the resulting estimated epidemiological impact and predicted economic fallout.

negative: SARS in Singapore: surveillance strategies in a globalising city Abstract Public health measures employed to fight against the spread of SARS need to be guided by biomedical knowledge as well as an understanding of the social science aspects of the disease. Using Singapore as a case study, we explore how the state constructs the disease and implements measures targeted at creating a ring of defense around the island and using surveillance to monitor and prevent its spread. While there is support, there is also resentment among some Singaporeans who complain that their right to privacy has been invaded and that over surveillance may have actually occurred. Marginalisation and discrimination have not only affected the local population but in this open economy which is striving to achieve global city status, businesses, tourism, foreign talent, foreign contract workers and foreign students studying in Singapore have also been negatively affected. While Singapore has been applauded by WHO and used as an example of quick and effective response, a holistic approach to the management of infectious disease must address the social implications of strategies that are drawn from medical knowledge alone because it impinges on the social lives of people and how people interact with each other under stressful circumstances.

negative: Estimates of the severity of coronavirus disease 2019: a model-based analysis BACKGROUND: In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases. METHODS: We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation. FINDINGS: Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older. INTERPRETATION: These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death. FUNDING: UK Medical Research Council.

negative: Correlation between hypophosphatemia and the severity of Corona Virus Disease 2019 patients Objective: Retrospectively analyze the clinical data of Corona Virus Disease 2019 (COVID-19) patients and explore the value of serum phosphorus level in evaluating the severity and prognosis of the disease. Methods: COVID-19 patients transferred from the first emergency ward of Taiyuan fourth people's Hospital from February 8 to March 3, 2020 were selected. The information of general conditions, clinical manifestations, laboratory indexes, nucleic acid detection and treatment were collected. The changes of blood phosphorus level and absolute value of lymphocytes in ordinary and severe/critical patients were recorded and compared. Results: A total of 32 patients with COVID-19 were collected, including 12 cases of common type and 20 cases of severe/critical type. Before treatment, the serum phosphorus levels of the two groups were significantly lower than the normal level, and the serum phosphorus levels of the severe/critical patients were lower than those of the common type patients (t = 2.767, P < 0.010). After treatment, the serum phosphorus levels of the two groups reached normal, and there was no significant difference between the two groups (t = 0.231, P > 0.819). The level of lymphocytes in severe/critical patients was lower than that in normal patients (t = 4.636, P < 0.001) before treatment. After treatment, the absolute value of lymphocytes in the two groups reached normal, and there was no significant difference between the two groups (t=1.208, P=0.237). There was a positive correlation between lymphocytes and serum phosphorus, and the correlation coefficient was 0.479. Conclusion: hypophosphatemia is related to the severity of COVID-19, and strengthening the monitoring of serum phosphorus level of COVID-19's severe/critical patients and correcting hypophosphatemia in time are of significance to improve the prognosis.

negative: Review of Artificial Intelligence Techniques in Imaging Data Acquisition, Segmentation and Diagnosis for COVID-19 (This paper was submitted as an invited paper to IEEE Reviews in Biomedical Engineering on April 6, 2020.) The pandemic of coronavirus disease 2019 (COVID-19) is spreading all over the world. Medical imaging such as X-ray and computed tomography (CT) plays an essential role in the global fight against COVID-19, whereas the recently emerging artificial intelligence (AI) technologies further strengthen the power of the imaging tools and help medical specialists. We hereby review the rapid responses in the community of medical imaging (empowered by AI) toward COVID-19. For example, AI-empowered image acquisition can significantly help automate the scanning procedure and also reshape the workflow with minimal contact to patients, providing the best protection to the imaging technicians. Also, AI can improve work efficiency by accurate delination of infections in X-ray and CT images, facilitating subsequent quantification. Moreover, the computer-aided platforms help radiologists make clinical decisions, i.e., for disease diagnosis, tracking, and prognosis. In this review paper, we thus cover the entire pipeline of medical imaging and analysis techniques involved with COVID-19, including image acquisition, segmentation, diagnosis, and follow-up. We particularly focus on the integration of AI with X-ray and CT, both of which are widely used in the frontline hospitals, in order to depict the latest progress of medical imaging and radiology fighting against COVID-19.

negative: High Temperature and High Humidity Reduce the Transmission of COVID-19 With the ongoing global pandemic of COVID-19, a question is whether the coming summer in the northern hemisphere will reduce the transmission intensity of COVID-19 with increased humidity and temperature. In this paper, we investigate this problem using the data from the cases with symptom-onset dates from January 19 to February 10, 2020 for 100 Chinese cities, and cases with confirmed dates from March 15 to April 25 for 1,005 U.S. counties. Statistical analysis is performed to assess the relationship between the transmissibility of COVID-19 and the temperature/humidity, by controlling for various demographic, socio-economic, geographic, healthcare and policy factors and correcting for cross-sectional correlation. We find a similar influence of the temperature and relative humidity on effective reproductive number (R values) of COVID-19 for both China and the U.S. before lockdown in both countries: one-degree Celsius increase in temperature reduces R value by about 0.023 (0.026 (95% CI [-0.0395,-0.0125]) in China and 0.020 (95% CI [-0.0311, -0.0096]) in the U.S.), and one percent relative humidity rise reduces R value by 0.0078 (0.0076 (95% CI [-0.0108,-0.0045]) in China and 0.0080 (95% CI [-0.0150,-0.0010]) in the U.S.). If assuming a 30 degree and 25 percent increase in temperature and relative humidity from winter to summer in the northern hemisphere, we expect the R values to decline about 0.89 (0.69 by temperature and 0.20 by humidity). Given the notion that the non-intervened R values are around 2.5 to 3, only weather factors cannot make the R values below their critical condition of R<1, under which the epidemic diminishes gradually. Therefore, public health intervention such as social distancing is crucial to block the transmission of COVID-19 even in summer.

negative: Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.

negative: World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Abstract An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.

negative: Preventing respiratory illness in older adults aged 60 years and above living in long-term care: A rapid overview of reviews Background: The overall objective of this rapid overview of reviews (overview hereafter) was to identify evidence from systematic reviews (SRs) for infection control and prevention practices for adults aged 60 years and older in long-term care settings. Methods: Comprehensive searches in MEDLINE, EMBASE, the Cochrane Library, biorxiv.org/medrxiv.org, clinicaltrials.gov and the Global Infectious Disease Epidemiology Network (GIDEON) were carried out in early March 2020. Title/abstract and full-text screening, data abstraction, and quality appraisal (AMSTAR 2) were carried out by single reviewers. Results: A total of 6 SRs published between 1999 and 2018 were identified and included in the overview. The SRs included between 1 and 37 primary studies representing between 140 to 908 patients. All of the primary studies included in the SRs were carried out in long-term care facilities (LTCF) and examined pharmacological, non-pharmacological, or combined interventions. One high quality SR found mixed results for the effectiveness of hand hygiene to prevent infection (2 studies statistically significant positive results, 1 study non-statistically significant results). One moderate quality SR with meta-analysis found a moderate non-statistically significant effect for personal protective equipment (PPE) in preventing infection and found no statistically significant results for the effectiveness of social isolation. One moderate quality SR reported statically significant evidence for the effectiveness of amantadine and amantadine + PPE to prevent infection with respiratory illness in LTCF. Conclusion: The current evidence suggests that with antiviral chemoprophylaxis with adamantine is effective in managing respiratory illness in residents of long-term care facilities. The rest of the strategies can be used in long-term care facilities, yet have limited evidence supporting their use from systematic reviews.

negative: Harmonizing the COVID-19 cacophony: People need guidance

negative: Human Saliva: Non-Invasive Fluid for Detecting Novel Coronavirus (2019-nCoV) The breakthrough of novel coronavirus (2019-nCoV) in Wuhan, a city of China, has damaged the status of health and quality of life. In the sequel of this epidemic or contagious disease, the patient experiences fever, chest paint, chills, a rapid heartbeat, breathing difficulties, pneumonia, and kidney failure. It has been suggested that this disease can spread through human-to-human transmission or by super spreading. By the help of the non-invasive fluid “saliva”, it is easy to detect the virus. This can help with the comfort of the patient as well as healthcare personnel. Under this perspective, we discuss the epidemic situation of 2019-nCOV and its relationship with human saliva.

negative: Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, initially termed 2019-nCoV and subsequently SARS-CoV-2. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.

negative: And now for something completely different: from 2019-nCoV and COVID-19 to 2020-nMan

negative: Middle East respiratory syndrome The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.

negative: Cats, coronaviruses and coronavirus antibody tests Feline infectious peritonitis and other coronavirus infections of cats are briefly reviewed. Interpretation and applications of feline coronavirus antibody tests are described, and general recommendations are provided for practitioners. Some of the major unresolved questions regarding coronavirus infections of cats are delineated.

negative: Induction of caspase-dependent apoptosis in cultured rat oligodendrocytes by murine coronavirus is mediated during cell entry and does not require virus replication. Murine coronavirus mouse hepatitis virus (MHV) causes demyelination of the central nervous system (CNS) in rats and mice. Apoptotic oligodendrocytes have been detected in the vicinity of the CNS demyelinating lesions in these animals. However, whether MHV can directly induce oligodendrocyte apoptosis has not been documented. Here, we established a rat oligodendrocyte culture that is morphologically and phenotypically indistinguishable from the primary rat oligodendrocytes. Using this culture, we showed that mature rat oligodendrocytes were permissive to MHV infection but did not support productive virus replication. Significantly, oligodendrocytes infected with both live and ultraviolet light-inactivated viruses underwent apoptosis to a similar extent, which was readily detectable at 24 h postinfection as revealed by apoptotic bodies and DNA fragmentation, indicating that MHV-induced apoptosis is mediated during the early stages of the virus life cycle and does not require virus replication. Prior treatment of cells with the lysosomotropic agents NH(4)Cl and chloroquine as well as the vacuolar proton pump-ATPase inhibitor bafilomycin A1, all of which block the acidification of the endosome, prevented oligodendrocytes from succumbing to apoptosis induced by MHV mutant OBLV60, which enters cells via endocytosis, indicating that fusion between the viral envelope and cell membranes triggers the apoptotic cascade. Treatment with the pan-caspase inhibitor Z-VAD-fmk blocked MHV-induced apoptosis, suggesting an involvement of the caspase-dependent pathway. Our results, thus, for the first time provide unequivocal evidence that infection of oligodendrocytes with MHV directly results in apoptosis. This finding provides an explanation for the destruction of oligodendrocytes and the damage of myelin sheath in MHV-infected CNS and suggests that oligodendrocyte apoptosis may be one of the underlying mechanisms for the pathogenesis of MHV-induced demyelinating diseases in animals.

negative: Early Prediction of Disease Progression in 2019 Novel Coronavirus Pneumonia Patients Outside Wuhan with CT and Clinical Characteristics Objective: To determine the predictive value of CT and clinical characteristics for short-term disease progression in patients with 2019 novel coronavirus pneumonia (NCP). Materials and Methods: 224 patients with confirmed 2019 novel coronavirus (COVID-19) infection outside Wuhan who had chest CT examinations were retrospectively screened. Clinical data were obtained from electronic medical records. CT images were reviewed and scored for lesion distribution, lobe and segment involvement, ground-glass opacities, consolidation, and interstitial thickening. All included patients with moderate NCP were observed for at least 14 days from admission to determine whether they exacerbated to severe NCP (progressive group) or not (stable group). CT and clinical characteristics between the two groups were compared, and multivariate logistic regression and sensitivity analyses were performed to identify the risk factors for developing severe NCP. Results: A total of 141 patients with moderate NCP were included, of which 15 (10.6%) patients developed severe NCP during hospitalization and assigned to the progressive group. Multivariate logistic regression analysis showed that higher neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] and 95% confidence interval [CI], 1.26 [1.04-1.53]; P = 0.018) and CT severity score (OR and 95% CI, 1.25 [1.08-1.46]; P = 0.004) on admission were independent predictors for progression to severe NCP, and sensitivity analysis confirmed the consistent results in nonimported patients but not in imported patients. However, no significant difference in lung involvement was found on CT between imported and nonimported patients (all P > 0.05). Patients who were admitted more than 4 days from symptom onset tended to have more severe lung involvement. Spearman correlation analysis showed the close association between CT severity score and inflammatory indexes (r = 0.17~0.47, all P < 0.05). Conclusion: CT severity score was associated with inflammatory levels and higher NLR and CT severity score on admission were independent risk factors for short-term progression in patients with NCP outside Wuhan. Furthermore, early admission and surveillance by CT should be recommended to improve clinical outcomes.

negative: Strongly heterogeneous transmission of COVID-19 in mainland China: local and regional variation Background The outbreak of novel coronavirus disease 2019 (COVID-19) started in the city of Wuhan, China, with a period of rapid initial spread. Transmission on a regional and then national scale was promoted by intense travel during the holiday period of the Chinese New Year. We studied the variation in transmission of COVID-19, locally in Wuhan, as well as on a larger spatial scale, among different cities and even among provinces in mainland China. Methods In addition to reported numbers of new cases, we have been able to assemble detailed contact data for some of the initial clusters of COVID-19. This enabled estimation of the serial interval for clinical cases, as well as reproduction numbers for small and large regions. Findings We estimated the average serial interval was 4.8 days. For early transmission in Wuhan, any infectious case produced as many as four new cases, transmission outside Wuhan was less intense, with reproduction numbers below two. During the rapid growth phase of the outbreak the region of Wuhan city acted as a hot spot, generating new cases upon contact, while locally, in other provinces, transmission was low. Interpretation COVID-19 is capable of spreading very rapidly. The sizes of outbreak in provinces of mainland China mainly depended on the numbers of cases imported from Wuhan as the local reproduction numbers were low. The COVID-19 epidemic should be controllable with appropriate interventions. Funding No specific funding.

negative: Battle against novel coronavirus 2019-nCoV: International commitment to develop worldwide informing campaigns

negative: Body temperature of free-ranging koalas (Phascolarctos cinereus) in south-east Queensland The distribution of the koala (Phascolarctos cinereus) in Queensland is predicted to contract as a result of climate change, driven by the frequency, intensity and duration of heatwaves and drought. However, little is known about the physiological responses of this species to environmental extremes under field conditions. This study aimed to establish the efficacy of surgically implanted thermal radio transmitters and data loggers to measure the body temperature of free-ranging koalas across a range of environmental conditions and ambient temperatures. Five free-ranging koalas in southeast Queensland were implanted with thermal transmitters and data loggers waxed together as a single package. Body temperatures were recorded for variable periods ranging from 3 to 12 months. Diurnal rhythms in body temperature were detected irrespective of season. The long-term diurnal body temperature peak for all koalas occurred between 16:00 and 17:00 h and body temperature was 36.7-36.9 °C, the long-term nadir occurred between 07:00 and 08:00 h and body temperature was 35.4-35.7 °C. Koala body temperatures as low as 34.2 °C and as high as 39.0 °C were recorded. Thermolability became apparent when ambient temperatures were outside the deduced thermal neutral zone for koalas (14.5-24.5 °C): heat was accumulated during the day and dissipated during the cool of the night. While this study is the first to report on body temperature of free-ranging koalas in their normal behavioural context, further investigations are necessary to determine the physiological boundaries of the thermal niche for this species, in order to better equip models that will more accurately predict the impacts of climate change on koalas.

negative: Passerine and Softbill Therapeutics Passerines (songbirds) and softbills (toucans and mynahs) are increasingly presented for veterinary care as pet owners and aviculturists recognize that successful medical and surgical treatment can be performed in these often tiny patients. Even with an increasing amount of pharmacokinetic data in birds, the use of extrapolated drug regimens continues to be a common practice for these species. The extrapolation, using allometric scaling from human, mammalian, and avian drugs to passeriformes and softbills, is complicated and limited. In this article, the choice of the therapeutic approach is discussed. Once the choice for a specific drug is made, tables help calculate the dose in milligrams per kilocalorie without using complicated formulas.

negative: An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog β-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N(4)-hydroxycytidine-5′-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.

negative: Similar environmental survival patterns of Streptococcus pyogenes strains of different epidemiologic backgrounds and clinical severity

negative: Minimising droplet and virus spread during and after tracheal extubation

negative: An update on feline infectious peritonitis: Diagnostics and therapeutics Abstract This review is concerned with what has been learned about feline infectious peritonitis (FIP) diagnostics and therapeutics since the publication of an extensive overview of literature covering the period 1963–2009. Although progress has been made in both areas, obtaining a definitive diagnosis of FIP remains a problem for those veterinarians and/or cat owners who require absolute certainty. This review will cover both indirect and direct diagnostic tests for the disease and will emphasize their limitations, as well as their specificity and sensitivity. There is still no effective treatment for FIP, although there are both claims that such therapies exist and glimmers of hope coming from new therapies that are under research. FIP has also been identified in wild felids and FIP-like disease is now a growing problem among pet ferrets.

negative: Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biological treatment and renal transplanted recipients in maintenance immunosuppressive treatment

negative: Indoor air as a vehicle for human pathogens: Introduction, objectives, and expectation of outcome Airborne spread of pathogens can be rapid, widespread, and difficult to prevent. In this international workshop, a panel of 6 experts will expound on the following: (1) the potential for indoor air to spread a wide range of human pathogens, plus engineering controls to reduce the risk for exposure to airborne infectious agents; (2) the behavior of aerosolized infectious agents indoors and the use of emerging air decontamination technologies; (3) a survey of quantitative methods to recover infectious agents and their surrogates from indoor air with regard to survival and inactivation of airborne pathogens; (4) mathematical models to predict the movement of pathogens indoors and the use of such information to optimize the benefits of air decontamination technologies; and (5) synergy between different infectious agents, such as legionellae and fungi, in the built environment predisposing to possible transmission-related health impacts of aerosolized biofilm-based opportunistic pathogens. After the presentations, the panel will address a set of preformulated questions on selection criteria for surrogate microbes to study the survival and inactivation of airborne human pathogens, desirable features of technologies for microbial decontamination of indoor air, knowledge gaps, and research needs. It is anticipated that the deliberations of the workshop will provide the attendees with an update on the significance of indoor air as a vehicle for transmitting human pathogens with a brief on what is currently being done to mitigate the risks from airborne infectious agents.

negative: Preliminary epidemiological analysis on children and adolescents with novel coronavirus disease 2019 outside Hubei Province, China: an observational study utilizing crowdsourced data Background: The outbreak of coronavirus disease 2019 (COVID-19) continues to expand across the world. Though both the number of cases and mortality rate in children and adolescents is reported to be low in comparison to adults, limited data has been reported on the outbreak with respect to pediatric patients. To elucidate information, we utilized crowdsourced data to perform a preliminary epidemiologic analysis of pediatric patients with COVID-19 Methods: In this observational study, data was collected from two open-access, line list crowdsourced online databases. Pediatric cases of COVID-19 were defined as patients ≤19 years of age with a laboratory confirmed diagnosis. The primary outcomes were case counts and cumulative case counts. Secondary outcomes included days between symptoms onset and first medical care and days between first medical care and reporting. Tertiary outcomes were rate of travel to Wuhan, rate of infected family members and rates of symptoms. Results: A total of 82 patients were included. The median age was 10 [IQR: 5-15] years. Patients from mainland China (outside Hubei) accounted for 46.3% of cases, while the remaining 53.7% of cases were international. Males and females accounted for 52.4% and 32.9% of cases, respectively, with the remaining 14.6% being designated as unknown. A male skew persisted across subgroup analyses by age group (p=1.0) and location (inside/outside China) (p=0.22). While the number of reported international cases has been steadily increasing over the study period, the number of reported cases in China rapidly decreased from the start point. The median reporting delay was 3 [IQR: 2-4.8] days. The median delay between symptom onset and first seeking medical care was 1 [IQR: 0-3.25] day. In international cases, time to first seeking medical care was a median of 2.5 days longer than in China (p=0.04). When clinical features were reported, fever was the most common presentation (68.0%), followed by cough (36.0%). Conclusions: The number of reported international pediatric COVID-19 cases is rapidly increasing. COVID-19 infections are, to-date, more common in males than females in both the children and adolescent age groups. Additionally, this male predominance remains the case both inside and outside of China. Crowdsourced data enabled early analysis of epidemiologic variables in pediatric patients with COVID-19. Further data sharing is required to enable analyses that are required to understand the course of this infection in children.

negative: Inhibition of SARS-CoV-2 infection (previously 2019-nCoV) by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be confirmed. Therefore, we herein used a SARS-CoV-2 spike (S) protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed plasma membrane fusion capacity superior to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. We then generated a series of lipopeptides and found that the EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than that of EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, potently inhibiting replication of 4 live human coronaviruses, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by currently circulating SARS-CoV-2 and emerging SARSr-CoVs.

negative: Reply to Notes and Comments on “Proposed Approach 1 for Re-using Surgical Masks in COVID-19 Pandemic”

negative: Potential T-cell and B-cell Epitopes of 2019-nCoV As of early March, 2019-nCoV has infected more than one hundred thousand people and claimed thousands of lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 and has high similarity with SARS-CoV. No approved vaccine yet exists for any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein receptor binding domain. Based on these findings, the spike protein is likely immunogenic and a potential vaccine candidate. We validated our computational pipeline with SARS-CoV experimental data. The novel coronavirus 2019-nCoV has affected more than 100 countries and continues to spread. There is an immediate need for effective vaccines that contain antigens which trigger responses from human T-cells and B-cells (known as epitopes). Here we identify potential T-cell epitopes through an analysis of human antigen presentation, as well as B-cell epitopes through an analysis of protein structure. We identify a list of top candidates, including an epitope located on 2019-nCoV spike protein that potentially triggers both T-cell and B-cell responses. Analyzing 68 samples, we observe that viral mutations are more likely to happen in regions with strong antigen presentation, a potential form of immune evasion. Our computational pipeline is validated with experimental data from SARS-CoV.

negative: Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020 A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6–7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.

negative: Respuesta a la carta: Crisis Sanitaria COVID-19: el papel de un cirujano

negative: Coronavirus disease 2019 (COVID-19): current status and future perspectives ABSTRACT Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.

negative: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain Coronaviruses have developed various measures to evade innate immunity. We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. M protein from human coronavirus HKU1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response.

negative: Introduction: A Short History of Virology Viral infections have been recorded unknowingly from the beginning of recorded history. The ancient Greeks and Romans described plagues of unknown origin. In general, infections were blamed on sins and punishment, balances of “vital humors” or on “miasma,” (rotten smells). In the sixteenth century, Girolamo Fracastoro suggested that infectious agents might spread disease, as did Agostino Bassi, studying diseases of silkworms. The development of the microscope by Hook and Van Leeuwenhoek in the seventeenth century led to the discovery of a new living world inhabited by very small creatures. Edward Jenner in England demonstrated that smallpox, a dreaded disease, could be prevented by inoculation with an organism that caused pockmarks on cows and dairymaids; this was the beginning of the concept of vaccination. Louis Pasteur proved that fermentation only occurred in the presence of air and was due to microorganisms. Pasteur and Pierre Roux, a colleague, as well as Jacob Henle and Robert Koch, proved that germs caused bacterial diseases such as anthrax and tuberculosis; Pasteur and Roux developed a vaccine against rabies by passaging the infectious material through rabbits. By the end of the nineteenth century it had been established that most infectious diseases were the result of germs. In parallel with this research, plant scientists had isolated material that passed through a low pore filter that was infectious to tobacco plants. This was called a “virus,” from the Latin for poison. Viruses were also found to be associated with leukemia and other cancers of chickens. The twentieth century saw the discovery of bacteriophage, viruses that attack bacteria, and the use of such bacteriophage to launch studies of molecular biology, and DNA and RNA structure.

negative: SARS‐CoV‐2: At the Crossroad Between Aging and Neurodegeneration The recent global severe acute respiratory distress syndrome coronavirus 2 pandemic is changing the world we live in. As we learn about the virus and the pandemic, it is becoming evident that it is an age-associated problem that affects the human population. Severe acute respiratory distress syndrome coronavirus 2 is one of seven coronaviruses known to infect humans. These are large enveloped non-segmented positive-sense RNA viruses. Our knowledge of severe acute respiratory distress syndrome coronavirus 2 is extremely recent but is growing daily. There are currently no antiviral treatments against the virus or vaccines for its prevention. The long term consequences of the infection on human health remain uncertain but extrapolations can be made about the potential effects of the virus on cellular lifespan as well as on organismal healthspan. Here, we posit that severe acute respiratory distress syndrome coronavirus 2 infection may, in the long-term, lead to accelerated aging phenotypes in survivors, not only in affected tissues but also in other organs, including the brain. Since some of the effects could manifest months or years after infection, it will be necessary to follow carefully people affected by coronavirus disease 2019. Keeping accurate registries may enable us to, in the future, establish connections with aging-associated disorders, such as Parkinson's disease and other neurodegenerative disorders. This article is protected by copyright. All rights reserved.

negative: Coronaviruses Coronaviruses of humans were first identified more than 60 years ago from individuals with respiratory infections, mainly mild. Two different viruses, 229E and OC43 were initially recognized. Because of difficulty in isolating them using standard techniques, many of the early studies of their occurrence were seroepidemiologic. They were confirmed to be worldwide in distribution, and, in the North Temperate Zone, mainly occurring in the winter season. With the development of the reverse transcriptase polymerase chain reaction (PCR) technique, two additional distinct viruses have been identified, HKU1 and NL63. The four viruses have now been recognized as important in the etiology of common respiratory infections, second only to the rhinoviruses. In 2002, a previously unrecognized betacoronavirus emerged from a zoonotic reservoir in Southern China and spread during the following year to several major cities of the world. The resulting illness was termed Severe Acute Respiratory Syndrome (SARS) because of its potential lethality. More than 8,000 probable cases were reported during 2003, mainly from Hong Kong and mainland China, producing social and economic disruption in those areas affected. A constant feature of the outbreak was the importance of nosocomial spread. In spite of an estimated basic reproductive number higher than influenza, the outbreak was ended, in large part because of control of in-hospital transmission. In 2012, another betacoronavirus has emerged in the Arabian peninsula which is producing a somewhat similar illness, termed Middle East Respiratory Syndrome (MERS), also marked by extensive nosocomial transmission. The outcome of this emergence is currently unknown.

negative: The COVID-19 Pandemic: Effects on Low- and Middle-Income Countries Coronavirus Disease 2019 (COVID-19) is spreading rapidly around the world with devastating consequences on patients, health care workers, health systems, and economies. As it reaches low- and middle-income countries, its effects could be even more dire, because it will be difficult for them to respond aggressively to the pandemic. There is a great shortage of all health care providers, who will be at risk due to a lack of personal protection equipment. Social distancing will be almost impossible. The necessary resources to treat patients will be in short supply. The end result could be a catastrophic loss of life. A global effort will be required to support faltering economies and health care systems.

negative: Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19) that has resulted in a global pandemic. It is a highly contagious positive strand RNA virus and its clinical presentation includes severe to critical respiratory disease that appears to be fatal in ∼3-5% of the cases. The viral spike (S) coat protein engages the human angiotensin-converting enzyme2 (ACE2) cell surface protein to invade the host cell. The SARS-CoV-2 S-protein has acquired mutations that increase its affinity to human ACE2 by ∼10-15-fold compared to SARS-CoV S-protein, making it highly infectious. In this study, we assessed if ACE2 polymorphisms might alter host susceptibility to SARS-CoV-2 by affecting the ACE2 S-protein interaction. Our comprehensive analysis of several large genomic datasets that included over 290,000 samples representing >400 population groups identified multiple ACE2 protein-altering variants, some of which mapped to the S-protein-interacting ACE2 surface. Using recently reported structural data and a recent S-protein-interacting synthetic mutant map of ACE2, we have identified natural ACE2 variants that are predicted to alter the virus-host interaction and thereby potentially alter host susceptibility. In particular, human ACE2 variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R are predicted to increase susceptibility. The T92I variant, part of a consensus NxS/T N-glycosylation motif, confirmed the role of N90 glycosylation in immunity from non-human CoVs. Other ACE2 variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y are putative protective variants predicted to show decreased binding to SARS-CoV-2 S-protein. Overall, ACE2 variants are rare, consistent with the lack of selection pressure given the recent history of SARS-CoV epidemics, however, are likely to play an important role in altering susceptibility to CoVs.

negative: Epidemiological characteristics and incubation period of 7,015 confirmed cases with Coronavirus Disease 2019 outside Hubei Province in China BACKGROUND: Disease caused by SARS-CoV-2 broke out in Wuhan in December 2019. We utilized confirmed cases outside Hubei Province to analyze epidemiologic characteristics and evaluate the effect of traffic restrictions implemented in Hubei beginning on January 23, 2020. METHOD: Information on 7,015 confirmed cases from January 19 to February 8, 2020, in all provinces outside Hubei was collected from the national and local health commissions in China. Incubation period and interval times were calculated using dates of the following events: contact with an infected person, onset, first visit and diagnosis. We evaluated changes in incubation period and interval times. RESULTS: The average age of all cases was 44.24 years old. The median incubation period was 5 days and extended from 2 days on January 23 to 15 days on February 8. The proportion of imported cases decreased from 85.71% to 33.19% after January 23. In addition, the lengths of the intervals between onset and diagnosis, onset and first visit, and first visit and diagnosis decreased over time. CONCLUSION: Rapidly transmitting COVID-19 has a short incubation period. The onset mainly occurs among young to middle-aged adults. Traffic restrictions played an important role in the decreased number of imported cases outside Hubei.

negative: Clinical trial on the effects of a free-access acidified milk replacer feeding program on the health and growth of dairy replacement heifers and veal calves Abstract The objectives of this study were to evaluate the effects of free-access acidified milk replacer feeding on the pre- and postweaning health of dairy and veal calves. Individually housed calves were systematically assigned at birth to 1 of 2 feeding programs: free-access feeding (ad libitum) of acidified milk replacer (ACD, n=249) or traditional restricted feeding (3L fed twice daily) of milk replacer (RES, n=249). Calves were fed milk replacer containing 24% crude protein and 18% fat. Acidified milk replacer was prepared to a target pH between 4.0 and 4.5 using formic acid. Calves were weaned off milk replacer at approximately 6wk of age. Weaning occurred over 5d, and during this weaning period, ACD calves had access to milk replacer for 12h/d and RES calves were offered only one feeding of milk replacer (3 L) daily. Calves were monitored daily for signs of disease. Fecal consistency scores were assigned each week from birth until weaning. A subset of calves was systematically selected for fecal sampling at 3 time points between 7 and 27d of age. Fecal samples were analyzed for enterotoxigenic Escherichia coli F5, Cryptosporidium parvum, rotavirus, and coronavirus. Hip width, hip height, body length, heart girth, and body weight were measured at birth and weaning. Postweaning body weight measurements were collected from the heifers at approximately 8mo of age. Postweaning body weight and carcass grading information was collected from the veal calves at slaughter once a live weight between 300 and 350kg had been achieved. The odds of ACD calves being treated for a preweaning disease event tended to be lower than that of the RES calves (1.2 vs. 5.2%, respectively). Preweaning mortality, postweaning disease treatment, and postweaning mortality did not differ between feeding treatments. The ACD feeding treatment supported greater preweaning average daily gain (0.59 vs. 0.43kg/d) and structural growth than RES feeding. Postweaning average daily gain and carcass characteristics were similar for ACD and RES calves. These results indicate that free-access acidified milk replacer feeding tended to support improved health, and greater body weight gain and structural growth during the preweaning period; these effects did not persist in the postweaning period. The growth advantage observed before weaning in the ACD calves likely disappeared due to the weaning methods used.

negative: Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust “HTR communities” (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.

negative: Partial RdRp sequences offer a robust method for Coronavirus subgenus classification The recent reclassification of the Riboviria, and the introduction of multiple new taxonomic categories including both subfamilies and subgenera for coronaviruses (family Coronaviridae, subfamily Orthocoronavirinae) represents a major shift in how official classifications are used to designate specific viral lineages. While the newly defined subgenera provide much-needed standardisation for commonly cited viruses of public health importance, no method has been proposed for the assignment of subgenus based on partial sequence data, or for sequences that are divergent from the designated holotype reference genomes. Here, we describe the genetic variation of a partial region of the coronavirus RNA-dependent RNA polymerase (RdRp), which is one of the most used partial sequence loci for both detection and classification of coronaviruses in molecular epidemiology. We infer Bayesian phylogenies from more than 7000 publicly available coronavirus sequences and examine clade groupings relative to all subgenus holotype sequences. Our phylogenetic analyses are largely coherent with genome-scale analyses based on designated holotype members for each subgenus. Distance measures between sequences form discrete clusters between taxa, offering logical threshold boundaries that can attribute subgenus or indicate sequences that are likely to belong to unclassified subgenera both accurately and robustly. We thus propose that partial RdRp sequence data of coronaviruses is sufficient for the attribution of subgenus-level taxonomic classifications and we supply the R package, “MyCoV”, which provides a method for attributing subgenus and assessing the reliability of the attribution. The analysis of polymerase chain reaction amplicons derived from biological samples is the most common modern method for detection and classification of infecting viral agents, such as Coronaviruses. Recent updates to the official standard for taxonomic classification of Coronaviruses, however, may leave researchers unsure as to whether the viral sequences they obtain by these methods can be classified into specific viral taxa due to variations in the sequences when compared to type strains. Here, we present a plausible method for defining genetic dissimilarity cut-offs that will allow researchers to state which taxon their virus belongs to and with what level of certainty. To assist in this, we also provide the R package ‘MyCoV’ which classifies user generated sequences.

negative: Role of nucleotides immediately flanking the transcription-regulating sequence core in coronavirus subgenomic mRNA synthesis. The generation of subgenomic mRNAs in coronavirus involves a discontinuous mechanism of transcription by which the common leader sequence, derived from the genome 5' terminus, is fused to the 5' end of the mRNA coding sequence (body). Transcription-regulating sequences (TRSs) precede each gene and include a conserved core sequence (CS) surrounded by relatively variable sequences (5' TRS and 3' TRS). Regulation of transcription in coronaviruses has been studied by reverse-genetics analysis of the sequences immediately flanking a unique CS in the Transmissible gastroenteritis virus genome (CS-S2), located inside the S gene, that does not lead to detectable amounts of the corresponding mRNA, in spite of its canonical sequence. The transcriptional inactivity of CS-S2 was genome position independent. The presence of a canonical CS was not sufficient to drive transcription, but subgenomic synthesis requires a minimum base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) provided by the CS and its adjacent nucleotides. A good correlation was observed between the free energy of TRS-L and cTRS-B duplex formation and the levels of subgenomic mRNA S2, demonstrating that base pairing between the leader and body beyond the CS is a determinant regulation factor in coronavirus transcription. In TRS mutants with increasing complementarity between TRS-L and cTRS-B, a tendency to reach a plateau in DeltaG values was observed, suggesting that a more precise definition of the TRS limits might be proposed, specifically that it consists of the central CS and around 4 nucleotides flanking 5' and 3' the CS. Sequences downstream of the CS exert a stronger influence on the template-switching decision according to a model of polymerase strand transfer and template switching during minus-strand synthesis.

negative: Healthcare needs of vulnerable patient groups: available data and existing gaps in Germany with respect to long-term mechanical ventilation AIM: Long-term invasively ventilated patients exhibit exceptional and resource-intensive healthcare needs. However, major knowledge gaps in Germany complicate appropriate approaches to best address these demands. This paper evaluates available information on the patient group and their healthcare needs from German data sources and derives implications for healthcare planning and regulation by national/federal self-governing bodies, political decision-makers, and specialized providers. METHODS: Based on the concept of needs, we addressed the normative dimension typically characterized by epidemiological data. Based on existing German health system data resources, an explorative approach was utilized to identify and characterize available databases providing information on the patient group and/or their healthcare. RESULTS: To date, no available database provides information on the healthcare needs of this patient group. As of the reporting year 2017, the diagnosis-related groups (DRG) statistics will provide hospital-specific data on home invasive ventilation interventions, but the data do not provide information on long-term care. Claims data may be a promising source for cross-sectoral evaluation of healthcare needs but feature methodological challenges. These results call for efforts to address limited data eligibility, adopt a broader understanding of healthcare needs, and identify actions needed to evidence informed and needs-oriented healthcare. CONCLUSION: Future approaches on needs-oriented specialized healthcare should close the existing knowledge gap based on reliable data. In addition to normative information, they should consider subjective dimensions on a life course perspective and quantitative and qualitative service performance characteristics across multiple sectors and professions.

negative: SARS vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector Abstract A SARS vaccine based on a live-attenuated vesicular stomatitis virus (VSV) recombinant expressing the SARS-CoV S protein provides long-term protection of immunized mice from SARS-CoV infection (Kapadia, S.U., Rose, J. K., Lamirande, E., Vogel, L., Subbarao, K., Roberts, A., 2005. Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine. Virology 340(2), 174–82.). Because it is difficult to obtain regulatory approval of vaccine based on live viruses, we constructed a replication-defective single-cycle VSV vector in which we replaced the VSV glycoprotein (G) gene with the SARS-CoV S gene. The virus was only able to infect cells when pseudotyped with the VSV G protein. We measured the effectiveness of immunization with the single-cycle vaccine in mice. We found that the vaccine given intramuscularly induced a neutralizing antibody response to SARS-CoV that was approximately ten-fold greater than that required for the protection from SARS-CoV infection, and significantly greater than that generated by the replication-competent vector expressing SARS-CoV S protein given by the same route. Our results, along with earlier studies showing potent induction of T-cell responses by single-cycle vectors, indicate that these vectors are excellent alternatives to live-attenuated VSV.

negative: Radiotherapy Workflow and Protection Procedures During the Coronavirus Disease 2019 (COVID-19) Outbreak: Experience of the Hubei Cancer Hospital in Wuhan, China Abstract The epidemic of Coronavirus Disease 2019 (COVID-19) first broke out in Wuhan in December 2019, and reached its peak in Wuhan in February 2020. It became a major public health challenge for China, and evolved into a global pandemic in March 2020. For radiation oncology departments, the COVID-19 pandemic presents a unique challenge for disease protection and prevention for both patients and staff, owing to the weakened immune systems of cancer patients and the need to deliver timely and uninterrupted radiotherapy. At the Hubei Cancer Hospital, the only hospital in Wuhan that specializes in oncology, we organized an emergency infection control team to lead special efforts to combat COVID-19 during this challenging time. Under its lead, the following measures were implemented in the radiation oncology department: the radiotherapy clinic was divided into different infection control zones with varying levels of protection; special staff and patient infection control training sessions were conducted and appropriate measures deployed; daily symptom testing criteria were implemented for patients undergoing treatment; special rotating schedules and infection control methods were implemented for various staff members such as medical physicists/dosimetrists and radiation therapists; modified radiotherapy workflow and specialized treatment area cleaning and disinfection policies and procedures were designed and executed; and special medical waste disposal methods were implemented. We began treating patients using this new COVID-19 radiotherapy treatment workflow and infection control measures on January 30, 2020. During more than one and a half months of uninterrupted radiation oncology clinical operation through the worst of the Wuhan outbreak, no known COVID-19 infection occurred at our radiotherapy center to our patients or employees. This report may provide valuable information for other radiation oncology departments during this unprecedented public health crisis.

negative: The Effectiveness of Targeted Quarantine for Minimising Impact of COVID-19 We model the extent to which age targeted quarantine can be used to reduce ICU admissions caused by novel coronavirus COVID-19. Using demographic data from New Zealand, we demonstrate that lowering the age threshold for quarantine to 50 years of age reduces ICU admissions drastically, and show that for sufficiently strict isolation protocols, isolating one third of the countries population for a total of 6 months is sufficient to avoid overwhelming ICU capacity throughout the entire course of the epidemic. Similar results are expected to hold for other countries, though some minor adaption will be required based on local age demographics and hospital facilities.

negative: Vaccination Against Coronaviruses In Domestic Animals Abstract The current pandemic of COVID-19 has set off an urgent search for an effective vaccine. This search may well benefit from the experiences of the animal health profession in the development and use of coronavirus vaccines in domestic animal species. These animal vaccines will in no way protect humans against COVID-19 but knowledge of the difficulties encountered in vaccinating animals may help avoid or minimize similar problems arising in humans. Diverse coronaviruses can infect the domestic species from dogs and cats, to cattle and pigs to poultry. Many of these infections are controlled by the routine vaccination. Thus, canine coronavirus vaccines are protective in puppies but the disease itself is mild and self-limiting. Feline coronavirus infections may be mild or may result in a lethal immune-mediated disease – feline infectious peritonitis. As a result, vaccination of domestic cats must seek to generated protective immunity without causing immune-mediated disease. Vaccines against bovine coronavirus are widely employed in cattle where they protect against enteric and respiratory disease in young calves. Two major livestock species suffer from economically significant and severe coronavirus diseases. Thus, pigs may be infected with six different coronaviruses, one of which, porcine epidemic diarrhea, has proven difficult to control despite the development of several innovative vaccines. Porcine epidemic diarrhea virus undergoes frequent genetic changes. Likewise, infectious bronchitis coronavirus causes an economically devastating disease of chickens. It too undergoes frequent genetic shifts and as a result, can only be controlled by extensive and repeated vaccination. Other issues that have been encountered in developing these animal vaccines include a relatively short duration of protective immunity, and a lack of effectiveness of inactivated vaccines. On the other hand, they have been relatively cheap to make and lend themselves to mass vaccination procedures.

negative: [Health management of breast cancer patients outside the hospital during the outbreak of 2019 novel coronavirus disease]. The outbreak of 2019 novel coronavirus disease (COVID-19) is spreading rapidly. In order to prevent cluster outbreaks, the government strengthened the management and control of personnel mobility, which had a great impact on the examination and treatment of breast cancer patients. This paper discusses how to realize scientific health management of breast cancer patients outside the hospital based on the existing epidemic situation, characteristics of breast cancer patients and public health safety factors. The breast cancer patients should synthetically consider the epidemic prevention situation of inhabitance, the disease stage and previous therapeutic schedule to decide the next therapeutic schedule. If necessary, after professional discussion and communication between doctors and patients online or offline, the hospital visiting time should be delayed through seeking alternative treatment schemes, and psychological counseling for patients should be paid attention to at the same time.

negative: Emergency tracheostomy during COVID 19 Pandemic in a head and neck surgical oncology unit • Awake, Emergency, Intervention for an Unsecured 'Unable to intubate' Critical upper airway obstruction is a surgical challenge. • Aerosolization and risk COVID 19 transmission add to the already existing difficulty of surgical restoration of critical airway obstruction. • Adequate personal protection, rapid restoration of the airway with the minimum aerosol generation, and prevention of COVID 19 dissemination are keys to the success of Emergency Tracheostomy during the Pandemic.

negative: The interface of animal and human vaccines

negative: Reflection on Disruptions: Managing the City in Need, Saving the City in Need At the time when mostly negative news flow between countries, the reactions of national-level and city-level governments should reflect on their full preparedness and responsive management.

negative: Coronavirus disease 2019 (COVID-19) pandemic and pregnancy The current coronavirus disease 2019 (COVID-19) pneumonia pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally at an accelerated rate, with a basic reproduction number (R0) of 2–2.5, indicating that 2–3 persons will be infected from an index patient. A serious public health emergency, it is particularly deadly in vulnerable populations and communities in which healthcare providers are insufficiently prepared to manage the infection. As of March 16, 2020, there are more than 180,000 confirmed cases of COVID-19 worldwide, with more than 7000 related deaths. The SARS-CoV-2 virus has been isolated from asymptomatic individuals, and affected patients continue to be infectious 2 weeks after cessation of symptoms. The substantial morbidity and socioeconomic impact have necessitated drastic measures across all continents, including nationwide lockdowns and border closures. Pregnant women and their fetuses represent a high-risk population during infectious disease outbreaks. To date, the outcomes of 55 pregnant women infected with COVID-19 and 46 neonates have been reported in the literature, with no definite evidence of vertical transmission. Physiological and mechanical changes in pregnancy increase susceptibility to infections in general, particularly when the cardiorespiratory system is affected, and encourage rapid progression to respiratory failure in the gravida. Furthermore, the pregnancy bias toward T-helper 2 (Th2) system dominance, which protects the fetus, leaves the mother vulnerable to viral infections, which are more effectively contained by the Th1 system. These unique challenges mandate an integrated approach to pregnancies affected by SARS-CoV-2. Here we present a review of COVID-19 in pregnancy, bringing together the various factors integral to the understanding of pathophysiology and susceptibility, diagnostic challenges with real-time reverse transcription polymerase chain reaction (RT-PCR) assays, therapeutic controversies, intrauterine transmission, and maternal−fetal complications. We discuss the latest options in antiviral therapy and vaccine development, including the novel use of chloroquine in the management of COVID-19. Fetal surveillance, in view of the predisposition to growth restriction and special considerations during labor and delivery, is addressed. In addition, we focus on keeping frontline obstetric care providers safe while continuing to provide essential services. Our clinical service model is built around the principles of workplace segregation, responsible social distancing, containment of cross-infection to healthcare providers, judicious use of personal protective equipment, and telemedicine. Our aim is to share a framework that can be adopted by tertiary maternity units managing pregnant women in the flux of a pandemic while maintaining the safety of the patient and healthcare provider at its core.

negative: Rapid and cost-effective development of stable clones for the production of anti-Ebola monoclonal antibodies in HEK293T cells The Ebola virus (EBOV) disease has caused serious and recurrent epidemics in recent years, resulting in a fatality rate of nearly 50%. The most effective experimental therapy against the EBOV is the use of monoclonal antibodies (mAbs). In this work, we describe the development of HEK293T cells engineered for the transient and stable expression of mAb13C6, a neutralizing anti-EBOV monoclonal antibody. We transfected the HEK293T cells with a tricistronic vector to produce the heavy and the light chain of the antibody 13C6 and intracellular Green Fluorescent Protein (GFP) using Lipofectamine 3000. We then selected the transfected cells using puromycin pressure, dilution cloning, and cloning disks. This integrated strategy generated mAb-producing cells in 7 days with a transient expression of ∼1 mg/L. Stable pools were produced after 4 weeks, with expression levels of ∼0.8 mg/L. Stable clones with expression levels of ∼1.8 mg/L were obtained within 10 weeks. The produced antibodies exhibited the expected functionality; they recognized the GP glycoprotein of the Ebola virus in both ELISA assays and cell binding experiments using HEK293T cells engineered to express the EBOV GP at their membrane surface. By the combined use of GFP and the set of selection techniques here described, we drastically reduced the time from transfection to stable clone generation without resorting to costly equipment. In outbreaks or emergencies, this platform can significantly shorten the development of new biopharmaceuticals and vaccines.

negative: Epidemiology and clinical features of coronavirus disease 2019 in children Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.

negative: Hazards There are many known hazards, including natural, man-made, and intentional. The source of risk is the wide range of hazards that are faced in almost every facet of life. The global society must contend with an array of hazards that may seem limitless, but which is actually limited owing to an individual’s genetics, spatial movements, habits, activities, and geographic locations. Physical location is the primary factor dictating what natural hazards a nation faces. Economic, industrial, and sociopolitical factors dictate hazards of technological and intentional origin. Moreover, with globalization, the speed and ease of international travel, and the emergence of global climate change patterns, every nation is connected to every other nation on the planet. This chapter begins with a short description of the disaster management processes of hazard identification and hazard analysis. Following this is a listing and descriptions of many of the hazards that possess catastrophic potential—in other words, those hazards that are capable of causing a disaster. Awareness of the hazards that affect a nation or region and full understanding of the causes and consequences of that hazard “portfolio” are the first steps in the disaster reduction process known as disaster risk management.

negative: 47 The Aircraft Cabin Environment Abstract Travel by air is a safe means of transport, but from the physiologic point of view it is a means of putting people at risk as well as a potential means of spreading infectious disease. Atmospheric pressure falls with altitude and above about 10,000 feet, blood desaturation leads to hypoxia. The aircraft cabin is pressurized to maintain an effective altitude below 8000 feet, which provides adequate protection for healthy travelers. Those individuals with cardiopulmonary impairment or other conditions affecting fitness to travel should seek advice from the airline in consultation with their medical provider. People are the primary source of microorganisms in aircraft cabins and are the most important reservoirs of infectious agents on aircraft. Recirculated cabin air is filtered to remove microorganisms, but this does not prevent person-to-person spread of infectious disease in vulnerable people. The World Health Organization and Centers for Disease Control and Prevention produce guidelines; and people with febrile illnesses should postpone air travel.

negative: Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei Background: Since December 2019, a novel coronavirus pneumonia (COVID-19) rapidly spread in China, reached multiple continents currently.We aimed to reveal the infectious characteristics of COVID-19 that provide more information for the research of novel coronavirus. Methods: We performed a retrospective study on the clinical characteristics of 128 COVID-19 cases with laboratory-confirmed from Xiangyang No 1 Hospitalad during January 2020 to 16 February 2020. Results: Female patients account for 53.1%. The aged below 20 years that accounts for 1.6% of overall patients. The aged in 21~50, 51~65, over 66 years were accounts for 44.5%, 35.1%,18.8%, respectively. In the difference age spectrum, all severe groups compared with non-severe groups were difference significantly ( P < 0.01 ). Fever ( 89.8% ) and Cough ( 67.2% ) were common clinical symptoms. The rate of patients with sore throats (14.1%) was rare. The rate of chest computed tomography scan showing ground glass opacity in overall, non-severe, severe groups were 63.3%, 60.7%, 76.2%, respectively. White blood cell counts in the normal range of overall patients, but severe group patients were increased significantly ( P < 0.01). Lymphocytes of overall patients were decreased. Alanine transaminase (ALT) and aspartate transaminase (AST) in the normal range of overall patients, but its were elevated in the severe group. Creatinine (CR) and blood urea nitrogen (BUN) of overall patients in the normal range. C-reactive protein (CRP) level of all patients were increased markedly, but it in the severe group was significantly higher than that in the non-severe group ( P < 0.01 ). Conclusions: Our data provide more information that advanced age, lower lymphocytes levels at the diagnosed COVID-19 patients may be a risk factor for unfavourable prognosis. The white blood cells and C-reactive protein level elevated in severe COVID-19 patients may be accompanying bacterial infection. 2019-nCov may be carries a risk factor of impaired liver and kidney function.

negative: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity The spike (S) glycoprotein of SARS-CoV-2 is responsible for the binding to the permissive cells. The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. In this study, we used computational saturation mutagenesis approaches, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18,354 mutations in S protein were analyzed and we discovered that most of these mutations could destabilize the entire S protein and its RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. In addition, we investigated 3,705 mutations in SARS-CoV-2 RBD and 11,324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD-ACE2 interaction. The findings comprehensively provide potential target sites in the development of drugs and vaccines against COVID-19.

negative: Genotyping coronavirus SARS-CoV-2: Methods and implications Abstract The emerging global infectious COVID-19 disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. To understand the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. This study presents an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The single-nucleotide polymorphism (SNP) genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. The proposed method serves an effective tool for monitoring and tracking the epidemic of pathogenic viruses in their global and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.

negative: Insight into 2019 novel coronavirus — an updated intrim review and lessons from SARS-CoV and MERS-CoV Abstract Background The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta-coronavirus entitled 2019 novel coronavirus (2019-nCoV), has become a global threat. Awareness of the biological features of 2019-nCoV should be updated in time and needs to be comprehensively summarized to help optimize control measures and make therapeutic decisions. Methods Based on recently published literatures, official documents and selected up-to-date preprint studies, we reviewed the virology and origin, epidemiology, clinical manifestations, pathology and treatment of 2019-nCoV infection, in comparison with severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV) infection. Results The genome of 2019-nCoV partially resembled SARS-CoV and MERS-CoV, and indicating a bat origin. The COVID-19 generally had a high reproductive number, a long incubation period, a short serial interval and a low case fatality rate (much higher in patients with comorbidities) than SARS and MERS. Clinical presentation and pathology of COVID-19 greatly resembled SARS and MERS, with less upper respiratory and gastrointestinal symptoms, and more exudative lesions in post-mortems. Potential treatments included remdesivir, chloroquine, tocilizumab, convalescent plasma and vaccine immunization (when possible). Conclusion The initial experience from the current pandemic and lessons from the previous two pandemics can help improve future preparedness plans and combat disease progression.

negative: Chinese Society of Anesthesiology Expert Consensus on Anesthetic Management of Cardiac Surgical Patients With Suspected or Confirmed Coronavirus Disease 2019 The outbreak of a new coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) in China in December 2019 has brought serious challenges to disease prevention and public health. Patients with severe coronavirus disease 2019 (COVID-19) who undergo cardiovascular surgery necessitate extremely high demands from anesthesia personnel, and face high risks of mortality and morbidity. Based on the current understanding of COVID-19 and the clinical characteristics of cardiovascular surgical patients, the authors provide anesthesia management guidelines for cardiovascular surgery along with the prevention and control of COVID-19.

negative: Protection of Mice against Infection with Mouse Hepatitis Virus Type 3 by Injection of Silica Injection of silica did not brake the resistance against MHV3 conferred to C57BL/6 mice by injection of C. parvum. However, silica itself had a marked protective effect against MHV3 infection that was maximal when injecting 1 mg 2 hrs before virus infection. The protective effect of silica was observed in a number of inbred mouse strains that differ in their relative resistance to MHV3 infection. No viral titers were observed in the spleen and liver of mice which had received MHV3 plus silica, whereas high titers were observed in the virus-infected controls. Injection of silica caused a marked decrease in the number of esterase-positive macrophages in the peritoneal wash-out population, that may be compatible with the possibility that the cause of the protection is the depletion of target cells for the viral infection. This latter effect, however, was short-lived and 24–48 hrs after injection of silica, high numbers of esterase-positive cells were again observed. This may explain why only little protection was observed when silica was administered 2 days before virus infection.

negative: Role of a Habitat's Air Humidity in Covid-19 Mortality Transient local over-dry environment might be a contributor and an explanation for the observed asynchronous local rises in Covid-19 mortality. We propose that a habitat's air humidity negatively correlate with Covid-19 morbidity and mortality, and support this hypothesis on the example of publicly available data from German federal states.

negative: Synchronized travel restrictions across cities can be effective in COVID-19 control Mobility control measures are of crucial importance for public health planning in combating the COVID-19 pandemic. Previous studies established the impact of population outflow from Wuhan on the spatial spread of coronavirus in China and hinted the impact of the other three mobility patterns, i.e., population outflow from Hubei province excluding Wuhan, population inflow from cities outside Hubei, and intra-city population movement. However, the overall impact of all mobility patterns, or the impact of the different timing of mobility restriction intervention, are not systematically analyzed. Here we apply the cumulative confirmed cases and mobility data of 350 Chinese cities outside Hubei to explore the relationships between all mobility patterns and epidemic spread, and estimate the impact of local travel restrictions, both in terms of level and timing, on the epidemic control based on mobility change. The relationships were identified by using Pearson correlation analysis and stepwise multivariable linear regression, while scenario simulation was used to estimate the mobility change caused by local travel restrictions. Our analysis shows that: (1) all mobility patterns correlated with the spread of the coronavirus in Chinese cities outside Hubei, while the corrleations droppd with the implemetation of travel restrictions; (2) the cumulative confirmed cases in two weeks after the Wuhan lockdown was mainly brought by three patterns of inter-city population movement, while those in the third and fourth weeks after was significantly influenced by the number of intra-city population movement; (3) the local travel restrictions imposed by cities outside Hubei have averted 1,960 (95%PI: 1,474-2,447) more infections, taking 22.4% (95%PI: 16.8%-27.9%) of confirmed ones, in two weeks after the Wuhan lockdown, while more synchronized implementation would further decrease the number of confirmed cases in the same period by 15.7% (95%PI:15.4%-16.0%) or 1,378 (95%PI: 1,353-1,402) cases; and (4) local travel restrictions on different mobility patterns have different degrees of protection on cities with or without initial confirmed cases until the Wuhan lockdown. Our results prove the effectiveness of local travel restrictions and highlight the importance of synchronized implementation of mobility control across cities in mitigating the COVID-19 transmission.

negative: Aquatic invasive species: challenges for the future Humans have effectively transported thousands of species around the globe and, with accelerated trade; the rate of introductions has increased over time. Aquatic ecosystems seem at particular risk from invasive species because of threats to biodiversity and human needs for water resources. Here, we review some known aspects of aquatic invasive species (AIS) and explore several new questions. We describe impacts of AIS, factors limiting their dispersal, and the role that humans play in transporting AIS. We also review the characteristics of species that should be the greatest threat for future invasions, including those that pave the way for invasions by other species (“invasional meltdown”). Susceptible aquatic communities, such as reservoirs, may serve as stepping stones for invasions of new landscapes. Some microbes disperse long distance, infect new hosts and grow in the external aquatic medium, a process that has consequences for human health. We also discuss the interaction between species invasions and other human impacts (climate change, landscape conversion), as well as the possible connection of invasions with regime shifts in lakes. Since many invaders become permanent features of the environment, we discuss how humans live with invasive species, and conclude with questions for future research.

negative: Coronavirus mRNA synthesis involves fusion of non-contiguous sequences. Positive-stranded genomic RNA of coronavirus MHV and its six subgenomic mRNAs are synthesized in the cytoplasm of the host cell. The mRNAs are composed of leader and body sequences which are non-contiguous on the genome and are fused together in the cytoplasm by a mechanism which appears to involve an unusual and specific 'polymerase jumping' event.

negative: A special case of COVID-19 with long duration of viral shedding for 49 days Prolonged viral shedding is associated with severe status and poor prognosis of COVID-19 patients. Unexpectedly, here we report a non-severe patient with the longest duration of viral shedding. According to the investigation on the clinical and epidemiological information of this case, we concluded that this type of virus might have a low toxicity and transmissibility, but have a prolonged infective ability and was hardly to be eliminated in the body with regular therapy. However, infusion of plasma from recovered patients showed high efficiency in elimination of this virus. Our findings might shed light on the management of COVID-19.

negative: Aerosol-Transmitted Infections—a New Consideration for Public Health and Infection Control Teams Since the emergence of the 2003 severe acute respiratory syndrome (SARS), the 2003 reemergence of avian A/H5N1, the emergence of the 2009 pandemic influenza A/H1N1, the 2012 emergence of Middle East respiratory syndrome (MERS), the 2013 emergence of avian A/H7N9 and the 2014 Ebola virus outbreaks, the potential for the aerosol transmission of infectious agents is now routinely considered in the investigation of any outbreak. Although many organisms have traditionally been considered to be transmitted by only one route (e.g. direct/indirect contact and/or faecal-orally), it is now apparent that the aerosol transmission route is also possible and opportunistic, depending on any potentially aerosol-generating procedures, the severity of illness and the degree and duration of pathogen-shedding in the infected patient, as well as the environment in which these activities are conducted.This article reviews the evidence and characteristics of some of the accepted (tuberculosis, measles, chickenpox, whooping cough) and some of the more opportunistic (influenza, Clostridium difficile, norovirus) aerosol-transmitted infectious agents and outlines methods of detecting and quantifying transmission.

negative: Coronavirus Disease 2019 (COVID-19): we shall overcome

negative: Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicenter) and outside Hubei (non-epicenter): A Nationwide Analysis of China BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China has been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients in and outside of Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicenter as well the administrative center of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: Upon data cut-off (Jan 31st, 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597/647, 92.3%) were older (mean: 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations, and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei [severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, hazards ratio (HR) for critical illness 1.59, 95%CI 1.05–2.41] have a poorer prognosis compared with patients outside of Hubei after adjusting for age and comorbidity. However, among patients outside of Hubei, the duration from symptom onset to hospitalisation (mean: 4.4 versus 4.7 days) and prognosis (HR 0.84, 95%CI 0.40–1.80) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR 1.05, 1.01–1.08). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicenter. Future studies to determine the reason for delaying hospitalisation are warranted.

negative: 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings

negative: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study BACKGROUND: Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. METHODS: In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. FINDINGS: 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. INTERPRETATION: The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

negative: Mouse Hepatitis Virus This chapter attempts to provide an overview of the important aspects of mouse hepatitis virus (MHV) experimental biology while emphasizing the virus as a naturally occurring mouse pathogen. Even this is complicated, as it is impossible to generalize with this virus, due to marked differences in the biologic behavior of the myriad virus strains, plus the marked effects of a large number of host factors. It is now known that the MHV group is represented by numerous variants that are constantly mutating, and that these viruses can be biologically separated into respiratory (polytropic) MHVs and enterotropic MHVs, with distinctly different patterns of tissue tropism. This dichotomy is emphasized for discussion, but biology is never absolute. Many of the early MHV isolations are made as a result of contamination of biological materials that correlated with their polytropic biologic behavior. Their stated tropisms frequently were the result of the investigators' research interests and many have therefore been subjected to selective passage that favors a particular tissue tropism. All MHV isolates are related genetically and antigenically, but isolates can be differentiated by genetic sequencing, cross-serum neutralization, or with monoclonal antibodies. Genetic and antigenic relationships are not predictive of biologic behavior.

negative: SARS-CoV-2 strategically mimics proteolytic activation of human ENaC Molecular mimicry is an evolutionary strategy adopted by viruses to exploit the host cellular machinery. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site, absent in any previous coronavirus sequenced, resulting in the striking mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic alteration of ENaC-α causes aldosterone dysregulation in patients, highlighting that the FURIN site is critical for activation of ENaC. Single cell RNA-seq from 66 studies shows significant overlap between expression of ENaC-α and the viral receptor ACE2 in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular characterization with cleavage signatures of 178 proteases highlights proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. Evolution of SARS-CoV-2 into a global pandemic may be driven in part by its targeted mimicry of ENaC-α, a protein critical for the homeostasis of airway surface liquid, whose misregulation is associated with respiratory conditions.

negative: Coronavirus immunogens Abstract Coronaviruses (CV) infect a variety of livestock, poultry and companion animals. They belong to at least five antigenic groups. CV cause localized infections of the respiratory and/or intestinal tracts, with the exception of feline infectious peritonitis virus (FIVP) and hemagglutinating encephalomyelitis (HEV) which cause systemic infections. The enteropathogenic CV infect the villous enterocytes resulting in villous atrophy leading to malabsorptive diarrhea. Several CV (bovine CV-BCV, porcine respiratory CV-PRCV, infectious bronchitis virus-IBV) cause respiratory disease. Current evidence indicates that protection against enteric and respiratory CV infections is mediated by passive or active immunity at the primary site of CV replication. Maternal vaccination approaches to induce passive immunity include the use of inactivated and modified live viral vaccines. Modified live viruses and a Ts mutant CV (FIPV) are also used as oral or intranasal vaccines to induce active mucosal immunity. The success of these vaccines in the field is often compromised by a number of potential problems. Coronaviruses are spherical, enveloped viruses, ranging from 80–160 nm in diameter and containing a positive-stranded RNA genome. They possess prominent surface spikes and some species display a fringe of smaller surface projections believed to be the hemagglutinin (HE). Coronaviruses possess 3 to 4 structural proteins: the spike (S) glycoprotein (150–200 kDa), the integral membrane glycoprotein (M; 20–30 kDa) and the nucleocapsid phosphoprotein (N; 43–50 kDa). A subset of CV (BCV, HEV, turkey CV) possess a third glycoprotein on the virion surface, the HE (60–65 kDa). These proteins can be quantitated using pooled monoclonal antibodies (mAb) to distinct epitopes of each protein in ELISA. Most research has focused on the S protein as a candidate antigen for CV vaccines since it induces virus neutralizing (VN) antibodies. However the HE protein stimulates the production of VN and HE inhibiting antibodies and the M protein induces antibodies that neutralize virus in the presence of complement. Attempts to correlate in vitro VN antibody activity with in vivo protection have shown that the passive transfer of VN mAb to the S or HE protein conferred passive protection against CV challenge in some studies, but not others. Additional research has implicated a possible role for other CV proteins in immunity. Studies of mAb to the M protein of transmissible gastroenteritis (TGEV) have provided evidence for a direct role of the M protein in the induction of αIFN by porcine blood leukocytes. The potential significance of this phenomenon to immunity to TGEV is unclear. Similarly, studies of IBV have suggested that determinants recognized by T cells reside on the N protein and these determinants may be shared among heterologous strains of IBV, resulting in the induction of cross-protection. Thus epitopes on the N protein may be important for induction of cell mediated immunity (CMI). CMI may play an important role in protection of cats against FIPV, since induction of circulating antibodies to the S protein of FIPV contributes to disease pathogenesis by the induction of immune complexes and antibody dependent enhancement of the infectivity of FIPV for macrophages. An increased understanding of antibody and CMI responses following natural CV infections in animals is needed to identify the antigens and epitopes that induce protective immune responses. The expression of CV structural protein genes in various vectors will provide the recombinant proteins needed for future immunogenicity studies in the host species. Furthermore, live rDNA vectors that replicate in the gut and express coronavirus genes may provide a new generation of coronavirus vaccines.

negative: Effects of personalized ventilation interventions on airborne infection risk and transmission between occupants The role of personalized ventilation (PV) in protecting against airborne disease transmission between occupants was evaluated by considering two scenarios with different PV alignments. The possibility that PV may facilitate the transport of exhaled pathogens was explored by performing experiments with droplets and applying PV to a source or/and a target manikin. The risk of direct and indirect exposure to droplets in the inhalation zone of the target was estimated, with these exposure types defined according to their different origins. The infection risk of influenza A, a typical disease transmitted via air, was predicted based on a dose-response model. Results showed that the flow interactions between PV and the infectious exhaled flow would facilitate airborne transmission between occupants in two ways. First, application of PV to the source caused more than 90% of indirect exposure of the target. Second, entrainment of the PV jet directly from the infectious exhalation increased direct exposure of the target by more than 50%. Thus, these scenarios for different PV application modes indicated that continuous exposure to exhaled influenza A virus particles for 2 h would correspond with an infection probability ranging from 0.28 to 0.85. These results imply that PV may protect against infection only when it is maintained with a high ventilation efficiency at the inhalation zone, which can be realized by reduced entrainment of infectious flow and higher clean air volume. Improved PV design methods that could maximize the positive effects of PV on disease control in the human microenvironment are discussed.

negative: Post COVID-19 lesson: Understand the environment for human survival and sustenance

negative: Interaction rituals and ‘social distancing’: New haptic trajectories and touching from a distance in the time of COVID-19 Previous research in the social sciences has shown that haptic interaction rituals are critical for maintaining social relationships. However, during the coronavirus (COVID-19) pandemic, ‘social distancing’ was encouraged in order to avoid the spread of disease. Drawing on data from self-ethnography as well as publicly available resources, in this study we explore some new, locally negotiated haptic trajectories to accomplish interaction rituals in the time of coronavirus. First, we present self-ethnographic observations of distancing in face-to-face encounters from our everyday lives. Second, utilizing methods of microanalysis of naturally occurring interaction, we investigate video recordings of the embodied negotiation of space and touch among politicians. We analyze three different ways in which politicians negotiate transitional moves in this haptic ritual when one party initiates a handshake: repairing, declining and apologizing. Our analysis shows that politicians adapt their entire bodies in conjunction with talk, gestures and laughter not only to accomplish the greeting but also to remedy the potentially face-threatening situation of not getting the greeting right. This research has implications for better understanding the spontaneous ability of human beings to invent new ways of engaging with each other. Moreover, it adds to our knowledge of how the materiality of human bodies can impact forms of sociality.

negative: Epidemiologic and Clinical Characteristics of 26 Cases of COVID-19 Arising from Patient-to-Patient Transmission in Liaocheng, China INTRODUCTION: Over 40,000 cases of coronavirus (CoV) disease 2019 (COVID-19) have been confirmed in China. The causative agent, 2019 novel CoV (2019-nCoV), has spread rapidly to more than 25 countries worldwide. Human-to-human transmission has accounted for most of the infections outside Wuhan. Most studies to date on COVID-19 have focused on disease etiology and the genomics of 2019-nCoV, with few reports on the epidemiologic and clinical characteristics of infected patients. METHODS: We report early clinical features of 26 patients with confirmed COVID-19 who were admitted to Liaocheng Infectious Disease Hospital in Shandong Province. RESULTS: The median age of the 26 patients with COVID-19 in this study was 42 years. The most common occupation was retail staff (16 patients, 61.54%), with 11 patients or their family members working at the same supermarket. Only 2 patients had visited Wuhan since December 2019; the other cases of 2019-nCoV infection arose from patient-to-patient transmission. Twelve patients had more than one sign or symptom; however, seven patients had no sign or symptom. The average time from symptom onset to admission was 4.5 days. CT revealed signs of bronchitis in 2 patients and unilateral and bilateral pneumonia in 9 and 15 patients, respectively. The patients received the following treatments: antiviral therapy (100%), Chinese medicine (76.92%), antibiotics (50%), gastric mucosal protection (19.23%), immunotherapy (7.69%), and glucocorticoids (3.85%). Most patients (25/26) required ≥1 treatment. DISCUSSION: In contrast to previous reports, most patients (24/26) had not been in close contact with individuals from Wuhan. Additionally, 11 patients or their family members worked at the same supermarket, suggesting active viral transmission in a location frequented by a large number of people. Close monitoring is essential for preventing the large-scale spread of the virus in such places.

negative: Fatalism in the context of COVID-19: Perceiving coronavirus as a death sentence predicts reluctance to perform recommended preventative behaviors() To manage the spread of coronavirus, health entities have urged the public to take preventative measures such as social distancing and handwashing. Yet, many appear reluctant to take these measures. Research is needed to understand factors underlying such reluctance, with the aim of developing targeted health interventions. We identify associating coronavirus with death as one such factor. 590 participants completed surveys in mid-March 2020, which included attitudes toward coronavirus, preventative behavioral intentions, and sociodemographic factors. Associating coronavirus with death negatively predicted intentions to perform preventative behaviors. Further, associating coronavirus with death was not evenly distributed throughout the sample and was related with a number of sociodemographic factors including age, race, and availability of sick leave. Following recommended preventative measures to slow the spread of coronavirus appears to relate to the degree to which people associate coronavirus with death. These findings can be used by public health researchers and practitioners to identify those for whom targeted health communication and interventions would be most beneficial, as well as to frame health messaging in ways that combat fatalism.

negative: Do children need a longer time to shed SARS-CoV-2 in stool than adults? Abstract SARS-CoV-2 can be shed in the stool of patients in the recovery phase. Children show a longer shedding time than adults. We analyzed the possible causes of this finding and recommend that a negative stool sample be included in a patient's discharge criteria.

negative: [Epidemic trend of corona virus disease 2019 (COVID-19) in mainland China]. Objective: In order to master the epidemic trend of corona virus disease 2019 (COVID-19) and evaluate the effect of prevention and control, we evaluate the epidemic dynamics of COVID-19 in mainland China, Hubei province, Wuhan city and other provinces outside Hubei from January 16 to February 14, 2020. Methods: We collected the daily number of new confirmed COVID-19 cases by nucleic acid detection reported by the National Health Commission from January 16, 2020 to February 14, 2020. The analysis includes the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in mainland China was 50 031, including 37 930 in Hubei province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of the number of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion: The epidemic prevention and control measures taken by the state and governments at all levels have shown very significant effects, effectively curbing the spread of the COVID-19 epidemic in China.

negative: Is Sexual Route a Matter of Concern for the SARS-CoV-2/COVID-19?

negative: Possibility of Disinfection of SARS-CoV-2 (COVID-19) in Human Respiratory Tract by Controlled Ethanol Vapor Inhalation Viruses such as SARS-CoV-2 and Influenza are lipophilic, enveloped viruses, and are relatively easy to inactivate by exposure to alcohols. The envelope mainly consists of the lipid bilayer, taken from the host cells at assembly/budding stage of the viral life cycle. Therefore the constitution of the lipid bilayer should be common in all SARS, MERS and influenza viruses, even after mutations, and thus these closely-related viruses will be disinfected by exposure to ethanol with the same concentration. Existing experimental data indicate that an ethanol concentration of 30~40 v/v% is sufficient to inactivate Influenza-A viruses in solution[1,2,3]. The author suggests that it may be possible to use alcoholic beverages of 16~20 v/v% concentration for this disinfection process, such as Whisky (1:1 hot water dilution) or Japanese Sake, because they are readily available and safe (non-toxic). By inhaling the alcohol vapor at 50~60$^\circ$C (122~140$^\circ$F) through the nose for one or two minutes, it will condense on surfaces inside the respiratory tract; mainly in the nasal cavity. The alcohol concentration will be intensified to ~36 v/v% by this process, which is enough to disinfect the corona virus on the mucous membrane. This method also provides more moisture into respiratory tract, and helps to clean the inside of the nasal cavity by stimulating blowing of the nose, and also makes the mucous escalator work actively so that the self-clearing mechanism in the trachea will remove viruses faster. An alternative prompt method is also discussed. We use 40 v/v% whisky or similar alcohol, dripping on a gauze, inhale the vapor slowly at room temperature. This method works well for the front part of the nasal cavity. This is suitable for clinical workers, because they may need to use prompt preventative measures at any time.

negative: Shelter Hospital: Glimmers of Hope in Treating Coronavirus 2019 Since the first report of the 2019 novel coronavirus disease (COVID-19) in December 2019 in Wuhan, China, the outbreak of the disease has been continuously evolving. Until March 17, 2020, 185, 178 cases had been confirmed, including 81,134 cases in China and 104,044 cases outside of China. In this comment, we report the unexpected beneficial effect of a deployable rapid-assembly shelter hospital on the prevention and treatment of COVID-19. We describe the shelter hospital maintenance, treatment mode and primary treatment methods, which will provide a valuable experience in dealing with public health emergencies, such as COVID-19, for other countries and areas.

negative: Main factors influencing recovery in MERS Co-V patients using machine learning Abstract Background Middle East Respiratory Syndrome (MERS) is a major infectious disease which has affected the Middle Eastern countries, especially the Kingdom of Saudi Arabia (KSA) since 2012. The high mortality rate associated with this disease has been a major cause of concern. This paper aims at identifying the major factors influencing MERS recovery in KSA. Methods The data used for analysis was collected from the Ministry of Health website, KSA. The important factors impelling the recovery are found using machine learning. Machine learning models such as support vector machine, conditional inference tree, naïve Bayes and J48 are modelled to identify the important factors. Univariate and multivariate logistic regression analysis is also carried out to identify the significant factors statistically. Result The main factors influencing MERS recovery rate are identified as age, pre-existing diseases, severity of disease and whether the patient is a healthcare worker or not. In spite of MERS being a zoonotic disease, contact with camels is not a major factor influencing recovery. Conclusion The methods used were able to determine the prime factors influencing MERS recovery. It can be comprehended that awareness about symptoms and seeking medical intervention at the onset of development of symptoms will make a long way in reducing the mortality rate.

negative: Short-term forecasts and long-term mitigation evaluations for the COVID-19 epidemic in Hubei Province, China As an emerging infectious disease, the 2019 coronavirus disease (COVID-19) has developed into a global pandemic. During the initial spreading of the virus in China, we demonstrated the ensemble Kalman filter performed well as a short-term predictor of the daily cases reported in Wuhan City. Second, we used an individual-level network-based model to reconstruct the epidemic dynamics in Hubei Province at its early stage and examine the effectiveness of non-pharmaceutical interventions on the epidemic spreading with various scenarios. Our simulation results show that without continued control measures, the epidemic in Hubei Province could have become persistent. Only by continuing to decrease the infection rate through 1) protective measures and 2) social distancing can the actual epidemic trajectory that happened in Hubei Province be reconstructed in simulation. Finally, we simulate the COVID-19 transmission with non-Markovian processes and show how these models produce different epidemic trajectories, compared to those obtained with Markov processes. Since recent studies show that COVID-19 epidemiological parameters do not follow exponential distributions leading to Markov processes, future works need to focus on non-Markovian models to better capture the COVID-19 spreading trajectories. In addition, shortening the infectious period via early case identification and isolation can slow the epidemic spreading significantly.

negative: Strategy for the practice of digestive and oncological surgery during the Covid-19 epidemic()() The Covid-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery–go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer–colon, pancreas, oesogastric, hepatocellular carcinoma–morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3-4 and/or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting period) to reduce time of exposure in the hospital and to prevent infections. Most complex surgery with high morbidity and mortality–oesogastric, hepatic or pancreatic–is most often best deferred.

negative: Climatic changes and their role in emergence and re-emergence of diseases Global warming and the associated climate changes are predictable. They are enhanced by burning of fossil fuels and the emission of huge amounts of CO(2) gas which resulted in greenhouse effect. It is expected that the average global temperature will increase with 2–5 °C in the next decades. As a result, the earth will exhibit marked climatic changes characterized by extremer weather events in the coming decades, such as the increase in temperature, rainfall, summertime, droughts, more frequent and stronger tornadoes and hurricanes. Epidemiological disease cycle includes host, pathogen and in certain cases intermediate host/vector. A complex mixture of various environmental conditions (e.g. temperature and humidity) determines the suitable habitat/ecological niche for every vector host. The availability of suitable vectors is a precondition for the emergence of vector-borne pathogens. Climate changes and global warming will have catastrophic effects on human, animal and environmental ecosystems. Pathogens, especially neglected tropical disease agents, are expected to emerge and re-emerge in several countries including Europe and North America. The lives of millions of people especially in developing countries will be at risk in direct and indirect ways. In the present review, the role of climate changes in the spread of infectious agents and their vectors is discussed. Examples of the major emerging viral, bacterial and parasitic diseases are also summarized.

negative: Coronaviruses: An Overview of Their Replication and Pathogenesis Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. Coronaviruses cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease chickens to potentially lethal human respiratory infections. Here we provide a brief introduction to coronaviruses discussing their replication and pathogenicity, and current prevention and treatment strategies. We will also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).

negative: The role of seabirds of the Iles Eparses as reservoirs and disseminators of parasites and pathogens Abstract The role of birds as reservoirs and disseminators of parasites and pathogens has received much attention over the past several years due to their high vagility. Seabirds are particularly interesting hosts in this respect. In addition to incredible long-distance movements during migration, foraging and prospecting, these birds are long-lived, site faithful and breed in dense aggregations in specific colony locations. These different characteristics can favor both the local maintenance and large-scale dissemination of parasites and pathogens. The Iles Eparses provide breeding and feeding grounds for more than 3 million breeding pairs of seabirds including at least 13 species. Breeding colonies on these islands are relatively undisturbed by human activities and represent natural metapopulations in which seabird population dynamics, movement and dispersal can be studied in relation to that of circulating parasites and pathogens. In this review, we summarize previous knowledge and recently-acquired data on the parasites and pathogens found in association with seabirds of the Iles Eparses. These studies have revealed the presence of a rich diversity of infectious agents (viruses, bacteria and parasites) carried by the birds and/or their local ectoparasites (ticks and louse flies). Many of these agents are widespread and found in other ecosystems confirming a role for seabirds in their large scale dissemination and maintenance. The heterogeneous distribution of parasites and infectious agents among islands and seabird species suggests that relatively independent metacommunities of interacting species may exist within the western Indian Ocean. In this context, we discuss how the patterns and determinants of seabird movements may alter parasite and pathogen circulation. We conclude by outlining key aspects for future research given the baseline data now available and current concerns in eco-epidemiology and biodiversity conservation.

negative: Factors associated with prolonged viral RNA shedding in patients with COVID-19 BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from two hospitals outside Wuhan. RESULTS: The median duration of SARS-CoV-2 RNA detection was 17 days (Interquartile Range [IQR], 13-22 days) as measured from illness onset. When comparing patients with early (<15 days) and late viral RNA clearance (≥15 days after illness onset), prolonged SARS-CoV-2 RNA shedding was associated with male sex (p=0.009), old age (p=0.033), concomitated with hypertension (p=0.009), delayed admission to hospital after illness onset (p=0.001), severe illness at admission (p=0.049), invasive mechanical ventilation (p=0.006), and corticosteroid treatment (p=0.025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (p<0.001) and focal absorption on radiograph images (p<0.001) than patients with early SARS-CoV-2 RNA clearance. Male sex (odds ratio [OR], 3.24 [95% CI, 1.31-8.02]), delayed hospital admission (OR, 1.30 [95% CI, 1.10-1.54]), and invasive mechanical ventilation (OR, 9.88 [95% CI, 1.11-88.02]) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

negative: Chapter 5 Host Range, Host–Virus Interactions, and Virus Transmission Summary Three intricate and intertwined biological features in the replication cycle of viruses are covered in this chapter: The range of cellular entities that support virus replication and/or virus transmission, and the various relationships viruses establish with their hosts and biological vectors. Although in its infancy, an explosion of research on virus–host interactions has already revealed surprising relationships ranging from strictly parasitic to mutualistic, and some others in between. A clearer picture is emerging as regards to our understanding of the full spectrum of these interactions, even with varying experimental approaches and differing opinions on terminology and data interpretation.

negative: COVID-19: An Ophthalmological Update Ever since the newscast of the novel coronavirus outbreak in Wuhan and its subsequent spread to several countries worldwide, the possible modes of spread are being anticipated by various health care professionals. Tear and other conjunctival secretions, being one of the body fluids, can potentially help transmit the disease inadvertently. Conjunctival secretions from patients and asymptomatic contacts of COVID-19 cases may also spread the disease further into the community. Direct inoculation of body fluids into the conjunctiva of healthy individual is also postulated to be another mode of spread. The risk to heath care providers thus becomes strikingly high. A vigilant ophthalmologist can play a critical role in breaking the chain of transmission.

negative: Social Consequences of Ebola Containment Measures in Liberia INTRODUCTION: In the Ebola Virus Disease (EVD) outbreak in Liberia, two major emergency disease-control measures were cremation of bodies and enforcement of quarantine for asymptomatic individuals suspected of being in contact with a positive case. Enforced by State-related actors, these were promoted as the only method to curtail transmissions as soon as possible. However, as with other harsh measures witnessed by Liberian citizens, in many cases those measures elicited uncontrolled negative reactions within the communities (stigma; fear) that produced, in some cases, the opposite effect of that intended. METHODOLOGY: The research has been conducted in two phases, for a total of 8 weeks. Ethnography of local practices was carried out in 7 neighbourhoods in Monrovia and 5 villages in Grand Cape Mount County in Liberia. 45 Focus Group Discussions (432 participants) and 30 semi-structured interviews sustained the observing participation. Randomly selected people from different social layers were targeted. The principal investigator worked with the help of two local assistants. Perceptions and practices were both analysed. RESULTS: Participants stressed how cremation perpetuated the social breakdown that started with the isolation for the sickness. Socio-economical divides were created by inequitable management of the dead: those who could bribe the burial teams obtained a burial in a private cemetery or the use of Funeral Homes. Conversely, those in economic disadvantage were forced to send their dead for cremation. State-enforced quarantine, with a mandatory prohibition of movement, raised condemnation, strengthened stigmatization and created serious socio-economic distress. Food was distributed intermittently and some houses shared latrines with non-quarantined neighbours. Escapes were also recorded. Study participants narrated how they adopted local measures of containment, through local task forces and socially-rooted control of outsiders. They also stressed how information that was not spread built up rumours and suspicion. CONCLUSIONS: Populations experiencing an epidemic feel a high degree of social insecurity, in addition to the health hazards. Vertical and coercive measures increase mistrust and fear, producing a counter-productive effect in the containment of the epidemic. On the other hand, local communities show a will to be engaged and a high degree of flexibility in participating to the epidemic response. Efforts in the direction of awareness and community involvement could prove to be better strategy to control the epidemic and root the response on social participation.

negative: Public Health Interventions and SARS Spread, 2003 The 2003 outbreak of severe acute respiratory syndrome (SARS) was contained largely through traditional public health interventions, such as finding and isolating case-patients, quarantining close contacts, and enhanced infection control. The independent effectiveness of measures to "increase social distance" and wearing masks in public places requires further evaluation. Limited data exist on the effectiveness of providing health information to travelers. Entry screening of travelers through health declarations or thermal scanning at international borders had little documented effect on detecting SARS cases; exit screening appeared slightly more effective. The value of border screening in deterring travel by ill persons and in building public confidence remains unquantified. Interventions to control global epidemics should be based on expert advice from the World Health Organization and national authorities. In the case of SARS, interventions at a country's borders should not detract from efforts to identify and isolate infected persons within the country, monitor or quarantine their contacts, and strengthen infection control in healthcare settings.

negative: Environmental Cleaning and Disinfection The guidelines in this article provide veterinarians, veterinary technicians, and veterinary health care workers with an overview of evidence-based recommendations for the best practices associated with environmental cleaning and disinfection of a veterinary clinic that deals with small animals. Hospital-associated infections and the control and prevention programs necessary to alleviate them are addressed from an environmental perspective. Measures of hospital cleaning and disinfection include understanding mechanisms and types of contamination in veterinary settings, recognizing areas of potential concern, addressing appropriate decontamination techniques and selection of disinfectants, the management of potentially contaminated equipment, laundry, and waste management, and environmental surveillance strategies.

negative: Rapid and accurate identification of COVID-19 infection through machine learning based on clinical available blood test results Since the sudden outbreak of coronavirus disease 2019 (COVID-19), it has rapidly evolved into a momentous global health concern. Due to the lack of constructive information on the pathogenesis of COVID-19 and specific treatment, it highlights the importance of early diagnosis and timely treatment. In this study, 11 key blood indices were extracted through random forest algorithm to build the final assistant discrimination tool from 49 clinical available blood test data which were derived by commercial blood test equipments. The method presented robust outcome to accurately identify COVID-19 from a variety of suspected patients with similar CT information or similar symptoms, with accuracy of 0.9795 and 0.9697 for the cross-validation set and test set, respectively. The tool also demonstrated its outstanding performance on an external validation set that was completely independent of the modeling process, with sensitivity, specificity, and overall accuracy of 0.9512, 0.9697, and 0.9595, respectively. Besides, 24 samples from overseas infected patients with COVID-19 were used to make an in-depth clinical assessment with accuracy of 0.9167. After multiple verification, the reliability and repeatability of the tool has been fully evaluated, and it has the potential to develop into an emerging technology to identify COVID-19 and lower the burden of global public health. The proposed tool is well-suited to carry out preliminary assessment of suspected patients and help them to get timely treatment and quarantine suggestion. The assistant tool is now available online at http://lishuyan.lzu.edu.cn/COVID2019_2/.

negative: Chemotherapeutic control of Gram-positive infection in white sea bream (Diplodus sargus, Linnaeus 1758) broodstock. Aim This study aimed to identify the pathogenic bacteria responsible for the septicemic disease affecting white sea bream brooders and determining the sensitivity of the recovered isolates to different antibiotics followed by estimation of long-acting oxytetracycline (OTC) efficacy in controlling this disease, and finally, determining the proper dose regimen. Materials and Methods Biolog microbial identification system was used for determination of the pathogens which are responsible for this disease. Agar disk diffusion test and minimum inhibitory concentration (MIC) were used to determine the antibiotic susceptibility of recovered isolates. Oxytetracycline (OTC) was used at a dose level of 100 mg/kg body weight for the treatment of diseased fish, and the OTC concentration in the serum samples was determined by high-performance liquid chromatography. Results Fifteen Staphylococcus epidermidis and 11 Bacillus cereus isolates were recovered from the lesion of muscle, tail, eye, and heart blood. S. epidermidis isolates were sensitive to OTC, ciprofloxacin, enrofloxacin, spiramycin, erythromycin (E), and florfenicol. B. cereus isolates were sensitive to all mentioned antibiotics except E. Based on the MIC test, all B. cereus isolates were sensitive to OTC with MIC ranging between <0.125 and 4 µg/ml and 11 S. epidermidis isolates were sensitive with MIC ranging between <0.125 and 8 µg/ml, while four isolates were resistant. Different degrees of degenerative changes were present in the hepatopancreas, posterior kidney, eye, and skin tissues of diseased fish. Conclusion Single intraperitoneal injection of long-acting OTC at a dose of 100 mg/kg body weight was effective in termination of S. epidermidis and B. cereus infection in white sea bream (D. sargus) broodstock.

negative: Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19. Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world. To date, seven known strains of HCoVs belonging to four genera (i.e., α?, β?, γ, and δ-CoV) have been recognized; the latest one has been identified as the SARS-CoV-2. Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body. Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19. Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19. There is a greater need to better understand the mechanisms and risk factors of transmission routes. To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear. Therefore, there is an urgent need for update data on SARS-CoV-2. Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020.

negative: ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged in Chinese people in December 2019 and has currently spread worldwide causing the COVID-19 pandemic with more than 150,000 deaths. In order for a SARS-CoV like virus circulating in wild life for a very long time to infect the index case-patient, a number of conditions must be met, foremost among which is the encounter with humans and the presence in homo sapiens of a cellular receptor allowing the virus to bind. Recently it was shown that the SARS-CoV-2 spike protein, binds to the human angiotensin I converting enzyme 2 (ACE2). This molecule is a peptidase expressed at the surface of lung epithelial cells and other tissues, that regulates the renin-angiotensin-aldosterone system. Humans are not equal with respect to the expression levels of the cellular ACE2. Moreover, ACE2 polymorphisms were recently described in human populations. Here we review the most recent evidence that ACE2 expression and/or polymorphism could influence both the susceptibility of people to SARS-CoV-2 infection and the outcome of the COVID-19 disease. Further exploration of the relationship between the virus, the peptidase function of ACE2 and the levels of angiotensin II in SARS-CoV-2 infected patients should help to better understand the pathophysiology of the disease and the multi-organ failures observed in severe COVID-19 cases, particularly heart failure.

negative: Study of cell to cell transmission of SARS CoV 2 virus particle using gene network from microarray data Microarray data from SARS CoV2 patients helps to construct a gene network relating to this disease. Analysis of these genes, present in network, highlights their biological functions and related cellular pathways. With the assistance of these information, a drug(s) can be identified to treat COVID-19. A detailed analysis of the human host response to SARS CoV 2 with expression profiling by high throughput sequencing has executed with primary human lung epithelium cell lines. Clustered genes annotation and gene network construction are performed with the help of String database. Among four cluster of genes from microarray data, cluster 1 is identified as basal cells with p= 1.37e−05 with 44 genes. Functional enrichment analysis of genes present in gene network has completed using String database, ToppFun online tool and NetworkAnalyst tool. For SARS CoV2 virus particles, keratin proteins, which are part of cytoskeleton structure of host cell, play a major role in cell to cell virus particle transmission. Among three types of cell- cell communication, only anchoring junction between basal cell membrane and basal lamina, is involved in this virus transmission. In this junction point, hemidesmosome structure play a vital role in virus spread from one cell to basal lamina in respiratory tract. In this protein complex structure, keratin, integrin and laminin proteins of host cell is used to promote the spread of virus infection into extracellular matrix. So, small molecular blockers of different anchoring junction proteins i.e. ITGA3, ITGA2 can provide efficient protection against this deadly virus disease. Understanding the human host response against this virus is very important to develop novel therapeutics for the treatment of SARS-CoV 2.

negative: Democracy and the Politics of Coronavirus: Trust, Blame and Understanding This article explores the relationship between crises and democracy through a focus on the unfolding coronavirus pandemic. Its central argument is that to interpret the current pandemic purely in terms of its epidemiology and public health implications risks overlooking its potentially more significant socio-political consequences. This is because the challenges posed by the coronavirus crisis have themselves become overlaid or layered-upon a pre-existing set of concerns regarding the performance, efficiency and capacity of democratic political structures. The aim of this article is to try and understand and warn against what might be termed a rather odd form of cross-contamination whereby the cynicism, negativity and frustration concerning politicians, political processes and political institutions that existed before the coronavirus outbreak is allowed to direct, define and automatically devalue how democratic structures are subsequently judged in terms of how they responded to the challenge. As such, this article focuses on the link between the Coronavirus crisis and the democratic crisis; or, more precisely, the risk that the Coronavirus crisis may mutate into and fuel a broader crisis of democracy.

negative: Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science Summary The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.

negative: A mathematical model for the spatiotemporal epidemic spreading of COVID19 An outbreak of a novel coronavirus, named SARS-CoV-2, that provokes the COVID-19 disease, was first reported in Hubei, mainland China on 31 December 2019. As of 20 March 2020, cases have been reported in 166 countries/regions, including cases of human-to-human transmission around the world. The proportions of this epidemics is probably one of the largest challenges faced by our interconnected modern societies. According to the current epidemiological reports, the large basic reproduction number, R_0 ~ 2.3, number of secondary cases produced by an infected individual in a population of susceptible individuals, as well as an asymptomatic period (up to 14 days) in which infectious individuals are undetectable without further analysis, pave the way for a major crisis of the national health capacity systems. Recent scientific reports have pointed out that the detected cases of COVID19 at young ages is strikingly short and that lethality is concentrated at large ages. Here we adapt a Microscopic Markov Chain Approach (MMCA) metapopulation mobility model to capture the spread of COVID-19. We propose a model that stratifies the population by ages, and account for the different incidences of the disease at each strata. The model is used to predict the incidence of the epidemics in a spatial population through time, permitting investigation of control measures. The model is applied to the current epidemic in Spain, using the estimates of the epidemiological parameters and the mobility and demographic census data of the national institute of statistics (INE). The results indicate that the peak of incidence will happen in the first half of April 2020 in absence of mobility restrictions. These results can be refined with improved estimates of epidemiological parameters, and can be adapted to precise mobility restrictions at the level of municipalities. The current estimates largely compromises the Spanish health capacity system, in particular that for intensive care units, from the end of March. However, the model allows for the scrutiny of containment measures that can be used for health authorities to forecast with accuracy their impact in prevalence of COVID--19. Here we show by testing different epidemic containment scenarios that we urge to enforce total lockdown to avoid a massive collapse of the Spanish national health system.

negative: New Insights of Emerging SARS-CoV-2: Epidemiology, Etiology, Clinical Features, Clinical Treatment, and Prevention Since the first reports that the novel coronavirus was showing human-to-human transmission characteristics and asymptomatic cases, the number of patients with associated pneumonia has continued to rise and the epidemic has grown. It now threatens the health and lives of people across the world. The governments of many countries have attached great importance to the prevention of SARS-CoV-2, via research into the etiology and epidemiology of this newly emerged disease. Clinical signs, treatment, and prevention characteristics of the novel coronavirus pneumonia have been receiving attention worldwide, especially from medical personnel. However, owing to the different experimental methods, sample sizes, sample sources, and research perspectives of various studies, results have been inconsistent, or relate to an isolated aspect of the virus or the disease it causes. Currently, systematic summary data on the novel coronavirus are limited. This review combines experimental and clinical evidence into a systematic analysis and summary of the current progress of research into SARS-CoV-2, from multiple perspectives, with the aim of gaining a better overall understanding of the disease. Our report provides important information for current clinicians, for the prevention and treatment of COVID-19 pneumonia.

negative: Chapter Two Pathogen and Particle Associations in Wastewater Significance and Implications for Treatment and Disinfection Processes Abstract Disinfection guidelines exist for pathogen inactivation in potable water and recycled water, but wastewater with high numbers of particles can be more difficult to disinfect, making compliance with the guidelines problematic. Disinfection guidelines specify that drinking water with turbidity ≥1 Nephelometric Turbidity Units (NTU) is not suitable for disinfection and therefore not fit for purpose. Treated wastewater typically has higher concentrations of particles (1–10NTU for secondary treated effluent). Two processes widely used for disinfecting wastewater are chlorination and ultraviolet radiation. In both cases, particles in wastewater can interfere with disinfection and can significantly increase treatment costs by increasing operational expenditure (chemical demand, power consumption) or infrastructure costs by requiring additional treatment processes to achieve the required levels of pathogen inactivation. Many microorganisms (viruses, bacteria, protozoans) associate with particles, which can allow them to survive disinfection processes and cause a health hazard. Improved understanding of this association will enable development of cost-effective treatment, which will become increasingly important as indirect and direct potable reuse of wastewater becomes more widespread in both developed and developing countries. This review provides an overview of wastewater and associated treatment processes, the pathogens in wastewater, the nature of particles in wastewater and how they interact with pathogens, and how particles can impact disinfection processes.

negative: Visualization of Putative Coronavirus in Kidney

negative: Assisted respiration using CPAP via face-mask in patients with blunt chest trauma. An alternative to intubation and mechanical ventilation: Eine Alternative zur Intubation Intubation and Positive End Expiratory Pressure Ventilation (PEEP) is a well established therapeutic strategy for impaired lung function, particularly following blunt chest trauma. Complications of this regime are however also well known and pose the question why non-invasive forms of respiratory assistance such as Continuous Positive Airway Pressure (CPAP) have only gained minor popularity. In a prospective study, 30 patients who had suffered blunt chest trauma were treated with CPAP administered by mask. The regime consisted of continuous administration of CPAP by a face-mask, with gradually increasing periods of spontaneous breathing. Initially a FiO(2) of 0.33 (range 0,28–0,38) proved necessary. The initial CPAP level was 7 mbar (range 5–8) with an (Assisted Spontaneous Breathing) ASB of 15 mbar (range 13–18). FiO(2) and CPAP/ASB levels were subsequently gradually reduced until no longer necessary. In all patients intubation and ventilation was avoided by this regimen. The treatment was well accepted by all patients and common ventilation associated complications such as pneumonia did not occur. In comparison with the former standard method of treatment the average ICU stay was dramatically reduced, principally due to not having to gradually wean patients from ventilation and sedation. Other positive benefits include normal communication and feeding with active early mobilisation leading to faster recovery, both physical and psychological. We conclude that non-invasive respiratory techniques should be used more frequently and recommend further studies are undertaken to define the indications.

negative: Wild-type human coronaviruses prefer cell-surface TMPRSS2 to endosomal cathepsins for cell entry Abstract Human coronaviruses (HCoVs) enter cells via two distinct pathways: the endosomal pathway using cathepsins to activate spike protein and the cell-surface or early endosome pathway using extracellular proteases such as transmembrane protease serine 2 (TMPRSS2). We previously reported that clinical isolates of HCoV-229E preferred cell-surface TMPRSS2 to endosomal cathepsin for cell entry, and that they acquired the ability to use cathepsin L by repeated passage in cultured cells and were then able to enter cells via the endosomal pathway. Here, we show that clinical isolates of HCoV-OC43 and -HKU1 preferred the cell-surface TMRRSS2 to endosomal cathepsins for cell entry, similar to HCoV-229E. In addition, the cell-culture-adapted HCoV-OC43 lost the ability to infect and replicate in air-liquid interface cultures of human bronchial tracheal epithelial cells. These results suggest that circulating HCoVs in the field generally use cell-surface TMPRSS2 for cell entry, not endosomal cathepsins, in human airway epithelial cells.

negative: Unique and Conserved Features of Genome and Proteome of SARS-coronavirus, an Early Split-off From the Coronavirus Group 2 Lineage Abstract The genome organization and expression strategy of the newly identified severe acute respiratory syndrome coronavirus (SARS-CoV) were predicted using recently published genome sequences. Fourteen putative open reading frames were identified, 12 of which were predicted to be expressed from a nested set of eight subgenomic mRNAs. The synthesis of these mRNAs in SARS-CoV-infected cells was confirmed experimentally. The 4382- and 7073 amino acid residue SARS-CoV replicase polyproteins are predicted to be cleaved into 16 subunits by two viral proteinases (bringing the total number of SARS-CoV proteins to 28). A phylogenetic analysis of the replicase gene, using a distantly related torovirus as an outgroup, demonstrated that, despite a number of unique features, SARS-CoV is most closely related to group 2 coronaviruses. Distant homologs of cellular RNA processing enzymes were identified in group 2 coronaviruses, with four of them being conserved in SARS-CoV. These newly recognized viral enzymes place the mechanism of coronavirus RNA synthesis in a completely new perspective. Furthermore, together with previously described viral enzymes, they will be important targets for the design of antiviral strategies aimed at controlling the further spread of SARS-CoV.

negative: Standardized diagnosis and treatment of colorectal cancer during the outbreak of novel coronavirus pneumonia in Renji hospital/ 中华胃肠外科杂志 Novel coronavirus pneumonia (NCP) is currently raging in China. It has been proven that NCP can be transmitted from human to human and cause hospital infection, which seriously threatens surgical staffs and inpatients. Although colorectal surgery is not a front-line subject in the fight against the epidemic, but in this special situation, now it is a difficult task that with the premise of how to maximize the protection for patients and their families, health of medical staff, and the safety of wards and hospitals, we can provide the highest quality medical services to ensure the orderly development of previous clinical work. Referring to the "Diagnosis and Treatment Scheme for NCP (Trial Version 4 and 5)" and combining the actual practice situation in our hospital with the "Summary of New Coronavirus Files of Shanghai Renji Hospital", we summarize how to carry out the clinical practice of colorectal surgery under the situation of the prevention and control of the NCP epidemiology, meanwhile under such situation aiming the procedure of diagnose and treatment for emergency patients with colorectal tumor, we share the experiences of the diagnosis of colorectal tumor, the management of patients with colorectal cancer who are scheduled to be admitted for surgery, the protection of wards, the perioperative management. More importantly, we introduce in detail the operative management and perioperative management of colorectal surgery patients suspected or diagnosed with new coronary pneumonia, including prevention and control measures for medical staff, operating rooms and surgical instruments. The main points are as follows: (1) Multidisciplinary team (MDT) must be run through the diagnosis and treatment of colorectal cancer. The members include not only routine departments, but also respiratory department and infectious department. (2) Colonoscopy examination may cause cross infection of NCP to patients and doctors. Therefore, it is prior to examine the emergency cases and life-threatening patients (bleeding, obstruction, gastrointestinal foreign bodies, etc.). If the emergent patients (intestinal obstruction) with suspected or confirmed NCP, the surgeons must perform emergency surgery, and intestinal decompressive tube through colonoscopy is not recommended. (3) The colorectal cancer patients with suspected or confirmed NCP should be placed in the isolated room with separate medical devices, and the operative room with negative pressure (under-5 Pa) must be separated. All disposable medical items, body fluids and feces of the patients in perioperative periods must be unified disposed according to the medical waste standard. (4) The surgical medical workers who process colorectal cancer patients with NCP must be protected by three-level. After operation, the medical workers must receive medical observation and be isolated for 14 days. We hope our "Renji experience" will be beneficial to colleagues.

negative: Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS‐CoV) and its putative receptor, angiotensin‐converting enzyme 2 (ACE2) Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a new coronavirus, SARS‐CoV. Pulmonary involvement is the dominant clinical feature but extra‐pulmonary manifestations are also common. Factors that account for the wide spectrum of organ system involvement and disease severity are poorly understood and the pathogenesis of SARS‐CoV infection remains unclear. Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional cellular receptor for SARS‐CoV. Studies of the tissue and cellular distribution of SARS‐CoV, and ACE2 protein expression, reveal new insights into the pathogenesis of this deadly disease. ACE2 is expressed at high level in the primary target cells of SARS‐CoV, namely pneumocytes and surface enterocytes of the small intestine. Despite the fact that SARS‐CoV can infect the lung and intestine, the tissue responses in these two organs are different. All other tissues and cell types expressing ACE2 may be potential targets of SARS‐CoV infection. Remarkably, endothelial cells, which express ACE2 to a high level, have not been shown to be infected by SARS‐CoV. There is also evidence that cell types without detectable ACE2 expression may also be infected by the virus. Furthermore, studies in a new human cell culture model have indicated that the presence of ACE2 alone is not sufficient for maintaining viral infection. Therefore, other virus receptors or co‐receptors may be required in different tissues. Moreover, the interaction between SARS‐CoV and the immunological or lymphoid system remains to be defined. It is clear that we are only at the dawn of our understanding of the pathogenesis of SARS. As our knowledge of the pathogenic mechanisms improves, a more rational approach to therapeutic and vaccine development can be designed in order to combat this new and fatal human disease. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

negative: Chapter Eight Molecular Basis of Coronavirus Virulence and Vaccine Development Abstract Virus vaccines have to be immunogenic, sufficiently stable, safe, and suitable to induce long-lasting immunity. To meet these requirements, vaccine studies need to provide a comprehensive understanding of (i) the protective roles of antiviral B and T-cell-mediated immune responses, (ii) the complexity and plasticity of major viral antigens, and (iii) virus molecular biology and pathogenesis. There are many types of vaccines including subunit vaccines, whole-inactivated virus, vectored, and live-attenuated virus vaccines, each of which featuring specific advantages and limitations. While nonliving virus vaccines have clear advantages in being safe and stable, they may cause side effects and be less efficacious compared to live-attenuated virus vaccines. In most cases, the latter induce long-lasting immunity but they may require special safety measures to prevent reversion to highly virulent viruses following vaccination. The chapter summarizes the recent progress in the development of coronavirus (CoV) vaccines, focusing on two zoonotic CoVs, the severe acute respiratory syndrome CoV (SARS-CoV), and the Middle East respiratory syndrome CoV, both of which cause deadly disease and epidemics in humans. The development of attenuated virus vaccines to combat infections caused by highly pathogenic CoVs was largely based on the identification and characterization of viral virulence proteins that, for example, interfere with the innate and adaptive immune response or are involved in interactions with specific cell types, such as macrophages, dendritic and epithelial cells, and T lymphocytes, thereby modulating antiviral host responses and viral pathogenesis and potentially resulting in deleterious side effects following vaccination.

negative: Capacity in the time of Coronavirus Abstract In the course of a few short weeks, many of the established legal frameworks relating to decision-making in England & Wales in respect of those with impaired decision-making capacity have been ripped up, or apparently rendered all but unusable. Although the Mental Capacity Act 2005 itself was not amended, the impact of other legislation (especially the Coronavirus Act 2020) means that duties towards those with impaired decision-making capacity have been radically changed. This article reflects the experience of a practising barrister in England & Wales grappling with the impact of COVID-19 upon the Mental Capacity Act 2005 across a range of fields in the weeks after the world appeared to change in mid-March 2020.

negative: Guidelines for preventing respiratory illness in older adults aged 60 years and above living in long-term care: A rapid review of clinical practice guidelines Background: The overall objective of this rapid review was to identify infection protection and control recommendations from published clinical practice guidelines (CPGs) for adults aged 60 years and older in long-term care settings Methods: Comprehensive searches in MEDLINE, EMBASE, the Cochrane Library, and relevant CPG publishers/repositories were carried out in early March 2020. Title/abstract and full-text screening, data abstraction, and quality appraisal (AGREE-II) were carried out by single reviewers. Results: A total of 17 relevant CPGs were identified, published in the USA (n=8), Canada (n=6), Australia (n=2), and the United Kingdom (n=1). All of the CPGs dealt with infection control in long-term care facilities (LTCF) and addressed various types of viral respiratory infections (e.g., influenza, COVID-19, severe acute respiratory syndrome). Ten or more CPGs recommended the following infection control measures in LTCF: hand hygiene (n=13), wearing personal protective equipment (n=13), social distancing or isolation (n=13), disinfecting surfaces (n=12), droplet precautions (n=12), surveillance and evaluation (n=11), and using diagnostic testing to confirm illness (n=10). While only two or more CPGs recommended these infection control measures: policies and procedures for visitors, staff and/or residents (n=9), respiratory hygiene/cough etiquette (n=9), providing supplies (n=9), staff and/or residents education (n=8), increasing communication (n=6), consulting or notifying health professionals (n=6), appropriate ventilation practices (n=2), and cohorting equipment (n=2). Ten CPGs also addressed management of viral respiratory infections in LTCF and recommended antiviral chemoprophylaxis (n=10) and one CPG recommended early mobilization of residents. Conclusion: The recommendations from current guidelines overall seem to support environmental measures for infection prevention and antiviral chemoprophylaxis for infection management as the most appropriate first-line response to viral respiratory illness in long-term care.

negative: Coronavirus Disease 2019: Coronaviruses and Blood Safety Abstract With the outbreak of unknown pneumonia in Wuhan, China, in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19). The World Health Organization declared COVID-19 in China as a Public Health Emergency of International Concern. Two other coronavirus infections—SARS in 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2012—both caused severe respiratory syndrome in humans. All 3 of these emerging infectious diseases leading to a global spread are caused by β-coronaviruses. Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS–CoV, and SARS-CoV-2 through blood products as of February 10, 2020, and also discuss pathogen inactivation methods on coronaviruses.

negative: The Perfect Storm: Coronavirus (Covid-19) Pandemic Meets Overfat Pandemic

negative: Potentiating health and the crisis of the immune system: integrative approaches to prevention and healing of modern diseases

negative: The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease Abstract Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.

negative: Gastrointestinal Infection Could Be New Focus for Coronavirus Diagnosis It's not news to tell you that the coronavirus, known as COVID-19, is a worldwide pandemic. The initial outbreak of this novel virus in Wuhan in the Hubei province of China, first described in December 2019, has since moved on to being declared a pandemic by the World Health Organization. The classic description of COVID-19 is a respiratory illness that manifests with fever, dry cough, and dyspnea on exertion. However, gastrointestinal (GI) complication of COVID-19 is emerging as well. This was observed with similar viral respiratory illnesses, such as severe acute respiratory syndrome (SARS), which emerged in 2003, and the Middle East respiratory syndrome (MERS), which emerged in 2012. In a recently published, single-center case series of 138 consecutive hospitalized patients with confirmed COVID-19, investigators reported that approximately 10% of patients initially presented with GI symptoms, prior to the subsequent development of respiratory symptoms. Common and often very subtle symptoms included diarrhea, nausea, and abdominal pain, with a less common symptom being nonspecific GI illness. New studies are expanding our understanding of the possible fecal transmission of COVID-19. Assessment by polymerase chain reaction (PCR) has provided evidence of the virus in the stool and the oropharynx outside the nasopharynx and respiratory tract. Virus in the stool may be evident on presentation and last throughout the course of illness resolution for up to 12 days after the respiratory virus evidence is gone. In fact, in one of the most recent studies looking at 73 patients, approximately 24% remained positive in their stool for evidence of the virus, though not necessarily infection, after showing negative in respiratory samples. The Centers for Disease Control and Prevention (CDC) recommends that after two negative respiratory tests separated by ≥ 24 hours, patients can be dismissed from having transmissibility infection risk for COVID-19. The potential for fecal-oral transmission of COVID-19 needs to be strongly considered. Considering these cases and the lessons from SARS, many authors recommend that real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from feces should be performed routinely in SARS-CoV-2 patients.

negative: Prevalence of Underlying Diseases in Hospitalized Patients with COVID-19: a Systematic Review and Meta-Analysis INTRODUCTION: In the beginning of 2020, an unexpected outbreak due to a new corona virus made the headlines all over the world. Exponential growth in the number of those affected makes this virus such a threat. The current meta-analysis aimed to estimate the prevalence of underlying disorders in hospitalized COVID-19 patients. METHODS: A comprehensive systematic search was performed on PubMed, Scopus, Web of science, and Google scholar, to find articles published until 15 February 2020. All relevant articles that reported clinical characteristics and epidemiological information of hospitalized COVID-19 patients were included in the analysis. RESULTS: The data of 76993 patients presented in 10 articles were included in this study. According to the meta-analysis, the pooled prevalence of hypertension, cardiovascular disease, smoking history and diabetes in people infected with SARS-CoV-2 were estimated as 16.37% (95%CI: 10.15%-23.65%), 12.11% (95%CI 4.40%-22.75%), 7.63% (95%CI 3.83%-12.43%) and 7.87% (95%CI 6.57%-9.28%), respectively. CONCLUSION: According to the findings of the present study, hypertension, cardiovascular diseases, diabetes mellitus, smoking, chronic obstructive pulmonary disease (COPD), malignancy, and chronic kidney disease were among the most prevalent underlying diseases among hospitalized COVID-19 patients, respectively.

negative: Immunity after natural exposure to enteric canine coronavirus does not provide complete protection against infection with the new pantropic CB/05 strain Abstract Recently, an outbreak of fatal infection caused by a pantropic variant (strain CB/05) of canine coronavirus (CCoV) has been reported. In this study, evidence is provided that immunity induced by natural exposure to enteric CCoV is not fully protective against strain CB/05. Twenty-two, 10-week-old beagles with a recent natural infection by enteric CCoV were randomly distributed in two experimental groups of eight (groups A and B) and one control group of six (group C) dogs. Dogs in groups A and B were inoculated oronasally with different doses (4×105 or 4×103 TCID50) of the pantropic strain CB/05, whereas dogs in group C were used as negative controls. Clinical, post-mortem and virological investigations showed that, despite the high serum antibody titres induced by the prior natural infection with enteric CCoV, dogs were susceptible to experimental infection with strain CB/05. This was shown by the occurrence of faecal shedding, and dogs displaying moderate clinical signs, mainly vomiting and diarrhoea. Involvement of the lymphoid tissues was evident as demonstrated by the acute lymphopenia (below 70% of the initial counts), gross lesions in spleen and lymph nodes and detection of CB/05 RNA in thymus, spleen and lymph nodes of some infected dogs. The presence of viral RNA in lymphoid tissues was observed only in dogs euthanised in the early stages of infection and the clinical course of the infection was unrelated to the viral dose administered. The present study demonstrates that strain CB/05 is able to induce infection and disease in dogs seropositive to enteric CCoV, thus highlighting the need for extensive epidemiological investigation and for the possible development of novel antigenically relevant vaccines.

negative: Metagenomics detection and characterisation of viruses in faecal samples from Australian wild birds We present an optimised metagenomics method for detection and characterisation of all virus types including single and double stranded DNA/RNA and enveloped and non-enveloped viruses. Initial evaluation included both spiked and non-spiked bird faecal samples as well as non-spiked human faecal samples. From the non-spiked bird samples (Australian Muscovy duck and Pacific black ducks) we detected 21 viruses, and we also present a summary of a few viruses detected in human faecal samples. We then present a detailed analysis of selected virus sequences in the avian samples that were somewhat similar to known viruses, and had good quality (Q20 or higher) and quantity of next-generation sequencing reads, and was of interest from a virological point of view, for example, avian coronavirus and avian paramyxovirus 6. Some of these viruses were closely related to known viruses while others were more distantly related with 70% or less identity to currently known/sequenced viruses. Besides detecting viruses, the technique also allowed the characterisation of host mitochondrial DNA present and thus identifying host species, while ribosomal RNA sequences provided insight into the “ribosomal activity microbiome”; of gut parasites; and of food eaten such as plants or insects, which we correlated to non-avian host associated viruses.

negative: [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Objective: An outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. Here, we report results of a descriptive, exploratory analysis of all cases diagnosed as of February 11, 2020. Methods: All COVID-19 cases reported through February 11, 2020 were extracted from China's Infectious Disease Information System. Analyses included: 1) summary of patient characteristics; 2) examination of age distributions and sex ratios; 3) calculation of case fatality and mortality rates; 4) geo-temporal analysis of viral spread; 5) epidemiological curve construction; and 6) subgroup analysis. Results: A total of 72 314 patient records-44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, 10567 (14.6%) clinical diagnosed cases (Hubei only), and 889 asymptomatic cases (1.2%)-contributed data for the analysis. Among confirmed cases, most were aged 30-79 years (86.6%), diagnosed in Hubei (74.7%), and considered mild (80.9%). A total of 1 023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%. The COVID-19 spread outward from Hubei sometime after December 2019 and by February 11, 2020, 1 386 counties across all 31 provinces were affected. The epidemic curve of onset of symptoms peaked in January 23-26, then began to decline leading up to February 11. A total of 1 716 health workers have become infected and 5 have died (0.3%). Conclusions: The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest of Mainland China. With many people returning from a long holiday, China needs to prepare for the possible rebound of the epidemic.

negative: Can we contain the COVID-19 outbreak with the same measures as for SARS? Summary The severe acute respiratory syndrome (SARS) outbreak in 2003 resulted in more than 8000 cases and 800 deaths. SARS was eventually contained by means of syndromic surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine. By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82 000 confirmed cases of COVID-19 have been reported with more than 2800 deaths. Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19. COVID-19 differs from SARS in terms of infectious period, transmissibility, clinical severity, and extent of community spread. Even if traditional public health measures are not able to fully contain the outbreak of COVID-19, they will still be effective in reducing peak incidence and global deaths. Exportations to other countries need not result in rapid large-scale outbreaks, if countries have the political will to rapidly implement countermeasures.

negative: Infection with a pathogenic turkey coronavirus isolate negatively affects growth performance and intestinal morphology of young turkey poults in Canada. Turkey coronavirus (TCoV) is an important viral pathogen causing diarrhoea of young turkey poults that is associated with sizeable economic losses for the turkey industry. Using a field isolate that was found to be free from turkey astrovirus and avian reovirus we were able to reproduce the clinical disease associated with TCoV. Clinical signs and weight gain of poults during experimental infections were compared with age-matched, uninfected controls. Poults infected at 2 days of age had 100% morbidity and 10% mortality, and birds infected at 28 days of age showed 75% morbidity and no mortality. Diarrhoea was consistently seen in infected poults at 2 to 3 days post infection (d.p.i.) with a duration of about 3 to 5 days. Mean body weights of birds infected at 2 or 28 days of age were significantly reduced compared with uninfected birds by 7 d.p.i. and remained significantly lower for the duration of the study. At 44 days of age, poults infected at 2 or 28 days of age weighed only 68.1% or 77.7%, respectively, compared with uninfected turkeys of the same age on the same diet, a mean difference in body weights of 683 or 477g, respectively. Infected birds had profound villus atrophy with some compensatory crypt hyperplasia at 5 to 7 d.p.i. Villus heights in the duodenum were significantly reduced at 7 d.p.i. We were able to reproduce enteric disease using only a pathogenic field isolate (MG10) of TCoV that negatively affected growth performance and intestinal morphology of young turkey poults.

negative: Further studies on human enteric coronaviruses Comparisons were made between human enteric coronaviruses and the enteric coronaviruses of pigs and calves by negative staining. Examination of human intestinal organ culture fluids at various time intervals after inoculation with the human enteric coronavirus showed increasing numbers of particles in the fluids. Thin sections of the columnar epithelial cells of these explants showed a number of features consistent with the replication of known human and animal coronaviruses. Virus particles found in thin sections had a mean diameter of 68 nm. In addition, a structure was found in thin sections which has not been described previously. This structure may represent the viral nucleocapsid.

negative: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

negative: Coronavirus Disease 2019 (COVID-19): An Evidence Map of Medical Literature Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of May 2020, gaps in the existing literature remain unidentified and, hence, unaddressed. In this paper, we summarise the medical literature on COVID-19 between 1 January and 24 March 2020 using evidence maps and bibliometric analysis in order to systematically identify gaps and propose areas for valuable future research. The examined COVID-19 medical literature originated primarily from Asia and focussed mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health research, the use of novel technologies and artificial intelligence, research on the pathophysiology of COVID-19 within different body systems, and research on indirect effects of COVID-19 on the care of non-COVID-19 patients. Research collaboration at the international level was limited although improvements may aid global containment efforts.

negative: Computed Tomography Manifestations of 5 Cases of the Novel Coronavirus Disease 2019 (COVID-19) Pneumonia From Patients Outside Wuhan Clinical, laboratory, and computed tomography (CT) findings of 5 cases of the novel Coronavirus Disease 2019 (COVID-19) pneumonia from patients outside of Wuhan were reviewed. The human-to-human transmission of the virus may explain the infection of the disease outside of Wuhan. CT examination is important in the early detection and follow-up of the disease. With a history of exposure or travelling, symptoms of fever and cough, and the typical CT manifestation such as ground-glass opacity with a peripheral distribution, we should also think of the possibility of the COVID-19 pneumonia in patients outside of Wuhan.

negative: The Search for a Practical Approach to Emerging Diseases: The Case of Severe Acute Respiratory Syndrome (SARS) The plague, which the Board of Health had feared might enter with the German troops into the Milanese, had entered it indeed, as is well known; and it is likewise well known, that it paused not here, but invaded and ravaged a great part of Italy. (A. Manzoni, The Bethrothed, 1826)

negative: [Clinical symptoms and diagnosis of feline infectious peritonitis]. Body effusions from 197 cats and blood serum samples from 252 cats, where Feline Infectious Peritonitis (FIP) was part of the differential diagnosis, were analysed. The diagnoses were confirmed by clinical follow up or histopathology. The final diagnosis FIP was always confirmed by histopathology. The median age of cats with FIP was 1.6 years. FIP was responsible for 41% of the body effusions, whereas malignomas caused 24%, cardial insufficiencies 14% and purulent serositis 12% of the body effusions. The rivalta test was highly sensitive for FIP. Predictive value of a negative result was 100%, predictive value of a positive result was 84%. In half of the cases with purulent serositis and in 20% of malignomas rivalta reacted positive. The cardial insufficiencies were negative for rivalta. Coronavirus antigen could be demonstrated by immunofluorescence in 34 of 49 body effusions caused by FIP, whereas in the 50 body effusions caused by other diseases no coronavirus antigen was detected. An albumin globulin ratio of < 0.6 was highly diagnostic for an inflammatory process, nearly exclusively for FIP. An albumin globulin ratio of > or = 0.8 almost excluded FIP. Only a negative or very high (1:1600) FIP titer could contribute to confirm diagnosis. Low and medium titers, however, should not be interpreted.

negative: Zoonotic origins of human coronaviruses Mutation and adaptation have driven the co-evolution of coronaviruses (CoVs) and their hosts, including human beings, for thousands of years. Before 2003, two human CoVs (HCoVs) were known to cause mild illness, such as common cold. The outbreaks of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) have flipped the coin to reveal how devastating and life-threatening an HCoV infection could be. The emergence of SARS-CoV-2 in central China at the end of 2019 has thrusted CoVs into the spotlight again and surprised us with its high transmissibility but reduced pathogenicity compared to its sister SARS-CoV. HCoV infection is a zoonosis and understanding the zoonotic origins of HCoVs would serve us well. Most HCoVs originated from bats where they are non-pathogenic. The intermediate reservoir hosts of some HCoVs are also known. Identifying the animal hosts has direct implications in the prevention of human diseases. Investigating CoV-host interactions in animals might also derive important insight on CoV pathogenesis in humans. In this review, we present an overview of the existing knowledge about the seven HCoVs, with a focus on the history of their discovery as well as their zoonotic origins and interspecies transmission. Importantly, we compare and contrast the different HCoVs from a perspective of virus evolution and genome recombination. The current CoV disease 2019 (COVID-19) epidemic is discussed in this context. In addition, the requirements for successful host switches and the implications of virus evolution on disease severity are also highlighted.

negative: CT Manifestations of Two Cases of 2019 Novel Coronavirus (2019-nCoV) Pneumonia

negative: Mechanisms of synergy in polymicrobial infections Communities of microbes can live almost anywhere and contain many different species. Interactions between members of these communities often determine the state of the habitat in which they live. When these habitats include sites on the human body, these interactions can affect health and disease. Polymicrobial synergy can occur during infection, in which the combined effect of two or more microbes on disease is worse than seen with any of the individuals alone. Powerful genomic methods are increasingly used to study microbial communities, including metagenomics to reveal the members and genetic content of a community and metatranscriptomics to describe the activities of community members. Recent efforts focused toward a mechanistic understanding of these interactions have led to a better appreciation of the precise bases of polymicrobial synergy in communities containing bacteria, eukaryotic microbes, and/or viruses. These studies have benefited from advances in the development of in vivo models of polymicrobial infection and modern techniques to profile the spatial and chemical bases of intermicrobial communication. This review describes the breadth of mechanisms microbes use to interact in ways that impact pathogenesis and techniques to study polymicrobial communities.

negative: Flu or a Bug? Of late, apart from the four calendar seasons, there is yet another season referred to as the “flu season.” During this time of the year, we routinely hear the phrase “the flu is going around.” I was surprised last week when I heard my 6-year-old son mention to me that there is some bug going around in his class and that his best friend was sick. I asked him to define the bug and he said it causes stuffy nose. The word “bug” is used so callously by adults that it has been registered wrongly in the minds of the little ones.

negative: Tackling the Global Challenge: Humanitarian Catastrophes “Humanitarian catastrophes,” conflicts and calamities generating both widespread human suffering and destructive events, require a wide range of emergency resources. This paper answers a number of questions that humanitarian catastrophes generate: Why and how do the most-developed countries—those with the resources, capabilities, and willingness to help—intervene in specific types of disasters? What ethical and legal guidelines shape our interventions? How well do we achieve our goals? It then suggests a number of changes to improve humanitarian responses, including better NGO-government cooperation, increased research on the best disaster response methods, clarification of the criteria and roles for humanitarian (military) interventions, and development of post-2015 Millennium Development Goals with more accurate progress measures.

negative: Safety and efficacy of a modified-live canine coronavirus vaccine in dogs Abstract The safety and the efficacy of a modified-live (ML) canine coronavirus (CCoV) vaccine strain 257/98-3c was evaluated in 14 dogs seronegative and virus negative for CCoV. For the safety test, four dogs were inoculated, two by intramuscular and two by oronasal route, with 10 times the vaccinal dose. During the observation period (28 days) all dogs did not display any local or systemic reaction. For the efficacy test, eight dogs were vaccinated by intramuscular (four dogs—group A) or by oronasal route (four dogs—group B). Two dogs were maintained as non-vaccinated controls. In the dogs of group A, vaccinal virus was not detected in faecal samples by virus isolation (VI) and by PCR assay, while in the dogs of group B, the virus was revealed for six median days only by PCR. Twenty-eight days later, the vaccinated and control dogs were challenged with a field CCoV strain. After the challenge, the vaccinated dogs did not display clinical signs and the dogs of group A shed virus for 5.5 median days, evaluated by VI, and for 10 median days evaluated by PCR. Virus shedding was not observed, both by VI and PCR assay, in the dogs of group B. The two control dogs displayed moderate clinical signs and the virus was detected by VI for 14.5 median days starting from day 3 post-challenge (dpc 3) and by PCR assay for 23 median days starting from dpc 1.

negative: SARS Coronavirus Pathogenesis and Therapeutic Treatment Design Emerging pathogens are either new or newly recognized or those that are increasing in incidence and spread. Since the identity of emerging pathogens from animal reservoirs is difficult to predict, the development for pathogen-specific therapeutics and vaccines is problematic. The highly pathogenic SARS coronavirus (SARS-CoV) emerged from zoonotic pools in 2002 to cause a global epidemic of severe acute respiratory syndrome (SARS). Many patients with SARS-CoV experienced an exacerbated form of disease called acute respiratory distress syndrome (ARDS) requiring mechanical ventilation and supplemental oxygen and half of these patients died. Similar to other viral pathogens like influenza and West Nile Virus, the severity of SARS-CoV disease increased with age. Unfortunately, successful vaccination in the most vulnerable populations is a difficult task because of immunological deficiencies associated with aging (immune senescence). Due to the rapidity of virus emergence, technologies like synthetic biology can be harnessed to facilitate rapid recombinant virus construction for studying the novel virus biology, pathogenesis and the evaluation of therapeutic interventions. Since predicting the antigenic identity of future emergence is difficult, candidate vaccines and therapeutics should have a maximal breadth of cross-protection, and panels of antigenically divergent synthetically reconstructed viruses can be used as tools for this evaluation. We discuss how synthetic reconstruction of many animal and human SARS-CoV has provided a model to study the molecular mechanisms governing emergence and pathogenesis of viral diseases. In addition, we review the evolution, epidemiology, and pathogenesis of epidemic and zoonotic SARS-CoV with focus on the development of broadly reactive therapeutics and vaccines that protect aged populations from the zoonotic pool.

negative: COVID-19 outbreak: less stethoscope, more ultrasound

negative: Chapter 14 The Human Microbiome and Personalized Medicine As the group of organisms living most closely with humans, the relationship between microbes and humans is a very tight and intimate one. They live in nearly every possible ecological niche in or on the human body and play diverse and important roles in human health; some microbes influence our ability to digest food, some help protect the human body against pathogens, and some may become the cause of disease. As disease states caused by diverse members of various microbial communities have been identified, microbial genomes have been paid a lot of attention, and scientists have uncovered a notably high individual level of microbial diversity that promises increasing relevance to personalized medicine. Keywords disease, gut microbe, human microbiome, nasal microbe, oral microbe, personalized medicine, skin microbe, vaginal microbe

negative: New insights about the regulation of Nidovirus subgenomic mRNA synthesis Abstract The members of the Order Nidovirales share a similar genome organization with two overlapping nonstructural polyproteins encoded in the 5′ two-thirds and the structural proteins encoded in the 3′ third. They also express their 3′ region proteins from a nested set of 3′ co-terminal subgenomic messenger RNAs (sg mRNAs). Some but not all of the Nidovirus sg mRNAs also have a common 5′ leader sequence that is acquired by a discontinuous RNA synthesis mechanism regulated by multiple 3′ body transcription regulating sequences (TRSs) and the 5′ leader TRS. Initial studies detected a single major body TRS for each 3′ sg mRNA with a few alternative functional TRSs reported. The recent application of advanced techniques, such as next generation sequencing and ribosomal profiling, in studies of arteriviruses and coronaviruses has revealed an expanded sg mRNA transcriptome and coding capacity.

negative: [The War Against the Coronavirus Disease (COVID-2019): Keys to Successfully Defending Taiwan] The outbreak of COVID-19 triggered the largest human-virus war in this century. Current evidence indicates that the SARS-CoV-2 strain of coronavirus is mainly transmitted by droplets either by direct or indirect contact. The duration of infectiousness of COVID-19 ranges from 1-2 days before and 7-10 days after the onset of symptoms. It is often difficult to detect the signs and symptoms of infection and to implement timely intervention during the very early stage of infection. Thus, finding and isolating symptomatic patients may not be sufficient to contain this epidemic. Therefore, it is very important to wear masks, take personal precautions, and practice recommended social distancing to achieve source control and stop transmission. Taiwan has learned from its previous experience with the SARS epidemic and prepared for the potential of new disease outbreaks for at least 17 years. This helped the government to implement a multifaceted strategy in the early stages of the COVID-19 outbreak. Taiwan's effective response has made the country a model for pandemic response policy that has been appreciated internationally. This paper examines COVID-19 epidemic prevention from the perspective of infection control strategies. In Taiwan, hospital infection control, which is practiced nationwide, emphasizes the importance to epidemic prevention of collecting and tracking travel history, occupation, contact history, cluster (TOCC) information; practicing hand hygiene; promoting the correct use of personal protective equipment; and maintaining safe distances from others. Personal control measures are recognized as critical to providing a safe environment for patients and staff.

negative: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission in Patients With Cancer Still Being Described

negative: Global epidemiology of coronavirus disease 2019 (COVID-19): disease incidence, daily cumulative index, mortality, and their association with country healthcare resources and economic status ABSTRACT It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. So far, COVID-19 has affected 85 403 patients in 57 countries/territories and has caused 2924 deaths in 9 countries. However, epidemiological data differ between countries. Although China had higher morbidity and mortality than other sites, the number of new daily cases in China has been lower than outside of China since 26 February 2020. The incidence ranged from 61.44 per 1 000 000 people in the Republic of Korea to 0.0002 per 1 000 000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and 29 February 2020) was greatest in China (1320.85), followed by the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). However, the DCIs in other countries/territories were <10 per day. Several effective measures including restricting travel from China, controlling the distribution of masks, extensive investigation of COVID-19 spread, and once-daily press conferences by the government to inform and educate people were aggressively conducted in Taiwan. This is probably the reason why there was only 39 cases (as of 29 February 2020) with a DCI of 1 case per day in Taiwan, which is much lower than that of nearby countries such as the Republic of Korea and Japan. In addition, the incidence and mortality were correlated with the DCI. However, further study and continued monitoring are needed to better understand the underlying mechanism of COVID-19.

negative: A model of bi-mode transmission dynamics of hepatitis C with optimal control In this paper, we present a rigorous mathematical analysis of a deterministic model for the transmission dynamics of hepatitis C. The model is suitable for populations where two frequent modes of transmission of hepatitis C virus, namely unsafe blood transfusions and intravenous drug use, are dominant. The susceptible population is divided into two distinct compartments, the intravenous drug users and individuals undergoing unsafe blood transfusions. Individuals belonging to each compartment may develop acute and then possibly chronic infections. Chronically infected individuals may be quarantined. The analysis indicates that the eradication and persistence of the disease is completely determined by the magnitude of basic reproduction number R (c). It is shown that for the basic reproduction number R (c) < 1, the disease-free equilibrium is locally and globally asymptotically stable. For R (c) > 1, an endemic equilibrium exists and the disease is uniformly persistent. In addition, we present the uncertainty and sensitivity analyses to investigate the influence of different important model parameters on the disease prevalence. When the infected population persists, we have designed a time-dependent optimal quarantine strategy to minimize it. The Pontryagin’s Maximum Principle is used to characterize the optimal control in terms of an optimality system which is solved numerically. Numerical results for the optimal control are compared against the constant controls and their efficiency is discussed.

negative: Operative team checklist for aerosol generating procedures to minimise exposure of healthcare workers to SARS-CoV-2 Abstract Objectives In many countries around the world, the COVID-19 pandemic has resulted in health services being diverted to manage patients with the condition. There are situations however that still require the undertaking of aerosol generating procedures (AGP) with potentially high exposure of healthcare workers to SARS-CoV-2 transmission through droplet, contact and possibly airborne routes. The objective of this paper is to explore a structured way for the operative team to approach AGP to reduce aerosolisation of secretions, decrease open airway time and minimise staff exposure. Methods The authors (otolaryngologists, anaesthetists and nursing staff) created a unified operative team checklist based on collation of national and international specialty society statements, local state government recommendations, hospital policies and literature review. Simulation was undertaken and the checklist was refined after performing AGP on patients with unknown (presumed positive) COVID-19 status. Results An 8 step operative team checklist is provided describing details for the immediate pre-operative, intra-operative and post-operative journey of the patient to encourage healthcare workers to reflect upon and modify usual practice during AGP to mitigate exposure to SARS-CoV-2. The example of paediatric laryngo-bronchoscopy for diagnostic purposes or retrieval of an inhaled airway foreign body is used to illustrate the steps however the checklist structure is modifiable for other AGP and adaptable for local needs. Conclusions At a time of overwhelming and changing information and recommendations, an operative team checklist may provide some structure to healthcare workers undertaking AGP to reduce anxiety, maintain focus, prompt consideration of alternatives and potentially reduce risk.

negative: Advancing the global health security agenda in light of the 2015 annual Hajj pilgrimage and other mass gatherings

negative: Protection from SARS coronavirus conferred by live measles vaccine expressing the spike glycoprotein Abstract The recent identification of a novel human coronavirus responsible of a SARS-like illness in the Middle-East a decade after the SARS pandemic, demonstrates that reemergence of a SARS-like coronavirus from an animal reservoir remains a credible threat. Because SARS is contracted by aerosolized contamination of the respiratory tract, a vaccine inducing mucosal long-term protection would be an asset to control new epidemics. To this aim, we generated live attenuated recombinant measles vaccine (MV) candidates expressing either the membrane-anchored SARS-CoV spike (S) protein or its secreted soluble ectodomain (Ssol). In mice susceptible to measles virus, recombinant MV expressing the anchored full-length S induced the highest titers of neutralizing antibodies and fully protected immunized animals from intranasal infectious challenge with SARS-CoV. As compared to immunization with adjuvanted recombinant Ssol protein, recombinant MV induced stronger and Th1-biased responses, a hallmark of live attenuated viruses and a highly desirable feature for an antiviral vaccine.

negative: Transportation: Travel by Air, Car, and Train This chapter deals with issues of transportation and how they interact with the world of tourism security. The chapter examines such issues as air transportation security and safety, issues of fire at airport terminals, and issues of health and international travel, both from the perspective of the traveler and from the perspective of the host community. The chapter also examines some of the issues dealing with both train travel and motor coach travel and develops a template for how tourism security professionals need to deal with these issues.

negative: Severe acute respiratory syndrome (SARS) in Hong Kong Abstract: Severe acute respiratory syndrome (SARS) is a recently recognized and highly contagious pneumonic illness, caused by a novel coronavirus. While developments in diagnostic, clinical and other aspects of SARS research are well underway, there is still great difficulty for frontline clinicians as validated rapid diagnostic tests or effective treatment regimens are lacking. This article attempts to summarize some of the recent developments in this newly recognized condition from the Asia Pacific perspective.

negative: From SARS to COVID-19: A previously unknown SARS- related coronavirus (SARS-CoV-2) of pandemic potential infecting humans – Call for a One Health approach Human coronaviruses continue to pose a threat to human health. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 which causes coronavirus disease-2019 (COVID-19), an acute respiratory disease marked the third introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. This recent emergence of a previously unknown coronavirus in China leads to huge impacts on humans globally. Covid-19 is a challenge to global public health. Here, we discuss the COVID-19 outbreak in a one health context, highlighting the need for the implementation of one health measures and practices to improve human health and reduce the emergence of pandemic viruses.

negative: Estimating the daily trend in the size of the COVID-19 infected population in Wuhan There has been an outbreak of coronavirus disease (COVID-19) in Wuhan city, Hubei province, China since December 2019. Cases have been exported to other parts of China and more than 20 countries. We provide estimates of the daily trend in the size of the epidemic in Wuhan based on detailed information of 10,940 confirmed cases outside Hubei province.

negative: Factors associated with duration of viral shedding in adults with COVID-19 outside of Wuhan, China: A retrospective cohort study Abstract Objectives To investigate factors associated with the duration of viral shedding in patients with COVID-19 outside of Wuhan. Methods In this retrospective cohort study, patients with laboratory-confirmed COVID-19 in Changsha, China were included. Clinical characteristics, laboratory findings, treatment and outcome were retrieved. Univariable and multivariable analysis were performed to explore potential factors. Results Totally 147 patients with COVID-19 were included. The median duration of viral shedding (the number of days from symptoms onset till the successive negative detection of SARS-CoV-2 RNA) was 17 days (interquartile range [IQR], 12 to 21). Multivariable Logistic regression analysis indicated that the highest temperature at admission (odds ratio [OR], 5.200; 95% confidence interval [CI]: 1.190-22.726; p = 0.028) and time from symptom onset to admission (OR, 1.740; 95% CI: 1.296-2.337; p < 0.001) and hospital length of stay (OR, 1.604; 95% CI: 1.262-2.040; p < 0.001) were risk factors for prolonged duration of viral shedding. Conclusions This is the study with relatively large sample size that mainly focused on the duration of viral shedding and relevant factors in patients with COVID-19 outside of Wuhan, China. Potential risk factors were identified and should be taken into consideration for the strategy of quarantine of infected patients.

negative: Recognition of the murine coronavirus genomic RNA packaging signal depends on the second RNA-binding domain of the nucleocapsid protein. UNLABELLED The coronavirus nucleocapsid (N) protein forms a helical ribonucleoprotein with the viral positive-strand RNA genome and binds to the principal constituent of the virion envelope, the membrane (M) protein, to facilitate assembly and budding. Besides these structural roles, N protein associates with a component of the replicase-transcriptase complex, nonstructural protein 3, at a critical early stage of infection. N protein has also been proposed to participate in the replication and selective packaging of genomic RNA and the transcription and translation of subgenomic mRNA. Coronavirus N proteins contain two structurally distinct RNA-binding domains, an unusual characteristic among RNA viruses. To probe the functions of these domains in the N protein of the model coronavirus mouse hepatitis virus (MHV), we constructed mutants in which each RNA-binding domain was replaced by its counterpart from the N protein of severe acute respiratory syndrome coronavirus (SARS-CoV). Mapping of revertants of the resulting chimeric viruses provided evidence for extensive intramolecular interactions between the two RNA-binding domains. Through analysis of viral RNA that was packaged into virions we identified the second of the two RNA-binding domains as a principal determinant of MHV packaging signal recognition. As expected, the interaction of N protein with M protein was not affected in either of the chimeric viruses. Moreover, the SARS-CoV N substitutions did not alter the fidelity of leader-body junction formation during subgenomic mRNA synthesis. These results more clearly delineate the functions of N protein and establish a basis for further exploration of the mechanism of genomic RNA packaging. IMPORTANCE This work describes the interactions of the two RNA-binding domains of the nucleocapsid protein of a model coronavirus, mouse hepatitis virus. The main finding is that the second of the two domains plays an essential role in recognizing the RNA structure that allows the selective packaging of genomic RNA into assembled virions.

negative: ReScan, a Multiplex Diagnostic Pipeline, Pans Human Sera for SARS-CoV-2 Antigens Serologic assays are needed to determine SARS-CoV-2 seroprevalence, but poor specificity can overestimate exposures. Here, we built a pan-human coronavirus proteome-wide programmable phage display assay (VirScan) to profile coronavirus antigens specifically enriched by 20 COVID-19 patient serum IgG. With ReScan, a new diagnostic development workflow which combines the isolation of phage expressing the most immunogenic peptides with paper-based microarrays manufactured via acoustic liquid handling, we identified 9 candidate antigens from a library of 534 SARS-CoV-2 peptides. These arrays could form the basis of a multiplexed COVID-19 serologic assay with enhanced specificity. ReScan has broad applicability for serologic assay development.

negative: Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Severe acute respiratory syndrome (SARS)-coronavirus (CoV) produces a devastating primary viral pneumonia with diffuse alveolar damage and a marked increase in circulating cytokines. One of the major cell types to be infected is the alveolar type II cell. However, the innate immune response of primary human alveolar epithelial cells infected with SARS-CoV has not been defined. Our objectives included developing a culture system permissive for SARS-CoV infection in primary human type II cells and defining their innate immune response. Culturing primary human alveolar type II cells at an air-liquid interface (A/L) improved their differentiation and greatly increased their susceptibility to infection, allowing us to define their primary interferon and chemokine responses. Viral antigens were detected in the cytoplasm of infected type II cells, electron micrographs demonstrated secretory vesicles filled with virions, virus RNA concentrations increased with time, and infectious virions were released by exocytosis from the apical surface of polarized type II cells. A marked increase was evident in the mRNA concentrations of interferon-β and interferon-λ (IL-29) and in a large number of proinflammatory cytokines and chemokines. A surprising finding involved the variability of expression of angiotensin-converting enzyme-2, the SARS-CoV receptor, in type II cells from different donors. In conclusion, the cultivation of alveolar type II cells at an air-liquid interface provides primary cultures in which to study the pulmonary innate immune responses to infection with SARS-CoV, and to explore possible therapeutic approaches to modulating these innate immune responses.

negative: What makes a foodborne virus: comparison between coronaviruses with human noroviruses In order to answer the question whether coronaviruses (CoVs) can be transmitted via foods, this review made a comparison between CoVs with the most recognized foodborne virus, human noroviruses (NoVs). As a result, although CoVs indeed have shown the possibilities to remain infectious on foods and/or food packaging materials long enough (from several days to several weeks) to potentially cause transmission, they seem to be less persistent than NoVs towards common disinfection practices with alcohols, chlorine and ultraviolet (UV). More importantly, the chance of foodborne transmission of CoVs is considered low as CoVs mainly spread through the respiratory tract and there is no clear evidence showing CoVs can follow fecal-oral routes like human NoVs and other foodborne viruses.

negative: The novel coronavirus outbreak in Wuhan, China The novel coronavirus (2019-nCoV, or COVID-19) epidemic first broke out in Wuhan and has been spreading in whole China and the world. The numbers of new infections and deaths in Wuhan are still increasing, which have posed major public health and governance concerns. A series of mandatory actions have been taken by the municipal and provincial governments supported by the central government, such as measures to restrict travels across cities, case detection and contact tracing, quarantine, guidance and information to the public, detection kit development, etc. Challenges such as lacking effective drugs, insufficient hospital services and medical supplies, logistics, etc. have much alleviated with the solidarity of the whole society. The pandemic will definitely be ended with the continuous efforts of both national and international multi-sectoral bodies.

negative: Dead Body Management in Times of Covid‐19 and its Potential Impact on the Availability of Cadavers for Medical Education in India Technology integration in teaching is an evolving concept in modern medical education like other study disciplines in India. The domain of medical science education is presently deficient of deploying technology-based practices. Currently, majority of medical schools and colleges continue to choose traditional wet laboratory dissections over new virtual dissections which are being followed in institutions such as All India Institute of Medical Sciences (AIIMS) and handful of other governmental as well as private medical schools of India like AIIMS Rishikesh, AIIMS Jodhpur, Government Medical College Vimsar, Burla, Odisha, GSL Medical College Rajahmundry, Andhra Pradesh, Yennapoya University Mangalore, Dutta Megha Medical College, GMC Chindwara Madhya Pradesh, Symbiosis Institute Pune and Apollo Medical College Chitoor. Not to mention, as the current push for technology integration increases, it is likely that a large number of Indian academic scholars will begin seeing virtual dissections as beneficial to their classroom.

negative: Human infections associated with wild birds Summary Introduction Wild birds and especially migratory species can become long-distance vectors for a wide range of microorganisms. The objective of the current paper is to summarize available literature on pathogens causing human disease that have been associated with wild bird species. Methods A systematic literature search was performed to identify specific pathogens known to be associated with wild and migratory birds. The evidence for direct transmission of an avian borne pathogen to a human was assessed. Transmission to humans was classified as direct if there is published evidence for such transmission from the avian species to a person or indirect if the transmission requires a vector other than the avian species. Results Several wild and migratory birds serve as reservoirs and/or mechanical vectors (simply carrying a pathogen or dispersing infected arthropod vectors) for numerous infectious agents. An association with transmission from birds to humans was identified for 10 pathogens. Wild birds including migratory species may play a significant role in the epidemiology of influenza A virus, arboviruses such as West Nile virus and enteric bacterial pathogens. Nevertheless only one case of direct transmission from wild birds to humans was found. Conclusion The available evidence suggests wild birds play a limited role in human infectious diseases. Direct transmission of an infectious agent from wild birds to humans is rarely identified. Potential factors and mechanisms involved in the transmission of infectious agents from birds to humans need further elucidation.

negative: The scientific rationale for the use of simple masks or improvised facial coverings to trap exhaled aerosols and possibly reduce the breathborne spread of COVID-19 The medical community agrees that breathborne infectious materials can be spread with exhaled aerosols and that asymptomatic people, i.e., those showing no symptoms, could be unknowingly infectious. With the current worldwide pandemic of the respiratory coronavirus disease 2019 (COVID-19), various health bodies and governments are recommending that the population wear some form of mask or improvised facial covers while out in public in an effort to reduce the spread of disease . The general concept is that more accessible masks or mask-like materials (scarves, bandanas, etc.) could serve to reduce the amount of infectious aerosol from infected people, and reduce the viral load in the environment. This editorial addresses the underlying scientific rationale that such inexpensive or improvised could indeed serve to reduce the emissions of infectious aerosol by the mechanism of surface adhesion and particle kinetics in addition to the filtration effect.

negative: Autophagy in viral replication and pathogenesis Autophagy is a catabolic process that is important for the removal of damaged organelles and long-lived proteins for the maintenance of cellular homeostasis. It can also serve as innate immunity to remove intracellular microbial pathogens. A growing list of viruses has been shown to affect this cellular pathway. Some viruses suppress this pathway for their survival, while others enhance or exploit this pathway to benefit their replication. The effect of viruses on autophagy may also sensitize cells to death or enhance cell survival and play a critical role in viral pathogenesis. In this article, we review the relationships between different viruses and autophagy and discuss how these relationships may affect viruses and their host cells.

negative: Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat.

negative: Main Factors Influencing College Student Health and Countermeasures Proposal in Network Environment—From Physical Health Education Perspective This dissertation adopts document-data method, comparative analysis method and Inductive deductive method to analyze main factors influencing college students’ physical and mental health from physical health education perspective. It elaborates the significance of physical health education and put up “health first” guideline for promoting health knowledge and cultivate sports skills, creating favorable conditions for physical health education implementation and switching college physical education focus to reform colleges and universities physical education assessment system.

negative: Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans A novel human coronavirus (HCoV-EMC/2012) was isolated from a man with acute pneumonia and renal failure in June 2012. This report describes the complete genome sequence, genome organization, and expression strategy of HCoV-EMC/2012 and its relation with known coronaviruses. The genome contains 30,119 nucleotides and contains at least 10 predicted open reading frames, 9 of which are predicted to be expressed from a nested set of seven subgenomic mRNAs. Phylogenetic analysis of the replicase gene of coronaviruses with completely sequenced genomes showed that HCoV-EMC/2012 is most closely related to Tylonycteris bat coronavirus HKU4 (BtCoV-HKU4) and Pipistrellus bat coronavirus HKU5 (BtCoV-HKU5), which prototype two species in lineage C of the genus Betacoronavirus. In accordance with the guidelines of the International Committee on Taxonomy of Viruses, and in view of the 75% and 77% amino acid sequence identity in 7 conserved replicase domains with BtCoV-HKU4 and BtCoV-HKU5, respectively, we propose that HCoV-EMC/2012 prototypes a novel species in the genus Betacoronavirus. HCoV-EMC/2012 may be most closely related to a coronavirus detected in Pipistrellus pipistrellus in The Netherlands, but because only a short sequence from the most conserved part of the RNA-dependent RNA polymerase-encoding region of the genome was reported for this bat virus, its genetic distance from HCoV-EMC remains uncertain. HCoV-EMC/2012 is the sixth coronavirus known to infect humans and the first human virus within betacoronavirus lineage C.

negative: Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review BACKGROUND: The coronavirus disease (COVID-19) has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. As of 31 January 2020, this epidemic had spread to 19 countries with 11 791 confirmed cases, including 213 deaths. The World Health Organization has declared it a Public Health Emergency of International Concern. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O’Malley. In this scoping review, 65 research articles published before 31 January 2020 were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors’ affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. RESULTS: Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus’ origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as ways to reduce transmission. To date, no specific antiviral treatment has proven effective; hence, infected people primarily rely on symptomatic treatment and supportive care. CONCLUSIONS: There has been a rapid surge in research in response to the outbreak of COVID-19. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies are relevant to control the current public emergency, more high-quality research is needed to provide valid and reliable ways to manage this kind of public health emergency in both the short- and long-term.

negative: Updating the diagnostic criteria of COVID-19 “suspected case” and “confirmed case” is necessary On 6 February 2020, our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infection, and this guideline provided our experience and make well reference for fighting against this pandemic worldwide. However, the coronavirus disease 2019 (COVID-19) is a new disease, our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience; hence, the strategies of diagnosis and treatment are also continually updated. In this letter, we answered one comment on our guideline and provided the newest diagnostic criteria of “suspected case” and “confirmed case” according to the latest Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People’s Republic of China.

negative: Feline infectious peritonitis The article discusses feline infectious peritonitis (FIP), an important disease frequently seen in veterinary practice. FIP causes many problems to the veterinarian as it can be difficult to definitively diagnose the disease, as there is no effective treatment, and as prophylactic interventions are not very successful. Although intense research has created a lot of new knowledge about this disease in the last years, there are still many unanswered questions. The objective of this article is to review recent knowledge and to increase understanding of the complex pathogenesis of FIP.

negative: Science Science today studies phenomena lasting less than 10(−21) s and phenomena which occurred more than 13 billion years ago; science also studies phenomena occurring over distances greater than 10(28) cm and shorter than 10(−13) cm; that is, science studies phenomena occurring over times and distances varying by a factor of about 10(40) (Fig. 3.1). In those incomprehensible ranges of time and space, the description of the physical world presented by science is most impressive. Based on what we know today everything in this enormous cosmos everywhere is made up of the same microscopic particles, the atoms and their constituents; their behavior is governed by the same physical laws everywhere.

negative: Towards a ‘virtual’ world: Social isolation and struggles during the COVID‐19 pandemic as single women living alone This article is a personal reflection of how the current COVID‐19 pandemic affects our working lives and wellbeing, as single female academics who live alone in the UK. We offer a dialogue of our daily lives of being confined at home with lockdown measures extended. In particular, we focus on the experience of, and coping with, isolation and loneliness. Is isolation making us more socially connected? Through ‘virtual’ working and changing learning environments for us as teachers and learners, we explore changes in our working life and subsequent changes in the domestic environment. By capturing our lived experiences, we create an intellectual and safe space to voice our emotional struggles — as ‘invisible’ isolated individuals containing and consuming loneliness on our own. We foster alternative conversations as to how we might engender new perspectives from single female academics to combat social isolation in the workplace.

negative: Antiviral Action of Tryptanthrin Isolated from Strobilanthes cusia Leaf against Human Coronavirus NL63 Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as β-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC(50) = 0.64 μg/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC(50) values against virus yield were 1.52 μM and 2.60 μM for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC(50) = 0.06 μM) and indigodole B (IC(50) = 2.09 μM) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection.

negative: Epidemiological and Genomic Analysis of SARS-CoV-2 in Ten Patients from a Mid-sized City outside of Hubei, China A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from ten patients in Shaoxing, a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with > 99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR Ct values less than 28. We found that a cluster of 4 patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium and Australia, highlighting how quickly this virus spread to the globe. The virus from another cluster of husband and wife without travel history but with a sick contact of a confirmed case from another city outside of Hubei accumulated significantly more mutations (9 SNPs vs average 4 SNPs), suggesting a complex and dynamic nature of this outbreak. We also found 70% patients in this study had the S genotype, consistent with an early study showing a higher prevalence of S genotype out of Hubei than that inside Hubei. We calculated an average mutation rate of 1.37x10-3 nucleotide substitution per site per year, which is similar to that of other coronaviruses. Our findings add to the growing knowledge of the epidemiological and genomic characteristics of SARS-CoV-2 that are important for guiding outbreak containment and vaccine development. The moderate mutation rate of this virus also lends hope that development of an effective, long-lasting vaccine may be possible.

negative: Point-of-care testing for COVID-19 using SHERLOCK diagnostics The recent outbreak of the novel coronavirus SARS-CoV-2, which causes COVID-19, can be diagnosed using RT-qPCR, but inadequate access to reagents and equipment has slowed disease detection and impeded efforts to mitigate viral spread. Alternative approaches based on combinations of isothermal amplification and CRISPR-mediated detection, such as the SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) technique, offer reduced dependence on RT-qPCR equipment, but previously reported methods required multiple fluid handling steps, complicating their deployment outside clinical labs. Here we developed a simple test chemistry called STOP (SHERLOCK Testing in One Pot) for detecting SARS-CoV-2 in one hour that is suitable for point-of-care use. This simplified test, STOPCovid, provides sensitivity comparable to RT-qPCR-based SARS-CoV-2 tests and has a limit of detection of 100 copies of viral genome input in saliva or nasopharyngeal swabs per reaction. Using lateral flow readout, the test returns result in 70 minutes, and using fluorescence readout, the test returns result in 40 minutes. Moreover, we validated STOPCovid using nasopharyngeal swabs from COVID-19 patients and were able to correctly diagnose 12 positive and 5 negative patients out of 3 replicates. We envision that implementation of STOPCovid will significantly aid “test-trace-isolate” efforts, especially in low-resource settings, which will be critical for long-term public health safety and effective reopening of the society.

negative: Air care: an 'aerography' of breath, buildings and bugs in the cystic fibrosis clinic With significant relevance to the Covid-19 pandemic, this paper contributes to emerging 'aerographic' research on the socio-materialities of air and breath, based on an in-depth empirical study of three hospital-based lung infection clinics treating people with cystic fibrosis. We begin by outlining the changing place of atmosphere in hospital design from the pre-antibiotic period and into the present. We then turn to the first of three aerographic themes where air becomes a matter of grasping and visualising otherwise invisible airborne infections. This includes imagining patients located within bodily spheres or 'cloud bodies', conceptually anchored in Irigaray's thoughts on the 'forgetting of the air' and Sloterdijk's immunitary 'spherology' of the body. Our second theme explores the material politics of air, air conditioning, window design and the way competing 'air regimes' come into conflict with each other at the interface of buildings, bodies and the biotic. Our final theme attends to the 'cost of air', the aero-economic problem of atmospheric scarcity within modern high-rise, deep-density healthcare architectures.

negative: Murine coronavirus induces an acute and long-lasting disease of the retina. The ability of the coronavirus mouse hepatitis virus, strain JHM, to grow in the retinas of BALB/c mice was examined. Inoculation into the vitreous chamber produced significant changes. Immunoperoxidase staining of frozen sections with either monoclonal or polyclonal antiserum revealed coronaviral antigens in the iris, ciliary body, and a few ganglion cells on day 1. The retinal pigment epithelial cells began expressing viral antigen on day 2 and large amounts of antigen were present in these cells on day 3. Viral antigens were detected in all layers of the neural retina by day 6 and were absent after day 7. Infectious virus was recovered from retinas harvested at 5 days. The drop in viral antigen expression was correlated with an elevation in virus-specific antibody; the latter began to rise on day 5 and plateaued after day 8. In hematoxylin and eosin- or periodic acid -Schiff-stained sections of virus-inoculated left eyes, but not mock-inoculated right eyes, lesions spanning all layers of the neural retina were detected by day 3. Subsequently abnormalities in retinal pigment epithelial cells appeared, sometimes around the entire circumference of the retina. Significant retinal abnormalities, notably photoreceptor degeneration, persisted through 6 weeks. These results demonstrate that coronaviruses can cause acute infection of the posterior pole of the eye, resulting in only a mild inflammatory response and long-lasting disease. This murine disease may be considered a model for degenerative diseases of the pigment epithelium and photoreceptors in man.

negative: The different clinical characteristics of corona virus disease cases between children and their families in China – the character of children with COVID-19 This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.

negative: Abortion at the edges: Politics, practices, performances Abstract This article provides a brief overview of the state of discourse, politics and provision of abortion in the Anglophone West, including developments in the wake of the COVID-19 pandemic. It then surveys three promising directions for feminist abortion scholarship. The first is work inspired by the Reproductive Justice Movement, that points to the intersectional axes of inequality that shape abortion discourse and position us in relation to reproductive choice and access issues. The second is work that examines the particularity of the constitution of the aborting body, reflecting the particularity of the pregnant body. This is a specific body, with a specific history; abortion discourse draws from and makes a significant contribution to the meaning and lived experience of this body. The third area of scholarship we highlight is that which seeks to amplify the meaning of abortion as a social good. Much abortion scholarship is attuned to a critique of negative aspects of abortion—from its representation in popular culture to restrictive law and access issues. This is critical work but/and the performative nature of abortion scholarship, like all discourse, means that it can amplify the association of negativity with abortion. The article concludes by introducing the articles contained in the special section of Women's Studies International Forum, ‘Abortion at the edges: Politics, practices, performances’.

negative: Effects of colostrum instead of formula feeding for the first 2 days postnatum on whole-body energy metabolism and its endocrine control in neonatal calves ABSTRACT Colostrum provides high amounts of nutritive and non-nutritive substrates, which are essential for calf nutrition and passive immunization. Colostral growth factors and hormones have beneficial effects on postnatal maturation and may affect substrate utilization and energy expenditure in neonatal calves. We tested the hypothesis that energy metabolism and its endocrine regulation differ during the first 10 d of life in calves fed either colostrum or a milk-based formula with a similar nutrient composition to colostrum, but largely depleted of bioactive substances, for the first 2 d postnatum. Male Holstein calves (n = 18) were fed either pooled colostrum (COL; n = 9) or a milk-based formula (FOR; n = 9) for the first 2 d of life. From d 3 on, all calves received same milk replacer. On d 2 and 7 of life, calves were placed in a respiration chamber for indirect calorimetric measurements to calculate heat production, fat (FOX) and carbohydrate oxidation (COX), as well as respiratory quotient. Blood was sampled on d 1 before first colostrum intake and on d 2, 3, 7, 8, 9, and 10 before morning feeding, to measure plasma concentrations of immunoglobulins, metabolites, and hormones. Additional postprandial blood samples were taken on d 1 and 9 at 30, 60, 120, 240, and 420 min after milk feeding. Liver samples were collected on d 10 of life to determine gene expression related to energy metabolism. Formula-fed calves showed lower plasma concentrations of total protein, immunoglobulins, haptoglobin, leptin, adiponectin, and insulin-like growth factor (IGF) binding protein (IGFBP)-4 during the whole study but temporarily higher plasma concentrations of urea, insulin, glucagon, triglyceride, and cholesterol on the first day after feeding, compared with concentrations in COL. The temporary increase in glucagon, triglyceride, and cholesterol on d 1 reversed on d 2 or 3, showing higher concentrations in COL than in FOR calves. In FOR, IGF-I, IGFBP-2, and IGFBP-3 were lower on d 3 than in COL. Interestingly, FOR calves had higher heat production during respiratory measurements on d 2 and higher body temperature on d 2, 3, and 5 than those of COL. The hepatic mRNA abundance of cytosolic phosphoenolpyruvate carboxykinase was higher in FOR than in COL. Our results indicate that first milk feeding after birth influenced whole-body energy expenditure but not FOX and COX in neonatal calves, and the absorption of colostral leptin and adiponectin might affect insulin sensitivity on d 1 of life.

negative: Guidance for management of cancer surgery during the COVID-19 pandemic Summary: During the coronavirus disease 2019 (COVID-19) pandemic, delaying lifesaving cancer surgeries must be done with extreme caution and thoughtfulness. Modelling indicates that delays in high-risk cancer surgeries beyond 6 weeks could affect long-term outcomes for thousands of Canadians. Consequently, it is possible that postponing cancer surgery without consideration of its implications could cost more lives than can be saved by diverting all surgical resources to COVID-19. This article provides general guidance on supporting curative surgical treatment where appropriate and with available resources.

negative: Protection and disinfection policies against SARS-CoV-2 (COVID-19) In late December 2019, reports from China of the incidence of pneumonia with unknown etiology were sent to the World Health Organization (WHO). Shortly afterwards, the cause of this disease was identified as the novel beta-coronavirus, SARS-CoV-2, and its genetic sequence was published on January 12, 2020. Human-to-human transmission via respiratory droplets and contact with aerosol infected surfaces are the major ways of transmitting this virus. Here we attempted to collect information on virus stability in the air and on surfaces and ways of preventing of SARS-CoV-2 spreading.

negative: Occupational risks for COVID-19 infection

negative: One Health approach and Coronavirus Disease 2019

negative: COVID-19 Clinical Trials: A Primer for the Cardiovascular and Cardio-Oncology Communities Abstract The COVID-19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS-CoV-2 infection; accordingly, the cardiovascular and cardio-oncology communities are playing a major role in caring for COVID-19 patients. Many of the therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here we have provided a foundation for cardiovascular and cardio-oncology physicians who are on the frontline providing care to COVID-19 patients, so that they can better understand the emerging cardiovascular epidemiology of COVID-19, as well as the biological rationale for the clinical trials that are ongoing for the treatment of COVID-19 patients.

negative: Emergence of Novel Coronavirus and COVID-19: whether to stay or die out? The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus “SARS-CoV-2” (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect naïve, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.

negative: CHAPTER 13 FERRETS Publisher Summary This chapter familiarizes veterinarians with basic knowledge of ferret biology, medicine, surgery, and care. Ferrets have a long, slender body with short muscular legs, a long thin tail, small eyes, and short ears. The life span of the ferret is 5 to 8 years. Ferrets may be housed singly or in groups, inside or outside of a house. When kept outdoors, however, they must be protected from extreme weather. Ferrets have difficulty tolerating temperatures above 90°F or below 20°F, and appropriate precautions must be taken to prevent their exposure to these extremes. Ferrets are carnivorous and require a suitable diet. A diet that is high in good-quality animal protein and fat and low in complex carbohydrates and fiber is recommended. Ferrets are routinely immunized against canine distemper virus (CDV) and rabies virus. Ferrets are quite susceptible to CDV, and there is a 100% mortality rate in unvaccinated ferrets infected with CDV. When a new ferret is brought into the household, a quarantine period is recommended before introducing it to other animals, particularly other ferrets. The purpose of the quarantine period is to identify and prevent transmission of infectious disease potentially carried by the new ferret. The duration of this period allows for the development of any clinical signs in a seemingly healthy ferret following entrance into the new household.

negative: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing BACKGROUND: The Manila clam (Ruditapes philippinarum) is a worldwide cultured bivalve species with important commercial value. Diseases affecting this species can result in large economic losses. Because knowledge of the molecular mechanisms of the immune response in bivalves, especially clams, is scarce and fragmentary, we sequenced RNA from immune-stimulated R. philippinarum hemocytes by 454-pyrosequencing to identify genes involved in their immune defense against infectious diseases. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput deep sequencing of R. philippinarum using 454 pyrosequencing technology yielded 974,976 high-quality reads with an average read length of 250 bp. The reads were assembled into 51,265 contigs and the 44.7% of the translated nucleotide sequences into protein were annotated successfully. The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. We have found sequences from molecules never described in bivalves before, especially in the complement pathway where almost all the components are present. CONCLUSIONS: This study represents the first transcriptome analysis using 454-pyrosequencing conducted on R. philippinarum focused on its immune system. Our results will provide a rich source of data to discover and identify new genes, which will serve as a basis for microarray construction and the study of gene expression as well as for the identification of genetic markers. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum.

negative: Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies Since the outbreak of the COVID-19 pandemic in early December 2019, 81 174 confirmed cases and 3242 deaths have been reported in China as of March 19, 2020. The Chinese people and government have contributed huge efforts to combat this disease, resulting in significant improvement of the situation, with 58 new cases (34 were imported cases) and 11 new deaths reported on March 19, 2020. However, as of March 19, 2020, the COVID-19 pandemic continues to develop in 167 countries/territories outside of China, and 128 665 confirmed cases and 5536 deaths have been reported, with 16 498 new cases and 817 new deaths occurring in last 24 hours. Therefore, the world should work together to fight against this pandemic. Here, we review the recent advances in COVID-19, including the insights in the virus, the responses of the host cells, the cytokine release syndrome, and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm. By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis, we believe that the community can efficiently develop effective vaccines and drugs, and the mankind will eventually win this battle against this pandemic.

negative: Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2 Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen A [HLA-A], -B, and -C genes) may affect susceptibility to and severity of the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We performed a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA-A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explored the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome was successfully sampled and was represented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting that individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (M. Lin, H.-T. Tseng, J. A. Trejaut, H.-L. Lee, et al., BMC Med Genet 4:9, 2003, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting that it could enable cross-protective T-cell-based immunity. Finally, we reported global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic.IMPORTANCE Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.

negative: Clinical Pathway for Early Diagnosis of COVID-19: Updates from Experience to Evidence-Based Practice The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.

negative: Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2 The outbreak of a novel coronavirus, which was later formally named the severe acute respiratory coronavirus 2 (SARS-CoV-2), has caused a worldwide public health crisis. Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. Here, we have systematically studied the molecular mechanisms of human infection with SARS-CoV-2 and SARS-CoV by protein-protein docking and MD simulations. It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. In addition, the spike protein of SARS-CoV-2 has a significantly lower free energy than that of SARS-CoV, suggesting that SARS-CoV-2 is more stable and may survive a higher temperature than SARS-CoV. This provides insights into the evolution of SARS-CoV-2 because SARS-like coronaviruses have originated in bats. Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV. Thus, it is expected that SARS-CoV-2 would decrease its infection ability much faster than SARS-CoV when the temperature rises. These findings would be beneficial for the disease prevention and drug/vaccine development of SARS-CoV-2.

negative: Decontamination of Bacillus subtilis var. niger spores on selected surfaces by chlorine dioxide gas. OBJECTIVE Chlorine dioxide (CD) gas has been used as a fumigant in the disinfection of biosafety laboratories. In this study, some experiments were conducted to assess the inactivation of spores inoculated on six materials [stainless steel (SS), painted steel (PS), polyvinyl chlorid (PVC), polyurethane (PU), glass (GS), and cotton cloth (CC)] by CD gas. The main aims of the study were to determine the sporicidal efficacy of CD gas and the effect of prehumidification before decontamination on sporicidal efficacy. METHODS Material coupons (1.2 cm diameter of SS, PS, and PU; 1.0 cm×1.0 cm for PVC, GS, and CC) were contaminated with 10 μl of Bacillus subtilis var. niger (ATCC 9372) spore suspension in mixed organic burden and then dried in a biosafety cabinet for 12 h. The spores were recovered by soaking the coupons in 5 ml of extraction liquid for 1 h and then vortexing the liquid for 1 min. RESULTS The log reductions in spore numbers on inoculated test materials exposed to CD gas [0.080% (volume ratio, v/v) for 3 h] were in the range of from 1.80 to 6.64. Statistically significant differences were found in decontamination efficacies on test material coupons of SS, PS, PU, and CC between with and without a 1-h prehumidification treatment. With the extraction method, there were no statistically significant differences in the recovery ratios between the porous and non-porous materials. CONCLUSIONS The results reported from this study could provide information for developing decontamination technology based on CD gas for targeting surface microbial contamination.

negative: Effect of faecal consistency on virological diagnosis A study was set up to investigate the effect of consistency of routine faecal specimens on the diagnostic yield by electron microscopy (EM) and virus isolation. A total of 3078 specimens were characterized as solid, semisolid, or liquid. Of 2568 specimens processed by EM a virus was demonstrated in 8.6% of liquid, 19.9% of semisolid and 25.2% of solid specimens (Chi-squared for lienar trend, P value <0.0001). This observation was valid for both adenovirus (2.4%, 5.0% and 6.6%) and rotavirus (5.2% , 13.6% and 16.6%). Virus isolation was positive in 3.6% of liquid, 17.4% of semisolid and 18.1% of solid specimens. (Chi-squared for linear trend, P value <0.0001). We suggest that solid faecal specimens at the end of an episode of diarrhoea will have a higher diagnostic yield than liquid specimens at the peak of symptoms. Our findings repudiate the commonly held dogma that viruses of gastroenteritis are more likely to be found in liquid than in solid faecal specimens. This finding has important implications for those establishing diagnostic algorithms for the investigation of viral gastroenteritis.

negative: The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

negative: Body Mass Index, Weight Discrimination, and Psychological, Behavioral, and Interpersonal Responses to the Coronavirus Pandemic OBJECTIVE: To examine whether body mass index (BMI) and weight discrimination are associated with psychological, behavioral, and interpersonal responses to the coronavirus pandemic. METHODS: Using a prospective design, participants (N=2,094) were first assessed in early February 2020 before the coronavirus crisis in the United States and again in mid-March 2020 during the President's 15 Days to Slow the Spread guidelines. Weight, height, and weight discrimination were assessed in the February survey. Psychological, behavioral, and interpersonal responses to the coronavirus were assessed in the March survey. RESULTS: Pre-pandemic experiences with weight discrimination were associated with greater concerns about the virus, engaging in more preventative behaviors, less trust in people and institutions to manage the outbreak, and greater perceived declines in connection to one's community. BMI tended to be unrelated to these responses. CONCLUSIONS: Despite the risks of complications of COVID-19 associated with obesity, individuals with higher BMI were neither more concerned about the virus nor taking more behavioral precautions than individuals in other weight categories. Weight discrimination, in contrast, may heighten vigilance to threat, which may have contributed to both positive (greater concern, more precautionary behavior) and negative (less trust, declines community connection) responses to the pandemic.

negative: Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world's healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. "First come, first served" is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.

negative: Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 - United States, January-February 2020. In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact† with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.

negative: A study of non-prescription usage of antibiotics in the upper respiratory tract infections in the urban population

negative: Excretion and persistence of bovine coronavirus in neonatal calves Following oral inoculation, the excretion of a virulent or an attenuated strain of bovine coronavirus in calf feces and their persistence in spiral colon, ileum, and jejunum were studied using hemagglutination and direct fluorescent antibody tests, respectively. The virus was excreted in feces for only 3 days at high titers and then intermittently at low titers. However, viral antigen was detected in crypt or Peyer's patches for at least 3 weeks after infection in 1 of 3 calves given virulent virus and 1 of 2 calves given attenuated virus.

negative: Cities and population health A majority of the world's population will live in urban areas by 2007 and cities are exerting growing influence on the health of both urban and non-urban residents. Although there long has been substantial interest in the associations between city living and health, relatively little work has tried to understand how and why cities affect population health. This reflects both the number and complexity of determinants and of the absence of a unified framework that integrates the multiple factors that influence the health of urban populations. This paper presents a conceptual framework for studying how urban living affects population health. The framework rests on the assumption that urban populations are defined by size, density, diversity, and complexity, and that health in urban populations is a function of living conditions that are in turn shaped by municipal determinants and global and national trends. The framework builds on previous urban health research and incorporates multiple determinants at different levels. It is intended to serve as a model to guide public health research and intervention.

negative: The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated The novel coronavirus (2019-nCoV) is a recently emerged human pathogen that has spread widely since January 2020. Initially, the basic reproductive number, R0, was estimated to be 2.2 to 2.7. Here we provide a new estimate of this quantity. We collected extensive individual case reports and estimated key epidemiology parameters, including the incubation period. Integrating these estimates and high-resolution real-time human travel and infection data with mathematical models, we estimated that the number of infected individuals during early epidemic double every 2.4 days, and the R0 value is likely to be between 4.7 and 6.6. We further show that quarantine and contact tracing of symptomatic individuals alone may not be effective and early, strong control measures are needed to stop transmission of the virus.

negative: Privilege and burden of im‐/mobility governance: On the reinforcement of inequalities during a pandemic lockdown In order to contain the COVID‐19 pandemic, nation states have focused on governance of im‐/mobilities: Certain mobility restrictions were enforced, while simultaneously some forms of mobility were maintained or even enhanced in order to keep the system running in crisis mode. With a special focus on Austria, we analyze specific politics of im‐/mobilities concerning the organization of paid work and show how the socio‐spatial conditions of who is permitted, denied or urged to work are inextricably linked to inequalities. It becomes apparent that while in principle all bodies are equally dependent on collective social relations and enduring infrastructure, not everybody contributes equally to their maintenance. In fact, the governance of im‐/mobilities follows and reinforces already prevalent inequality regimes based on class, gender and migration relations, thereby differentiating between bodies perceived as highly valuable and worth protecting and those categorized as less valued and potentially disposable.

negative: Robot assisted surgery during the COVID-19 pandemic, especially for gynecological cancer: a statement of the Society of European Robotic Gynaecological Surgery (SERGS) All surgery performed in an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, irrespective of the known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status of the patient, should be regarded as high risk and protection of the surgical team at the bedside should be at the highest level. Robot assisted surgery (RAS) may help to reduce hospital stay for patients that urgently need complex-oncological-surgery, thus making room for COVID-19 patients. In comparison to open or conventional laparoscopic surgery, RAS potentially reduces not only contamination with body fluids and surgical gasses of the surgical area but also the number of directly exposed medical staff. A prerequisite is that general surgical precautions under COVID-19 circumstances must be taken, with the addition of prevention of gas leakage: â¢ Use highest protection level III for bedside assistant, but level II for console surgeon. â¢ Reduce the number of staff at the operation room. â¢ Ensure safe and effective gas evacuation. â¢ Reduce the intra-abdominal pressure to 8 mmHg or below. â¢ Minimize electrocautery power and avoid use of ultrasonic sealing devices. â¢ Surgeons should avoid contact outside theater (both in and out of the hospital).

negative: Transcending the Professional–Client Divide: Supporting Young People with Complex Support Needs Through Transitions Young people with complex support needs frequently experience multiple intersecting forms of disadvantage including experiences of violence, abuse and neglect, housing instability and homelessness, problematic substance use, exclusion from education, and contact with the criminal justice system. Many of these young people have mental health, cognitive disability and/or other health issues that also impact on their lives. These young people need to navigate multiple, diverse, and often difficult transitions between services, adding to the existing chaos in their lives. This article explores the experiences of young people with complex support needs in transition, specifically young people’s viewpoints and experiences of supports they receive from paid professionals. This qualitative study used body mapping research methods and in-depth interviews with 38 young people aged 16 to 26 years in three Australian states. Helpful and trusting paid relationships could serve as an anchor to young people during complex transitions and other highly turbulent life periods. These relationships were contingent on a deep and non-judgmental knowing of the young person, contributed constructive outcomes and stability in young people’s lives, and for some young people, had ‘life-saving’ effects. These findings present opportunities and challenges for policymakers and practitioners to balance the tensions between authentic relationship-based work with young people and risk-averse, economically-driven imperatives in contemporary youth service provision.

negative: Transient CFD simulation of the respiration process and inter-person exposure assessment Abstract It is known that the person-to-person spreading of certain infectious diseases is related with the transmission of human exhaled air in the indoor environments, and this is suspected to be the case with the severe acute respiratory syndrome (SARS) outbreak. This paper presents the numerical analysis of the human respiration process and the transport of exhaled air by breathing, sneezing, and coughing and their potential impact on the adjacent person in a modeled room with displacement ventilation. In order to account for the influence of the thermal plume around the human body, a three-dimensional computational thermal manikin (CTM) with an accurate description of body geometry was applied. Some of the results were compared with those from former simulations and experiments. It was found that personal exposure to the exhaled air from the normal respiration process of other persons is very low in a modeled room with displacement ventilation. Personal exposure to pollution caused by sneezing or coughing is highly directional. When two occupants face each other the cross-infection may happen due to the long transport distance of the exhalation.

negative: Modulation of the immune response by Middle East respiratory syndrome coronavirus Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus‐Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS‐CoV). MERS‐CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS‐CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus‐host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS‐CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS‐CoV inhibit the type I interferon (IFN) and nuclear factor‐κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double‐stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS‐CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ‐induced protein 10 and monocyte chemoattractant protein‐1 can suppress proliferation of human myeloid progenitor cells.

negative: SARS-CoV-2 and the Testis: similarity to other viruses and routes of infection Abstract Since the latest coronavirus outbreak, the number of infected individuals and COVID-19 cases have been increasing exponentially worldwide. Of interest is the evidence that orchitis can develop due coronavirus infection. Therefore, it is not unreasonable to believe that the latest coronavirus, SARS-CoV-2, could be transmitted by semen. Consequently, it is paramount that individuals who could potentially be infected take all possible care to mitigate the likely risk of infection through sexual intercourse.

negative: Frequent respiratory viral infections in a young child in a 27-month follow-up study INTRODUCTION: Viruses are major aetiological agents of acute respiratory infection in young children. Although many studies have reported detection and analysis of respiratory viruses in sporadic cases, there have been few follow-up studies of individuals. The purpose of this study was to investigate the frequency of respiratory viral infections in a young child and to examine the duration of viral genome detection in clinical specimens. CASE PRESENTATION: A total of 284 nasal swabs were collected during symptomatic (196 specimens) and asymptomatic (88 specimens) periods of respiratory symptoms from a young female child (from 4 months to 31 months of age, who was admitted to a nursery school at 9 months). Multiplex real-time PCR for 19 respiratory viruses or subtypes was performed. One hundred and ninety-eight of the tested specimens were virus positive (69.7 %) (symptomatic periods, 149/196, 76.0 %; asymptomatic periods, 49/88, 55.7 %). Rhinovirus was the most frequently detected (26 times). Long durations of detection were observed for human coronavirus NL63 (30 days), rhinovirus (28 days) and human bocavirus 1 (22 days). CONCLUSION: Young children living in a group context have a high risk of respiratory virus infections, especially rhinovirus. In some instances, viral genomes were detectable for about 1 month by PCR.

negative: Update on therapeutic options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Introduction: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an important emerging respiratory pathogen. MERS-CoV resulted in multiple hospital outbreaks within and outside the Arabian Peninsula. The disease has a high case fatality rate, with the need for a therapeutic option. Areas covered: In this review, we provide an overview of the progress in the development of therapeutic strategies for MERS. We searched PubMed, Embase, Cochrane, Scopus, and Google Scholar, using the following terms: ‘MERS’, ‘MERS-CoV’, ‘Middle East respiratory syndrome’ in combination with ‘treatment’ or ‘therapy’. Expert commentary: There are multiple agents tried in vitro and in vivo. None of these agents were used in large clinical studies. Available clinical studies are limited to the use of the combination of interferon and other agents. These clinical studies are based solely on case reports and case series. There are no prospective or randomized trials. There is a need to have prospective and randomized clinical trials for the therapy of MERS-CoV. However, this strategy might be hampered by the sporadic cases outside the large hospital outbreaks.

negative: Behavior of Single Cats and Groups in the Home

negative: Airborne spread of infectious agents in the indoor environment BACKGROUND: Since the 2003 severe acute respiratory syndrome epidemic, scientific exploration of infection control is no longer restricted to microbiologists or medical scientists. Many studies have reported on the release, transport, and exposure of expiratory droplets because of respiratory activities. This review focuses on the airborne spread of infectious agents from mucus to mucus in the indoor environment and their spread as governed by airflows in the respiratory system, around people, and in buildings at different transport stages. METHODS: We critically review the literature on the release of respiratory droplets, their transport and dispersion in the indoor environment, and the ultimate exposure of a susceptible host, as influenced by airflows. RESULTS: These droplets or droplet nuclei are transported by expired airflows, which are sometimes affected by the human body plume and use of a face mask, as well as room airflow. Room airflow is affected by human activities such as walking and door opening, and some droplets are eventually captured by a susceptible individual because of his or her inspired flows; such exposure can eventually lead to long-range spread of airborne pathogens. Direct exposure to the expired fine droplets or droplet nuclei results in short-range airborne transmission. Deposition of droplets and direct personal exposure to expired large droplets can lead to the fomite route and the droplet-borne route, respectively. CONCLUSIONS: We have shown the opportunities for infection control at different stages of the spread. We propose that the short-range airborne route may be important in close contact, and its control may be achieved by face masks for the source patients and use of personalized ventilation. Our discussion of the effect of thermal stratification and expiratory delivery of droplets leads to the suggestion that displacement ventilation may not be applicable to hospital rooms where respiratory infection is a concern.

negative: When Darkness Becomes a Ray of Light in the Dark Times: Understanding the COVID-19 via the Comparative Analysis of the Dark Proteomes of SARS-CoV-2, Human SARS and Bat SARS-Like Coronaviruses Recently emerged coronavirus designated as SARS-CoV-2 (also known as 2019 novel coronavirus (2019-nCoV) or Wuhan coronavirus) is a causative agent of coronavirus disease 2019 (COVID-19), which is rapidly spreading throughout the world now. More than 9,00,000 cases of SARS-CoV-2 infection and more than 47,000 COVID-19-associated mortalities have been reported worldwide till the writing of this article, and these numbers are increasing every passing hour. World Health Organization (WHO) has declared the SARS-CoV-2 spread as a global public health emergency and admitted that the COVID-19 is a pandemic now. The multiple sequence alignment data correlated with the already published reports on the SARS-CoV-2 evolution and indicated that this virus is closely related to the bat Severe Acute Respiratory Syndrome-like coronavirus (bat SARS-like CoV) and the well-studied Human SARS coronavirus (SARS CoV). The disordered regions in viral proteins are associated with the viral infectivity and pathogenicity. Therefore, in this study, we have exploited a set of complementary computational approaches to examine the dark proteomes of SARS-CoV-2, bat SARS-like, and human SARS CoVs by analysing the prevalence of intrinsic disorder in their proteins. According to our findings, SARS-CoV-2 proteome contains very significant levels of structural order. In fact, except for Nucleocapsid, Nsp8, and ORF6, the vast majority of SARS-CoV-2 proteins are mostly ordered proteins containing less intrinsically disordered protein regions (IDPRs). However, IDPRs found in SARS-CoV-2 proteins are functionally important. For example, cleavage sites in its replicase 1ab polyprotein are found to be highly disordered, and almost all SARS-CoV-2 proteins were shown to contain molecular recognition features (MoRFs), which are intrinsic disorder-based protein-protein interaction sites that are commonly utilized by proteins for interaction with specific partners. The results of our extensive investigation of the dark side of the SARS-CoV-2 proteome will have important implications for the structural and non-structural biology of SARS or SARS-like coronaviruses. Significance The infection caused by a novel coronavirus (SARS-CoV-2) that causes severe respiratory disease with pneumonia-like symptoms in humans is responsible for the current COVID-19 pandemic. No in-depth information on structures and functions of SARS-CoV-2 proteins is currently available in the public domain, and no effective anti-viral drugs and/or vaccines are designed for the treatment of this infection. Our study provides the first comparative analysis of the order- and disorder-based features of the SARS-CoV-2 proteome relative to human SARS and bat CoV that may be useful for structure-based drug discovery.

negative: Airborne bioaerosols and their impact on human health Abstract Bioaerosols consist of aerosols originated biologically such as metabolites, toxins, or fragments of microorganisms that are present ubiquitously in the environment. International interests in bioaerosols have increased rapidly to broaden the pool of knowledge on their identification, quantification, distribution, and health impacts (e.g., infectious and respiratory diseases, allergies, and cancer). However, risk assessment of bioaerosols based on conventional culture methods has been hampered further by several factors such as: (1) the complexity of microorganisms or derivatives to be investigated; (2) the purpose, techniques, and locations of sampling; and (3) the lack of valid quantitative criteria (e.g., exposure standards and dose/effect relationships). Although exposure to some microbes is considered to be beneficial for health, more research is needed to properly assess their potential health hazards including inter-individual susceptibility, interactions with non-biological agents, and many proven/unproven health effects (e.g., atopy and atopic diseases).

negative: Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Coronaviruses and Ocular Implications in Humans and Animals In December 2019, a novel coronavirus (CoV) epidemic, caused by the severe acute respiratory syndrome coronavirus – 2 (SARS-CoV-2) emerged from China. This virus causes the coronavirus disease 2019 (COVID-19). Since then, there have been anecdotal reports of ocular infection. The ocular implications of human CoV infections have not been widely studied. However, CoVs have been known to cause various ocular infections in animals. Clinical entities such as conjunctivitis, anterior uveitis, retinitis, and optic neuritis have been documented in feline and murine models. In this article, the current evidence suggesting possible human CoV infection of ocular tissue is reviewed. The review article will also highlight animal CoVs and their associated ocular infections. We hope that this article will serve as a start for further research into the ocular implications of human CoV infections.

negative: News at a glance. In science news around the world, the World Health Organization cautions governments against introducing "immunity passports that declare people immune to COVID-19 after they test positive for antibodies to the new coronavirus;the group notes a lack of evidence that people with such antibodies are protected from a second infection The U S National Institutes of Health ends a long-standing grant for research on how viruses spread from bats and other wildlife to humans after conservative politicians criticize the project's ties to a lab in Wuhan, China, that they blame, without evidence, for being the source of the COVID-19 virus The U S Food and Drug Administration advises physicians not to prescribe the antimalarial drugs chloroquine and hydroxychloroquine for COVID-19 patients outside of hospitals or clinical trials, citing safety concerns The U S Supreme Court gives hydrologic science top billing in a closely watched ruling affirming that the federal Clean Water Act covers groundwater pollution Donald Kennedy, former editor-in-chief of Science, dies at the age of 88 from COVID-19

negative: COVID-19 in a Designated Infectious Diseases HospitalOutside Hubei Province,China Background A new type of novel coronavirus infection (COVID-19) occurred in Wuhan, Hubei Province. Previous investigations reported patients in Wuhan city often progressed into severe or critical and had a high mortality rate.The clinical characteristics of affected patients outside the epicenter of Hubei province are less well understood. Methods All confirmed COVID-19 case treated in the Third People's Hospital of Shenzhen,from January 11, 2020 to February 6, 2020, were included in this study. We analyzed the epidemiological and clinical features of these cases to better inform patient management in normal hospital settings. Results Among the 298 confirmed cases, 233(81.5%) had been to Hubei while 42(14%) had not clear epidemiological history. Only 192(64%) cases presented with fever as initial symptom. The lymphocyte count decreased in 38% patients after admission. The number (percent) of cases classified as non-severe and severe was 240(80.6%) and 58(19.4%) respectively. Thirty-two patients (10.7%) needed ICU care. Compared to the non-severe cases, severe cases were associated with older age, underlying diseases, as well as higher levels of CRP, IL-6 and ESR. The median (IRQ) duration of positive viral test were 14(10-19). Slower clearance of virus was associated with higher risk of progression to severe clinical condition. As of February 14, 2020, 66(22.1%) patients were discharged and the overall mortality rate remains 0. Conclusions In a designated hospital outside the Hubei Province, COVID-19 patients were mainly characterized by mild symptoms and could be effectively manage by properly using the existing hospital system.

negative: Saliva: potential diagnostic value and transmission of 2019-nCoV 2019-nCoV epidemic was firstly reported at late December of 2019 and has caused a global outbreak of COVID-19 now. Saliva, a biofluid largely generated from salivary glands in oral cavity, has been reported 2019-nCoV nucleic acid positive. Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2. Close contact or short-range transmission of infectious saliva droplets is a primary mode for 2019-nCoV to disseminate as claimed by WHO, while long-distance saliva aerosol transmission is highly environment dependent within indoor space with aerosol-generating procedures such as dental practice. So far, no direct evidence has been found that 2019-nCoV is vital in air flow for long time. Therefore, to prevent formation of infectious saliva droplets, to thoroughly disinfect indoor air and to block acquisition of saliva droplets could slow down 2019-nCoV dissemination. This review summarizes diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-nCoV by saliva droplets, expecting to contribute to 2019-nCoV epidemic control.

negative: Protease inhibitors broadly effective against feline, ferret and mink coronaviruses Abstract Ferret and mink coronaviruses typically cause catarrhal diarrhea in ferrets and minks, respectively. In recent years, however, systemic fatal coronavirus infection has emerged in ferrets, which resembles feline infectious peritonitis (FIP) in cats. FIP is a highly fatal systemic disease caused by a virulent feline coronavirus infection in cats. Despite the importance of coronavirus infections in these animals, there are no effective commercial vaccines or antiviral drugs available for these infections. We have previously reported the efficacy of a protease inhibitor in cats with FIP, demonstrating that a virally encoded 3C-like protease (3CLpro) is a valid target for antiviral drug development for coronavirus infections. In this study, we extended our previous work on coronavirus inhibitors and investigated the structure-activity relationships of a focused library of protease inhibitors for ferret and mink 3CLpro. Using the fluorescence resonance energy transfer assay, we identified potent inhibitors broadly effective against feline, ferret and mink coronavirus 3CLpro. Multiple amino acid sequence analysis and modelling of 3CLpro of ferret and mink coronaviruses were conducted to probe the structural basis for these findings. The results of this study provide support for further research to develop broad-spectrum antiviral agents for multiple coronavirus infections. To the best of our knowledge, this is the first report on small molecule inhibitors of ferret and mink coronaviruses.

negative: Understanding Viral Transmission Behavior via Protein Intrinsic Disorder Prediction: Coronaviruses Besides being a common threat to farm animals and poultry, coronavirus (CoV) was responsible for the human severe acute respiratory syndrome (SARS) epidemic in 2002–4. However, many aspects of CoV behavior, including modes of its transmission, are yet to be fully understood. We show that the amount and the peculiarities of distribution of the protein intrinsic disorder in the viral shell can be used for the efficient analysis of the behavior and transmission modes of CoV. The proposed model allows categorization of the various CoVs by the peculiarities of disorder distribution in their membrane (M) and nucleocapsid (N). This categorization enables quick identification of viruses with similar behaviors in transmission, regardless of genetic proximity. Based on this analysis, an empirical model for predicting the viral transmission behavior is developed. This model is able to explain some behavioral aspects of important coronaviruses that previously were not fully understood. The new predictor can be a useful tool for better epidemiological, clinical, and structural understanding of behavior of both newly emerging viruses and viruses that have been known for a long time. A potentially new vaccine strategy could involve searches for viral strains that are characterized by the evolutionary misfit between the peculiarities of the disorder distribution in their shells and their behavior.

negative: Identification of novel subgenomic RNAs and noncanonical transcription initiation signals of severe acute respiratory syndrome coronavirus. The expression of the genomic information of severe acute respiratory syndrome coronavirus (SARS CoV) involves synthesis of a nested set of subgenomic RNAs (sgRNAs) by discontinuous transcription. In SARS CoV-infected cells, 10 sgRNAs, including 2 novel ones, were identified, which were predicted to be functional in the expression of 12 open reading frames located in the 3' one-third of the genome. Surprisingly, one new sgRNA could lead to production of a truncated spike protein. Sequence analysis of the leader-body fusion sites of each sgRNA showed that the junction sequences and the corresponding transcription-regulatory sequence (TRS) are unique for each species of sgRNA and are consistent after virus passages. For the two novel sgRNAs, each used a variant of the TRS that has one nucleotide mismatch in the conserved hexanucleotide core (ACGAAC) in the TRS. Coexistence of both plus and minus strands of SARS CoV sgRNAs and evidence for derivation of the sgRNA core sequence from the body core sequence favor the model of discontinuous transcription during minus-strand synthesis. Moreover, one rare species of sgRNA has the junction sequence AAA, indicating that its transcription could result from a noncanonical transcription signal. Taken together, these results provide more insight into the molecular mechanisms of genome expression and subgenomic transcription of SARS CoV.

negative: Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset Background Timely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated. Method A patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial sera of COVID-19 patients were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described. Results The seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively. Conclusions Typical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection.

negative: Intrinsic growth rules of patients infected, dead and recovered with 2019 novel coronavirus in mainland China An outbreak of a novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) was first diagnosed in Wuhan, China, in December 2019 and then spread rapidly to other regions. We collected the time series data of the cumulative number of confirmed infected, dead, and cured cases from the health commissions in 31 provinces in mainland China. A descriptive model in a logistic form was formulated to infer the intrinsic epidemic rules of COVID-19, which illustrates robustness spatially and temporally. Our model is robust (R2>0.95) to depict the intrinsic growth rule for the cumulative number of confirmed infected, dead, and cured cases in 31 provinces in mainland China. Furthermore, we compared the intrinsic epidemic rules of COVID-19 in Hubei with that of severe acute respiratory syndrome (SARS) in Beijing, which was obtained from the Ministry of Public Health of China in 2003. We found that the infected case is the earliest to be saturated and has the lowest semi-saturation period compared with deaths and cured cases for both COVID-19 and SARS. All the three types of SARS cases are later to saturate and have longer semi-saturation period than that of COVID-19. Despite the virus caused SARS (SARS-CoV) and the virus caused COVID-19 (SARS-CoV-2) are homologous, the duration of the outbreak would be shorter for COVID-19.

negative: Origin and evolution of pathogenic coronaviruses Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.

negative: Mutations across murine hepatitis virus nsp4 alter virus fitness and membrane modifications. UNLABELLED A common feature of infection by positive-sense RNA virus is the modification of host cell cytoplasmic membranes that serve as sites of viral RNA synthesis. Coronaviruses induce double-membrane vesicles (DMVs), but the role of DMVs in replication and virus fitness remains unclear. Coronaviruses encode 16 nonstructural proteins (nsps), three of which, nsp3, nsp4, and nsp6, are necessary and sufficient for DMV formation. It has been shown previously that mutations in murine hepatitis virus (MHV) nsp4 loop 1 that alter nsp4 glycosylation are associated with disrupted DMV formation and result in changes in virus replication and RNA synthesis. However, it is not known whether DMV morphology or another function of nsp4 glycosylation is responsible for effects on virus replication. In this study, we tested whether mutations across nsp4, both alone and in combination with mutations that abolish nsp4 glycosylation, affected DMV formation, replication, and fitness. Residues in nsp4 distinct from glycosylation sites, particularly in the endoplasmic reticulum (ER) luminal loop 1, independently disrupted both the number and morphology of DMVs and exacerbated DMV changes associated with loss of glycosylation. Mutations that altered DMV morphology but not glycosylation did not affect virus fitness while viruses lacking nsp4 glycosylation exhibited a loss in fitness. The results support the hypothesis that DMV morphology and numbers are not key determinants of virus fitness. The results also suggest that nsp4 glycosylation serves roles in replication in addition to the organization and stability of MHV-induced double-membrane vesicles. IMPORTANCE All positive-sense RNA viruses modify host cytoplasmic membranes for viral replication complex formation. Thus, defining the mechanisms of virus-induced membrane modifications is essential for both understanding virus replication and development of novel approaches to virus inhibition. Coronavirus-induced membrane changes include double-membrane vesicles (DMVs) and convoluted membranes. Three viral nonstructural proteins (nsps), nsp3, nsp4, and nsp6, are known to be required for DMV formation. It is unknown how these proteins induce membrane modification or which regions of the proteins are involved in DMV formation and stability. In this study, we show that mutations across nsp4 delay virus replication and disrupt DMV formation and that loss of nsp4 glycosylation is associated with a substantial fitness cost. These results support a critical role for nsp4 in DMV formation and virus fitness.

negative: Additional challenges faced by cancer patients in Gaza due to COVID-19 Cancer patients in conflict settings experience significant barriers in accessing chemotherapy and radiotherapy as well as palliative care and psychosocial support. Now they face an additional possible risk of infection by SARS-CoV-2 novel coronavirus and the indirect impact of the COVID-19 pandemic on movement restrictions and their access to care. In this commentary, we highlight that despite the low COVID-19 burden in conflict settings like Gaza, COVID-19 could lead to further inequity in cancer care and poorer outcomes for Palestinians with cancer. This is due to the pre-existing shortage in cancer resources as well as the lack of context-specific guidelines to prepare for COVID-19 in war-torn settings.

negative: Strict Isolation Strict isolation: suspected highly infectious and transmissible virulent and pathogenic microbes, highly resistant bacterial strains and agents that are not accepted in any form of distribution in the society or in the environment. Examples are completely resistant Mycobacterium tuberculosis, viral haemorrhagic fevers like Ebola and Lassa, pandemic severe influenza and coronavirus like SARS, MERS, etc. In most countries, strict isolation is a rarely used isolation regime but should be a part of the national preparedness plan. For instance, in Norway, strict isolation has not been used for the last 50–60 years, except for one case of imported Ebola infection in 2014. Patients in need of strict isolation should be placed in a separate isolation ward or building. Infection spread by contact, droplet and airborne infection, aerosols, re-aerosols, airborne microbe-carrying particles, skin cells, dust, droplets and droplet nuclei. At the same time, it is always contact transmission (contaminated environment, equipment, textiles and waste). The source of infection is usually a patient but may also be a symptomless carrier or a zoonotic disease.

negative: Vortex dynamics and scalar transport in the wake of a bluff body driven through a steady recirculating flow The air ventilation system in wide-body aircraft cabins provides passengers with a healthy breathing environment. In recent years, the increase in global air traffic has amplified contamination risks by airborne flu-like diseases and terrorist threats involving the onboard release of noxious materials. In particular, passengers moving through a ventilated cabin may transport infectious pathogens in their wake. This paper presents an experimental investigation of the wake produced by a bluff body driven through a steady recirculating flow. Data were obtained in a water facility using particle image velocimetry and planar laser induced fluorescence. Ventilation attenuated the downward convection of counter-rotating vortices produced near the free-end corners of the body and decoupled the downwash mechanism from forward entrainment, creating stagnant contaminant regions.

negative: Advance in research of beta coronavirus receptors on ocular surface/ 中华实验眼科杂志 Novel coronavirus (2019-nCoV) caused an outbreak of corona virus disease 2019 (COVID-19) from December 2019 in China. 2019-nCoV which was identified is a kind of beta coronavirus belongs to one of four coronavirus genera. Except 2019-nCoV, two other beta coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are also quite harmful to human beings. 2019-nCoV uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV. And dipeptidyl peptidase 4 (DPP4) or CD26 is the cell receptor for MERS-CoV. The expression of ACE2 was found to have obvious positive expression in human corneal and conjunctival epithelium, and corneal endothelium. DPP4 activity was presented in normal animal conjunctival epithelium and fibroblasts of the subjacent connective tissue. It was also presented in the whole corneal epithelium and tear fluid of animal with severe injured corneas. The two receptors, ACE2 and DPP4, involve in many cellular signaling pathways and pathophysiological processes. Their expression in the cells of ocular surface may be an access route of corona virus in eye, which provides clues to elucidating the pathogenesis of corona virus in the eyeballs.

negative: Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.

negative: Protease Inhibitors: Candidate Drugs to Inhibit Severe Acute Respiratory Syndrome Coronavirus 2 Replication The number of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly increased, although the WHO declared a pandemic. However, drugs that function against SARS-CoV-2 have not been established. SARS-CoV-2 has been suggested to bind angiotensin-converting enzyme 2, the receptor of the SARS coronavirus. SARS coronavirus and coronavirus 229E, the cause of the common cold, replicate through cell-surface and endosomal pathways using a protease, the type II transmembrane protease. To examine the effects of protease inhibitors on the replication of coronavirus 229E, we pretreated primary cultures of human nasal epithelial (HNE) cells with camostat or nafamostat, each of which has been used for the treatment of pancreatitis and/or disseminated intravascular coagulation. HNE cells were then infected with coronavirus 229E, and viral titers in the airway surface liquid of the cells were examined. Pretreatment with camostat (0.1-10 µg/mL) or nafamostat (0.01-1 µg/mL) reduced the titers of coronavirus 229E. Furthermore, a significant amount of type II transmembrane protease protein was detected in the airway surface liquid of HNE cells. Additionally, interferons have been reported to have antiviral effects against SARS coronavirus. The additive effects of interferons on the inhibitory effects of other candidate drugs to treat SARS-CoV-2 infection, such as lopinavir, ritonavir and favipiravir, have also been studied. These findings suggest that protease inhibitors of this type may inhibit coronavirus 229E replication in human airway epithelial cells at clinical concentrations. Protease inhibitors, interferons or the combination of these drugs may become candidate drugs to inhibit the replication of SARS-CoV-2.

negative: Chapter 31 Coronaviruses Abstract Coronaviruses possess a distinctive morphology, the name being derived from the outer fringe, or “corona” of embedded envelope protein. Members of the family Coronaviridae cause a broad spectrum of animal and human diseases. Uniquely, replication of the RNA genome proceeds through the generation of a nested set of viral mRNA molecules. Until 2003, coronaviruses attracted little interest beyond causing mild upper respiratory tract infections. This changed dramatically in 2003 with the zoonotic SARS-CoV and the more recent emergence of MERS-CoV has confirmed the coronaviruses as significant causes of severe respiratory disease.

negative: Inter nation social lockdown versus medical care against COVID-19, a mild environmental insight with special reference to India Abstract Infection by coronavirus (CoV-19) has led to emergence of a pandemic called as Coronavirus Disease (COVID-19) that has so far affected about 210 countries. The dynamic data indicate that the pandemic by CoV-19 so far has infected 2,403,963 individuals, and among these 624,698 have recovered while, it has been fatal for 165,229. Without much experience, currently, the medicines that are clinically being evaluated for COVID-19 include chloroquine, hydroxychloroquine, azithromycin, tocilizumab, lopinavir, ritonavir, tocilizumab and corticosteroids. Therefore, countries such as Italy, USA, Spain and France with the most advanced health care system are partially successful to control CoV-19 infection. India being the 2nd largest populous country, where, the healthcare system is underdeveloped, major portion of population follow unhygienic lifestyle, is able to restrict the rate of both infection and death of its citizens from COVID-19. India has followed an early and a very strict social distancing by lockdown and has issued advisory to clean hands regularly by soap and/or by alcohol based sterilizers. Rolling data on the global index of the CoV infection is 13,306, and the index of some countries such as USA (66,148), Italy (175,055), Spain (210,126), France (83,363) and Switzerland (262,122) is high. The index of India has remained very low (161) so far, mainly due to early implementation of social lockdown, social distancing, and sanitizing hands. However, articles on social lockdown as a preventive measure against COVID-19 in PubMed are scanty. It has been observed that social lockdown has also drastic impacts on the environment especially on reduction of NO2 and CO2 emission. Slow infection rate under strict social distancing will offer time to researchers to come up with exact medicines/vaccines against CoV-19. Therefore, it is concluded that stringent social distancing via lockdown is highly important to control COVID-19 and also to contribute for self-regeneration of nature.

negative: Cumulative biological source index: Volumes 1–20

negative: Do COVID-19 and crude oil prices drive the US economic policy uncertainty? This paper investigates the effect of the novel coronavirus and crude oil prices on the United States (US) economic policy uncertainty (EPU). Using daily data for the period January 21-March 13, 2020, our Autoregressive Distributed Lag (ARDL) model shows that the new infection cases reported at global level, and the death ratio, have no significant effect on the US EPU, whereas the oil price negative dynamics leads to increased uncertainty. However, analyzing the situation outside China, we discover that both new case announcements and the COVID-19 associated death ratio have a positive influence on the US EPU.

negative: Corticosteroid use for 2019-nCoV infection: A double-edged sword

negative: Risk of COVID-19 importation to the Pacific islands through global air travel On 30 January 2020, WHO declared coronavirus (COVID-19) a global public health emergency. As of 12 March 2020, 125 048 confirmed COVID-19 cases in 118 countries had been reported. On 12 March 2020, the first case in the Pacific islands was reported in French Polynesia; no other Pacific island country or territory has reported cases. The purpose of our analysis is to show how travellers may introduce COVID-19 into the Pacific islands and discuss the role robust health systems play in protecting health and reducing transmission risk. We analyse travel and Global Health Security Index data using a scoring tool to produce quantitative estimates of COVID-19 importation risk, by departing and arriving country. Our analysis indicates that, as of 12 March 2020, the highest risk air routes by which COVID-19 may be imported into the Pacific islands are from east Asian countries (specifically, China, Korea and Japan) to north Pacific airports (likely Guam, Commonwealth of the Northern Mariana Islands or, to a less extent, Palau); or from China, Japan, Singapore, the United States of America or France to south Pacific ports (likely, Fiji, Papua New Guinea, French Polynesia or New Caledonia). Other importation routes include from other east Asian countries to Guam, and from Australia, New Zealand and other European countries to the south Pacific. The tool provides a useful method for assessing COVID-19 importation risk and may be useful in other settings.

negative: Effectiveness of Social Networks for Studying Biological Agents and Identifying Cancer Biomarkers Social networks form phenomena that exist and evolve; they are dynamic. These phenomena have been realized and studied by the anthropology and sociology research communities since 1930. However, the recent rapid development in information technology and the internet has increased the interest in social networks and as a model they have been adapted to more applications and domains. Though researchers first studied social networks of humans, for our study described in this chapter we argue that genes and proteins act collaboratively and exist in communities analogous to humans, animals, insects, etc. They complement each other and collectively achieve specific tasks where some would have major roles appearing upfront and others may play minor background roles. However, molecules turn into aggressive actors when their internal structure is augmented; consequently, they may deviate from their target, change camp, and disturb other molecules leading to disaster. Such mutations may be uncontrolled and unintentionally occur inside a body, or they may be intentional and controlled by humans to serve one of two purposes, treatment or bioterrorism. In other words, mutation in the molecules (genes) can lead to a change in behavior. This may lead to good or bad effect, e.g., recovery from illness or diseases that may severely affect the body causing disability or death. Once mutated outside the body, molecules may turn into harmful biological weapons of mass destruction. The latter process does not require sophisticated equipment and hence is extremely dangerous with the uprising global terrorism activities. Bioterrorism is therefore a serious concern for humanity. One could say that mutated biological agents outside the body once misused could be way more dangerous than mutated molecules within the body. In this chapter, we will elaborate on bioterrorism and its consequences; we will also propose a model to study social networks of genes within the body leading to the identification of disease biomarkers.

negative: Screening and managing of suspected or confirmed novel coronavirus (COVID-19) patients: experiences from a tertiary hospital outside Hubei province Objectives: To report our experiences screening and managing patients with suspected or confirmed novel coronavirus (COVID-19) disease using a hospital-specific protocol. Design: Longitudinal cohort study. Setting: A 1,200 bed tertiary care teaching hospital in Chengdu, Sichuan, China. Participants: 802 adults presenting to hospital with concerns of having COVID-19, 1,246 inpatients and 2,531 hospital visitors. Interventions: Screening and management of patients using a hospital-specific protocol, which included fever triage, monitoring visitors and patients, emergency response, personnel training for healthcare team members, health education for patients and family, medical materials management, disinfection and wastes disposal protocols. Results: Between 23 January and 28 February 2020, 73 people were identified as having fever plus respiratory signs with/without a history of exposure and were tested for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by our hospital lab using RT PCR. Forty-five of these 73 people were subsequently excluded based on one negative RT PCR result plus positive results to quick screening tests for flu or other respiratory viruses. The remaining 28 people received a second RT PCR test 24 h later. Three people were confirmed positive for COVID-19 based on two consecutive positive RT PCR tests whilst 25 people were excluded based on two consecutive negative tests. The three COVID-19 confirmed cases received non-critical care. There were no new infections of medical staff or new infections of other hospital inpatients. Conclusions: All three cases were detected as a result of vigilant monitoring of hospital visitors. Whilst screening out-patients presenting to a fever clinic remains important, monitoring visitors must not be overlooked.

negative: Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV–IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV–IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

negative: Optical sensor for berberine utilizing its intrinsic fluorescence enhanced by the formation of inclusion complex with butylated-β-cyclodextrin Abstract An optical sensor for berberine, the basic ingredient of the widely used traditional Chinese medicine Coptis Chinensis, based on its intrinsic fluorescence enhanced by butylated-β-cyclodextrin (HDB-β-CD) immobilized in plasticized poly(vinyl chloride) (PVC) membrane has been developed. The drastic enhancement of fluorescence intensity of berberine was attributed to the formation of an inclusion complex between HDB-β-CD and berberine, which has been utilized as the basis of the fabrication of a berberine-sensitive fluorescence sensor. The proposed sensor was quite distinct from those fluorescent sensors for berberine reported so far which relied upon quenching the fluorescence of the sensing reagent immobilized on membrane by berberine. The response mechanism of optode membrane was discussed in detail from the view of molecular dynamics and the optimum steric configuration of the inclusion complex was presented by molecular dynamics simulation. The analytical performance characteristics of the proposed berberine-sensitive sensor were investigated. The sensor can be applied to the quantification of berberine with a linear range covering from 4.0×10−7 to 2.0×10−5 moll−1 with a detection limit of 8.0×10−8 moll−1. The sensor exhibits excellent reproducibility, reversibility and selectivity. The recommended method was successfully used for the determination of berberine in pharmaceutical preparations.

negative: Systematic Survey of Zoonotic and Sapronotic Microbial Agents Viruses, bacteria, fungi, protozoa, and metazoa (parasitic worms and arthropods) are among the aetiological agents of zoonoses and sapronoses. Our survey only concerns the agents of microbial diseases (i.e., not the metazoan invasions and infestations), and is arranged according to systematic position. In addition, a new zoonotic disease caused by prions – variant of Creutzfeld-Jakob disease – is included.

negative: Complete Genome Sequence of Human Coronavirus Strain 229E Isolated from Plasma Collected from a Haitian Child in 2016 Human coronavirus strain 229E (HCoV-229E) and human alphaherpesvirus 1 were isolated from the plasma of a Haitian child in 2016 with suspected arbovirus diseases. To our knowledge, this is the first description of HCoV-229E in human plasma, which is the focus of this article.

negative: Protocolo de manejo clínico do Coronavírus (covid-19) na atenção primária à saúde: versão 8 No fim de 2019, o Novo Coronavírus foi nomeado como SARS-CoV-2 Este Novo Coronavírus produz a doença classificada como COVID-19, sendo agente causador de uma série de casos de pneumonia na cidade de Wuhan (China) [1] Ainda não há informações plenas sobre a história natural, nem medidas de efetividade inquestionáveis para manejo clínico dos casos de infecção humana pelo SARS-CoV-2, restando ainda muitos detalhes a serem esclarecidos [1] No entanto, sabe-se que o vírus tem alta transmissibilidade e provoca uma síndrome respiratória aguda que varia de casos leves  cerca de 80%  a casos muito graves com insuficiência respiratória entre 5% e 10% dos casos Sua letalidade varia, principalmente, conforme a faixa etária (Quadro 1) e condições clínicas associadas Portanto, é necessário agir Para esse fim, as melhores e mais recentes evidências foram utilizadas na redação deste documento Pela dinâmica da epidemia e da produção de conhecimento associada a ela, as informações podem sofrer alterações conforme avance o conhecimento sobre a doença dessa forma, este protocolo específico para serviços de Atenção Primária à Saúde / Estratégia Saúde da Família (APS/ESF) nos cenários de transmissão comunitária vai ser atualizado sempre que necessário A APS/ESF é a porta de entrada do Sistema Único de Saúde Durante surtos e epidemias, a APS/ESF tem papel fundamental na resposta global à doença em questão a APS/ESF oferece atendimento resolutivo, além de manter a longitudinalidade e a coordenação do cuidado em todos os níveis de atenção à saúde, com grande potencial de identificação precoce de casos graves que devem ser manejados em serviços especializados O objetivo deste documento é definir o papel dos serviços de APS/ESF no manejo e controle da infecção COVID-19, bem como disponibilizar os instrumentos de orientação clínica para os profissionais que atuam na porta de entrada do SUS a partir da transmissão comunitária de CoVId-19 no Brasil Considerando a existência de fase de transmissão comunitária da COVID-19, é imprescindível que os serviços de APS/ESF trabalhem com abordagem sindrômica do problema, não exigindo mais a identificação do fator etiológico por meio de exame específico Desta forma, este protocolo foca na abordagem clínica da Síndrome Gripal e da Síndrome Respiratória Aguda Grave (SRAG), independentemente do agente etiológico Como é de conhecimento de todos, múltiplos agentes virais são responsáveis por essas duas síndromes, sendo o vírus da Influenza o de maior magnitude nos últimos anos Entretanto, há evidências e dados internacionais indicando que a transcendência da COVID-19 pode superar a da Influenza Portanto, a abordagem pragmática deste protocolo unifica as condutas referentes a esses dois grupos de vírus

negative: Effects of humidity and other factors on the generation and sampling of a coronavirus aerosol Suspensions of transmissible gastroenteritis virus (TGEV), a porcine coronavirus, were nebulized at rates of 0.1–0.2 ml/min into moving air using a Collison nebulizer or a plastic medical nebulizer operating at pressures ranging from 7 to 15 psi. The airborne viruses were collected on heating, ventilating, and air conditioning (HVAC) filters in an experimental apparatus and also sampled upstream of these test filters using AGI-30 and BioSampler impinger samplers. To study the effects of relative humidity (RH) on TGEV collection by the filters and samplers, the virus was nebulized into air at 30, 50, 70, and 90% RH. There were no significant changes in virus titer in the nebulizer suspension before and after nebulization for either nebulizer at any of the pressures utilized. Aerosolization efficiency – the ratio of viable virus sampled with impingers to the quantity of viable virus nebulized – decreased with increasing humidity. BioSamplers detected more airborne virus than AGI-30 samplers at all RH levels. This difference was statistically significant at 30 and 50% RH. Nebulizer type and pressure did not significantly affect the viability of the airborne virus. Virus recovery from test filters relative to the concentration of virus in the nebulizer suspension was less than 10%. The most and the least virus were recovered from filter media at 30% and 90% RH, respectively. The results suggest that TGEV, and perhaps other coronaviruses, remain viable longer in an airborne state and are sampled more effectively at low RH than at high humidity.

negative: Potential challenges of employing a formal environmental scanning approach in hospitality organizations Most previous studies on environmental scanning (ES) in the field of hospitality management suggest that hospitality organizations establish formal systematic ES procedures and have a freestanding ES unit to identify opportunities and threats in their external environment. However, some serious criticisms have been raised in the field of strategic management against the employment of such a formal and systematic approach to ES. These opposing views have rarely been discussed in the hospitality management literature. The aim of this paper, therefore, is to bring these views to the fore in the process of reviewing previous research into ES, and to discuss the major challenges involved for hospitality organizations in employing such a formal approach to ES. The discussion throughout this paper reveals that ES is essential for every organization; however, it is even more complex and difficult to accomplish than portrayed in most previous studies in the hospitality management field. The paper identifies and discusses major challenges and problems in employing a form ES approach in hospitality organizations. It also provides recommendations about how ES activities can best be carried out in complex and dynamic environments.

negative: Pathogenesis: Infection and the Spread of Viruses in the Body At the molecular and cellular levels, viruses behave quite differently from bacteria and protozoa but to some extent, this distinction disappears when viruses are considered at the levels of the whole animal and the population. Viruses, like other infectious agents, enter the animal body through one of its surfaces. They then spread either locally on one of the body surfaces or through lymphatic and blood vessels to produce systemic infection. To infect its host, a virus first attaches to and infects cells of one of the body surfaces: the skin, the mucosa of the digestive, respiratory, or urogenital tract, or the conjunctiva. Parenteral injection, either by needle or by the bite of an arthropod or vertebrate, bypasses the body surfaces. A lesion may be produced at the site of entry, although invasion may occur without the development of any local evidence of infection. The infection may remain localized in the skin, respiratory tract, or digestive tract or it may spread through the animal via the lymphatics, blood vessels, or nerves.

negative: Demyelination and remyelination in the dorsal funiculus of the rat spinal cord after heat injury Part of the dorsal funiculus of the adult male rat (Wistar) spinal cord was treated for l h at the thoracolumbar level by running hot water, at approximately 48–50 ° C, through a polyethylene tube 2 mm in diameter in contact with the dura. Animals were fixed 1 day to 4 weeks later and the spinal cords were examined by light and electron microscopy. The affected area in the dorsal funiculus was approximately 1 mm long and less than 1 mm wide at the dorsal surface, and varied from 0.4 to 0.7 mm in depth. Within 3 days after treatment, almost all the myelin sheaths in the affected area were degraded, leaving the axons denuded, and at the same time astrocyte endfeet at the glial limiting membrane were swollen and partly destroyed. Almost all the denuded axons remained intact, exhibiting no noticeable morphological changes. There was evidence of a moderate vasogenic oedema, but minimal signs of haemorrhage in the lesion. Seven days after treatment, many immature Schwann cells but no oligodendrocytes were found between the denuded axons. By 2 weeks many of the denuded axons were remyelinated, and by 4 weeks almost all of those axons located near the pial and perivascular surfaces had been remyelinated by Schwann cells, while most of those located in the deep and marginal zones bordering the adjoining intact areas were remyelinated by oligodendrocytes. Longitudinal sections revealed that at nodes of Ranvier PNS-type myelin sheaths were apposed by either intact or newly formed CNS-type myelin sheaths. A typical glial limiting membrane was not reformed beneath the pial surface, but an inconspicuous one was found between the PNS- and CNS-type fibre areas.

negative: Airway Management in the Operating Room and Interventional Suites in Known or Suspected Coronavirus Disease 2019 Adult Patients: A Practical Review Current evidence suggests that Coronavirus Disease 2019 (COVID-19) spread occurs via respiratory droplets (particles >5 µm) and possibly through aerosol. The rate of transmission remains high during airway management. This was evident during the 2003 severe acute respiratory syndrome epidemic where those who were involved in tracheal intubation had a higher risk of infection than those who were not involved (odds ratio 6.6). We describe specific airway management principles for patients with known or suspected COVID-19 disease for an array of critical care and procedural settings. We conducted a thorough search of the available literature of airway management of COVID-19 across a variety of international settings. In addition, we have analyzed various medical professional body recommendations for common procedural practices such as interventional cardiology, gastroenterology, and pulmonology. A systematic process that aims to protect the operators involved via appropriate personal protective equipment, avoidance of unnecessary patient contact and minimalization of periprocedural aerosol generation are key components to successful airway management. For operating room cases requiring general anesthesia or complex interventional procedures, tracheal intubation should be the preferred option. For interventional procedures, when tracheal intubation is not indicated, cautious conscious sedation appears to be a reasonable approach. Awake intubation should be avoided unless it is absolutely necessary. Extubation is a high-risk procedure for aerosol and droplet spread and needs thorough planning and preparation. As updates and modifications in the management of COVID-19 are still evolving, local guidelines, appraised at regular intervals, are vital in optimizing clinical management.

negative: Virological and serological analysis of a recent Middle East respiratory syndrome coronavirus infection case on a triple combination antiviral regimen Abstract Serological, molecular and phylogenetic analyses of a recently imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) in Greece are reported. Although MERS-CoV remained detectable in the respiratory tract secretions of the patient until the fourth week of illness, viraemia was last detected 2 days after initiation of triple combination therapy with pegylated interferon, ribavirin and lopinavir/ritonavir, administered from Day 13 of illness. Phylogenetic analysis of the virus showed close similarity with other human MERS-CoVs from the recent Jeddah outbreak in Saudi Arabia. Immunoglobulin G (IgG) titres peaked 3 weeks after the onset of illness, whilst IgM levels remained constantly elevated during the follow-up period (second to fifth week of illness). Serological testing confirmed by virus neutralisation assay detected an additional case that was a close contact of the patient.

negative: The effect of COVID-19 and subsequent social distancing on travel behavior Abstract The spread of the COVID-19 virus has resulted in unprecedented measures restricting travel and activity participation in many countries. Social distancing, i.e., reducing interactions between individuals in order to slow down the spread of the virus, has become the new norm. In this viewpoint I will discuss the potential implications of social distancing on daily travel patterns. Avoiding social contact might completely change the number and types of out-of-home activities people perform, and how people reach these activities. It can be expected that the demand for travel will reduce and that people will travel less by public transport. Social distancing might negatively affect subjective well-being and health status, as it might result in social isolation and limited physical activity. As a result, walking and cycling, recreationally or utilitarian, can be important ways to maintain satisfactory levels of health and well-being. Policymakers and planners should consequently try to encourage active travel, while public transport operators should focus on creating ways to safely use public transport.

negative: How can airborne transmission of COVID-19 indoors be minimised? Abstract During the rapid rise in COVID-19 illnesses and deaths globally, and notwithstanding recommended precautions, questions are voiced about routes of transmission for this pandemic disease. Inhaling small airborne droplets is probable as a third route of infection, in addition to more widely recognized transmission via larger respiratory droplets and direct contact with infected people or contaminated surfaces. While uncertainties remain regarding the relative contributions of the different transmission pathways, we argue that existing evidence is sufficiently strong to warrant engineering controls targeting airborne transmission as part of an overall strategy to limit infection risk indoors. Appropriate building engineering controls include sufficient and effective ventilation, possibly enhanced by particle filtration and air disinfection, avoiding air recirculation and avoiding overcrowding. Often, such measures can be easily implemented and without much cost, but if only they are recognised as significant in contributing to infection control goals. We believe that the use of engineering controls in public buildings, including hospitals, shops, offices, schools, kindergartens, libraries, restaurants, cruise ships, elevators, conference rooms or public transport, in parallel with effective application of other controls (including isolation and quarantine, social distancing and hand hygiene), would be an additional important measure globally to reduce the likelihood of transmission and thereby protect healthcare workers, patients and the general public.

negative: ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection The COVID-19 pandemics is posing unprecedented challenges and threats to patients and healthcare systems worldwide. Acute respiratory complications that require intensive care unit (ICU) management are a major cause of morbidity and mortality in COVID-19 patients. Patients with worst outcomes and higher mortality are reported to include immunocompromised subjects, namely older adults and polymorbid individuals and malnourished people in general. ICU stay, polymorbidity and older age are all commonly associated with high risk for malnutrition, representing per se a relevant risk factor for higher morbidity and mortality in chronic and acute disease. Also importantly, prolonged ICU stays are reported to be required for COVID-19 patients stabilization, and longer ICU stay may per se directly worsen or cause malnutrition, with severe loss of skeletal muscle mass and function which may lead to disability, poor quality of life and additional morbidity. Prevention, diagnosis and treatment of malnutrition should therefore be routinely included in the management of COVID-19 patients. In the current document, the European Society for Clinical Nutrition and Metabolism (ESPEN) aims at providing concise guidance for nutritional management of COVID-19 patients by proposing 10 practical recommendations. The practical guidance is focused to those in the ICU setting or in the presence of older age and polymorbidity, which are independently associated with malnutrition and its negative impact on patient survival.

negative: Correlation between weather and Covid-19 pandemic in Jakarta, Indonesia This study aims to analyze the correlation between weather and covid-19 pandemic in Jakarta Indonesia. This study employed a secondary data analysis of surveillance data of covid-19 from the Ministry of Health of the Republic of Indonesia and weather from the Meteorological Department of the Republic of Indonesia. The components of weather include minimum temperature (°C), maximum temperature (°C), temperature average (°C), humidity (%), and amount of rainfall (mm). Spearman-rank correlation test was used for data analysis. Among the components of the weather, only temperature average (°C) was significantly correlated with covid-19 pandemic (r = 0.392; p < .01). The finding serves as an input to reduce the incidence rate of covid-19 in Indonesia.

negative: A Social Network Model of the COVID-19 Pandemic In the COVID-19 coronavirus pandemic, currently vaccines and specific anti-viral treatment are not yet available. Thus, preventing viral transmission by case isolation, quarantine, and social distancing is essential to slowing its spread. Here we model social networks using weighted graphs, where vertices represent individuals and edges represent contact. As public health measures are implemented, connectivity in the graph decreases, resulting in lower effective reproductive numbers, and reduced viral transmission. For COVID-19, model parameters were derived from the coronavirus epidemic in China, validated by epidemic data in Italy, then applied to the United States. We calculate that, in the U.S., the public is able to contain viral transmission by limiting the average number of contacts per person to less than 7 unique individuals over each 5 day period. This increases the average social distance between individuals to 10 degrees of separation.

negative: Antiviral drug screening by assessing epithelial functions and innate immune responses in human 3D airway epithelium model Abstract Respiratory viral infections cause mild to severe diseases, such as common cold, bronchiolitis and pneumonia and are associated with substantial burden for society. To test new molecules for shortening, alleviating the diseases or to develop new therapies, relevant human in vitro models are mandatory. MucilAir™, a human standardized air-liquid interface 3D airway epithelial culture holds in vitro specific mechanisms to counter invaders comparable to the in vivo situation, such as mucus production, mucociliary clearance, and secretion of defensive molecules. The objective of this study was to test the relevance of such a model for the discovery and validation of antiviral drugs. Fully differentiated 3D nasal epithelium cultures were inoculated with picornaviruses, a coronavirus and influenza A viruses in the absence or in the presence of reference antiviral drugs. Results showed that, rupintrivir efficiently inhibits the replication of respiratory picornaviruses in a dose dependent manner and prevents the impairment of the mucociliary clearance. Similarly, oseltamivir reduced the replication of influenza A viruses in a dose dependent manner and prevented the impairment of the epithelial barrier function and cytotoxicity until 4 days of infection. In addition we found that Rhinovirus B14, C15 and influenza A(H1N1) induce significant increase of β Defensins 2 and Cathelicidin release with different time course. These results reveal that a large panel of epithelial functions is modified upon viral infection and validate MucilAir™ as a pertinent tool for pre-clinical antiviral drug testing.

negative: Two simple comments regarding coronavirus Abstract Two thought provoking comments related to understanding the problems with the coronavirus are presented.

negative: Lack of transmission among healthcare workers in contact with a case of Middle East respiratory syndrome coronavirus infection in Thailand INTRODUCTION: A hospital-associated outbreak of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was reported. We aimed to assess the effectiveness of infection control measures among healthcare workers (HCWs) who were exposed to a MERS patient and/or his body fluids in our institute. METHODS: A descriptive study was conducted among HCWs who worked with a MERS patient in Bamrasnaradura Infectious Diseases Institute, Thailand, between 18 June and 3 July 2015. Contacts were defined as HCWs who worked in the patient’s room or with the patient’s body fluids. Serum samples from all contacts were collected within 14 days of last contact and one month later. Paired sera were tested for detection of MERS‐CoV antibodies by using an indirect ELISA. RESULTS: Thirty-eight (88.4 %) of 43 identified contacts consented to enroll. The mean (SD) age was 38.1 (11.1) years, and 79 % were females. The median (IQR) cumulative duration of work of HCWs in the patient’s room was 35 (20–165) minutes. The median (IQR) cumulative duration of work of HCWs with the patient’s blood or body fluids in laboratory was 67.5 (43.7–117.5) minutes. All contacts reported 100 % compliance with hand hygiene, using N95 respirator, performing respirator fit test, wearing gown, gloves, eye protection, and cap during their entire working period. All serum specimens of contacts tested for MERS-CoV antibodies were negative. CONCLUSIONS: We provide evidence of effective infection control practices against MERS-CoV transmission in a healthcare facility. Strict infection control precautions can protect HCWs. The optimal infection control measures for MERS-CoV should be further evaluated.

negative: Guidelines for the Laboratory Diagnosis of Middle East Respiratory Syndrome Coronavirus in Korea The recent outbreak of Middle East respiratory syndrome (MERS) in Korea was unexpected that laboratory response had to be built up urgently during the outbreak. The outbreak was almost all healthcare-associated, which was aggravated by lack of availability in laboratory diagnosis of MERS-CoV on site. On behalf of the MERS joint public and private sector response committee (MERS Joint committee), the Korean Society for Laboratory Medicine (KSLM) launched a MERS response task force (MERS KSLM TF) to facilitate clinical laboratories set up MERS molecular diagnosis. MERS TF established guidelines for laboratory diagnosis of MERS-CoV and provided it to all participating laboratories as the official guidance of MERS Joint committee. This guideline was used for procedure manual of molecular diagnosis of MERS-CoV and laboratory safety manual.

negative: Including 793/B type avian infectious bronchitis vaccine in 1-day-old chicken increased the protection against QX genotype Infectious bronchitis virus (IBV) is a highly infectious pathogen, which affects the respiratory tract, reproductive system, and kidney of chickens. Many different genotypes of IBV are recognized which cause different clinical manifestations. According to the antigenic differences, different serotypes of the virus do not cross-protect. Massachusetts serotype induces the best cross-protection against other serotypes. Recently, the IBV QX genotype has been detected in Iran. QX genotype causes permanent damage to the oviduct in layer and breeder flock if it occurs in the early life cycle. In this study, we compared two vaccination program using 793/B type and Massachusetts type vaccine. One-day-old SPF chickens were divided into four groups. Groups 1 and 2 were unvaccinated groups. Group 3 was vaccinated with the H120 vaccine at day 1 and 793/B at day 14 (eye drop), and group 4 was vaccinated with H120+793/B (eye drop) on the first day and 793/B at day 14. Groups 2, 3, and 4 challenged (oculonasal) with QX genotype (10(4) EID50) at day 35. Five days post challenge, the sample were clollected for ciliostasis test, histopathology, and quantitative real-time RT-PCR from trachea, lung, and kidneys. Results showed that two vaccination programs created more than 80% of protection against challenge virus, but no significant difference was recorded between two programs. Based on our results, it can be concluded that vaccination with two mixed vaccines (H120+793/B) on the first day of the life of a chick does not make any difference in comparison to single vaccine (H120) in reducing of pathological damages and viral load. As long as the second vaccination against IB may not be applied properly in farm situation, applying the mixture of 793/B type vaccine with H120 at day 1 (ocular or spray) may help to increase vaccination program efficacy.

negative: Propagation of Respiratory Aerosols by the Vuvuzela Vuvuzelas, the plastic blowing horns used by sports fans, recently achieved international recognition during the FIFA World Cup soccer tournament in South Africa. We hypothesised that vuvuzelas might facilitate the generation and dissemination of respiratory aerosols. To investigate the quantity and size of aerosols emitted when the instrument is played, eight healthy volunteers were asked to blow a vuvuzela. For each individual the concentration of particles in expelled air was measured using a six channel laser particle counter and the duration of blowing and velocity of air leaving the vuvuzela were recorded. To allow comparison with other activities undertaken at sports events each individual was also asked to shout and the measurements were repeated while using a paper cone to confine the exhaled air. Triplicate measurements were taken for each individual. The mean peak particle counts were 658×10(3) per litre for the vuvuzela and 3.7×10(3) per litre for shouting, representing a mean log(10) difference of 2.20 (95% CI: 2.03,2.36; p<0.001). The majority (>97%) of particles captured from either the vuvuzela or shouting were between 0.5 and 5 microns in diameter. Mean peak airflows recorded for the vuvuzela and shouting were 6.1 and 1.8 litres per second respectively. We conclude that plastic blowing horns (vuvuzelas) have the capacity to propel extremely large numbers of aerosols into the atmosphere of a size able to penetrate the lower lung. Some respiratory pathogens are spread via contaminated aerosols emitted by infected persons. Further investigation is required to assess the potential of the vuvuzela to contribute to the transmission of aerosol borne diseases. We recommend, as a precautionary measure, that people with respiratory infections should be advised not to blow their vuvuzela in enclosed spaces and where there is a risk of infecting others.

negative: Chapter 18 Electrochemical virus detections with nanobiosensors Abstract Infectious diseases are caused from pathogens, which need a reliable and fast diagnosis. Today, expert personnel and centralized laboratories are needed to afford much time in diagnosing diseases caused from pathogens. Recent progress in electrochemical studies shows that biosensors are very simple, accurate, precise, and cheap at virus detection, for which researchers find great interest in this field. The clinical levels of these pathogens can be easily analyzed with proposed biosensors. Their working principle is based on affinity between antibody and antigen in body fluids. The progress still continues on these biosensors for accurate, rapid, reliable sensors in future.

negative: Detection of feline coronavirus RNA in feces, tissues, and body fluids of naturally infected cats by reverse transcriptase PCR. A nested reverse transcriptase PCR (RT-nPCR) was developed for the detection of feline coronavirus (FCoV) RNA in the feces, tissues, and body fluids of infected cats. The RT-nPCR was targeted to the highly conserved 3'-untranslated region of the viral genome and will detect most, if not all, feline coronaviruses in the field. With the RT-nPCR, FCoV RNA was detected in plasma samples from experimentally infected cats as early as 2 days postinoculation. FCoV RNA was also detected in serum, plasma, or ascitic fluid samples from 14 of 18 cats (78%) with naturally occurring feline infectious peritonitis (FIP). The use of RT-PCR for FIP diagnosis is limited because of the occurrence of apparently healthy FCoV carriers. These asymptomatic cats shed the virus in the feces and, in a number of cases, also had detectable virus in the plasma. Because of the nature of FCoV infections, our RT-PCR assay with plasma or serum cannot be used to establish a definite diagnosis of FIP. However, this assay does provide a new means to identify asymptomatic FCoV carriers. As such, RT-nPCR will be of use to screen cats before their introduction into FCoV-free catteries. Moreover, this assay provides an important tool to study the epidemiology of FCoV.

negative: The third coronavirus epidemic in the third millennium: what’s next?

negative: Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak Public health measures were decisive in controlling the SARS epidemic in 2003. Isolation is the separation of ill persons from non-infected persons. Quarantine is movement restriction, often with fever surveillance, of contacts when it is not evident whether they have been infected but are not yet symptomatic or have not been infected. Community containment includes measures that range from increasing social distancing to community-wide quarantine. Whether these measures will be sufficient to control 2019-nCoV depends on addressing some unanswered questions.

negative: The novel Coronavirus (SARS-CoV-2) is a one health issue

negative: Diversity of Coronavirus Spikes: Relationship to Pathogen Entry and Dissemination Coronaviruses are widespread in the environment, infecting humans, domesticated and wild mammals, and birds. Infections cause a variety of diseases including bronchitis, gastroenteritis, hepatitis, and encephalitis, with symptoms ranging from being nearly undetectable to rapidly fatal. A combination of interacting variables determine the pattern and severity of coronavirus-induced disease, including the infecting virus strain, its transmission strategy, and the age and immune status of the infected host. Coronavirus pathogenesis is best understood by discerning how each of these variables dictates clinical outcomes. This chapter focuses on variabilities amongst the spike (S) proteins of infecting virus strains. Diversity of coronavirus surface proteins likely contributes to epidemic disease, an important and timely topic given the recent emergence of the human SARS coronavirus.

negative: Coronavirus in Continuous Flux: From SARS‐CoV to SARS‐CoV‐2 The world is currently experiencing a global pandemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes severe respiratory disease similar to SARS. Previous studies have suggested that SARS‐CoV‐2 shares 79% and 96% sequence identity to SARS‐CoV and to bat coronavirus RaTG13, respectively at the whole‐genome level. Furthermore, a series of studies have shown that SARS‐CoV‐2 induces clusters of severe respiratory illnesses (i.e., pneumonia, acute lung injury (ALI), acute respiratory distress syndrome (ARDS)) resembling SARS‐CoV. Moreover, the pathological syndrome may, in part, be caused by cytokine storms and dysregulated immune responses. Thus, in this work the recent literature surrounding the biology, clinical manifestations, and immunology of SARS‐CoV‐2 is summarized, with the aim of aiding prevention, diagnosis, and treatment for SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved

negative: In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds Abstract Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics.

negative: Coronavirus Disease 19 (COVID-19): Implications for Clinical Dental Care The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease has gripped the entire international community and caused widespread public health concerns. Despite global efforts to contain the disease spread, the outbreak is still on a rise because of the community spread pattern of this infection. This is a zoonotic infection, similar to other coronavirus infections, that is believed to have originated in bats and pangolins and later transmitted to humans. Once in the human body, this coronavirus (SARS-CoV-2) is abundantly present in nasopharyngeal and salivary secretions of affected patients, and its spread is predominantly thought to be respiratory droplet/contact in nature. Dental professionals, including endodontists, may encounter patients with suspected or confirmed SARS-CoV-2 infection and will have to act diligently not only to provide care but at the same time prevent nosocomial spread of infection. Thus, the aim of this article is to provide a brief overview of the epidemiology, symptoms, and routes of transmission of this novel infection. In addition, specific recommendations for dental practice are suggested for patient screening, infection control strategies, and patient management protocol.

negative: Long-Term Care Facilities and the Coronavirus Epidemic: Practical Guidelines for a Population at Highest Risk

negative: Personal protective equipment and possible routes of airborne spread during the COVID-19 pandemic

negative: 2013 Update on Current Vaccination Strategies in Puppies and Kittens Vaccines remain one of the practitioner’s greatest tools in preventing disease and maintaining individual and population health. This article is an update to “Current Vaccination Strategies in Puppies and Kittens” published in Veterinary Clinics of North America, Small Animal Practitioner, in May 2006. There are now comprehensive guidelines readily available for small animal practitioners regarding canine and feline pediatric (and adult) vaccination recommendations. Perhaps more importantly, there is an increased dialogue regarding all aspects of preventive medicine, of which vaccination is only a small, yet significant portion; and an increased drive to provide scientific evidence for developing vaccination recommendations.

negative: Evidence for systematic autopsies in COVID-19 positive deceased: Case report of the first German investigated COVID-19 death Forensic medicine and pathology involve specific health risks, whereby health workers are dealing with microorganisms, cells or parasites, which are referred to as biological agents. Biological agents are divided into four categories according to § 3 of the Biological Agents Ordinance. The newly identified coronavirus, severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2) that has spread rapidly around the world is placed into category 3 of the Biological Agents Ordinance, meaning pathogens that can cause serious illnesses in humans and may pose a risk to workers. The Robert Koch Institute, the German government’s central scientific institution in the field of biomedicine issued the announcement, that aerosol-producing measures (including autopsies) of SARS-CoV‑2 infected bodies should be avoided, despite the fact that autopsies are an important source of understanding the pathomorphological course of new diseases. The first German case of death due to a proven SARS-CoV‑2 infection is presented with global multifocal reticular consolidation in the post-mortem computed tomography (CT) scan, a macroscopic and microscopic viral pneumonia and viral RNA of SARS-CoV‑2 in pharyngeal mucosa and lung tissue.

negative: Analysis on the Clinical Characteristics of 36 Cases of Novel Coronavirus Pneumonia in Kunming Objective: To analyze the clinical characteristics of patients with novel coronavirus pneumonia in Kunming City, and to study the correlation between nutritional status and immune function. Methods: Clinical data of 36 patients with novel coronavirus pneumonia in isolation area of Kunming Third People's Hospital from January 31 to February 15, 2020 were collected, and the basic situation, clinical characteristics, laboratory examination and CT imaging characteristics were analyzed. Serum albumin (ALB), prealbumin (PAB), hypersensitive c-reactive protein (hs-crp), CD3T cells, CD4T cells, CD8T cells and normal control group were analyzed. A simple linear regression analysis of the relationship between proalbumin and T cell subpopulation counts in the blood of patients. Results: (1) The patients with new coronavirus pneumonia in Kunming were mainly of common type. (2) 50% of the patients' first symptoms were fever and cough; (3) The total number of white blood cells in peripheral blood was normal or decreased in 23 cases (79%), and the lymphocyte count decreased in 5 cases (13.89%), without anemia. Hypersensitive c-reactive protein increased in 19 (52.78%) cases, and procalcitonin increased in 1 case. Albumin decreased in 5 cases (13.89%), proalbumin decreased in 15 cases (41.67%), alanine transaminase increased slightly in 4 cases (11.11%), alanine transaminase increased slightly in 4 cases (11.11%), total bilirubin increased slightly in 11 cases (30.56%), and renal function and blood coagulation were normal. Absolute value of CD3+T cells is with a decrease in 21 cases (58.3%), CD4+T in 28 cases (77.8%), CD8+T in 17 cases (47.2%), and CD4+/ CD8+ inverse in 6 cases (16.7%). (4) The prealbumin, CD3 T cells, CD4 T cells and CD8 T cells in the new coronavirus pneumonia group were significantly lower than those in the normal control group, and the hypersensitive c-reactive protein was higher than that in the normal control group. (5) The levels of PAB in the serum of the patients were linearly correlated with hs-crp, CD3 T cells, CD4 T cells and CD8 T cells, and the correlation coefficients were -0.474, 0.558, 0.467 and 0.613, respectively, showing statistical differences. Conclusion: The clinical characteristics of the novel coronavirus pneumonia in Kunming are different from those in Wuhan. The changes of serum proalbumin and T cell subsets are relatively obvious. Changes in serum proalbumin may contribute to the early warning of novel coronavirus pneumonia. The nutritional status of patients with common and mild pneumonia should be considered.

negative: Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases PURPOSE: Infection with COVID-19 potentially can result in severe outcomes and death from “cytokine storm syndrome”, resulting in novel coronavirus pneumonia (NCP) with severe dyspnea, acute respiratory distress syndrome (ARDS), fulminant myocarditis and multiorgan dysfunction with or without disseminated intravascular coagulation. No published treatment to date has been shown to adequately control the inflammation and respiratory symptoms associated with COVID-19, apart from oxygen therapy and assisted ventilation. We evaluated the effects of using high dose oral and/or IV glutathione in the treatment of 2 patients with dyspnea secondary to COVID-19 pneumonia. METHODS: Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms. CONCLUSION: Oral and IV glutathione, glutathione precursors (N-acetyl-cysteine) and alpha lipoic acid may represent a novel treatment approach for blocking NF-κB and addressing “cytokine storm syndrome” and respiratory distress in patients with COVID-19 pneumonia.

negative: Vaccine against Middle East respiratory syndrome coronavirus

negative: Introducing Ebola (EVD): An Unnecessary Surprise Chapter 4 tackles the Ebola (Ebola Virus Disease, EVD) pandemic of 2014/2015. It notes that coming in the wake of the ongoing HIV pandemic, the rights of those infected with Ebola to be identified and treated were largely uncontested. The questions of who would be treated, by whom, with what, remained however extremely contentious. The international response to the pandemic also saw, for the first time, not only non-state actors involved in mediating and mitigating a health crisis, but also military intervention. This chapter lays out both the uses and the dilemmas of military response. It explores the impact of these interventions in this Ebola pandemic, with a view towards possible future military deployments against health threats, and offers an initial analysis of the consequences thereof on the relationship between individual and state rights and responsibilities.

negative: [Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing]. Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte , and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.

negative: The Novel Coronavirus Outbreak: What We Know and What We Don’t

negative: Quantitative analysis of Glycyrrhizic acid from a polyherbal preparation using liquid chromatographic technique Glycyrrhizic acid has been used in Indian traditional medicine for ages. It is obtained from the root extract of Glycyrrhizaglabra. There is seasonal variation of Glycyrrhizic acid content in the roots of the plant. So a proper method for quantification of the same is necessary from the polyherbal preparation available in the market. A simple, rapid, sensitive and specific reverse phase high performance liquid chromatographic method have been developed for the quantitative estimation of glycyrrhizic acid from polyherbal preparation containing aqueous root extract of Glycyrrhizaglabra using a photodiode array detector. The identity confirmation was carried out using mass spectrometry. Baseline resolution of the glycyrrhizic acid peak was achieved on a reverse phase C18 column (125 mm × 4.0 mm, 5 μ) using an isocratic mobile phase consisting of 5.3 mM phosphate buffer and acetonitrile in the ratio 65:35 v/v. Chromatograms were monitored at 252 nm.5.3 mM phosphate buffer was replaced with 0.5mM ammonium acetate buffer in the mobile phase when MS detector was used. The method was found to be linear in the concentration range of 12.4 to124 μg/ml with a correlation co-efficient of 0.999. The limit of detection and the limit of quantitation were 3.08 μg/ml and 10.27 μg/ml respectively. The average recovery from three spike levels was 99.93 ± 0.26%. Identity confirmation of the chromatographic peak was achieved by electrospray ionization mass spectrometry and similar molecular ion peak was obtained for both sample and standard. The developed method is suitable for the routine analysis, stability testing and assay of glycyrrhizic acid from polyherbal preparations containing aqueous extracts of Glycyrrhizaglabra.

negative: Infectious Diseases: The Role of the Healthcare Professional For the healthcare professional dealing with infections presents two main problems. First, managing detainees or police personnel who have contracted a disease and may be infectious or unwell, and second, handling complainants of assault, including police officers, who have potentially been exposed to an infectious disease. This chapter addresses some general principles of infection control and safety in the working environment and then goes on to discuss some infections that may be encountered in police custody and how they can best be managed.

negative: Spatial modeling cannot currently differentiate SARS-CoV-2 coronavirus and human distributions on the basis of climate in the United States The SARS-CoV-2 coronavirus is wreaking havoc globally, yet knowledge of its biology is limited. Climate and seasonality influence the distributions of many diseases, and studies suggest a link between SARS-CoV-2 and cool weather. One such study, building species distribution models (SDMs), predicted SARS-CoV-2 risk may remain concentrated in the Northern Hemisphere, shifting northward in summer months. Others have highlighted issues with SARS-CoV-2 SDMs, notably: the primary niche of the virus is the host it infects, climate may be a weak distributional predictor, global prevalence data have issues, and the virus is not in a population equilibrium. While these issues should be considered, climate still may be important for predicting the future distribution of SARS-CoV-2. To further examine if there is a link, we model with raw cases and population scaled cases for SARS-CoV-2 county-level data from the United States. We show that SDMs built from population scaled cases data cannot be distinguished from control models built from raw human population data, while SDMs built on raw data fail to predict the current known distribution of cases in the US. The population scaled analyses indicate that climate may not play a central role in current US viral distribution and that human population density is likely a primary driver. Still, we do find slightly more population scaled viral cases in cooler areas. This coupled with our geographically constrained focus make it so we cannot rule out climate as a partial driver of the US SARS-CoV-2 distribution. Climate's role on SARS-CoV-2 should continue to be cautiously examined, but at this time we should assume that SARS-CoV-2 can spread anywhere in the US.

negative: Methusaleh's Zoo: how nature provides us with clues for extending human health span. As impressive as the accomplishments of modern molecular biologists have been in finding genetic alterations that lengthen life in short-lived model organisms, they pale in comparison to the remarkable diversity of lifespans produced by evolution. Some animal species are now firmly documented to live for more than four centuries and even some mammals, like the bowhead whale, appear to survive 200 years or more. Another group of species may not be as absolutely long-lived, but they are remarkably long-lived for their body size and metabolic rate. These species include a number of bats, some of which live for at least 40 years in the wild, as well as the naked mole-rat, which is the same size, but lives nearly 10 times as long as the laboratory mouse. Together these exceptionally long-lived organisms have important roles to play in our future understanding of the causal mechanisms and modulation of ageing. Bats and naked mole-rats in particular have already contributed in the following ways: (1) they have contributed to the abandonment of the rate-of-living theory and weakened enthusiasm for the oxidative stress hypothesis of ageing, (2) they have helped evaluate how the tumour-suppressing role of cellular senescence is affected by the evolution of diverse body sizes as well as diverse longevities, (3) they have shed light on the relationship between specific types of DNA repair and ageing and (4) they have yielded insight into new processes, specifically the maintenance of the proteome and hypotheses concerning how evolution shapes ageing. The continuing acceleration of progress in genome sequencing and development of more and more cross-species investigatory techniques will facilitate even more contributions of these species in the near future.

negative: Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe. Considering the potential threat of a pandemic, scientists and physicians have been racing to understand this new virus and the pathophysiology of this disease to uncover possible treatment regimens and discover effective therapeutic agents and vaccines. To support the current research and development, CAS has produced a special report to provide an overview of published scientific information with an emphasis on patents in the CAS content collection. It highlights antiviral strategies involving small molecules and biologics targeting complex molecular interactions involved in coronavirus infection and replication. The drug-repurposing effort documented herein focuses primarily on agents known to be effective against other RNA viruses including SARS-CoV and MERS-CoV. The patent analysis of coronavirusrelated biologics includes therapeutic antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression as well as various types of vaccines. More than 500 patents disclose methodologies of these four biologics with the potential for treating and preventing coronavirus infections, which may be applicable to COVID-19. The information included in this report provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines.

negative: Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.

negative: The progress of 2019 novel coronavirus event in China It has been more than one month since the first 2019-nCov infected person was diagnosed. However, the number of cumulative cases is keeping upward, including the severe cases and death cases. It has been proved that droplets transmission is the major route for 2019-nCov infection, and interpersonal contact could also cause the disease. Due to the fast-growing of Wuhan pneumonia and relative low cure rate, Chinese government is facing great challenges, and has taken emergency measures on disease prevention and clinical treatment, including population mobility control, building five or more hospitals for Wuhan pneumonia treatment, such as "Huo Shen Shan" hospital as well as developing a specific vaccine. In the meanwhile, the government shared the updated Genome Sequence of 2019-nCoV to the public, and scientists from China and oversea are working tightly and efficiently on public health emergency. This article is protected by copyright. All rights reserved.

negative: SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. However, as SARS-CoV-2 is an emerging virus, we know little about it. In this review, we summarize the key events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the pathogen, the signs and symptoms of the infected patients as well as the possible transmission pathways of the virus. Furthermore, we also review the current knowledge on the origin and evolution of the SARS-CoV-2. We highlight bats as the potential natural reservoir and pangolins as the possible intermediate host of the virus, but their roles are waiting for further investigation. Finally, the advances in the development of chemotherapeutic options are also briefly summarized.

negative: Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines. With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2'O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the severe acute respiratory syndrome-CoV mouse model, an NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2'O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2'O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live attenuated coronavirus vaccines.IMPORTANCE Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations such as the aged and immunocompromised. This study illustrates that despite success in young models, the 2'O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the 2'O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2'O methyltransferase attenuation as a major component of future live attenuated coronavirus vaccines.

negative: Recent transmission of a novel alphacoronavirus, bat coronavirus HKU10, from Leschenault's rousettes to pomona leaf-nosed bats: first evidence of interspecies transmission of coronavirus between bats of different suborders. Although coronaviruses are known to infect various animals by adapting to new hosts, interspecies transmission events are still poorly understood. During a surveillance study from 2005 to 2010, a novel alphacoronavirus, BatCoV HKU10, was detected in two very different bat species, Ro-BatCoV HKU10 in Leschenault's rousettes (Rousettus leschenaulti) (fruit bats in the suborder Megachiroptera) in Guangdong and Hi-BatCoV HKU10 in Pomona leaf-nosed bats (Hipposideros pomona) (insectivorous bats in the suborder Microchiroptera) in Hong Kong. Although infected bats appeared to be healthy, Pomona leaf-nosed bats carrying Hi-BatCoV HKU10 had lower body weights than uninfected bats. To investigate possible interspecies transmission between the two bat species, the complete genomes of two Ro-BatCoV HKU10 and six Hi-BatCoV HKU10 strains were sequenced. Genome and phylogenetic analyses showed that Ro-BatCoV HKU10 and Hi-BatCoV HKU10 represented a novel alphacoronavirus species, sharing highly similar genomes except in the genes encoding spike proteins, which had only 60.5% amino acid identities. Evolution of the spike protein was also rapid in Hi-BatCoV HKU10 strains from 2005 to 2006 but stabilized thereafter. Molecular-clock analysis dated the most recent common ancestor of all BatCoV HKU10 strains to 1959 (highest posterior density regions at 95% [HPDs], 1886 to 2002) and that of Hi-BatCoV HKU10 to 1986 (HPDs, 1956 to 2004). The data suggested recent interspecies transmission from Leschenault's rousettes to Pomona leaf-nosed bats in southern China. Notably, the rapid adaptive genetic change in BatCoV HKU10 spike protein by ~40% amino acid divergence after recent interspecies transmission was even greater than the ~20% amino acid divergence between spike proteins of severe acute respiratory syndrome-related Rhinolophus bat coronavirus (SARSr-CoV) in bats and civets. This study provided the first evidence for interspecies transmission of coronavirus between bats of different suborders.

negative: A Comparative Study of On-Body Radio-Frequency Links in the 420 MHz⁻2.4 GHz Range. While there exists a wide variety of radio frequency (RF) technologies amenable for usage in Wireless Body Area Networks (WBANs), which have been studied separately before, it is currently still unclear how their performance compares in true on-body scenarios. In this paper, a single reference on-body scenario-that is, propagation along the arm-is used to experimentally compare six distinct RF technologies (between 420 MHz and 2.4 GHz) in terms of path loss. To further quantify on-body path loss, measurements for five different on-body scenarios are presented as well. To compensate for the effect of often large path losses, two mitigation strategies to (dynamically) improve on-body links are introduced and experimentally verified: beam steering using a phased array, and usage of on-body RF repeaters. The results of this study can serve as a tool for WBAN designers to aid in the selection of the right RF frequency and technology for their application.

negative: Neurological Impact of Coronavirus Disease (COVID-19): Practical Considerations for the Neuroscience Community Abstract Background The coronavirus disease of 2019 (COVID-19) that is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been designated a pandemic by the World Health Organization, affecting 2.7 million individuals globally as of April 25, 2020 with over 187,000 deaths. A growing body of evidence supports central nervous system (CNS) involvement. Methods We conducted a review of the literature for articles concerning COVID-19 pathophysiology, neurological manifestations, and neuroscience provider recommendations and guidelines. Results CNS manifestations range from vague non-focal complaints to severe neurologic impairment associated with encephalitis. It is unclear whether neurological dysfunction is due to direct viral injury or systemic disease. The virus may affect brainstem pathways that lead to indirect respiratory dysfunction in addition to direct pulmonary injury. Necessary adaptations in patient management, triage, and diagnosis are evolving in light of ongoing scientific and clinical findings. Conclusions This review consolidates the current body of literature regarding the neurological impact of coronaviruses, discusses the reported neurologic manifestations of COVID-19, and highlights recommendations for patient management. Specific recommendations pertaining to clinical practice for neurologists and neurosurgeons are provided.

negative: SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.

negative: Long-term infection of SARS-CoV-2 changed the body's immune status The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4(+) T cells significantly increased, while total lymphocytes and CD8(+) T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4(+) T cell differentiation.

negative: ELM—the database of eukaryotic linear motifs Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.

negative: Temporal Variation in Physiological Biomarkers in Black Flying-Foxes (Pteropus alecto), Australia Bats of the genus Pteropus (Pteropodidae) are recognised as the natural host of multiple emerging pathogenic viruses of animal and human health significance, including henipaviruses, lyssaviruses and ebolaviruses. Some studies have suggested that physiological and ecological factors may be associated with Hendra virus infection in flying-foxes in Australia; however, it is essential to understand the normal range and seasonal variability of physiological biomarkers before seeking physiological associations with infection status. We aimed to measure a suite of physiological biomarkers in P. alecto over time to identify any seasonal fluctuations and to examine possible associations with life-cycle and environmental stressors. We sampled 839 adult P. alecto in the Australian state of Queensland over a 12-month period. The adjusted population means of every assessed hematologic and biochemical parameter were within the reported reference range on every sampling occasion. However, within this range, we identified significant temporal variation in these parameters, in urinary parameters and body condition, which primarily reflected the normal annual life cycle. We found no evident effect of remarkable physiological demands or nutritional stress, and no indication of clinical disease driving any parameter values outside the normal species reference range. Our findings identify underlying temporal physiological changes at the population level that inform epidemiological studies and assessment of putative physiological risk factors driving Hendra virus infection in P. alecto. More broadly, the findings add to the knowledge of Pteropus populations in terms of their relative resistance and resilience to emerging infectious disease.

negative: The Coronavirus Disease 2019 (COVID-19) Pandemic The present study provides an overview of the coronavirus disease 2019 (COVID-19) outbreak which has rapidly extended globally within a short period. COVID-19 is a highly infectious respiratory disease caused by a new coronavirus known as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2). SARS-CoV-2 is different from usual coronaviruses responsible for mild sickness such as common cold among human beings. It is crucial to understand the impact and outcome of this pandemic. We therefore overview the changes in the curves of COVID-19 confirmed cases and fatality rate in China and outside of China from 31st of December 2019 to 25th of March 2020. We also aimed to assess the temporal developments and death rate of COVID-19 in China and worldwide. More than 414,179 confirmed cases of COVID-19 have been reported in 197 countries, including 81,848 cases in China and 332,331 outside of China. Furthermore, 18,440 infected patients died from COVID-19 infection; 3,287 cases were from China and 15,153 fatalities were reported worldwide. Among the worldwide infected cases, 113,802 patients have been recovered and discharged from different hospitals. Effective prevention and control measures should be taken to control the disease. The presented Chinese model (protocol) of disease prevention and control could be utilized in order to curb the pandemic situation.

negative: Differences in the origin of philosophy between Chinese medicine and western medicine: Exploration of the holistic advantages of Chinese medicine To explore advantages of Chinese medicine (CM) by analyzing differences in the origin of philosophy for human health between CM and Western medicine (WM). Methodologically, a distinctive feature of CM is its systems theory, which is also the difference between CM and WM. Since the birth of CM, it has taken the human body as a whole from the key concepts of “qi, blood, yin-yang, viscera (Zang-Fu), and meridian and channel”, rather than a single cell or a particular organ. WM evolves from the Western philosophic way of thinking and merely uses natural sciences as the foundation. The development of WM is based on human structures, or anatomy, and therefore, research of WM is also based on the way of thinking of decomposing the whole human body into several independent parts, which is the impetus of promoting the development of WM. The core of CM includes the holistic view and the dialectical view. Chinese herbal medicines contain various components and treat a disease from multiple targets and links. Therefore, Chinese herbal medicines treat a diseased state by regulating and mobilizing the whole body rather than just regulating a single factor, since the diseased state is not only a problem in a local part of the body but a local reflection of imbalance of the whole body.

negative: Diagnostic challenges and treatment options of a suspected pericardial metallic projectile foreign body in a dog. OBJECTIVE To describe a case of a suspected pericardial metallic projectile foreign body in a dog with a history of trauma to the left shoulder and to review the literature regarding the management of cardiac and intracardiac foreign bodies. CASE SUMMARY A 3-year-old male, neutered Brittany spaniel presented with a 10-day history of decreased activity and partial anorexia. Serial thoracic radiographs identified a migrating pericardial metallic projectile foreign body and an echocardiogram diagnosed pericardial effusion and abdominal ultrasound identified the presence of ascites. Concern for a possible effusive-constrictive pericarditis prompted a subphrenic pericardectomy performed via thoracoscopy. The foreign body was not recovered. Six months postsurgery, the dog remained asymptomatic. NEW OR UNIQUE INFORMATION PROVIDED Considering the high rate of complications that develop in human patients where the foreign bodies are not removed, veterinarians should be aware of risks associated with long standing pericardial foreign bodies even when no clinical signs are present. Guidelines from the human literature may be considered for investigation of, and treatment options for, cardiac and intracardiac metallic projectile foreign bodies in dogs.

negative: A sensitive and specific antigen detection assay for Middle East respiratory syndrome coronavirus Since its emergence in 2012, more than 900 laboratory-confirmed cases of Middle East respiratory syndrome (MERS) have been reported with a fatality rate of more than 30%. However, no antigen detection assay for commercial use is available for diagnosis. In this study, the full-length nucleocapsid protein (NP) gene of MERS coronavirus (MERS-CoV) was cloned and expressed in Escherichia coli. A MERS-CoV NP capture enzyme-linked immunosorbent assay (ELISA) using two MERS-CoV-NP-specific monoclonal antibodies (MAbs) generated was developed. The ELISA was evaluated using 129 nasopharyngeal aspirates (NPAs) positive for various respiratory viruses and simulated positive NPAs by adding serial dilutions of MERS-CoV. Using a cutoff OD of 0.19, all 129 NPAs positive for respiratory viruses showed very low OD, with a specificity of 100%. For the two simulated MERS-CoV-positive NPAs with serial dilutions of live MERS-CoV, all samples with ≥10 50% tissue culture infective dose (TCID(50))/0.1 mL showed positive results. For the 10 additional NPAs with 20 and 200 TCID(50)/0.1 mL of live MERS-CoV added, all were positive. A highly sensitive and specific MAbs-based antigen capture ELISA has been developed for MERS. This sensitive and specific antigen capture ELISA should be useful for detection of MERS-CoV in human and dromedaries and in field studies.

negative: Ophthalmologic Diseases in Small Pet Mammals

negative: Cross‐species transmission of the newly identified coronavirus 2019‐nCoV The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.

negative: Enteric coronavirus TGEV: partial sequence of the genomic RNA, its organization and expression Abstract The sequence of the 3′-most 8300 nucleotides of the genome RNA of the Purdue-115 strain of the transmissible gastroenteritis virus TGEV, a porcine coronavirus, was determined from cDNA clones. The available sequence corresponds to the part of the genome (total length > 20 kb) expressed through subgenomic mRNAs. The 5 subgenomic and the genomic RNA species detected in TGEV-infected cells form a 3′-coterminal ‘nested’ structure, a unique feature of Coronaviridae. The transcription initiation site of the TGEV subgenomic RNAs appears to involve the hexameric sequence 5′CTAAAC, which is present upstream from each coding region. In addition to the previously identified genes encoding the three structural proteins, E2, E1 and N, two regions, X1 and X2, corresponding to the non-overlapping portion of mRNAs 4 and 3, may code for so far unidentified non-structural polypeptides. The predicted X1 polypeptide (9.2 kDa) is highly hydrophobic. The sequence of the X2 region allows the translation of two non-ovelapping products, i.e., X2a (7.7 kDa).and x2b (18.8 kDa). No RNA species liable to express the extreme 3′ open reading frame X3 was found.

negative: A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

negative: Disparate temperature-dependent virus – host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium The human conductive respiratory tract spans a long anatomical distance and represents an important barrier to constrain invading respiratory pathogens. The disparate ambient temperatures found in the upper and lower respiratory tract have been demonstrated to influence the replication kinetics of common cold viruses as well as the associated host responses. Here, we employed the human airway epithelial cell (hAEC) culture model to investigate the impact of ambient temperatures found in the upper and lower respiratory tract, 33°C and 37°C, respectively, on the viral replication kinetics and host innate immune response dynamics during SARS-CoV-2 and SARS-CoV infections. Strikingly, SARS-CoV-2, in contrast to SARS-CoV, replicated more efficiently at temperatures encountered in the upper respiratory tract, and displayed higher sensitivity to type I and type III IFNs than SARS-CoV. Time-resolved transcriptome analysis highlighted a temperature-dependent induction of IFN-mediated antiviral response, whose amplitude inversely correlated with the replication kinetic efficiencies of both SARS-CoV-2 and SARS-CoV at temperatures found in the upper and lower respiratory tract. Altogether, these data reflect clinical features of SARS-CoV-2 and SARS-CoV and subsequently, their associated human-to-human transmission efficiencies. They provide crucial insights of the profound impact of ambient temperatures on viral replication and associated pivotal virus - host interaction dynamics. This knowledge can be exploited for the development of novel intervention strategies against SARS-CoV-2.

negative: Clinical significance of IgM and IgG test for diagnosis of highly suspected COVID-19 infection Quick, simple and accurate diagnosis of suspected COVID-19 is very important for the screening and therapy of patients. Although several methods were performed in clinical practice, however, the IgM and IgG diagnostic value evaluation was little performed. 57 suspected COVID-19 infection patients were enrolled in our study. 24 patients with positive and 33 patients with negative nucleic acid test. The positive rate of COVID-19 nucleic acid was 42.10%. The positive detection rate of combination of IgM and IgG for patients with COVID-19 negative and positive nucleic acid test was 72.73% and 87.50%. The results were significantly higher than the nucleic acid or IgM, IgG single detection. hsCRP in the COVID-19 nucleic acid negative group showed significantly higher than the positive groups (P=0.0298). AST in the COVID-19 IgM negative group showed significantly lower than the positive groups (P=0.0365). We suggest a quick, simple, accurate aided detection method for the suspected patients and on-site screening in close contact with the population.

negative: Teicoplanin potently blocks the cell entry of 2019-nCoV Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection.

negative: Q&A: The novel coronavirus outbreak causing COVID-19

negative: The infection evidence of SARS-COV-2 in ocular surface： a single-center cross-sectional study Purpose: The aim of this study was to identify whether SARS-COV-2 infected in ocular surface. Methods: Cross-sectional study of patients presenting for who received a COVID-19 diagnosis, from December 30, 2019 to February 7, 2020, at Tongji hospital, Tongji medical college, Huazhong University of Science and Technology. Demographics, temperature was recorded, blood routine test (Rt), chest Computed Tomography (CT) were took intermittently, and SARS-COV-2 real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay were arranged for the nasopharyngeal and conjunctival swab samples. Results: A total of 102 patients (48 Male [50%] and 54 Female [50%]) with clinical symptoms, Rt, and chest Computed Tomography (CT) abnormalities were identified with a clinical diagnosis of COVID-19. Patients had a mean [SD] gestational age of 57.63 [14.90] years. Of a total of 102 patients identified, 72 patients (36 men [50%] and 36 women [50%]; mean [SD] age, 58.68 [14.81] years) confirmed by laboratory diagnosis with SARS-COV-2 RT-PCR assay. Only two patients (2.78%) with conjunctivitis was identified from 72 patients with a laboratory confirmed COVID-19. However, SARS-COV-2 RNA fragments was found in ocular discharges by SARS-COV-2 RT-PCR only in one patient with conjunctivitis. Conclusions: Although we suspect the incidence of SARS-COV-2 infection through the ocular surface is extremely low, the nosocomial infection of SARS-CoV-2 through the eyes after occupational exposure is a potential route. The inefficient diagnostic method and the sampling time lag may contribute to the lower positive rate of conjunctival swab samples of SARS-COV-2. Therefore, to lower the SARS-COV-2 nosocomial infection, the protective goggles should be wore in all the health care workers.

negative: Understanding the impact of the COVID-19 pandemic on well-being and virtual care for people living with dementia and care partners living in the community The COVID-19 pandemic has necessitated public health measures that have impacted the provision of care for people living with dementia and their families. Additionally, the isolation that results from social distancing may be harming well-being for families, as formal and informal supports become less accessible. For those with living with dementia and experiencing agitation, social distancing may be even harder to maintain, or social distancing could potentially aggravate dementia-related neuropsychiatric symptoms. To understand the lived experience of social and physical distancing during the COVID-19 pandemic in Canada we remotely interviewed 21 participants who normally attend a dementia specialty clinic in Calgary, Alberta, during a period where essential businesses were closed and healthcare had abruptly transitioned to telemedicine. The impacts of the public health measures in response to the pandemic emerged in three main categories of experience: 1) personal; 2) health services; and 3) health status (of both person living with dementia and care partner). This in-depth understanding of the needs and experiences of the pandemic for people living with dementia suggests that innovative means are urgently needed to facilitate provision of remote medicine and also social interaction and integration.

negative: What Dentists Need to Know about COVID-19 Abstract This article aims at collecting all information needed for dentists regarding the COVID-19 pandemic throughout the world by reviewing articles published by now. In late 2019, a pneumonia outbreak of uncertain etiology happened in Wuhan, China. There were many reports related to a live-animal and seafood market, supporting that the pathogens were transferred from animals to humans, rapidly evolving into transmission from human to human. The pathogen was classified as 2019 Novel Corona Virus (2019-nCoV), and the disease was named COrona VIrus Disease 2019 (COVID-19). Given that COVID-19 has lately been detected in infected patients’ saliva, the COVID-19 outbreak is an alert that all dental and other health professionals must be vigilant in defending against the infectious disease spread, and it may enable to assess whether non-invasive saliva diagnostic for COVID-19. There has so far been no evidence from randomized controlled trials to prescribe any particular anti-nCoV treatment or vaccine, and COVID-19 management has been widely supportive. Since the ACE-2 was expressing on oral cavity mucosa, there is a potentially huge COVID-19 infectious vulnerability risk for oral cavity and brought up a proof for the future prevention procedure in dental practice and daily life. As a result, the whole dental teams should be vigilant and keep patients and themselves in a safe environment by following the guideline in this study.

negative: Duration of viral detection in throat and rectum of a patient with COVID-19 The rapid spread of coronavirus disease 2019 (COVID-19) raises concern about a global pandemic. Knowledge about the duration of viral shedding remains important for patient management and infection control. We report the duration of viral detection in throat and rectum of a COVID-19 patient treated at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Despite clinical recovery, SARS-CoV-2 RNA remained detectable by real time RT-PCR in throat and rectal swabs until day 11 and 18 of hospitalization, respectively. Because live SARS-CoV-2 has been successfully isolated from a stool sample from a COVID-19 patient in China, the results demonstrate that COVID-19 patients may remain infectious for long periods, and fecal-oral transmission may be possible. Therefore, our finding has important implications for infection control.

negative: Beneficial effects of Houttuynia cordata polysaccharides on “two-hit” acute lung injury and endotoxic fever in rats associated with anti-complementary activities Houttuynia cordata Thunb. is a traditional herb used for clearing heat and eliminating toxins, and has also been used for the treatment of severe acute respiratory syndrome (SARS). In vitro, the crude H. cordata polysaccharides (CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury (ALI) induced by hemorrhagic shock plus lipopolysaccharide (LPS) instillation (two-hit) and LPS-induced fever in rats. CHCP significantly attenuated pulmonary injury in the “two-hit” ALI model by reducing pulmonary edema and protein exudation in bronchoalveolar lavage fluid (BALF). In addition, it reduced the deposit of complement activation products in the lung and improved oxidant-antioxidant imbalance. Moreover, CHCP administration inhibited fever in rats, reduced the number of leukocytes and restored serum complement levels. The inhibition on the inappropriate activation of complement system by CHCP may play an important role in its beneficial effects on inflammatory diseases. The anti-complementary polysaccharides are likely to be among the key substances for the heat-clearing function of H. cordata.

negative: Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge Abstract Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1–5 μm) suitable for inhalation. The physical and biological characteristics of both WIV and Advax remained unaltered both by admixing WIV with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization, both liquid and dry powder formulations containing Advax induced significantly higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led to robust memory B cell responses along with an increase of lung localization factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect of Advax was seen on memory T cell responses. In contrast to animals immunized with WIV alone, all animals pulmonary immunized with a single dose of Advax-adjuvanted WIV were fully protected with no visible clinical symptoms against a lethal dose of influenza virus. These data confirm that Advax is a potent mucosal adjuvant that boosts vaccine-induced humoral and cellular immune responses both in the lung and systemically with major positive effects on B-cell memory and complete protection against live virus. Hence, respiratory tract immunization, particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or dry powder is a promising alternative to parenteral influenza vaccination.

negative: Embryo vaccination of chickens using a novel adjuvant formulation stimulates protective immunity against Eimeria maxima infection Abstract Our previous study demonstrated that chickens immunized subcutaneously with an Eimeria recombinant profilin protein vaccine emulsified in a Quil A/cholesterol/DDA/Carbopol (QCDC) adjuvant developed partial protection against experimental avian coccidiosis compared with animals immunized with profilin alone. Because in ovo vaccination is presently used in commercial applications worldwide throughout the poultry industry, the current study was undertaken to investigate chicken embryo vaccination with profilin plus QCDC adjuvant. Eighteen day-old embryos were immunized with isotonic saline (control), profilin alone, QCDC alone, or profilin plus QCDC, and orally challenged with live Eimeria maxima at 7 days post-hatch. Body weight gain, fecal oocyst output, and intestinal cytokine transcript levels were assessed as measures of protective immunity. While immunization with profilin alone or QCDC alone did not alter body weight gain of infected chickens compared with the saline control group, vaccination with profilin plus QCDC increased body weight gain such that it was equal to the uninfected controls. Immunization with profilin plus QCDC also reduced fecal oocyst shedding compared with unimmunized controls, although in this case QCDC failed to provide an adjuvant effect since no difference was observed between the profilin-only and profilin/QCDC groups. Finally, increased levels of transcripts encoding IL-1β, IL-15, and IFN-γ were seen in the intestinal tissues of animals given profilin plus QCDC compared with the profilin-only or QCDC-only groups. In summary, this study demonstrates an adjuvant effect of QCDC on body weight gain and intestinal cytokine responses following in ovo vaccination of chickens with an Eimeria profilin vaccine.

negative: Correlating glycoforms of DC-SIGN with stability using a combination of enzymatic digestion and ion mobility MS The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection. How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported. Here, we develop and apply a mass spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN. We first quantify the Core 1 & 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein via sequential exoglycosidase sequencing. We then use ion mobility mass spectrometry to show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the glycoprotein isoforms of DC-SIGN. We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites. Collectively, our results exemplify a combined multi-dimensional MS approach, proficient in evaluating protein stability in response to both glycoprotein macro- and micro-heterogeneity and adding structural detail to the infection enhancer DC-SIGN.

negative: An Experimental Model for Dilated Cardiomyopathy after Rabbit Coronavirus Infection A rabbit model for coronavirus-induced dilated cardiomyopathy is described. Acute rabbit coronavirus infection results in virus-induced myocarditis and congestive heart failure. Of the survivors of rabbit coronavirus infection, 41% had increased heart weight and heart weight-to-body weight ratios, biventricular dilation, myocyte hypertrophy, myocardial fibrosis, and myocarditis consistent with the development of dilated cardiomyopathy. These changes were also seen in the remaining 59% of the survivors, except that the degree of myocyte hypertrophy was reduced and only right ventricular dilation was present. In most survivors, myocarditis was usually mild (1–5 foci/transverse section), but in some cases it was severe (>20 foci/transverse section). Interstitial and replacement fibrosis was more pronounced in the papillary muscles. These data suggest that rabbit coronavirus infection may progress to dilated cardiomyopathy.

negative: Mobility Mobility and movement are of concern to academics working across the social sciences, and this article provides a critical evaluation of current geographical research on mobility. Mobilities are fundamental to our daily lives and to the functioning of societies and economies, and the article begins by examining how geographers have approached mobility and fixity during the past half century and why there appears to have been a resurgence of research on mobility in the past decade. Mobilities are entwined with complex power relationships and the article examines how governments and businesses have attempted to encourage and facilitate the movements of people and things, while controlling and regulating mobilities which are deemed to be threatening, out of place, and uncontrolled – such as the mobility of gypsies and illegal immigrants. The article examines how mobilities have frequently been pushed into the background in accounts of landscape and place, before showing how geographers have more recently begun to take account of movement, change, and dynamism in conceptualizing place and landscape. The final section examines how human geographers and social scientists have been paying increasing attention to the social and cultural dimensions of travel and transport, and focuses on recent work on the geographies of the car and driving.

negative: An efficient virus aerosol sampler enabled by adiabatic expansion Abstract Protection of public health against pathogenic viruses transmitted through the airborne route requires effective sampling of airborne viruses for determination of their concentration and distribution. However, sampling viable airborne viruses is challenging as conventional bioaerosol sampling devices operate on inertia-based mechanisms that inherently have low sampling efficiency for virus aerosols in the ultrafine size range (< 100nm). Herein, a Batch Adiabatic-expansion for Size Intensification by Condensation (BASIC) approach was developed for efficient sampling of virus aerosols. The BASIC utilizes adiabatic expansion in a supersaturated container to activate condensation of water vapor onto virus aerosol particles, thus amplifying the size of the particles by orders of magnitude. Using aerosolized MS2 bacteriophage, the BASIC's performance was evaluated and optimized both from the perspectives of physical size amplification as well as preservation of the viability of the MS2 bacteriophage. Experimental results show that one compression/expansion (C/E) cycle under a compression pressure of 103.5kPa and water temperature of 25°C was sufficient to increase the particle diameter from < 100nm to > 1µm; further increases in the number of C/E cycles neither increased particle number concentration nor diameter. An increase in compression pressure was associated with physical size amplification and a higher concentration of collected viable MS2. Water temperature of 40°C was found to be the optimal for size amplification as well as viability preservation. No significant effect on particle size enlargement was observed by changing the dwell time after expansion. The results illustrate the BASIC's capability as a simple, quick and inexpensive tool for rapid sampling of viable airborne viruses.

negative: Estimating the number of undetected COVID-19 cases exported internationally from all of China During the early phase of the COVID-19 pandemic, when SARS-CoV-2 was chiefly reported in the city of Wuhan, cases exported to other locations were largely predicted using flight travel data from Wuhan. However, given Wuhan’s connectivity to other cities in mainland China prior to the lockdown, there has likely been a substantial risk of exportation of cases from other Chinese cities. It is likely that many of these exportations remained undetected because early international case definitions for COVID-19 required a recent travel history from Wuhan. Here, we combine estimates of prevalence in 18 Chinese cities with estimates of flight volume, accounting for the effects of travel bans and the timing of Lunar New Year, to approximate the number of cases exported from cities outside of Wuhan from early December 2019 to late February 2020. We predict that for every one case from Wuhan exported internationally, there were approximately 2.9 cases from large Chinese cities exported internationally that likely remained undetected. Additionally, we predict the number of exported cases in six destinations for which predictions on exported cases have yet to be made, surveillance has likely been low, and where health care systems will likely face issues in managing current or potential outbreaks. We observe heterogeneities in exported case counts across these destinations. The predicted number of cases exported to Egypt and South Africa exceeds the predicted number of cases exported to Mauritania. These trends may anticipate differences in the timing and emergence of local transmission in these countries. Our findings highlight the importance of setting accurate travel history requirements for case definition guidelines in the initial phase of an epidemic, and actively updating these guidelines as the epidemic advances.

negative: Editorial: EAERE, ERE and the Research Challenges of the Coronavirus Pandemic

negative: Transmission and evolutionary dynamics of human coronavirus OC43 strains in coastal Kenya investigated by partial spike sequence analysis, 2015–16 Human coronavirus OC43 (HCoV-OC43) is a major contributor to seasonal outbreaks of acute respiratory illness (ARI). The origins of locally circulating HCoV-OC43 strains and characteristics of their genetic diversity are unknown for most settings despite significance to effective HCoV control strategies. Between December 2015 and June 2016, we undertook ARI surveillance in coastal Kenya in nine outpatients and one inpatient health facility (HF). Ninety-two patient samples tested HCoV-OC43 positive and forty (43.5%) were successfully sequenced in spike (S) gene region (2,864 long, ∼70%). Phylogenetic analysis confirmed co-circulation of two distinct HCoV-OC43 clades that closely clustered with genotype G (n = 34, 85%) and genotype H (n = 6, 15%) reference strains. Local viruses within the same clade displayed low genetic diversity yielding identical sequences in multiple HF. Furthermore, the newly sequenced Kenyan viruses showed close phylogenetic relationship to other contemporaneous sampled strains (2015–16) including those originating from distant places (e.g. USA and China). Using a genetic similarity threshold of 99.1 per cent at nucleotide level, the HCoV-OC43 strains sampled globally between 1967 and 2019 fell into nine sequence clusters. Notably, some of these clusters appeared to have become extinct, or occurred only sporadically in a few geographical areas while others persisted globally for multiple years. In conclusion, we found that HCoV-OC43 strains spread rapidly both locally and across the globe with limited genetic evolution in the spike gene. Full-genome sequences that are spatio-temporally representative are required to advance understanding of the transmission pathways of this important human respiratory pathogen.

negative: Virus strain specificity of challenge immunity to coronavirus The resistance of immunized mice to challenge with the same or a different strain of mouse hepatitis virus (MHV) was examined as a model of challenge immunity to coronavirus infection. Genetically susceptible BALB/cByJ mice were given an intranasal immunizing infection of respiratory-type MHV-JHM, MHV-S, or enterotropic MHV-Y. Control mice were sham-immunized with sterile tissue culture fluid. Recovered mice were challenged intranasally with MHV-JHM, MHV-S or sterile tissue culture fluid at 30 days after immunization. Resistance to challenge inoculation was evaluated in groups of mice at 4 and 30 days after challenge. At 4 days, the prevalence of MHV lesions in nose and liver was tabulated and MHV titers in liver were determined. At 30 days, the prevalence of residual brainstem spongiform lesions was tabulated and serum antibody to MHV-JHM and MVH-S was quantified by enzyme immunoassay. Mice immunized with MHV-JHM or MHV-S resisted challenge with the MHV homotype, but MHV-S-immunized mice were fully susceptible to challenge with MVH-JHM. Mice immunized with enterotropic MHV-Y were only partially protected against challenge with antigenically related, but biologically different MHV-S. Serum antibody responses to MHV supported these observations. These data indicate that challenge immunity to coronaviruses is strong, but highly virus strain-specific.

negative: Modelling of evaporation of cough droplets in inhomogeneous humidity fields using the multi-component Eulerian-Lagrangian approach Abstract This study employed a multi-component Eulerian-Lagrangian approach to model the evaporation and dispersion of cough droplets in quiescent air. The approach is featured with a continuity equation being explicitly solved for water vapor, which allows comprehensively considering the effects of inhomogeneous humidity field on droplets evaporation and movement. The computational fluid dynamics (CFD) computations based on the approach achieved a satisfactory agreement with the theoretical models reported in the literature. The results demonstrated that the evaporation-generated vapor and super-saturated wet air exhaled from the respiratory tracks forms a “vapor plume” in front of the respiratory track opening, which, despite the short life time, significantly impedes the evaporation of the droplets captured in it. The study also revealed that due to the droplet size reduction induced by evaporation, both the number density of airborne droplets and mass concentration of inhalable pathogens remarkably increased, which can result in a higher risk of infection. Parametric studies were finally conducted to evaluate the factors affecting droplet evaporation. Summary The study demonstrated the importance of considering inhomogeneous humidity field when modelling the evaporation and dispersion of cough droplets. The multi-component Eulerian-Lagrangian model presented in this study provides a comprehensive approach to address different influential factors in a wide parametric range, which will enhance the assessment of the health risks associated with droplet exposure.

negative: Detection of alpha- and betacoronaviruses in rodents from Yunnan, China BACKGROUND: Rodents represent the most diverse mammals on the planet and are important reservoirs of human pathogens. Coronaviruses infect various animals, but to date, relatively few coronaviruses have been identified in rodents worldwide. The evolution and ecology of coronaviruses in rodent have not been fully investigated. RESULTS: In this study, we collected 177 intestinal samples from thress species of rodents in Jianchuan County, Yunnan Province, China. Alphacoronavirus and betacoronavirus were detected in 23 rodent samples from three species, namely Apodemus chevrieri (21/98), Eothenomys fidelis (1/62), and Apodemus ilex (1/17). We further characterized the full-length genome of an alphacoronavirus from the A. chevrieri rat and named it as AcCoV-JC34. The AcCoV-JC34 genome was 27,649 nucleotides long and showed a structure similar to the HKU2 bat coronavirus. Comparing the normal transcription regulatory sequence (TRS), 3 variant TRS sequences upstream the spike (S), ORF3, and ORF8 genes were found in the genome of AcCoV-JC34. In the conserved replicase domains, AcCoV-JC34 was most closely related to Rattus norvegicus coronavirus LNRV but diverged from other alphacoronaviruses, indicating that AcCoV-JC34 and LNRV may represent a novel alphacoronavirus species. However, the S and nucleocapsid proteins showed low similarity to those of LRNV, with 66.5 and 77.4% identities, respectively. Phylogenetic analysis revealed that the S genes of AcCoV-JC34, LRNV, and HKU2 formed a distinct lineage with all known coronaviruses. CONCLUSIONS: Both alphacoronaviruses and betacoronaviruses were detected in Apodemus chevrieri in the Yunnan Province of China, indicating that Apodemus chevrieri is an important host for coronavirus. Several new features were identified in the genome of an Apodemus chevrieri coronavirus. The phylogenetic distance to other coronaviruses suggests a variable origin and evolutionary route of the S genes of AcCoV-JC34, LRNV, and HKU2. These results indicate that the diversity of rodent coronaviruses is much higher than previously expected. Further surveillance and functional studies of these coronaviruses will help to better understand the importance of rodent as host for coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0766-9) contains supplementary material, which is available to authorized users.

negative: In silico Design of novel Multi-epitope recombinant Vaccine based on Coronavirus surface glycoprotein It is of special significance to find a safe and effective vaccine against coronavirus disease 2019 (COVID-19) that can induce T cell and B cell -mediated immune responses. There is currently no vaccine to prevent COVID-19. In this project, a novel multi-epitope vaccine for COVID-19 virus based on surface glycoprotein was designed through application of bioinformatics methods. At the first, seventeen potent linear B-cell and T-cell binding epitopes from surface glycoprotein were predicted in silico, then the epitopes were joined together via different linkers. The ability of the selected epitopes to induce interferon-gamma was evaluate using IFNepitope web server. One final vaccine was constructed which composed of 398 amino acids and attached to 50S ribosomal protein L7/L12 as adjuvant. Physicochemical properties, as well as antigenicity in the proposed vaccines, were checked for defining the vaccine stability and its ability to induce cell-mediated immune responses. Three-dimensional structure of the mentioned vaccine was subjected to the molecular docking studies with MHC-I and MHC-II molecules. The results proposed that the multi-epitope vaccine with 50S ribosomal protein L7/L12 was a stable construct with high aliphatic content and high antigenicity.

negative: A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19 The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates against a specific coronavirus. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 is able to suppress the CpG-induced IL-6 production in peripheral blood mononuclear cells, suggesting that it may also have anti-inflammatory effect that is highly relevant to the prevention immunopathology induced by SARS-CoV-2 infection. Further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed a high concentration of CVL218 in lung and observed no apparent signs of toxicity, indicating the appealing potential of this drug for the treatment of the pneumonia caused by SARS-CoV-2 infection. Moreover, molecular docking simulation suggested that CVL218 may bind to the N-terminal domain of nucleocapsid (N) protein of SARS-CoV-2, providing a possible model to explain its antiviral action. We also proposed several possible mechanisms to explain the antiviral activities of PARP1 inhibitors against SARS-CoV-2, based on the data present in this study and previous evidences reported in the literature. In summary, the PARP1 inhibitor CVL218 discovered by our data-driven drug repositioning framework can serve as a potential therapeutic agent for the treatment of COVID-19.

negative: Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19 In 2015, the Middle East respiratory syndrome coronavirus (MERS-CoV) reached the Republic of Korea, resulting from nosocomial transmission, and was the largest epidemic outside of the Arabian Peninsula. To date, despite various strategies to identify CoV interventions, there are only limited therapeutic options available. To address these unmet medical needs, we used a South Korean MERS-CoV clinical isolate and screened 5,406 compounds, including US Food and Drug Administration (FDA)-approved drugs and bioactive molecules, confirmed 221 hits by dose-response curve analysis in the primary assay, and selected 54 hits with a therapeutic index (TI) greater than 6. Time-of-addition studies with 12 FDA-approved drugs demonstrated that eight and four therapeutics act on the early- and late stages of the viral life cycle, respectively. Among the early acting drugs, three therapeutics with a TI greater than 100 were cardiotonic agents. Together, our results identify potential therapeutic options for treatment of MERS-CoV infections and could provide a basis for a wider range of coronaviruses, including the currently emerging coronavirus disease 2019 (COVID-19) outbreak.

negative: Genome structure and transcriptional regulation of human coronavirus NL63 BACKGROUND: Two human coronaviruses are known since the 1960s: HCoV-229E and HCoV-OC43. SARS-CoV was discovered in the early spring of 2003, followed by the identification of HCoV-NL63, the fourth member of the coronaviridae family that infects humans. In this study, we describe the genome structure and the transcription strategy of HCoV-NL63 by experimental analysis of the viral subgenomic mRNAs. RESULTS: The genome of HCoV-NL63 has the following gene order: 1a-1b-S-ORF3-E-M-N. The GC content of the HCoV-NL63 genome is extremely low (34%) compared to other coronaviruses, and we therefore performed additional analysis of the nucleotide composition. Overall, the RNA genome is very low in C and high in U, and this is also reflected in the codon usage. Inspection of the nucleotide composition along the genome indicates that the C-count increases significantly in the last one-third of the genome at the expense of U and G. We document the production of subgenomic (sg) mRNAs coding for the S, ORF3, E, M and N proteins. We did not detect any additional sg mRNA. Furthermore, we sequenced the 5' end of all sg mRNAs, confirming the presence of an identical leader sequence in each sg mRNA. Northern blot analysis indicated that the expression level among the sg mRNAs differs significantly, with the sg mRNA encoding nucleocapsid (N) being the most abundant. CONCLUSIONS: The presented data give insight into the viral evolution and mutational patterns in coronaviral genome. Furthermore our data show that HCoV-NL63 employs the discontinuous replication strategy with generation of subgenomic mRNAs during the (-) strand synthesis. Because HCoV-NL63 has a low pathogenicity and is able to grow easily in cell culture, this virus can be a powerful tool to study SARS coronavirus pathogenesis.

negative: Clinical characteristics of 25 death cases infected with COVID-19 pneumonia: a retrospective review of medical records in a single medical center, Wuhan, China Summary Background The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2) is a highly infectious disease, which was occurred in Wuhan, Hubei Province, China in December 2019. As of February 13, 2020, a total of 59883 cases of COVID-19 in China have been confirmed and 1368 patients have died from the disease. However, the clinical characteristics of the dyed patients were still not clearly clarified. This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiologic assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Findings The mean age of the dead was 71.48 years, the average course of the disease was 10.56 days, all patients eventually died of respiratory failure. All of those who died had underlying diseases, the most common of which was hypertension (16/25, 64%), followed by diabetes (10/25, 40%), heart diseases (8/25, 32%), kidney diseases (5/25, 20%), cerebral infarction (4/25, 16%), chronic obstructive pulmonary disease (COPD, 2/25, 8%), malignant tumors (2/25, 8%) and acute pancreatitis (1/25, 4%). The most common organ damage outside the lungs was the heart, followed by kidney and liver. In the patients' last examination before death, white blood cell and neutrophil counts were elevated in 17 patients (17/25, 68%) and 18 patients (18/25, 72%), lymphocyte counts were decreased in 22 patients (22/25, 88%). Most patients' PCT, CRP and SAA levels were elevated, the percentages were 90.5% (19/21), 85% (19/20) and 100% (21/21) respectively. The levels of the last test of neutrophils (15/16, 93.8%), PCT (11/11, 100%), CRP (11/13, 84.6%), cTnI (8/9, 88.9%), D-Dimer (11/12, 91.6%) and LDH (9/9, 100%) were increased as compared to the first test, while the levels of lymphocytes were decreased (14/16, 87.5%). Interpretation The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-Dimer and LDH levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts.

negative: Coronaviruses pandemics: Can neutralizing antibodies help? For the first time in Homo sapiens history, possibly, most of human activities is stopped by coronavirus disease 2019 (COVID-19). Nearly eight billion people of this world are facing a great challenge, maybe not “to be or not to be” yet, but unpredictable. What happens to other major pandemics in the past, and how human beings went through these hurdles? The human body is equipped with the immune system that can recognize, respond and fight against pathogens such as viruses. Following the innate response, immune system processes the adaptive response by which each pathogen is encoded and recorded in memory system. The humoral reaction containing cytokines and antibodies is expected to activate when the pathogens come back. Exploiting this nature of body protection, neutralizing antibodies have been investigated. Learning from past, in parallel to SARS-CoV-2, other coronaviruses SARS-CoV and MERS-CoV who caused previous pandemics, are recalled in this review. We here propose insights of origin and characteristics and perspective for the future of antibodies development.

negative: To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17–45% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34–58%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24–65% (and peak deaths 15–69%), compared to 2–9% mortality reduction in New York (peak death reduction 9–18%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.

negative: Coronavirus Disease: A Review of a New Threat to Public Health In December 2019, several patients from Wuhan, China were admitted to hospitals with symptoms of pneumonia. As the number of patients presenting with similar symptoms started to rise, the causative agent was eventually isolated from samples. It was initially called the 2019 novel coronavirus (2019-nCoV) and has been recently relabelled as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); the disease it causes has been named coronavirus disease 2019 (COVID-19). Over the next few weeks, the virus spread from Wuhan to affect different provinces in China and, after a few months, it is now present in 109 countries. As of March 10, 2020, there have been 113,702 confirmed cases globally, and 4,012 deaths have been registered. The World Health Organization (WHO) called COVID-19 a pandemic on March 11, 2020. There are multiple drug trials going on with some positive results. However, since no vaccine is available, the best way to combat the virus is by preventive methods.

negative: Viral replicase gene products suffice for coronavirus discontinuous transcription. We have used vaccinia virus as a vector to clone a 22.5-kbp cDNA that represents the 5' and 3' ends of the human coronavirus 229E (HCoV 229E) genome, the HCoV 229E replicase gene, and a single reporter gene (coding for green fluorescent protein [GFP]) located downstream of a regulatory element for coronavirus mRNA transcription. When RNA transcribed from this cDNA was transfected into BHK-21 cells, a small percentage of cells displayed strong fluorescence. A region of the mRNA encoding GFP was amplified by PCR and shown to have the unique mRNA leader-body junction indicative of coronavirus-mediated transcription. These data show that the coronavirus replicase gene products suffice for discontinuous subgenomic mRNA transcription.

negative: Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff BACKGROUND: In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES: To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA: We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS: Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants) coveralls were more difficult to doff than isolation gowns (very low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). According to three studies that tested more recently introduced full-body PPE ensembles, there may be no difference in contamination. Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS: We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.

negative: E-Quarantine: A Smart Health System for Monitoring Coronavirus Patients for Remotely Quarantine Coronavirus becomes officially a global pandemic due to the speed spreading off in various countries. An increasing number of infected with this disease causes the Inability problem to fully care in hospitals and afflict many doctors and nurses inside the hospitals. This paper proposes a smart health system that monitors the patients holding the Coronavirus remotely. Due to protect the lives of the health services members (like physicians and nurses) from infection. This smart system observes the people with this disease based on putting many sensors to record many features of their patients in every second. These parameters include measuring the patient's temperature, respiratory rate, pulse rate, blood pressure, and time. The proposed system saves lives and improves making decisions in dangerous cases. It proposes using artificial intelligence and Internet-of-things to make remotely quarantine and develop decisions in various situations. It provides monitoring patients remotely and guarantees giving patients medicines and getting complete health care without anyone getting sick with this disease. It targets two people's slides the most serious medical conditions and infection and the lowest serious medical conditions in their houses. Observing in hospitals for the most serious medical cases that cause infection in thousands of healthcare members so there is a big need to uses it. Other less serious patients slide, this system enables physicians to monitor patients and get the healthcare from patient's houses to save places for the critical cases in hospitals.

negative: One-health approach as counter-measure against “autoimmune” responses in biosecurity Abstract This Swine flu pandemic of 2009 and the potential Avian flu threat of 2011–2012 have revived a most challenging debate on protection against infectious diseases. The response to the Swine flu pandemic has been ambivalent, both on the societal (political) and the scientific level. While some scientists warned against potential massive loss of human lives and urged for immediate and large-scale vaccination, others accused them of unnecessary scaremongering, arguing that the pandemic would not be that severe. The lab-created virulent Avian flu virus – which has been created in order to ‘fight’ a potential Avian flu pandemic – sparked a fierce debate on the dual-use risks of such a pre-emptive strategy. This article involves an analysis of the medical-political response to these recent viral threats using Peter Sloterdijk's immunological framework as diagnostic tool. In his trilogy Spheres Sloterdijk uses immunological concepts to analyse and assess the contemporary biopolitical situation. It shows how drawing a parallel between the functioning of the biological immune system and “immune responses” on socio-political level enables to assess and reconceptualise biosecurity. It demonstrates that ideas such as “nature is the biggest terrorist” – as advanced by many virologists – sometimes result in exaggerated “immunisation responses”. This strong defensive attitude sometimes brings about collateral damage. In other words, fierce biosecurity measures sometimes risk developing into “autoimmune” responses that actually destruct the body politic they are meant to protect. By drawing on recent insights in the functioning of the biological immune system it is shown how a One-Health approach that incorporates a broader and nuanced “immunological” repertoire could act as counter-measure against “autoimmune” responses in biosecurity.

negative: Stability of RNA sequences derived from the coronavirus genome in human cells Abstract Most viruses inhibit the innate immune system and/or the RNA degradation processes of host cells to construct an advantageous intracellular environment for their survival. Characteristic RNA sequences within RNA virus genomes or RNAs transcribed from DNA virus genomes contribute toward this inhibition. In this study, we developed a method called “Fate-seq” to comprehensively identify the RNA sequences derived from RNA and DNA viruses, contributing RNA stability in the cells. We examined the stabilization activity of 5,924 RNA fragments derived from 26 different viruses (16 RNA viruses and 10 DNA viruses) using next-generation sequencing of these RNAs fused 3′ downstream of GFP reporter RNA. With the Fate-seq approach, we detected multiple virus-derived RNA sequences that stabilized GFP reporter RNA, including sequences derived from severe acute respiratory syndrome-related coronavirus (SARS-CoV). Comparative genomic analysis revealed that these RNA sequences and their predicted secondary structures are highly conserved between SARS-CoV and the novel coronavirus, SARS-CoV-2, which is responsible for the global outbreak of the coronavirus-associated disease that emerged in December 2019 (COVID-19). These sequences have the potential to enhance the stability of viral RNA genomes, thereby augmenting viral replication efficiency and virulence.

negative: Civet Cats, Fried Grasshoppers, and David Beckham's Pajamas: Unruly Bodies after SARS This article discusses the viscerality of consumption; in particular, consumption‐as‐eating and consumption‐as‐spending as a set of heterogeneous, contestatory discourses and practices of identity production and subject formation. To do so, I bring together two intersecting events: the Chinese government's ban on wild animal markets during the Severe Acute Respiratory Syndrome (SARS) outbreak, and Chinese and European media frenzy over the visit to China by the Spanish football club Real Madrid in the wake of the epidemic. In discussing these events, I pay specific attention to unruly bodies—both human and nonhuman—as consumables and those who consume them. In examining translocal encounters of these unruly bodies, I suggest that, in post‐SARS China, discourses and practices of consumption produce emergent socialities that at once refigure racialized Orientalist tropes and conjure up discrepant neoliberal imaginaries of lifestyle and consumer choice.

negative: Body Recovery Abstract Appropriate precautions are critical to minimize damage to the body during recovery and removal from a scene and transit to the mortuary to allow for accurate interpretation of injury and the minimization of contamination. Many elements of the investigation may be affected by the way in which tasks are conducted. Members of numerous jurisdictions must all work together to ensure the best outcome both from a forensic point of view and also in preserving and respecting the dignity of the deceased. This chapter will outline the techniques necessary for preserving the body and associated evidence during transport, including specific considerations for different types of cases.

negative: Recombinant Turkey Coronavirus Nucleocapsid Protein Expressed in Escherichia coli Expression and purification of turkey coronavirus (TCoV) nucleocapsid (N) protein from a prokaryotic expression system as histidine-tagged fusion protein are presented in this chapter. Expression of histidine-tagged fusion N protein with a molecular mass of 57 kDa is induced with isopropyl β-d-1-thiogalactopyranoside (IPTG). The expressed N protein inclusion body is extracted and purified by chromatography on nickel-agarose column to near homogeneity. The protein recovery can be 10 mg from 100 ml of bacterial culture. The purified N protein is a superior source of TCoV antigen for antibody-capture ELISA for detection of antibodies to TCoV.

negative: What are the risks of COVID-19 infection in pregnant women?

negative: [Epidemic trend of corona virus disease 2019 (COVID-19) in mainland China] Objective: In order to master the epidemic trend of corona virus disease 2019 (COVID-19) and evaluate the effect of prevention and control, we evaluate the epidemic dynamics of COVID-19 in mainland China, Hubei province, Wuhan city and other provinces outside Hubei from January 16 to February 14, 2020. Methods: We collected the daily number of new confirmed COVID-19 cases by nucleic acid detection reported by the National Health Commission from January 16, 2020 to February 14, 2020. The analysis includes the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in mainland China was 50 031, including 37 930 in Hubei province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of the number of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion: The epidemic prevention and control measures taken by the state and governments at all levels have shown very significant effects, effectively curbing the spread of the COVID-19 epidemic in China.

negative: The spatiotemporal estimation of the dynamic risk and the international transmission of 2019 Novel Coronavirus (COVID-19) outbreak: A global perspective An ongoing novel coronavirus SARS-CoV-2 pneumonia infection outbreak called COVID-19 started in Wuhan, Hubei Province, China, in December 2019. It both spread rapidly to all provinces in China and started spreading around the world quickly through international human movement from January 2020. Currently, the spatiotemporal epidemic transmission patterns, prediction models, and possible risk analysis for the future are insufficient for COVID-19 but we urgently need relevant information, particularly from the global perspective. We have developed a novel two-stage simulation model to simulate the spatiotemporal changes in the number of COVID-19 cases and estimate the future worldwide risk. Based on the connectivity of countries to China and the country's medical and epidemic prevention capabilities, different scenarios are generated to analyze the possible transmission throughout the world and use this information to evaluate each country's vulnerability to and the dynamic risk of COVID-19. Countries' vulnerability to the COVID-19 outbreak from China is calculated for 63 countries around the world. Taiwan, South Korea, Hong Kong, and Japan are the most vulnerable areas. The relationship between each country's vulnerability and days before the first imported case occurred shows a very high exponential decrease. The cumulative number of cases in each country also has a linear relationship with vulnerability, which can compare and quantify the initial epidemic prevention capabilities to various countries' management strategies. In total, 1,000 simulation results of future cases around the world are generated for the spatiotemporal risk assessment. According to the simulation results of this study, if there is no specific medicine for it, it will likely form a global pandemic. This method can be used as a preliminary risk assessment of the spatiotemporal spread for a new global epidemic. * Note: This study was completed on February 15, 2020.

negative: Cardiac involvement in COVID‐19 patients: Risk factors, predictors, and complications: A review BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS‐CoV‐2/COVID‐19), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID‐19. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID‐19. RESULTS: Notably, COVID‐19 patients with pre‐existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID‐19, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID‐19 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID‐19 patients to promote more informed treatment and, ultimately, better clinical outcomes.

negative: Ebola virus disease and critical illness As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa. EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death. Males and females have been equally affected, with children (0–14 years of age) accounting for 19 %, young adults (15–44 years) 58 %, and older adults (≥45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40–90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission. While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1325-2) contains supplementary material, which is available to authorized users.

negative: The impact of super-spreaders in COVID-19: mapping genome variation worldwide The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the 21st century. We analyzed >4,700 SARS-CoV-2 genomes and associated meta-data retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and >160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a uniform mutation occurrence along branches that could complicate the design of future vaccines. The root of SARS-CoV-2 genomes locates at the Chinese haplogroup B1, with a TMRCA dating to 12 November 2019 - thus matching epidemiological records. Sub-haplogroup A2a originates in China and represents the major non-Asian outbreak. Multiple founder effect episodes, most likely associated with super-spreader hosts, explain COVID-19 pandemic to a large extent.

negative: Ca2+ ions promote fusion of Middle East Respiratory Syndrome coronavirus with host cells and increase infectivity Middle East respiratory syndrome coronavirus (MERS-CoV) is a major emerging zoonotic infectious disease. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans with 2,468 confirmed cases, causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. A critical step in the life cycle of MERS-CoV is the fusion with the host cell with its spike (S) protein as main determinant of viral entry. Proteolytic cleavage of S exposes its fusion peptide (FP), which initiates membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium (Ca2+) plays an important role for fusogenic activity via a Ca2+ binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FP share a high sequence homology and here, we investigated whether Ca2+ is required for MERS-CoV fusion by substituting E and D residues in the MERS-CoV FP with neutrally charged alanines. Upon verifying mutant cell surface expression and proteolytic cleavage, we tested the mutants ability to mediate infection of pseudo-particles (PPs) on host cells without and with Ca2+. Our results demonstrate that intracellular Ca2+ enhances MERS-CoV WT PPs infection by approximately two-fold and that E891 is a crucial residue for Ca2+ interaction. Electron spin resonance revealed that this enhancement could be attributed to Ca2+ increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry titration showed that MERS-CoV FP binds one Ca2+, as opposed to SARS-CoV FP which binds two. Our data suggests that there are significant differences in FP-Ca2+ interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity and that the number of Ca2+ ions interacting with the FP has implications on the fusion dynamics of the virus.

negative: Strategies and Solutions for Team Sports Athletes in Isolation due to COVID-19 In December of 2019, there was an outbreak of a severe acute respiratory syndrome caused by the Coronavirus 2 (SARS-CoV-2 or COVID-19) in China. The virus rapidly spread into the whole World causing an unprecedented pandemic and forcing governments to impose a global quarantine, entering an extreme unknown situation. The organizational consequences of quarantine/isolation are: absence of organized training and competition, lack of communication among athletes and coaches, inability to move freely, lack of adequate sunlight exposure, inappropriate training conditions. Based on the current scientific, we strongly recommend encouraging the athlete to reset their mindset to understand quarantine as an opportunity for development, organizing appropriate guidance, educating and encourage athletes to apply appropriate preventive behavior and hygiene measures to promote immunity and ensuring good living isolation conditions. The athlete’s living space should be equipped with cardio and resistance training equipment (portable bicycle or rowing ergometer). Some forms of body mass resistance circuit-based training could promote aerobic adaptation. Sports skills training should be organized based on the athlete’s needs. Personalized conditioning training should be carried out with emphasis on neuromuscular performance. Athletes should also be educated about nutrition (Vitamin D and proteins) and hydration. Strategies should be developed to control body composition. Mental fatigue should be anticipated and mental controlled. Adequate methods of recovery should be provided. Daily monitoring should be established. This is an ideal situation in which to rethink personal life, understanding the situation, that can be promoted in these difficult times that affect practically the whole world.

negative: Pollen likely seasonal factor in inhibiting flu-like epidemics. A Dutch study into the inverse relation between pollen counts, hay fever and flu-like incidence 2016–2019 Abstract There is uncertainty if current models for the Covid-19 pandemic should already take into account seasonality. That is because current environmental factors do not provide a powerful explanation of such seasonality, especially given climate differences between countries with moderate climates. It is hypothesized that one major factor is overlooked: pollen count. Pollen are documented to invoke strong immune responses and might create an environmental factor that makes it more difficult for flu-like viruses to survive outside a host. This Dutch study confirms that there is a (highly) significant inverse correlation between pollen count and weekly changes in medical flu consults, and that there is a highly significant inverse correlation between hay fever incidence, as measured by prescribed medication revenues, and weekly flu consults. This supports the idea that pollen are a direct or indirect factor in the seasonality of flu-like epidemics. If seasonality will be observed during the covid-19 spread as well, it is not unlikely that pollen play a role.

negative: A Familial Cluster of Infection Associated With the 2019 Novel Coronavirus Indicating Possible Person-to-Person Transmission During the Incubation Period An ongoing outbreak of pneumonia associated with 2019 novel coronavirus was reported in China. It is unclear whether the virus is infective exists during the incubation period, although person-to-person transmission has been reported elsewhere. We report the epidemiological features of a familial cluster of 4 patients in Shanghai, including an 88-year-old man with limited mobility who was exposed only to asymptomatic family members whose symptoms developed later. The epidemiological evidence has shown possible transmission of 2019 novel coronavirus during the incubation period.

negative: Transmission of airborne virus through sneezed and coughed droplets The spread of COVID19 through droplets ejected by infected individuals in the air during sneezing and coughing has been considered as a matter of key concern. Therefore, a quantitative understanding of the propagation of droplets containing the virus assumes immense importance in formulating the preventive strategies. In the present work we rigorously investigate the evolution of droplets in space and time under varying external conditions of temperature, humidity, air flow by using laws of statistical mechanics. The effects of drag, diffusion and the gravity on the droplets of different sizes and ejection velocities have been taken into consideration during its motion in the air. In still air it is found that bigger droplets traverse larger distance but the smaller droplets remain suspended in the air for longer time. Therefore, in still air the horizontal distance that a healthy individual should maintain from an infected one is determined by the bigger droplets but the time interval to be maintained between the two is determined by the smaller droplets. Here we show that in places with flowing air the lighter droplets travel larger distance and have the ability to remain suspended in the air for longer time. Therefore, we conclude that both temporal as well as the geometric distance that a healthy individual should maintain from an infected one is determined by the smaller droplets if there is flowing air. The small droplets travel larger distance and remain suspended in the air for long time under the influence of flow making the use of mask mandatory to prevent the virus. The the maintenance of only stationary separation between healthy and infected individual is not substantiated. The quantitative results obtained here will be useful to devise strategies for preventing also the spread of other types of droplets containing microorganisms.

negative: New preventative measures against coronavirus disease 2019 for home care aides in Taiwan

negative: [Health management of breast cancer patients outside the hospital during the outbreak of 2019 novel coronavirus disease] The outbreak of 2019 novel coronavirus disease (COVID-19) is spreading rapidly. In order to prevent cluster outbreaks, the government strengthened the management and control of personnel mobility, which had a great impact on the examination and treatment of breast cancer patients. This paper discusses how to realize scientific health management of breast cancer patients outside the hospital based on the existing epidemic situation, characteristics of breast cancer patients and public health safety factors. The breast cancer patients should synthetically consider the epidemic prevention situation of inhabitance, the disease stage and previous therapeutic schedule to decide the next therapeutic schedule. If necessary, after professional discussion and communication between doctors and patients online or offline, the hospital visiting time should be delayed through seeking alternative treatment schemes, and psychological counseling for patients should be paid attention to at the same time.

negative: Eco-epidemiological assessment of the COVID-19 epidemic in China, January-February 2020 Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance elsewhere. Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation. Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25° latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5-7 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios. Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 cases. Weekly means of maximum daily temperature varied from -28.0 to 30.1 °C, minimum daily temperature from -42.4 to 23.0 °C, maximum solar radiation from 0.04 to 2.74 MJm-2 and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence. Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.

negative: Impact of abdominal shape on living liver donor outcomes in mini-incision right hepatic lobectomy: Comparison among 3 techniques. Although minimally invasive techniques for living donor hepatectomy have been developed, the surgical feasibility and limitations remain to be elucidated. The risks and outcomes involved need to be better understood prior to their widespread application. The aim of this study was to assess feasibility of minimally invasive donor hepatectomy by reviewing our experience. A total of 99 living donor liver transplantations performed between 2000 and 2016 were retrospectively reviewed. All 99 living liver donors underwent right hepatectomy. The breakdown of the techniques is as follows: the standard technique in 33 patients; the laparoscopic-assisted minilaparotomy technique (hybrid technique group) in 19 patients; and the upper midline incision technique without laparoscopic assistance (minilaparotomy group) in 47 patients. An association between donor operative outcomes and body habitus, such as body mass index (BMI), abdominal truncal depth (approximated by celiac axis [CA] depth ratio), and umbilical circumference (UC) were assessed. Perioperative factors were compared between the standard technique and the minimally invasive technique. The minilaparotomy group had significantly shorter operative time (P = 0.046) and hospital stay (P = 0.005) than the standard technique group. Postoperative complication rates were similar between the 3 groups (P = 0.16). In the minilaparotomy group, greater BMI (P = 0.02), CA depth ratio (P = 0.04), and UC (P = 0.004) were found to be risk factors for postoperative complications. In the minilaparotomy group, CA depth ratio > 0.41, UC > 90 cm, and BMI > 30 kg/m2 were significantly associated with longer operative time and hospital stay. In the standard technique group, none of the body size factors were associated with postoperative outcomes. In conclusion, the minilaparotomy technique is safe and feasible, though technical difficulties may be encountered when performed on donors with larger body habitus. Ongoing efforts are required to ensure living donor safety. Liver Transplantation 24 516-527 2018 AASLD.

negative: Serodiagnostic Aids and Management Practice for Feline Retrovirus and Coronavirus Infections

negative: Face Coverings, Aerosol Dispersion and Mitigation of Virus Transmission Risk The SARS-CoV-2 virus is primarily transmitted through virus-laden fluid particles ejected from the mouth of infected people. In some countries, the public has been asked to use face covers to mitigate the risk of virus transmission - yet, their outward effectiveness is not ascertained. We used a Background Oriented Schlieren technique to investigate the air flow ejected by a person while quietly and heavily breathing, while coughing, and with different face covers. We found that all face covers without an outlet valve reduce the front flow through jet by more than 90 per cent. For the FFP1 and FFP2 masks without exhalation valve, the front throughflow does not extend beyond one half and one quarter of a metre, respectively. Surgical and hand-made masks, and face shields, generate several leakage jets, including intense backward and downwards jets that may present major hazards. We also simulated an aerosol generating procedure (extubation) and we showed that this is a major hazard for clinicians. These results can aid policy makers to make informed decisions and PPE developers to improve their product effectiveness by design.

negative: Take precautions beforehand: calling for clinical trials of pediatric drugs for treating coronavirus disease 2019

negative: CO.ME.T.A. -- covid-19 media textual analysis. A dashboard for media monitoring The focus of this paper is to trace how mass media, particularly newspapers, have addressed the issues about the containment of contagion or the explanation of epidemiological evolution. We propose an interactive dashboard: CO.ME.T.A.. During crises it is important to shape the best communication strategies in order to respond to critical situations. In this regard, it is important to monitor the information that mass media and social platforms convey. The dashboard allows to explore the mining of contents extracted and study the lexical structure that links the main discussion topics. The dashboard merges together four methods: text mining, sentiment analysis, textual network analysis and latent topic models. Results obtained on a subset of documents show not only a health-related semantic dimension, but it also extends to social-economic dimensions.

negative: Masks and thermometers: Paramount measures to stop the rapid spread of SARS-CoV-2 in the United States Abstract In the United States, there is currently an exponential growth for the COVID-19 cases. The US president’s coronavirus guidelines for Americans “30 Days to Slow The Spread” are necessary. To effectively curb the rapid spread of SARS-CoV-2, two more control measures masks and thermometers are strongly suggested to be included in the Guidelines.

negative: Trends in clinical features of novel coronavirus disease (COVID-19): A systematic review and meta-analysis of studies published from December 2019 to February 2020 BACKGROUND: Since novel coronavirus disease (COVID-19) emerged, various clinical features of COVID-19 have been reported. METHODS: We conducted a systematic review of published studies reporting the clinical features of COVID-19. Two investigators independently searched PubMed (December 2019–February 2020) for eligible articles. A meta-analysis was performed to measure the frequencies of clinical outcomes and symptoms of COVID-19. A stratified analysis was conducted according to the timeline of outbreak and exposure histories: Group I, most patients were exposed to the Hunan seafood wholesale market and lived in Wuhan, Hubei province; Group II, patients lived in Hubei province but were not directly exposed to the market; and Group III, patients lived outside Hubei. RESULTS: Thirteen studies, all from China, were eligible. The estimated mortality rate among all studies was 2.12%, but that in Group I was 8.66%. The incidence of acute respiratory distress syndrome in Group I was 20.00%. Both fever and cough were major symptoms, and their frequencies were higher in Group I than in Groups II and III, while the frequency of diarrhea in Group I was lower than that in Group III. The estimated frequency of dyspnea in Group I was 37.18%, while those in Groups II and III were 16.95% and 7.03%, respectively. CONCLUSIONS: The trends in the clinical features of COVID-19 changed from December 2019 to February 2020. During this observation period, as the infection continued to spread, the clinical conditions for majority of patients became less severe with the changes in the route of transmission.

negative: Positive SARS-Cov-2 test in a woman with COVID-19 at 22 days after hospital discharge: A case report Abstract Background In a few discharged patients with coronavirus disease 2019 (COVID-19), the nucleic acid test shows positive results again. Whether this is due to relapse of the disease, reinfection by the virus, or a false-positive result at hospital discharge is worth exploring. Case presentation A woman with COVID-19 was discharged from the hospital after integrative treatment with traditional Chinese and Western medicine because she met the discharge standards. However, she obtained positive results on a nucleic acid test 22 days later. Conclusion Based on this positive test result in a discharged patient with COVID-19, anal tests and coronavirus antibody tests should be combined with throat swab tests to further develop the diagnosis and discharge standards for patients with COVID-19.

negative: Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study Background The COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. Methods We collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level. Results The median age of the cases was 44 years, with an increasing of cases in younger age groups and the elderly as the epidemic progressed. The delay from symptom onset to hospital admission decreased from 4.4 days (95%CI: 0.0-14.0) until January 27 to 2.6 days (0.0-9.0) from January 28 to February 17. The mean incubation period was estimated at 5.2 days (1.8-12.4) and the mean serial interval at 5.1 days (1.3-11.6). The epidemic dynamics in provinces outside Hubei was highly variable, but consistently included a mix of case importations and local transmission. We estimate that the epidemic was self-sustained for less than three weeks with Rt reaching peaks between 1.40 (1.04-1.85) in Shenzhen City of Guangdong Province and 2.17 (1.69-2.76) in Shandong Province. In all the analyzed locations (n=10) Rt was estimated to be below the epidemic threshold since the end of January. Conclusion Our findings suggest that the strict containment measures and movement restrictions in place may contribute to the interruption of local COVID-19 transmission outside Hubei Province. The shorter serial interval estimated here implies that transmissibility is not as high as initial estimates suggested.

negative: Evaluation of Enzyme-Linked Immunoassay and Colloidal Gold- Immunochromatographic Assay Kit for Detection of Novel Coronavirus (SARS-Cov-2) Causing an Outbreak of Pneumonia (COVID-19) Abstract BACKGROUND: In December 2019, a novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19) occurred in Wuhan, China. Travel-associated cases have also been reported in other countries. The number of cases has increased rapidly but laboratory diagnosis is limited. METHODS: We collect two groups of cases diagnosed with COVID-19 for experiments. One group collected 63 samples for Enzyme-linked immunosorbent assay (ELISA) IgG and IgM antibodies. The other group collected 91 plasma samples for colloidal gold-immunochromatographic assay (GICA). RESULTS: The sensitivity of the combined ELISA IgM and ELISA IgG detection was 55/63 ( 87.3%), The sensitivity of the combined GICA IgM and GICA IgG detection was 75/91 ( 82.4%), Both methods are negative for healthy controls, specificity of 100% .There is no significant difference between the sensitivity of between ELISA and GICA (IgM+ IgG). CONCLUSIONS: ELISA and GICA for specific IgM and IgG antibodies are conventional serological assays, they are simple, fast, and safe, the results can be used for clinical reference, and the huge clinical diagnosis and treatment pressure can be greatly relieved.

negative: COVID-19 in the Cancer Patient The novel Coronavirus Disease 2019 (COVID-19) was first reported in China in December 2019. Since then, it has spread across the world to become one of the most serious life-threatening pandemics since the influenza pandemic of 1918. This review article will focus on the specific risks and nuanced considerations of COVID-19 in the cancer patient. Important perioperative management recommendations during this outbreak are emphasized, in addition to discussion of current treatment techniques and strategies available in the battle against COVID-19.

negative: A Community Transmitted Case of Severe Acute Respiratory Distress Syndrome due to SARS CoV2 in the United States

negative: Conserved antigenic sites between MERS-CoV and Bat-coronavirus are revealed through sequence analysis BACKGROUND: MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV. RESULTS: Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein’s antigenic sites are found to be conserved with those in HKU4 and HKU5. CONCLUSION: This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13029-016-0049-7) contains supplementary material, which is available to authorized users.

negative: A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses The H1 subtype of influenza A viruses (IAVs) has been circulating in swine since the 1918 human influenza pandemic. Over time, and aided by further introductions from nonswine hosts, swine H1 viruses have diversified into three genetic lineages. Due to limited global data, these H1 lineages were named based on colloquial context, leading to a proliferation of inconsistent regional naming conventions. In this study, we propose rigorous phylogenetic criteria to establish a globally consistent nomenclature of swine H1 virus hemagglutinin (HA) evolution. These criteria applied to a data set of 7,070 H1 HA sequences led to 28 distinct clades as the basis for the nomenclature. We developed and implemented a web-accessible annotation tool that can assign these biologically informative categories to new sequence data. The annotation tool assigned the combined data set of 7,070 H1 sequences to the correct clade more than 99% of the time. Our analyses indicated that 87% of the swine H1 viruses from 2010 to the present had HAs that belonged to 7 contemporary cocirculating clades. Our nomenclature and web-accessible classification tool provide an accurate method for researchers, diagnosticians, and health officials to assign clade designations to HA sequences. The tool can be updated readily to track evolving nomenclature as new clades emerge, ensuring continued relevance. A common global nomenclature facilitates comparisons of IAVs infecting humans and pigs, within and between regions, and can provide insight into the diversity of swine H1 influenza virus and its impact on vaccine strain selection, diagnostic reagents, and test performance, thereby simplifying communication of such data. IMPORTANCE A fundamental goal in the biological sciences is the definition of groups of organisms based on evolutionary history and the naming of those groups. For influenza A viruses (IAVs) in swine, understanding the hemagglutinin (HA) genetic lineage of a circulating strain aids in vaccine antigen selection and allows for inferences about vaccine efficacy. Previous reporting of H1 virus HA in swine relied on colloquial names, frequently with incriminating and stigmatizing geographic toponyms, making comparisons between studies challenging. To overcome this, we developed an adaptable nomenclature using measurable criteria for historical and contemporary evolutionary patterns of H1 global swine IAVs. We also developed a web-accessible tool that classifies viruses according to this nomenclature. This classification system will aid agricultural production and pandemic preparedness through the identification of important changes in swine IAVs and provides terminology enabling discussion of swine IAVs in a common context among animal and human health initiatives.

negative: Environmental Impact, Concept and Measurement of Abstract Environments on Earth are always changing, and living systems evolve within them. For most of their history, human beings did the same. But in the last two centuries, humans have become the planet's dominant species, changing and impoverishing the environment for all life on Earth and even decimating humans' own cultural diversity. Contemporary cultural worldviews that have severed humans' ancient connections with the natural world, along with consumption and population growth, have deepened this impoverishment. Understanding, measuring, and managing human environmental impacts – the most important of which is the impoverishment of living systems – is the 21st century's greatest challenge.

negative: Changes in Police Calls for Service During the Early Months of the 2020 Coronavirus Pandemic The coronavirus pandemic poses multiple challenges for policing, including the need to continue responding to calls from the public. Several contingency plans warned police to expect a large and potentially overwhelming increase in demand from the public during a pandemic, but (to the author’s knowledge) there is no empirical work on police demand during a major public health emergency. This study used calls-for-service data from 10 large cities in the USA to analyse how calls for service changed during the early months of the 2020 COVID-19 outbreak, compared to forecasts of call volume based on data from previous years. Contrary to previous warnings, overall the number of calls went down during the early weeks of the pandemic. There were substantial reductions in specific call types, such as traffic collisions, and significant increases in others, such as calls to dead bodies. Other types of calls, particularly those relating to crime and order maintenance, continued largely as before. Changes in the frequency of different call types present challenges to law enforcement agencies, particularly since many will themselves be suffering from reduced staffing due to the pandemic. Understanding changes to calls in detail will allow police leaders to put in place evidence-based plans to ensure they can continue to serve the public.

negative: Modelling the spread of COVID-19 with new fractal-fractional operators: Can the lockdown save mankind before vaccination? Countries around the world are implementing lock-down measures in a bid to flatten the curve of the new deadly COVID-19 disease. Our paper does not claim to have found the cure for COVID-19, neither does it claim that the suggested model have taken into account all the complexities around the spread of the disease. Nonetheless, the fundamental question asked in this paper is to know if within the conditions taken into account in this suggested model, the integral lock-down is effective in saving human lives. To answer this question, a mathematical model was suggested taking into account the possibility of transmission of COVID-19 from dead bodies to humans and the effect of lock-down. Three cases were considered. The first case suggested that there is transmission from dead to the living (medical staffs as they perform postmortem procedures on corpses, and direct contacts with during burial ceremonies). This case has no equilibrium points except for disease free equilibrium, a clear indication that care must be taken when dealing with corpses due to corona-19. In the second case we removed the transmission rate from dead bodies. This case showed an equilibrium point, although the number of deaths, carriers and infected grew exponentially up to a certain stability level. In the last case, we incorporated a lock-down and social distancing effect, using the next generation matrix. We could achieve a zero reproduction number, with number of deaths, infected and carriers decaying very rapidly. This is a clear indication that if lock-down recommendations are observed the threat of COVID-19 can be reduced to zero in few months.While our mathematical model agrees with the effectiveness of the lock-down, it is important to mention damaging effects of inadequate testing. The long waiting period of few days before confirmation of status, can only lead to more infections. The asymptomatic tested person could be positive and spread the infection, or could contact the virus in days after testing and will spread the disease further, after being given a false result. Testing kit that with immediate results are needed for more efficient measures. We used Italy’s Data to guide the construction of the mathematical model. To include non-locality into mathematical formulas, differential and integral operators were suggested. Properties and numerical approximations were presented in details. Finally, the suggested differential and integral operators were applied to the model.

negative: Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong PURPOSE: Coronavirus disease (COVID-19) has rapidly emerged as a global health threat. The purpose of this article is to share our local experience of stepping up infection control measures in ophthalmology to minimise COVID-19 infection of both healthcare workers and patients. METHODS: Infection control measures implemented in our ophthalmology clinic are discussed. The measures are based on detailed risk assessment by both local ophthalmologists and infection control experts. RESULTS: A three-level hierarchy of control measures was adopted. First, for administrative control, in order to lower patient attendance, text messages with an enquiry phone number were sent to patients to reschedule appointments or arrange drug refill. In order to minimise cross-infection of COVID-19, a triage system was set up to identify patients with fever, respiratory symptoms, acute conjunctivitis or recent travel to outbreak areas and to encourage these individuals to postpone their appointments for at least 14 days. Micro-aerosol generating procedures, such as non-contact tonometry and operations under general anaesthesia were avoided. Nasal endoscopy was avoided as it may provoke sneezing and cause generation of droplets. All elective clinical services were suspended. Infection control training was provided to all clinical staff. Second, for environmental control, to reduce droplet transmission of COVID-19, installation of protective shields on slit lamps, frequent disinfection of equipment, and provision of eye protection to staff were implemented. All staff were advised to measure their own body temperatures before work and promptly report any symptoms of upper respiratory tract infection, vomiting or diarrhoea. Third, universal masking, hand hygiene, and appropriate use of personal protective equipment (PPE) were promoted. CONCLUSION: We hope our initial experience in stepping up infection control measures for COVID-19 infection in ophthalmology can help ophthalmologists globally to prepare for the potential community outbreak or pandemic. In order to minimise transmission of COVID-19, ophthalmologists should work closely with local infection control teams to implement infection control measures that are appropriate for their own clinical settings.

negative: Coda: Transformative Encounters: Desiring Aliens and Hospitality in District 9 This final chapter considers Neill Blomkamp’s film District 9 for its commentary on human and non-human alien relationships. Returning to many of the issues raised in the previous chapters, this coda analyzes the overt biopolitical dimensions of the film and considers how desire works to challenge the violent machinations of the multinational security company, Multi-National United. It examines how the film’s protagonist gets caught up in logics of exclusion in his experience of becoming-alien and approaches a position of bare life, outside the protections of the community. Ultimately, the chapter concludes the project by arguing that new, creative modes of resisting neocolonial and capitalist violence will be needed in response to biopolitical regimes, and that such creativity might arise from different desires and other modes of affect.

negative: Genomic characterization of equine coronavirus Abstract The complete genome sequence of the first equine coronavirus (ECoV) isolate, NC99 strain was accomplished by directly sequencing 11 overlapping fragments which were RT–PCR amplified from viral RNA. The ECoV genome is 30,992 nucleotides in length, excluding the polyA tail. Analysis of the sequence identified 11 open reading frames which encode two replicase polyproteins, five structural proteins (hemagglutinin esterase, spike, envelope, membrane, and nucleocapsid) and four accessory proteins (NS2, p4.7, p12.7, and I). The two replicase polyproteins are predicted to be proteolytically processed by three virus-encoded proteases into 16 non-structural proteins (nsp1–16). The ECoV nsp3 protein had considerable amino acid deletions and insertions compared to the nsp3 proteins of bovine coronavirus, human coronavirus OC43, and porcine hemagglutinating encephalomyelitis virus, three group 2 coronaviruses phylogenetically most closely related to ECoV. The structure of subgenomic mRNAs was analyzed by Northern blot analysis and sequencing of the leader–body junction in each sg mRNA.

negative: Analyzing the epidemiological outbreak of COVID‐19: A visual exploratory data analysis approach There is an obvious concern globally regarding the fact about the emerging coronavirus 2019 novel coronavirus (2019‐nCoV) as a worldwide public health threat. As the outbreak of COVID‐19 causes by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) progresses within China and beyond, rapidly available epidemiological data are needed to guide strategies for situational awareness and intervention. The recent outbreak of pneumonia in Wuhan, China, caused by the SARS‐CoV‐2 emphasizes the importance of analyzing the epidemiological data of this novel virus and predicting their risks of infecting people all around the globe. In this study, we present an effort to compile and analyze epidemiological outbreak information on COVID‐19 based on the several open datasets on 2019‐nCoV provided by the Johns Hopkins University, World Health Organization, Chinese Center for Disease Control and Prevention, National Health Commission, and DXY. An exploratory data analysis with visualizations has been made to understand the number of different cases reported (confirmed, death, and recovered) in different provinces of China and outside of China. Overall, at the outset of an outbreak like this, it is highly important to readily provide information to begin the evaluation necessary to understand the risks and begin containment activities.

negative: Feline immunodeficiency. ABCD guidelines on prevention and management Abstract Overview Feline immunodeficiency virus (FIV) is a retrovirus closely related to human immunodeficiency virus. Most felids are susceptible to FIV, but humans are not. Feline immunodeficiency virus is endemic in domestic cat populations worldwide. The virus loses infectivity quickly outside the host and is susceptible to all disinfectants. Infection Feline immunodeficiency virus is transmitted via bites. The risk of transmission is low in households with socially well-adapted cats. Transmission from mother to kittens may occur, especially if the queen is undergoing an acute infection. Cats with FIV are persistently infected in spite of their ability to mount antibody and cell-mediated immune responses. Disease signs Infected cats generally remain free of clinical signs for several years, and some cats never develop disease, depending on the infecting isolate. Most clinical signs are the consequence of immunodeficiency and secondary infection. Typical manifestations are chronic gingivostomatitis, chronic rhinitis, lymphadenopathy, weight loss and immune-mediated glomerulonephritis. Diagnosis Positive in-practice ELISA results obtained in a low-prevalence or low-risk population should always be confirmed by a laboratory. Western blot is the ‘gold standard’ laboratory test for FIV serology. PCR-based assays vary in performance. Disease management Cats should never be euthanased solely on the basis of an FIV-positive test result. Cats infected with FIV may live as long as uninfected cats, with appropriate management. Asymptomatic FIV-infected cats should be neutered to avoid fighting and virus transmission. Infected cats should receive regular veterinary health checks. They can be housed in the same ward as other patients, but should be kept in individual cages. Vaccination recommendations At present, there is no FIV vaccine commercially available in Europe. Potential benefits and risks of vaccinating FIV-infected cats should be assessed on an individual cat basis. Needles and surgical instruments used on FIV-positive cats may transmit the virus to other cats, so strict hygiene is essential.

negative: Infectious Diseases: The Role of the Forensic Physician Infections have plagued doctors for centuries, both in the diagnosis of the specific diseases, and the identification and subsequent management of the causative agents. There is a constant need for information as new organisms emerge, existing ones develop resistance to current drugs or vaccines and there are changes in epidemiology and prevalence. In the twenty-first century, obtaining this information has never been more important. Population migration, and the relatively low cost of flying, means that unfamiliar infectious diseases may be brought into industrialised countries. An example of this was an outbreak of severe acute respiratory syndrome (SARS), which was first recognised in 2003. Despite modern technology and a huge input of money, it took months for the agent to be identified, a diagnostic test to be produced, and a strategy for disease reporting and isolation to be established.

negative: The Human Nature of Infectious Disease Infectious disease raises questions about humans’ abilities to eliminate harm through the control of nature. People work to understand microbial life in order to manage the ways microbes mutate, adapt, and evolve, even while recognizing organisms’ essential nature. Public health practices from the past and present exemplify this ongoing quest to “solve” disease. Eradicating pathogens persists as a public health objective, even as new microbes emerge in the human environment. “Superbugs” and antibiotic resistance exemplify the problem-solution-problem cycle of disease. Moving from solutions-based thinking enables new imaginings of the microbial world in which humans reside.

negative: Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding The global outbreak of SARS in 2002-2003 was caused by the infection of a new human coronavirus SARS-CoV. The infection of SARS-CoV is mediated mainly through the viral surface glycoproteins, which consist of S1 and S2 subunits and form trimer spikes on the envelope of the virions. Here we report the ectodomain structures of the SARS-CoV surface spike trimer in different conformational states determined by single-particle cryo-electron microscopy. The conformation 1 determined at 4.3 Å resolution is three-fold symmetric and has all the three receptor-binding C-terminal domain 1 (CTD1s) of the S1 subunits in “down” positions. The binding of the “down” CTD1s to the SARS-CoV receptor ACE2 is not possible due to steric clashes, suggesting that the conformation 1 represents a receptor-binding inactive state. Conformations 2-4 determined at 7.3, 5.7 and 6.8 Å resolutions are all asymmetric, in which one RBD rotates away from the “down” position by different angles to an “up” position. The “up” CTD1 exposes the receptor-binding site for ACE2 engagement, suggesting that the conformations 2-4 represent a receptor-binding active state. This conformational change is also required for the binding of SARS-CoV neutralizing antibodies targeting the CTD1. This phenomenon could be extended to other betacoronaviruses utilizing CTD1 of the S1 subunit for receptor binding, which provides new insights into the intermediate states of coronavirus pre-fusion spike trimer during infection.

negative: COVID-19 length of hospital stay: a systematic review and data synthesis Background The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care. Methods We performed a systematic review to gather data on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach we provide distributions for general hospital and ICU LoS from studies in China and elsewhere, for use by the community. Results We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies - four each within and outside China - with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR: 10-19) days for China, compared with 5 (IQR: 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date. Conclusion Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.

negative: The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention. One sentence summary The novel 2019 coronavirus and the SARS-coronavirus share central biological properties which can guide risk assessment and intervention.

negative: Vaccines against Middle East respiratory syndrome coronavirus for humans and camels Middle East respiratory syndrome coronavirus (MERS‐CoV) is caused by a novel betacoronavirus that was isolated in late 2012 in Saudi Arabia. The viral infections have been reported in more than 1700 humans, ranging from asymptomatic or mild cases to severe pneumonia with a mortality rate of 40%. It is well documented now that dromedary camels contract the infection and shed the virus without notable symptoms, and such animals had been infected by at least the early 1980s. The mechanism of camel to human transmission is still not clear, but several primary cases have been associated with camel contact. There is no approved antiviral drug or vaccine against MERS‐CoV despite the active research in this area. Vaccine candidates have been developed using various platforms and regimens and have been tested in several animal models. Here, this article reviews the published studies on MERS‐CoV vaccines with more focus on vaccines tested in large animals, including camels. It is foreseeable that the 1‐health approach could be the best way of tackling the MERS‐CoV endemic in the Arabian Peninsula, by using the mass vaccination of camels in the affected areas to block camel to human transmission. Camel vaccines can be developed in a faster time with fewer regulations and lower costs and could clear this virus from the Arabian Peninsula if accompanied by efficient public health measures.

negative: 2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine readiness. On 31 December 2019 the Wuhan Health Commission reported a cluster of atypical pneumonia cases that was linked to a wet market in the city of Wuhan, China. The first patients began experiencing symptoms of illness in mid-December 2019. Clinical isolates were found to contain a novel coronavirus with similarity to bat coronaviruses. As of 28 January 2020, there are in excess of 4,500 laboratory-confirmed cases, with > 100 known deaths. As with the SARS-CoV, infections in children appear to be rare. Travel-related cases have been confirmed in multiple countries and regions outside mainland China including Germany, France, Thailand, Japan, South Korea, Vietnam, Canada, and the United States, as well as Hong Kong and Taiwan. Domestically in China, the virus has also been noted in several cities and provinces with cases in all but one provinence. While zoonotic transmission appears to be the original source of infections, the most alarming development is that human-to-human transmission is now prevelant. Of particular concern is that many healthcare workers have been infected in the current epidemic. There are several critical clinical questions that need to be resolved, including how efficient is human-to-human transmission? What is the animal reservoir? Is there an intermediate animal reservoir? Do the vaccines generated to the SARS-CoV or MERS-CoV or their proteins offer protection against 2019-nCoV? We offer a research perspective on the next steps for the generation of vaccines. We also present data on the use of in silico docking in gaining insight into 2019-nCoV Spike-receptor binding to aid in therapeutic development. Diagnostic PCR protocols can be found at https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus.

negative: Global transmission network of SARS-CoV-2: from outbreak to pandemic BACKGROUND. The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is straining health systems around the world. Although the Chinese government implemented a number of severe restrictions on people’s movement in an attempt to contain its local and international spread, the virus had already reached many areas of the world in part due to its potent transmissibility and the fact that a substantial fraction of infected individuals develop little or no symptoms at all. Following its emergence, the virus started to generate sustained transmission in neighboring countries in Asia, Western Europe, Australia, Canada and the United States, and finally in South America and Africa. As the virus continues its global spread, a clear and evidence-based understanding of properties and dynamics of the global transmission network of SARS-CoV-2 is essential to design and put in place efficient and globally coordinated interventions. METHODS. We employ molecular surveillance data of SARS-CoV-2 epidemics for inference and comprehensive analysis of its global transmission network before the pandemic declaration. Our goal was to characterize the spatial-temporal transmission pathways that led to the establishment of the pandemic. We exploited a network-based approach specifically tailored to emerging outbreak settings. Specifically, it traces the accumulation of mutations in viral genomic variants via mutation trees, which are then used to infer transmission networks, revealing an up-to-date picture of the spread of SARS-CoV-2 between and within countries and geographic regions. RESULTS AND CONCLUSIONS. The analysis suggest multiple introductions of SARS-CoV-2 into the majority of world regions by means of heterogeneous transmission pathways. The transmission network is scale-free, with a few genomic variants responsible for the majority of possible transmissions. The network structure is in line with the available temporal information represented by sample collection times and suggest the expected sampling time difference of few days between potential transmission pairs. The inferred network structural properties, transmission clusters and pathways and virus introduction routes emphasize the extent of the global epidemiological linkage and demonstrate the importance of internationally coordinated public health measures.

negative: Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins As cell-invading molecular machinery, coronavirus spike proteins pose an evolutionary conundrum due to their high divergence. In this study, we determined the cryo-EM structure of avian infectious bronchitis coronavirus (IBV) spike protein from the γ-genus. The trimeric IBV spike ectodomain contains three receptor-binding S1 heads and a trimeric membrane-fusion S2 stalk. While IBV S2 is structurally similar to those from the other genera, IBV S1 possesses structural features that are unique to different other genera, thereby bridging these diverse spikes into an evolutionary spectrum. Specifically, among different genera, the two domains of S1, the N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), diverge from simpler tertiary structures and quaternary packing to more complex ones, leading to different functions of the spikes in receptor usage and membrane fusion. Based on the above structural and functional comparisons, we propose that the evolutionary spectrum of coronavirus spikes follows the order of α-, δ-, γ-, and β-genus. This study has provided insight into the evolutionary relationships among coronavirus spikes and deepened our understanding of their structural and functional diversity.

negative: Detection of the Severe Acute Respiratory Syndrome‐Related Coronavirus and Alphacoronavirus in the Bat Population of Taiwan Bats have been demonstrated to be natural reservoirs of severe acute respiratory syndrome coronavirus (SARS CoV) and Middle East respiratory syndrome (MERS) CoV. Faecal samples from 248 individuals of 20 bat species were tested for partial RNA‐dependent RNA polymerase gene of CoV and 57 faecal samples from eight bat species were tested positive. The highest detection rate of 44% for Scotophilus kuhlii, followed by 30% for Rhinolophus monoceros. Significantly higher detection rates of coronaviral RNA were found in female bats and Scotophilus kuhlii roosting in palm trees. Phylogenetic analysis classified the positive samples into SARS‐related (SARSr) CoV, Scotophilus bat CoV 512 close to those from China and Philippines, and Miniopterus bat CoV 1A‐related lineages. Coronaviral RNA was also detected in bat guano from Scotophilus kuhlii and Myotis formosus flavus on the ground and had potential risk for human exposure. Diverse bat CoV with zoonotic potential could be introduced by migratory bats and maintained in the endemic bat population in Taiwan.

negative: Properties of Coronavirus and SARS-CoV-2 were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (α,ß,Î³,Î´), human coronaviruses (HCoVs) are classified under α-CoV (HCoV-229E and NL63) and ß-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a ß-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.

negative: Detection of Covid-19 From Chest X-ray Images Using Artificial Intelligence: An Early Review In 2019, the entire world is facing a situation of health emergency due to a newly emerged coronavirus (COVID-19). Almost 196 countries are affected by covid-19, while USA, Italy, China, Spain, Iran, and France have the maximum active cases of COVID-19. The issues, medical and healthcare departments are facing in delay of detecting the COVID-19. Several artificial intelligence based system are designed for the automatic detection of COVID-19 using chest x-rays. In this article we will discuss the different approaches used for the detection of COVID-19 and the challenges we are facing. It is mandatory to develop an automatic detection system to prevent the transfer of the virus through contact. Several deep learning architecture are deployed for the detection of COVID-19 such as ResNet, Inception, Googlenet etc. All these approaches are detecting the subjects suffering with pneumonia while its hard to decide whether the pneumonia is caused by COVID-19 or due to any other bacterial or fungal attack.

negative: In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel Recent outbreak of Coronavirus disease (COVID-19) pandemic around the world is associated with ‘severe acute respiratory syndrome’ (SARS-CoV2) in humans. SARS-CoV2 is an enveloped virus and E proteins present in them are reported to form ion channels, which is mainly associated with pathogenesis. Thus, there is always a quest to inhibit these ion channels, which in turn may help in controlling diseases caused by SARS-CoV2 in humans. Considering this, in the present study, authors employed computational approaches for studying the structure as well as function of the human ‘SARS-CoV2 E’ protein as well as its interaction with various phytochemicals. Result obtained revealed that α-helix and loops present in this protein experience random movement under optimal condition, which in turn modulate ion channel activity; thereby aiding the pathogenesis caused via SARS-CoV2 in human and other vertebrates. However, after binding with Belachinal, Macaflavanone E, and Vibsanol B, the random motion of the human ‘SARS-CoV2 E’ protein gets reduced, this, in turn, inhibits the function of the ‘SARS-CoV2 E’ protein. It is pertinent to note that two amino acids, namely VAL25 and PHE26, play a key role while interacting with these three phytochemicals. As these three phytochemicals, namely, Belachinal, Macaflavanone E & Vibsanol B, have passed the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) property as well as ‘Lipinski’s Rule of 5s’, they may be utilized as drugs in controlling disease caused via SARS-COV2, after further investigation. Communicated by Ramaswamy H. Sarma

negative: Precautions in ophthalmic practice in a hospital with a major acute SARS outbreak: an experience from Hong Kong Many new infectious diseases in humans have been derived from animal sources in the past 20 years. Some are highly contagious and fatal. Vaccination may not be available and antiviral drugs are not effective enough. Infectious control is important in clinical medicine and in Ophthalmology. Severe acute respiratory syndrome (SARS), as an example, is a highly contagious respiratory disease that has recently been reported in Asia, North America, and Europe. Within a matter of weeks, the outbreak has evolved to become a global health threat and more than 30 countries have been afflicted with a novel Coronavirus strain (SARS-CoV) that is the aetiologic agent of SARS. The primary route of transmission of SARS appears involving close person-to-person contact through droplets. Ophthalmologists may be particularly susceptible to the infection as routine ophthalmic examinations like direct ophthalmoscopy and slit-lamp examination are usually performed in a setting that has close doctor–patient contact. Being the Ophthalmology Department of the only hospital in the world that has just gone through the largest outbreak of SARS, we would like to share our strategy, measures, and experiences of preventing contracting or spreading of SARS infection as an infection control model. SARS is one of the many viruses against which personnel will need protecting in an ophthalmic setting. The experiences attained and the measures established might also apply to other infectious conditions spreading by droplets such as the avian influenza with H5N1.

negative: ElaD, a Deubiquitinating Protease Expressed by E. coli BACKGROUND: Ubiquitin and ubiquitin-like proteins (Ubl) are designed to modify polypeptides in eukaryotes. Covalent binding of ubiquitin or Ubls to substrate proteins can be reversed by specific hydrolases. One particular set of cysteine proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in eukaryotes, prokaryotes, and viruses. FINDINGS: We have cloned and analyzed the E. coli protein elaD, which is distantly related to eukaryotic CE clan members of the ULP/SENP protease family that are specific for SUMO and Nedd8. Previously misannotated as a putative sulfatase/phosphatase, elaD is an efficient and specific deubiquitinating enzyme in vitro. Interestingly, elaD is present in all intestinal pathogenic E. coli strains, but conspicuously absent from extraintestinal pathogenic strains (ExPECs). Further homologs of this protease can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and Gammaproteobacteria. CONCLUSION: The expression of ULP/SENP-related hydrolases in bacteria therefore extends to plant pathogens and medically relevant strains of Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and Salmonellae, in which the elaD ortholog sseL has recently been identified as a virulence factor with deubiquitinating activity. As a counterpoint, our phylogenetic and functional examination reveals that ancient eukaryotic ULP/SENP proteases also have the potential of ubiquitin-specific hydrolysis, suggesting an early common origin of this peptidase clan.

negative: Identifying Research Trends and Gaps in the Context of COVID-19 The COVID-19 pandemic has affected the world in different ways. Not only are people’s lives and livelihoods affected, but the virus has also affected people’s lifestyles. In the research sector, there have been significant changes, and new research is coming very strongly in the related fields of virology and epidemiology. Similar trends were observed after the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) episodes of 2003 and 2012, respectively. Analyzing 20 years of published scientific papers, this article points out the highlights of coronavirus-related research. Significant progress is observed in the past research related to virology, epidemiology, infectious diseases among others. However, in research linked to public health, its governance, technology, and risk communication there seem to be gap areas. Although the World Health Organization (WHO) global research road map has identified social science-related research as a priority area, more focus needs to be given in the upcoming days for multi, cross and trans-disciplinary research related to public health and disaster risk reduction.

negative: Middle East Respiratory Syndrome Coronavirus Transmission Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.

negative: Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases RNA-dependent RNA polymerase (RdRp) is essential to viral replication and is therefore one of the primary targets of countermeasures against these dangerous infectious agents. Development of broad-spectrum therapeutics targeting polymerases has been hampered by the extreme sequence variability of these sequences. RdRps range in length from 400–800 residues, yet contain only ∼20 residues that are conserved in most species. In this study, we made structure-based comparisons that are independent of sequence composition using a recently developed algorithm. We identified residue-to-residue correspondences of multiple protein structures and created (two-dimensional) structure-based alignment maps of 37 polymerase structures that provide both sequence and structure details. Using these maps, we determined that ∼75% of each polymerase species consists of seven protein segments, each of which has high structural similarity to segments in other species, though they are widely divergent in sequence composition and order. We define each of these segments as a ‘homomorph’, and each includes (though most are much larger than) the well-known conserved polymerase motifs. All homomorphs contact the template tunnel or nucleoside triphosphate (NTP) entry tunnel and the exterior of the protein, suggesting they constitute a structural and functional skeleton common among the polymerases.

negative: A machine learning-based model for survival prediction in patients with severe COVID-19 infection The sudden increase of COVID-19 cases is putting a high pressure on healthcare services worldwide. At the current stage, fast, accurate and early clinical assessment of the disease severity is vital. To support decision making and logistical planning in healthcare systems, this study leverages a database of blood samples from 404 infected patients in the region of Wuhan, China to identify crucial predictive biomarkers of disease severity. For this purpose, machine learning tools selected three biomarkers that predict the survival of individual patients with more than 90% accuracy: lactic dehydrogenase (LDH), lymphocyte and high-sensitivity C-reactive protein (hs-CRP). In particular, relatively high levels of LDH alone seem to play a crucial role in distinguishing the vast majority of cases that require immediate medical attention. This finding is consistent with current medical knowledge that high LDH levels are associated with tissue breakdown occurring in various diseases, including pulmonary disorders such as pneumonia. Overall, this paper suggests a simple and operable formula to quickly predict patients at the highest risk, allowing them to be prioritised and potentially reducing the mortality rate.

negative: COVID-19 research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine What is new? KEY FINDINGS: Clinical decision-makers must be informed by the best, most trustworthy, highest-quality, robust evidence. This translates into how much confidence we can have in the research findings and thus be optimally informed for decision-making. The estimates of effect in clinical research depends on the underlying research methodology. COVID-19 disease is presenting global health systems, clinicians, and patients grave challenges. No treatment or prophylaxis currently exists for COVID-19. The overall body of COVID-19 research is very flawed methodologically. An examination of hydroxychloroquine-azithromycin research findings due to the recent media focus revealed very low-quality methodology underpins the research. Vast amounts of time and resources are being allocated to COVID-19 research, and being potentially squandered. WHAT THIS ADDS TO WHAT WAS KNOWN: Flawed methodology and sub-optimal reporting of research findings could lead to biased estimates of effect. This could lead to treatment decisions that are not optimal based on biased estimates which could harm the patient. This article provides specific suggestions for improving on the COVID-19 methods and reporting with a focus on the issues that researchers must consider in their methodology and reporting if we are to have confidence in the estimates of effect. Failure to consider harms in research could be detrimental to the patient. This article focuses on the potential harms when therapeutic agents such as hydroxychloroquine, are being considered. WHAT IS THE IMPLICATION AND WHAT SHOULD CHANGE NOW: Research thus far on finding an optimal therapeutic agent (s) for COVID-19 could be hampered by methodologically flawed research. COVID-19 researchers must immediately and acutely focus on improving their methodology and reporting.

negative: Manure and Microbes: Public and Animal Health Problem? Most environmental concerns about waste management either have focused on the effects of nutrients, especially N and P, on water quality or have emphasized odor problems and air quality. Microbes from manure are often low on the priority list for control and remediation, despite the fact that several out-breaks of gastroenteritis have been traced to livestock operations. The pathogens discussed in this paper include protozoans (Cryptosporidium parvum, Giardia spp.), bacteria (Listeria monocytogenes, Escherichia coli O157:H7, Salmonella spp., and Mycobacterium paratuberculosis), and some enteric viruses. Clinical symptoms, prospects for zoonotic infection, and control methods other than the use of antimicrobials are considered. Recommendations to avoid disease transmission include taking steps to ensure the provision of clean, unstressful environments to reduce disease susceptibility and the careful handling and spreading of manure from animals at high risk for infection, especially young calves. Composting and drying of manure decrease the number of viable pathogens. Environmental controls, such as filter strips, also reduce the risk of water contamination.

negative: Psoriasis health care in the time of the coronavirus pandemic: insights from dedicated centers in sardinia (Italy) Psoriasis is a major chronic inflammatory skin disease, affecting about 3% of the population in Italy, whose management require experienced specialists in order to guarantee high‐quality standards of care. The pandemic coronavirus (2019‐nCoV; COVID‐19) has changed the approach to all patients requiring close contact during a visit, including dermatologic consultations. In Italy, true outbreak begun in Lombardy, by February 21, 2020 with exponential contagion, surpassing China in the number of deaths.

negative: COVID-19 pneumonia patient without clear epidemiological history outside Wuhan: An analysis of the radiographic and clinical features Abstract The purpose of this case report is to describe the CT and clinical features of a COVID-19 pneumonia patient without clear epidemiological history outside Wuhan, China.

negative: SARS-like virus in the Middle East: A truly bat-related coronavirus causing human diseases

negative: Bacterial Infections: Overview Bacterial infections have a large impact on public health. Disease can occur at any body site and can be caused by the organism itself or by the body's response to its presence. Bacteria are transmitted to humans through air, water, food, or living vectors. The principal modes of transmission of bacterial infection are contact, airborne, droplet, vectors, and vehicular. Preventive measures have a dramatic impact on morbidity and mortality. Such measures include water treatment, immunization of animals and humans, personal hygiene measures, and safer sex practices. Bacterial resistance to antibiotics is a growing concern mandating their prudent use.

negative: In vitro exposure system for study of aerosolized influenza virus Abstract Infection of adherent cell monolayers using a liquid inoculum represents an established method to reliably and quantitatively study virus infection, but poorly recapitulates the exposure and infection of cells in the respiratory tract that occurs during infection with aerosolized pathogens. To better simulate natural infection in vitro, we adapted a system that generates viral aerosols similar to those exhaled by infected humans to the inoculation of epithelial cell monolayers. Procedures for cellular infection and calculation of exposure dose were developed and tested using viruses characterized by distinct transmission and pathogenicity phenotypes: an HPAI H5N1, an LPAI H7N9, and a seasonal H3N2 virus. While all three aerosolized viruses were highly infectious in a human bronchial epithelial cell line (Calu-3) cultured submerged in media, differences between the viruses were observed in primary human alveolar epithelial cells and in Calu-3 cells cultured at air-liquid interface. This system provides a novel enhancement to traditional in vitro experiments, particularly those focused on the early stages of infection.

negative: Infection Density and Epidemic Size of COVID-19 in China outside the Hubei province The novel coronavirus (COVID-19) has spread to almost all countries in the world, claiming more than 160,000 lives and sickening more than 2,400,000 people by April 21, 2020. There has been research showing that on average, each infected person spreads the infection to more than two persons. Therefore the majority of the population is at risk of infection if no intervention measures were undertaken. The true size of the COVID-19 epidemic remains unknown, as a significant proportion of infected individuals only exhibit mild symptoms or are even asymptomatic. A timely assessment of the evolving epidemic size is crucial for resource allocation and triage decisions. In this article, we modify the back-calculation algorithm to obtain a lower bound estimate of the number of COVID-19 infected persons in China outside the Hubei province. We estimate the infection density among infected and show that the drastic control measures enforced throughout China following the lockdown of Wuhan City effectively slowed down the spread of the disease in two weeks. Our findings from China are expected to provide guidelines and enlightenment for surveillance and control activities of COVID-19 in other countries around the world.

negative: Restructured society and environment: A review on potential technological strategies to control the COVID-19 pandemic Abstract The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in China at December 2019 had led to a global outbreak of coronavirus disease 2019 (COVID-19) and the disease started to spread all over the world and became an international public health issue. The entire humanity has to fight in this war against the unexpected and each and every individual role is important. Healthcare system is doing exceptional work and the government is taking various measures that help the society to control the spread. Public, on the other hand, coordinates with the policies and act accordingly in most state of affairs. But the role of technologies in assisting different social bodies to fight against the pandemic remains hidden. The intention of our study is to uncover the hidden roles of technologies that ultimately help for controlling the pandemic. On investigating, it is found that the strategies utilizing potential technologies would yield better benefits and these technological strategies can be framed either to control the pandemic or to support the confinement of the society during pandemic which in turn aids in controlling the spreading of infection. This study enlightens the various implemented technologies that assists the healthcare systems, government and public in diverse aspects for fighting against COVID-19. Furthermore, the technological swift that happened during the pandemic and their influence in the environment and society is discussed. Besides the implemented technologies, this work also deals with untapped potential technologies that have prospective applications in controlling the pandemic circumstances. Alongside the various discussion, our suggested solution for certain situational issues is also presented.

negative: Chapter 5 Aeromicrobiology Biological material including microorganisms and toxins can be found in air or the atmosphere, and the study of this area is termed “aeromicrobiology.” Airborne biological materials are known as bioaerosols. This chapter introduces the basics of aeromicrobiology including the nature of bioaerosols and fundamentals of the aeromicrobiological (AMB) pathway. The nature of the atmosphere as a microbial habitat, and the factors that influence microbial survival in the air are described. This is followed by a discussion of extramural aeromicrobiology related to aerosolization of indigenous soil pathogens; influenza pandemics; microbiology in the clouds; agriculture; waste disposal; and airborne toxins. Intramural microbiology within buildings is discussed with respect to public health within buildings, hospitals and laboratories. Finally, measures to control bioaerosols including biosafety in the laboratory are documented.

negative: Reducing mortality from 2019-nCoV: host-directed therapies should be an option

negative: A Novel AI-enabled Framework to Diagnose Coronavirus COVID 19 using Smartphone Embedded Sensors: Design Study Coronaviruses are a famous family of viruses that cause illness in both humans and animals. The new type of coronavirus COVID-19 was firstly discovered in Wuhan, China. However, recently, the virus has widely spread in most of the world and causing a pandemic according to the World Health Organization (WHO). Further, nowadays, all the world countries are striving to control the COVID-19. There are many mechanisms to detect coronavirus including clinical analysis of chest CT scan images and blood test results. The confirmed COVID-19 patient manifests as fever, tiredness, and dry cough. Particularly, several techniques can be used to detect the initial results of the virus such as medical detection Kits. However, such devices are incurring huge cost, taking time to install them and use. Therefore, in this paper, a new framework is proposed to detect COVID-19 using built-in smartphone sensors. The proposal provides a low-cost solution, since most of radiologists have already held smartphones for different daily-purposes. Not only that but also ordinary people can use the framework on their smartphones for the virus detection purposes. Nowadays Smartphones are powerful with existing computation-rich processors, memory space, and large number of sensors including cameras, microphone, temperature sensor, inertial sensors, proximity, colour-sensor, humidity-sensor, and wireless chipsets/sensors. The designed Artificial Intelligence (AI) enabled framework reads the smartphone sensors signal measurements to predict the grade of severity of the pneumonia as well as predicting the result of the disease.

negative: CHAPTER 28 Coronaviridae Publisher Summary Coronaviruses are ssRNA viruses that infect a wide range of mammalian and avian species; they are important causes of respiratory and enteric disease, encephalomyelitis, hepatitis, serositis, and vasculitis in domestic animals. In humans, coronaviruses are one of several groups of viruses that cause the common cold. The prototype of the family, avian infectious brochitis virus, is one of the most infectious of all viruses and causes an acute respiratory disease, which in young chicks can cause very high mortality. Outbreaks can be explosive, involving nearly every bird in the flock at about the same time, because of respiratory transmission and a very short incubation period. In many ways, transmissible gastroenteritis virus of swine and mouse hepatitis virus behave similarly, affecting young animals most severely, spreading very quickly to all animals at risk, and causing major economic losses before control strategies can be put into place. The strategy of expression of the coronavirus genome is unique. The input virion RNA molecule is translated directly, one of the products being an RNA polymerase that then transcribes a full-length (—) sense copy RNA, from which in turn is transcribed a 3′-coterminal nested set of subgenomic mRNAs. The nested set comprises six overlapping species of mRNAs that extend for different lengths from a common 3′ terminus. Only the unique sequence toward the 5′ end, which is not shared with the next smallest mRNA in the nested set, is translated, each product, therefore, being a unique protein.

negative: Pathogenesis of Mouse Hepatitis Virus Infection: The Role of Nasal Epithelial Cells as a Primary Target of Low‐Virulence Virus, MHV‐S The pathogenesis of mouse hepatitis virus (MHV‐S) infection in suckling and weanling mice was comparatively studied after intranasal inoculation. In sucklings, infectious virus as well as specific antigen was first detected in the nasal mucosa at 12 hr, then in the nerve cells of the olfactory bulbs. At this stage viral particles were demonstrated both in the supporting cells and olfactory cells of the nasal mucosa. In the posterior part of the brain and spinal cord, virus was detected on days 3 to 4 postinoculation when viral growth was clearly demonstrable in the liver, spleen and intestines. In weanlings too, infection was first established in the nasal mucosa, shedding infectious virus in the nasal washing until day 6 postinoculation, and later infection spread to the brain and spinal cord. In weanling mice, however, neither infectious virus nor viral antigen was detected in the liver or other visceral organs, while serum neutralizing antibody became detectable on day 5 postinoculation, increasing in titer thereafter. Histopathologically degenerative and necrotic changes were observed in the nasal mucosa and central nervous system of both age groups of animals coincidentally with the presence of viral specific antigen, while inflammatory response was much less prominent in sucklings. In the liver, spleen and intestines, however, some lesions were observed only in sucklings.

negative: Chapter 8 The Middle East Respiratory Syndrome Coronavirus: An Emerging Virus of Global Threat Abstract Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (CoV), first identified in Saudi Arabia in 2012. Since then, almost 2000 cases have been reported from 27 countries, with Saudi Arabia being the epicenter. This newly emerging virus is highly pathogenic and has a case mortality rate of 35%. It is similar to the CoV causing severe acute respiratory syndrome CoV (SARS-CoV) in that both belong to the genus beta CoVs that are of zoonotic origin and cause lower respiratory infection. The natural reservoir for MERS-CoV remains unknown. Serological studies indicate that most dromedary camels in the Middle East have been infected with this virus, and they maybe the potential intermediate host. However, the mode of transmission from camels to humans is poorly understood. The majority of confirmed human cases have resulted from human-to-human transmission, most probably via respiratory route. Patients most at risk of developing severe MERS-CoV infection appear to be those with underlying conditions such as diabetes, hypertension, obesity, cardiac diseases, chronic respiratory diseases, and cancer. Unlike SARS-CoV, MERS-CoV is considered an ongoing public health problem, particularly for the Middle East region. In this chapter, we outline the prevailing information regarding the emergence and epidemiology of this virus, its mode of transmission and pathogenicity, its clinical features, and the potential strategies for prevention.

negative: SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence? In a side-by-side comparison of evolutionary dynamics between the 2019/2020 SARS-CoV-2 and the 2003 SARS-CoV, we were surprised to find that SARS-CoV-2 resembles SARS-CoV in the late phase of the 2003 epidemic after SARS-CoV had developed several advantageous adaptations for human transmission. Our observations suggest that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV. However, no precursors or branches of evolution stemming from a less human-adapted SARS-CoV-2-like virus have been detected. The sudden appearance of a highly infectious SARS-CoV-2 presents a major cause for concern that should motivate stronger international efforts to identify the source and prevent near future re-emergence. Any existing pools of SARS-CoV-2 progenitors would be particularly dangerous if similarly well adapted for human transmission. To look for clues regarding intermediate hosts, we analyze recent key findings relating to how SARS-CoV-2 could have evolved and adapted for human transmission, and examine the environmental samples from the Wuhan Huanan seafood market. Importantly, the market samples are genetically identical to human SARS-CoV-2 isolates and were therefore most likely from human sources. We conclude by describing and advocating for measured and effective approaches implemented in the 2002-2004 SARS outbreaks to identify lingering population(s) of progenitor virus.

negative: The epidemiological and clinical features of COVID-19 and lessons from this global infectious public health event Abstract Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a potentially fatal disease of great global public health importance. As of March 26, 2020, the outbreak of COVID-19 has resulted in 462,801 confirmed cases and 20,839 deaths globally, which is more than those caused by SARS and Middle East respiratory syndrome (MERS) in 2003 and 2013, respectively. The epidemic has posed considerable challenges worldwide. Under a strict mechanism of massive prevention and control, China has seen a rapid decrease in new cases of coronavirus; however, the global situation remains serious. Additionally, the origin of COVID-19 has not been determined and no specific antiviral treatment or vaccine is currently available. Based on the published data, this review systematically discusses the etiology, epidemiology, clinical characteristics, and current intervention measures related to COVID-19 in the hope that it may provide a reference for future studies and aid in the prevention and control of the COVID-19 epidemic.

negative: Prospect and application of Internet of Things technology for prevention of SARIs Abstract The Internet of Things (IoT) includes three core procedures: full spectrum perception, reliable transmission, and intelligent processing. It can be applied for the prevention and control of SARI (severe acute respiratory infection). By combining sensors, information technology, artificial intelligence, and available dynamic networking devices, IoT could realize long-distance communication between hospitals, patients, and medical devices, which could ultimately improve current medical conditions.

negative: Apps Gone Rogue: Maintaining Personal Privacy in an Epidemic Containment, the key strategy in quickly halting an epidemic, requires rapid identification and quarantine of the infected individuals, determination of whom they have had close contact with in the previous days and weeks, and decontamination of locations the infected individual has visited. Achieving containment demands accurate and timely collection of the infected individual's location and contact history. Traditionally, this process is labor intensive, susceptible to memory errors, and fraught with privacy concerns. With the recent almost ubiquitous availability of smart phones, many people carry a tool which can be utilized to quickly identify an infected individual's contacts during an epidemic, such as the current 2019 novel Coronavirus crisis. Unfortunately, the very same first-generation contact tracing tools have been used to expand mass surveillance, limit individual freedoms and expose the most private details about individuals. We seek to outline the different technological approaches to mobile-phone based contact-tracing to date and elaborate on the opportunities and the risks that these technologies pose to individuals and societies. We describe advanced security enhancing approaches that can mitigate these risks and describe trade-offs one must make when developing and deploying any mass contact-tracing technology. With this paper, our aim is to continue to grow the conversation regarding contact-tracing for epidemic and pandemic containment and discuss opportunities to advance this space. We invite feedback and discussion.

negative: Current status of treatment for 2019 novel coronavirus pneumonia/ 中华微生物学和免疫学杂志 2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus (SARS-CoV) and middle east respiratory syndrome-coronavirus (MERS-CoV). At present, there is no specific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019 novel coronavirus pneumonia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.

negative: Human Coronavirus-229E, -OC43, -NL63, and -HKU1 Abstract Seven human coronaviruses (HCoVs) have been so far identified, namely HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the novel coronavirus (2019-nCoV, a.k.a. SARS-CoV-2). Unlike the highly pathogenic SARS-CoV, MERS-CoV, and 2019-nCoV, the four so-called common HCoVs generally cause mild upper-respiratory tract illness and contribute to 15%–30% of cases of common colds in human adults, although severe and life-threatening lower respiratory tract infections can sometimes occur in infants, elderly people, or immunocompromised patients. In this article, we review the molecular virology of these common HCoVs, and summarize current knowledge on HCoV-host interaction, pathogenesis, and other clinically relevant perspectives.

negative: Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.

negative: The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China Abstract The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002–2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.

negative: A database of geopositioned Middle East Respiratory Syndrome Coronavirus occurrences As a World Health Organization Research and Development Blueprint priority pathogen, there is a need to better understand the geographic distribution of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and its potential to infect mammals and humans. This database documents cases of MERS-CoV globally, with specific attention paid to zoonotic transmission. An initial literature search was conducted in PubMed, Web of Science, and Scopus; after screening articles according to the inclusion/exclusion criteria, a total of 208 sources were selected for extraction and geo-positioning. Each MERS-CoV occurrence was assigned one of the following classifications based upon published contextual information: index, unspecified, secondary, mammal, environmental, or imported. In total, this database is comprised of 861 unique geo-positioned MERS-CoV occurrences. The purpose of this article is to share a collated MERS-CoV database and extraction protocol that can be utilized in future mapping efforts for both MERS-CoV and other infectious diseases. More broadly, it may also provide useful data for the development of targeted MERS-CoV surveillance, which would prove invaluable in preventing future zoonotic spillover.

negative: SARS – a perspective from a school of nursing in Hong Kong Background. Severe acute respiratory syndrome (SARS) is a new infectious disease with significant morbidity and mortality that has had a major impact on health and health care services worldwide. Hong Kong has had a significant number of cases and deaths. Nurses, at the vanguard of the clinical health care team, have been particularly affected by it. The outbreak prompted the health authorities to implement a series of public health measures and hospital policies, including a guideline for the diagnosis and management of patients with SARS. Aims and objectives. This paper aims at providing an overview of what is known about SARS and the impact it has had in Hong Kong and to highlight from the perspective of a school of nursing the major clinical, educational and public health implications. Conclusions. The lack of understanding and uncertainty about the disease led to significant variation in the provision of information, contributing to the confusion and anxiety in the community. Therefore, there is a need to revise the nursing curriculum, to provide continuing education to all health care professionals, particularly with regard to infection control measures, and to revisit the range of public health policies to ensure the health of the community is protected by these policies. There also has been a reaffirmation of the importance of health promotion that highlights the importance of the partnership between nurses, health policy makers and public health personnel. It is evident that the organization and delivery of clinical practice, teaching and health promotion have to be flexible and responsive to a changing health scenario. Relevance to clinical practice. Nurses must play a crucial role in the prevention, detection and containment of SARS. They will need to implement and ensure strict adherence to infection control measures and, in some circumstances, isolation and quarantine may be warranted. Attention to the psychological state of patients and family members should not be overlooked. Paramount is education of patients, families and members of the public at large.

negative: Efficiency of Airborne Sample Analysis Platform (ASAP) bioaerosol sampler for pathogen detection The threat of bioterrorism and pandemics has highlighted the urgency for rapid and reliable bioaerosol detection in different environments. Safeguarding against such threats requires continuous sampling of the ambient air for pathogen detection. In this study we investigated the efficacy of the Airborne Sample Analysis Platform (ASAP) 2800 bioaerosol sampler to collect representative samples of air and identify specific viruses suspended as bioaerosols. To test this concept, we aerosolized an innocuous replication-defective bovine adenovirus serotype 3 (BAdV3) in a controlled laboratory environment. The ASAP efficiently trapped the surrogate virus at 5 × 10(3) plaque-forming units (p.f.u.) [2 × 10(5) genome copy equivalent] concentrations or more resulting in the successful detection of the virus using quantitative PCR. These results support the further development of ASAP for bioaerosol pathogen detection.

negative: Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

negative: Higher Body Mass Index is an Important Risk factor in COVID-19 patients: A Systematic Review Background: Globally, both obesity and underweight are severe health risks for various diseases. The current study systematically examines the emerging evidence to identify an association between Body Mass Index (BMI) and COVID-19 disease outcome. Methods: Online literature databases (e.g., Google Scholar, PubMed, MEDLINE, EMBASE, Scopus, Medrixv and BioRixv) were screened following standard search strategy having the appropriate keyword such as Obesity, Underweight, BMI, Body Mass Index, 2019-nCov, COVID-19, novel coronavirus, coronavirus disease. Studies published till 20th April 2020 were included without language restriction. These studies include case reports, case series, cohort, and any other which reported BMI, overweight/obesity or underweight, and its complication with COVID-19 disease. Findings: Obesity plays a significant part in the pathogenesis of COVID-19 patients, though the role of BMI in the COVID-19 pandemic must not be ignored. Interpretation: Consequences of inflammation of adipose tissue has been reported as a leading cause of insulin resistance and hypertension due to metabolic dysfunction. The results of the current study show that BMI plays a significant role in COVID-19 severity in all ages, especially the elderly population. A panel should review COVID-19 patients with higher BMI and other co-morbidities, and they should be given increased vigilance, testing priority, and therapy. Further, the COVID-19 patients whose illness entered 7-10 days, age >50 yrs, and elevated CRP levels should have additional medical considerations. Recommendation: Population and patients with high BMI have moderate to high risk of medical complications with COVID-19, and hence their health status should be monitored more frequently. Keywords: Age, BMI, COVID-19, Obesity.

negative: Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and shedding BACKGROUND: The prevalence, symptom course, and shedding in persons infected with the 4 most common human coronaviruses (HCoV)‐229E, HKU1, NL63, and OC43 are poorly described. OBJECTIVES: We estimate their prevalence and associated symptoms among college students identified via a social network study design. PATIENTS/METHODS: We collected 1‐3 samples (n = 250 specimens) from 176 participants between October 2012 and January 17, 2013: participants with acute respiratory infection (ARI; cough and body aches or chills or fever/feverishness) and their social contacts. Virus was detected using RT‐PCR. RESULTS: 30.4% (76/250) of specimens tested positive for any virus tested, and 4.8% (12/250) were positive for 2 or more viruses. Human coronaviruses (HCoVs [22.0%; 55/250]), rhinovirus (7.6%; 19/250), and influenza A (6.4%; 16/250) were most prevalent. Symptoms changed significantly over time among ARI participants with HCoV: the prevalence of cough and chills decreased over 6 days (P = .04, and P = .01, respectively), while runny nose increased over the same period (P = .02). HCoV‐NL63 was the most frequent virus detected 6 days following symptom onset (8.9%), followed by rhinovirus (6.7%). CONCLUSIONS: During a 3‐month period covering a single season, HCoVs were common, even among social contacts without respiratory symptoms; specific symptoms may change over the course of HCoV‐associated illness and were similar to symptoms from influenza and rhinovirus.

negative: An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemic, epidemic and bat coronavirus Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV 2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to another nucleoside analog inhibitor. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (b-D-N4-hydroxycytidine-5’-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.

negative: The Novel Coronavirus – A Snapshot of Current Knowledge Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.

negative: Management of the dead during COVID-19 outbreak in Malaysia The emergence of a novel human coronavirus, SARS-CoV-2, causing severe respiratory tract infections in humans, is affecting all countries of the world and has become a global health concern. Since the virus was first identified in December 2019, the number of deaths have been propagating exponentially, causing countries across the world, including Malaysia, to increase emergency measures to combat the virus. Due to the fact that the COVID-19 pandemic does not discriminate its victims, it is of paramount importance to construct a plan for management of the dead for all suspected or confirmed COVID-19 cases, including the unidentified deceased, as an essential portion of the humanitarian forensic action approach. This document provides an overview on ways to maximize the local collective capacity from various government agencies to manage the dead based on the prevailing regulations and legislation in the country, in preparation for possible large scale deaths from this pandemic. The National Institute of Forensic Medicine Malaysia has improvised procedures and guidelines for management of the dead within the existing regulations in order to achieve a balance between medicolegal requirements and the safety of personnel managing the bodies of the deceased with suspected or confirmed COVID-19 infection; at the site of death, during transport, during postmortem procedures, storage and preparation before and during burial or cremation as well as environmental cleaning and disinfection, involving various agencies in the country. A form of temporary controlled burial is as an option to allow the reinvestigation of a decedent to help formally identify victims of the pandemic such as undocumented migrants or refugees who were previously not identified. Due to the different legal requirements and mortality rates between countries, there is no one-size-fits-all approach to the management of the dead. Whenever possible, every opportunity and assistance must be given to families to mourn their loved ones, even in times of crisis or an outbreak, in order to sustain an appropriate level of dignity and respect.

negative: Coronavirus, humanpathogenes Humanes Coronavirus, Gruppe 1 Coronavirus

negative: COVID-19: what has been learned and to be learned about the novel coronavirus disease The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.

negative: Return of the Coronavirus: 2019-nCoV The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.

negative: Chapter 12 Quality control and testing evaluation of pharmaceutical aerosols Abstract Drug delivery to the respiratory tract locally has become an increasingly effective and important therapeutic method for treating a variety of pulmonary disorders, including chronic abstractive disease, asthma, bronchitis, pneumonia, and cystic fibrosis. Increase in prevalence respiratory disorders is a major factor driving the growth of global respiratory inhaler devices market. The effectiveness of pharmaceutical aerosols therapeutic performance is affected by various factors such as type and characteristics of propellants, whose properties are vapor pressure of propellants, viscosity and density flash point and also other factors such as type and characteristics of active ingredients, containers, valves, and actuators, along with percentage of moisture content and mechanism of emitted dose deposition, spray pattern, efficiency of valve crimping, and measurement of particle size aerosols. The purpose of this book chapter is to discuss the in-process and finished product quality control tests for pharmaceutical aerosols based on pharmacopeia standards and specifications.

negative: Social and administrative issues related to the COVID-19 pandemic in Pakistan: better late than never The study critically reviewed Pakistan’s provincial updates of coronavirus disease 2019 (COVID-19) and discussed the current challenges faced by the government in a given context. The coronavirus-associated death tolls have been increasing rapidly in a country. The provincial status of confirmed cases of coronavirus is higher in Punjab, followed by the Sindh, Khyber Pakhtunkhwa (KPK), and Balochistan. The case fatality ratio shows that KPK has a higher ratio, i.e., 5.11%, followed by the Punjab, i.e., 1.82%; Sindh, i.e., 1.80%; Balochistan, i.e., 1.28%; Gilgit-Baltistan, i.e., 0.71%; and Federal territory, i.e., 0.66%. The country has a less testing capacity to identify more suspected coronavirus patients. The study calculated that if we increase five times our testing capacity from the current date, the total registered cases will be reached to 137,370 and death tolls will increase up to 3090. It is highly needed to increase testing capacity across Pakistan in order to minimize the outbreak of coronavirus. The provincial government should follow the Federal Government instructions to contain coronavirus by increasing testing capacities, tracing suspected patients, smart lockdowns, emergency relief to the poor, and vigilant monitoring system.

negative: β-coronavirus infectious diseases: recommended strategies for the prevention and control of transmission. In recent years, the incidence and mortality of infectious diseases in China are increasing. Infectious diseases, especially new infectious diseases, seriously threaten people's lives. Recent works found that most of the emerging infectious diseases come from wild life. At the same time, the impact of human activities on the environment has further deteriorated the living environment of wildlife. However, with the conducted in-depth research on virus, human beings increase the risk of getting infected. Taking Beta Coronavirus as the example, we analyzed the transmission risks of coronavirus in the prevention and control of the outbreaks of emerging infectious diseases, and recommend the prevention and control strategies before, during and after the viral outbreak. Additional works are urgently needed to better define the biological and epidemiological characteristics of these viruses.

negative: Transmission Cycle of SARS-CoV and SARS-CoV-2 Severe acute respiratory syndrome (SARS) is a pandemic that has shocked the world twice over the last two decades caused by a highly transmissible and pathogenic coronavirus (CoV). It causes disease in the lower respiratory tract in humans that was first reported in late 2002 in Guangdong province, China, and later on in December 2019 in Wuhan, China. The two viruses designated as SARS-CoV and SARS-CoV-2, respectively, originated probably from the bat and infected humans via carrier animals. The constant recombination and evolution in the CoV genome may have facilitated their cross-species transmission resulting in recurrent emergence as a pandemic. This chapter intends to accumulate recent findings related to CoV transmission and tentative molecular mechanisms governing the process.

negative: Evolutionary Medicine: A Powerful Tool for Improving Human Health Modern evolutionary research has much to contribute to medical research and health care practices. Conversely, evolutionary biologists are tapping into the rapidly expanding databases of medical genomic information to further their research. These two fields, which have historically functioned in almost complete isolation, are finding mutual benefit in the exchange of information. The long-term benefits of this synthesis of two major areas of research include improved health care. Recently, efforts to catalyze this relationship have brought together evolutionary biologists, medical practitioners, anthropologists, and ethicists to lay the groundwork for further collaboration and exploration. The range of overlap is surprisingly broad and potentially invaluable.

negative: Indoor Microbial Aerosol and Its Health Effects: Microbial Exposure in Public Buildings – Viruses, Bacteria, and Fungi Mechanisms of aerosolization of microorganisms, composition and dynamics of microbioaerosol are characterized. As well as methods of its detection, incl. modern equipment set-ups and sampling procedures recommended are outlined. Medical impact of (indoor) air disperged viral, bacterial and fungal propagules (allergies, intoxications, infections), together with the related European legislation is summarized. An overview of real mycoaerosol conditions in our dwellings and their outdoors with different microclimate, settlement and building types, household characteristics and health state of occupants is given, too. Finally, examples of several possible health damages due to exposition to (aerosolized) fungal toxicants in vitro and in vivo are demonstrated.

negative: COVID-19 in a Designated Infectious Diseases Hospital Outside Hubei Province, China. BACKGROUND The clinical characteristics of novel coronavirus disease (COVID-2019) patients outside the epicenter of Hubei province are less understood. METHODS We analyzed the epidemiological and clinical features of all COVID-2019 cases in the only referral hospital in Shenzhen city, China from January 11, 2020 to February 6, 2020 and followed until March 6, 2020. RESULTS Among the 298 confirmed cases, 233 (81.5%) had been to Hubei while 42 (14%) did not have a clear travel history. Only 192(64.4%) cases had a fever as the initial symptom. Compared to the non-severe cases, severe cases were associated with older age, those with underlying diseases, as well as higher levels of C-reactive protein, interleukin-6, and erythrocyte sedimentation rate. Slower clearance of the virus was associated with a higher risk of progression to critical condition. As of March 6, 2020, 268 (89.9%) patients were discharged and the overall case fatality ratio was 1.0%. CONCLUSIONS In a designated hospital outside Hubei Province, COVID-2019 patients could be effectively managed by properly using the existing hospital system. Mortality may be lowered when cases are relatively mild and there are sufficient medical resources to care and treat the disease.

negative: Why are pregnant women susceptible to COVID-19? An immunological viewpoint Abstract The 2019 novel coronavirus disease (COVID-19) was first detected in December 2019 and became epidemic in Wuhan, Hubei Province, China. COVID-19 has been rapidly spreading out in China and all over the world. The virus causing COVID-19, SARS-CoV-2 has been known to be genetically similar to severe acute respiratory syndrome coronavirus (SARS-CoV) but distinct from it. Clinical manifestation of COVID-19 can be characterized by mild upper respiratory tract infection, lower respiratory tract infection involving non-life threatening pneumonia, and life-threatening pneumonia with acute respiratory distress syndrome. It affects all age groups, including newborns, to the elders. Particularly, pregnant women may be more susceptible to COVID-19 since pregnant women, in general, are vulnerable to respiratory infection. In pregnant women with COVID-19, there is no evidence for vertical transmission of the virus, but an increased prevalence of preterm deliveries has been noticed. The COVID-19 may alter immune responses at the maternal-fetal interface, and affect the well-being of mothers and infants. In this review, we focused on the reason why pregnant women are more susceptible to COVID-19 and the potential maternal and fetal complications from an immunological viewpoint.

negative: Mouse hepatitis coronavirus replication induces host translational shutoff and mRNA decay, with concomitant formation of stress granules and processing bodies Many viruses, including coronaviruses, induce host translational shutoff, while maintaining synthesis of their own gene products. In this study we performed genome‐wide microarray analyses of the expression patterns of mouse hepatitis coronavirus (MHV)‐infected cells. At the time of MHV‐induced host translational shutoff, downregulation of numerous mRNAs, many of which encode protein translation‐related factors, was observed. This downregulation, which is reminiscent of a cellular stress response, was dependent on viral replication and caused by mRNA decay. Concomitantly, phosphorylation of the eukaryotic translation initiation factor 2α was increased in MHV‐infected cells. In addition, stress granules and processing bodies appeared, which are sites for mRNA stalling and degradation respectively. We propose that MHV replication induces host translational shutoff by triggering an integrated stress response. However, MHV replication per se does not appear to benefit from the inhibition of host protein synthesis, at least in vitro, since viral replication was not negatively affected but rather enhanced in cells with impaired translational shutoff.

negative: The cutting edge of thoracic anesthesia during the 2019 coronavirus disease (COVID-19) outbreak Coronavirus disease 2019 (COVID-19) has quickly spread globally, causing a real pandemic. In this critical scenario, lung cancer patients scheduled for surgical treatment need to continue to receive optimal care while protecting them from an eventual severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Adequate use of personal protective equipment (PPE) during aerosol-generating procedures (AGPs) and a COVID-19 specific intraoperative management are paramount in order to prevent cross infections. New suggestions or improvement of existing contagion control guidance are needed, even in case of non-symptomatic patients, possibly responsible for virus spread.

negative: Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China Background: Cases with coronavirus disease 2019 (COVID-19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside-Wuhan patients to assess the transmission and clinical characteristics of this illness. Methods: Contact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 12, 2020. Demographic, clinical, laboratory and radiological characteristics, medication therapy and outcomes were collected and analyzed. Patients were confirmed by PCR test. Results: Of the 104 patients, 48 (46.15%) were imported cases and 56 (53.85%) were indigenous cases; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 &ldquo:generations” was observed. Mean age was 43 (rang, 8-84) years (including 3 children) and 49 (47.12%) were male. Most patients had typical symptoms, 5 asymptomatic infections were found and 2 of them infected their relatives. The median incubation period was 6 (rang, 1-32) days, of 8 patients ranged from 18 to 32 days. Just 9 of 16 severe patients required ICU care. Until Feb 12, 2020, 40 (38.46%) discharged and 1 (0.96%) died. For the antiviral treatment, 80 (76.92%) patients received traditional Chinese medicine therapy. Conclusions: Family but not community transmission occupied the main body of infections in the two centers. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID-19. The incubation period of 8 patients exceeded 14 days.

negative: Resistance of Berne virus to physical and chemical treatment Thermal inactivation of Berne virus proceeded at a linear rate between 31°C and 43°C. Storage at temperatures lower than −20°C preserved the infectivity, while at 4°C appreciable loss occurred between 92 and 185 days. Freeze-drying or desiccation at 22°C caused only insignificant loss of infectivity. Virus preparations were not affected by pH values between 2.5 and 10.3. Inactivation by UV occurred more rapidly than with herpes, toga and rhabdoviruses. Berne virus infectivity was sensitive to pronase and B. subtilis proteinase. It was not inactivated by trypsin and chymotrypsin treatment, which resulted in enhancement of infectivity; low concentrations of pronase (< 10 μg ml(−1)) had a similar effect on Berne virus. Neither phospholipase C or RNase, alone or in combination, nor sodium deoxycholate (0.1%) inactivated the virus; in contrast, Triton X-100 (0.1%, 1.0%) caused rapid inactivation with a constant level of residual infectivity.

negative: Perspectives from the Cancer and Aging Research Group: Caring for the vulnerable older patient with cancer and their caregivers during the COVID-19 crisis in the United States

negative: 27 Evolution of SARS Coronavirus and the Relevance of Modern Molecular Epidemiology Severe acute respiratory syndrome (SARS) is the first major zoonotic infectious disease of the twenty-first century. The disease, originally termed “atypical pneumonia,” was first recognized in November 2002 in Guangdong Province, China, which spread rapidly to 26 countries within 5 months and eventually led to 8096 human infection cases and 774 deaths. A previously unrecognized coronavirus, SARS coronavirus (SARS-CoV), was later identified as the causative agent of the SARS. Subsequent investigation indicated that the source of the human infections was most likely originated from infected wildlife animals traded in the live animal markets, with masked palm civets being considered the most prominent and important carrier. Large-scale culling of civets appeared to have prevented further outbreaks in the region. Further epidemiological studies showed that civets are intermediate hosts of SARS-CoV, and bats are the likely natural reservoir of SARS-CoV and a large number of SARS-like coronaviruses (SL-CoVs). Detailed analysis of the massive SARS-CoV genomic sequence data accumulated indicated that SARS-CoV experienced a strong selection pressure during different outbreak phases in humans as well as interspecies transmission from animals to humans. The spike glycoprotein (S) of SARS-CoV plays a key role in virus–host interaction and hence is a key determinant of interspecies transmission. It has been shown that minor changes of amino acid (aa) residues in the S protein could lead to dramatic changes in virus susceptibility in animal and human hosts. This chapter will focus on the genetics and evolution of SARS-CoVs and SL-CoVs in humans, civets, and bats. The events of SARS outbreaks and the accompanying response activities highlight the importance of modern molecular epidemiology in disease investigation and the urgent need to broaden the screening and investigation of unknown viruses in wildlife animals.

negative: Activity profiling and structures of inhibitor-bound SARS-CoV-2-PLpro protease provides a framework for anti-COVID-19 drug design In December 2019, the first cases of a novel coronavirus infection causing COVID-19 were diagnosed in Wuhan, China. Viral Papain-Like cysteine protease (PLpro, NSP3) is essential for SARS-CoV-2 replication and represents a promising target for the development of antiviral drugs. Here, we used a combinatorial substrate library containing natural and a wide variety of nonproteinogenic amino acids and performed comprehensive activity profiling of SARS-CoV-2-PLpro. On the scaffold of best hits from positional scanning we designed optimal fluorogenic substrates and irreversible inhibitors with a high degree of selectivity for SARS PLpro variants versus other proteases. We determined crystal structures of two of these inhibitors (VIR250 and VIR251) in complex with SARS-CoV-2-PLpro which reveals their inhibitory mechanisms and provides a structural basis for the observed substrate specificity profiles. Lastly, we demonstrate that SARS-CoV-2-PLpro harbors deISGylating activities similar to SARS-CoV-1-PLpro but its ability to hydrolyze K48-linked Ub chains is diminished, which our sequence and structure analysis provides a basis for. Altogether this work has revealed the molecular rules governing PLpro substrate specificity and provides a framework for development of inhibitors with potential therapeutic value or drug repositioning.

negative: [Detection of the anti-SARS-coronavirus specific antibody levels in 156 SARS patients]. The objective of this study was to explore the development of IgG and IgM against SARS CoV and characteristics of changes of antibody titers in patients with severe acute respiratory syndrome (SARS) and to search the opportunity for collecting specific anti-serum from convalescent patients with SARS. The anti-SARS-coronavirus specific antibody levels in 156 SARS patients were measured with ELISA. The results showed that the total positive rates of IgG and IgM were 75.6% and 41.7% respectively, and the negative rate of both IgG and IgM was 23.7%. The average titers of IgG and IgM antibody in positive samples were 18.23 +/- 24.72 and 2.18 +/- 1.13, respectively. There was no significant correlation between the titers of IgG/IgM and sex, age, course of diseases and duration of body temperature recovery. It was concluded that not all SARS patients could produce the anti-SARS-coronavirus specific antibody. The titers of the anti-body are diversified even if the antibodies have been emerged in them. In order to obtain effective anti-serum, the titers of antibody must be tested just before collection of convalescent serum, and it ensures the therapeutic effect and provides a measurable index for clinical transfusion.

negative: Anthropocenic war: coronavirus and total demobilization This paper argues that the covid-19 coronavirus pandemic of 2019–2020 constituted the first Anthropocenic war: as an anthropogenic virus and biological attack on the human body and as the first global pandemic requiring a truly global response since our recognition of the Anthropocene. The paper explores how each nation was forced by the virus into a pause of global connections and relationships and a war against the human body, with the ‘total demobilization’ and bunkerization of their domestic populations. With space cut-off, this became a war of time and of endurance, with relations reduced, as Virilio suggests, to those of the connected ‘terminal citizen’. Beyond the civil war against the body, however, there was also the civil war within the domestic populations who were active participants in this imploded home front line, producing and sharing both feel-good and disciplinary propaganda and engaging in debates around politics, conspiracy theories and disinformation. The paper explores the problems governments face in remobilization, the new data regime of informational totalitarianism remobilization will help produce and the likely instability of the post-covid-19 international order. It concludes that this ‘war’ was only the beginning and that anthropogenic environmental factors will play an increasing role in human conflicts in coming years.

negative: Recent progress in understanding 2019 novel coronavirus (SARS-CoV-2) associated with human respiratory disease: detection, mechanisms and treatment ABSTRACT Viral respiratory diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) always pose a severe threat to people. First identified in late December 2019, a novel coronavirus (2019-nCoV; SARS-CoV-2) has affected many provinces in China and multiple countries worldwide. The viral outbreak has aroused panic and a public-health emergency around the world, and the number of infections continues to rise. However, the causes and consequences of the pneumonia remain unknown. To effectively implement epidemic prevention, early identification and diagnosis are critical to disease control. Here we scrutinise a series of available studies by global scientists on the clinical manifestations, detection methods and treatment options for the disease caused by SARS-CoV-2, named coronavirus disease 2019 (COVID-19), and also propose potential strategies for preventing the infection.

negative: Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.

negative: Habitat disturbance results in chronic stress and impaired health status in forest-dwelling paleotropical bats Anthropogenic habitat disturbance is a major threat to biodiversity worldwide. Yet, before population declines are detectable, individuals may suffer from chronic stress and impaired immunity in disturbed habitats, making them more susceptible to pathogens and adverse weather conditions. Here, we tested in a paleotropical forest with ongoing logging and fragmentation, whether habitat disturbance influences the body mass and immunity of bats. We measured and compared body mass, chronic stress (indicated by neutrophil to lymphocyte ratios) and the number of circulating immune cells between several bat species with different roost types living in recovering areas, actively logged forests, and fragmented forests in Sabah, Malaysia. In a cave-roosting species, chronic stress levels were higher in individuals from fragmented habitats compared with conspecifics from actively logged areas. Foliage-roosting species showed a reduced body mass and decrease in total white blood cell counts in actively logged areas and fragmented forests compared with conspecifics living in recovering habitats. Our study highlights that habitat disturbance may have species-specific effects on chronic stress and immunity in bats that are potentially related to the roost type. We identified foliage-roosting species as particularly sensitive to forest habitat deterioration. These species may face a heightened extinction risk in the near future if anthropogenic habitat alterations continue.

negative: Putting a balance on the aerosolization debate around SARS-CoV-2

negative: Operating during the COVID-19 pandemic: How to reduce medical error Our professional and private lives changed on March 11 2020 when the coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO. By March 16, surgical training was suspended, MRCS and FRCS examinations cancelled and all courses postponed. In theory, essential cancer surgery, emergency and trauma operating will continue. All elective, non-essential cases are currently cancelled. While we adapt to our new ways of working, we remind ourselves that surgeons are flexible, resilient and, ultimately, we are doctors in the first instance. We present a short article on operating during the COVID-19 pandemic.

negative: Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S(1)/S(2) subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

negative: [Rotavirus and other viruses of diarrhea]. Rotaviruses represent 80% of recognized viral etiologies and 140 million cases of diarrhea per year. They strike young children with similar frequency throughout the world, but the mortality rate is high in developing countries only, with some 870,000 deaths per year (WHO, 1997). Rotaviruses belong to the family of Reoviridae; they are segmented bicatenary RNA viruses, which explains their genetic variability, the presence of mixed infections, the establishment for some time already of a molecular epidemiology by electrophore types. The viruses are "naked" and thus resistant to the outside environment; their massive elimination, 10(8) to 10(10)viral particles per gram of faeces, begins with the first day of diarrhea. They are found in used water and can also be concentrated by shellfish; the environment thus constitutes a notable reservoir for the virus. Oral-faecal transmission is facilitated by deficient sanitary conditions. The 11 fragments of the genome each codify for 1 viral protein; 2 surface proteins, VP4 and VP7, bring about the formation of neutralizing antibodies, which are important for the protection and determination of different serotypes. A non structural protein--NSP4--would seem to intervene in the cytopathogenic effect and may act as a veritable viral enterotoxine. Numerous animal species are infected by rotaviruses which are district from the human ones. The pathology as it affects animals is of economic importance and of interest as an experimental and vaccinal model. Between human and animal rotaviruses there can be genetic rematchings and the VP6 protein is an antigen common to the group. The description of the other viruses responsible for diarrhea has benefited from widespread use of electronic microscopes from the very first years of study of rotaviruses. These other viruses belong to 6 different types: adenovirus, calcivirus, astrovirus, Norwalk agent and related viruses, coronavirus, enterovirus. They therefore have a structural and antigenic polymorphism but, except for the coronavirus, they are all "naked" virions with resistance in outside environments and means of transmission analogous to the rotaviruses. Clinical signs of viral gastroenterites, the age of the patient and epidemiological circumstances help in making an etiological diagnosis; the biological diagnosis has been simplified for the rotaviruses and the adenoviruses. Epidemics related to food, or of hydric and nosocomial origin, especially those due to the Norwalk agent, are under-declared and more frequent than those of bacterial origin. The prevention of dangers related to faeces, the improvement of sanitary conditions, health education, and better nutrition contribute to rotavirus prevention, but rotavirus diarrheas, the incidence of which is similar in developed and developing countries, would be more efficiently controlled through vaccination.

negative: A framework for capturing the interactions between laypersons’ understanding of disease, information gathering behaviors, and actions taken during an epidemic Abstract This paper provides a description of a methodological framework designed to capture the inter-relationships between the lay publics’ understanding of health-related processes, information gathering behaviors, and actions taken during an outbreak. We developed and refined our methods during a study involving eight participants living in severe acute respiratory syndrome (SARS)-affected areas (Hong Kong, Taiwan, and Toronto). The framework is an adaptation of narrative analysis, a qualitative method that is used to investigate a phenomenon through interpretation of the stories people tell about their experiences. From our work, several hypotheses emerged that will contribute to future research. For example, our findings showed that many decisions in an epidemic are carefully considered and involve use of significant information gathering. Having a good model of lay actions based on information received and beliefs held will contribute to the development of more effective information support systems in the event of a future epidemic.

negative: The basic reproduction number of SARS-CoV-2 in Wuhan is about to die out, how about the rest of the World? The virologically confirmed cases of a new coronavirus disease (COVID-19) in the world are rapidly increasing, leading epidemiologists and mathematicians to construct transmission models that aim to predict the future course of the current pandemic. The transmissibility of a virus is measured by the basic reproduction number ( R0 ), which measures the average number of new cases generated per typical infectious case. This review highlights the articles reporting rigorous estimates and determinants of COVID-19 R0 for the most affected areas. Moreover, the mean of all estimated R0 with median and interquartile range is calculated. According to these articles, the basic reproduction number of the virus epicentre Wuhan has now declined below the important threshold value of 1.0 since the disease emerged. Ongoing modelling will inform the transmission rates seen in the new epicentres outside of China, including Italy, Iran and South Korea.

negative: Emerging diseases at the interface of people, domestic animals and wildlife. The role of wildlife in our understanding of highly pathogenic avian influenza.

negative: Molecular basis of COVID-19 relationships in different species: a one health perspective Abstract Outside the Hubei province, China, the mild form of infection and the progressive recover of the COVID-19 patients suggest the intervention of “unconventional” biological mechanisms worthy of attention. Based on the high-homology between the Spike protein epitopes of taxonomically-related coronaviruses, we hypothesized that past contact with infected dogs shield humans against the circulating SARS-CoV-2. Elseways, the recurrent virus exposure over a short time-lapse might result in the Antibody Dependent Enhancement, triggering the violent immune reaction responsible for the severe clinical outcomes observed in the Hubei province. Nevertheless, further experimental studies are desired for a confidential evaluation of the postulated hypotheses.

negative: New understanding of the damage of SARS-CoV-2 infection outside the respiratory system Abstract Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3,000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.

negative: Novel coronavirus infection in children outside of Wuhan, China BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID‐19) has spread rapidly, but information about children with COVID‐19 is limited. METHODS: This retrospective and the single‐center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID‐19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019‐nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019‐nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground‐glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT‐PCR for 2019‐nCoV and were discharged. The median time from exposure to a negative RT‐PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.

negative: Gastrointestinal Disease in Exotic Small Mammals Abstract Exotic small mammal medicine is a relatively new specialty area within veterinary medicine. Ferrets, rabbits, and rodents have long been used as animal models in human medical research investigations, resulting in a body of basic anatomic and physiologic information that can be used by veterinarians treating these species. Unfortunately, there is a paucity of veterinary articles that describe clinical presentation, diagnosis, and treatment options of gastrointestinal (GI) disease as it affects exotic small mammals. Although there is little reference material relating to exotic small mammal GI disease, patients are commonly presented to veterinary hospitals with digestive tract disorders. This article provides the latest information available for GI disease in ferrets (Helicobacter mustelae gastritis, inflammatory bowel disease [IBD], GI lymphoma, systemic coronavirus, coccidiosis, and liver disease), rabbits (GI motility disorders, liver lobe torsion, astrovirus, and coccidiosis), guinea pigs (gastric dilatation volvulus [GDV]), rats (Taenia taeniaeformis), and hamsters (Clostridium difficile). Both noninfectious diseases and emerging infectious diseases are reviewed as well as the most up-to-date diagnostics and treatment options.

negative: The ocular surface, coronaviruses and COVID‐19 The ocular surface has been suggested as a site of infection with Coronavirus‐2 (SARS‐CoV‐2) responsible for the coronavirus disease‐19 (COVID‐19). This review examines the evidence for this hypothesis, and its implications for clinical practice. Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2), responsible for the COVID‐19 pandemic, is transmitted by person‐to‐person contact, via airborne droplets, or through contact with contaminated surfaces. SARS‐CoV‐2 binds to angiotensin converting enzyme‐2 (ACE2) to facilitate infection in humans. This review sets out to evaluate evidence for the ocular surface as a route of infection. A literature search in this area was conducted on 15 April 2020 using the Scopus database. In total, 287 results were returned and reviewed. There is preliminary evidence for ACE2 expression on corneal and conjunctival cells, but most of the other receptors to which coronaviruses bind appear to be found under epithelia of the ocular surface. Evidence from animal studies is limited, with a single study suggesting viral particles on the eye can travel to the lung, resulting in very mild infection. Coronavirus infection is rarely associated with conjunctivitis, with occasional cases reported in patients with confirmed COVID‐19, along with isolated cases of conjunctivitis as a presenting sign. Coronaviruses have been rarely isolated from tears or conjunctival swabs. The evidence suggests coronaviruses are unlikely to bind to ocular surface cells to initiate infection. Additionally, hypotheses that the virus could travel from the nasopharynx or through the conjunctival capillaries to the ocular surface during infection are probably incorrect. Conjunctivitis and isolation of the virus from the ocular surface occur only rarely, and overwhelmingly in patients with confirmed COVID‐19. Necessary precautions to prevent person‐to‐person transmission should be employed in clinical practice throughout the pandemic, and patients should be reminded to maintain good hygiene practices.

negative: COVID-19 vaccines: A race against time in the middle of death and devastation! The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in Research & Development (R&D) by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.

negative: A novel subset of putative stem/progenitor CD34(+)Oct-4(+) cells is the major target for SARS coronavirus in human lung Identification of the nature of severe acute respiratory syndrome (SARS)-infected cells is crucial toward understanding the pathogenesis. Using multicolor colocalization techniques, we previously reported that SARS(+) cells in the lung of fatally infected patients expressed the only known functional receptor, angiotensin-converting enzyme 2, and also a binding receptor, liver/lymph node–specific ICAM-3–grabbing non-integrin (CD209L). In this study, we show that SARS-infected cells also express the stem/progenitor cell markers CD34 and Oct-4, and do not express cytokeratin or surfactant. These putative lung stem/progenitor cells can also be identified in some non-SARS individuals and can be infected by SARS-coronavirus ex vivo. Infection of these cells may contribute to the loss of lung repair capacity that leads to respiratory failure as clinically observed.

negative: COVID-19 Outbreak: An Overview BACKGROUND: In late December 2019, Chinese health authorities reported an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province. SUMMARY: A few days later, the genome of a novel coronavirus was released (http://virological.org/t/novel-2019-coronavirus-genome/319; Wuhan-Hu-1, GenBank accession No. MN908947) and made publicly available to the scientific community. This novel coronavirus was provisionally named 2019-nCoV, now SARS-CoV-2 according to the Coronavirus Study Group of the International Committee on Taxonomy of Viruses. SARS-CoV-2 belongs to the Coronaviridae family, Betacoronavirus genus, subgenus Sarbecovirus. Since its discovery, the virus has spread globally, causing thousands of deaths and having an enormous impact on our health systems and economies. In this review, we summarize the current knowledge about the epidemiology, phylogenesis, homology modeling, and molecular diagnostics of SARS-CoV-2. KEY MESSAGES: Phylogenetic analysis is essential to understand viral evolution, whereas homology modeling is important for vaccine strategies and therapies. Highly sensitive and specific diagnostic assays are key to case identification, contact tracing, identification of the animal source, and implementation of control measures.

negative: The incubation period of 2019-nCoV infections among travellers from Wuhan, China Currently, a novel coronavirus 2019-nCoV causes an outbreak of viral pneumonia in Wuhan, China. Little is known about its epidemiological characteristics. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan, we estimate the mean incubation period to be 6.4 (5.6 - 7.7, 95% CI) days, ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values help to inform case definitions for 2019-nCoV and appropriate durations for quarantine.

negative: Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region.

negative: Safeguarding the Maintenance Hemodialysis Patient Population during the Coronavirus Disease 19 Pandemic The World Health Organization has recognized the pandemic nature of the coronavirus disease 19 (COVID-19) outbreak. A large proportion of positive patients require hospitalization, while 5-6% of them may need more aggressive therapies in intensive care. Most governments have recommended social separation and severe measures of prevention of further spreading of the epidemic. Because hemodialysis (HD) patients need to access hospital and dialysis center facilities 3 times a week, this category of patients requires special attention. In this editorial, we tried to summarize the experience of our centers that hopefully may contribute to help other centers and colleagues that are facing the coming wave of the epidemic. Special algorithms for COVID-19 spreading in the dialysis population, recommendations for isolation and preventive measures in positive HD patients, and finally directions to manage logistics and personnel are reported. These recommendations should be considered neither universal nor absolute. Instead, they require local adjustments based on geographic location, cultural and social environments, and level of available resources.

negative: Human Mobility Restrictions and the Spread of the Novel Coronavirus (2019-nCoV) in China We quantify the causal impact of human mobility restrictions, particularly the lockdown of the city of Wuhan on January 23, 2020, on the containment and delay of the spread of the Novel Coronavirus (2019-nCoV). We employ a set of difference-in-differences (DID) estimations to disentangle the lockdown effect on human mobility reductions from other confounding effects including panic effect, virus effect, and the Spring Festival effect. We find that the lockdown of Wuhan reduced inflow into Wuhan by 76.64%, outflows from Wuhan by 56.35%, and within-Wuhan movements by 54.15%. We also estimate the dynamic effects of up to 22 lagged population inflows from Wuhan and other Hubei cities, the epicenter of the 2019-nCoV outbreak, on the destination cities' new infection cases. We find, using simulations with these estimates, that the lockdown of the city of Wuhan on January 23, 2020 contributed significantly to reducing the total infection cases outside of Wuhan, even with the social distancing measures later imposed by other cities. We find that the COVID-19 cases would be 64.81% higher in the 347 Chinese cities outside Hubei province, and 52.64% higher in the 16 non-Wuhan cities inside Hubei, in the counterfactual world in which the city of Wuhan were not locked down from January 23, 2020. We also find that there were substantial undocumented infection cases in the early days of the 2019-nCoV outbreak in Wuhan and other cities of Hubei province, but over time, the gap between the officially reported cases and our estimated "actual" cases narrows significantly. We also find evidence that enhanced social distancing policies in the 63 Chinese cities outside Hubei province are effective in reducing the impact of population inflows from the epicenter cities in Hubei province on the spread of 2019-nCoV virus in the destination cities elsewhere.

negative: Cumulative index 1984–1988 volume 86 through volume 95

negative: A Review of Asymptomatic and Subclinical Middle East Respiratory Syndrome Coronavirus Infections The epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) since 2012 has been largely characterized by recurrent zoonotic spillover from dromedary camels followed by limited human-to-human transmission, predominantly in health-care settings. The full extent of infection of MERS-CoV is not clear, nor is the extent and/or role of asymptomatic infections in transmission. We conducted a review of molecular and serological investigations through PubMed and EMBASE from September 2012 to November 15, 2018, to measure subclinical or asymptomatic MERS-CoV infection within and outside of health-care settings. We performed retrospective analysis of laboratory-confirmed MERS-CoV infections reported to the World Health Organization to November 27, 2018, to summarize what is known about asymptomatic infections identified through national surveillance systems. We identified 23 studies reporting evidence of MERS-CoV infection outside of health-care settings, mainly of camel workers, with seroprevalence ranges of 0%–67% depending on the study location. We identified 20 studies in health-care settings of health-care worker (HCW) and family contacts, of which 11 documented molecular evidence of MERS-CoV infection among asymptomatic contacts. Since 2012, 298 laboratory-confirmed cases were reported as asymptomatic to the World Health Organization, 164 of whom were HCWs. The potential to transmit MERS-CoV to others has been demonstrated in viral-shedding studies of asymptomatic MERS infections. Our results highlight the possibility for onward transmission of MERS-CoV from asymptomatic individuals. Screening of HCW contacts of patients with confirmed MERS-CoV is currently recommended, but systematic screening of non-HCW contacts outside of health-care facilities should be encouraged.

negative: SARS — beginning to understand a new virus The 114-day epidemic of the severe acute respiratory syndrome (SARS) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralysed the Asian economy. Aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of SARS and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. Here, we review the genomics of the SARS coronavirus (SARS-CoV), its phylogeny, antigenic structure, immune response and potential therapeutic interventions should the SARS epidemic flare up again.

negative: Comparison of SARS-CoV-2 Exit Strategies Building Blocks We consider and compare various exit strategy building blocks and key measures to mitigate the current SARS-CoV-2 pandemic, some already proposed as well as improvements we suggest. Our comparison is based on a computerized simulation integrating accumulated SARS-CoV-2 epidemiological knowledge. Our results stress the importance of immediate on-symptom isolation of suspected cases and household members, and the beneficial effects of prompt testing capacity. Our findings expose significant epidemic-suppression differences among strategies with seemingly similar economic cost stressing the importance of not just the portion of population and business that is released, but also the pattern. The most effective building blocks are the ones that integrate several base strategies - they allow to release large portions of the population while still achieving diminishing viral spread. However, it may come with a price on somewhat more complex schemes. For example, our simulations indicate that dividing the population into two groups completely released except for taking turns on a long weekend (Fri-Tue) self-isolation once every two weeks, while protecting the 5% most sensitive population would reduce R below 1 even if ten percent of the population does not follow it. We further simulate the contrasting approach of a stratified population release in a hope to achieve herd immunity, which for the time being seems inferior to other suggested building blocks. Knowing the tradeoff between building blocks could help optimize exit strategies to be more effective and suitable for a particular area or country, while maximizing human life as well as economic value. Given our results, we believe that pandemic can be controlled within a reasonable amount of time and at a reasonable socio-economic burden.

negative: The Anxiety of Being Asian American: Hate Crimes and Negative Biases During the COVID-19 Pandemic In this essay, we review how the COVID-19 (coronavirus) pandemic that began in the United States in early 2020 has elevated the risks of Asian Americans to hate crimes and Asian American businesses to vandalism. During the COVID-19 pandemic, the incidents of negative bias and microaggressions against Asian Americans have also increased. COVID-19 is directly linked to China, not just in terms of the origins of the disease, but also in the coverage of it. Because Asian Americans have historically been viewed as perpetually foreign no matter how long they have lived in the United States, we posit that it has been relatively easy for people to treat Chinese or Asian Americans as the physical embodiment of foreignness and disease. We examine the historical antecedents that link Asian Americans to infectious diseases. Finally, we contemplate the possibility that these experiences will lead to a reinvigoration of a panethnic Asian American identity and social movement.

negative: Practical strategies for a safe and effective delivery of aerosolized medications to patients with COVID-19 Abstract The COVID-19, the disease caused by a novel coronavirus and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe. It has caused outbreaks of illness due to person-to-person transmission of the virus mainly via close contacts and droplets produced by an infected person's cough or sneeze. Exhaled droplets from infected patients with COVID-19 can be inhaled into the lungs and leads to respiratory illness such as pneumonia and acute respiratory distress syndrome. Although aerosol therapy is a mainstay procedure used to treat pulmonary diseases at home and healthcare settings, it has a potential for fugitive emissions during therapy due to the generation of aerosols and droplets as a source of respiratory pathogens. Delivering aerosolized medications to patients with COVID-19 can aggravate the spread of the novel coronavirus. This has been a real concern for caregivers and healthcare professionals who are susceptible to unintended inhalation of fugitive emissions during therapy. Due to a scarcity of information in this area of clinical practice, the purpose of this paper is to explain how to deliver aerosolized medications to mild-, sub-intensive, and intensive patients with COVID-19 and how to protect staff from exposure to exhaled droplets during aerosol therapy.

negative: Acute peristome edema disease in juvenile and adult sea cucumbers Apostichopus japonicus (Selenka) reared in North China Acute peristome edema disease (APED) is a new disease that broke out in cultured sea cucumber along the Shangdong and Liaoning province coasts in China, PR, and has caused a great deal of death in Apostichopus japonicus (Selenka) since 2004. Here we report virus-like particles found in intestine epithelium of sea cucumbers reared in North China. It is the first time that sea cucumbers are reported to be infected by virus. Histological examinations showed that the viral inclusion bodies existed in intestine epithelium cells. Electron microscopic examinations show that the virions were spherical, 80–100 nm in diameter, and composed of a helical nucleocapsid within an envelope with surface projections. Detailed studies on the morphogenesis of these viruses found many characteristics previously described for coronaviruses. Virus particles always congregated, and formed a virus vesicle with an encircling membrane. The most obvious cellular pathologic feature is large granular areas of cytoplasm, relatively devoid of organelles. Tubular structures within virus-containing vesicles, nucleocapsid inclusions, and double-membrane vesicles are also found in the cytopathic cells. No rickettsia, chlamydia, bacteria, or other parasitic organisms were found.

negative: Measles-derived vaccines to prevent emerging viral diseases Abstract Infectious disease epidemics match wars and natural disasters in their capacity to threaten lives and damage economies. Like SARS previously and Zika recently, the Ebola crisis in 2015 showed how vulnerable the world is to these epidemics, with over 11,000 people dying in the outbreak. In addition to causing immense human suffering, these epidemics particularly affect low- and middle-income countries. Many of these deadly infectious diseases that have epidemic potential can become global health emergencies in the absence of effective vaccines. But very few vaccines against these threats have been developed to create proven medical products. The measles vaccine is an efficient, live attenuated, replicating virus that has been safely administered to 2 billion children over the last 40 years, affording life-long protection after a single dose. Taking advantage of these characteristics, this attenuated virus was transformed into a versatile chimeric or recombinant vaccine vector with demonstrated proof-of-principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens. Clinical trials have shown the safety and immunogenicity of this vaccine platform in individuals with preexisting immunity to measles. This review describes the potential of this platform to develop new vaccines against emerging viral diseases.

negative: Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections The World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine

negative: Global task force for influenza Early detection and rapid response to bird flu, on a global scale, will drastically cut the costs of dealing with a full-blown human flu pandemic, argue Ron Fouchier, Thijs Kuiken, Guus Rimmelzwaan and Albert Osterhaus.

negative: Broad-spectrum coronavirus antiviral drug discovery Introduction: The highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are lethal zoonotic viruses that have emerged into human populations these past 15 years. These coronaviruses are associated with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high morbidity and mortality caused by the progression to Acute Respiratory Distress Syndrome (ARDS). Areas covered: The risks of re-emergence of SARS-CoV from bat reservoir hosts, the persistence of MERS-CoV circulation, and the potential for future emergence of novel coronaviruses indicate antiviral drug discovery will require activity against multiple coronaviruses. In this review, approaches that antagonize viral nonstructural proteins, neutralize structural proteins, or modulate essential host elements of viral infection with varying levels of efficacy in models of highly pathogenic coronavirus disease are discussed. Expert opinion: Treatment of SARS and MERS in outbreak settings has focused on therapeutics with general antiviral activity and good safety profiles rather than efficacy data provided by cellular, rodent, or nonhuman primate models of highly pathogenic coronavirus infection. Based on lessons learned from SARS and MERS outbreaks, lack of drugs capable of pan-coronavirus antiviral activity increases the vulnerability of public health systems to a highly pathogenic coronavirus pandemic.

negative: In vitro Acquisition and Retention of Low-Pathogenic Avian Influenza H9N2 by Musca domestica (Diptera: Muscidae) Avian influenza virus (AIV) H9N2 emerged in the 1990s as an economically important disease in poultry and occasionally infects humans and other mammals. The aim of this study was to evaluate the acquisition and retention of H9N2 AIV on and within the house fly, Musca domestica (Linnaeus 1758), under laboratory conditions. In first experiment, 100 adult house flies were divided into control and treatment groups equally. Treatment group was fed with a meal containing H9N2 virus, while control group was supplied with an identical meal without virus. Fifteen minutes after exposure in each group, flies were washed twice to remove surface particles, disinfected and then homogenized for testing. The two external body surface washes and the homogenate samples were tested for H9N2 to distinguish exterior from interior viral load. Second experiment was performed likewise but five flies from each group were taken at 0, 6, 24, 48, 72, 96, and 120 h post-exposure. All samples were subjected to real-time reverse-transcription polymerase chain reaction (RRT-PCR) for detecting H9-Specific viral RNA. Results of the first experiment showed that viral RNA was detectable in both of external surface and homogenates samples. Second experiment revealed that persistence of H9N2 AIVs on external body surface and within the body of M. domestica were 24 and 96 h, respectively. Moreover, viral RNAs concentration declined during the time after exposure to AIV H9N2 either outside or within house flies. Overall, house fly was able to acquire and preserve H9N2 AIV experimentally, which may contribute the spread of virus among poultry farms.

negative: The lockdown of Hubei Province causing different transmission dynamics of the novel coronavirus (2019-nCoV) in Wuhan and Beijing Background: After the outbreak of novel coronavirus (2019-nCoV) starting in late 2019, a number of researchers have reported the predicted the virus transmission dynamics. However, under the strict control policy the novel coronavirus does not spread naturally outside Hubei Province, and none of the prediction closes to the real situation. Methods and findings: We used the traditional SEIR model, fully estimated the effect of control measures, to predict the virus transmission in Wuhan, the capital city of Hubei Province, and Beijing. We forecast that the outbreak of 2019-nCoV would reach its peak around March 6±10 in Wuhan and March 20±16 in Beijing, respectively. The infectious population in Beijing would be much less (only 0.3%) than those in Wuhan at the peak of this transmission wave. The number of confirmed cases in cities inside Hubei Province grow exponentially, whereas those in cities outside the province increase linearly. Conclusions: The unprecedented province lockdown substantially suspends the national and global outbreak of 2019-nCoV.

negative: Mechanisms of increased morbidity and mortality of SARS-CoV-2 infection in individuals with diabetes: what this means for an effective management strategy

negative: Long-term SARS Coronavirus Excretion from Patient Cohort, China This study investigated the long-term excretion of severe acute respiratory syndrome–associated coronavirus in sputum and stool specimens from 56 infected patients. The median (range) duration of virus excretion in sputa and stools was 21 (14–52) and 27 (16–126) days, respectively. Coexisting illness or conditions were associated with longer viral excretion in stools.

negative: Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. METHODS: We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (R(t)) at the provincial level. FINDINGS: We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33–56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4·4 days (95% CI 0·0–14·0) for the period of Dec 24 to Jan 27, to 2·6 days (0·0–9·0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5·2 days (1·8–12·4) and the mean serial interval at 5·1 days (1·3–11·6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1·08 (95% CI 0·74–1·54) in Shenzhen city of Guangdong province and 1·71 (1·32–2·17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, <1) after Jan 30. INTERPRETATION: Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province. FUNDING: National Science Fund for Distinguished Young Scholars, National Institute of General Medical Sciences, and European Commission Horizon 2020.

negative: Critical community size for COVID-19 -- a model based approach to provide a rationale behind the lockdown Background: Restrictive mass quarantine or lockdown has been implemented as the most important controlling measure to fight against COVID-19. Many countries have enforced 2 - 4 weeks' lockdown and are extending the period depending on their current disease scenario. Most probably the 14-day period of estimated communicability of COVID-19 prompted such decision. But the idea that, if the susceptible population drops below certain threshold, the infection would naturally die out in small communities after a fixed time (following the outbreak), unless the disease is reintroduced from outside, was proposed by Bartlett in 1957. This threshold was termed as Critical Community Size (CCS). Methods: We propose an SEIR model that explains COVID-19 disease dynamics. Using our model, we have calculated country-specific expected time to extinction (TTE) and CCS that would essentially determine the ideal number of lockdown days required and size of quarantined population. Findings: With the given country-wise rates of death, recovery and other parameters, we have identified that, if at a place the total number of susceptible population drops below CCS, infection will cease to exist after a period of TTE days, unless it is introduced from outside. But the disease will almost die out much sooner. We have calculated the country-specific estimate of the ideal number of lockdown days. Thus, smaller lockdown phase is sufficient to contain COVID-19. On a cautionary note, our model indicates another rise in infection almost a year later but on a lesser magnitude.

negative: Two things can be true at once: Surviving Covid‐19

negative: Early dynamics of transmission and control of COVID-19: a mathematical modelling study BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 95 333 confirmed cases as of March 5, 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Combining a mathematical model of severe SARS-CoV-2 transmission with four datasets from within and outside Wuhan, we estimated how transmission in Wuhan varied between December, 2019, and February, 2020. We used these estimates to assess the potential for sustained human-to-human transmission to occur in locations outside Wuhan if cases were introduced. METHODS: We combined a stochastic transmission model with data on cases of coronavirus disease 2019 (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January, 2020, and February, 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. To estimate the early dynamics of transmission in Wuhan, we fitted a stochastic transmission dynamic model to multiple publicly available datasets on cases in Wuhan and internationally exported cases from Wuhan. The four datasets we fitted to were: daily number of new internationally exported cases (or lack thereof), by date of onset, as of Jan 26, 2020; daily number of new cases in Wuhan with no market exposure, by date of onset, between Dec 1, 2019, and Jan 1, 2020; daily number of new cases in China, by date of onset, between Dec 29, 2019, and Jan 23, 2020; and proportion of infected passengers on evacuation flights between Jan 29, 2020, and Feb 4, 2020. We used an additional two datasets for comparison with model outputs: daily number of new exported cases from Wuhan (or lack thereof) in countries with high connectivity to Wuhan (ie, top 20 most at-risk countries), by date of confirmation, as of Feb 10, 2020; and data on new confirmed cases reported in Wuhan between Jan 16, 2020, and Feb 11, 2020. FINDINGS: We estimated that the median daily reproduction number (R(t)) in Wuhan declined from 2·35 (95% CI 1·15–4·77) 1 week before travel restrictions were introduced on Jan 23, 2020, to 1·05 (0·41–2·39) 1 week after. Based on our estimates of R(t), assuming SARS-like variation, we calculated that in locations with similar transmission potential to Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. INTERPRETATION: Our results show that COVID-19 transmission probably declined in Wuhan during late January, 2020, coinciding with the introduction of travel control measures. As more cases arrive in international locations with similar transmission potential to Wuhan before these control measures, it is likely many chains of transmission will fail to establish initially, but might lead to new outbreaks eventually. FUNDING: Wellcome Trust, Health Data Research UK, Bill & Melinda Gates Foundation, and National Institute for Health Research.

negative: Noninvasive ventilation in acute respiratory failure due to H1N1 influenza: A word of caution

negative: SARS, MERS and COVID-19 among Healthcare Workers: A Narrative Review Abstract In the recent two decades, three global viral infectious diseases, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and coronavirus disease (COVID-19), have occurred worldwide. SARS occurred in November 2002, causing 8,096 infected cases, as well as 774 deaths. MERS occurred in June, 2012, causing 2,519 confirmed cases, along with 866 associated deaths. COVID-19 occurred in December 2019, as of 30 April 2020, a total of 3,024,059 clinical cases have been reported, including 208,112 deaths. Healthcare workers (HCWs) need to be in close contact with these virus-infected patients and their contaminated environments at work, thus leading to be infected in some of them, even a few of them are died in line of duty. In this review, we summarized the infection status of HCWs during the outbreak of SARS, MERS and COVID-19, with in-depth discussion, hoping to provoke sufficient attention to the HCWs infection status by more people.

negative: Inactivating influenza viruses on surfaces using hydrogen peroxide or triethylene glycol at low vapor concentrations BACKGROUND: Surfaces in congregate settings, such as vehicles used for mass transportation, can become contaminated with infectious microorganisms and facilitate disease transmission. We disinfected surfaces contaminated with H1N1 influenza viruses using hydrogen peroxide (HP) vapor at concentrations below 100 ppm and triethylene glycol (TEG)-saturated air containing 2 ppm of TEG at 25°C. METHODS: Influenza viruses in aqueous suspensions were deposited on stainless-steel coupons, allowed to dry at ambient conditions, and then exposed for up to 15 minutes to 10 to 90 ppm of HP vapor or TEG-saturated air. Virus assays were done on the solution used to wash the viruses from these coupons and from coupons treated similarly but without exposure to HP or TEG vapor. RESULTS: After 2.5 minutes, exposure to 10-ppm HP vapor resulted in 99% inactivation. For air saturated with TEG at 25 to 29°C, the disinfection rate was about 1.3 log(10) reductions per hour, about 16 times faster than the measured natural inactivation rate under ambient conditions. CONCLUSIONS: Vapor concentrations of 10 ppm HP or 2 ppm TEG can provide effective surface disinfection. At these low concentrations, the potential for damage to even the avionics of an airplane would be expected to be minimal. At a TEG vapor concentration of 2 ppm, there are essentially no health risks to people.

negative: Genomics-guided molecular maps of coronavirus targets in human cells: a path toward the repurposing of existing drugs to mitigate the pandemic Human genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomics-guided maps of up-stream regulatory elements, their expression and functions in human body, including pathophysiologically-relevant cell types. Genes acting as repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors (VDR; GATA5; SFTPC; HIF1a) and activators (HMGA2; INSIG1) were then employed to identify existing drugs that could be repurposed to mitigate the coronavirus infection. Present analyses identify Vitamin D and Quercetin as promising pandemic mitigation agents. Gene expression profiles of Vitamin D and Quercetin activities and their established safety records as over-the-counter medicinal substances suggest that they may represent viable candidates for further assessment and considerations of their potential as coronavirus pandemic mitigation agents. Notably, gene set enrichment analyses and expression profiling experiments identify multiple drugs, most notably testosterone, dexamethasone, and doxorubicin, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of Testosterone versus Estradiol impacts on SCARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during coronavirus pandemic.

negative: STABILITY ANALYSIS OF THE HIV MODEL THROUGH INCOMMENSURATE FRACTIONAL-ORDER NONLINEAR SYSTEM In this study, it is employed a new model of HIV infection in the form of incommensurate fractional differential equations systems involving the Caputo fractional derivative. Existence of the model's equilibrium points has been investigated. According to some special cases of the derivative-orders in the proposed model, the asymptotic stability of the infection-free equilibrium and endemic equilibrium has been proved under certain conditions. These stability conditions related to the derivative-orders depend on not only the basic reproduction rate frequently emphasized in the literature but also the newly obtained conditions in this study. Qualitative analysis results were complemented by numerical simulations in Matlab, illustrating the obtained stability result.

negative: Ninety-day inhalation study in rats, comparing smoke from cigarettes that heat tobacco with those that burn tobacco Abstract Eight groups of 30 male and 30 female rats were exposed 1 hr per day, 5 days per week for 13 weeks, to smoke from reference (tobacco burned) or test (tobacco only heated) cigarettes, at nicotine concentrations of 5, 15, or 30 μg/liter of air. Similar smoke concentrations of wet total particulate matter and carbon monoxide were produced in each of the test/reference comparisons. There was a pronounced depression of minute ventilation of animals in the reference groups, but not in the test animals. Blood carboxyhemoglobin concentrations were similar in animals exposed to smoke from test and reference cigarettes. Plasma concentrations of nicotine and cotinine in the test groups were higher than in the reference groups. There were no differences between the smoke-exposed groups in terms of body weight or feed consumption. At necropsy, an increase in heart weight was noted in both high exposure groups. There were notable differences in histopathology, with fewer and less-pronounced changes in the test groups than in the reference groups. Many of the histopathological responses induced in the reference groups were absent in the test groups. Overall, the study demonstrated a substantial reduction in the biological activity of smoke from the test cigarette when compared with the reference.

negative: Chapter 18 Combustion, Reactive Hazard, and Bioprocess Safety Abstract Is bioprocess dangerous? How do we maintain safety? What is reactive hazard? What is biohazard? Chemical transformation, or biotransformation, means change. Any changes have irreversible consequences. Managing the changes can help us, but changes can also be harmful. The first line of defense on any potential unwanted transformations is isolation or containment. WHO defines four risk groups of biosafety levels. There are six key knowledge bases for biosafety. With chemical safety, substance identification is the first step. The global harmonized system of classification and labeling is generally accepted by the world health safety bodies. The hazards are divided into three categories: physical, health, and environmental. Chemical reactivity hazard is a situation where an uncontrolled reaction could result directly or indirectly in serious harm to people, property, or equipment. Fire and explosion are common reactivity hazards. To safeguard processes and facilities, one needs to first identify the threat by screening for reactivity hazards. Combustion processes proceed with chain reactions and the reaction is highly exothermic. Combined with the high activation energy, combustion depends largely on temperature. The overall reaction products can also vary (partial oxidation versus total oxidation). Partial oxidation reactions are important in the chemical industry. Pyrolysis and gasification of biomass, for example, are useful technologies in biomass conversion. An explosion is a fast, transient, exothermic reaction. Unintended and accidental explosions can occur due to: (1) the accumulation of reactive chemicals (gas, liquid, or solid) in confined space; (2) leakage of a “significant amount” of reactive chemicals (gas, liquid, or solid) to the atmosphere or environment; or (3) reactor runaway. As a bioprocess engineer, you will be responsible for creating safe processes and protecting the lives and health of your colleagues.

negative: Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (2019 coronavirus disease, COVID-19) since December 2019, from Wuhan, China, has been posing a significant threat to global human health. The clinical features and outcomes of Chinese patients with COVID-19 have been widely reported. Increasing evidence has witnessed the frequent incident liver injury in COVID-19 patients, and it is often manifested as transient elevation of serum aminotransferases; however, the patients seldom have liver failure and obvious intrahepatic cholestasis, unless pre-existing advanced liver disease was present. The underlying mechanisms of liver injury in cases of COVID-19 might include psychological stress, systemic inflammation response, drug toxicity, and progression of pre-existing liver diseases. However, there is insufficient evidence for SARS-CoV-2 infected hepatocytes or virus-related liver injury in COVID-19 at present. The clinical, pathological and laboratory characteristics as well as underlying pathophysiology and etiology of liver injury in COVID-19 remain largely unclear. In this review, we highlight these important issues based on the recent developments in the field, for optimizing the management and treatment of liver injury in Chinese patients with COVID-19.

negative: Nidovirales Nidoviruses form a phylogenetically compact but diverse group of enveloped positive-stranded RNA viruses with the largest RNA genome known. They infect a broad range of hosts, including humans, other mammals, birds, fish, and shrimp. Nidovirus infection starts by binding to a receptor on the cell surface, and fusion of the viral and cellular membranes mediated by one of the major surface glycoproteins. Following genome uncoating, the translation of the two overlapping replicase open reading frames (ORFs) yields two large polyprotein precursors that undergo autoproteolysis to produce the mature nonstructural proteins that eventually assemble into a membrane-bound, replication–transcription complex. The complex, which also contains several cellular proteins, mediates negative-strand RNA synthesis, amplification of the genome RNA, and production of a nested set of subgenomic messenger RNAs (sg mRNAs). Whereas nidovirus genome replication proceeds through the synthesis of a full-length negative-strand RNA, transcription involves the synthesis of subgenome-length, negative-strand templates for mRNA synthesis. In arteriviruses and coronaviruses, and probably bafiniviruses, transcription involves a mechanism of discontinuous negative-strand synthesis (template switch) to equip each subgenomic RNA with a 5′ common leader sequence identical to the genomic 5′ end. Except for the largest torovirus sg RNA, torovirus and ronivirus sgRNAs do not share such a common leader sequence and discontinuous RNA synthesis does not appear to be involved in this case. New nidovirus particles are assembled in the cytoplasm. There is increasing evidence that nidovirus infections modify a variety of host cell functions and structures, and induce a variety of immune and stress responses.

negative: Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.

negative: Concerns for activated breathing control (ABC) with breast cancer in the era of COVID-19: Maximizing infection control while minimizing heart dose

negative: Towards a Practical Cosmopolitanism Claiming the airport as an exemplar of contemporary global space and the incessant logics of movement seen to be at the heart of globalisation, the introductory chapter asks what is it to move in the airport space? What is the choreography of the airport? Reviewing debates on critical cosmopolitanism, and the corporeal and spatial turns, this chapter argues for the need to further embodied analysis of global movement through a kind of kinaesthetic ethnography, which puts the wealth of thinking about moving bodies in space from dance studies into dialogue with mobility studies. Such an approach, the chapter argues, can lead us to important knowledge about the ongoing tensions between sameness and difference, national and transnational, self and other, as experienced in the transit spaces of global mobility—a practice of cosmopolitanism.

negative: Sudden hyposmia as a prevalent symptom of COVID-19 infection. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has recently caused a pandemic that has involved Italy as the second worldwide nation in terms of infected patients and deaths. The clinical manifestation of Covid-19 ranges from asymptomatic carrier status to severe pneumonia. Asymptomatic individuals in Covid-19 are those who are carriers of the virus but do not show clinical symptoms and are able to transmit the disease in the same degree as symptomatic carriers. In order to contain contagions is of supreme importance to identify asymptomatic patients because this subpopulation is one of the main factors contributing to the spread of this disease. We report on six Italian patients with COVID-19 who presented sudden hyposmia as the only or most prominent disease manifestation, without upper or lower respiratory tract involvement or other major features of the disease. A supra-threshold olfaction test confirmed the hyposmia in all patients. The onset of hyposmia during a Covid-19 outbreak should be considered as a warning sign of an infection that requires a diagnostic test for Covid-19

negative: [The War Against the Coronavirus Disease (COVID-2019): Keys to Successfully Defending Taiwan]. The outbreak of COVID-19 triggered the largest human-virus war in this century. Current evidence indicates that the SARS-CoV-2 strain of coronavirus is mainly transmitted by droplets either by direct or indirect contact. The duration of infectiousness of COVID-19 ranges from 1-2 days before and 7-10 days after the onset of symptoms. It is often difficult to detect the signs and symptoms of infection and to implement timely intervention during the very early stage of infection. Thus, finding and isolating symptomatic patients may not be sufficient to contain this epidemic. Therefore, it is very important to wear masks, take personal precautions, and practice recommended social distancing to achieve source control and stop transmission. Taiwan has learned from its previous experience with the SARS epidemic and prepared for the potential of new disease outbreaks for at least 17 years. This helped the government to implement a multifaceted strategy in the early stages of the COVID-19 outbreak. Taiwan's effective response has made the country a model for pandemic response policy that has been appreciated internationally. This paper examines COVID-19 epidemic prevention from the perspective of infection control strategies. In Taiwan, hospital infection control, which is practiced nationwide, emphasizes the importance to epidemic prevention of collecting and tracking travel history, occupation, contact history, cluster (TOCC) information; practicing hand hygiene; promoting the correct use of personal protective equipment; and maintaining safe distances from others. Personal control measures are recognized as critical to providing a safe environment for patients and staff.

negative: Chapter 2 Virus Structure and Classification Abstract Viruses have several common characteristics: they are small, have DNA or RNA genomes, and are obligate intracellular parasites. The virus capsid functions to protect the nucleic acid from the environment, and some viruses surround their capsid with a membrane envelope. Most viruses have icosahedral or helical capsid structure, although a few have complex virion architecture. An icosahedron is a geometric shape with 20 sides, each composed of an equilateral triangle, and icosahedral viruses increase the number of structural units in each face to expand capsid size. The classification of viruses is very useful, and the International Committee on Taxonomy of Viruses is the official body that classifies viruses into order, family, genus, and species taxa. There are currently seven orders of viruses.

negative: The “Common Cold” in Frail Older Persons: Impact of Rhinovirus and Coronavirus in a Senior Daycare Center OBJECTIVE: To evaluate the incidence and impact of rhino‐virus and Coronavirus infections in older persons attending daycare. DESIGN: Prospective descriptive study. SETTING: Three senior daycare centers in Rochester, New York. PATIENTS: Frail older persons and staff members of the daycare centers who developed signs or symptoms of an acute respiratory illness MEASUREMENTS: Demographic, medical, and physical findings were recorded on subjects at baseline and during respiratory illness. Nasopharyngeal specimens for viral culture as well as acute and convalescent sera for Coronavirus 229E enzyme immunoassay (EIA) were obtained for all illnesses. RESULTS: During the 44 months of study, 352 older persons experienced 522 illnesses. Thirty‐five (7%) of 522 cultures were positive for rhinovirus and 37 (8%) of 451 serologies were positive for Coronavirus 229E infection. The clinical syndromes associated with rhinovirus and Coronavirus infection were similar and characterized by nasal congestion, cough, and constitutional symptoms. No patient died or was hospitalized, but approximately 50% had evidence of lower respiratory tract involvement. The average illness lasted 14 days. During the same period, 113 staff developed 338 respiratory illnesses. Eight percent were identified as Coronavirus and 9% as rhinovirus. Cough, sputum production, and constitutional symptoms were significantly more common among older persons. CONCLUSIONS: Rhinovirus and Coronavirus 229E are common causes of moderately debilitating acute respiratory illnesses among older persons attending daycare.

negative: A methodology for optimal placement of sensors in enclosed environments: A dynamical systems approach Abstract Air quality has been an important issue in public health for many years. Sensing the level and distributions of impurities help in the control of building systems and mitigate long term health risks. Rapid detection of infectious diseases in large public areas like airports and train stations may help limit exposure and aid in reducing the spread of the disease. Complete coverage by sensors to account for any release scenario of chemical or biological warfare agents may provide the opportunity to develop isolation and evacuation plans that mitigate the impact of the attack. All these scenarios involve strategic placement of sensors to promptly detect and rapidly respond. This paper presents a data driven sensor placement algorithm based on a dynamical systems approach. The approach utilizes the finite dimensional Perron-Frobenius (PF) concept. The PF operator (or the Markov matrix) is used to construct an observability gramian that naturally incorporates sensor accuracy, location constraints, and sensing constraints. The algorithm determines the response times, sensor coverage maps, and the number of sensors needed. The utility of the procedure is illustrated using four examples: a literature example of the flow field inside an aircraft cabin and three air flow fields in different geometries. The effect of the constraints on the response times for different sensor placement scenarios is investigated. Knowledge of the response time and coverage of the multiple sensors aides in the design of mechanical systems and response mechanisms. The methodology provides a simple process for place sensors in a building, analyze the sensor coverage maps and response time necessary during extreme events, as well as evaluate indoor air quality. The theory established in this paper also allows for future work in topics related to construction of classical estimator problems for the sensors, real-time contaminant transport, and development of agent dispersion, contaminant isolation/removal, and evacuation strategies.

negative: An under-aisle air distribution system facilitating humidification of commercial aircraft cabins Abstract Air environment in aircraft cabins has long been criticized especially for the dryness of the air within. Low moisture content in cabins is known to be responsible for headache, tiredness and many other non-specific symptoms. In addition, current widely used air distribution systems on airplanes dilute internally generated pollutants by promoting air mixing and thus impose risks of infectious airborne disease transmission. To boost air humidity level while simultaneously restricting air mixing, this investigation uses a validated computational fluid dynamics (CFD) program to design a new under-aisle air distribution system for wide-body aircraft cabins. The new system supplies fully outside, dry air at low momentum through a narrow channel passage along both side cabin walls to middle height of the cabin just beneath the stowage bins, while simultaneously humidified air is supplied through both perforated under aisles. By comparing with the current mixing air distribution system in terms of distribution of relative humidity, CO2 concentration, velocity, temperature and draught risk, the new system is found being able to improve the relative humidity from the existent 10% to the new level of 20% and lessen the inhaled CO2 concentration by 30%, without causing moisture condensation on cabin interior and inducing draught risks for passengers. The water consumption rate in air humidification is only around 0.05kg/h per person, which should be affordable by airliners.

negative: Continuous on-line glucose measurement by microdialysis in a central vein. A pilot study. INTRODUCTION Tight glucose control in the ICU has been proven difficult with an increased risk for hypoglycaemic episodes. Also the variability of glucose may have an impact on morbidity. An accurate and feasible on-line/continuous measurement is therefore desired. In this study a central vein catheter with a microdialysis membrane in combination with an on-line analyzer for continuous monitoring of circulating glucose and lactate by the central route was tested. METHODS A total of 10 patients scheduled for major upper abdominal surgery were included in this observational prospective study at a university hospital. The patients received an extra central venous catheter with a microdialysis membrane placed in the right jugular vein. Continuous microdialysis measurement proceeded for 20 hours and on-line values were recorded every minute. Reference arterial plasma glucose and blood lactate samples were collected every hour. RESULTS Mean microdialysis-glucose during measurements was 9.8 ± 2.4 mmol/l.No statistical difference in the readings was seen using a single calibration compared to eighth hour calibration (P =0.09; t-test). There was a close agreement between the continuous reading and the reference plasma glucose values with an absolute difference of 0.6+0.8 mmol, or 6.8+9.3% and measurements showed high correlation to plasma readings (r = 0.92). The limit of agreement was 23.0%(1.94 mmol/l) compared to arterial plasma values with a line of equality close to zero.However, in a Clarke-Error Grid 93.3% of the values are in the A-area,and the remaining part in the B-area.Mean microdialysis-lactate was 1.3 ± 1.1 mmol/l. The measurements showed high correlation to the blood readings (r = 0.93). CONCLUSION Continuous on-line microdialysis glucose measurement in a central vein is a potential useful technique for continuous glucose monitoring in critically ill patients, but more improvements and testing are needed.

negative: ICU management of severe acute respiratory syndrome BACKGROUND: Severe acute respiratory syndrome (SARS) is a contagious viral illness first recognized in late 2002. It has now been documented in 26 countries worldwide, with significant outbreaks in China, Hong Kong, Singapore, and Toronto. Research into identifying the etiological agent, evaluating modes of disease transmission, and treatment options is currently ongoing. DISCUSSION: The disease can produce a severe bilateral pneumonia, with progressive hypoxemia. Up to 20% of patients require mechanical ventilatory support, with a fatal outcome occurring in about 5% of cases. CONCLUSIONS: We review the current knowledge about this disease, with particular emphasis on ICU management and infection control precautions to prevent disease transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available if you access this article at http://dx.doi.org/10.1007/s00134-003-1821-0. On that page (frame on the left side) a link takes you directly to the supplementary material.

negative: Modelling strategies to organize healthcare workforce during pandemics: application to COVID-19 Protection of healthcare workforce is of paramount relevance for the care of infected and non-infected patients in the setting of a pandemic such as coronavirus disease 2019 (COVID-19). Healthcare workers are at increased risk to become infected because of contact to infected patients, infected co-workers and their community outside the hospital. The ideal organisational strategy to protect the healthcare workforce in a situation in which social distancing cannot be maintained at the workplace remains to be determined. In this study, we have mathematically modelled strategies for the employment of hospital workforce with the goal to simulate health and productivity of the workers. Therefore, deterministic models were extended to account for stochastic influences potentially occurring in rather small populations. The models were also designed to determine if desynchronization of medical teams by dichotomizing the workers may protect the workforce. Our studies model workforce productivity depending on the infection rate, the presence of reinfection and the efficiency of home office. As an application example, we apply our theory to the case of coronavirus disease 2019 (COVID-19). The results of the models reveal that a desynchronization strategy in which two medical teams work alternating for 7 days reduces the infection rate of the healthcare workforce. In case of immunity to the infectious agent this affect is mainly relevant at early stages of the pandemic. This effect is independent on infection rates and increases the overall workforce productivity under certain situations.

negative: Viral Diarrhea Viral gastroenteritis is among the most common illnesses affecting humans and has greatest impact at the extremes of age. The spectrum of disease can range from asymptomatic infections to severe disease with dehydration. Intensive investigation of enteric infections in the past three decades has made it increasingly clear that viruses cause a significant proportion of enteric illnesses worldwide. In contrast to bacterial pathogens, enteric viruses cannot multiply outside their host; hence, the original inoculum into the common source determines infectivity. Prevention of contamination of food and water will help control primary cases, whereas careful nursing and handwashing prevent secondary cases.

negative: Chemical disinfection of non-porous inanimate surfaces experimentally contaminated with four human pathogenic viruses. The chemical disinfection of virus-contaminated non-porous inanimate surfaces was investigated using coxsackievirus B3, adenovirus type 5, parainfluenza virus type 3 and coronavirus 229E as representatives of important nosocomial viral pathogens. A 10 microliter amount of the test virus, suspended in either faeces or mucin, was placed onto each stainless steel disk (about 1 cm in diameter) and the inoculum allowed to dry for 1 h under ambient conditions. Sixteen disinfectant formulations were selected for this study based on the findings of an earlier investigation with a human rotavirus. After 1 min exposure to 20 microliters of the disinfectant, the virus from the disks was immediately eluted into tryptose phosphate broth and plaque assayed. Using an efficacy criterion of a 3 log10 or greater reduction in virus infectivity titre and irrespective of the virus suspending medium, only the following five disinfectants proved to be effective against all the four viruses tested: (1) 2% glutaraldehyde normally used as an instrument soak, (2) a strongly alkaline mixture of 0.5% sodium o-benzyl-p-chlorophenate and 0.6% sodium lauryl sulphate, generally used as a domestic disinfectant cleaner for hard surfaces, (3) a 0.04% solution of a quaternary ammonium compound containing 7% hydrochloric acid, which is the basis of many toilet bowl cleaners, (4) chloramine T at a minimum free chlorine level of 3000 p.p.m. and (5) sodium hypochlorite at a minimum free chlorine concentration of 5000 p.p.m. Of those chemicals suitable for use as topical antiseptics, 70% ethanol alone or products containing at least 70% ethanol were ineffective only against coxsackievirus B3. These results emphasize the care needed in selecting chemical disinfectants for routine use in infection control.

negative: Estimate the incubation period of coronavirus 2019 (COVID-19) Motivation: Wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus (COVID-19). It is being treated as a Class A infectious disease though it was classified as Class B according to the Infectious Disease Prevention Act of China. Accurate estimation of the incubation period of the coronavirus is essential to the prevention and control. However, it remains unclear about its exact incubation period though it is believed that symptoms of COVID-19 can appear in as few as 2 days or as long as 14 or even more after exposure. The accurate incubation period calculation requires original chain-of-infection data that may not be fully available in the Wuhan regions. In this study, we aim to accurately calculate the incubation period of COVID-19 by taking advantage of the chain-of-infection data, which is well-documented and epidemiologically informative, outside the Wuhan regions. Methods: We acquired and collected officially reported COVID-19 data from 10 regions in China except for Hubei province. To achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. We excluded those without relevant epidemiological descriptions, working or living in Wuhan for a long time, or hard to determine the possible exposure time. We proposed a Monte Caro simulation approach to estimate the incubation of COVID-19 as well as employed nonparametric ways. We also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. Result: The incubation period of COVID-19 did not follow general incubation distributions such as lognormal, Weibull, and Gamma distributions. We estimated that the mean and median of its incubation were 5.84 and 5.0 days via bootstrap and proposed Monte Carlo simulations. We found that the incubation periods of the groups with age>=40 years and age<40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter. It further suggested that different quarantine time should be applied to the groups for their different incubation periods. Our machine learning analysis also showed that the two groups were linearly separable. incubation of COVID-19 along with previous statistical analysis. Our results further indicated that the incubation difference between males and females did not demonstrate a statistical significance.

negative: Identification, Characterization, and In Vitro Culture of Highly Divergent Arenaviruses from Boa Constrictors and Annulated Tree Boas: Candidate Etiological Agents for Snake Inclusion Body Disease Inclusion body disease (IBD) is an infectious fatal disease of snakes typified by behavioral abnormalities, wasting, and secondary infections. At a histopathological level, the disease is identified by the presence of large eosinophilic cytoplasmic inclusions in multiple tissues. To date, no virus or other pathogen has been definitively characterized or associated with the disease. Using a metagenomic approach to search for candidate etiologic agents in snakes with confirmed IBD, we identified and de novo assembled the complete genomic sequences of two viruses related to arenaviruses, and a third arenavirus-like sequence was discovered by screening an additional set of samples. A continuous boa constrictor cell line was established and used to propagate and isolate one of the viruses in culture. Viral nucleoprotein was localized and concentrated within large cytoplasmic inclusions in infected cells in culture and tissues from diseased snakes. In total, viral RNA was detected in 6/8 confirmed IBD cases and 0/18 controls. These viruses have a typical arenavirus genome organization but are highly divergent, belonging to a lineage separate from that of the Old and New World arenaviruses. Furthermore, these viruses encode envelope glycoproteins that are more similar to those of filoviruses than to those of other arenaviruses. These findings implicate these viruses as candidate etiologic agents of IBD. The presence of arenaviruses outside mammals reveals that these viruses infect an unexpectedly broad range of species and represent a new reservoir of potential human pathogens.

negative: CT Manifestations of Novel Coronavirus Pneumonia: A Case Report BACKGROUND: Since December 2019, the outbreak of the novel coronavirus has impacted nearly >90,000 people in more than 75 countries. In this case report, we aim to define the chest computed tomography findings of 2019-novel coronavirus associated with pneumonia and its successful resolution after treatment. CASE REPORT: A fifty-year-old female patient, who is a businesswoman, presented with chief complaints of “fever for one week, diarrhea, anorexia, and asthenia.” Initially, she was given Tamiflu. The influenza A virus serology was negative. Three days later, levofloxacin was started because the patient’s symptoms did not improve. The novel coronavirus nucleic acid test was negative. It was noted that before the onset of the disease, the patient went to Wuhan on a business trip. Despite the given treatment, her body temperature rose to 39.2°C and she was referred to our clinic for further evaluation. Then, chest computed tomography was performed and showed bilateral multifocal ground glass opacities with consolidation which suggested viral pneumonia as a differential diagnosis, and the subsequent 2019-novel coronavirus pneumonia nucleic acid test was positive. CONCLUSION: Chest computed tomography offers fast and convenient evaluation of patients with suspected 2019-novel coronavirus pneumonia.

negative: A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters. The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-DeltaE) were studied using hamsters. Hamsters immunized with rSARS-CoV-DeltaE developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-DeltaE-immunized hamsters remained active following wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication in the respiratory tract, rSARS-CoV-DeltaE is an immunogenic and efficacious vaccine in hamsters.

negative: Production of soluble truncated spike protein of porcine epidemic diarrhea virus from inclusion bodies of Escherichia coli through refolding Abstract The emergence of highly pathogenic variant porcine epidemic diarrhea virus (PEDV) strains, from 2013 to 2014, in North American and Asian countries have greatly threatened global swine industry. Therefore, development of effective vaccines against PEDV variant strains is urgently needed. Recently, it has been reported that the N-terminal domain (NTD) of S1 domain of PEDV spike protein is responsible for binding to the 5-N-acetylneuraminic acid (Neu5Ac), a possible sugar co-receptor. Therefore, the NTD of S1 domain could be an attractive target for the development of subunit vaccines. In this study, the NTD spanning amino acid residues 25-229 (S25-229) of S1 domain of PEDV variant strain was expressed in Escherichia coli BL21 (DE3) in the form of inclusion bodies (IBs). S25-229 IBs were solubilized in 20 mM sodium acetate (pH 4.5) buffer containing 8 M urea and 1 mM dithiothreitol with 95% yield. Solubilized S25-229 IBs were refolded by 10-fold flash dilution and purified by one-step cation exchange chromatography with >95% purity and 20% yield. The CD spectrum of S25-229 showed the characteristic pattern of alpha helical structure. In an indirect ELISA, purified S25-229 showed strong reactivity with mouse anti-PEDV sera. In addition, immunization of mice with 20 μg of purified S25-229 elicited highly potent serum IgG titers. Finally, mouse antisera against S25-229 showed immune reactivity with native PEDV S protein in an immunofluorescence assay. These results suggest that purified S25-229 may have potential to be used as a subunit vaccine against PEDV variant strains.

negative: Imaging Axonal Degeneration and Repair in Preclinical Animal Models of Multiple Sclerosis Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Over time, this neurologic damage manifests clinically as debilitating motor and cognitive symptoms. Existing MS therapies focus on symptom relief and delay of disease progression through reduction of neuroinflammation. However, long-term strategies to remyelinate, protect, or regenerate axons have remained elusive, posing a challenge to treating progressive forms of MS. Preclinical mouse models and techniques, such as immunohistochemistry, flow cytometry, and genomic and proteomic analysis have provided advances in our understanding of discrete time-points of pathology following disease induction. More recently, in vivo and in situ two-photon (2P) microscopy has made it possible to visualize continuous real-time cellular behavior and structural changes occurring within the CNS during neuropathology. Research utilizing 2P imaging to study axonopathy in neuroinflammatory demyelinating disease has focused on five areas: (1) axonal morphologic changes, (2) organelle transport and health, (3) relationship to inflammation, (4) neuronal excitotoxicity, and (5) regenerative therapies. 2P imaging may also be used to identify novel therapeutic targets via identification and clarification of dynamic cellular and molecular mechanisms of axonal regeneration and remyelination. Here, we review tools that have made 2P accessible for imaging neuropathologies and advances in our understanding of axonal degeneration and repair in preclinical models of demyelinating diseases.

negative: All eyes on Coronavirus—What do we need to know as ophthalmologists

negative: Seeding COVID-19 across sub-Saharan Africa: an analysis of reported importation events across 40 countries Background: The first case of COVID-19 in sub-Saharan Africa (SSA) was reported by Nigeria on February 27, 2020. While case counts in the entire region remain considerably less than those being reported by individual countries in Europe, Asia, and the Americas, SSA countries remain vulnerable to significant COVID morbidity and mortality due to systemic healthcare weaknesses, less financial resources and infrastructure to address the new crisis, and untreated comorbidities. Variation in preparedness and response capacity as well as in data availability has raised concerns about undetected transmission events. Methods: Confirmed cases reported by SSA countries were line-listed to capture epidemiological details related to early transmission events into and within countries. Data were retrieved from publicly available sources, including institutional websites, situation reports, press releases, and social media accounts, with supplementary details obtained from news articles. A data availability score was calculated for each imported case in terms of how many indicators (sex, age, travel history, date of arrival in country, reporting date of confirmation, and how detected) could be identified. We assessed the relationship between time to first importation and overall Global Health Security Index (GHSI) using Cox regression. K-means clustering grouped countries according to healthcare capacity and health and demographic risk factors. Results: A total of 2417 confirmed cases of COVID-19 were reported by 40 countries in sub-Saharan Africa during the 30 days after the first known introduction to the region. Out of the 876 cases for which information was publicly available, 677 (77.3%) were considered importation events. At the regional level, imported cases tended to be male (67.3%), were a median 43.0 years old (Range: 6 weeks - 88 years), and most frequently had recent travel history from Europe (43.3%). The median time to reporting an introduction was 19 days; a country's time to report its first importation was not related to GHSI. Mean data availability scores were lowest for countries that had, on average, the highest case fatality rates, lowest healthcare capacity, and highest probability of premature death due to non-communicable diseases. Conclusion: Countries with systemic, demographic, and pre-existing health vulnerabilities to severe COVID-related morbidity and mortality are less likely to report any cases or are reporting with limited public availability of information. Reporting of information on COVID detection and response efforts, as well as on trends in non-COVID illness and care-seeking behavior, is critical to assessing direct and indirect consequences and capacity needs in resource-constrained settings. Such assessments aid in the ability to make data-driven decisions about interventions, country priorities, and risk assessment.

negative: Trace, Quarantine, Test, Isolate and Treat: A Kerala Model of Covid-19 Response Kerala reported the first three cases of coronavirus in India in late January. Kerala, one of Indias most densely populated states, which makes its success in fighting the Covid-19 all the more commendable. Moreover, an estimated 17% of its 35 million population employed or lives elsewhere, more than 1 million tourists visit each year, and hundreds of students study abroad, including in China. All of this mobility makes the state more vulnerable to contagious outbreaks. What is the strategy behind the success story? This paper compares the situation of COVID-19 pandemic in major states and Kerala by the different phase of lockdown, and also highlights Keralas fight against the pandemic. We used publicly available data from https://www.covid19india.org/ and Covid-19 Daily Bulletin (Jan 31-May 31), Directorate of Health Services, Kerala (https://dashboard.kerala.gov.in/). We calculate the phase-wise period prevalence rate (PPR) and the case fatality rate (CFR) of the last phase. Compared to other major states, Kerala showed better response in preventing pandemic. The equation for the Keralas success has been simple, prioritized testing, widespread contact tracing, and promoting social distance. They also imposed uncompromising controls, that were supported by an excellent healthcare system, government accountability, transparency, public trust, civil rights and importantly the decentralized governance and strong grass-root level institutions. The proactive measures taken by Kerala such as early detection of cases and extensive social support measures can be a model for India and the world. Keywords: Covid-19, Kerala, India, Testing, Tracing, Pandemic.

negative: Can Search Query Forecast successfully in China's 2019-nCov pneumonia? Recently the novel coronavirus (2019-nCov) pneumonia outbreak in China then the world, and the Number of infections and death continues to increases. Search Query performs well in forecasting the epidemics. It is still a question whether search engine data can forecast the drift and the inflexion in 2019-nCov pneumonia. Based on the Baidu Search Index, we propose three prediction models: composite Index, composite Index with filtering and suspected NCP(Novel Coronavirus Pneumonia). The result demonstrates that the predictive model of composite index with filtering performs the best while the model of suspected NCP has the highest forecast error. We further predict the out-of-the-set NCP confirmed cases and monitor that the next peak of new diagnoses will occur on February 16th and 17th.

negative: Recombinant PRRSV expressing porcine circovirus sequence reveals novel aspect of transcriptional control of porcine arterivirus Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) expresses its genes via a set of nested subgenomic (sg) mRNAs. Such discontinuous transcription is unique yet poorly understood for arterivirus. The utilization of transcription-regulating sequence (TRS) remains a puzzle, as many TRS-like sequences exist in viral genome, yet only six or seven sg mRNAs were transcribed in arterivirus infected cells. To investigate the transcriptional control of the porcine arterivirus, a recombinant PRRSV infectious cDNA clone pCPV expressing the capsid gene of porcine circovirus 2 (PCV2) between PRRSV ORF1b and ORF2a was developed. The rescued recombinant viruses contained a range of disparate deletions of the inserted PCV2 sequence, yet two stable recombinant viruses containing 41 and 275nt of foreign sequences were generated upon plaque purification and serial passages. Further analysis of the sg RNA2 profile revealed that an array of novel sg RNA species was generated in cells infected with the recombinant virus. One group was formed by utilizing the inserted PCV2 sequence as TRS; another group was generated from cryptic TRS-like PRRSV sequences located 19, 37 and 97nt immediately downstream of the PRRSV ORF2 AUG. These results demonstrated that (1) the recombinant virus from direct insertion of foreign sequences was genetically unstable, while two recombinant PRRSVs containing foreign sequence of 41 or 275nt in length, respectively, became stable upon plaque purification and further serial passages; (2) PRRSV can utilize foreign TRS-like sequence as transcriptional promoter; (3) the insertion of foreign sequence provoked the generation of novel subgenomic RNAs utilizing cryptic TRS-like sequences that remain non-functional in native PRRSV.

negative: The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.

negative: Case Report: Viral Shedding for 60 Days in a Woman with COVID-19 Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription–polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.

negative: Real-time monitoring the transmission potential of COVID-19 in Singapore, March 2020 BACKGROUND: As of March 31, 2020 the ongoing COVID-19 epidemic that started in China in December 2019 is now generating local transmission around the world. The geographic heterogeneity and associated intervention strategies highlight the need to monitor in real time the transmission potential of COVID-19. Singapore provides a unique case example for monitoring transmission, as there have been multiple disease clusters, yet transmission remains relatively continued. METHODS: Here we estimate the effective reproduction number, R(t), of COVID-19 in Singapore from the publicly available daily case series of imported and autochthonous cases by date of symptoms onset, after adjusting the local cases for reporting delays as of March 17, 2020. We also derive the reproduction number from the distribution of cluster sizes using a branching process analysis that accounts for truncation of case counts. RESULTS: The local incidence curve displays sub-exponential growth dynamics, with the reproduction number following a declining trend and reaching an estimate at 0.7 (95% CI: 0.3, 1.0) during the first transmission wave by February 14, 2020 while the overall R based on the cluster size distribution as of March 17, 2020 was estimated at 0.6 (95% CI: 0.4, 1.02). The overall mean reporting delay was estimated at 6.4 days (95% CI: 5.8, 6.9), but it was shorter among imported cases compared to local cases (mean 4.3 vs. 7.6 days, Wilcoxon test, p<0.001). CONCLUSION: The trajectory of the reproduction number in Singapore underscores the significant effects of successful containment efforts in Singapore, but it also suggests the need to sustain social distancing and active case finding efforts to stomp out all active chains of transmission.

negative: Effect of intergenic consensus sequence flanking sequences on coronavirus transcription. Insertion of a region, including the 18-nucleotide-long intergenic sequence between genes 6 and 7 of mouse hepatitis virus (MHV) genomic RNA, into an MHV defective interfering (DI) RNA leads to transcription of subgenomic DI RNA in helper virus-infected cells (S. Makino, M. Joo, and J. K. Makino, J. Virol. 66:6031-6041, 1991). In this study, the subgenomic DI RNA system was used to determine how sequences flanking the intergenic region affect MHV RNA transcription and to identify the minimum intergenic sequence required for MHV transcription. DI cDNAs containing the intergenic region between genes 6 and 7, but with different lengths of upstream or downstream flanking sequences, were constructed. All DI cDNAs had an 18-nucleotide-long intergenic region that was identical to the 3' region of the genomic leader sequence, which contains two UCUAA repeat sequences. These constructs included 0 to 1,440 nucleotides of upstream flanking sequence and 0 to 1,671 nucleotides of downstream flanking sequence. An analysis of intracellular genomic DI RNA and subgenomic DI RNA species revealed that there were no significant differences in the ratios of subgenomic to genomic DI RNA for any of the DI RNA constructs. DI cDNAs which lacked the intergenic region flanking sequences and contained a series of deletions within the 18-nucleotide-long intergenic sequence were constructed to determine the minimum sequence necessary for subgenomic DI RNA transcription. Small amounts of subgenomic DI RNA were synthesized from genomic DI RNAs with the intergenic consensus sequences UCUAAAC and GCUAAAC, whereas no subgenomic DI RNA transcription was observed from DI RNAs containing UCUAAAG and GCTAAAG sequences. These analyses demonstrated that the sequences flanking the intergenic sequence between genes 6 and 7 did not play a role in subgenomic DI RNA transcription regulation and that the UCUAAAC consensus sequence was sufficient for subgenomic DI RNA transcription.

negative: Why is it difficult to accurately predict the COVID-19 epidemic? Since the COVID-19 outbreak in Wuhan City in December of 2019, numerous model predictions on the COVID-19 epidemics in Wuhan and other parts of China have been reported. These model predictions have shown a wide range of variations. In our study, we demonstrate that nonidentifiability in model calibrations using the confirmed-case data is the main reason for such wide variations. Using the Akaike Information Criterion (AIC) for model selection, we show that an SIR model performs much better than an SEIR model in representing the information contained in the confirmed-case data. This indicates that predictions using more complex models may not be more reliable compared to using a simpler model. We present our model predictions for the COVID-19 epidemic in Wuhan after the lockdown and quarantine of the city on January 23, 2020. We also report our results of modeling the impacts of the strict quarantine measures undertaken in the city after February 7 on the time course of the epidemic, and modeling the potential of a second outbreak after the return-to-work in the city.

negative: Clinical trials on drug repositioning for COVID-19 treatment The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants’ clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.

negative: Cellular Superspreaders: An Epidemiological Perspective on HIV Infection inside the Body

negative: SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium Various reports indicate an association between COVID-19 and anosmia, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2), and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. We then observed that the ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.

negative: ABSL-4 Aerobiology Biosafety and Technology at the NIH/NIAID Integrated Research Facility at Fort Detrick The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require direct body-to-body contact for transmission, due to the potential for infection of numerous people rather than a single individual. Additionally, disease containment is much more difficult to achieve for aerosolized viral pathogens than for pathogens that spread solely via direct person-to-person contact. Thus, aerobiology has become an increasingly necessary component for studying viral pathogens that are naturally or intentionally transmitted by aerosol. The goal of studying aerosol viral pathogens is to improve public health preparedness and medical countermeasure development. Here, we provide a brief overview of the animal biosafety level 4 Aerobiology Core at the NIH/NIAID Integrated Research Facility at Fort Detrick, Maryland, USA.

negative: Responding to the COVID-19 pandemic in complex humanitarian crises

negative: Clinical management of pregnancy in cats Average gestation length in domestic cats is 65.6 days, with a range of 52–74 days. Average reported litter size is 4.0 kittens per litter; litter size is not correlated with number of matings in a given estrus. Superfecundation is common in domestic cats; superfetation never has been definitively proven to occur. Eclampsia may occur during pregnancy in queens, with non-specific clinical signs. Ectopic pregnancy and uterine torsion have been reported. Pregnancy loss may be due to infectious causes, including bacteria, viruses or protozoa, or non-infectious causes, such as hypoluteoidism and chromosome errors.

negative: Antibody therapies for the treatment of COVID-19 An outbreak of COVID-19, the disease caused by infection of the coronavirus SARS-CoV-2, that began in December 2019 in Wuhan, China has caused more than 2,990,559 confirmed human infections and 207,446 deaths as of April 27, 2020 (Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University). Scientists are working quickly on multiple aspects of the pandemic. Genetic analyses are conducted to reveal the source and evolution of SARS-CoV-2, providing knowledge that can be used to contain it and to avoid future outbreaks. Epidemiological studies which incorporates lessons learned from outbreaks of previous related viral diseases can guide development of public health measures effective to contain the current and future outbreaks. Basic virology studies reveal viral structure and function. Pathology studies inform development of strategies to interfere with infection. COVID-19 prevention and treatment strategies are being developed in preclinical and clinical studies. Antibody-based therapy is one viable treatment option. Here, we discuss some of the most active areas of developing strategies to treat COVID-19, focusing on approaches to generate neutralizing antibodies against SARS-CoV-2 for prophylactic and therapeutic treatment of COVID-19. SIGNIFICANCE: Development of SARS-CoV-2 neutralizing antibodies with the desired efficacy and safety profile is a critical part of the toolbox of therapies for the treatment of COVID-19. We discuss in this review the current state of discovery and development of such antibodies.

negative: The risk factors associated with MERS-CoV patient fatality: A global survey Abstract Risk factors associated with Middle East respiratory syndrome coronavirus (MERS-CoV) infection outcome were established by analyses of WHO data from September 23, 2012 to 18 June 2018. Of the 2220 reported cases, 1408 cases, including 451 MERS-CoV deaths, were analyzed. The case fatality rate was 32% (95% CI: 29.4–34.5). Compared to MERS patients ≤30 years old, those with >30 years had the adjusted odds ratio estimate for death of 2.38 [95% CI: 1.75–3.22]. This index was 1.43 [95% CI: 1.06–1.92] for Saudi patients in comparison to non-Saudi; 1.76 [95% CI: 1.39–2.22] for patient with comorbidity in comparison to those without comorbidity; 0.58 [95% CI: 0.44–0.75] for those who had close contact to a camel in the past 14 days and 0.42 [95% CI: 0.31–0.57] for patients with >14 days with onset of signs and hospital admission compared to patients with ≤14 days.

negative: Duration of protection from reinfection following exposure to sialodacryoadenitis virus in Wistar rats. Wistar rats [Cr1:(WI)BR] were inoculated intranasally with approximately 10(3) median mouse lethal infective doses of sialodacryoadenitis (SDA) virus. Animals were subsequently selected at random, removed to a separate isolation room, and reinfected with SDA virus at 3, 6, 9, 12 or 15 months. Pre- and postinoculation serum samples were collected from all animals during the course of the study and evaluated for antibody titers to SDA virus. All experimental, control and sentinel animals, following inoculation with SDA virus, were necropsied and examined for lesions consistent with SDA. Salivary gland lesions were minimal to absent in rats reinfected with SDA virus for up to 12 to 15 months after the initial exposure and minimal to moderate in the respiratory tract at 12 or 15 months. SDA-associated lesions were extensive in age matched control animals examined at each time period of reinfection with SDA virus. Thus, prior exposure to SDA virus did protect against the development of typical salivary gland lesions for up to 15 months. Recovered animals were evaluated for their ability to transmit the virus following reinfection. Rats reinfected at 6 or 9 months were infectious to their naive cage mates. The results indicate that reinfection with homologous rat coronavirus can occur as early as 6 months after the initial infection, and such rats can transmit the infection to contact controls.

negative: Chapter 4 Viral Diseases Transmissible by Kissing Abstract Viral infections can be transmitted by various routes. At one extreme, airborne or droplet viral infections (e.g., varicella zoster, ebola) are highly contagious. Most viruses can be spread by touching surfaces contaminated by the virus and then touching the mouth or eyes. Mass gatherings, clinical, and chronic care facilities may be hotspots for virus spread when transmission is via aerosols, droplets, or fomites (contaminated surfaces). Environmental factors which are often important for virus survival may include the ambient humidity, temperature, and pH of the environment they are in, so many viruses survive only a few hours in the environment and are often readily inactivated by common hygiene techniques, such as using soap and water, and some detergents, disinfectants, and antiseptics. Sexually transmitted viral infections, such as herpes simplex, are often transmitted by close mucosal contacts.

negative: Epidemiological and Clinical Characteristics of 17 Hospitalized Patients with 2019 Novel Coronavirus Infections Outside Wuhan, China An increasing number of cases of novel coronavirus pneumonia (NCP) infected with 2019-nCoV have been identified in Wuhan and other cities in China, since December 2019. We analyzed data on the 17 confirmed cases in Dazhou to provide the epidemiologic characteristics of NCP outside Wuhan. Among them, 12 patients were still quarantined in the hospital, 5 patients were discharged NCP patients according to the national standards. Compared with non-discharged NCP patients, the discharged NCP patients had younger ages. Moreover, discharged NCP patients had higher heart rate, lymphocytes levels and monocytes levels than non-discharged NCP patients on admission to the hospital. Notably, all of 17 patients had abnormal increased C-reactive protein levels, and 16 patients had abnormal computed tomography images. This study provided some information that younger age, higher lymphocytes levels and monocytes levels at the diagnoses of 2019-nCoV may contributed to faster recovery and better therapeutic outcome.

negative: Review article: gastrointestinal features in COVID‐19 and the possibility of faecal transmission BACKGROUND: There is little published evidence on the gastrointestinal features of COVID‐19. AIMS: To report on the gastrointestinal manifestations and pathological findings of patients with COVID‐19, and to discuss the possibility of faecal transmission. METHODS: We have reviewed gastrointestinal features of, and faecal test results in, COVID‐19 from case reports and retrospective clinical studies relating to the digestive system published since the outbreak. RESULTS: With an incidence of 3% (1/41)‐79% (159/201), gastrointestinal symptoms of COVID‐19 included anorexia 39.9% (55/138)‐50.2% (101/201), diarrhoea 2% (2/99)‐49.5% (146/295), vomiting 3.6% (5/138)‐66.7% (4/6), nausea 1% (1/99)‐29.4% (59/201), abdominal pain 2.2% (3/138)‐6.0% (12/201) and gastrointestinal bleeding 4% (2/52)‐13.7% (10/73). Diarrhoea was the most common gastrointestinal symptom in children and adults, with a mean duration of 4.1 ± 2.5 days, and was observed before and after diagnosis. Vomiting was more prominent in children. About 3.6% (5/138)‐15.9% (32/201) of adult and 6.5% (2/31)‐66.7% (4/6) of children patients presented vomiting. Adult and children patients can present with digestive symptoms in the absence of respiratory symptoms. The incidence of digestive manifestations was higher in the later than in the early stage of the epidemic, but no differences in digestive symptoms among different regions were found. Among the group of patients with a higher proportion of severe cases, the proportion of gastrointestinal symptoms in severe patients was higher than that in nonsevere patients (anorexia 66.7% vs 30.4%; abdominal pain 8.3% vs 0%); while in the group of patients with a lower severe rate, the proportion with gastrointestinal symptoms was similar in severe and nonsevere cases (nausea and vomiting 6.9% vs 4.6%; diarrhoea 5.8% vs 3.5%). Angiotensin converting enzyme 2 and virus nucleocapsid protein were detected in gastrointestinal epithelial cells, and infectious virus particles were isolated from faeces. Faecal PCR testing was as accurate as respiratory specimen PCR detection. In 36% (5/14)‐53% (39/73) faecal PCR became positive, 2‐5 days later than sputum PCR positive. Faecal excretion persisted after sputum excretion in 23% (17/73)‐82% (54/66) patients for 1‐11 days. CONCLUSIONS: Gastrointestinal symptoms are common in patients with COVID‐19, and had an increased prevalence in the later stage of the recent epidemic in China. SARS‐CoV‐2 enters gastrointestinal epithelial cells, and the faeces of COVID‐19 patients are potentially infectious.

negative: Asymptomatic novel coronavirus pneumonia patient outside Wuhan: The value of CT images in the course of the disease Abstract The purpose of this case report is to describe the imaging and associated clinical features of an asymptomatic novel coronavirus pneumonia (COVID-19) patient outside Wuhan, China. The principle findings are that in this patient with laboratory-confirmed COVID-19, CT findings preceded symptoms and included bilateral pleural effusions, previously not reported in association with COVID-19. The role of this case report is promotion of potential recognition amongst radiologists of this new disease, which has been declared a global health emergency by the World Health Organization (WHO).

negative: How to handle patients with autoimmune rheumatic and inflammatory bowel diseases in the COVID-19 era: An expert opinion • A correct patient risk stratification is of paramount importance for the proper management of economic and human resources. • It's fundamental to prioritize clinical trials evaluating dosing, prophylaxis, and treatment with immunosuppressant in COVID-19 in order to avoid either an overuse and a treatment shortage. • Future controlled studies may highlight in our patients a potential preventive role of immunosuppressant therapies in the development of severe forms of Covid-19. • Despite the overall risk of infection in rheumatic and gastroenterological diseases a conclusive association between these diseases and COVID −19 remains questionable.

negative: COVID-19; Systematic and literature review of transmission, case definitions, clinical management and clinical trials. Background: SARS-CoV-2, the viral agent responsible for coronavirus disease 2019 (COVID-19) was identified in Wuhan, China at the end of December 2019. It rapidly spread to the rest of the world, and was declared a Public Health Emergency of International Concern on the 30th of January 2020. Our understanding of the virus, it is clinical manifestations and treatment options continues to evolve at an unparalleled pace. Objective: This review sought to summarise the key literature regarding transmission, case definitions, clinical management and trials, and performed a systematic review of reported clinical data on COVID-19. Synthesis methods: Two reviewers selected all the literature independently, and extracted information according to pre-defined topics. Results: COVID-19 is pandemic with ~4 million cases and 270,000 deaths in 210 countries as of 8 May 2020. Our review of reports showed that SARS-CoV-2 was mainly transmitted via inhalation of respiratory droplets containing the virus and had an incubation period of four to six days. The commonly reported symptoms were fever (80%) and cough (60%) across the spectrum of clinical disease - mild, moderate, severe and critical. Categorization of these cases for home care or hospital management need to be well defined considering the age of the patient and the presence of underlying co-morbidities. The case definitions we reviewed varied among affected countries, which could have contributed to the differences observed in the mean case fatality rates among continents: Oceania (1%), Asia (3%), Africa (4%), South America (5%), North America (6%) and Europe (10%). Asymptomatic cases, which constituted an estimated 80% of COVID-19 cases are a huge threat to control efforts. Conclusion: The presence of fever and cough may be sufficient to warrant a COVID-19 testing but using these symptoms in isolation will miss a proportion of cases. A clear definition of a COVID-19 case is important for managing, treating and tracking clinical illness. While several treatments are in development or in clinical trials for COVID-19, home care of mild/moderate cases and hospital care for severe and critical cases remain the recommended management for the disease. Quarantine measures and social distancing can help control the spread of SARS-CoV-2.

negative: Clinical and imaging features of COVID-19 Abstract Since December 2019, multiple cases of 2019 coronavirus disease (COVID-19) have been reported in Wuhan in China's Hubei Province, a disease which has subsequently spread rapidly across the entire country. Highly infectious, COVID-19 has numerous transmission channels and humans are highly susceptible to infection. The main clinical symptoms of COVID-19 are fever, fatigue, and a dry cough. Laboratory examination in the early stage of the disease shows a normal or decreased white blood cell count, and a decreased lymphocyte count. While CT examination serves as the screening and diagnostic basis for COVID-19, its accuracy is limited. The nucleic acid testing is the gold standard for the diagnosis of COVID-19, but has a low sensitivity is low. There is clearly a divide between the two means of examination. This paper reviews the published literature, guidelines and consensus, and summarizes the clinical and imaging characteristics of COVID-19, in order to provide a reliable basis for early diagnosis and treatment.

negative: Coronavirus infection of rat dorsal root ganglia: Ultrastructural characterization of viral replication, transfer, and the early response of satellite cells Abstract Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to gain access to the cell bodies of sensory neurons after peripheral inoculation, resulting in ganglionic infection. It is not clearly understood how this virus is replicated within and released from the sensory neurons, and it remains to know how satellite cells response to the HEV invasion. By ultrastructurally examining HEV-infected rat dorsal root ganglia, we found that HEV in the cell bodies of infected neurons budded from endoplasmic reticulum–Golgi intermediate compartments, and were assembled either individually within small vesicles or in groups within large vesicles. The progeny virions were released from the sensory neurons mainly by smooth-surfaced vesicle-mediated secretory pathway, which occurred predominantly at the perikaryal projections and infoldings of sensory neurons. Released HEV particles were subsequently taken up by the adjacent satellite cells. Almost all virus particles in the cytoplasm of satellite cells were contained in groups within vesicles and lysosome-like structures, suggesting that these glial cells may restrict the local diffusion of HEV. These observations give some insights into the pathogenesis of coronavirus infection and are thought to help understand the interactions between sensory neurons and their satellite cells.

negative: An Ecological Framework for Modeling the Geography of Disease Transmission Ecological niche modeling (ENM) is widely employed in ecology to predict species’ potential geographic distributions in relation to their environmental constraints and is rapidly becoming the gold-standard method for disease risk mapping. However, given the biological complexity of disease systems, the traditional ENM framework requires reevaluation. We provide an overview of the application of ENM to disease systems and propose a theoretical framework based on the biological properties of both hosts and parasites to produce reliable outputs resembling disease system distributions. Additionally, we discuss the differences between biological considerations when implementing ENM for distributional ecology and epidemiology. This new framework will help the field of disease ecology and applications of biogeography in the epidemiology of infectious diseases.

negative: Sentinel Event Surveillance to Estimate Total SARS-CoV-2 Infections, United States Human infections with a novel coronavirus (SARS-CoV-2) were first identified via syndromic surveillance in December of 2019 in Wuhan China. Since identification, infections (coronavirus disease-2019; COVID-19) caused by this novel pathogen have spread globally, with more than 180,000 confirmed cases as of March 16, 2020. Effective public health interventions, including social distancing, contact tracing, and isolation/quarantine rely on the rapid and accurate identification of confirmed cases. However, testing capacity (having sufficient tests and laboratory throughput) to support these non-pharmaceutical interventions remains a challenge for containment and mitigation of COVID-19 infections. We undertook a sentinel event strategy (where single health events signal emerging trends) to estimate the incidence of COVID-19 in the US. Data from a recent national conference, the Conservative Political Action Conference, (CPAC) near Washington, DC and from the outbreak in Wuhan, China were used to fit a simple exponential growth model to estimate the total number of incident SARS- CoV-2 infections in the United States on March 1, 2020, and to forecast subsequent infections potentially undetected by current testing strategies. Our analysis and forecasting estimates a total of 54,100 SARS-CoV-2 infections (80 % CI 5,600 to 125,300) have occurred in the United States to March 12, 2020. Our forecast predicts that a very substantial number of infections are undetected, and without extensive and far-reaching non-pharmaceutical interventions, the number of infections should be expected to grow at an exponential rate.

negative: Systematic review and critical appraisal of prediction models for diagnosis and prognosis of COVID-19 infection Objective To review and critically appraise published and preprint reports of models that aim to predict either (i) presence of existing COVID-19 infection, (ii) future complications in individuals already diagnosed with COVID-19, or (iii) models to identify individuals at high risk for COVID-19 in the general population. Design Rapid systematic review and critical appraisal of prediction models for diagnosis or prognosis of COVID-19 infection. Data sources PubMed, EMBASE via Ovid, Arxiv, medRxiv and bioRxiv until 24th March 2020. Study selection Studies that developed or validated a multivariable COVID-19 related prediction model. Two authors independently screened titles, abstracts and full text. Data extraction Data from included studies were extracted independently by at least two authors based on the CHARMS checklist, and risk of bias was assessed using PROBAST. Data were extracted on various domains including the participants, predictors, outcomes, data analysis, and prediction model performance. Results 2696 titles were screened. Of these, 27 studies describing 31 prediction models were included for data extraction and critical appraisal. We identified three models to predict hospital admission from pneumonia and other events (as a proxy for covid-19 pneumonia) in the general population; 18 diagnostic models to detect COVID-19 infection in symptomatic individuals (13 of which were machine learning utilising computed tomography (CT) results); and ten prognostic models for predicting mortality risk, progression to a severe state, or length of hospital stay. Only one of these studies used data on COVID-19 cases outside of China. Most reported predictors of presence of COVID-19 in suspected patients included age, body temperature, and signs and symptoms. Most reported predictors of severe prognosis in infected patients included age, sex, features derived from CT, C-reactive protein, lactic dehydrogenase, and lymphocyte count. Estimated C-index estimates for the prediction models ranged from 0.73 to 0.81 in those for the general population (reported for all 3 general population models), from 0.81 to > 0.99 in those for diagnosis (reported for 13 of the 18 diagnostic models), and from 0.85 to 0.98 in those for prognosis (reported for 6 of the 10 prognostic models). All studies were rated at high risk of bias, mostly because of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, and poor statistical analysis, including high risk of model overfitting. Reporting quality varied substantially between studies. A description of the study population and intended use of the models was absent in almost all reports, and calibration of predictions was rarely assessed. Conclusion COVID-19 related prediction models are quickly entering the academic literature, to support medical decision making at a time where this is urgently needed. Our review indicates proposed models are poorly reported and at high risk of bias. Thus, their reported performance is likely optimistic and using them to support medical decision making is not advised. We call for immediate sharing of the individual participant data from COVID-19 studies to support collaborative efforts in building more rigorously developed prediction models and validating (evaluating) existing models. The aforementioned predictors identified in multiple included studies could be considered as candidate predictors for new models. We also stress the need to follow methodological guidance when developing and validating prediction models, as unreliable predictions may cause more harm than benefit when used to guide clinical decisions. Finally, studies should adhere to the TRIPOD statement to facilitate validating, appraising, advocating and clinically using the reported models. Systematic review registration protocol: osf.io/ehc47/, registration: osf.io/wy245

negative: Regulation of relative abundance of arterivirus subgenomic mRNAs. The subgenomic (sg) mRNAs of arteriviruses (order Nidovirales) form a 5'- and 3'-coterminal nested set with the viral genome. Their 5' common leader sequence is derived from the genomic 5'-proximal region. Fusion of sg RNA leader and "body" segments involves a discontinuous transcription step. Presumably during minus-strand synthesis, the nascent RNA strand is transferred from one site in the genomic template to another, a process guided by conserved transcription-regulating sequences (TRSs) at these template sites. Subgenomic RNA species are produced in different but constant molar ratios, with the smallest RNAs usually being most abundant. Factors thought to influence sg RNA synthesis are size differences between sg RNA species, differences in sequence context between body TRSs, and the mutual influence (or competition) between strand transfer reactions occurring at different body TRSs. Using an Equine arteritis virus infectious cDNA clone, we investigated how body TRS activity affected sg RNA synthesis from neighboring body TRSs. Flanking sequences were standardized by head-to-tail insertion of several copies of an RNA7 body TRS cassette. A perfect gradient of sg RNA abundance, progressively favoring smaller RNA species, was observed. Disruption of body TRS function by mutagenesis did not have a significant effect on the activity of other TRSs. However, deletion of body TRS-containing regions enhanced synthesis of sg RNAs from upstream TRSs but not of those produced from downstream TRSs. The results of this study provide considerable support for the proposed discontinuous extension of minus-strand RNA synthesis as a crucial step in sg RNA synthesis.

negative: Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside‐Wuhan patients, China OBJECTIVE: Cases with coronavirus disease 2019 (COVID‐19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside‐Wuhan patients to assess the transmission and clinical characteristics of this illness. METHODS: Contact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 23, 2020. Patients were confirmed by PCR test. Demographic, clinical and outcomes were collected and analyzed. RESULTS: Of the 104 patients, 48 (46.15%) were imported cases who were immigrated from Wuhan; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 “generations” was observed. Five asymptomatic infections were found and 2 of them infected their relatives. Mean age was 43 (rang, 8‐84) years and 49 (47.12%) were male. The median incubation period was 6 (rang, 1‐32) days, of 8 patients ranged from 18 to 32 days, 96 (92.31%) discharged and 1 (0.96%) died. Average hospital stay was 10 (rang, 8‐14) days. CONCLUSIONS: Family but not community transmission occupied the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown wok well. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID‐19. A 14‐day quarantine may need to be prolonged. This article is protected by copyright. All rights reserved.

negative: AutoTriage - An Open Source Edge Computing Raspberry Pi-based Clinical Screening System With the recent COVID-19 pandemic, healthcare systems all over the world are struggling to manage the massive increase in emergency department (ED) visits. This has put an enormous demand on medical professionals. Increased wait times in the ED increases the risk of infection transmission. In this work we present an open-source, low cost, off-body system to assist in the automatic triage of patients in the ED based on widely available hardware. The system initially focuses on two symptoms of the infection - fever and cyanosis. The use of visible and far-infrared cameras allows for rapid assessment at a 1m distance, thus reducing the load on medical staff and lowering the risk of spreading the infection within hospitals. Its utility can be extended to a general clinical setting in non-emergency times as well to reduce wait time, channel the time and effort of healthcare professionals to more critical tasks and also prioritize severe cases. Our system consists of a Raspberry Pi 4, a Google Coral USB accelerator, a Raspberry Pi Camera v2 and a FLIR Lepton 3.5 Radiometry Long-Wave Infrared Camera with an associated IO module. Algorithms running in real-time detect the presence and body parts of individual(s) in view, and segments out the forehead and lip regions using PoseNet. The temperature of the forehead-eye area is estimated from the infrared camera image and cyanosis is assessed from the image of the lips in the visible spectrum. In our preliminary experiments, an accuracy of 97% was achieved for detecting fever and 77% for the detection of cyanosis, with a sensitivity of 91% and area under the receiver operating characteristic curve of 0.91. Although preliminary results are promising, we note that the entire system needs to be optimized before use and assessed for efficacy. The use of low-cost instrumentation will not produce temperature readings and identification of cyanosis that is acceptable in many situations. For this reason, we are releasing the full code stack and system design to allow others to rapidly iterate and improve the system. This may be of particular benefit in low-resource settings, and low-to-middle income countries in particular, which are just beginning to be affected by COVID-19.

negative: Mental health at the age of coronavirus: time for change

negative: Severe Acute Respiratory Syndrome–associated Coronavirus Infection Whether severe acute respiratory syndrome–associated coronavirus (SARS-CoV) infection can be asymptomatic is unclear. We examined the seroprevalence of SARS-CoV among 674 healthcare workers from a hospital in which a SARS outbreak had occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321 (48%) were asymptomatic throughout the course of these observations. None of these healthcare workers had antibody to SARS CoV, indicating that subclinical or mild infection attributable to SARS CoV in adults is rare.

negative: Viruses and Evolution – Viruses First? A Personal Perspective The discovery of exoplanets within putative habitable zones revolutionized astrobiology in recent years. It stimulated interest in the question about the origin of life and its evolution. Here, we discuss what the roles of viruses might have been at the beginning of life and during evolution. Viruses are the most abundant biological entities on Earth. They are present everywhere, in our surrounding, the oceans, the soil and in every living being. Retroviruses contributed to about half of our genomic sequences and to the evolution of the mammalian placenta. Contemporary viruses reflect evolution ranging from the RNA world to the DNA-protein world. How far back can we trace their contribution? Earliest replicating and evolving entities are the ribozymes or viroids fulfilling several criteria of life. RNA can perform many aspects of life and influences our gene expression until today. The simplest structures with non-protein-coding information may represent models of life built on structural, not genetic information. Viruses today are obligatory parasites depending on host cells. Examples of how an independent lifestyle might have been lost include mitochondria, chloroplasts, Rickettsia and others, which used to be autonomous bacteria and became intracellular parasites or endosymbionts, thereby losing most of their genes. Even in vitro the loss of genes can be recapitulated all the way from coding to non-coding RNA. Furthermore, the giant viruses may indicate that there is no sharp border between living and non-living entities but an evolutionary continuum. Here, it is discussed how viruses can lose and gain genes, and that they are essential drivers of evolution. This discussion may stimulate the thinking about viruses as early possible forms of life. Apart from our view “viruses first”, there are others such as “proteins first” and “metabolism first.”

negative: Scientific report on the effects of farming systems on dairy cow welfare and disease

negative: Molecular immune pathogenesis and diagnosis of COVID-19 Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.

negative: Tracking the origin of early COVID-19 cases in Canada Abstract The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country’s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world’s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada’s first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.

negative: Heat warning and public and workers' health at the time of COVID-19 pandemic The humanity is currently facing the COVID-19 pandemic challenge, the largest global health emergency after the Second World War. During summer months, many countries in the northern hemisphere will also have to counteract an imminent seasonal phenomenon, the management of extreme heat events. The novelty this year concerns that the world population will have to deal with a new situation that foresees the application of specific measures, including adjunctive personal protective equipment (i.e. facemasks and gloves), in order to reduce the potential transmission of the SARS-CoV-2 virus. These measures should help to decrease the risk of the infection transmission but will also represent an aggravating factor to counteract the heat effects on the population health both at occupational and environmental level. The use of a specific heat health warning system with personalized information based on individual, behavioural and environmental characteristics represents a necessary strategy to help a fast adaptation of the population at a time where the priority is to live avoiding SARS-CoV-2 infection.

negative: Viral Inclusion Bodies in Tracheobronchial Epithelium of Asymptomatic Subjects During a survey conducted for the cytodiagnosis of early bronchogenic carcinoma, cytoplasmic viral inclusion bodies were found sporadically in tracheobronchial smears of asymtomatic patients of both sexes (ages ranging from 18 to 80 years) undergoing general endotracheal anesthesia for surgery. A review of 3,049 cases performed to assess the frequency of occurrence of this phenomenon showed a 1.1 percent incidence in all smears studied. There was no relationship between smoking habit, age, or sex and the presence of inclusion bodies; however, there was a marked seasonal incidence, with 60 percent of inclusion-bearing smears being found during the months of January through March.

negative: 13 Health effects of water consumption and water quality

negative: Immunity to Infection This chapter describes immune responses to the six major types of pathogens: extracellular bacteria, intracellular bacteria, viruses, parasites, fungi and prions. Innate immunity mediated by neutrophils, NK cells, NKT cells, γδ T cells, complement and microbicidal molecules prevents infection or slows it until adaptive immunity can also respond to the pathogen. Extracellular entities are coated in antibody and cleared by antibody- and complement-mediated mechanisms. Parasitic worms are prevented from anchoring in the host by IgA and IgE antibodies. IgE triggers mast cell, basophil and eosinophil degranulation and the release of toxic mediators. Intracellular bacteria and parasites as well as viruses are eliminated by CTLs, NK cells, NKT cells and γδ T cells secreting cytotoxic cytokines and/or carrying out target cell cytolysis. Macrophage hyperactivation and granuloma formation may be triggered to confine persistent invaders. Th1 and Th17 responses support cell-mediated immunity against internal threats, whereas Th2 responses support humoral immunity against external threats. Each type of pathogen has evolved to evade immune responses by avoiding recognition or inactivating various leukocyte effector mechanisms.

negative: Aberrant remyelination of axons after heat injury in the dorsal funiculus of rat spinal cord We studied the course of demyelination and subsequent remyelination of nerve fibers after heat injury in the dorsal funiculus of the rat spinal cord. Four weeks after heat treatment, we observed, in addition to normally remyelinated axons, a few aberrantly remyelinated axons which had both CNS-and PNS-type myelin sheaths: the CNS-type myelin sheaths were always situated inside the PNS-type sheaths. This finding indicates that in some conditions Schwann cells can form myelin sheaths around those formed by oligodendrocytes.

negative: Healthcare worker infected with Middle East Respiratory Syndrome during cardiopulmonary resuscitation in Korea, 2015 OBJECTIVES: During the outbreak of the Middle East Respiratory Syndrome (MERS) in Korea in 2015, the Korea Centers for Disease Control and Prevention (KCDC) confirmed a case of MERS in a healthcare worker in Daejeon, South Korea. To verify the precise route of infection for the case, we conducted an in-depth epidemiological investigation in cooperation with the KCDC. METHODS: We reviewed the MERS outbreak investigation report of the KCDC, and interviewed the healthcare worker who had recovered from MERS. Using the media interview data, we reaffirmed and supplemented the nature of the exposure. RESULTS: The healthcare worker, a nurse, was infected while performing cardiopulmonary resuscitation (CPR) for a MERS patient in an isolation room. During the CPR which lasted for an hour, a large amount of body fluid was splashed. The nurse was presumed to have touched the mask to adjust its position during the CPR. She suggested that she was contaminated with the MERS patient’s body fluids by wiping away the sweat from her face during the CPR. CONCLUSIONS: The possible routes of infection may include the following: respiratory invasion of aerosols contaminated with MERS-coronavirus (MERS-CoV) through a gap between the face and mask; mucosal exposure to sweat contaminated with MERS-CoV; and contamination during doffing of personal protective equipment. The MERS guidelines should reflect this case to decrease the risk of infection during CPR.

negative: Does temperature and humidity influence the spread of Covid-19?: A preliminary report INTRODUCTION: Climate change has been known to influence infectious diseases. The reason for this being the fact; disease agents and their vectors each have particular environments that are optimal for growth, survival, transport, and dissemination. MATERIALS AND METHODS: The WHO's website was accessed to look for the Novel Coronavirus (COVID-19) situation dashboard and comprehensively study and assess the report. An attempt was made to look for countries, areas or territories with maximum and minimum number of cases of lab confirmed COVID cases. Further, we entered the words “Climate“ in google for each of the aforementioned countries and searched for the results. A comparison was established by including countries from both the hemispheres (northern and southern). The preliminary analysis was based on the reports from countries with established testing facilities for Covid-19. RESULTS: The report suggests that countries with higher number of cases are the countries with cold weather. These are also the countries with low humidity which could be favoring the transmission and survival of the SARS-COV-2. CONCLUSIONS: The results though preliminary point to a pattern which favors the hypothesis that the extensive spread of Covid-19 maybe limited by temperature and humidity.

negative: The architecture of SARS-CoV-2 transcriptome SARS-CoV-2 is a betacoronavirus that is responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 was reported recently, but its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we here present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic RNA and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces a large number of transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif being AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the internal modification and the 3′ tail. Functional investigation of the unknown ORFs and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2. Highlights We provide a high-resolution map of SARS-CoV-2 transcriptome and epitranscriptome using nanopore direct RNA sequencing and DNA nanoball sequencing. The transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces transcripts encoding unknown ORFs. We discover at least 41 potential RNA modification sites with an AAGAA motif.

negative: Cell-Type-Specific Expression of Renin-Angiotensin-System Components in the Human Body and Its Relevance to SARS-CoV-2 Infection We have analyzed the cell-type-specific expression of the renin-angiotensin system (RAS) components across 141 cell types or subtypes as defined by single-cell RNA-seq (scRNA-seq) analysis. ACE2, one of the components of RAS, also facilitates SARS-CoV-2 entry into cells in cooperation with its associated protease TMPRSS2. Therefore, our analysis also contributes to the understanding of SARS-CoV-2 infection, spreading of the virus throughout the body, and potential viral interference with RAS in COVID-19 patients.

negative: Animal viral diseases and global change: bluetongue and West Nile fever as paradigms Environmental changes have an undoubted influence on the appearance, distribution, and evolution of infectious diseases, and notably on those transmitted by vectors. Global change refers to environmental changes arising from human activities affecting the fundamental mechanisms operating in the biosphere. This paper discusses the changes observed in recent times with regard to some important arboviral (arthropod-borne viral) diseases of animals, and the role global change could have played in these variations. Two of the most important arboviral diseases of animals, bluetongue (BT) and West Nile fever/encephalitis (WNF), have been selected as models. In both cases, in the last 15 years an important leap forward has been observed, which has lead to considering them emerging diseases in different parts of the world. BT, affecting domestic ruminants, has recently afflicted livestock in Europe in an unprecedented epizootic, causing enormous economic losses. WNF affects wildlife (birds), domestic animals (equines), and humans, thus, beyond the economic consequences of its occurrence, as a zoonotic disease, it poses an important public health threat. West Nile virus (WNV) has expanded in the last 12 years worldwide, and particularly in the Americas, where it first occurred in 1999, extending throughout the Americas relentlessly since then, causing a severe epidemic of disastrous consequences for public health, wildlife, and livestock. In Europe, WNV is known long time ago, but it is since the last years of the twentieth century that its incidence has risen substantially. Circumstances such as global warming, changes in land use and water management, increase in travel, trade of animals, and others, can have an important influence in the observed changes in both diseases. The following question is raised: What is the contribution of global changes to the current increase of these diseases in the world?

negative: An update on the 2019-nCoV outbreak Cases of 2019-nCoV are now being reported in different regions around the globe, concerning for a possible SARS like epidemic that infected for than 8000 people in 2002-03. Though, major health authorities are still working on understanding the virus and its transmission, here we present a brief report regarding the 2019-nCoV outbreak and what is known so far.

negative: Analysis of false-negative results for 2019 novel coronavirus nucleic acid test and related countermeasures/ 中华检验医学杂志 In December 2019, a cluster of patients with pneumonia of unknown cause were linked to a seafood wholesale market in Wuhan, China. Some studies found that the virus was a new kind of virus which had never been found in the human body. Then, the virus was named 2019 Novel Coronavirus (2019-nCoV) by the World Health Organization (WHO). 2019-nCoV nucleic acid detection is one of the essential indicators of NCP (Novel Coronavirus Pneumonia). Recently, some false-negative cases in China-Japan Friendship Hospital and Hangzhou Hospital led the clinical doctors to question the value of the nucleic acid detection. In this paper, more than 3 000 results of 2019-nCoV detection in Zhongnan Hospital, Wuhan University were analyzed. Attention should be paid to the root cause of false-negative results and the related countermeasures should be taken.

negative: Feeding sentinels: Logics of care and biosecurity in farms and labs This article compares the treatment of living beings (unvaccinated chickens and infected cells) considered as sentinel devices in a farm and in a lab in Hong Kong. Sentinel devices are defined as living beings posted on a boundary from which they send signals of invisible threats. The ethnography looks at how they transform differences between ordinary lives and lives exposed, between good death and bad death, through the practices of those who feed them. In farms and labs exposed to Avian Influenza viruses, the logic of biosecurity intersects with a logic of care, blurring the distinction between self and other, friend and enemy through aesthetic judgments concerning what is a ‘good death’. Metabolism and immunity are redefined when sentinels are fed to produce clear signals of the mutations of viruses.

negative: A systematic risk-based strategy to select personal protective equipment for infectious diseases BACKGROUND: Personal protective equipment (PPE) is a primary strategy to protect health care personnel (HCP) from infectious diseases. When transmission-based PPE ensembles are not appropriate, HCP must recognize the transmission pathway of the disease and anticipate the exposures to select PPE. Because guidance for this process is extremely limited, we proposed a systematic, risk-based approach to the selection and evaluation of PPE ensembles to protect HCP against infectious diseases. METHODS: The approach used in this study included the following 4 steps: (1) job hazard analysis, (2) infectious disease hazard analysis, (3) selection of PPE, and (4) evaluation of selected PPE. Selected PPE should protect HCP from exposure, be usable by HCP, and fit for purpose. RESULTS: The approach was demonstrated for the activity of intubation of a patient with methicillin-resistant Staphylococcus aureus or Severe Acute Respiratory Syndrome coronavirus. As expected, the approach led to the selection of different ensembles of PPE for these 2 pathogens. DISCUSSION: A systematic risk-based approach to the selection of PPE will help health care facilities and HCP select PPE when transmission-based precautions are not appropriate. Owing to the complexity of PPE ensemble selection and evaluation, a team with expertise in infectious diseases, occupational health, the health care activity, and related disciplines, such as human factors, should be engaged. CONCLUSIONS: Participation, documentation, and transparency are necessary to ensure the decisions can be communicated, critiqued, and understood by HCP.

negative: Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world’s healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. “First come, first served” is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.

negative: Microbial Exchange via Fomites and Implications for Human Health PURPOSE OF REVIEW: Fomites are inanimate objects that become colonized with microbes and serve as potential intermediaries for transmission to/from humans. This review summarizes recent literature on fomite contamination and microbial survival in the built environment, transmission between fomites and humans, and implications for human health. RECENT FINDINGS: Applications of molecular sequencing techniques to analyze microbial samples have increased our understanding of the microbial diversity that exists in the built environment. This growing body of research has established that microbial communities on surfaces include substantial diversity, with considerable dynamics. While many microbial taxa likely die or lay dormant, some organisms survive, including those that are potentially beneficial, benign, or pathogenic. Surface characteristics also influence microbial survival and rates of transfer to and from humans. Recent research has combined experimental data, mechanistic modeling, and epidemiological approaches to shed light on the likely contributors to microbial exchange between fomites and humans and their contributions to adverse (and even potentially beneficial) human health outcomes. SUMMARY: In addition to concerns for fomite transmission of potential pathogens, new analytical tools have uncovered other microbial matters that can be transmitted indirectly via fomites, including entire microbial communities and antibiotic-resistant bacteria. Mathematical models and epidemiological approaches can provide insight on human health implications. However, both are subject to limitations associated with study design, and there is a need to better understand appropriate input model parameters. Fomites remain an important mechanism of transmission of many microbes, along with direct contact and short- and long-range aerosols.

negative: Prevention and Control Strategies for SARS-CoV-2 Infection The population of 168 countries all over the world is struggling with the outbreak of COVID-19. The outbreak is declared as pandemic and public health emergency of international concern declared by WHO. SARS-CoV-2 responsible for the present health emergency exhibited close resemblance with SARS-CoV. Both the viruses are zoonotic and belong to a large family of viruses Coronaviridae. The complete virus particle is made up of four major structural proteins, namely spikes (S), nucleocapsid (N), membrane (M), and envelope (E) encoded by virus genome. The S protein of virus shows similarity to S protein of SARS-CoV. COVID-19 spreads from person to person, and this makes it more vulnerable for causing infection. Several efforts are taken to find prevention strategies for COVID-19. Researchers across the globe are working to find effective vaccination for SARS-CoV-2. There is no vaccine or medication available till date for COVID-19. Preventive measures such as social distancing, awareness, maintenance of hygiene, isolation, and movement restrictions can help in control of COVID-19 spread. Proper sanitization and cleaned and sanitized public transport can be effective in inhibiting the spread of the virus. In the present situation of medical emergency, cooperation and support by following advices from the WHO and government only facilitate everyone to come over.

negative: Avian coronavirus infectious bronchitis attenuated live vaccines undergo selection of subpopulations and mutations following vaccination In this study, we were interested in determining if high titered egg adapted modified live infectious bronchitis virus (IBV) vaccines contain spike gene related quasispecies that undergo selection in chickens, following vaccination. We sequenced the spike glycoprotein of 12 IBV vaccines (5 different serotypes from 3 different manufacturers) directly from the vaccine vial, then compared that sequence with reisolated viruses from vaccinated and contact-exposed birds over time. We found differences in the S1 sequence within the same vaccine serotype from different manufacturers, differences in S1 sequence between different vaccine serials from the same manufacturer, and intra-vaccine differences or quasispecies. Comparing the sequence data of the reisolated viruses with the original vaccine virus, we were able to identify in vivo selection of viral subpopulations as well as mutations. To our knowledge, this is the first report showing selection of a more fit virus subpopulation as well as mutations associated with replication of modified live IBV vaccine viruses in chickens. This information is important for our understanding of how attenuated virus vaccines, including potential vaccines against the SARS-CoV, can ensure long-term survival of the virus and can lead to changes in pathogenesis and emergence of new viral pathogens. This information is also valuable for the development of safer modified live coronavirus vaccines.

negative: Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study BACKGROUND: The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. METHODS: This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. RESULTS: Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29). CONCLUSIONS: In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

negative: Chapter Four Coronavirus cis-Acting RNA Elements Abstract Coronaviruses have exceptionally large RNA genomes of approximately 30 kilobases. Genome replication and transcription is mediated by a multisubunit protein complex comprised of more than a dozen virus-encoded proteins. The protein complex is thought to bind specific cis-acting RNA elements primarily located in the 5′- and 3′-terminal genome regions and upstream of the open reading frames located in the 3′-proximal one-third of the genome. Here, we review our current understanding of coronavirus cis-acting RNA elements, focusing on elements required for genome replication and packaging. Recent bioinformatic, biochemical, and genetic studies suggest a previously unknown level of conservation of cis-acting RNA structures among different coronavirus genera and, in some cases, even beyond genus boundaries. Also, there is increasing evidence to suggest that individual cis-acting elements may be part of higher-order RNA structures involving long-range and dynamic RNA–RNA interactions between RNA structural elements separated by thousands of nucleotides in the viral genome. We discuss the structural and functional features of these cis-acting RNA elements and their specific functions in coronavirus RNA synthesis.

negative: Effects of inhalation exposure to a high-boiling (288 to 454°C) coal liquid Abstract Coal liquids have been evaluated in a variety of short-term toxicological assays; however, few studies have been conducted to determine the systemic effects after inhalation exposure to these materials. To extend the data base on potential health effects from coal liquefaction materials, we performed a study with solvent refined coal (SRC)-II heavy distillate (HD). Fischer-344 rats were exposed for 6 hr/day, 5 days/week for 5 or 13 weeks to an aerosol of HD (boiling range, 288 to 454°C) at concentrations of 0.69, 0.14, 0.03, or 0.0 mg/liter of air for the high, middle, low, and control groups, respectively. Survival through 13 weeks of exposure was greater than 90% for all groups; body weights for exposed animals were decreased in a dose-dependent manner. significant increases in liver weights and decreases in thymus and ovary weights were observed for treated animals compared with controls. There were also significant treatment-related decreases in erythrocytes, hemoglobin, volume of packed red blood cells, lymphocytes, eosinophils, and total white blood cells. After 5 weeks of exposure serum cholesterol concentrations increased in a dose-dependent manner for both sexes and serum triglyceride amounts decreased for males but not for females. After 13 weeks of exposure, high-dose animals had significant increases in cholesterol (males only), triglycerides, blood urea nitrogen, and serum glutamic pyruvic transaminase (SGPT; males) and significant decreases in albumin, SGPT (females), and lactate dehydrogenase (LDH). Examination of bone-marrow preparations from exposed animals demonstrated consistent decreases in the degree of cellularity, suggesting that this organ is a target for HD. Microscopic evaluation of organ sections indicated exposure-related changes for nasal mucosa, pulmonary macrophages, thymus, liver, kidney, bone marrow, ovaries, and cecum. Results from this study indicated dose-dependent increases in the severity of the lesions observed, with few effects in the low-exposure group that were attributable to the exposure.

negative: A spatial model of CoVID-19 transmission in England and Wales: early spread and peak timing Background: An outbreak of a novel coronavirus, named CoVID-19, was first reported in China on 31 December 2019. As of 9 February 2020, cases have been reported in 25 countries, including probable cases of human-to-human transmission in England. Methods: We adapted an existing national-scale metapopulation model to capture the spread of CoVID-19 in England and Wales. We used 2011 census data to capture population sizes and population movement, together with parameter estimates from the current outbreak in China. Results: We predict that a CoVID-19 outbreak will peak 126 to 147 days (~4 months) after the start of person-to-person transmission in England and Wales in the absence of controls, assuming biological parameters remain unchanged. Therefore, if person-to-person transmission persists from February, we predict the epidemic peak would occur in June. The starting location has minimal impact on peak timing, and model stochasticity varies peak timing by 10 days. Incorporating realistic parameter uncertainty leads to estimates of peak time ranging from 78 days to 241 days after person-to-person transmission has been established. Seasonal changes in transmission rate substantially impact the timing and size of the epidemic peak, as well as the total attack rate. Discussion: We provide initial estimates of the potential course of CoVID-19 in England and Wales in the absence of control measures. These results can be refined with improved estimates of epidemiological parameters, and permit investigation of control measures and cost effectiveness analyses. Seasonal changes in transmission rate could shift the timing of the peak into winter months, which will have important implications for healthcare capacity planning.

negative: SARS Coronaviruses and Highly Pathogenic Influenza Viruses: Safety and Occupational Health for Laboratory Workers

negative: Immunological Implications of Physical Inactivity among Older Adults during the COVID-19 Pandemic Social distancing has been adopted worldwide to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Social isolation is likely to lead to a decline in physical activity, which could result in immune system dysfunction, thereby increasing infection susceptibility and exacerbating the pathophysiology of conditions that are common among older adults, including cardiovascular disease, cancer, and inflammatory disorders. Older adults and people living with these comorbidities are at a greater risk for complications during coronavirus disease 2019 (COVID-19). In this review, we discuss the negative impact of physical inactivity on immune function and showcase evidence that regular physical activity may be an effective strategy to counter some of the deleterious effects of social isolation. Furthermore, we briefly highlight key research questions in exercise immunology, with a focus on older adults in the context of COVID-19. Although it is worth emphasizing that there is no direct evidence that physical activity can prevent or treat COVID-19, promoting an active lifestyle is a key intervention to counteract the effects of social isolation, especially in older adults and other at-risk individuals, such as those living with chronic diseases associated with ageing and lifestyle.

negative: Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review INTRODUCTION: Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies. METHODS: We searched five general, three Chinese and four coronavirus disease (COVID-19)–specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments. RESULTS: We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps. CONCLUSION: While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.

negative: Correction for Li et al., “Discovery of Bat Coronaviruses through Surveillance and Probe Capture-Based Next-Generation Sequencing”

negative: Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation. Severe acute respiratory syndrome (SARS) coronavirus (SCoV) causes a recently emerged human disease associated with pneumonia. The 5' end two-thirds of the single-stranded positive-sense viral genomic RNA, gene 1, encodes 16 mature proteins. Expression of nsp1, the most N-terminal gene 1 protein, prevented Sendai virus-induced endogenous IFN-beta mRNA accumulation without inhibiting dimerization of IFN regulatory factor 3, a protein that is essential for activation of the IFN-beta promoter. Furthermore, nsp1 expression promoted degradation of expressed RNA transcripts and host endogenous mRNAs, leading to a strong host protein synthesis inhibition. SCoV replication also promoted degradation of expressed RNA transcripts and host mRNAs, suggesting that nsp1 exerted its mRNA destabilization function in infected cells. In contrast to nsp1-induced mRNA destablization, no degradation of the 28S and 18S rRNAs occurred in either nsp1-expressing cells or SCoV-infected cells. These data suggested that, in infected cells, nsp1 promotes host mRNA degradation and thereby suppresses host gene expression, including proteins involved in host innate immune functions. SCoV nsp1-mediated promotion of host mRNA degradation may play an important role in SCoV pathogenesis.

negative: A Method to Model Outbreaks of New Infectious Diseases with Pandemic Potential such as COVID-19 The emergence of the novel coronavirus (a.k.a. COVID-19, SARS-CoV-2) out of Wuhan, Hubei Province, China caught the world by surprise. As the outbreak began to spread outside of China, too little was known about the virus to model its transmission with any acceptable accuracy. World governments responded to rampant misinformation about the virus leading to collateral disasters, such as plunging financial markets, that could have been avoided if better models of the outbreak had been available. This is an engineering approach to model the spread of a new infectious disease from sparse data when little is known about the infectious agent itself. The paper is not so much about the model itself - because there are many good scientific approaches to model an epidemic - as it is about crunching numbers when there are barely any numbers to crunch. The coronavirus outbreak in USA is used to illustrate the implementation of this modeling approach. A Monte Carlo approach is implemented by using incubation period and testing efficiency as variables. Among others it is demonstrated that imposing early travel restrictions from infected countries slowed down the outbreak in the USA by about 26 days.

negative: A New Virulent Human Coronavirus: How Much Does Tissue Culture Tropism Tell Us?

negative: Barriers of the Human Organism and Their Achilles’ Heels The human body is covered by barriers separating it from the external and internal surroundings. The “milieu enterieur” has to be stabilised in spite of the variable external and internal conditions of toxic, osmotic, microbial and climatic environmental circumstances. This first line of barriers is composed of skin and mucous membranes of complicated structures. A second line of barrier system is present in our organisms. Certain organs have to be separated from the immune system and other parts of the body because of evolutionary reasons (eye-bulb and testicles) because of unique proteins “unknown” for the acquired immune system. The blood-brain barrier (BBB) is providing enhanced safety circumstances for the central nervous system. The second line of barriers is represented by the special properties of the capillary endothelial system. The maternal-fetal barrier is the most complex. At the maternal fetal interface two individuals of two different haplotypes has to be live 9 months separated by a very complicated dynamic barrier. The placenta is the organ, which is separating the maternal and fetal tissues. Similar to others the bidirectional transport of gasses, metabolites, cells, proteins, regulatory substances, are transported by active or passive transcellular and intercellular mechanisms. The fetal immune system develops immunotolerance to all maternal cells and antigens transferred transplacentally. The problem is to mitigate the maternal immune system to tolerate the paternal haplotype of the fetus. In the case of normal pregnancy a complex series of physiological modifications can solve the problem without harmful consequences to the mother and fetus. The outermost contact cells of trophoblasts express instead of HLA-class Ia and class II antigens non-variable HLA-C, HLA-E, HLA-F and HLA-G antigens. The first consequence of this is reduction of the activity of maternal natural killer cells and maternal dendritic cells; Progesteron, micro-RNA and mediators influence the development of T effector-cells. The production of soluble HLA-G(5 and 6) and IL-10 supports the differentiation of Th-2 CD4(+) helper cells, reducing the ability of maternal cells to kill fetal cells. Series of receptors and costimulators are expressed by the different lines of semi-allogenic trophoblast cells to bind HLA-G and mitigate maternal immune response; The maternal immunotolerance is further facilitated by the activation of CD4(+)CD25(bright)Foxp3(+) regulatory T (T(REG)) cells. Infections have to be prevented during pregnancy. The cells of placenta express 10 Toll-like receptors a group of pattern recognition receptors responsible for innate immunity. The interferon level is also higher in the placental tissues than in the somatic fetal or maternal cells. The complement system is also adapted to the requirements of the pregnancy and fetal damage is inhibited by the production of “assymmetric IgG antibodies” under hormonal and placental-regulation. These modifications prevent the activation of complement, cytotoxic activity, opsonising ability, antigen clearance and precipitating activity of the molecules. The Achilles’ heels of the different barriers are regularly found by virus infections. Lamina cribrosa of the blood-brain barrier, optical nerve of the eyes, etc. the risk factors of the maternal-fetal barrier has been summarised in Table 1.1.

negative: Influence of Dietary Fat and Protein on Body Composition of Jersey Bull Calves 1 Abstract Thirty-nine bull calves between 6 and 9 d of age, were assigned to either baseline slaughter or 1 of 4 diets to determine the influence of dietary fat and protein content, at 2 levels of intake, on growth and body composition changes. Calves were assigned to the following diets a 28.5% protein and 16.4% fat milk replacer [MR; 29/16 (n=9)], 27.3% protein and 33.4% fat MR [27/33 (n=8)], 20.6% protein and 20.6% fat MR [20/20 (8)], or whole milk [WM (n=8)]. Calves fed 27/33, 29/16, and WM received 180 g/d of CP to support 650g of ADG based on predictions from the 2001 NRC. Calves were fed 3 times daily for 4 wk. Weight, hip height, wither height, heart girth, and body length were measured weekly. Weekly plasma samples were analyzed for plasma urea nitrogen, nonesterified fatty acids, and glucose. A subset of calves from each treatment was killed [29/16 (n=7), 27/33 (n=6), 20/20 (n=6), and WM (n=5)] at the end of wk 4 of treatment; processed for whole-body analysis of fat, protein, ash, and DM; and compared with baseline slaughter calves to estimate composition of empty BW gain. Calves did not differ in average weekly scour score or medication days. Feed efficiency and ADG were greatest for calves fed WM and least for calves fed 20/20; calves fed 29/16 and 27/33 did not differ. Calves fed 27/33 or WM had the greatest % body fat and gained more grams of fat than calves fed other diets. Calves fed 29/16 or 20/20 had similar % fat in empty body as baseline. Differences in % CP, % ash, or % water in empty body and empty BW gain were not detected. Calves fed 27/33 had a trend toward higher NEFA in wk 1 and 2 than calves fed 29/16 or WM. Growth of calves fed 27/33 and 29/16 were similar except that calves fed 29/16 had lower body fat % than calves fed 27/33. Calves on all diets gained less than predicted by the 2001 NRC.

negative: Coronavirus and financial volatility: 40 days of fasting and fear 40 days after the start of the international monitoring of COVID-19, we search for the effect of official announcements regarding new cases of infection and death ratio on the financial markets volatility index (VIX). Whereas the new cases reported in China and outside China have a mixed effect on financial volatility, the death ratio positively influences VIX, that outside China triggering a more important impact. In addition, the higher the number of affected countries, the higher the financial volatility is.

negative: Predict the next moves of COVID-19: reveal the temperate and tropical countries scenario The spread of COVID-19 engulfs almost all the countries and territories of the planet, and infections and fatality are increasing rapidly. The first epi-center of its' massive spread was in Wuhan, Hubei province, China having a temperate weather, but the spread has got an unprecedented momentum in European temperate countries mainly in Italy and Spain (as of March 30, 2020). However, Malaysia and Singapore and the neighboring tropical countries of China got relatively low spread and fatality that created a research interest on whether there are potential impacts of weather condition on COVID-19 spread. Adopting the SIR (Susceptible Infected Removed) deviated model to predict potential cases and death in the coming days from COVID-19 was done using the secondary and official sources of data. This study shows that COVID-19 spread and fatality tend to be high across the world but compared to tropical countries, it is going to be incredibly high in the temperate countries having lower temperature (7-16°C) and humidity (80-90%) in last March. However, some literature predicted that this might not to be true, rather irrespective of weather conditions there might be a continuous spread and death. Moreover, a large number of asymptotic COVID-19 carrier in both temperate and tropical countries may re-outbreak in the coming winter. Therefore, a comprehensive global program with the leadership of WHO for testing of entire population of the world is required, which will be very useful for the individual states to take proper political action, social movement and medical services.

negative: Antibacterial activity evaluation of selected essential oils in liquid and vapor phase on respiratory tract pathogens BACKGROUND: The increasing number of multidrug-resistant bacteria and the fact of antibiotic resistance is leading to a continuous need for discovering alternative treatments against infections, e.g. in the case of respiratory tract diseases. Essential oils (EOs), because of their volatility, can easily reach both the upper and lower parts of the respiratory tract via inhalation. Therefore, the aim of the present study was the antibacterial evaluation of clove, cinnamon bark, eucalyptus, thyme, scots pine, peppermint, and citronella EOs against respiratory tract pathogens such as Streptococcus pneumoniae, S. mutans, S. pyogenes, Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis. Furthermore, we wanted to compare the antibacterial effect of these EOs in two different test systems to provide data for the development of an appropriate product formulation. METHODS: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined with in vitro vapor phase test (VPT) and broth macrodilution test (BDT). The chemical and percentage compositions of the EOs were determined by GC-MS and GC-FID analysis. RESULTS: Among the EOs, thyme was the most effective against S. mutans (MIC: 0.04 mg/mL in BDT, but cinnamon bark and clove oils also presented high inhibition in liquid medium with MIC values of 0.06 mg/mL and 0.1 mg/mL against S. pneumoniae and S. pyogenes, respectively. M. catarrhalis was the most sensitive to thyme EO (MIC: 0.09 mg/mL). Cinnamon bark EO was the most effective against Haemophilus spp. (MIC: 0.06 mg/mL). In the VPT, cinnamon bark was the most effective oil against all investigated pathogens with MIC values in the range of 15.62–90 μl/L. Surprisingly, the eucalyptus and scots pine showed weak activity against the test bacteria in both test systems. CONCLUSIONS: The EO of thyme, clove and cinnamon bark may provide promising antibacterial activity against respiratory tract pathogens either in liquid medium or in vapor phase. However, their effect is lower than that of the reference antibiotics. The combination of EOs and antibiotics may be beneficial in the alternative treatment of respiratory tract diseases. In vivo studies are necessary to calculate the effective dose of EOs in patients and determine their possible side effects and toxicity.

negative: Purified coronavirus Spike protein nanoparticles induce coronavirus neutralizing antibodies in mice Development of vaccination strategies for emerging pathogens are particularly challenging because of the sudden nature of the emergence of these viruses and the long process needed for traditional vaccine development. Therefore, there is a need for development of a rapid method of vaccine development that can respond to emerging pathogens in a short time frame. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome (MERS-CoV) in late 2012 demonstrate the importance of coronaviruses as emerging pathogens. The spike glycoproteins of coronaviruses reside on the surface of the virion and are responsible for virus entry. The spike glycoprotein is the major immunodominant antigen of coronaviruses and has proven to be an excellent target for vaccine designs that seek to block coronavirus entry and promote antibody targeting of infected cells. Vaccination strategies for coronaviruses have involved live attenuated virus, recombinant viruses, non-replicative virus-like particles expressing coronavirus proteins or DNA plasmids expressing coronavirus genes. None of these strategies has progressed to an approved human coronavirus vaccine in the ten years since SARS-CoV emerged. Here we describe a novel method for generating MERS-CoV and SARS-CoV full-length spike nanoparticles, which in combination with adjuvants are able to produce high titer antibodies in mice.

negative: A mathematical model of COVID-19 transmission between frontliners and the general public The number of COVID-19 cases is continuously increasing in different countries (as of March 2020) including the Philippines. It is estimated that the basic reproductive number of COVID-19 is around 1.5 to 4. The basic reproductive number characterizes the average number of persons that a primary case can directly infect in a population full of susceptible individuals. However, there can be superspreaders that can infect more than this estimated basic reproductive number. In this study, we formulate a conceptual mathematical model on the transmission dynamics of COVID-19 between the frontliners and the general public. We assume that the general public has a reproductive number between 1.5 to 4, and frontliners (e.g. healthcare workers, customer service and retail personnel, food service crews, and transport or delivery workers) have a higher reproduction number. Our simulations show that both the frontliners and the general public should be protected or resilient against the disease. Protecting only the frontliners will not result in flattening the epidemic curve. Protecting only the general public may flatten the epidemic curve but the infection risk faced by the frontliners is still high, which may eventually affect their work. Our simple model does not consider all factors involved in COVID-19 transmission in a community, but the insights from our model results remind us of the importance of community effort in controlling the transmission of the disease. All in all, the take-home message is that everyone in the community, whether a frontliner or not, should be protected or should implement preventive measures to avoid being infected.

negative: Intubation outside of the operating room: new challenges and opportunities in COVID-19 era. PURPOSE OF REVIEW Airway management in patients outside the operating room is associated with increased difficulties and risks, and the setting of the COVID-19 global pandemic adds another layer of complexity. Therefore, endotracheal intubation (ETT) of a patient who is presumptive COVID-19 or COVID-19 positive presents an additional challenge to an anesthesiologist. The aim of this review is to summarize the important principles of airway management outside of the operating room during the COVID-19 pandemic. RECENT FINDINGS Several professional societies have formulated guidelines on airway management COVID-19 suspect and proven patients. Additionally, anesthesiologists working in hospitals treating many infected patients have developed specialized teams responsible for airway management outside the operating room. These documents and protocols focus on the importance of wearing personal protective equipment and the skills of the providers responsible for securing the airway. Staff safety is always a priority when performing ETT outside operating room. SUMMARY The COVID-19 pandemic redefined the management of patients requiring aerosol generating procedures (droplet and airborne precautions). ETT is one of them and anesthesiologists are experts in performing airway management. Although the operating room is a highly controlled environment, airway management outside of this setting is not always the easiest task.

negative: Chapter 13 Epidemiology of Viral Infections Abstract Epidemiology is the study of the distribution, the dynamics, and the determinants of diseases in populations. The risk of virus infection and/or clinical disease is determined by characteristics both of the virus, and the levels of innate and acquired resistance in the community. Virus transmission is affected by behavioral, environmental, and ecological factors. Knowledge of these factors contributes to evidence-based policy decisions as to how best to control and prevent virus diseases. Considerable use of genome sequencing of isolates now provides useful information as to the identification of outbreak sources as well as informing the design and testing of candidate vaccines.

negative: The unsynchronized changes of CT image and nucleic acid detection in COVID-19: reports the two cases from Gansu, China The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been considered as a criterion for ending antiviral treatment. We compared the two COVID-19 cases with similar backgrounds and CT image repeated intervals under treatment. Our report highlighted the unsynchronized expression in the changes of CT image and nucleic acid detection in COVID-19, and lasting positive nucleic acid test result in patients recovered from pneumonia. It may be contributed to recognize the disease and improve prevention.

negative: Advances in the Relationship Between Coronavirus Infection and Cardiovascular Diseases The outbreak of coronavirus disease 2019 (COVID-19) has once again aroused people's concern about coronavirus. Seven human coronaviruses (HCoVs) have been discovered so far, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU115, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2. Existing studies show that the cardiovascular disease increased the incidence and severity of coronavirus infection. At the same time, myocardial injury caused by coronavirus infection is one of the main factors contributing to poor prognosis. In this review, the recent clinical findings about the relationship between coronaviruses and cardiovascular diseases and the underlying pathophysiological mechanisms are discussed. This review aimed to provide assistance for the prevention and treatment of COVID-19.

negative: Mobile phones represent a pathway for microbial transmission: A scoping review Abstract Background Mobile phones have become an integral part of modern society. As possible breeding grounds for microbial organisms, these constitute a potential global public health risk for microbial transmission. Objective Scoping review of literature examining microbial's presence on mobile phones in both health care (HC) and community settings. Methods A search (PubMed&GoogleScholar) was conducted from January 2005–December 2019 to identify English language studies. Studies were included if samples from mobile phones were tested for bacteria, fungi, and/or viruses; and if the sampling was carried out in any HC setting, and/or within the general community. Any other studies exploring mobile phones that did not identify specific microorganisms were excluded. Results A total of 56 studies were included (from 24 countries). Most studies identified the presence of bacteria (54/56), while 16 studies reported the presence of fungi. One study focused solely on RNA viruses. Staphylococcus aureus, and Coagulase-Negative Staphylococci were the most numerous identified organisms present on mobile phones. These two species and Escherichia coli were present in over a third of studies both in HC and community samples. Methicillin-resistant S. aureus, Acinetobacter sp., and Bacillus sp. were present in over a third of the studies in HC settings. Conclusions While this scoping review of literature regarding microbial identification on mobile phones in HC and community settings did not directly address the issue of SARS-CoV-2 responsible for COVID-19, this work exposes the possible role of mobile phones as a ‘Trojan horse’ contributing to the transmission of microbial infections in epidemics and pandemics.

negative: From the “Madding Crowd” to mass gatherings-religion, sport, culture and public health Abstract Human behavior has long engaged in collective behavior assembling in crowds. The Christian pilgrimage to the Holy Land has been recorded since the 4th century, while the Hajj, Islam's great pilgrimage, has existed for fourteen centuries, of which a body of literature devoted to the travelogues of the Hajj has been recorded for over ten centuries. Football is a sport played worldwide by more than 1.5 million teams and in 300,000 clubs. Most however play outside of the officially organized sphere: more than 4 percent of the global population plays football, including 270 million amateur players. Assembling for specific events is a uniquely human behavior, though the formal study of crowds did not begin until the mid-Twentieth Century. Today Mass Gathering Medicine focuses on the public health challenges to hosting events attended by a large enough number of people, at a specific site, for a defined period of time, likely to strain both the planning and response to the mass gathering of a community, state, or nation. All of us can recall attending a mass gathering, whether it be watching one's favorite rock group in performance or assembling for religious pilgrimage. Certainly, the event itself is transporting and transforming and the unison of behaviors and activities can be enormously enriching, uplifting and overwhelming, just as much as they may be at times dangerous and high risk. This review seeks to draw contrasts and comparisons between sporting gatherings and religious gatherings with a chief focus on Hajj, among the largest of all mass gatherings today. We will find there are some powerful similarities as well as stark differences. Each bequeaths a legacy which can inform the other and, as we make our observations, we join with you and the legions of other investigators who continue to remain fascinated and enthralled by mass gatherings which are among the most beloved and beholden events of modern humanity.

negative: Unraveling the Structure of Viral Replication Complexes at Super-Resolution During infection, many RNA viruses produce characteristic inclusion bodies that contain both viral and host components. These structures were first described over a century ago and originally termed “X-bodies,” as their function was not immediately appreciated. Whilst some inclusion bodies may represent cytopathic by-products of viral protein over-accumulation, X-bodies have emerged as virus “factories,” quasi-organelles that coordinate diverse viral infection processes such as replication, protein expression, evasion of host defenses, virion assembly, and intercellular transport. Accordingly, they are now generally referred to as viral replication complexes (VRCs). We previously used confocal fluorescence microscopy to unravel the complex structure of X-bodies produced by Potato virus X (PVX). Here we used 3D-structured illumination (3D-SIM) super-resolution microscopy to map the PVX X-body at a finer scale. We identify a previously unrecognized membrane structure induced by the PVX “triple gene block” (TGB) proteins, providing new insights into the complex interplay between virus and host within the X-body.

negative: Animal virus ecology and evolution are shaped by the virus host-body infiltration and colonization pattern The current classification of animal viruses primarily relates to the virus molecular world, the genomic architecture and the corresponding host-cell infection cycle. This virus centered perspective does not make allowance for the precept that virus fitness hinges on the virus transmission success. Virus transmission reflects the infection-shedding-transmission dynamics and, with it, the organ system involvement and other, macroscopic dimensions of the host environment. This study examines the transmission ecology of the world main livestock viruses, 36 in total, belonging to eleven different families, and a mix of RNA, DNA and retroviruses. Viruses are virtually ranked in an outer- to inner-body fashion, based on the shifting organ system involvement and associated infection-shedding-transmission dynamics. As a next step, this ranking is disentangled with the aim to contrast two main host ecologies, poultry plus pig production and ruminant plus equine husbandry, as well as to create a distinction among the RNA, DNA and retroviruses, also ranked in an outer- to inner-body fashion. Spearman correlation reveals the matches among these various virus traits, as pertaining to the two host-ecologies, four infection-shedding-transmission related variables, and the three virus genomes. The collective results reveal the outer- to inner-body shifts in the interplay of host environment, virus-host interactions, and nature of the virus. Two opposing virus evolution pathways emerge, respectively for generalist type, outer-body and for specialist type, inner-body viruses. The ecological virus classification here presented is broadly consistent with the current virus classification system and offers the advantage of bringing substance and cohesion to the interrelationships among viruses and virus families. Author Summary It remains unknown how exactly viruses fit in the tree of life. Still, there is growing awareness that viruses as biological replicators are subjected to ecological sorting and so require a viable propagation strategy. In the current analysis I depart from the precept that virus fitness hinges on the virus transmission success. I examine the transmission ecologies of the world main livestock viruses, 36 in total, a collection of pathogens well described in terms of the organ system involvement, infection course, the extent of host damage, virus shedding profile, and virus transmission modes. The viruses are on this basis ranked in an outer- to inner-body fashion, virtually. As a next step, this ranking is disentangled with a view to contrast two main host ecologies, poultry plus pig production and ruminant plus equine husbandry, as well as to create a distinction among the RNA, DNA and retrovirus in the study. The matches among these various virus traits serve to establish the outer- to inner-body shifts in the interplay of host environment, virus-host interactions, and nature of the virus. Two opposing virus evolution pathways emerge, respectively for generalist type, outer-body and for specialist, inner-body viruses.

negative: COVID-19 in a designated infectious diseases hospital outside Hubei Province, China BACKGROUND: The clinical characteristics of novel coronavirus disease (COVID-2019) patients outside the epicenter of Hubei Province are less understood. METHODS: We analyzed the epidemiological and clinical features of all COVID-2019 cases in the only referral hospital in Shenzhen City, China, from January 11, 2020, to February 6, 2020, and followed until March 6, 2020. RESULTS: Among the 298 confirmed cases, 233 (81.5%) had been to Hubei, while 42 (14%) did not have a clear travel history. Only 218 (73.15%) cases had a fever as the initial symptom. Compared with the nonsevere cases, severe cases were associated with older age, those with underlying diseases, and higher levels of C-reactive protein, interleukin-6, and erythrocyte sedimentation rate. Slower clearance of the virus was associated with a higher risk of progression to critical condition. As of March 6, 2020, 268 (89.9%) patients were discharged and the overall case fatality ratio was 1.0%. CONCLUSIONS: In a designated hospital outside Hubei Province, COVID-2019 patients could be effectively managed by properly using the existing hospital system. Mortality may be lowered when cases are relatively mild, and there are sufficient medical resources to care and treat the disease.

negative: Representations of SARS in the British newspapers In the Spring of 2003, there was a huge interest in the global news media following the emergence of a new infectious disease: severe acute respiratory syndrome (SARS). This study examines how this novel disease threat was depicted in the UK newspapers, using social representations theory and in particular existing work on social representations of HIV/AIDS and Ebola to analyse the meanings of the epidemic. It investigates the way that SARS was presented as a dangerous threat to the UK public, whilst almost immediately the threat was said to be ‘contained’ using the mechanism of ‘othering’: SARS was said to be unlikely to personally affect the UK reader because the Chinese were so different to ‘us’; so ‘other’. In this sense, the SARS scare, despite the remarkable speed with which it was played out in the modern global news media, resonates with the meanings attributed to other epidemics of infectious diseases throughout history. Yet this study also highlights a number of differences in the social representations of SARS compared with earlier epidemics. In particular, this study examines the phenomena of ‘emerging and re-emerging infectious diseases’ over the past 30 or so years and suggests that these have impacted on the faith once widely held that Western biomedicine could ‘conquer’ infectious disease.

negative: Psoriatic disease and body composition: a systematic review of the literature Background. Obesity is a leading comorbidity in psoriatic disease, including both psoriasis (Pso) and psoriatic arthritis (PsA), and is associated with adverse metabolic and cardiovascular (CV) outcomes. Anthropometric parameters, such as weight, body mass index (BMI) and waist-to-hip ratio, have been extensively reported in psoriatic disease. However, the associations of body composition and fat distribution with psoriasis have not been fully defined. Objectives. To identify whether patients with psoriatic disease, including psoriatic arthritis, have altered body composition compared with the general population, and to review existing modalities for the assessment of body composition. Methods. Electronic searches of the literature were conducted in PubMed, Medline (Ovid), Embase (Ovid), Cochrane Central Register and Google Scholar. Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria. Results. Twenty-five full text articles met the inclusion criteria and were included in the final narrative analysis. The studies were of heterogeneous design and used a range of objective measures to assess body composition, including simple anthropometric measures, bioimpedance analysis (BIA), dual energy X-ray absorptiometry (DXA) and computed tomography (CT). Few studies met all the quality assessment criteria. Conclusions. Patients with psoriatic disease reveal defined body composition changes that are independent of obesity and the customary metabolic syndrome, including higher overall body fat, visceral fat and sarcopenia. These findings emphasize that patients with psoriatic disease should be screened for abnormal adipose effects beyond their weight and body mass index (BMI). Our findings show that the last decade has seen an exciting expansion of research interest in the development and validation of new modalities for the assessment of body composition. There is no consensus on the optimal assessment method of body composition for this diverse group, hence there is a need for validation of existing modalities and standardization of assessment tools.

negative: Determination of Air Filter Anti-Viral Efficiency against an Airborne Infectious Virus Recently, various studies have reported the prevention and treatment of respiratory infection outbreaks caused by lethal viruses. Consequently, a variety of air filters coated with antimicrobial agents have been developed to capture and inactivate virus particles in continuous airflow conditions. However, since aerosolized infectious viral-testing is inadvisable due to safety concerns, their anti-viral capability has only been tested by inserting the filters into liquid media, where infectious virus particles disperse. In this study a novel method of determining anti-viral performance of an air filter against airborne infectious viruses is presented. Initially, anti-viral air filter tests were conducted. Firstly, by an air-media test, in which the air filter was placed against an aerosolized non-infectious virus. Secondly, by a liquid-media test, in which the filter was inserted into a liquid medium containing a non-infectious virus. Subsequently, a correlation was established by comparing the susceptibility constants obtained between the two medium tests and an association was found for the air medium test with infectious virus. After ensuring the relationship did not depend on the virus species, the correlation was used to derive the results of the air-medium test from the results of the liquid-medium test.

negative: Secondary structure and function of the 5'-proximal region of the equine arteritis virus RNA genome. Nidoviruses produce an extensive 3'-coterminal nested set of subgenomic mRNAs, which are used to express their structural proteins. In addition, arterivirus and coronavirus mRNAs contain a common 5' leader sequence, derived from the genomic 5' end. The joining of this leader sequence to different segments (mRNA bodies) from the genomic 3'-proximal region presumably involves a unique mechanism of discontinuous minus-strand RNA synthesis. Key elements in this process are the so-called transcription-regulating sequences (TRSs), which determine a base-pairing interaction between sense and antisense viral RNA that is essential for leader-to-body joining. To identify RNA structures in the 5'-proximal region of the equine arteritis virus genome that may be involved in subgenomic mRNA synthesis, a detailed secondary RNA structure model was established using bioinformatics, phylogenetic analysis, and RNA structure probing. According to this structure model, the leader TRS is located in the loop of a prominent hairpin (leader TRS hairpin; LTH). The importance of the LTH was supported by the results of a mutagenesis study using an EAV molecular clone. Besides evidence for a direct role of the LTH in subgenomic RNA synthesis, indications for a role of the LTH region in genome replication and/or translation were obtained. Similar LTH structures could be predicted for the 5'-proximal region of all arterivirus genomes and, interestingly, also for most coronaviruses. Thus, we postulate that the LTH is a key structural element in the discontinuous subgenomic RNA synthesis and is likely critical for leader TRS function.

negative: Stress resilience during the coronavirus pandemic The epidemic of the 2019 novel coronavirus SARS-CoV-2, causing the coronavirus disease 2019 (COVID-19) is a global public health emergency with multifaceted severe consequences for people's lives and their mental health. In this article, as members of the European College of Neuropsychopharmacology (ECNP) Resilience, we will discuss the urgent need for a focus on resilience during the current coronavirus pandemic. Resilience is pivotal to cope with stress and vital to stay in balance. We will discuss the importance of resilience at the individual and societal level, but also the implication for patients with a psychiatric condition and health care workers. We not only advocate for an increased focus on mental health during the coronavirus pandemic but also highlight the urgent need of augmenting our focus on resilience and on strategies to enhance it.

negative: Respiratory Tract Diseases That May Be Mistaken for Infection The differential diagnosis of lung infiltrates in transplant patients includes non-infectious processes that may mimic pneumonia. Hydrostatic and non-cardiogenic pulmonary edema, as well as transfusion-related lung injury, may cause bilateral airspace opacification that may be confused with an infectious process. Chemotherapeutic agents, whether administered for treatment of an underlying hematologic malignancy, for induction prior to transplant, or for the treatment of GVHD or graft rejection after transplant, may cause lung injury that in some cases may not become apparent until years later. Radiation-induced lung injury may cause a distinct pattern of lung injury, which may present months after exposure. In hematopoietic stem cell transplant patients, pulmonary diagnoses such as engraftment syndrome, idiopathic pneumonia syndrome, and diffuse alveolar hemorrhage can mimic pneumonia. After lung transplantation, infiltrates may be seen as a consequence of primary graft dysfunction or allograft rejection. Organizing pneumonia may be seen both in recipients of solid organ and hematopoietic stem cell transplants. Organizing pneumonia may be cryptogenic or associated with the use of the mTOR inhibitor sirolimus. Failure to accurately diagnose non-infectious infiltrates may lead to unnecessary antibiotic treatment and failure to address the underlying pathophysiologic process.

negative: Epidemiological and Clinical Characteristics of Children with Coronavirus Disease 2019 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen which mainly spreads by droplets. Most published studies focused on adult patients with coronavirus disease 2019 (COVID-19), but data concerning pediatric patients is limited. This study aimed to determine epidemiological characteristics and clinical features of pediatric patients with COVID-19. Methods: We reviewed and analyzed data on pediatric patients with laboratory-confirmed COVID-19, including basic information, epidemiological history, clinical manifestations, laboratory and radiologic findings, treatment, outcome and follow-up results. Results: From January 20th to February 27th of 2020, a total of 74 pediatric patients with COVID-19 were included in this study. Of the 68 cases whose epidemiological data were complete, 65 (65/68, 95.59%) cases were household contacts of adults whose symptoms developed earlier. Forty (59.46%) of the infected children were male, and the median age and body weight are 6 (0.10-15.08) years and 24 (4.20-87.00) kg, respectively. Except for one critically ill case, 20 (27.03%) patients did not show any symptoms of infection, 24 (32.43%) patients had acute upper respiratory tract infection and 29 (39.19%) patients were diagnosed with mild pneumonia. Cough (24/74, 32.43%) and fever (20, 27.03%) were the predominant symptoms of 44 (59.46%) symptomatic patients at onset of the illness. Abnormalities in leukocyte count were found in 23 (31.08%) children and 10 (13.51%) children presented with abnormal lymphocyte count. Of the 34 (45.95%) patients who had nucleic acid testing results for common respiratory pathogens, 19 (19 / 34, 51.35%) showed co-infection with other pathogens other than SARS-CoV-2.Ten (13.51%) children had RT-PCR analysis of SARS-CoV-2 for fecal specimens and 8 of them showed prolonged existence of SARS-CoV-2 RNA 11 (5-23) days after nasopharynx swabs turning negative. Abnormalities in chest imaging were observed in 37 (50.00%) patients and 28 (37.84%) of them only presented with nontypical changes.All children had good prognosis with a median hospitalization duration of 11 days and follow-up period of 16.5 days. During the follow-up period, all the patients remained in quarantine at designated site and home for two 14-day obervation periods and showed no clinical manifestation,but 3 of the 8 cases with prolonged fecal shedding of SARS-CoV-2 still showed positive result of feces test.

negative: Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.

negative: Inactivation of Viruses on Surfaces by Ultraviolet Germicidal Irradiation In many outbreaks caused by viruses, the transmission of the agents can occur through contaminated environmental surfaces. Because of the increasing incidence of viral infections, there is a need to evaluate novel engineering control methods for inactivation of viruses on surfaces. Ultraviolet germicidal irradiation (UVGI) is considered a promising method to inactivate viruses. This study evaluated UVGI effectiveness for viruses on the surface of gelatin-based medium in a UV exposure chamber. The effects of UV dose, viral nucleic acid type (single-stranded RNA, ssRNA; single-stranded DNA, ssDNA; double-stranded RNA, dsRNA; and double-stranded DNA, dsDNA), and relative humidity on the virus survival fraction were investigated. For 90% viral reduction, the UV dose was 1.32 to 3.20 mJ/cm(2) for ssRNA, 2.50 to to 4.47 mJ/cm(2) for ssDNA, 3.80 to 5.36 mJ/cm(2) for dsRNA, and 7.70 to 8.13 mJ/cm(2) for dsDNA. For all four tested viruses, the UV dose for 99% viral reduction was 2 times higher than those for 90% viral reduction. Viruses on a surface with single-stranded nucleic acid (ssRNA and ssDNA) were more susceptible to UV inactivation than viruses with double-stranded nucleic acid (dsRNA and dsDNA). For the same viral reduction, the UV dose at 85% relative humidity (RH) was higher than that at 55% RH. In summary, results showed that UVGI was an effective method for inactivation of viruses on surfaces.

negative: Risk Stratification and Personal Protective Equipment Use in Pediatric Endoscopy During the Coronavirus Disease 2019 Outbreak: A Single-center Protocol SARS-CoV-2, the novel coronavirus causing coronavirus disease 2019 (COVID-19), is now a global pandemic. Human-to-human transmission has been documented to occur through respiratory secretions, feces, aerosols, and contaminated environmental surfaces. Pediatric patients present a unique challenge as they may have minimal symptoms and yet transmit disease. Endoscopists face risk for infection with viruses like SARS-CoV-2, as the aerosol generating nature of endoscopy diffuses respiratory disease that can be spread via an airborne and droplet route. We describe our center's methodology for pediatric patient risk stratification to facilitate responsible use of endoscopic resources during this crisis. We also describe our recommendations for use of personal protective equipment by endoscopists, with the goal of ensuring the safety of ourselves, our anesthesiology and endoscopy staff, and our patients.

negative: Coronavirus Pneumonia Following Autologous Bone Marrow Transplantation for Breast Cancer Infectious bronchitis virus, otherwise known as coronavirus, can cause mild upper respiratory tract illnesses in children and adults. Rarely has coronavirus been linked, either by serology or nasal wash, to pneumonia. We report a case of a young woman who, following treatment for stage IIIA breast cancer using a high-dose chemotherapy regimen followed by autologous bone marrow and stem cell transplantation, developed respiratory failure and was found to have coronavirus pneumonia as diagnosed by electron microscopy from BAL fluid. We propose that coronavirus should be considered in the differential diagnosis of acute respiratory failure in cancer patients who have undergone high-dose chemotherapy and autologous hematopoietic support.

negative: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics.

negative: Chronic Living in a Communicable World. By April 2020, COVID-19 lockdowns had restricted the movements of over half the world's population. As health authorities advise people living with chronic conditions to self-isolate because they are at particular risk of serious complications and death, the epidemiological split between communicable and noncommunicable disease is tenuous. We argue that much more is at stake for people living with (multiple) medical conditions than being "at risk" of infection of coronavirus. We emphasize the need to attend to the long-term effects of COVID-19, but also the importance of the continued care of people living with other lifelong medical conditions.

negative: Epidemiological analysis of COVID‐19 and practical experience from China The rapid spread of the epidemic has aroused widespread concern in the international community. Severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) originated from Wuhan's Huanan wholesale seafood market, with bats as the likely original hosts and pangolins as potential intermediate hosts. The current source of the disease is mainly patients infected with SARS‐COV‐2. Patients in the incubation period may also become sources of infection. The virus is mainly transmitted via respiratory droplets and contact, and the population is generally susceptible. The epidemic has progressed through the local outbreak stage and community transmission stage due to exposure at Wuhan's Huanan wholesale seafood market and is now in the stage of large‐scale transmission due to the spread of the epidemic. The basic productive number (R0) at the beginning of the epidemic was 2.2, with an average incubation period of 5.2 days. The proportion of critically ill patients was 23.4%, the mortality rate was lower than those of SARS and Middle East respiratory syndrome, and 96.5% of deaths occurred in Hubei Province, where the outbreak occurred first. Among them, elderly men with underlying diseases had a higher mortality rate. Chinese medical staff have summarized a set of effective strategies and methods in the diagnosis and treatment of this disease that are worthy of reference for their international counterparts. With powerful government intervention and the efforts of Chinese medical staff, China's outbreak has gradually improved.

negative: Diet and physical activity during the COVID-19 lockdown period (March-May 2020): results from the French NutriNet-Sante cohort study Background: Since December 2019, the coronavirus disease (COVID-19) has massively spread, with overwhelming of health care systems and numerous deaths worldwide. To remedy this, several countries, including France, have taken strict lockdown measures, requiring the closure of all but essential places. This unprecedented disruption of daily routines has a strong potential for disrupting nutritional behaviours. Nutrition being one of the main modifiable risk factors for chronic disease risk, this may have further consequences for public health. Our objective was therefore to describe nutritional behaviours during the lockdown period and to put them in light of individual characteristics. Methods: 37,252 French adults from the web-based NutriNet-Sante cohort filled lockdown-specific questionnaires in April-May 2020 (nutritional behaviours, body weight, physical activity, 24h-dietary records). Nutritional behaviours were compared before and during lockdown using Student paired t-tests and associated to individual characteristics using multivariable logistic or linear regression models. Clusters of nutritional behaviours were derived from multiple correspondence analysis and ascending hierarchical classification. Results: During the lockdown, trends for unfavourable nutritional behaviours were observed: weight gain (for 35%; +1.8kg on average), decreased physical activity (53%), increased sedentary time (63%), increased snacking, decreased consumption of fresh food products (especially fruit and fish), increased consumption of sweets, biscuits and cakes. Yet, opposite trends were also observed: weight loss (for 23%, -2kg on average), increased home-made cooking (40%), increased physical activity (19%). These behavioural trends related to sociodemographic and economic position, professional situation during the lockdown (teleworking or not), initial weight status, having children at home, anxiety and depressive symptoms, as well as diet quality before the lockdown. Modifications of nutritional practices mainly related to routine change, food supply, emotional reasons but also to voluntary changes to adjust to the current situation. Conclusion: These results suggest that the lockdown led, in a substantial part of the population, to unhealthy nutritional behaviours that, if maintained in the long term, may increase the nutrition-related burden of disease and also impact immunity. Yet, the lockdown situation also created an opportunity for some people to improve their nutritional behaviours, with high stakes to understand the leverages to put these on a long-term footing.

negative: Real-time estimation and prediction of mortality caused by COVID-19 with patient information based algorithm Abstract The global COVID-19 outbreak is worrisome both for its high rate of spread, and the high case fatality rate reported by early studies and now in Italy. We report a new methodology, the Patient Information Based Algorithm (PIBA), for estimating the death rate of a disease in real-time using publicly available data collected during an outbreak. PIBA estimated the death rate based on data of the patients in Wuhan and then in other cities throughout China. The estimated days from hospital admission to death was 13 (standard deviation (SD), 6 days). The death rates based on PIBA were used to predict the daily numbers of deaths since the week of February 25, 2020, in China overall, Hubei province, Wuhan city, and the rest of the country except Hubei province. The death rate of COVID-19 ranges from 0.75% to 3% and may decrease in the future. The results showed that the real death numbers had fallen into the predicted ranges. In addition, using the preliminary data from China, the PIBA method was successfully used to estimate the death rate and predict the death numbers of the Korean population. In conclusion, PIBA can be used to efficiently estimate the death rate of a new infectious disease in real-time and to predict future deaths. The spread of 2019-nCoV and its case fatality rate may vary in regions with different climates and temperatures from Hubei and Wuhan. PIBA model can be built based on known information of early patients in different countries.

negative: Chapter 4 Adolescents and Pets Abstract This chapter describes the multiple stages present during adolescence and the importance of animals in the lives of adolescents. From the ages of 10–25, adolescents and the role that their pets play in each other’s lives change dramatically. Here, we present three adolescent stages and the value of relationships adolescents have with their pets during these distinct stages. How studies have looked at ways pets influence or impact an adolescent’s life will be explored. The chapter also looks more specifically at a pet’s impact on physical health, social-emotional development, and socialization during the adolescence. We examine specific populations of adolescents, such as college students, rural adolescents, homeless adolescents, at-risk adolescents including adolescents who are suicidal, adolescents participating in canine-assisted therapy, and how their pet’s aide the adolescent. Lastly, experiences from several adolescents are provided.

negative: Removal and retention of viral aerosols by a novel alumina nanofiber filter Nanomaterial, due to its unique physical, chemical and biological properties compared to its bulk counterparts, has the potential to provide a product superior to its bulk predecessor. In this study, a novel alumina nanofiber filter was assessed for its removal and retention capability for MS2 aerosol. Its physical removal efficiency in the 10–400nm range was 94.35%, while its viable removal efficiency was 98.87%, which was slightly lower than three conventional HEPA filters tested. However, its pressure drop was much lower than HEPA filters, yielding a higher filter quality than HEPA filters. The average extracted fraction from the nanofiber filter was 8.64×10−2±7.00×10−2, which is three orders lower than other HEPA filters, demonstrating that the viruses were effectively retained in the nanofiber filter. Furthermore, the performance of the nanofiber filter showed no dependence on relative humidity. In conclusion, this novel alumina nanofiber filter presents advantageous potential for removal and retention of viral aerosol agents.

negative: Nucleolus: the fascinating nuclear body Nucleoli are the prominent contrasted structures of the cell nucleus. In the nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is cell cycle regulated. The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle. In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus. Viruses interact with the nucleolus and recruit nucleolar proteins to facilitate virus replication. The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies. Perspectives on the evolution of this research area are proposed.

negative: Recommendations for standardized management of CML patients in the core epidemic area of COVID-19(Multi-center survey results in Hubei Province, China) Background Since late December 2019, the outbreak of the novel coronavirus disease, COVID-19, that began in Wuhan, has become endemic in China and more than 100 countries and regions in the world. There is no report about the prevalence of COVID-19 in CML patients untill now. We aimed to describe the clinical course, outcomes of CML patients with COVID-19 and prevalence of COVID-19 in CML patients. Methods In this multi-center survey, cross-sectional survey, observational study, the clinical data of CML patients with COVID-19 in each center were collected. Simultaneously, an online survey was conducted for information about the CML patients under the management at each center by asking the CML patients to complete a questionnaire,from February 15, 2020 to February 21, 2020. The questionnaire includes demographic data, place of residence, smoking status, CML diagnosis and treatment, comorbidities, combined medications, epidemiological history, symptoms(fever, cough, shortness of breath, etc) during the epidemic. Additional clinical data was collected on respondents suspected or confirmed to have COVID-19. We described and analyzed the prevalence of COVID-19 in CML patients, and focus on the clinical characteristics and outcomes of COVID-19 patients. Data were compared between the CML patients with optimal response and those with non-optimal response. The primary outcome was prevalence of COVID-19 in CML patients, as of Feb 21, 2020. Secondary outcomes included the history of epidemiology of CML patients, the clinical characteristics and outcomes of CML patients with COVID-19 . Findings Of 392 respondents, 223( 56.9%) were males, and 240( 61.2%) were 50 years or younger. Only 10 patients took drugs irregularly due to the influence of the epidemic because of traffic control, pharmacies unable to operate normally, etc. In the history of epidemiology, there were 4 patients with definite contact with COVID-19, of which 3 were remote contact and 1 was close contact. 12 respondents had fever, cough or shortness of breath during the epidemic, 1 case (common type) was confirmed with COVID-19 and cured after treatment. 1 patient was clinically diagnosed and succumbed. 1 of 299 (0.3%) patients with an optimal response was diagnosed with COVID-19. Of the 50 patients who failed to respond to CML treatment or had a poor response, 1 patient (2%) had a clinical diagnosis of COVID-19. Interpretation While the 392 CML respondents required regular referrals to hospitals, they did not have much contact with COVID-19 patients during the outbreak. Patients who failed to achieved an optimal response to CML therapy appear more likely to have a symptomatic infection with SARS-CoV-2. Older patients with comorbidities are at increased risk of death.

negative: Surgical treatment of latent infection of 2019 novel coronavirus (SARS-CoV-2) with esophageal foreign body perforation: A case report This study reports the surgical treatment of a female patient at age of 64 years with novel coronavirus (SARS-CoV-2) latent infection complicated with esophageal foreign body perforation with no significant changes in the lung CT The patient was confirmed as SARS-CoV-2 infection on the 4th day after surgery and then was transferred into the Department of Infectious Disease in our hospital for treatment This case has guiding value for the operation of thoracic surgery during the outbreak of novel coronavirus pneumonia

negative: Lessons learned and unlearned in periodontal microbiology Periodontal diseases are initiated by bacterial species living in polymicrobial biofilms at or below the gingival margin and progress largely as a result of the inflammation initiated by specific subgingival species. In the past few decades, efforts to understand the microbiota of periodontal diseases have led to an exponential increase in information about biofilms associated with periodontal health and disease. In fact, the oral microbiota is one of the best characterized microbiomes that colonize the human body. Despite this increased knowledge, one has to ask if our fundamental concepts of the etiology and pathogenesis of periodontal diseases have really changed. In this chapter we will review how our comprehension of the structure and function of the subgingival microbiota evolved over the years in search of lessons learned and unlearned in periodontal microbiology. More specifically, this review focuses on: 1) how the data obtained through molecular techniques has impacted our knowledge of the etiology of periodontal infections; 2) the potential role of viruses in the etiopathogenesis of periodontal diseases; 3) how concepts of microbial ecology have expanded our understanding of host microbial interactions that might lead to periodontal diseases; 4) the role of inflammation in the pathogenesis of periodontal diseases; and 5) the impact of these evolving concepts on treatment and preventive approaches to periodontal infections. We will conclude by reviewing how novel systems biology approaches promise to unravel new details of the pathogenesis of periodontal diseases and, hopefully, lead to a better understanding of periodontal disease mechanisms.

negative: Molecular biology of severe acute respiratory syndrome coronavirus The worldwide epidemic of severe acute respiratory syndrome (SARS) in 2003 was caused by a novel coronavirus called SARS-CoV. Coronaviruses and their closest relatives possess extremely large plus-strand RNA genomes and employ unique mechanisms and enzymes in RNA synthesis that separate them from all other RNA viruses. The SARS epidemic prompted a variety of studies on multiple aspects of the coronavirus replication cycle, yielding both rapid identification of the entry mechanisms of SARS-CoV into host cells and valuable structural and functional information on SARS-CoV proteins. These recent advances in coronavirus research have important implications for the development of anti-SARS drugs and vaccines.

negative: Oral Research Communications of the 22(nd) ECVIM‐CA Congress

negative: Long‐term coexistence of SARS‐CoV‐2 with antibody response in COVID‐19 patients Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causing coronavirus disease 2019 (COVID‐19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS‐CoV‐2 infection needs to be determined. Here, 26 cases of COVID‐19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms, and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SARS‐CoV‐2 and virus‐specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days. One COVID‐19 patient who did not produce any SARS‐CoV‐2–bound IgG successfully cleared SARS‐CoV‐2 after 46 days of illness, revealing that without antibody‐mediated adaptive immunity, innate immunity alone may still be powerful enough to eliminate SARS‐CoV‐2. This report may provide a basis for further analysis of both innate and adaptive immunity in SARS‐CoV‐2 clearance, especially in nonsevere cases.

negative: Fabrication of a lithium chloride solution based composite supported liquid membrane and its moisture permeation analysis Abstract A novel composite supported liquid membrane has been prepared for ventilation air moisture recovery. The membrane is composed of three layers: two hydrophobic protective layers and a sandwiched hydrophilic support layer in which LiCl solution is immobilized to facilitate water vapor transfer. A test is conducted to measure the moisture permeation rate through the composite membrane. Various resistances in the cell and in the composite membrane are clarified. Linear equilibrium relations between humidity, temperature, and LiCl concentration in the liquid solution layer are obtained to aid in the model set-up. It has been found that the mean moisture permeation rate through the composite membrane is around 1.14×10−4 kgm−2 s−1, almost two times higher than that through a solid hydrophilic cellulose acetate membrane with comparative thickness. Further, the supported liquid layer only accounts for 12% of the total moisture transfer resistance in the cell, indicating that there is much potential for further performance improvement.

negative: Drivers of airborne human-to-human pathogen transmission Airborne pathogens — either transmitted via aerosol or droplets — include a wide variety of highly infectious and dangerous microbes such as variola virus, measles virus, influenza A viruses, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Bordetella pertussis. Emerging zoonotic pathogens, for example, MERS coronavirus, avian influenza viruses, Coxiella, and Francisella, would have pandemic potential were they to acquire efficient human-to-human transmissibility. Here, we synthesize insights from microbiological, medical, social, and economic sciences to provide known mechanisms of aerosolized transmissibility and identify knowledge gaps that limit emergency preparedness plans. In particular, we propose a framework of drivers facilitating human-to-human transmission with the airspace between individuals as an intermediate stage. The model is expected to enhance identification and risk assessment of novel pathogens.

negative: On the corona infection model with contact restriction This article presents a mathematical infection model that is designed to estimate the course of coronavirus infection in Germany for several days in advance: How many people become ill or die, what is the temporal development? If the contact restriction is perfect, then the model predicts the development of the virus infection after the initial subsidence of the infection. However, since this restriction cannot always be strictly adhered to, the model is dynamically adapted to the development. This makes it possible to estimate the number of infected people, the number of new infections and deaths in Germany about a week in advance.

negative: When basic supplies are missing, what to do? Specific demands of the local street population in times of coronavirus – a concern of social psychiatry Abstract Background Homeless experts and some federal housing officials are sounding the alarm that the patchwork of government efforts to address the coronavirus outbreak risks leaving out one group of acutely vulnerable people: the homeless. In terms of isolation, it is too unclear what that looks like if you normally sleep on the streets. In this tough moment, when people should be turned away, not only it feels inhumane, but it is also a big public health risk, because where are they going to go? Method The studies were identified using large-sized newspapers with international circulation Results With more cities suspecting community transmission of the novel coronavirus, people who sleep in shelters or hunker down outside already have a lower life expectancy and often have underlying health conditions that put them at greater risk if they develop COVID-19 (Global News, 2020). These people face lack of sleep, malnutrition, and “extreme stress levels just to meet their daily needs”, all of which weakens the immune system. Along with mental illness or substance abuse disorders, they are “incredibly vulnerable to this virus”. Conclusions Health organizations are well aware of the risks involved in mental health. A large population of homeless people experience their pain and psychological distress intermittently. For low-income patients, the various borderline situations related to health/illness involve growing expectations regarding the basic needs. This is a serious concern when linked to the pandemic.

negative: Collection efficiencies of aerosol samplers for virus-containing aerosols Abstract Collection efficiencies of four bioaerosol samplers (Andersen impactor, AGI-30 impinger, gelatin filter, and nuclepore filter) were evaluated for virus-containing aerosols. Four different bacteriophages were used as surrogates for the mammalian viruses. Results showed that the collection efficiency was significantly affected by the morphology of the virus particles. For hydrophilic viruses, the collection efficiencies of the Andersen impactor, impinger, and gelatin filter were 10 times higher than that of the nuclepore filter. For hydrophilic viruses, the collection efficiencies of all four samplers were 10–100 times higher than hydrophobic viruses. The infectivity of the virus in collected samples was also evaluated for an AGI-30 impinger. Results showed that the viruses retained more infectivity when the samples were refrigerated (up to 1 day) during storage than when stored at room temperature (up to 8h). Therefore, even when refrigerated, airborne virus samples collected using an impinger should be processed as soon as possible to avoid loss of virus infectivity.

negative: Parasites and Their World Records in Their Fight for Survival Parasites are animals that enter plants, animals and humans – but are not welcome. Therefore they had to develop strategies for invasion and survival – outside and inside of hosts. For this purpose they developed amazing, often unbelievable skills during evolution. Thirteen of them are presented in this chapter showing that they are fit for the future thus threatening mankind, if there are no precautions in the future.

negative: Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990–2002) Objectives To review the clinicopathological findings in naturally‐occurring, histopathologically confirmed cases of feline infectious peritonitis in client‐owned cats in Sydney, Australia, with the purpose of identifying factors assisting in the diagnosis of this complex disease syndrome and to characterise the disease as it occurs in this region. Design Retrospective clinical study: the clinical records of all cats with histopathologically confirmed feline infectious peritonitis at the University Veterinary Centre Sydney and a private cat hospital in Sydney between 1990 and 2002 were reviewed for signalment, history, physical findings, diagnostic test results and the distribution of histological lesions throughout the body at necropsy. Results Forty‐two cats met the inclusion criteria. Significant features of this study that unique to the contemporary literature are i) the over‐representation of certain breeds (Burmese, Australian Mist, British Shorthaired, and Cornish Rex) and the under‐representation of other breeds (Domestic Shorthaired, Persian); ii) the overrepresentation of males; iii) the tendency for effusive disease in Australian Mist cats and non‐effusive disease in Burmese; iv) the even age distribution of disease seen in cats older than 2 years‐of‐age; and v) the presence of fulminant immune‐mediated haemolytic anaemia in two cats in this study. Conclusion The study highlights the diverse range of clinical manifestations and the complexities experienced by clinicians in diagnosing this fatal disease. Some aspects of the epidemiology and clinical manifestations of feline infectious peritonitis appear different to the disease encountered in Europe and North America, most notably the over‐representation of specific breeds and the presence of immune‐mediated haemolytic anaemia.

negative: What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review Background: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps. Materials and Methods: We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV. Results: Dipeptidyl peptidase 4 (DPP4/CD26) was identified as the human receptor for MERS-CoV, and a variety of molecular and serological assays developed. Dromedary camels remain the only documented zoonotic source of human infection, but MERS-like CoVs have been detected in bat species globally, as well as in dromedary camels throughout the Middle East and Africa. However, despite evidence of camel-to-human MERS-CoV transmission and cases apparently related to camel contact, the source of many primary cases remains unknown. There have been sustained health care-associated human outbreaks in Saudi Arabia and South Korea, the latter originating from one traveler returning from the Middle East. Transmission mechanisms are poorly understood; for health care, this may include environmental contamination. Various potential therapeutics have been identified, but not yet evaluated in human clinical trials. At least one candidate vaccine has progressed to Phase I trials. Conclusions: There has been substantial MERS-CoV research since 2012, but significant knowledge gaps persist, especially in epidemiology and natural history of the infection. There have been few rigorous studies of baseline prevalence, transmission, and spectrum of disease. Terms such as “camel exposure” and the epidemiological relationships of cases should be clearly defined and standardized. We strongly recommend a shared and accessible registry or database. Coronaviruses will likely continue to emerge, arguing for a unified “One Health” approach.

negative: Feline Infectious Peritonitis Feline infectious peritonitis (FIP) occurs most frequently in young animals from multicat households. Ocular manifestations of FIP are extremely common with the noneffusive form of the disease. All cats suspected of having FIP should undergo a thorough ophthalmic examination. Uveitis (inflarrunation of the iris, ciliary body, and choroid) is the primary clinical sign of ocular FIP. Treatment with anti-inflammatory medications is only supportive and aimed at disease palliation.

negative: Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens Pregnancy-associatedPlasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show here that human monoclonal IgG antibodies with specificity for variant surface antigens (VSA) specifically expressed by CSA-adhering IEs (VSA(PAM)) can be used in vitro to select parasites from nonpregnant donors to express VSA(PAM) and that this selection for VSA(PAM) expression results in preferential transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA.

negative: Clinical and laboratory-derived parameters of 119 hospitalized patients with coronavirus disease 2019 in Xiangyang, Hubei Province, China

negative: Seventy-two-hour emergency department revisits among adults with chronic diseases: a Saudi Arabian study BACKGROUND: Despite the increase in adult emergency department (ED) utilization in Saudi Arabia, no studies have evaluated the 72-hour revisits. This study estimates the rate of 72-hour ED revisits and identifies its reasons and predictive factors among adults with chronic diseases. PATIENTS AND METHODS: A hospital-based retrospective study that included 24,206 ED discharges for adults with chronic diseases at the adult ED of King Abdulaziz Medical City, Riyadh between September 13, 2015 and July 29, 2017 was performed. We extracted data on demographic information, reasons for ED visits/revisits, health insurance coverage, weekend ED arrival, and mortality. RESULTS: A sample of 24,206 ED discharges for 19,697 adults with at least one chronic disease was included in the analysis. The rate of 72-hour revisits in this study population was high: 3,144/24,206 (13%) had the first revisit and 319/3,144 (10.1%) had the second ED revisit within 72 hours. Diseases of the circulatory (19%) and genitourinary (15.8%) systems were the major reasons for the first ED revisit. The adjusted relative rate (aRR) of 72-hour ED revisits was higher in adults with chronic diseases and aged ≥60 years (aRR=1.360, 95% CI: 1.41–1.83; P=0.001), patients of female gender (aRR=1.24, 95% CI: 1.09–1.41; P=0.001), patients with health insurance coverage (aRR=4.23, 95% CI: 2.60–6.90; P=0.001), patients arriving to ED on a weekend (aRR=2.13, 95% CI: 1.03–4.41; P=0.041), and new patients (aRR=1.47, 95% CI: 1.25–1.73; P=0.001). CONCLUSION: The rate of 72-hour revisits is high among adults with chronic diseases. Advancing age, female gender, health insurance coverage, weekend ED arrival, and new patients are the important predictive factors of the high rate of 72-hour revisits. Continuous quality assessment and monitoring of factors related to patients are needed to reduce the frequency of early ED revisits after discharge.

negative: A case of imported COVID-19 diagnosed by PCR-positive lower respiratory specimen but with PCR-negative throat swabs A 35-year-old woman presented with fever and mild diarrhoea without any respiratory symptoms 9 days after travelling to Japan from Wuhan, China. Her computed tomography scan revealed pneumonia. The first polymerase chain reaction (PCR) test on throat swab for the novel corona virus upon admission was negative. Therefore, she was treated for community-acquired pneumonia, but fever persisted. On hospital day 5, PCR test on induced sputum was positive, but a second polymerase chain reaction test on throat swab remained negative. She was discharged, fully recovered, on hospital day 12. A lower respiratory tract specimen should be obtained for better diagnosis of corona virus disease 2019, even in the absence of respiratory symptoms for patients with significant travel or exposure history.

negative: Case Report: Viral Shedding for 60 Days in a Woman with COVID-19 Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription-polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.

negative: Tourism today: Why is it a global phenomenon embracing all our lives?

negative: Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19? In December 2019, a new coronavirus, named SARS-CoV-2, has emerged from China causing pneumonia outbreaks first in the Wuhan region and have now spread worldwide because of its probable high transmission efficiency. Due to the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the best tool to find therapeutic solution. Chloroquine, remdesivir, lopinavir, ribavirin or ritonavir have shown efficacy to inhibit coronavirus in vitro. Teicoplanin, an antibiotic used to treat staphylococci infection, previously showed efficacy to inhibit the first stage of MERS-coronarivus viral cycle in human cells. This activity is conserved on the SARS-Cov-2, thus placing teicoplanin as a potential treatment for patients with this virus.

negative: Lung Ultrasound in Patients with Acute Respiratory Failure Reduces Conventional Imaging and Health Care Provider Exposure to COVID-19 Lung ultrasound gained a leading position in the last year as an imaging technique for the assessment and management of patients with acute respiratory failure. In coronavirus disease 2019 (COVID-19), its role may be of further importance because it is performed bedside and may limit chest X-ray and the need for transport to radiology for computed tomography (CT) scan. Since February 21, we progressively turned into a coronavirus-dedicated intensive care unit and applied an ultrasound-based approach to avoid traditional imaging and limit contamination as much as possible. We performed a complete daily examination with lung ultrasound score computation and systematic search of complications (pneumothorax, ventilator-associated pneumonia); on-duty physicians were free to perform CT or chest X-ray when deemed indicated. We compared conventional imaging exams performed in the first 4 wk of the COVID-19 epidemic with those in the same time frame in 2019: there were 84 patients in 2020 and 112 in 2019; 64 and 22 (76.2% vs. 19.6%, p < 0.001) had acute respiratory failure, respectively, of which 55 (85.9%) were COVID-19 in 2020. When COVID-19 patients in 2020 were compared with acute respiratory failure patients in 2019, the median number of chest X-rays was 1.0 (1.0–2.0) versus 3.0 (1.0–4.0) (p = 0.0098); 2 patients 2 (3.6%) versus 7 patients (31.8%) had undergone at least one thoracic CT scan (p = 0.001). A self-imposed ultrasound-based approach reduces the number of chest X-rays and thoracic CT scans in COVID-19 patients compared with patients with standard acute respiratory failure, thus reducing the number of health care providers exposed to possible contamination and sparing personal protective equipment.

negative: Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-α in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-α. Further study indicated that IFN-γ+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV.

negative: SARS CTL Vaccine Candidates — HLA Supertype, Genome‐Wide Scanning and Biochemical Validation An effective SARS vaccine is likely to include components that can induce specific cytotoxic T‐cell (CTL) responses. The specificities of such responses are governed by HLA‐restricted presentation of SARS‐derived peptide epitopes. Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information. The latter was recently established when a causative coronavirus (SARS CoV) was isolated and full‐length sequenced. Here, we have combined advanced bioinformatics and high‐throughput immunology to perform an HLA supertype, genome‐wide scan for SARS‐specific cytotoxic T cell epitopes. The scan includes all nine human HLA supertypes in total covering >99% of all major human populations. For each HLA supertype, we have selected the 15 top candidates for test in biochemical‐binding assays. At this time (approximately 6 months after the genome was established), we have tested the majority of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.

negative: Family Coronaviridae Publisher Summary This chapter focuses on Coronaviridae family whose two subfamilies include Coronavirinae and Torovirinae. The member genera include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, Torovirus, and Bafinivirus. The members of the family Coronaviridae are enveloped and positive stranded RNA viruses of three classes of vertebrates, which include corona- and toroviruses for mammals, coronaviruses for birds, and bafiniviruses for fishes. The nucleocapsids are helical and can be released from the virion by treatment with detergents. Where the coronavirus nucleocapsid appears to be loosely wound, those of the Torovirinae are distinctively tubular. The entire replication cycle takes place in the cytoplasm and involves the production of full-length and subgenome-sized (sg) minus-strand RNA intermediates with the viral genome serving both as mRNA for the replicase polyproteins and as a template for minus-strand synthesis. Members of the family Coronaviridae all seem to share two envelope protein species, the membrane (M) and spike (S) proteins. Similarities in size, predicted structures and presumed function(s) suggest a common ancestry, and the remote, but significant sequence similarities observed for toro-, bafini-, and (to lesser extent) coronavirus S proteins lend further support to this view. The replicase polyproteins of the Coronaviridae comprise a number of characteristic domains arranged in a conserved order.

negative: Perceptions of the Adult US Population regarding the Novel Coronavirus Outbreak Background: COVID-19 outbreak is spreading globally. Although the risk of infection in the US is currently low, it is important to understand the public perception of risk and trust in sources of information to better inform public health messaging. In this study, we surveyed the adult US population to understand their risk perceptions about the COVID-19 outbreak. Methods and Findings: We used an online platform to survey 718 adults in the US in early February 2020 using a questionnaire that we developed. Our sample was fairly similar to the general adult US population in terms of age, gender, race, ethnicity and education. We found that 69% of the respondents wanted the scientific/public health leadership (either the CDC Director or NIH Director) to lead the US response to COVID-19 outbreak as compared to 14% who wanted the political leadership (either the president or the Congress) to lead the response. Risk perception was low (median score of 5 out of 10) with the respondents trusting health professionals and health officials for information on COVID-19. Majority of the respondents were in favor of strict infection prevention policies to control the outbreak. Conclusion: Given our results, the public health/scientific leadership should be at the forefront of the COVID-19 response to promote trust.

negative: Severe Acute Respiratory Syndrome Coronavirus Nonstructural Proteins 3, 4, and 6 Induce Double-Membrane Vesicles Coronaviruses (CoV), like other positive-stranded RNA viruses, redirect and rearrange host cell membranes for use as part of the viral genome replication and transcription machinery. Specifically, coronaviruses induce the formation of double-membrane vesicles in infected cells. Although these double-membrane vesicles have been well characterized, the mechanism behind their formation remains unclear, including which viral proteins are responsible. Here, we use transfection of plasmid constructs encoding full-length versions of the three transmembrane-containing nonstructural proteins (nsps) of the severe acute respiratory syndrome (SARS) coronavirus to examine the ability of each to induce double-membrane vesicles in tissue culture. nsp3 has membrane disordering and proliferation ability, both in its full-length form and in a C-terminal-truncated form. nsp3 and nsp4 working together have the ability to pair membranes. nsp6 has membrane proliferation ability as well, inducing perinuclear vesicles localized around the microtubule organizing center. Together, nsp3, nsp4, and nsp6 have the ability to induce double-membrane vesicles that are similar to those observed in SARS coronavirus-infected cells. This activity appears to require the full-length form of nsp3 for action, as double-membrane vesicles were not seen in cells coexpressing the C-terminal truncation nsp3 with nsp4 and nsp6.

negative: Biosafety Recommendations on the Handling of Animal Cell Cultures The first steps in tissue culture are dating back to the beginning of the nineteenth century when biosafety measures did not yet exist. Later on, animal cell culture became essential for scientific research, diagnosis and biotechnological activities. Along with this development, biosafety concerns have emerged pointing to the risks for human health and in a lesser extent for the environment associated to the handling of animal cell cultures. The management of these risks requires a thorough risk assessment of both the cell cultures and the type of manipulation prior the start of any activity. It involves a case-by-case evaluation of both the intrinsic properties of the cell culture genetically modified or not and the probability that it may inadvertently or intentionally become infected with pathogenic micro-organisms. The latter hazard is predominant when adventitious contaminants are pathogenic or have a better capacity to persist in unfavourable conditions. Consequently, most of the containment measures primarily aim at protecting cells from adventitious contamination. Cell cultures known to harbour an infectious etiologic agent should be manipulated in compliance with containment measures recommended for the etiologic agent itself. The manipulation of cell cultures from human or primate origin necessitates the use of a type II biosafety cabinet. The scope of this chapter is to highlight aspects relevant for the risk assessment and to summarize the main biosafety recommendations and the recent technological advances allowing a mitigation of the risk for the handling of animal cell cultures.

negative: Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma The objective of this study was to evaluate the effectiveness of the SurePure Turbulator ultraviolet-C (UV-C, 254 nm wavelength) irradiation equipment on inactivation of different enveloped and non-enveloped viruses in commercially collected liquid animal plasma. Specifically, Pseudorabies virus (PRV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine epidemic diarrhea virus (PEDV), Bovine viral diarrhea virus (BVDV), Classical swine fever virus (CSFV), Swine influenza virus (SIV) as enveloped viruses and Porcine parvovirus (PPV), Swine vesicular disease virus (SVDV), Porcine circovirus type 2 (PCV-2) and Senecavirus A (SVA) as non-enveloped viruses, were inoculated in bovine or porcine plasma and subjected to different UV-C irradiation doses (0, 750, 1500, 3000, 6000 and 9000 J/L) using an UV-C device developed for opaque liquid working under turbulent flow. The enveloped viruses tested were inactivated at < 3000 J/L of UV-C, being the dose needed to inactivate 4 log TCID(50) (4D) of 1612 J/L for PRV,1004 J/L for PRRSV, 1953 J/L for PEDV, 1639 J/L for SIV, 1641 J/L for CSFV and 1943 J/L for BVDV. The non-enveloped viruses tended to have higher 4D values: 2161 J/L for PPV, 3223 J/L for SVA and 3708 J/L for SVDV. Because the initial viral concentration was <4.0 Log for PCV-2, it was not possible to calculate the 4D value for this virus. In conclusion, these results demonstrated that the SurePure Turbulator UV-C treatment system is capable of inactivating significant levels of swine viruses inoculated in commercially collected porcine or bovine plasma. It was concluded that irradiation with UV-C can provide an additional redundant biosafety feature in the manufacturing process of spray-dried animal plasma.

negative: Mutualistic viruses and the heteronomy of life Abstract Though viruses have generally been characterized by their pathogenic and more generally harmful effects, many examples of mutualistic viruses exist. Here I explain how the idea of mutualistic viruses has been defended in recent virology, and I explore four important conceptual and practical consequences of this idea. I ask to what extent this research modifies the way scientists might search for new viruses, our notion of how the host immune system interacts with microbes, the development of new therapeutic approaches, and, finally, the role played by the criterion of autonomy in our understanding of living things. Overall, I suggest that the recognition of mutualistic viruses plays a major role in a wider ongoing revision of our conception of viruses.

negative: Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in the city of Wuhan in China and has widely spread worldwide. Currently, it is vital to explore potential intermediate hosts of SARS-CoV-2 to control COVID-19 spread. Therefore, we reinvestigated published data from pangolin lung samples from which SARS-CoV-like CoVs were detected by Liu et al. [1]. We found genomic and evolutionary evidence of the occurrence of a SARS-CoV-2-like CoV (named Pangolin-CoV) in dead Malayan pangolins. Pangolin-CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the whole-genome level. Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Five key amino acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and SARS-CoV-2, but four amino acid mutations are present in RaTG13. Both Pangolin-CoV and RaTG13 lost the putative furin recognition sequence motif at S1/S2 cleavage site that can be observed in the SARS-CoV-2. Conclusively, this study suggests that pangolin species are a natural reservoir of SARS-CoV-2-like CoVs.

negative: Discovery and Characterization of Novel Bat Coronavirus Lineages from Kazakhstan Coronaviruses are positive-stranded RNA viruses that infect a variety of hosts, resulting in a range of symptoms from gastrointestinal illness to respiratory distress. Bats are reservoirs for a high diversity of coronaviruses, and focused surveillance detected several strains genetically similar to MERS-coronavirus, SARS-coronavirus, and the human coronaviruses 229E and NL63. The bat fauna of central Asia, which link China to eastern Europe, are relatively less studied than other regions of the world. Kazakhstan is the world’s ninth largest country; however, little is understood about the prevalence and diversity of bat-borne viruses. In this study, bat guano was collected from bat caves in three different sites of southern Kazakhstan that tested positive for coronaviruses. Our phylogenetic reconstruction indicates these are novel bat coronaviruses that belong to the genus Alphacoronavirus. In addition, two distinct lineages of Kazakhstan bat coronaviruses were detected. Both lineages are closely related to bat coronaviruses from China, France, Spain, and South Africa, suggesting that co-circulation of coronaviruses is common in multiple bat species with overlapping geographical distributions. Our study highlights the need for collaborative efforts in understudied countries to increase integrated surveillance capabilities toward better monitoring and detection of infectious diseases.

negative: Carry forward advantages of traditional medicines in prevention and control of outbreak of COVID-19 pandemic Members of the China-ASEAN Joint Laboratory for International Cooperation in Traditional Medicine Research used the video conference platform to exchange and discuss the advantages of traditional medicine through the form of score exchange and report, and research and develop the amount and issues of the therapeutic COVID-19 products of concern. This paper manly reviews the achievements of the implementation of the epidemic prevention and control plan, advances of scientific basic studies on SARS-CoV-2, analysis and screening of potential targets and pathways of antiviral compounds based on network pharmacology and development of antiviral food dual-use products. The authors believe that the declaration of the (10+3) special meeting of national leaders on epidemic prevention and control should raise the medical and pharmaceutical issues of common concern. It is the responsibility of our joint laboratory members to accelerate the development of traditional medicine research and industry. Also the authors believe that this exchange will certainly promote the development of the cause of cooperation.

negative: The socio-economic determinants of the coronavirus disease (COVID-19) pandemic The magnitude of the coronavirus disease (COVID-19) pandemic has an enormous impact on the social life and the economic activities in almost every country in the world. Besides the biological and epidemiological factors, a multitude of social and economic criteria also govern the extent of the coronavirus disease spread in the population. Consequently, there is an active debate regarding the critical socio-economic determinants that contribute to the resulting pandemic. In this paper, we contribute towards the resolution of the debate by leveraging Bayesian model averaging techniques and country level data to investigate the potential of 29 determinants, describing a diverse set of socio-economic characteristics, in explaining the coronavirus pandemic outcome. We show that the true empirical model behind the coronavirus outcome is constituted only of few determinants, but the extent to which each determinant is able to provide a credible explanation varies between countries due to their heterogeneous socio-economic characteristics. To understand the relationship between the potential determinants in the specification of the true model, we develop the coronavirus determinants Jointness space. In this space, two determinants are connected with each other if they are able to jointly explain the coronavirus outcome. As constructed, the obtained map acts as a bridge between theoretical investigations and empirical observations, and offers an alternate view for the joint importance of the socio-economic determinants when used for developing policies aimed at preventing future epidemic crises.

negative: Lessons from mainland China's epidemic experience about the growth rules of infected and recovered cases of COVID-19 worldwide The novel coronavirus disease (COVID-19) that emerged at the end of 2019 has been controlled in mainland China so far, while it is still spreading globally. When the pandemic will end is a question of great concern. A logistic model depicting the growth rules of infected and recovered cases in mainland China may shed some light on this question. We extended this model to 31 countries outside China experiencing serious COVID-2019 outbreaks. The model well explained the data in our study (R2 >0.95). For infected cases, the semi-saturation period (SSP) ranges from 63 to 170 days (March 3 to June 18). The logistic growth rate of infected cases is positively correlated with that of recovered cases, and the same holds for the SSP. According to the linear connection between the growth rules for infected and recovered cases identified from the Chinese data, we predicted that the SSP of the recovered cases outside China ranges from 82 to 196 days (March 22 to July 8). More importantly, we found a strong positive correlation between the SSP of infected cases and the timing of the government's response, providing strong evidence for the effectiveness of rapid epidemic control measures in various countries.

negative: Molecular evolution and multilocus sequence typing of 145 strains of SARS-CoV Abstract In this study, we have identified 876 polymorphism sites in 145 complete or partial genomes of SARS-CoV available in the NCBI GenBank. One hundred and seventy-four of these sites existed in two or more SARS-CoV genome sequences. According to the sequence polymorphism, all SARS-CoVs can be divided into three groups: (I) group 1, animal-origin viruses (such as SARS-CoV SZ1, SZ3, SZ13 and SZ16); (II) group 2, all viruses with clinical origin during first epidemic; and (III) group 3, SARS-CoV GD03T0013. According to 10 special loci, group 2 again can be divided into genotypes C and T, which can be further divided into sub-genotypes C1–C4 and T1–T4. Positive Darwinian selections were identified between any pair of these three groups. Genotype C gives neutral selection. Genotype T, however, shows negative selection. By comparing the death rates of SARS patients in the different regions, it was found that the death rate caused by the viruses of the genotype C was lower than that of the genotype T. SARS-CoVs might originate from an unknown ancestor.

negative: Severe acute respiratory syndrome and dentistry A retrospective view ABSTRACT Background Severe acute respiratory syndrome, or SARS, which has created panic in Asia and in some parts of North America, is the first epidemic of the new century. Although it has been well-contained, sporadic cases continue to emerge. Objectives The authors trace the emergence of the SARS outbreak from southern China and its spread worldwide, discuss the viral etiology of the infection and its clinical features, and review the infection control guidelines issued during the outbreak by the health authorities in Hong Kong, the Centers for Disease Control and Prevention, the World Health Organization and the American Dental Association. They also review the prospects for a new outbreak and preventive measures. Overview The disease, which is caused by a novel coronavirus termed the “SARS coronavirus,” or SARS-CoV, essentially spreads through droplet infection and affects people of any age. It has a mortality rate ranging from 10 to 15 percent. A major hallmark of this disease has been the rate at which it has affected health care workers through nosocomial transmission; in some countries, up to one-fourth to one-third of those infected were in this category. However, no dental health care worker has been affected by SARS in a nosocomial or dental setting. Conclusions and Clinical Implications Researchers believe that a combination of factors, including the universal infection control measures that the dental community has implemented and/or the low degree of viral shedding in the prodromal phase of SARS, may have obviated the spread of the disease in dental settings. The dental community should reflect on this outbreak to reinforce the currently applied infection control measures.

negative: Human Coronaviruses: A Review of Virus–Host Interactions Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.

negative: Mechanism of thrombocytopenia in COVID-19 patients Since December 2019, a novel coronavirus has spread throughout China and across the world, causing a continuous increase in confirmed cases within a short period of time. Some studies reported cases of thrombocytopenia, but hardly any studies mentioned how the virus causes thrombocytopenia. We propose several mechanisms by which coronavirus disease 2019 causes thrombocytopenia to better understand this disease and provide more clinical treatment options.

negative: Chapter 7 Coronaviridae: 100,000 Years of Emergence and Reemergence Abstract The coronavirus family (Coronaviridae) is a positive-sense single-stranded RNA, with a size of 27kb. These viruses have a potential species specificity and interspecies transmission. The interspecies transmission of viruses from one host species to another is a major factor responsible for the majority of emerging and reemerging infections. The Coronaviridae is one of the most popular emerging viral families that threaten to the public health.

negative: The effect of human mobility and control measures on the COVID-19 epidemic in China The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19.

negative: A rapid scoping review of Middle East respiratory syndrome coronavirus in animal hosts Middle East respiratory syndrome coronavirus (MERS‐CoV) is an emerging zoonotic pathogen discovered in 2012. The purpose of this scoping review was to summarize the empirical evidence for MERS‐CoV in animals in order to map knowledge gaps and to extract data for modelling disease transmission in dromedary camels. A review protocol was developed a priori, and a systematic search, data extraction and summary were conducted using the Arksey and O'Malley framework. Ninety‐nine publications were identified for full review out of 1,368 unique records. Of these publications, 71 were articles in scientific journals. Ninety of the studies were observational and the remaining nine were experimental. We summarize characteristics of animal studies including study design, study population and outcomes of interest for future transmission modelling in the reservoir population. The majority of field studies reported measures of prevalence, while experimental studies provided estimates of transmission parameters that pertain to the natural course of disease.

negative: CONTAIN: An open-source shipping container laboratory optimised for automated COVID-19 diagnostics The COVID-19 pandemic has challenged diagnostic systems globally. Expanding testing capabilities to conduct population-wide screening for COVID-19 requires innovation in diagnostic services at both the molecular and industrial scale. No report to-date has considered the complexity of laboratory infrastructure in conjunction with the available molecular assays to offer a standardised solution to testing. Here we present CONTAIN. A modular biosafety level 2+ laboratory optimised for automated RT-qPCR COVID-19 testing based on a standard 40ft shipping container. Using open-source liquid-handling robots and RNA extraction reagents we demonstrate a reproducible workflow for RT-qPCR COVID-19 testing. With five OT2 liquid handlers, a single CONTAIN unit reaches a maximum daily testing capacity of 2400 tests/day. We validate this workflow for automated RT-qPCR testing, using both synthetic SARS-CoV-2 samples and patient samples from a local NHS hospital. Finally, we discuss the suitability of CONTAIN and its flexibility in a range of diagnostic testing scenarios including high-density urban environments and mobile response units. Visual abstract

negative: Asymptomatic COVID-19 in pregnant woman with typical chest CT manifestation: a case report/ 中华围产医学杂志 We report a case of maternal asymptomatic COVID-19 in a patient with typical CT image of pneumonia in the third trimester, and both the mother and baby were well. The patient, a 30-year-old female, was transferred to Yichun People's Hospital at 37 +3 gestational weeks because of a positive 2019 novel coronavirus nucleic acid result over seven hours. Her husband and mother-in-law were diagnosed with COVID-19 eight days before her admission and on the same day, respectively. The patient reported no discomfort before admission, and there were no abnormalities in the prenatal course during her pregnancy. On February 13 (the second day of admission), a patchy blurred shadow was observed in the lower lobe of the right lung in chest CT scan, and a live baby girl was delivered by a precaution-based emergent cesarean section because of suspected fetal distress shown in electrical fetal heart monitoring. Both the mother and the newborn were isolated separately after the operation without etiological examination of amniotic fluid, umbilical cord blood, placenta, etc. All the medical staff involved in the cesarean section were isolated as well. The mother was healthy and remained asymptomatic after delivery, while antiviral and anti-inflammatory treatment was offered. COVID-19 nucleic acid tests of pharyngeal swab were negative on the 4 th and 6 th day after operation. Chest CT on the 5 th day after delivery showed inflammation in the lower lobe of the right lung, and reexamination on the 8 th day showed a slight absorption of the inflammation. Samples of peripheral blood and pharynx swab were obtained from the newborn on the day of birth and four and seven days after birth and novel coronavirus nucleic acid test were all negative. The mother and baby dyad were discharged nine days after operation. And novel coronavirus nucleic acid tests were all negative in all medical staff involved.

negative: Viral indicators for tracking domestic wastewater contamination in the aquatic environment Waterborne enteric viruses are an emerging cause of disease outbreaks and represent a major threat to global public health. Enteric viruses may originate from human wastewater and can undergo rapid transport through aquatic environments with minimal decay. Surveillance and source apportionment of enteric viruses in environmental waters is therefore essential for accurate risk management. However, individual monitoring of the >100 enteric viral strains that have been identified as aquatic contaminants is unfeasible. Instead, viral indicators are often used for quantitative assessments of wastewater contamination, viral decay and transport in water. An ideal indicator for tracking wastewater contamination should be (i) easy to detect and quantify, (ii) source-specific, (iii) resistant to wastewater treatment processes, and (iv) persistent in the aquatic environment, with similar behaviour to viral pathogens. Here, we conducted a comprehensive review of 127 peer-reviewed publications, to critically evaluate the effectiveness of several viral indicators of wastewater pollution, including common enteric viruses (mastadenoviruses, polyomaviruses, and Aichi viruses), the pepper mild mottle virus (PMMoV), and gut-associated bacteriophages (Type II/III FRNA phages and phages infecting human Bacteroides species, including crAssphage). Our analysis suggests that overall, human mastadenoviruses have the greatest potential to indicate contamination by domestic wastewater due to their easy detection, culturability, and high prevalence in wastewater and in the polluted environment. Aichi virus, crAssphage and PMMoV are also widely detected in wastewater and in the environment, and may be used as molecular markers for human-derived contamination. We conclude that viral indicators are suitable for the long-term monitoring of viral contamination in freshwater and marine environments and that these should be implemented within monitoring programmes to provide a holistic assessment of microbiological water quality and wastewater-based epidemiology, improve current risk management strategies and protect global human health.

negative: COVID-19 and Environmental factors. A PRISMA-compliant systematic review The emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its airborne spread via droplets. The impact of environmental factors on the coronavirus disease 2019 (COVID-19) outbreak is under consideration. We therefore reviewed the literature on all available information about the impact of environmental factors on human coronaviruses. Temperature, humidity and other environmental factors have been recorded as environmental drivers of the COVID-19 outbreak in China and in other countries. Higher temperatures might be positive to decrease the COVID-19 incidence. In our review, the analysis of 23 studies show evidence that high temperature and high humidity reduce the COVID-19 transmission. However, further studies concerning other environmental (namely meteorological) factors role should be conducted in order to further prove this correlation. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.

negative: Threats from the coronavirus, lessons from the plague

negative: Coronavirus derived expression systems Abstract Both helper dependent expression systems, based on two components, and single genomes constructed by targeted recombination, or by using infectious cDNA clones, have been developed. The sequences that regulate transcription have been characterized mainly using helper dependent expression systems and it will now be possible to validate them using single genomes. The genome of coronaviruses has been engineered by modification of the infectious cDNA leading to an efficient (>20 μg ml−1) and stable (>20 passages) expression of the foreign gene. The possibility of engineering the tissue and species tropism to target expression to different organs and animal species, including humans, increases the potential of coronaviruses as vectors. Thus, coronaviruses are promising virus vectors for vaccine development and, possibly, for gene therapy.

negative: Modeling of Viral Aerosol Transmission and Detection In this paper, we propose studying the disease spread mechanism in the atmosphere as an engineering problem. Aerosol transmission is the most significant mode among the viral transmission mechanisms that do not include physical contact, where airflows carry virus-laden droplets over long distances. Throughout this work, we study the transport of these droplets as a molecular communication problem, where one has no control over the transmission source, but a robust receiver can be designed using bio-sensors. To this end, we present a complete system model and derive an end-to-end mathematical model for the transmission channel under certain constraints and boundary conditions. We derive the system response for both continuous sources such as breathing and jet or impulsive sources such as coughing and sneezing. In addition to transmitter and channel, we assumed a receiver architecture composed of air sampler and Silicon Nanowire field-effect transistor. Then, we formulate a detection problem to maximize the likelihood decision rule and minimize the corresponding missed detection probability. Finally, we present several numerical results to observe the impact of parameters that affect the performance and justify the feasibility of the proposed setup in related applications.

negative: Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis Background: Recently, Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan, China. Although the clinical features of COVID-19 have been reported previously, data regarding the risk factors associated with the clinical outcomes are lacking. Objectives: To summary and analyze the clinical characteristics and identify the predictors of disease severity and mortality. Methods: The PubMed, Web of Science Core Collection, Embase, Cochrane and MedRxiv databases were searched through February 25, 2020. Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations were followed. We extracted and pooled data using random-effects meta-analysis to summary the clinical feature of the confirmed COVID-19 patients, and further identify risk factors for disease severity and death. Heterogeneity was evaluated using the I2 method and explained with subgroup analysis and meta-regression. Results: A total of 30 studies including 53000 patients with COVID-19 were included in this study, the mean age was 49.8 years (95% CI, 47.5-52.2 yrs) and 55.5% were male. The pooled incidence of severity and mortality were 20.2% (95% CI, 15.1-25.2%) and 3.1% (95% CI, 1.9-4.2%), respectively. The predictor for disease severity included old age (≥ 50 yrs, odds ratio [OR] = 2.61; 95% CI, 2.29-2.98), male (OR =1.348, 95% CI, 1.195-1.521), smoking (OR =1.734, 95% CI, 1.146-2.626) and any comorbidity (OR = 2.635, 95% CI, 2.098-3.309), especially chronic kidney disease (CKD, OR = 6.017; 95% CI, 2.192-16.514), chronic obstructive pulmonary disease (COPD, OR = 5.323; 95% CI, 2.613-10.847) and cerebrovascular disease (OR = 3.219; 95% CI, 1.486-6.972). In terms of laboratory results, increased lactate dehydrogenase (LDH), C-reactive protein (CRP) and D-dimer and decreased blood platelet and lymphocytes count were highly associated with severe COVID-19 (all for P < 0.001). Meanwhile, old age (≥ 60 yrs, RR = 9.45; 95% CI, 8.09-11.04), followed by cardiovascular disease (RR = 6.75; 95% CI, 5.40-8.43) hypertension (RR = 4.48; 95% CI, 3.69-5.45) and diabetes (RR = 4.43; 95% CI, 3.49-5.61) were found to be independent prognostic factors for the COVID-19 related death. Conclusions: To our knowledge, this is the first evidence-based medicine research to explore the risk factors of prognosis in patients with COVID-19, which is helpful to identify early-stage patients with poor prognosis and adapt effective treatment.

negative: Improving epidemic surveillance and response: big data is dead, long live big data

negative: SLEDGE: A Simple Yet Effective Baseline for Coronavirus Scientific Knowledge Search With worldwide concerns surrounding the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there is a rapidly growing body of literature on the virus. Clinicians, researchers, and policy-makers need a way to effectively search these articles. In this work, we present a search system called SLEDGE, which utilizes SciBERT to effectively re-rank articles. We train the model on a general-domain answer ranking dataset, and transfer the relevance signals to SARS-CoV-2 for evaluation. We observe SLEDGE's effectiveness as a strong baseline on the TREC-COVID challenge (topping the learderboard with an nDCG@10 of 0.6844). Insights provided by a detailed analysis provide some potential future directions to explore, including the importance of filtering by date and the potential of neural methods that rely more heavily on count signals. We release the code to facilitate future work on this critical task at https://github.com/Georgetown-IR-Lab/covid-neural-ir

negative: Risk Factors for Middle East Respiratory Syndrome Coronavirus Infection among Healthcare Personnel Healthcare settings can amplify transmission of Middle East respiratory syndrome coronavirus (MERS-CoV), but knowledge gaps about the epidemiology of transmission remain. We conducted a retrospective cohort study among healthcare personnel in hospital units that treated MERS-CoV patients. Participants were interviewed about exposures to MERS-CoV patients, use of personal protective equipment, and signs and symptoms of illness after exposure. Infection status was determined by the presence of antibodies against MERS-CoV. To assess risk factors, we compared infected and uninfected participants. Healthcare personnel caring for MERS-CoV patients were at high risk for infection, but infection most often resulted in a relatively mild illness that might be unrecognized. In the healthcare personnel cohort reported here, infections occurred exclusively among those who had close contact with MERS-CoV patients.

negative: Coronavirus Disease (COVID-19): A primer for emergency physicians INTRODUCTION: Rapid worldwide spread of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic. OBJECTIVE: This review article provides emergency physicians with an overview of the most current understanding of COVID-19 and recommendations on the evaluation and management of patients with suspected COVID-19. DISCUSSION: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing COVID-19, is primarily transmitted from person-to-person through close contact (approximately 6 ft) by respiratory droplets. Symptoms of COVID-19 are similar to other viral upper respiratory illnesses. Three major trajectories include mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ARDS). Emergency physicians should focus on identifying patients at risk, isolating suspected patients, and informing hospital infection prevention and public health authorities. Patients with suspected COVID-19 should be asked to wear a facemask. Respiratory etiquette, hand washing, and personal protective equipment are recommended for all healthcare personnel caring for suspected cases. Disposition depends on patient symptoms, hemodynamic status, and patient ability to self-quarantine. CONCLUSION: This narrative review provides clinicians with an updated approach to the evaluation and management of patients presenting to the emergency department with suspected COVID-19.

negative: Experimental studies of a coronavirus and coronavirus-like agent in a barrier-maintained feline breeding colony Minimal-disease (MD) cats raised in a barrier-maintained feline breeding colony routinely become coronavirus (CV) antibody-positive at 5–8 weeks of age and remain seropositive indefinitely. In addition, they shed coronavirus-like particles (CVLPs) in their feces which are morphologically distinct from “typical” coronaviruses. Oronasal, intraperitoneal, intraduodenal, and intravenous inoculations of CVLPs were uniformly unsuccessful in the seroconversion of cats to CV, whereas subsequent prolonged close contact with colony cats did result in seroconversion. Such evidence indicates that MD cats in this barrier colony are infected with at least two non-cross-reactive agents: (1) feline enteric CVLPs, which are shed in feces and are morphologically and antigenically distinct from established coronaviruses (CVs), and (2) a virus which is antigenically cross-reactive with CVs, but which is apparently shed by some route other than the lower gastrointestinal tract.

negative: A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.

negative: Emerging Influenza and Psychosis: An Important Story in Psychological Medicine

negative: Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA) -mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC(50)] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10(−4)vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37 t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] × 10(−4)vs. 1.00 ± 0.43, t = 3.98, P < 0.05). CONCLUSIONS: Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.

negative: Complete genome sequence of bat coronavirus HKU2 from Chinese horseshoe bats revealed a much smaller spike gene with a different evolutionary lineage from the rest of the genome Abstract Apart from bat-SARS-CoV, we have identified a novel group 1 coronavirus, bat-CoV HKU2, in Rhinolophus sinicus (Chinese horseshoe bats). Since it has been suggested that the receptor-binding motif (RBM) of SARS-CoV may have been acquired from a group 1 coronavirus, we conducted a surveillance study and identified bat-SARS-CoV and bat-CoV HKU2 in 8.7% and 7.5% respectively of R. sinicus in Hong Kong and Guangdong. Complete genome sequencing of four strains of bat-CoV HKU2 revealed the smallest coronavirus genome (27164 nucleotides) and a unique spike protein evolutionarily distinct from the rest of the genome. This spike protein, sharing similar deletions with other group 2 coronaviruses in its C-terminus, also contained a 15-amino acid peptide homologous to a corresponding peptide within the RBM of spike protein of SARS-CoV, which was absent in other coronaviruses except bat-SARS-CoV. These suggest a common evolutionary origin in the spike protein of bat-CoV HKU2, bat-SARS-CoV, and SARS-CoV.

negative: Modelling strategies for controlling SARS outbreaks. Severe acute respiratory syndrome (SARS), a new, highly contagious, viral disease, emerged in China late in 2002 and quickly spread to 32 countries and regions causing in excess of 774 deaths and 8098 infections worldwide. In the absence of a rapid diagnostic test, therapy or vaccine, isolation of individuals diagnosed with SARS and quarantine of individuals feared exposed to SARS virus were used to control the spread of infection. We examine mathematically the impact of isolation and quarantine on the control of SARS during the outbreaks in Toronto, Hong Kong, Singapore and Beijing using a deterministic model that closely mimics the data for cumulative infected cases and SARS-related deaths in the first three regions but not in Beijing until mid-April, when China started to report data more accurately. The results reveal that achieving a reduction in the contact rate between susceptible and diseased individuals by isolating the latter is a critically important strategy that can control SARS outbreaks with or without quarantine. An optimal isolation programme entails timely implementation under stringent hygienic precautions defined by a critical threshold value. Values below this threshold lead to control, but those above are associated with the incidence of new community outbreaks or nosocomial infections, a known cause for the spread of SARS in each region. Allocation of resources to implement optimal isolation is more effective than to implement sub-optimal isolation and quarantine together. A community-wide eradication of SARS is feasible if optimal isolation is combined with a highly effective screening programme at the points of entry.

negative: Modelling the COVID-19 epidemic and implementation of population-wide interventions in Italy In Italy, 128,948 confirmed cases and 15,887 deaths of people who tested positive for SARS-CoV-2 were registered as of 5 April 2020. Ending the global SARS-CoV-2 pandemic requires implementation of multiple population-wide strategies, including social distancing, testing and contact tracing. We propose a new model that predicts the course of the epidemic to help plan an effective control strategy. The model considers eight stages of infection: susceptible (S), infected (I), diagnosed (D), ailing (A), recognized (R), threatened (T), healed (H) and extinct (E), collectively termed SIDARTHE. Our SIDARTHE model discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. The distinction between diagnosed and non-diagnosed individuals is important because the former are typically isolated and hence less likely to spread the infection. This delineation also helps to explain misperceptions of the case fatality rate and of the epidemic spread. We compare simulation results with real data on the COVID-19 epidemic in Italy, and we model possible scenarios of implementation of countermeasures. Our results demonstrate that restrictive social-distancing measures will need to be combined with widespread testing and contact tracing to end the ongoing COVID-19 pandemic.

negative: Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020 Abstract Background There’s an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. Methods 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. Results The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. Conclusions Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.

negative: Specific viral RNA drives the SARS CoV-2 nucleocapsid to phase separate A mechanistic understanding of the SARS-CoV-2 viral replication cycle is essential to develop new therapies for the COVID-19 global health crisis. In this study, we show that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with the viral genome, and propose a model of viral packaging through LLPS. N-protein condenses with specific RNA sequences in the first 1000 nts (5’-End) under physiological conditions and is enhanced at human upper airway temperatures. N-protein condensates exclude non-packaged RNA sequences. We comprehensively map sites bound by N-protein in the 5’-End and find preferences for single-stranded RNA flanked by stable structured elements. Liquid-like N-protein condensates form in mammalian cells in a concentration-dependent manner and can be altered by small molecules. Condensation of N-protein is sequence and structure specific, sensitive to human body temperature, and manipulatable with small molecules thus presenting screenable processes for identifying antiviral compounds effective against SARS-CoV-2.

negative: Coronavirus and its implications for psychiatry: a rapid review of the early literature BACKGROUND: The novel coronavirus pandemic has changed healthcare rapidly and dramatically. We provide a critical synthesis of the scientific literature on the pandemic’s implications for psychiatric practice. METHODS: A rapid literature review was undertaken to identify scientific literature linking psychiatric outcomes and practice changes due to coronavirus and the disease it causes (COVID-19). A structured quality assessment was used to assess those articles reporting quantitative data. RESULTS: Fifty articles were identified for inclusion, but only 12 contained original data. Eleven of those twelve were rated as poor quality. The literature described psychiatric sequelae of the coronavirus and related public health interventions through cross-sectional surveys among different populations; no studies include diagnostic or functional impairment data. Populations at risk include COVID-19 survivors, healthcare workers, the elderly, and those with pre-existing psychiatric disease. Impacts on psychiatric practice were described, again without data on changes to quality or access of care. CONCLUSIONS: There is a quickly accumulating body of evidence on the psychiatric implications of coronavirus including psychological effects on the general public and at-risk subgroups. Similarly, psychiatric practice has witnessed substantial adaptation to the pandemic. However, these reports are largely anecdotal at this point. Few data characterize these trends, and the early scientific findings are of generally poor quality.

negative: Epidemiology and disease control in everyday beef practice It is important for food animal veterinarians to understand the interaction among animals, pathogens, and the environment, in order to implement herd-specific biosecurity plans. Animal factors such as the number of immunologically protected individuals influence the number of individuals that a potential pathogen is able to infect, as well as the speed of spread through a population. Pathogens differ in their virulence and contagiousness. In addition, pathogens have various methods of transmission that impact how they interact with a host population. A cattle population's environment includes its housing type, animal density, air quality, and exposure to mud or dust and other health antagonists such as parasites and stress; these environmental factors influence the innate immunity of a herd by their impact on immunosuppression. In addition, a herd's environment also dictates the “animal flow” or contact and mixing patterns of potentially infectious and susceptible animals. Biosecurity is the attempt to keep infectious agents away from a herd, state, or country, and to control the spread of infectious agents within a herd. Infectious agents (bacteria, viruses, or parasites) alone are seldom able to cause disease in cattle without contributing factors from other infectious agents and/or the cattle's environment. Therefore to develop biosecurity plans for infectious disease in cattle, veterinarians must consider the pathogen, as well as environmental and animal factors.

negative: Long-term trends in seasonality of mortality in urban Madagascar: the role of the epidemiological transition Background: Seasonal patterns of mortality have been identified in Sub-Saharan Africa but their changes over time are not well documented. Objective: Based on death notification data from Antananarivo, the capital city of Madagascar, this study assesses seasonal patterns of all-cause and cause-specific mortality by age groups and evaluates how these patterns changed over the period 1976–2015. Methods: Monthly numbers of deaths by cause were obtained from death registers maintained by the Municipal Hygiene Office in charge of verifying deaths before the issuance of burial permits. Generalized Additive Mixed regression models (GAMM) were used to test for seasonality in mortality and its changes over the last four decades, controlling for long-term trends in mortality. Results: Among children, risks of dying were the highest during the hot and rainy season, but seasonality in child mortality has significantly declined since the mid-1970s, as a result of declines in the burden of infectious diseases and nutritional deficiencies. In adults aged 60 and above, all-cause mortality rates are the highest in the dry and cold season, due to peaks in cardiovascular diseases, with little change over time. Overall, changes in the seasonality of all-cause mortality have been driven by shifts in the hierarchy of causes of death, while changes in the seasonality within broad categories of causes of death have been modest. Conclusion: Shifts in disease patterns brought about by the epidemiological transition, rather than changes in seasonal variation in cause-specific mortality, are the main drivers of trends in the seasonality of all-cause mortality.

negative: Global Trends in Epidemiology of Coronavirus Disease 2019 (COVID-19) In December 2019, suddenly 54 cases of viral pneumonia emerged in Wuhan, China, caused by some unknown microorganism. The virus responsible for these pneumonia infections was identified as novel coronavirus of the family Coronaviridae. The novel coronavirus was renamed as COVID-19 by WHO. Infection from the virus has since increased exponentially and has spread all over the world in more than 196 countries. The WHO has declared a Public Health Emergency of International Concern due to the outbreak of COVID-19. The virus is highly infectious and can cause human-to-human transmission. Every 24 h, cases of COVID-19 increase severalfolds. The WHO is monitoring the SARS-CoV-2 spread very closely via a global surveillance system. The current situation demands the enforcement of strict laws which would help in inhibiting the further spread of COVID-19. Social distancing, international travel restrictions to affected countries, and hygiene are three important ways to nullify SARS-CoV-2.Government and private organizations need to come forward and work together during this pandemic. Public awareness, social distancing, and sterilization must be maintained to neutralize the viral infection, especially in major hot spots.

negative: The ocular surface, coronaviruses and COVID-19 The ocular surface has been suggested as a site of infection with Coronavirus-2 (SARS-CoV-2) responsible for the coronavirus disease-19 (COVID-19). This review examines the evidence for this hypothesis, and its implications for clinical practice. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), responsible for the COVID-19 pandemic, is transmitted by person-to-person contact, via airborne droplets, or through contact with contaminated surfaces. SARS-CoV-2 binds to angiotensin converting enzyme-2 (ACE2) to facilitate infection in humans. This review sets out to evaluate evidence for the ocular surface as a route of infection. A literature search in this area was conducted on 15 April 2020 using the Scopus database. In total, 287 results were returned and reviewed. There is preliminary evidence for ACE2 expression on corneal and conjunctival cells, but most of the other receptors to which coronaviruses bind appear to be found under epithelia of the ocular surface. Evidence from animal studies is limited, with a single study suggesting viral particles on the eye can travel to the lung, resulting in very mild infection. Coronavirus infection is rarely associated with conjunctivitis, with occasional cases reported in patients with confirmed COVID-19, along with isolated cases of conjunctivitis as a presenting sign. Coronaviruses have been rarely isolated from tears or conjunctival swabs. The evidence suggests coronaviruses are unlikely to bind to ocular surface cells to initiate infection. Additionally, hypotheses that the virus could travel from the nasopharynx or through the conjunctival capillaries to the ocular surface during infection are probably incorrect. Conjunctivitis and isolation of the virus from the ocular surface occur only rarely, and overwhelmingly in patients with confirmed COVID-19. Necessary precautions to prevent person-to-person transmission should be employed in clinical practice throughout the pandemic, and patients should be reminded to maintain good hygiene practices.

negative: Protecting patients and healthcare personnel from COVID-19: considerations for practice and outpatient care in cardiology

negative: Percutaneous closure of left ventricular pseudoaneurysm. BACKGROUND Left ventricular pseudoaneurysm is a rare but serious complication from myocardial infarction and cardiac surgery. Although standard treatment is surgical intervention, percutaneous closure of left ventricular pseudoaneurysm has become an option for high-risk surgical candidates. Experience with percutaneous treatment is limited to a few single case reports. This is the first series of percutaneous treatment of the left ventricular pseudoaneurysms. METHODS AND RESULTS This is a retrospective analysis of 9 procedures of percutaneous repair of left ventricular pseudoaneurysm in 7 consecutive patients (ages 51 to 83 years, 6 men) completed in our Structural Heart Disease center from June 2008 to December 2010. All patients were considered as a high risk for surgery because of multiple comorbidities. Multiple imaging modalities were used before, during, and after the procedures to improve success and efficacy. The left ventricular pseudoaneurysms of all 7 patients were successfully repaired. Fluoroscopy time on average was 36.5±24.0 minutes (range, 12.4 to 75.7 minutes). All patients were followed up for a period ranging from 3 to 32 months after the procedure. Each patient improved by at least 1 New York Heart Association functional class, and 4 patients improved by 2 classes. CONCLUSIONS Transcatheter closure of the left ventricular pseudoaneurysm is a feasible alternative for high-risk surgical candidates. The use of multiple imaging modalities is required for a detail planning and execution of the procedure.

negative: Disease Outbreaks: Critical Biological Factors and Control Strategies Disease outbreaks remain a major threat to human health and welfare especially in urban areas in both developed and developing countries. A large body of theoretical work has been devoted to modeling disease emergence, and critical factors that predict outbreak occurrence and severity have been proposed. In this chapter, we focus on biological factors that underlie both theoretical models and urban planning. We describe the SARS 2002–2003 pandemic as a case study of epidemic control of a human infectious disease. We then describe theoretical analyses of disease dynamics and control strategies. An important conclusion is that epidemic control will be strongly dependent on particular aspects of pathogen biology including host breadth, virulence, incubation time, and/or mutation rate. The probability, and potential cost, of future outbreaks, may be high and lessons from both past cases and theoretical work should inform urban design and policy. Interdisciplinary collaboration in planning, swiftness of information dissemination and response, and willingness to forgo personal liberties during a crisis may be key factors in resilience to infectious disease outbreaks.

negative: 2019-NCOV/COVID-19 - Approaches to viral vaccine development and preventive measures The severity assessment of COVID-19 and transmissibility of newly emerged novel-Coronavirus (2019-nCoV) can effectively help and support to quantify the ongoing pandemic risks. Among several epidemiological measures against COVID-19 severity, the case fatality risk (CFR) assessment is an important measure to track record the overall proportion/ratio of the cumulative number of infected patients with the known outcome (confirmed, recovered, or deceased). Considering the ongoing fatality rate, several case-based preventive measures, Coronavirus protein visualization, and approaches to viral vaccine development are discussed herein. The prompt identification of high-risk entities to confront the uncertainty in the risk of death using the approaches highlighted, herein, is of utmost requirement to tackle the current COVID-19 severity. Moreover, the protein visualization available at the viral surface/ body can give further insight into the appropriate vaccine development.

negative: Genomic variance of the 2019‐nCoV coronavirus There is a rising global concern for the recently emerged novel coronavirus (2019‐nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019‐nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019‐nCoV. Despite the low heterogeneity of the 2019‐nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8‐encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti‐coronavirus approaches.

negative: Time to realise the true potential of Ayurveda against COVID-19

negative: Respiratory droplets get suspended longer and spread wider in temperate environments compared to tropics and implications for SARS-CoV-2 transmission The new pandemic of SARS-CoV-2 has shown stark differences in number of affected patients between countries in the tropics and those with temperate environments. Though there have been many theories on reasons for these differences, we hypothesise that this could be due to differences in the fate of respiratory droplets in the two environments. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces. This paper discusses the possibility of differences in number of infections and spread between different countries based on the spread of droplets.

negative: Comparative dynamic aerosol efficiencies of three emergent coronaviruses and the unusual persistence of SARS-CoV-2 in aerosol suspensions The emergent coronavirus, designated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a zoonotic pathogen that has demonstrated remarkable transmissibility in the human population and is the etiological agent of a current global pandemic called COVID-19. We measured the dynamic (short-term) aerosol efficiencies of SARS-CoV-2 and compared the efficiencies with two other emerging coronaviruses, SARS-CoV (emerged in 2002) and Middle Eastern respiratory syndrome CoV (MERS-CoV; emerged starting in 2012). We also quantified the long-term persistence of SARS-CoV-2 and its ability to maintain infectivity when suspended in aerosols for up to 16 hours.

negative: The craniotomy box: an innovative method of containing hazardous aerosols generated during skull saw use in autopsy on a COVID-19 body During a disease pandemic, there is still a requirement to perform postmortem examinations within the context of legal considerations. The management of the dead from COVID-19 should not impede the medicolegal investigation of the death where required by the authorities and legislation but additional health and safety precautions should be adopted for the necessary postmortem procedures. The authors have therefore used the craniotomy box in an innovative way to enable a safe alternative for skull and brain removal procedures on suspected or confirmed COVID-19 bodies. The craniotomy box technique was tested on a confirmed COVID-19 positive body where a full postmortem examination was performed by a team of highly trained personnel in a negative pressure Biosafety Level 3 (BSL-3) autopsy suite in the National Institute of Forensic Medicine (IPFN) Malaysia. This craniotomy box is a custom-made transparent plastic box with five walls but without a floor. Two circular holes were made in one wall for the placement of arms in order to perform the skull opening procedure. A swab to detect the presence of the SARS-CoV-2 virus was taken from the interior surface of the craniotomy box after the procedure. The result from the test using real-time reverse transcriptase polymerase chain reaction (rRT-PCR) proved that an additional barrier provided respiratory protection by containing the aerosols generated from the skull opening procedure. This innovation ensures procedures performed inside this craniotomy box are safe for postmortem personnel performing high risk autopsies during pandemics.

negative: Seasonality and selective trends in viral acute respiratory tract infections Abstract Influenza A and B, and many unrelated viruses including rhinovirus, RSV, adenovirus, metapneumovirus and coronavirus share the same seasonality, since these viral acute respiratory tract infections (vARIs) are much more common in winter than summer. Unfortunately, early investigations that used recycled “pedigree” virus strains seem to have led microbiologists to dismiss the common folk belief that vARIs often follow chilling. Today, incontrovertible evidence shows that ambient temperature dips and host chilling increase the incidence and severity of vARIs. This review considers four possible mechanisms, M1 - 4, that can explain this link: (M1) increased crowding in winter may enhance viral transmission; (M2) lower temperatures may increase the stability of virions outside the body; (M3) chilling may increase host susceptibility; (M4) lower temperatures or host chilling may activate dormant virions. There is little evidence for M1 or M2, which are incompatible with tropical observations. Epidemiological anomalies such as the repeated simultaneous arrival of vARIs over wide geographical areas, the rapid cessation of influenza epidemics, and the low attack rate of influenza within families are compatible with M4, but not M3 (in its simple form). M4 seems to be the main driver of seasonality, but M3 may also play an important role.

negative: Immunotherapy could help against new coronavirus The new respiratory virus which emerged in the Middle East last year could be pegged back by artificially boosting the body's immune response

negative: Caution: The clinical characteristics of COVID-19 patients at admission are changing Background With the emergence of 4rd generation transmission, the prevention and treatment of the novel coronavirus disease 2019 (COVID-19) has entered a new period. We aimed to report several changes in the clinical characteristics at admission of patients with COVID-19. Methods Clinical records and laboratory results of patients suffering from COVID-19 were retrospectively reviewed and matched with the admission dates to analyze the changes in characteristics at the onset of illness. Results Of the 89 affected patients, 31 [34.8%] patients were admitted from January 16 to 22, and 58 [65.2%] were admitted from January 23 to 29. Patients were admitted with more systemic symptoms, such as fever (21 [67.7%] of 31), fatigue (13 [41.9%] of 31), and myalgia (7 [22.6%] of 31), before January 23. More patients (10 [32.3%] of 31) admitted before January 23 had a small amount of sputum production compared with a smaller proportion (4 [6.9%] of 58) of the patients admitted after January 23. Other symptoms, such as cough, nausea, diarrhea, and chest tightness, were not significantly different between the two groups. In addition, the group admitted before January 23 had a larger proportion of patients with reduced lymphocyte (13 [54.2%] of 24), CD3 (11 [54.4%] of 21), and CD8 (9 [42.9%] of 21) counts and elevated serum amyloid A (SAA, 18 [75%] of 24). Conclusions The initial symptoms of recently infected patients seem more insidious, indicating that the new coronavirus may gradually evolve into a virus similar to influenza and latent in asymptomatic carriers for a long time.

negative: COVID-19, SARS and MERS: are they closely related? Abstract Background The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. Aims To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. Sources The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. Content COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0–2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7–1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. Implications There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.

negative: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities. Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness. Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body toward a state of illness. Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens. Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient's unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process.

negative: Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients Abstract The nucleocapsid (N) protein is a structural component of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and can induce antibody responses in SARS patients during infection. However, it is not known whether SARS-CoV N protein can induce a long persistence of memory T-cell response in human. In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-γ and IL-2 following stimulation with a pool of overlapping peptides that cover the entire N protein sequence. The N-specific IFN-γ+CD4+ T cells were mainly composed of CD45RA−CCR7+CD62L− cells, whereas IFN-γ+CD8+ memory T cells were mostly contained within CD45RA+CCR7−CD62L− cell population. Epitope mapping study indicated that a cluster of overlapping peptides located in the C-terminal region (amino acids [aa] 331 to 362) of N protein contained at least two different T-cell epitopes. The results indicated that human memory T-cell responses specific for SARS-CoV N protein could persist for 2 years in the absence of antigen, which would be a valuable for the design of effective vaccines against SARS-CoV and for basic studies of human T-cell memory.

negative: Sequence requirements for RNA strand transfer during nidovirus discontinuous subgenomic RNA synthesis Nidovirus subgenomic mRNAs contain a leader sequence derived from the 5′ end of the genome fused to different sequences (‘bodies’) derived from the 3′ end. Their generation involves a unique mechanism of discontinuous subgenomic RNA synthesis that resembles copy-choice RNA recombination. During this process, the nascent RNA strand is transferred from one site in the template to another, during either plus or minus strand synthesis, to yield subgenomic RNA molecules. Central to this process are transcription-regulating sequences (TRSs), which are present at both template sites and ensure the fidelity of strand transfer. Here we present results of a comprehensive co-variation mutagenesis study of equine arteritis virus TRSs, demonstrating that discontinuous RNA synthesis depends not only on base pairing between sense leader TRS and antisense body TRS, but also on the primary sequence of the body TRS. While the leader TRS merely plays a targeting role for strand transfer, the body TRS fulfils multiple functions. The sequences of mRNA leader–body junctions of TRS mutants strongly suggested that the discontinuous step occurs during minus strand synthesis.

negative: The 5′-end sequence of the murine coronavirus genome: Implications for multiple fusion sites in leader-primed transcription Abstract The coronavirus leader-primed transcription model proposes that free leader RNA species derived from the 5′-end of the genomic RNA are utilized as a primer for the transcription of subgenomic mRNAs. To elucidate the precise mechanism of leader-priming, we cloned and sequenced the 5′-end of the mouse hepatitis virus genomic RNA. The 5′-terminal sequences are identical to the leader sequences present at the 5′-end of the subgenomic mRNAs. Two possible hairpin loop structures and an AU-rich region around the 3′-end of the leader sequence may provide the termination site for leader RNA synthesis. The comparison of 5′-end genomic sequences and the intergenic start sites for mRNA transcription revealed that there are homologous regions of 7–18 nucleotides at the putative leader/body junction sites. Some intergenic regions contain a mismatching nucleotide within this homologous region. We propose that free leader RNA binds to the intergenic region due to this homology and is cleaved at the mismatching nucleotide before serving as a primer. Thus, the free leader RNA species may be longer than the leader sequences in the subgenomic mRNAs and different mRNAs may have different leader/body junction sites.

negative: Differential Sensitivity of Bat Cells to Infection by Enveloped RNA Viruses: Coronaviruses, Paramyxoviruses, Filoviruses, and Influenza Viruses Bats (Chiroptera) host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat) or Yangochiroptera (genera Carollia and Tadarida) for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV), a porcine coronavirus, or to infection mediated by the Spike (S) protein of SARS-coronavirus (SARS-CoV) incorporated into pseudotypes based on vesicular stomatitis virus (VSV). The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3) were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus) and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed.

negative: Detection of feline Coronavirus in effusions of cats with and without feline infectious peritonitis using loop-mediated isothermal amplification Abstract Feline infectious peritonitis (FIP) is a fatal disease in cats worldwide. The aim of this study was to test two commercially available reaction mixtures in a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to detect feline Coronavirus (FCoV) in body cavity effusions of cats with and without FIP, in order to minimize the time from sampling to obtaining results. RNA was extracted from body cavity effusion samples of 71 cats, including 34 samples from cats with a definitive diagnosis of FIP, and 37 samples of control cats with similar clinical signs but other confirmed diseases. Two reaction mixtures (Isothermal Mastermix, OptiGene Ltd.and PCRun™ Molecular Detection Mix, Biogal) were tested using the same primers, which were designed to bind to a conserved region of the FCoV membrane protein gene. Both assays were conducted under isothermal conditions (61 °C–62 °C). Using the Isothermal Mastermix of OptiGene Ltd., amplification times ranged from 4 and 39 min with a sensitivity of 35.3% and a specificity of 94.6% for the reported sample group. Using the PCRun™ Molecular Detection Mix of Biogal, amplification times ranged from 18 to 77 min with a sensitivity of 58.8% and a specificity of 97.3%. Although the RT-LAMP assay is less sensitive than real time reverse transcription PCR (RT-PCR), it can be performed without the need of expensive equipment and with less hands-on time. Further modifications of primers might lead to a suitable in-house test and accelerate the diagnosis of FIP.

negative: Underweight, overweight, and obesity as independent risk factors for hospitalization in adults and children from influenza and other respiratory viruses BACKGROUND: The relationship between obesity and risk of complications described during the 2009 influenza pandemic is poorly defined for seasonal influenza and other viral causes of influenza‐like illness (ILI). METHODS: An observational cohort of hospitalized and outpatient participants with ILI was conducted in six hospitals in Mexico. Nasopharyngeal swabs were tested for influenza and other common respiratory pathogens. RESULTS: A total of 4778 participants were enrolled in this study and had complete data. A total of 2053 (43.0%) had severe ILI. Seven hundred and seventy‐eight (16.3%) were positive for influenza, 2636 (55.2%) were positive for other viral respiratory pathogens, and 1364 (28.5%) had no respiratory virus isolated. Adults with influenza were more likely to be hospitalized if they were underweight (OR: 5.20), obese (OR: 3.18), or morbidly obese (OR: 18.40) compared to normal‐weight adults. Obese adults with H1N1 had a sixfold increase in odds of hospitalization over H3N2 and B (obese OR: 8.96 vs 1.35, morbidly obese OR: 35.13 vs 5.58, respectively) compared to normal‐weight adults. In adults with coronavirus, metapneumovirus, parainfluenza, and rhinovirus, participants that were underweight (OR: 4.07) and morbidly obese (OR: 2.78) were more likely to be hospitalized as compared to normal‐weight adults. All‐cause influenza‐like illness had a similar but less pronounced association between underweight or morbidly obesity and hospitalization. CONCLUSIONS: There is an increased risk of being hospitalized in adult participants that are underweight or morbidly obese, regardless of their viral pathogen status. Having influenza, however, significantly increases the odds of hospitalization in those who are underweight or morbidly obese.

negative: Preparing Children for Pandemics COVID-19 has given us a food for thought that whether we are prepared for such pandemics or not. Developed nations may say that they have enough resources to tackle such situations, but when it comes to the physical and emotional security of the children, even they have to think manifolds because preparing children for such pandemics need lot of effort and apt planning. The purpose of this chapter is to reflect issues related to children during any infectious disease outbreak like COVID-19. Adults are mature enough to control their emotions and can act patiently, but immature minds are always perplexed and act in a very clingy way when some adverse situation is thrown to them. Children are ardent observers and act according to the reactions of the folks around them. It is difficult for them to conceal their behavior, and it is difficult for parents as well to manage their anxiety levels. During crisis period when social distancing and refrained outdoor activities have brought our children into a knotty situation, it is necessary that we understand their fears and myths, try to resolve their concerns in a polite way and strengthen their minds. At this stage the role of parents, teachers, educational institutes, social media, and international children’s organizations need to be redefined. The importance of the decisions taken by the governing bodies should be explained to the children in an effective way, so that they do not panic and reflect a brave attitude. UNICEF in collaboration with international health support systems and departments has a major role to play. Appropriate planning for preparing the children for pandemics has to be incorporated in our system, so that any future crisis can be dealt in an easier way. Schools colleges and other educational institutes should execute immunization and hygiene and health practices in advance to promote prevention.

negative: COVID-19: Knowns, Unknowns, and Questions The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months highlights the transmissibility of this family of viruses and the significant morbidity and mortality that they can cause. We highlight the current state of knowledge of coronavirus biology while answering questions concerning the current outbreak of SARS-CoV-2.

negative: Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m(6)A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

negative: Effects of body tilt on multifrequency admittance tympanometry. INTRODUCTION Hydrops and abnormalities of inner fluid pressure are involved in some otologic diseases such as Ménière's disease (MD). However, demonstrating abnormal perilymphatic or endolymphatic pressure is challenging. Multifrequency tympanometry studies in MD patients demonstrated an increase of the width of conductance tympanograms (outside an attack) compared with controls. To confirm that the increase in conductance width is caused by hyperpressure and not hypopressure in these patients tested outside an attack, we assessed the effect of changes in inner ear fluid pressure caused by body tilt on the results of multifrequency admittancemetry tympanograms. MATERIALS AND METHODS A multifrequency tympanometry including conductance (G) tympanogram at 2 kHz and resonance frequency measurements were performed in 20 volunteers (40 ears) free of otologic or neurologic disease. The measures were collected in three different positions: vertical, supine, and Trendelenburg positions. RESULTS Changes in inner ear fluid pressure caused by body tilt induced an increase in the width of G tympanograms. In the vertical position, the mean value was 141.7 ± 56.5 daPa; in the supine position, it increased to 158 ± 58.3 daPa; and increased even more in the Trendelenburg position (20 degrees), with a mean of 184 ± 69.6 daPa (p < 0.01). Resonance frequency also increased in the Trendelenburg position.We conclude that the increased width of G tympanograms in MD patients outside an attack may be caused by an increase in inner ear fluid pressure.

negative: Pneumonie unter allogener Stammzelltransplantation Die allogene Transplantation beinhaltet im Gegensatz zur autologen Transplantation die Übertragung von Knochenmark oder Blutstammzellen eines anderen Spenders. Im Falle einer Pneumonie reflektiert die Phase der Immunsuppression das zu erwartende Erregerspektrum. Im Unterschied zur autologen Stammzelltransplantation umfasst das Risiko für bestimmte Erreger je nach Phase nicht nur das der Neutropenie, sondern auch der zellulären und humoralen Immunsuppression durch die immunsuppressive Medikation bzw. die akute und chronische GvHD. Zudem besteht das Risiko für nichtinfektiöse pulmonale Komplikationen. Das Zytomegalievirus ist einer der wichtigsten Erreger von schweren Infektionen bzw. Pneumonien. Nach Etablierung der präventiven Therapien sind CMV-Pneumonien bis Tag 100 eher selten geworden; ein Problem bleiben weiterhin die späten CMV-Pneumonien durch ihre hohe Letalität. Die Indikation zur Bronchoskopie sollte den allgemeinen Prinzipien der Diagnostik von pulmonalen Komplikationen unter Immunsuppression folgen.

negative: A Review of Coronavirus Disease-2019 (COVID-19) There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

negative: Introducing special cutaneous “sign” tribute to healthcare workers managing new coronavirus disease (Covid −19)

negative: Particularités épidémiologiques et prévention des infections nosocomiales virales Résumé Objectifs Décrire les caractéristiques épidémiologiques des infections nosocomiales virales (INV) et les principes de leur prévention. Épidémiologie De nombreux facteurs concourent à une sous-évaluation des INV : l’intrication des infections communautaires et nosocomiales pour les viroses saisonnières, la durée d’incubation entraînant une manifestation après la sortie du patient, les difficultés diagnostiques. Les populations les plus à risques d’INV sont les enfants, les personnes âgées et tous les immunodéprimés. Chez ces derniers, le risque de formes cliniques graves et/ou chroniques est important. Le réservoir principal des virus responsables d’INV est constitué des sujets infectés, symptomatiques ou non. Les porteurs asymptomatiques, notamment le personnel de soins, représentent un risque élevé de transmission. Les principales voies de transmission sont les voies digestive, respiratoire, cutanéomuqueuse et l’exposition au sang et produits biologiques. Une revue des principaux virus impliqués en fonction des modes de transmission est présentée. Prévention Les mesures préventives des INV sont capitales. Au premier plan, figure l’application rigoureuse des précautions standard d’hygiène et, dans certaines situations, des précautions d’isolement septique. En cas d’épidémie de grande ampleur, le regroupement des patients infectés pourra être instauré. La prévention spécifique repose principalement sur la vaccination, la chimioprophylaxie (varicelle-zona, herpès, grippe, accident d’exposition au sang) et la sélection clinique et biologique des donneurs de sang, d’organes, de tissus et de cellules. Summary Objectives To describe epidemiological features of viral nosocomial infections (VNI) and their prevention principles. Epidemiology Many factors lead to underestimate VNI: difficulty to distinguish between community-acquired and nosocomial infections for seasonal viral diseases, incubation time leading to symptoms after patient discharge, difficulty for diagnosis. Population at high risks of VNI are the children, the elderly and the immunocompromized patients. The risk of severe diseases is high in this last population. The main reservoir of virus is infected symptomatic or asymptomatic individuals. Asymptomatic carriers, especially health care workers, are a major source of transmission. Main routes of transmission are the fecal–oral route, the respiratory route, cutaneous or mucous contact and blood and body fluids exposure. A review of the main virus involved in VNI is presented. Prevention Preventive measures, such as strict adherence to standard precautions and, in some instances, to isolation procedures, are critical to control VNI. In a major outbreak situation, it may be necessary to consider cohort isolation. Specific control measures rely on immunization, antiviral drug prophylaxis (varicella–zooster, herpes, influenza, exposure to blood) and clinical and biological screening of organ, blood, tissue and cell donors.

negative: Human microbiome: an academic update on human body site specific surveillance and its possible role Human body is inhabited by vast number of microorganisms which form a complex ecological community and influence the human physiology, in the aspect of both health and diseases. These microbes show a relationship with the human immune system based on coevolution and, therefore, have a tremendous potential to contribute to the metabolic function, protection against the pathogen and in providing nutrients and energy. However, of these microbes, many carry out some functions that play a crucial role in the host physiology and may even cause diseases. The introduction of new molecular technologies such as transcriptomics, metagenomics and metabolomics has contributed to the upliftment on the findings of the microbiome linked to the humans in the recent past. These rapidly developing technologies are boosting our capacity to understand about the human body-associated microbiome and its association with the human health. The highlights of this review are inclusion of how to derive microbiome data and the interaction between human and associated microbiome to provide an insight on the role played by the microbiome in biological processes of the human body as well as the development of major human diseases.

negative: 15 An overview of automated room disinfection systems: When to use them and how to choose them Abstract Conventional disinfection methods are limited by reliance on the operator to ensure appropriate selection, formulation, distribution, and contact time of the agent. Automated room disinfection (ARD) systems remove or reduce reliance on operators and so they have the potential to improve the efficacy of terminal disinfection. The most commonly used systems are hydrogen peroxide vapor (H2O2 vapor), aerosolized hydrogen peroxide (aHP), and ultraviolet (UV) light. These systems have important differences in their active agent, delivery mechanism, efficacy, process time, and ease of use. The choice of ARD system should be influenced by the intended application, the evidence base for effectiveness, practicalities of implementation, and cost considerations.