query: how long does coronavirus remain stable  on surfaces?

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: 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.

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: Does Copper treating of commonly touched surfaces reduce healthcare acquired infections? A Systematic Review and meta-analysis Background Healthcare acquired infections (HAIs) cause substantial morbidity and mortality. Copper appears to have strong viricidal properties under laboratory conditions. Aim We conducted a systematic review to examine the potential effect of copper treating of commonly touched surfaces in healthcare facilities. Methods We included controlled trials comparing the effect of copper-treated surfaces (furniture or bed linens) in hospital rooms versus standard rooms on hospital acquired infections (HAIs). Two reviewers independently screened retrieved articles, extracted data, and assessed the risk of bias of included studies. The primary outcome was the occurrence of healthcare acquired infections. Findings We screened 638 records; 7 studies comprising 12362 patients were included. All of included studies were judged to be at high risk in [≥]2 of the 7 domains of bias. All 7 included studies reported the effect of copper-treated surfaces HAIs. Overall, we found low quality evidence of a potential clinical importance that copper-treated hard surfaces and/or bed linens and clothes reduced healthcare acquired infections by 27% (RR 0.73; 95% CI 0.57 to 0.94). Conclusion Given the clinical and economic costs of healthcare acquired infections, the potentially protective effect of copper-treated surfaces appears important. The current evidence is insufficient to make a strong positive recommendation. However, it would appear worthwhile and urgent to conduct larger-scale publicly funded clinical trials of the impact of copper coating.

positive: Covid-19 and mobile phone hygiene in healthcare settings

positive: 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.

positive: Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions. The stability of Middle East respiratory syndrome coronavirus (MERS-CoV) was determined at 20°C--40% relative humidity (RH); 30°C--30% RH and 30°C--80% RH. MERS-CoV was more stable at low temperature/low humidity conditions and could still be recovered after 48 hours. During aerosolisation of MERS-CoV, no decrease in stability was observed at 20°C--40% RH. These data suggest the potential of MERS-CoV to be transmitted via contact or fomite transmission due to prolonged environmental presence.

positive: Prevalence and acceptance of glove wearing practice among general population when visiting high risk are during local COVID-19 outbreak . Background Healthcare authorities have generally advised against wearing glove by the general population. However, the use of gloves has become a common sight in public places raising the question of the necessity of glove wearing practice by the general population Objective This study aims to investigate the prevalence and types of glove used as well as the acceptance of the glove practice by individuals visiting the high-risk area during Covid-19 pandemic. Setting This prospective observational study was conducted among individuals visiting a wet market and district specialist hospital During Covid-19 pandemic. The required data was recorded based on observation by trained data collectors who were stationed at the strategic entry point. Methods Individuals entering through dedicated entry point were observed for the type, category and practice of wearing personal protective equipment. Inclusion criteria for this study were any individuals entering the facilities from entry points without respiratory symptoms. Exclusion criteria for this study were individuals less than 2 years old, visiting the emergency department, facility staff, individuals who are suspected of multiple entry and individuals who are exiting the treatment facility entrance. Patients were categorized into two groups of acceptable and unacceptable glove practice. The Pearson chi-square was used to test for differences in investigated variables in the univariate setting. Main outcome measure Prevalence, acceptance of glove wearing practice. Results A total of 75 individuals (2.3%) compromising of 45 (60.0%) individuals from hospitals and 30 (40.0%) individuals from wet markets were seen wearing glove amongst 3322 individuals observed during the data collection period. A higher proportion of individuals visiting wet market (30.0%) were observed with unacceptable glove practice compared to individuals visiting the hospital (8.9%), {chi}2 (1) = 5.60, p=.018. Similarly, a Higher proportion of glove use among non-Malay (53.3%) compared to Malay (46.7%) was observed in hospital compared to a higher proportion of glove use among Malay compared to non-Malay (16.7%) visiting wet market, {chi}2 (1) = 10.20, p=.001. As for glove use, we found that male were using more medical-grade glove (78.8%) compared to non-medical grade glove (21.2%) while an equal amount of medical (50.0%) and non-medical grade glove (50.0%) was used among female, {chi}2 (1) = 6.546, p=.011. Besides, we found that higher proportion of individual using medical-grade glove was using medical grade facemask (68.3%) which was similar to the proportion of individuals using non-medical glove was using non-medical facemask (66.7%), {chi}2 (1) = 5.25, p=.022. Conclusion We present the prevalence and characteristics of glove wearing practice in high-risk location during the current COVID-19 outbreak in Malaysia. Facing a worldwide public health emergency with limited effective clinical treatment, the role of glove-wearing in mitigating COVID-19 transmission is questionable. If needed, the compliance to proper glove-wearing could be improved through targeted public health education

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

positive: 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.

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: 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: Coronavirus disinfection in histopathology. The 2019 Coronavirus epidemic, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. There is an international push to contain the virus and prevent its spread. It is feasible that potentially infectious samples may be received in histopathology laboratories for diagnosis. This technical note presents disinfection procedures and histotechnology processes that should alleviate the risk of infection to laboratory staff. Using data obtained from similar coronaviruses, e.g. severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), experts are confident that 70% ethanol and 0.1% sodium hypochlorite should inactivate the virus. Formalin fixation and heating samples to 56oC, as used in routine tissue processing, were found to inactivate several coronaviruses and it is believed that 2019-nCoV would be similarly affected.

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: Operation of ultrasonography services in a dedicated paediatric hospital and a university hospital in Greece under the COVID-19 pandemic Ultrasonography (US) is one of the most common diagnostic imaging tests in children. During the coronavirus disease 2019 (COVID-19) pandemic, it is important to operate with a plan designed to protect health care workers, to prevent transmission of infection from child and parents to another child or an accompanying person in the US suite, and to save valuable protective material and resources. Measures during routine US in children can be challenging both in general hospitals with paediatric units and in dedicated paediatric hospitals. Special considerations include: a) cancellation or rescheduling of unnecessary imaging tests, b) a relevant questionnaire on the request form informing about patient and accompanying person’s symptoms and likely exposure in addition to general triage, c) appropriate patient and parent protective measures, d) recruitment and selection of US machines in different protected areas depending on the possibility or certainty for the infection, e) regular personnel protective measures and personal hand hygiene, f) routine disinfection of probes and adjacent surfaces and g) machine/room deep disinfection, if required. Our purpose is to present the modified US services in children during the COVID-19 pandemic in two hospitals based on the instructions of the national organization of public health in Greece and what is known about the mode of transmission of the virus.

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: COVID-19 outbreak: succinct advice for dentists and oral healthcare professionals

positive: Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals The ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly on a global scale. Although it is clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through human respiratory droplets and direct contact, the potential for aerosol transmission is poorly understood1-3. Here we investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the outbreak of COVID-19 in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols that was detected in isolation wards and ventilated patient rooms was very low, but it was higher in the toilet areas used by the patients. Levels of airborne SARS-CoV-2 RNA in the most public areas was undetectable, except in two areas that were prone to crowding; this increase was possibly due to individuals infected with SARS-CoV-2 in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions that showed peaks in the submicrometre and/or supermicrometre regions; however, these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted through aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.

positive: Reducing hand recontamination of healthcare workers during COVID-19

positive: Detection of Severe Acute Respiratory Syndrome Coronavirus 2 RNA on Surfaces in Quarantine Rooms We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in 2 rooms of a quarantine hotel after 2 presymptomatic persons who stayed there were laboratory-confirmed as having coronavirus disease. We detected SARS-CoV-2 RNA on 8 (36%) of 22 surfaces, as well as on the pillow cover, sheet, and duvet cover.

positive: Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride Introduction Viral disease spread by contaminated commonly touched surfaces is a global concern. Silicon nitride, an industrial ceramic that is also used as an implant in spine surgery, has known antibacterial activity. The mechanism of antibacterial action relates to the hydrolytic release of surface disinfectants. It is hypothesized that silicon nitride can also inactivate the coronavirus SARS-CoV-2. Methods SARS-CoV-2 virions were exposed to 15 wt.% aqueous suspensions of silicon nitride, aluminum nitride, and copper particles. The virus was titrated by the TCD50 method using VeroE6/TMPRSS2 cells, while viral RNA was evaluated by real-time RT-PCR. Immunostaining and Raman spectroscopy were used as additional probes to investigate the cellular responses to virions exposed to the respective materials. Results All three tested materials showed >99% viral inactivation at one and ten minutes of exposure. Degradation of viral RNA was also observed with all materials. Immunofluorescence testing showed that silicon nitride-treated virus failed to infect VeroE6/TMPRSS2 cells without damaging them. In contrast, the copper-treated virus suspension severely damaged the cells due to copper ion toxicity. Raman spectroscopy indicated differential biochemical cellular changes due to infection and metal toxicity for two of the three materials tested. Conclusions Silicon nitride successfully inactivated the SARS-CoV-2 in this study. The mechanism of action was the hydrolysis-mediated surface release of nitrogen-containing disinfectants. Both aluminum nitride and copper were also effective in the inactivation of the virus. However, while the former compound affected the cells, the latter compound had a cytopathic effect. Further studies are needed to validate these findings and investigate whether silicon nitride can be incorporated into personal protective equipment and commonly touched surfaces, as a strategy to discourage viral persistence and disease spread.

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: Persistence of infectious SARS-CoV-2 on inert surfaces and hand-mediated transmission.

positive: Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London. BACKGROUND Evaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London. METHODS We performed this prospective cross-sectional observational study in a multi-site London hospital. Air and surface samples were collected from seven clinical areas, occupied by patients with COVID-19, and a public area of the hospital. Three or four 1.0 m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS Viral RNA was detected on 114/218 (52.3%) of surfaces 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 than in other areas (67/105 (63.8%) vs. 29/64 (45.3%) (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Chi squared test)). The high PCR Ct value for all samples (>30) indicated that the virus 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 environmental contamination in managing COVID-19, and the need for effective use of PPE, physical distancing, and hand/surface hygiene.

positive: A new Sephadex™-based method for removing microbicidal and cytotoxic residues when testing antiseptics against viruses: Experiments with a human coronavirus as a model Abstract The relative lack of efficient methods for evaluating antiseptic antiviral activity, together with weaknesses in the existing European Standard (i.e. NF EN 14476+A1), underlines the need to seek a new method which could allow a more precise evaluation of the antiseptic antiviral activity of chemical agents. This protocol is based on an original gel-based filtration method, using “in-house” G-25 and G-10 Sephadex™ columns. This method allows the neutralization of both the activity and the cytotoxicity of a large range of molecules, according to their molecular size, in only 1min. The viral model used was the human coronavirus (HCoV) 229E chosen for (i) its increasing medical interest, (ii) its potential resistance and (iii) its representing enveloped viruses mentioned in the European Standard. First, the protocol was validated and it was demonstrated that it was fully operational for evaluating antiviral antiseptic potentiality and useful to screen potentially antiseptic molecules. Second, chlorhexidine (CHX) and hexamidine (HXM) were assessed for their potential anti-HCoV 229E antiseptic activities. It was demonstrated clearly that (i) HXM had no activity on the HCoV 229E and (ii) CHX showed a moderate anti-HCoV 229E activity but insufficient to be antiseptic.

positive: High-flow nasal cannula may be no safer than non-invasive positive pressure ventilation for COVID-19 patients

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: Novel 2019-coronavirus on new year's Eve. An ongoing apocalyptic outbreak of a new virus causing pneumonia-like clusters in Wuhan city, China, has gleamed the world. The outbreak, confirmed on the New Year's Eve 2020, has known no boundaries since then. The number has surpassed that of Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS), and is uninterruptedly escalating. Being an RNA virus, it has a propensity to mutate due to the low proofreading capacity of RNA-dependent RNA polymerase. Step-wise mutations have led to the gradual spillover of virus and after crossing the inter-species interface, the virus has adapted itself for a stable human-to-human transmission. The disease caused by severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2) can prove deadlier if the so-called 'super-spreading events' emerge with time. Recent research has shown the maximum homology of 99% of SARS-CoV-2 to pangolins associated coronavirus, owing to which these can serve as potential intermediate host. India is responding swiftly to the emergency situation, and the whole of the country is under lockdown since 25 March 2020, to ensure social distancing. All the international flights are padlocked and the travellers are being screened at airports and seaports via thermal sensors, and quarantine for a period of 14 days is recommended. Three hundred and forty-five patients across the country tested positive with six fatalities as of 22 March 2020. No specific anti-CoV drugs are currently available. Patients are being treated with protease drugs are inhibitors, remdesivir, chloroquine, angiotensin-converting enzyme 2 inhibitors, ivermectin, sarilumab and tocilizumab, though none of these is Food and Drug Administration approved and are undergoing trials. Preventive measures such as social distancing, quarantine, cough etiquettes, proper hand washing, cleaning and decontaminating the surfaces are the mainstay for curbing the transmission of this virus. The present review highlights the update of novel SARS-CoV-2 in context to the Indian scenario.

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: 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: Contact lens practice in the time of COVID-19

positive: SARS-CoV-2 RNA detection of hospital isolation wards hygiene monitoring during the Coronavirus Disease 2019 outbreak in a Chinese hospital Abstract Objectives The aim of this paper was to monitor the presence of SARS-Cov-2 among hospital environment surfaces, sewage, and personal protective equipment (PPE) of staffs in isolation wards in the First Affiliated Hospital of Zhejiang University, China. Methods Surfaces of objects were routinely wiped with 1000mg/L chlorine containing disinfectant. Air and sewage disinfection was proceeded routinely and strictly. Hospital environmental surfaces and PPE of staffs in isolation wards were sampled using swabs. The sewage from various inlet and outlets were sampled. The respiratory and stool specimens of patients were collected. The respiratory specimens of staffs in the isolation wards were also sampled once a week. Quantitative real-time reverse transcription PCR (qRT-PCR) methods were used to confirm the existence of SARS-Cov-2 RNA. Viral culture was done for the samples positive for SARS-Cov-2 RNA. Results During the study period, 33 laboratory-confirmed patients were hospitalized in isolation wards in the hospital. None of SARS-Cov-2 RNA was detected among the 36 objects surface samples and 9 staffs PPE samples in isolation wards. Though the 3 sewage samples from the inlet of preprocessing disinfection pool were positive for SARS-CoV-2 RNA and the sample from the outlet of preprocessing disinfection pool was weakly positive, the sewage sample from the outlet of the last disinfection pool was negative. All of the 5 sewage samples from various points were negative by viral culture of SARS-Cov-2. None of the respiratory specimens of staffs in the isolation wards were positive. Conclusions Though SARS-Cov-2 RNA of the sewage samples were positive from inlets of the sewage disinfection pool and negative from the outlet of the last sewage disinfection pool, no viable virus was detected by culture. The monitoring data in this study suggested that the strict disinfection and hand hygiene could decrease the hospital-associated COVID-19 infection risk of the staffs in isolation wards.

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: 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: [Technologies and requirements of protection and disinfection in key places during COVID-19 outbreak]. COVID-19 a new respiratory infectious disease, has become an important public health problem. Inappropriate protection and disinfection measures are potential risk factors of transmission and outbreak of COVID-19 in key places. This theme issue is concerned with the prevention and control of COVID-19. Comprehensive measures and suggestions for protection and disinfection are put forward from perspectives of functional areas in key places, such as hotels, mobile cabin hospitals, passenger transport stations and public transport facilities, environment and facilities, personal protection, operation management system, etc., so as to provide technical support for the prevention and control of new respiratory infectious diseases.

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: 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: Preparing for a COVID-19 pandemic: a review of operating room outbreak response measures in a large tertiary hospital in Singapore The coronavirus disease 2019 (COVID-19) outbreak has been designated a public health emergency of international concern. To prepare for a pandemic, hospitals need a strategy to manage their space, staff, and supplies so that optimum care is provided to patients. In addition, infection prevention measures need to be implemented to reduce in-hospital transmission. In the operating room, these preparations involve multiple stakeholders and can present a significant challenge. Here, we describe the outbreak response measures of the anesthetic department staffing the largest (1,700-bed) academic tertiary level acute care hospital in Singapore (Singapore General Hospital) and a smaller regional hospital (Sengkang General Hospital). These include engineering controls such as identification and preparation of an isolation operating room, administrative measures such as modification of workflow and processes, introduction of personal protective equipment for staff, and formulation of clinical guidelines for anesthetic management. Simulation was valuable in evaluating the feasibility of new operating room set-ups or workflow. We also discuss how the hierarchy of controls can be used as a framework to plan the necessary measures during each phase of a pandemic, and review the evidence for the measures taken. These containment measures are necessary to optimize the quality of care provided to COVID-19 patients and to reduce the risk of viral transmission to other patients or healthcare workers.

positive: 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.

positive: 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.

positive: Corrigendum to "Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents" [J Hosp Infect 104 (2020) 246-251]

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: Detection of SARS-CoV-2 on high-touch surfaces in a clinical microbiology laboratory

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: 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: Hygienic hand antiseptics: Should they not have activity and label claims against viruses? Abstract Enteric and respiratory viruses are among the most frequent causes of human infections, and hands play an important role in the spread of these and many other viral diseases. Regular and proper hand hygiene by caregivers and food handlers in particular is essential to decontaminate hands and potentially interrupt such spread. What would be considered a proper decontamination of hands? Handwashing with regular soap and water is often considered sufficient, but what of hygienic handwash and handrub antiseptic products? Are they more effective? The evidence suggests that some clearly are. Activity against bacteria may not reflect the ability of hygienic hand antiseptics to deal with viruses, especially those that are nonenveloped. In spite of the acknowledged importance of hands as vehicles for viruses, there is a lack of suitable regulatory mechanism for handwash or handrub products to make claims of efficacy against viruses. This is in contrast with the ability of general-purpose disinfectants to make antiviral claims, although transmission of viruses from surfaces other than those of reusable medical devices may play only a minor role in virus transmission. This review discusses the (1) recent information on the relative importance of viruses as human pathogens, particularly those causing enteric and respiratory infections; (2) the survival of relevant viruses on human hands in comparison with common gram-negative and gram-positive bacteria; (3) the potential of hands to transfer or receive such contamination on casual contact; (4) role of hands in the spread of viruses; (5) the potential of hygienic measures to eliminate viruses from contaminated hands; (6) relative merits of available protocols to assess the activity of hygienic hand antiseptics against viruses; and (7) factors considered crucial in any tests to assess the activity of hygienic hand antiseptics against viruses. In addition, this review proposes surrogate viruses in such testing and discusses issues for additional consideration by researchers, manufacturers, end-users, and regulators. (Am J Infect Control 2002;30:355-72)

positive: Statistical Explorations and Univariate Timeseries Analysis on COVID-19 Datasets to Understand the Trend of Disease Spreading and Death “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”, the novel coronavirus, is responsible for the ongoing worldwide pandemic. “World Health Organization (WHO)” assigned an “International Classification of Diseases (ICD)” code—“COVID-19”-as the name of the new disease. Coronaviruses are generally transferred by people and many diverse species of animals, including birds and mammals such as cattle, camels, cats, and bats. Infrequently, the coronavirus can be transferred from animals to humans, and then propagate among people, such as with “Middle East Respiratory Syndrome (MERS-CoV)”, “Severe Acute Respiratory Syndrome (SARS-CoV)”, and now with this new virus, namely “SARS-CoV-2”, or human coronavirus. Its rapid spreading has sent billions of people into lockdown as health services struggle to cope up. The COVID-19 outbreak comes along with an exponential growth of new infections, as well as a growing death count. A major goal to limit the further exponential spreading is to slow down the transmission rate, which is denoted by a “spread factor (f)”, and we proposed an algorithm in this study for analyzing the same. This paper addresses the potential of data science to assess the risk factors correlated with COVID-19, after analyzing existing datasets available in “ourworldindata.org (Oxford University database)”, and newly simulated datasets, following the analysis of different univariate “Long Short Term Memory (LSTM)” models for forecasting new cases and resulting deaths. The result shows that vanilla, stacked, and bidirectional LSTM models outperformed multilayer LSTM models. Besides, we discuss the findings related to the statistical analysis on simulated datasets. For correlation analysis, we included features, such as external temperature, rainfall, sunshine, population, infected cases, death, country, population, area, and population density of the past three months—January, February, and March in 2020. For univariate timeseries forecasting using LSTM, we used datasets from 1 January 2020, to 22 April 2020.

positive: Evaluation of Ultraviolet-C Light for Rapid Decontamination of Airport Security Bins in the Era of SARS-CoV-2 BACKGROUND: Contaminated surfaces are a potential source for spread of respiratory viruses including SARS-CoV-2. Ultraviolet-C (UV-C) light is effective against RNA and DNA viruses and could be useful for decontamination of high-touch fomites that are shared by multiple users. METHODS: A modification of the American Society for Testing and Materials standard quantitative carrier disk test method (ASTM E-2197-11) was used to examine the effectiveness of UV-C light for rapid decontamination of plastic airport security bins inoculated at 3 sites with methicillin-resistant Staphylococcus aureus (MRSA) and bacteriophages MS2, PhiX174, and Phi6, an enveloped RNA virus used as a surrogate for coronaviruses. Reductions of 3 log(10) on inoculated plastic bins were considered effective for decontamination. RESULTS: UV-C light administered as 10-, 20-, or 30-second cycles in proximity to a plastic bin reduced contamination on each of the test sites, including vertical and horizontal surfaces. The 30-second cycle met criteria for decontamination of all 3 test sites for all the test organisms except bacteriophage MS2 which was reduced by greater than 2 log(10) PFU at each site. CONCLUSIONS: UV-C light is an attractive technology for rapid decontamination of airport security bins. Further work is needed to evaluate the utility of UV-C light in real-world settings and to develop methods to provide automated movement of bins through a UV-C decontamination process.

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: 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: Role of the Microbial Burden in the Acquisition and Control of Healthcare Associated Infections: The Utility of Solid Copper Surfaces For more than a century, healthcare has been challenged to keep environmental surfaces clean to control microbes and improve patient outcomes. However despite an annual cost exceeding ten billion dollars cleaning with disinfection has done little to reduce the incidence of healthcare-associated infections (HAI). This chapter will review the scientific evidence delineating the role that the environment and healthcare workers play in the acquisition and movement of the microbes implicated in HAI and how through controlling the microbial burden of the built clinical environment it is possible to mitigate the rate of HAI acquisition. Specifically evidence demonstrating the effectiveness of solid copper surfaces for its ability to continuously limit the concentration of bacteria found on surfaces and objects within the built environment will be reviewed in concert with a discussion of how through the mitigation of the environmental burden copper surfaces are able to concomitantly reduce the incidence of HAI. Insights provided by this chapter are intended to facilitate an understanding and importance of the need to use a comprehensive or systems based approach to fight healthcare associated infections.

positive: Preventive and Control Measures for the ï»¿Coronavirus Pandemic in Clinical Dentistry A severe public health crisis has been declared worldwide since coronavirus disease 2019 (COVID-19) was classified as a pandemic of acute respiratory infectious disease by the World Health Organisation (WHO). China has taken strict measures to curb the spread of the disease to save lives, and has managed to control the outbreak. COVID-19 is mainly transmitted through respiratory droplets and close physical contact, so it is challenging to prevent nosocomial infection and possible spread during dental treatment. Since the initial phase of the COVID-19 outbreak, a disease prevention and control strategy based on the new concept of population risk classification and rational use of personal protective equipment has been implemented by the Peking University Hospital of Stomatology. Nosocomial infection prevention and control concepts and measures relating to dental diagnosis and treatment are critically checked in the hospital. Our experiences in handling this situation are shared here and may have wide-ranging implications for infection prevention and control (IPC) for COVID-19 in dental practices worldwide.

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: How should data on airborne transmission of SARS-CoV-2 change occupational health guidelines?

positive: Action and problems related to the COVID-19 outbreak in India

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: Changes in the Clinical Practice of Ophthalmology during the Coronavirus Disease 2019 (COVID-19) Outbreak: an Experience from Daegu, Korea

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: Non-pharmaceutical behavioural measures for droplet-borne biological hazards prevention: Health-EDRM for COVID-19 (SARS-CoV-2) pandemic Introduction: Non-pharmaceutical interventions to facilitate response to the COVID-19 pandemic, a disease caused by novel coronavirus SARS-CoV-2, are urgently needed. Using the WHO health emergency and disaster risk management (health-EDRM) framework, behavioural measures for droplet-borne communicable disease, with their enabling and limiting factors at various implementation levels were evaluated. Sources of data: Keyword search was conducted in PubMed, Google Scholar, Embase, Medline, Science Direct, WHO and CDC online publication database. Using OCEBM as review criteria, 105 English-language articles, with ten bottom-up, non-pharmaceutical prevention measures, published between January 2000 and May 2020 were identified and examined. Areas of Agreement: Evidence-guided behavioural measures against COVID-19 transmission for global at-risk communities are identified. Area of Concern: Strong evidence-based systematic behavioural studies for COVID-19 prevention are lacking. Growing points: Very limited research publications are available for non-pharmaceutical interventions to facilitate pandemic response. Areas timely for research: Research with strong implementation feasibility that targets resource-poor settings with low baseline Health-EDRM capacity is urgently need.

positive: Effectiveness of hand hygiene and provision of information in preventing influenza cases requiring hospitalization Abstract Background The objective of the study was to investigate the effectiveness of non-pharmacological interventions in preventing cases of influenza requiring hospitalization. Methods We performed a multicenter case-control study in 36 hospitals, in 2010 in Spain. Hospitalized influenza cases confirmed by reverse-transcription polymerase chain reaction and three matched controls (two hospital and one community control) per case were selected. The use of non-pharmacological measures seven days before the onset of symptoms (frequency of hand washing, use of alcohol-based hand sanitizers and handwashing after touching contaminated surfaces) was collected. Results We studied 813 cases hospitalized for influenza and 2274 controls. The frequency of hand washing 5-10 times (adjusted odds ratio [aOR]=0.65) and >10 times (aOR=0.59) and handwashing after contact with contaminated surfaces (aOR=0.65) were protective factors and were dose-responsive (p<0.001). Alcohol-based hand sanitizers were associated with marginal benefits (aOR=0.82). Conclusions Frequent handwashing should be recommended to prevent influenza cases requiring hospitalization.

positive: The COVID-19 pandemic: Important considerations for contact lens practitioners A novel coronavirus (CoV), the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), results in the coronavirus disease 2019 (COVID-19). As information concerning the COVID-19 disease continues to evolve, patients look to their eye care practitioners for accurate eye health guidance. There is currently no evidence to suggest an increased risk of contracting COVID-19 through contact lens (CL) wear compared to spectacle lens wear and no scientific evidence that wearing standard prescription spectacles provides protection against COVID-19 or other viral transmissions. During the pandemic there will potentially be significant changes in access to local eyecare. Thus, it is imperative CL wearers are reminded of the steps they should follow to minimise their risk of complications, to reduce their need to leave isolation and seek care. Management of adverse events should be retained within optometric systems if possible, to minimise the impact on the wider healthcare service, which will be stretched. Optimal CL care behaviours should be the same as those under normal circumstances, which include appropriate hand washing (thoroughly with soap and water) and drying (with paper towels) before both CL application and removal. Daily CL cleaning and correct case care for reusable CL should be followed according to appropriate guidelines, and CL exposure to water must be avoided. Where the availability of local clinical care is restricted, practitioners should consider advising patients to reduce or eliminate sleeping in their CL (where patients have the appropriate knowledge about correct daily care and access to suitable lens-care products) or consider the option of moving patients to daily disposable lenses (where patients have appropriate lens supplies available). Patients should also avoid touching their face, including their eyes, nose and mouth, with unwashed hands and avoid CL wear altogether if unwell (particularly with any cold or flu-like symptoms).

positive: epic2: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England Executive Summary National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were commissioned by the Department of Health (DH) and developed during 1998-2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were published in January 2001.1 These guidelines describe the precautions healthcare workers should take in three areas: standard principles for preventing HCAI, which include hospital environmental hygiene, hand hygiene, the use of personal protective equipment, and the safe use and disposal of sharps; preventing infections associated with the use of short-term indwelling urethral catheters; and preventing infections associated with central venous catheters. The evidence for these guidelines was identified by multiple systematic reviews of experimental and non-experimental research and expert opinion as reflected in systematically identified professional, national and international guidelines, which were formally assessed by a validated appraisal process. In 2003, we developed complementary national guidelines for preventing HCAI in primary and community care on behalf of the National Collaborating Centre for Nursing and Supportive Care (National Institute for Healthand Clinical Excellence).2 A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective in preventing HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. Consequently, the DH commissioned a review of new evidence published following the last systematic reviews. We have now updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the original epic guidelines published in 2001 remain robust, relevant and appropriate but that adjustments need to be made to some guideline recommendations following a synopsis of the evidence underpinning the guidelines. These updated national guidelines (epic2) provide comprehensive recommendations for preventing HCAI in hospitals and other acute care settings based on the best currently available evidence. Because this is not always the best possible evidence, we have included a suggested agenda for further research in each section of the guidelines. National evidence-based guidelines are broad principles of best practice which need to be integrated into local practice guidelines. To monitor implementation, we have suggested key audit criteria for each section of recommendations. Clinically effective infection prevention and control practice is an essential feature of protecting patients. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of healthcare in NHS hospitals in England can be minimised.

positive: Prevention of Infection and Disruption of the Pathogen Transfer Chain in Elective Surgery The COVID-19 pandemic has caused us all to stop our normal activities and consider how we can safely return to caring for our patients. There are many common practices (such as an increased use of personal protective equipment) which we are all familiar with that can be easily incorporated into our daily routines. Other actions, such as cleaning more surfaces with solutions such as dilute povidone iodine or changing the air filtration systems used within operating room theaters, may require more extensive efforts on our behalf. In this article, we have attempted to highlight some of the changes that arthroplasty surgeons may need to instigate when we are able to resume elective joint arthroplasty procedures in an effort to disrupt the chain of pathogen transfer.

positive: Extended use of face masks during the COVID-19 pandemic - Thermal conditioning and spray-on surface disinfection The current COVID-19 pandemic has resulted in globally constrained supplies for face masks and personal protective equipment (PPE). Production capacity is limited in many countries and the future course of the pandemic will likely continue with shortages for high quality masks and PPE in the foreseeable future. Hence, expectations are that mask reuse, extended wear and similar approaches will enhance the availability of personal protective measures. Repeated thermal disinfection could be an important option and likely easier implemented in some situations, at least on the small scale, than UV illumination, irradiation or hydrogen peroxide vapor exposure. An overview on thermal responses and ongoing filtration performance of multiple face mask types is provided. Most masks have adequate material properties to survive a few cycles (i.e. 30 min disinfection steps) of thermal exposure in the 75 °C regime. Some are more easily affected, as seen by the fusing of plastic liner or warping, given that preferred conditioning temperatures are near the softening point for some of the plastics and fibers used in these masks. Hence adequate temperature control is equally important. As guidance, disinfectants sprayed via dilute solutions maintain a surface presence over extended time at 25 and 37 °C. Some spray-on alcohol-based solutions containing disinfectants were gently applied to the top surface of masks. Neither moderate thermal aging (less than 24 h at 80 and 95 °C) nor gentle application of surface disinfectant sprays resulted in measurable loss of mask filter performance. Subject to bio-medical concurrence (additional checks for virus kill efficiency) and the use of low risk non-toxic disinfectants, such strategies, either individually or combined, by offering additional anti-viral properties or short term refreshing, may complement reuse options of professional masks or the now ubiquitous custom-made face masks with their often unknown filtration effectiveness.

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: 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: Environmental chemistry is most relevant to study coronavirus pandemics

positive: Performing dermoscopy in the COVID‐19 pandemic

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: Detection of Novel Coronavirus on the Surface of Environmental Materials Contaminated by COVID-19 Patients in the Republic of Korea This study aimed to determine the presence of SARS-CoV-2 on surfaces frequently touched by COVID-19 patients, and assess the scope of contamination and transmissibility in facilities where the outbreaks occurred. In the course of this epidemiological investigation, a total of 80 environmental specimens were collected from 6 hospitals (68 specimens) and 2 “mass facilities” (6 specimens from a rehabilitation center and 6 specimens from an apartment building complex). Specific reverse transcriptase-polymerase chain reaction targeting of RNA-dependent RNA polymerase, and envelope genes, were used to identify the presence of this novel coronavirus. The 68 specimens from 6 hospitals (A, B, C, D, E, and G), where prior disinfection/cleaning had been performed before environmental sampling, tested negative for SARS-CoV-2. However, 2 out of 12 specimens (16.7%) from 2 “mass facilities” (F and H), where prior disinfection/cleaning had not taken place, were positive for SARS-CoV-2 RNA polymerase, and envelope genes. These results suggest that prompt disinfection and cleaning of potentially contaminated surfaces is an effective infection control measure. By inactivating SARS-CoV-2 with disinfection/cleaning the infectivity and transmission of the virus is blocked. This investigation of environmental sampling may help in the understanding of risk assessment of the COVID-19 outbreak in “mass facilities” and provide guidance in using effective disinfectants on contaminated surfaces.

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: 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: Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. The ongoing COVID-19 outbreak has spread rapidly on a global scale. While the transmission of SARS-CoV-2 via human respiratory droplets and direct contact is clear, the potential for aerosol transmission is poorly understood1-3. This study investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the COVID-19 outbreak in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols detected in isolation wards and ventilated patient rooms was very low, but it was elevated in the patients' toilet areas. Levels of airborne SARS-CoV-2 RNA in the majority of public areas was undetectable except in two areas prone to crowding, possibly due to infected carriers in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions showing peaks in submicrometre and/or supermicrometre regions, but these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted via aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.

positive: The daily impact of COVID-19 in gastroenterology A new strain of coronavirus, called SARS-CoV-2, emerged in Wuhan, China, in December 2019, probably originating from a wild-animal contamination. Since then, the situation rapidly evolved from a cluster of patients with pneumonia, to a regional epidemic and now to a pandemic called COrona VIrus Disease 2019 (COVID-19). This evolution is related to the peculiar modes of transmission of the disease and to the globalization and lifestyle of the 21st century that created the perfect scenario for virus spread. Even though research has not evidenced particular susceptibility of inflammatory bowel disease (IBD) patients to SARS-CoV-2 infection, immunosuppressive and immunomodulatory treatments were considered potential risk factors. In this context, initiating treatments with these agents should be cautiously weighted and regular ongoing treatments shall be continued, while the dose of corticosteroids should be reduced whenever possible. Due to the increased risk of contamination, elective endoscopic procedures and surgeries should be postponed and IBD online appointments shall be considered. IBD patients shall also follow the recommendations provided to the general population, such as minimization of contact with infected or suspected patients and to wash hands frequently. In the absence of effective treatments and vaccines, this pandemic can only be controlled through prevention of SARS-CoV-2 transmission with the main objectives of providing patients the best healthcare possible and reduce mortality.

positive: An Environmental and Health Perspective for COVID-19 Outbreak: Meteorology and Air Quality Influence, Sewage Epidemiology Indicator, Hospitals Disinfection, Drug Therapies and Recommendations Abstract This Opinion Paper wishes to provide a summary of recent findings and solutions for a better understanding of the environmental and health problems associated with COVID-19. The list of topics covered is large: meteorology and air quality factors with correlation number of infections, sewage waters as a way to reveal the scale of COVID-19 outbreak, current hospital disinfection procedures and new eco-friendly technologies and list of drug therapies recommend waiting for the desired vaccine to come. During the last two months we did notice an increase in the scientific literature regarding COVID-19 with a partial vision of this problem. The current Opinion Paper is one of the first attempts, to my understanding, to summarize and integrate environmental and human health aspects related to the monitoring, fate and treatment solutions for COVID-19. That being said I believe that this Opinion Paper can serve as multipurpose document, not only for scientists of different disciplines but for social media and citizens in general.

positive: Analysis of the Worldwide Corona Virus (COVID-19) Pandemic Trend;A Modelling Study to Predict Its Spread Objective: The Coronavirus (COVID-19) has advanced into 197 countries and territories leaving behind a total of 372,757 confirmed cases and 16231 deaths. Methods: One the basis of WHO situation reports data of COVID-19 along with daily official reports from the Japan, China and the Korea we modeled the spread of COVID19 by using the Successive Approximation Method. We defined the two state of data to find the mean ratio (η) of the present cases count to the sum of previous and present cases. This ratio further predicts the future state of COVID-19 pandemic. Results: The mean ratio (η) of expected cases were found 0.485, while the mean ratio for deaths was found to be 0.49. We calculated worldwide expected lower bound value for confirmed cases 247007 cases with maximum limit of 1667719 cases and minimum deaths count 8660 with upper limit of 117397 deaths in next 30 days. While in the case of Iran, a large increase in the number of deaths are expected in the upcoming 30 days with lower bound value of 1140 deaths and maximum value of 598478 deaths. Interpretation: Iran whole population is on risk.

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: Stability of human metapneumovirus and human coronavirus NL63 on medical instruments and in the patient environment

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: Self-disinfecting surfaces and infection control Abstract According to World Health Organization, every year in the European Union, 4 million patients acquire a healthcare associated infection. Even though some microorganisms represent no threat to healthy people, hospitals harbor different levels of immunocompetent individuals, namely patients receiving immunosuppressors, with previous infections, or those with extremes of age (young children and elderly), requiring the implementation of effective control measures. Public spaces have also been found an important source of infectious disease outbreaks due to poor or none infection control measures applied. In both places, surfaces play a major role on microorganisms’ propagation, yet they are very often neglected, with very few guidelines about efficient cleaning measures and microbiological assessment available. To overcome surface contamination problems, new strategies are being designed to limit the microorganisms’ ability to survive over surfaces and materials. Surface modification and/or functionalization to prevent contamination is a hot-topic of research and several different approaches have been developed lately. Surfaces with anti-adhesive properties, with incorporated antimicrobial substances or modified with biological active metals are some of the strategies recently proposed. This review intends to summarize the problems associated with contaminated surfaces and their importance on infection spreading, and to present some of the strategies developed to prevent this public health problem, namely some already being commercialized.

positive: Ammonia as an In Situ Sanitizer: Influence of Virus Genome Type on Inactivation. UNLABELLED Treatment of human excreta and animal manure (HEAM) is key in controlling the spread of persistent enteric pathogens, such as viruses. The extent of virus inactivation during HEAM storage and treatment appears to vary with virus genome type, although the reasons for this variability are not clear. Here, we investigated the inactivation of viruses of different genome types under conditions representative of HEAM storage or mesophilic digestion. The goals were to characterize the influence of HEAM solution conditions on inactivation and to determine the potential mechanisms involved. Specifically, eight viruses representing the four viral genome types (single-stranded RNA [ssRNA], double-stranded RNA [dsRNA], single-stranded DNA [ssDNA], and double-stranded DNA [dsDNA]) were exposed to synthetic solutions with well-controlled temperature (20 to 35°C), pH (8 to 9), and ammonia (NH3) concentrations (0 to 40 mmol liter(-1)). DNA and dsRNA viruses were considerably more resistant than ssRNA viruses, resulting in up to 1,000-fold-longer treatment times to reach a 4-log inactivation. The apparently slower inactivation of DNA viruses was rationalized by the higher stability of DNA than that of ssRNA in HEAM. Pushing the system toward harsher pH (>9) and temperature (>35°C) conditions, such as those encountered in thermophilic digestion and alkaline treatments, led to more consistent inactivation kinetics among ssRNA and other viruses. This suggests that the dependence of inactivation on genome type disappeared in favor of protein-mediated inactivation mechanisms common to all viruses. Finally, we recommend the use of MS2 as a conservative indicator to assess the inactivation of ssRNA viruses and the stable ΦX174 or dsDNA phages as indicators for persistent viruses. IMPORTANCE Viruses are among the most environmentally persistent pathogens. They can be present in high concentrations in human excreta and animal manure (HEAM). Therefore, appropriate treatment of HEAM is important prior to its reuse or discharge into the environment. Here, we investigated the factors that determine the persistence of viruses in HEAM, and we determined the main mechanisms that lead to their inactivation. Unlike other organisms, viruses can have four different genome types (double- or single-stranded RNA or DNA), and the viruses studied herein represent all four types. Genome type appeared to be the major determinant for persistence. Single-stranded RNA viruses are the most labile, because this genome type is susceptible to degradation in HEAM. In contrast, the other genome types are more stable; therefore, inactivation is slower and mainly driven by the degradation of viral proteins. Overall, this study allows us to better understand the behavior of viruses in HEAM.

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

positive: Obstetricians on the Coronavirus Disease 2019 (COVID-19) Front Lines and the Confusing World of Personal Protective Equipment As health care systems struggle to maintain adequate supplies of personal protective equipment, there is confusion and anxiety among obstetricians and others about how to best protect themselves, their coworkers, and their patients. Although use of personal protective equipment is a critical strategy to protect health care personnel from coronavirus disease 2019 (COVID-19), other strategies also need to be implemented on labor and delivery units to reduce the risk of health care–associated transmission, including screening of all pregnant women who present for care (case identification), placing a mask on and rapidly isolating ill pregnant women, and minimizing the number of personnel who enter the room of an ill patient (physical distancing). Although the mechanism of transmission of COVID-19 is not known with certainty, current evidence suggests that COVID-19 is transmitted primarily through respiratory droplets. Therefore, strict adherence to hand hygiene and consistent use of recommended personal protective equipment are cornerstones for reducing transmission. In addition, it is critical that health care professionals receive training on and practice correct donning (putting on) and doffing (removing) of personal protective equipment and avoid touching their faces as well as their facial protection to minimize self-contamination.

positive: Presence of SARS-CoV-2 RNA in isolation ward environment 28 days after exposure Recent studies have reported that surfaces and objects in the rooms of infected patients that are frequently touched by both medical staff and patients could be contaminated with SARS-CoV-2. In December 2019, Wuhan China suffered the earliest from this COVID-19 pandemic, and we took that opportunity to investigate whether the SARS-CoV-2 RNA exists in the ward environment after a long time from exposure. We found that on the 28th day following the discharge of COVID-19 patients, SARS-CoV-2 RNA could still be detected on the surfaces of pagers and in drawers in the isolation wards. Thorough disinfection of the ward environment was subsequently performed, after which these surfaces in the isolation wards tested negative for the presence of SARS-CoV-2 RNA. The findings remind us that the contaminated environment in the wards may become potential infectious resources and that despite a long time from exposure, the thorough disinfection in the COVID-10 units after is still necessary.

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: 15 Cleaning and decontamination of the healthcare environment Abstract: Evidence is accumulating for the role of cleaning in controlling hospital infections. Hospital pathogens such as meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), norovirus, multi-resistant Gram-negative bacilli and Clostridium difficile persist in the healthcare environment for considerable lengths of time. Cleaning with both detergent and disinfectant-based regimens help control these pathogens in both routine and outbreak situations. The most important transmission risk comes from organisms on frequently handled items because hand contact with a contaminated site could deliver a pathogen to a patient. Cleaning practices should be tailored to clinical risk, near-patient areas and hand-touch-sites and scientifically evaluated for all surfaces and equipment in today’s hospitals.

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

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: 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: 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: Sentinel Coronavirus Environmental Monitoring Can Contribute to Detecting Asymptomatic SARS-CoV-2 Virus Spreaders and Can Verify Effectiveness of Workplace COVID-19 Controls Detecting all workplace asymptomatic COVID-19 virus spreaders would require daily testing of employees, which is not practical. Over a two week period, nine workplace locations were chosen to test employees for SARS-CoV-2 infection (841 tests) and high-frequency-touch point environmental surfaces (5,500 tests) for Coronavirus using Eurofins COVID-19 SentinelTM RT-PCR methods. Of the 9 locations, 3 had one or employees infected with SARS-CoV-2, neither of whom had symptoms at the time of testing nor developed symptoms. Locations with Coronavirus contaminated surfaces were 10 times more likely to have clinically positive employees than locations with no or very few positive surfaces. Break room chairs, workbenches, and door handles were the most frequently contaminated surfaces. Coronavirus RNA was detected at very low concentrations (RT-PCR 34 to 38 Cq). Environmental monitoring can be used to validate intervention strategies and be useful to verify the effectiveness of such strategies on a regular basis.

positive: Certainties and Uncertainties Facing Emerging Respiratory Infectious Diseases: Lessons from SARS Every emerging infectious disease is a challenge to the whole of mankind. There are uncertainties regarding whether there will be a pandemic, if it will be caused by the highly pathogenic H5N1 influenza virus, when or where it will occur, how imminent or how severe it will be. No one can accurately predict if and when a given virus will become a pandemic virus. Pandemic prevention strategies must be based on preparing for the unexpected and being capable of reacting accordingly. There is growing evidence that infection control measures were helpful in containment of severe acute respiratory syndrome (SARS) as well as avian influenza. Compliance of standard infection control measures, intensive promotion of hand and respiratory hygiene, vigilance and triage of patients with febrile illness, and specific infection control measures are key components to contain a highly contagious disease in hospital and to protect healthcare workers, patients and visitors. The importance of standard precautions for any patient and cleaning and disinfection for the healthcare environment cannot be overemphasized. SARS illustrated dramatically the potential of air travel and globalization for the dissemination of an emerging infectious disease. To prevent the potential serious consequences of pandemic influenza, timely implementation of pharmaceutical and non-pharmaceutical interventions locally within the outbreak area is the key to minimizing global spread. Herein, we relate our perspective on useful lessons derived from a review of the SARS epidemic that may be useful to physicians, especially when looking ahead to the next epidemic.

positive: How ophthalmologists should understand and respond to the current epidemic of novel coronavirus pneumonia/ 眼科医生和研究人员如何理解和应对新型冠状病毒肺炎的流行 The new coronavirus pneumonia (COVID-19)that caused by 2019 new coronavirus (2019-nCoV) and first appeared in Wuhan, China, in December 2019 has attracted great attention from both the Chinese government and the international community.The International Committee on Viral Classification named the virus "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2), and the WHO named the pneumonia it causesCOVID-19". At present, the disease is centered in Wuhan City and is spreading rapidly to all parts of China, as well as twenty other countries.About 20% of the people infected during the SARS epidemic in 2003 were employees in hospital environments.COVID-19 has infected an even greater number of heath care workers.Therefore, ophthalmologists need to understand the disease and recognize the importance of taking preventive measures.Although ophthalmologists do not work on the front lines of the outbreak, due to their area of expertise, a variety of situations, such as infection consultations or ophthalmic emergency treatments, can lead to the exposure of ophthalmologists to high-risk environments.This risk will only increase as the number of infected patients continues to increase.When dealing with seemingly normal ophthalmic patients, the vigilance of ophthalmologists and associated staff tends to be significantly reduced.To better protect patients, families, and health care workers, it is strongly recommended that in addition to the standard precautions for the care of all patients, strict contact precautions and droplet precautions need to be taken by ophthalmologists.These measures include (1) wearing an efficient mask (an N95 mask); (2) always performing hand hygiene before and after examining a patient; (3) wearing sterile gloves when entering a patient’s room and touching a patient; (4) wearing a gown when contact is expected with items and environmental surfaces surrounding a patient or when the patient is incontinent or has diarrhea or a surgical or other invasive wound with oozing fluid; (5) cleaning and disinfecting ophthalmic equipment and correctly handling medical waste after examination to prevent transmission to patients who are subsequently examined; (6) wearing goggles and a disposable mask to cover the front and sides of the face before touching a patient, as the virus could spread through the ocular surface; (7) performing the relevant screening for COVID-19 for regular patients who have conjunctivitis and respiratory symptoms at the same time; (8) prohibiting the use of infected patients as potential donors for corneal transplants and temporarily adding donor 2019-CoV screening to the medical standard of the eye bank during the outbreak; (9) for the purposes of scientific research, diagnosis, and other special needs, packing, shipping, and transporting collected specimens according to the relevant dangerous biological goods regulations.

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: 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: 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: Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID‐19 Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS‐CoV‐2 virus, cause of COVID‐19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS‐CoV‐2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS‐CoV‐2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate‐zone cities, with continued risk for re‐aerosolization and human infection. Conversely, the presented data indicate that SARS‐CoV‐2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate, and duration of coronavirus pandemics.

positive: Back to the Basics: Diluted Bleach for COVID-19

positive: Dermatology practices as vectors for COVID-19 transmission: A call for immediate cessation of nonemergent dermatology visits

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: COVID‐19: Infection prevention and control guidance for all ultrasound practitioners The severe acute respiratory syndrome coronavirus (SARS‐CoV‐2), an enveloped virus, is the causative agent of the disease known as COVID‐19 (coronavirus disease‐2019). Proper infection prevention and control measures and good hygiene practices are essential to prevent spread of COVID‐19 and protect both patients and the healthcare worker. These guidelines are relevant to all ultrasound practitioners and provides guidance on cleaning and disinfection of ultrasound equipment, the environment and PPE (protective personal equipment) during the COVID‐19 outbreak in the Australasian region.

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: Environmental contamination by SARS-CoV-2 of an imported case during incubation period Abstract We collected environmental surface samples prior to and after disinfection of a quarantine room to evaluate the stability of SARS-CoV-2 during the incubation period of an imported case traveling to Qingdao, China. Overall, 11 of 23 (47.8%) of the first batch of environmental surface samples (within 4 h after case confirmation) were tested positive for SARS-CoV-2. Whereas only 2 of 23 (8.7%) of the second batch of environmental samples (after first disinfection) were tested positive for SARS-CoV-2. The majority of samples from the bedroom (70%) were positive for SARS-CoV-2, followed by 50% of samples from the bathroom and that of 33% from the corridor. The inner walls of toilet bowl and sewer inlet were the most contaminated sites with the highest viral loads. SARS-CoV-2 was widely distributed on object surfaces in a quarantine room of a later diagnosed COVID-19 case during the incubation period. Proper disinfection is crucial to minimize community transmission of this highly contagious virus.

positive: Microbial transmission in an outpatient clinic and impact of an intervention with an ethanol-based disinfectant BACKGROUND: Halting the spread of harmful microbes requires an understanding of their transmission via hands and fomites. Previous studies explored acute and long-term care environments but not outpatient clinics. Objectives of this study were to track microbial movement throughout an outpatient clinic and evaluate the impact of a disinfectant spray intervention targeting high-touch point surfaces. METHODS: At the start of the clinic day, a harmless viral tracer was placed onto 2 fomites: a patient room door handle and front desk pen. Patient care, cleaning, and hand hygiene practices continued as usual. Facility fomites (n = 19), staff hands (n = 4), and patient hands (n = 3-4) were sampled after 2, 3.5, and 6 hours. Tracer concentrations at baseline (before intervention) were evaluated 6 hours after seeding. For the intervention trials, high-touch surfaces were cleaned 4 hours after seeding with an ethanol-based disinfectant and sampled 2 hours after cleaning. RESULTS: At 2, 3.5, and 6 hours after seeding, virus was detected on all surfaces and hands sampled, with examination room door handles and nurses’ station chair arms yielding the highest concentrations. Virus concentrations decreased by 94.1% after the disinfectant spray intervention (P = .001). CONCLUSIONS: Microbes spread quickly in an outpatient clinic, reaching maximum contamination levels 2 hours after inoculation, with the highest contamination on examination room door handles and nurses’ station chairs. This study emphasizes the importance of targeted disinfection of high-touch surfaces.

positive: The Potential Impact of Intensified Community Hand Hygiene Interventions on Respiratory tract Infections: A Modelling Study Increased hand hygiene amongst the general public has been widely promoted as one of the most important non-pharmaceutical interventions for reducing transmission during the ongoing COVID-19 pandemic and is likely to continue to play a key role in long-term efforts to suppress transmission before a vaccine can be deployed. For other respiratory tract infections community hand hygiene interventions are supported by evidence from randomised trials, but information on how effectiveness in reducing transmission scales with achieved changes in hand hygiene behaviour is lacking. This information is of critical importance when considering the potential value of substantially enhancing community hand hygiene frequency to help suppress COVID-19. Here, we developed a simple model-based framework for understanding the key determinants of the effectiveness of changes in hand hygiene behaviour in reducing transmission and use it to explore the potential impact of interventions aimed at achieving large-scale population-wide changes in hand hygiene behaviour. Our analyses show that the effect of hand hygiene is highly dependent on the duration of viral persistence on hands and that hand washing needs to be performed very frequently or immediately after hand contamination events in order to substantially reduce the probability of infection. Hand washing at a lower frequency, such as every 30 minutes or with a delay of 15 minutes after contamination events, may be adequate to reduce the probability of infection when viral survival on hands is longer, such as when hands are contaminated with mucus. Immediate hand washing after contamination is more effective than hand washing at fixed-time intervals even when the total number of hand washing events is similar. This event-prompted hand washing strategy is consistently more effective than fixed-time strategy regardless of hand contamination rates and should be highlighted in hand hygiene campaigns.

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: 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: Air contamination with SARS-CoV-2 in the operating room Angiotensin converting enzyme 2 (ACE2) is a target cell receptor for internalization and proliferation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). When ACE2-highly expressed tissues are manipulated, SARS-CoV-2 containing aerosols may be generated. Normal breathing and speaking are capable of producing aerosols so mask ventilation, suction of airway tract and bucking during tracheal intubation and extubation are clinical procedures capable of significant aerosol production. Whilst no data have been reported on the distribution of SARS-CoV-2 in the operating room (OR), contamination in the OR can be estimated from the intensive care unit (ICU) data. ICU data showed that SARS-CoV-2 was detected on all types of surface and in air within about 4 m from coronavirus disease 2019 (COVID-19) patients. High concentrations of SARS-CoV-2 was detected in the personal protective equipment (PPE) removal room and medical staff office. Submicron virus-laden aerosols could result from resuspension of particles containing SARS-CoV-2 sticking the PPE surface; removal could produce the initial velocity. Supermicron virus-laden aerosol could come from floor deposited SARS-CoV-2, which were carried across different areas by medical staff (e.g., shoe). Knowledge of aerosol generation and distribution in the OR will aid the design of strategies to reduce transmission risk.

positive: COVID-19: Transmission, prevention, and potential therapeutic opportunities The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Despite intense research efforts worldwide, an effective vaccine and viable treatment options have eluded investigators. Therefore, infection prevention, early viral detection and identification of successful treatment protocols provide the best approach in controlling disease spread. In this review, current therapeutic options, preventive methods and transmission routes of COVID-19 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: Coronavirus (COVID-19) outbreak: what the department of endoscopy should know Italy recorded its first case of confirmed acute respiratory illness because of coronavirus on February 18, 2020, soon after the initial reports in China. Since that time, Italy and nations throughout the world have adopted very stringent and severe measures to protect populations from spread of infection. Despite these measures, the number of infected people is growing exponentially, with a significant number of patients developing acute respiratory insufficiency. Endoscopy departments face significant risk for diffusion of respiratory diseases that can be spread via an airborne route, including aspiration of oral and fecal material via endoscopes. The purpose of this article is to discuss the measures, with specific focus on personal protection equipment and dress code modalities, implemented in our hospital to prevent further dissemination of COVID-19 infection.

positive: Preventive Behaviors Conveyed on YouTube to Mitigate Transmission of COVID-19: Cross-Sectional Study BACKGROUND: Accurate information and guidance about personal behaviors that can reduce exposure to severe acute respiratory syndrome coronavirus 2 are among the most important elements in mitigating the spread of coronavirus disease 2019 (COVID-19). With over 2 billion users, YouTube is a media channel that millions turn to when seeking information. OBJECTIVE: At the time of this study, there were no published studies investigating the content of YouTube videos related to COVID-19. This study aims to address this gap in the current knowledge. METHODS: The 100 most widely viewed YouTube videos uploaded throughout the month of January 2020 were reviewed and the content covered was described. Collectively, these videos were viewed over 125 million times. RESULTS: Fewer than one-third of the videos covered any of the seven key prevention behaviors listed on the US Centers for Disease Control and Prevention website. CONCLUSIONS: These results represent an important missed opportunity for disease prevention.

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: 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: COVID-19 Diagnostics, Tools, and Prevention The Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), outbreak from Wuhan City, Hubei province, China in 2019 has become an ongoing global health emergency. The emerging virus, SARS-CoV-2, causes coughing, fever, muscle ache, and shortness of breath or dyspnea in symptomatic patients. The pathogenic particles that are generated by coughing and sneezing remain suspended in the air or attach to a surface to facilitate transmission in an aerosol form. This review focuses on the recent trends in pandemic biology, diagnostics methods, prevention tools, and policies for COVID-19 management. To meet the growing demand for medical supplies during the COVID-19 era, a variety of personal protective equipment (PPE) and ventilators have been developed using do-it-yourself (DIY) manufacturing. COVID-19 diagnosis and the prediction of virus transmission are analyzed by machine learning algorithms, simulations, and digital monitoring. Until the discovery of a clinically approved vaccine for COVID-19, pandemics remain a public concern. Therefore, technological developments, biomedical research, and policy development are needed to decipher the coronavirus mechanism and epidemiological characteristics, prevent transmission, and develop therapeutic drugs.

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: Sports balls as potential SARS-CoV-2 transmission vectors Abstract Objects passed from one player to another have not been assessed for their ability to transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the surface of sport balls, notably a football, tennis ball, golf ball, and cricket ball could not harbour inactivated virus when it was swabbed onto the surface, even for 30 seconds. However, when high concentrations of 5,000 dC/mL and 10,000 dC/mL are directly pipetted onto the balls, it could be detected after for short time periods. Sports objects can only harbour inactivated SARS-CoV-2 under specific, directly transferred conditions, but wiping with a dry tissue or moist ‘baby wipe’ or dropping and rolling the balls removes all detectable viral traces. This has helpful implications to sporting events.

positive: COVID-19: Health prevention and control in non-healthcare settings

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: 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: Reply to “Does hand hygiene reduce SARS-CoV-2 transmission?”

positive: What Does COVID-19 Mean for the Pathology-Urology Interaction?

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: Coronavirus disease 2019 and the cardiovascular system: Impacts and implications

positive: Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2 The coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne® was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.

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: Can N95 respirators be reused after disinfection? And for how many times? The Coronavirus Disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which protect healthcare professionals and the public who may come into contact with the virus. It is necessary to determine the conditions that would allow the safe reuse respirators and personal protection in this crisis. We found that heating (<100 {degrees}C) under various humidities (up to 100% RH at 75 {degrees}C) and ultraviolet (UV) irradiation were the most promising candidates for mask reuse in the modern hospital infrastructure (up to 20 cycles), when tested on a fabric with particle filtration efficiency [≥]95%. Treatments involving certain liquids and vapors may require caution, as steam, alcohol, and bleach all led to degradation in filtration efficiency, leaving the user vulnerable to viral aerosols.

positive: Fecal-Oral Transmission of SARS-CoV-2 In Children: is it Time to Change Our Approach? Starting from 2 pediatric cases of COVID-19, with confirmation at nasopharyngeal and rectal swabs, we considered the lesson learnt from previous Coronavirus epidemics and reviewed evidence on the current outbreak. Surveillance with rectal swabs might be extended to infants and children, for the implications for household contacts and isolation timing.

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: Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: A Position Paper Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of healthcare facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It also demonstrates that the targeted hygiene approach offers a framework for maximizing protection against colonization and infections, thereby reducing antibiotic prescribing and minimizing selection pressure for the development of antibiotic resistance. If combined with the provision of clean water and sanitation, targeted hygiene can reduce the circulation of resistant bacteria in homes and communities, regardless of a country's Human Development Index (overall social and economic development). Achieving a reduction of AMR strains in healthcare settings requires a mirrored reduction in the community. The authors call upon national and international policy makers, health agencies and healthcare professionals to further recognize the importance of targeted hygiene in the home and everyday life settings for preventing and controlling infection, in a unified quest to tackle AMR.

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: 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 and Laparoscopic Surgery: Scoping Review of Current Literature and Local Expertise BACKGROUND: The current coronavirus disease (COVID-19) pandemic is holding the world in its grip. Epidemiologists have shown that the mortality risks are higher when the health care system is subjected to pressure from COVID-19. It is therefore of great importance to maintain the health of health care providers and prevent contamination. An important group who will be required to treat patients with COVID-19 are health care providers during semiacute surgery. There are concerns that laparoscopic surgery increases the risk of contamination more than open surgery; therefore, balancing the safety of health care providers with the benefit of laparoscopic surgery for the patient is vital. OBJECTIVE: We aimed to provide an overview of potential contamination routes and possible risks for health care providers; we also aimed to propose research questions based on current literature and expert opinions about performing laparoscopic surgery on patients with COVID-19. METHODS: We performed a scoping review, adding five additional questions concerning possible contaminating routes. A systematic search was performed on the PubMed, CINAHL, and Embase databases, adding results from gray literature as well. The search not only included COVID-19 but was extended to virus contamination in general. We excluded society and professional association statements about COVID-19 if they did not add new insights to the available literature. RESULTS: The initial search provided 2007 records, after which 267 full-text papers were considered. Finally, we used 84 papers, of which 14 discussed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Eight papers discussed the added value of performing intubation in a low-pressure operating room, mainly based on the SARS outbreak experience in 2003. Thirteen papers elaborated on the risks of intubation for health care providers and SARS-CoV-2, and 19 papers discussed this situation with other viruses. They conclude that there is significant evidence that intubation and extubation is a high-risk aerosol-producing procedure. No papers were found on the risk of SARS-CoV-2 and surgical smoke, although 25 papers did provide conflicting evidence on the infection risk of human papillomavirus, hepatitis B, polio, and rabies. No papers were found discussing tissue extraction or the deflation risk of the pneumoperitoneum after laparoscopic surgery. CONCLUSIONS: There seems to be consensus in the literature that intubation and extubation are high-risk procedures for health care providers and that maximum protective equipment is needed. On the other hand, minimal evidence is available of the actual risk of contamination of health care providers during laparoscopy itself, nor of operating room pressure, surgical smoke, tissue extraction, or CO(2) deflation. However, new studies are being published daily from current experiences, and society statements are continuously updated. There seems to be no reason to abandon laparoscopic surgery in favor of open surgery. However, the risks should not be underestimated, surgery should be performed on patients with COVID-19 only when necessary, and health care providers should use logic and common sense to protect themselves and others by performing surgery in a safe and protected environment.

positive: Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London BACKGROUND: Evaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London. METHODS: We performed this prospective cross-sectional observational study in a multi-site London hospital. Air and surface samples were collected from seven clinical areas, occupied by patients with COVID-19, and a public area of the hospital. Three or four 1.0 m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS: Viral RNA was detected on 114/218 (52.3%) of surfaces 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 than in other areas (67/105 (63.8%) vs. 29/64 (45.3%) (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Chi squared test)). The high PCR Ct value for all samples (>30) indicated that the virus 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 environmental contamination in managing COVID-19, and the need for effective use of PPE, physical distancing, and hand/surface hygiene.

positive: Survival of rhinoviruses on human fingers Abstract Rhinovirus is the main cause of the common cold, which remains the most frequent infection worldwide among humans. Knowledge and understanding of the rhinovirus transmission route is important to reduce morbidity as only preventive measures are effective. In this study, we investigated the potential of rhinovirus to survive on fingers. Rhinovirus-B14 was deposited on fingers for 30, 60, 90 and 120 min. Survival was defined as the ability of the virus to grow after 7 days, confirmed by immunofluorescence. Rhinovirus survival was not dependent on incubation time on fingers. Droplet disruption had no influence on survival. Survival was frequent with high rhinovirus concentrations, but rare with low-concentration droplets, which corresponded to the usual rhinovirus concentrations in mucus observed in children and adults, respectively. Our study confirms that rhinovirus infectiousness is related to the viral concentration in droplets and suggests that children represent the main transmission source, which occurs only rarely via adults. It confirms also that rhinovirus hand-related transmission is possible and supports hand hygiene as a key prevention measure.

positive: Detection of Severe Acute Respiratory Syndrome Coronavirus 2 RNA on Surfaces in Quarantine Rooms. We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in 2 rooms of a quarantine hotel after 2 presymptomatic persons who stayed there were laboratory-confirmed as having coronavirus disease. We detected SARS-CoV-2 RNA on 8 (36%) of 22 surfaces, as well as on the pillow cover, sheet, and duvet cover.

positive: The contribution of asymptomatic SARS-CoV-2 infections to transmission - a model-based analysis of the Diamond Princess outbreak Background: Some key gaps in the understanding of SARS-CoV-2 infection remain. One of them is the contribution to transmission from individuals experiencing asymptomatic infections. We aimed to characterise the proportion and infectiousness of asymptomatic infections using data from the outbreak on the Diamond Princess cruise ship. Methods: We used a transmission model of COVID-19 with asymptomatic and presymptomatic states calibrated to outbreak data from the Diamond Princess, to quantify the contribution of asymptomatic infections to transmission. Data available included the date of symptom onset for symptomatic disease for passengers and crew, the number of symptom agnostic tests done each day, and date of positive test for asymptomatic and presymptomatic individuals. Findings: On the Diamond Princess 74% (70-78%) of infections proceeded asymptomatically, i.e. a 1:3.8 case-to-infection ratio. Despite the intense testing 53%, (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. While the data did not allow identification of the infectiousness of asymptomatic infections, assuming no or low infectiousness resulted in posterior estimates for the net reproduction number of an individual progressing through presymptomatic and symptomatic stages in excess of 15. Interpretation: Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. This is essential to consider for countries when assessing the potential effectiveness of ongoing control measures to contain COVID-19.

positive: Understanding the Mosaic of COVID-19: A Review of the Ongoing Crisis In late 2019, a queer type of pneumonia emerged in Wuhan city in the central part of China. On investigation, it was found to be caused by the coronavirus. Human coronaviruses were discovered in the 1960s. There are a total of seven types of coronaviruses that infect humans: 229E and NL63 are the alpha coronaviruses; OC43, HKU1, MERS-CoV, and SARS-CoV are beta coronaviruses, and SARS-CoV-2 or COVID-19 is a novel coronavirus. COVID-19 surfaced in China at the culmination of the year 2019. The pandemic then fanned out rapidly, involving Italy, Japan, South Korea, Iran, and the rest of the world.

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: Perioperative Considerations in Urgent Surgical Care of Suspected and Confirmed Coronavirus Disease 2019 Orthopaedic Patients: Operating Room Protocols and Recommendations in the Current Coronavirus Disease 2019 Pandemic By April 7, 2020, severe acute respiratory syndrome coronavirus 2 was responsible for 1,383,436 confirmed cases of Coronavirus disease 2019 (COVID-19), involving 209 countries around the world; 378,881 cases have been confirmed in the United States. During this pandemic, the urgent surgical requirements will not stop. As an example, the most recent Centers of Disease Control and Prevention reports estimate that there are 2.8 million trauma patients hospitalized in the United States. These data illustrate an increase in the likelihood of encountering urgent surgical patients with either clinically suspected or confirmed COVID-19 in the near future. Preparation for a pandemic involves considering the different levels in the hierarchy of controls and the different phases of the pandemic. Apart from the fact that this pandemic certainly involves many important health, economic, and community ramifications, it also requires several initiatives to mandate what measures are most appropriate to prepare for mitigating the occupational risks. This article provides evidence-based recommendations and measures for the appropriate personal protective equipment for different clinical and surgical activities in various settings. To reduce the occupational risk in treating suspected or confirmed COVID-19 urgent orthopaedic patients, recommended precautions and preventive actions (triage area, ED consultation room, induction room, operating room, and recovery room) are reviewed.

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: Experimental and numerical study of potential infection risks from exposure to bioaerosols in one BSL-3 laboratory Laboratory-acquired infections (LAIs) are defined as infections of laboratory staff by exposure to pathogenic microorganisms during an experimental procedure. For a biosafety level-3 (BSL-3) laboratory with a high potential of exposure, reducing risks and threats relevant to LAIs has become a critical concern, especially after the recent outbreak of Novel Coronavirus causing COVID-19 in Wuhan, China. This study aimed to investigate the spatial-temporal characteristics of bioaerosol dispersion and deposition of two kinds of bioaerosols (Serratia marcescens and phage ΦX174). A combination of laboratory experiment and numerical simulation was adopted to explore bioaerosol removal. Three-dimensional concentration iso-surface mapping in conjunction with flow field analysis was employed to elucidate bioaerosol migration and deposition behavior. The total deposition number and unit area deposition ratio were calculated for different surfaces. The results indicate that bioaerosol concentration remains stable for up to 400 s after release, and that almost 70% of all bioaerosol particles become deposited on the surfaces of walls and equipment. Vortex flow regions and high-concentration regions were determined, and the most severely contaminated surfaces and locations were identified. Our results could provide the scientific basis for controlling the time interval between different experiments and also provide guidelines for a laboratory disinfection routine. Furthermore, future work regarding laboratory layout optimization and high efficiency air distribution for bioaerosol removal in a BSL-3 laboratory should be emphasized.

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

positive: Understanding the indoor pre-symptomatic transmission mechanism of COVID-19 Discovering the mechanism that enables pre-symptomatic individuals to transmit the SARS-CoV-2 virus has a significant impact on the possibility of controlling COVID-19 pandemic. To this end, we have developed an evidence based quantitative mechanistic mathematical model. The model explicitly tracks the dynamics of contact and airborne transmission between individuals indoors, and was validated against the observed fundamental attributes of the epidemic, the secondary attack rate (SAR) and serial interval distribution. Using the model we identified the dominant driver of pre-symptomatic transmission, which was found to be contact route, while the contribution of the airborne route is negligible. We provide evidence that a combination of rather easy to implement measures of frequent hand washing, cleaning fomites and avoiding physical contact decreases the risk of infection by an order of magnitude, similarly to wearing masks and gloves.

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

positive: Studies on the survival of canine coronavirus under different environmental conditions Abstract Canine coronavirus (CCV) is a common faecal agent which is difficult to isolate. This study shows CCV to survive well at temperatures below −20°C but not at temperatures above 4°C. The presence of faecal material markedly reduced CCV survival times at temperatures ranging from 20°C to −70°C. Thus, it is suggested that diagnostic faecal material should be diluted 1:10 (w/v) with growth medium and examined at the earliest opportunity.

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 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.

positive: An overview of COVID-19 Pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China in December 2019. By Feb. 11, 2020, the World Health Organization (WHO) officially named the disease resulting from infection with SARS-CoV-2 as coronavirus disease 2019 (COVID-19). COVID-19 represents a spectrum of clinical manifestations that typically include fever, dry cough, and fatigue, often with pulmonary involvement. SARS-CoV-2 is highly contagious and most individuals within the population at large are susceptible to infection. Wild animal hosts and infected patients are currently the main sources of disease which is transmitted via respiratory droplets and direct contact. Since the outbreak, the Chinese government and scientific community have acted rapidly to identify the causative agent and promptly shared the viral gene sequence, and have carried out measures to contain the epidemic. Meanwhile, recent research has revealed critical aspects of SARS-CoV-2 biology and disease pathogenesis; other studies have focused on epidemiology, clinical features, diagnosis, management, as well as drug and vaccine development. This review aims to summarize the latest research findings and to provide expert consensus. We will also share ongoing efforts and experience in China, which may provide insight on how to contain the epidemic and improve our understanding of this emerging infectious disease, together with updated guidance for prevention, control, and critical management of this pandemic.

positive: Meteorological factors and domestic new cases of coronavirus disease (COVID-19) in nine Asian cities: A time-series analysis AIM To investigate the associations of meteorological factors and the daily new cases of coronavirus disease (COVID-19) in nine Asian cities. METHOD Pearson correlation and generalized additive modeling were performed to assess the relationships between daily new COVID-19 cases and meteorological factors (daily average temperature and relative humidity) with the most updated data currently available. RESULTS The Pearson correlation showed that daily new confirmed cases of COVID-19 were more correlated with the average temperature than with relative humidity. Daily new confirmed cases were negatively correlated with the average temperature in Beijing (r=-0.565, P<0.01), Shanghai (r=-0.471, P<0.01), and Guangzhou (r=-0.530, P<0.01) , yet in contrast, positively correlated with that in Japan (r=0.441, P<0.01). In most of the cities (Shanghai, Guangzhou, Hong Kong, Seoul, Tokyo, and Kuala Lumpur), generalized additive modeling analysis showed the number of daily new confirmed cases was positively associated with both average temperature and relative humidity, especially in lagged 3d model, where a positive influence of temperature on the daily new confirmed cases was discerned in 5 cities except in Beijing, Wuhan, Korea, and Malaysia. Nevertheless, the results were inconsistent across cities and lagged time, suggesting meteorological factors were unlikely to greatly influence the COVID-19 epidemic. CONCLUSION The associations between meteorological factors and the number of COVID-19 daily cases are inconsistent across cities and lagged time. Large-scale public health measures and expanded regional research are still required until a vaccine becomes available and herd immunity is established.

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: How Ophthalmologists Should Understand and Respond to the Current Epidemic of Novel Coronavirus Pneumonia (COVID-19)/ 中华实验眼科杂志 The new coronavirus pneumonia that first appeared in Wuhan, China, in December 2019 has attracted great attention from both the Chinese government and the international community. The International Committee on Viral Classification named the virus "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2), and the WHO named the pneumonia it causes "Coronavirus Disease 2019" (COVID-19). At present, the disease is centered in Wuhan City and is spreading rapidly to all parts of China, as well as twenty other countries. About 20% of the people infected during the SARS epidemic in 2003 were employees in hospital environments. COVID-19 has infected an even greater number of heath care workers. Therefore, ophthalmologists need to understand the disease and recognize the importance of taking preventive measures. Although ophthalmologists do not work on the front lines of the outbreak, due to their area of expertise, a variety of situations, such as infection consultations or ophthalmic emergency treatments, can lead to the exposure of ophthalmologists to high-risk environments. This risk will only increase as the number of infected patients continues to increase. When dealing with seemingly normal ophthalmic patients, the vigilance of ophthalmologists and associated staff tends to be significantly reduced. To better protect patients, families, and health care workers, it is strongly recommended that in addition to the standard precautions for the care of all patients, strict contact precautions and droplet precautions need to be taken by ophthalmologists. These measures include 1) wearing an efficient mask (an N95 mask); 2) always performing hand hygiene before and after examining a patient; (3) wearing sterile gloves when entering a patient’s room and touching a patient; (4) wearing a gown when contact is expected with items and environmental surfaces surrounding a patient or when the patient is incontinent or has diarrhea or a surgical or other invasive wound with oozing fluid; 5) cleaning and disinfecting ophthalmic equipment and correctly handling medical waste after examination to prevent transmission to patients who are subsequently examined; 6) wearing goggles and a disposable mask to cover the front and sides of the face before touching a patient, as the virus could spread through the ocular surface; 7) performing the relevant screening for novel coronavirus pneumonia for regular patients who have conjunctivitis and respiratory symptoms at the same time; 8) prohibiting the use of infected patients as potential donors for corneal transplants and temporarily adding donor SARS-CoV-2 screening to the medical standard of the eye bank during the outbreak; and 9) for the purposes of scientific research, diagnosis, and other special needs, packing, shipping, and transporting collected specimens according to the relevant dangerous biological goods regulations.

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: Surface Disinfection The patient-care areas in a dental setting become contaminated with bacterial and viral pathogens during patient treatment. Incorporating standard precautions set forth by CDC and OSHA guidelines will reduce the risk of disease transmission. Contaminated environmental surfaces, including clinical contact and housekeeping surfaces, become a reservoir of infectious material with the potential to spread an infection to health-care personnel and patients. Transmission of pathogens can occur by direct or indirect contact of clinical contact surfaces and the hands of health-care personnel. Proper infection control protocol of these surfaces includes cleaning, disinfecting, and the use of barriers to prevent the spread of infectious pathogens. This chapter will provide an overview of the disinfection protocol of environmental surfaces in the dental setting. The topics include the various chemical formulations of hospital disinfectants and their proper use, as well as physical barriers that aim to reduce the degree of contamination in the dental treatment area thus decreasing the probability of cross-infection and disease transmission.

positive: Environmental investigation of respiratory pathogens during the Hajj 2016 and 2018 Abstract Background Respiratory tract infections are common in the context of the Hajj pilgrimage and respiratory pathogens can be transmitted via contact with contaminated surfaces. We sampled surfaces during the Hajj to detect the presence of respiratory bacteria and viruses. Methods Frequently touched surfaces at Mecca, Mina, Arafat and Medina were sampled. The common respiratory pathogens were tested by qPCR. Results 70/142 (49.3%) environmental samples collected were positive for at least one respiratory pathogen. Among the positive samples, Klebsiella pneumoniae was the bacterium most frequently tested positive (57.1%), followed by Streptococcus pneumoniae (12.9%), Staphylococcus aureus (10.0%) and Haemophilus influenzae (7.1%). 32.9% positive samples tested positive for rhinovirus and 1.4% for coronavirus. Surfaces with the highest rates of positive samples were kitchen tables (100%), water fountain faucet (73.3%) and edge of water coolers lid (84.6%). Samples collected in Mina were the most frequently contaminated with 68.8% being positive for at least one pathogen and 18.8% positive for a combination of multiple pathogens. Conclusion These preliminary results indicate that respiratory pathogens are common in environmental surfaces from areas frequented by Hajj pilgrims. Further larger-scale studies are needed to better assess the possible role of environmental respiratory pathogens in respiratory infections in Hajj pilgrims.

positive: Air and surface measurements of SARS-CoV-2 inside a bus during normal operation Transmission pathways of SARS-CoV-2 are through aerosol, droplet and touching infected material. Indoor locations are more likely environments for the diffusion of the virus contagion among people, but direct detection of SARS-CoV-2 in air or on surfaces is quite sparse, especially regarding public transport. In fact, an important demand is to know how and if it is safe to use them. To understand the possible spreading of COVID-19 inside a city bus during normal operation and the effectiveness of the protective measures adopted for transportation, we analysed the air and the surfaces most usually touched by passengers. The measurements were carried out across the last week of the lockdown and the first week when gradually all the travel restrictions were removed.

positive: Air and environmental sampling for SARS-CoV-2 around hospitalized patients with coronavirus disease 2019 (COVID-19) BACKGROUND: The role of severe respiratory coronavirus virus 2 (SARS-CoV-2)–laden aerosols in the transmission of coronavirus disease 2019 (COVID-19) remains uncertain. Discordant findings of SARS-CoV-2 RNA in air samples were noted in early reports. METHODS: Sampling of air close to 6 asymptomatic and symptomatic COVID-19 patients with and without surgical masks was performed with sampling devices using sterile gelatin filters. Frequently touched environmental surfaces near 21 patients were swabbed before daily environmental disinfection. The correlation between the viral loads of patients’ clinical samples and environmental samples was analyzed. RESULTS: All air samples were negative for SARS-CoV-2 RNA in the 6 patients singly isolated inside airborne infection isolation rooms (AIIRs) with 12 air changes per hour. Of 377 environmental samples near 21 patients, 19 (5.0%) were positive by reverse-transcription polymerase chain reaction (RT-PCR) assay, with a median viral load of 9.2 × 10(2) copies/mL (range, 1.1 × 10(2) to 9.4 × 10(4) copies/mL). The contamination rate was highest on patients’ mobile phones (6 of 77, 7.8%), followed by bed rails (4 of 74, 5.4%) and toilet door handles (4 of 76, 5.3%). We detected a significant correlation between viral load ranges in clinical samples and positivity rate of environmental samples (P < .001). CONCLUSION: SARS-CoV-2 RNA was not detectable by air samplers, which suggests that the airborne route is not the predominant mode of transmission of SARS-CoV-2. Wearing a surgical mask, appropriate hand hygiene, and thorough environmental disinfection are sufficient infection control measures for COVID-19 patients isolated singly in AIIRs. However, this conclusion may not apply during aerosol-generating procedures or in cohort wards with large numbers of COVID-19 patients.

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: 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: 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.

positive: A Surface Coating that Rapidly Inactivates SARS-CoV-2. SARS-CoV-2, the virus that causes the disease COVID-19, remains viable on solids for periods of up to one week, so one potential route for human infection is via exposure to an infectious dose from a solid. We have fabricated and tested a coating that is designed to reduce the longevity of SARS-CoV-2 on solids. The coating consists of cuprous oxide (Cu2O) particles bound with polyurethane. After one hour on coated glass or stainless steel, the viral titer was reduced by about 99.9% on average compared to the uncoated sample. An advantage of a polyurethane-based coating is that polyurethane is already used to coat a large number of everyday objects. Our coating adheres well to glass and stainless steel, as well as everyday items that people may fear to touch during a pandemic, such as a doorknob, a pen, and a credit card keypad button. The coating performs well in the cross-hatch durability test and remains intact and active after 13 days immersed in water, or after exposure to multiple cycles of exposure to virus and disinfection.

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: Povidone-Iodine Demonstrates Rapid In Vitro Virucidal Activity Against SARS-CoV-2, The Virus Causing COVID-19 Disease INTRODUCTION: As of 22 June 2020, Severe Acute Respiratory Syndrome (SARS)-coronavirus (CoV)-2 has infected more than 8.95 million people worldwide, causing > 468,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus. We report the in vitro virucidal activity of topical and oral povidone-iodine (PVP-I) products against SARS-CoV-2. METHODS: Suspension assays were used to assess the virucidal activity of PVP-I against SARS-CoV-2. Products were tested at a contact time of 30 s for virucidal activity. Viral titres were calculated using the Spearman–Kärber method and reported as median tissue culture infectious dose (TCID(50))/mL. RESULTS: All four products [antiseptic solution (PVP-I 10%), skin cleanser (PVP-I 7.5%), gargle and mouth wash (PVP-I 1%) and throat spray (PVP-I 0.45%)] achieved ≥ 99.99% virucidal activity against SARS-CoV-2, corresponding to ≥ 4 log(10) reduction of virus titre, within 30 s of contact. CONCLUSION: This study provides evidence of rapid and effective virucidal activity of PVP-I against SARS-CoV-2. PVP-I-based products are widely available for medical and personal use for hand hygiene and oral decontamination, and could be readily integrated into coronavirus disease, COVID-19, infection control measures in hospital and community settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40121-020-00316-3) contains supplementary material, which is available to authorized users.

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: 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.

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: Temporary carriage of bovine coronavirus and bovine respiratory syncytial virus by fomites and human nasal mucosa after exposure to infected calves BACKGROUND: In order to prevent spread of the endemic pathogens bovine coronavirus (BCoV) and bovine respiratory syncytial virus (BRSV) between herds, knowledge of indirect transmission by personnel and fomites is fundamental. The aims of the study were to determine the duration of viral RNA carriage and the infectivity of viral particles on fomites and human nasal mucosa after exposure to BCoV and BRSV. During two animal infection experiments, swabs were collected from personnel (nasal mucosa) and their clothes, boots and equipment after contact with calves shedding either virus. Viral RNA was quantified by RT-qPCR or droplet digital RT-PCR (RT-ddPCR), and selected samples with high levels of viral RNA were tested by cell culture for infectivity. RESULTS: For BCoV, 46% (n = 80) of the swabs from human nasal mucosa collected 30 min after exposure were positive by RT-qPCR. After two, four and six hours, 15%, 5% and 0% of the swabs were positive, respectively. Infective virions were not detected in mucosal swabs (n = 2). A high viral RNA load was detected on 97% (n = 44) of the fomites 24 h after exposure, and infective virions were detected in two of three swabs. For BRSV, 35% (n = 26) of the human nasal mucosa swabs collected 30 min after exposure, were positive by RT-ddPCR, but none were positive for infective virions. Of the fomites, 89% (n = 38) were positive for BRSV RNA 24 h after exposure, but all were negative for infective viruses. CONCLUSIONS: The results indicate that human nasal mucosa can carry both BCoV and BRSV RNA after exposure to virus shedding calves, but the carriage seems short-lived and the transmission potential is likely limited. High viral loads on contaminates fomites 24 h after exposure to infected animals, and detection of infective BCoV, indicate that contaminated fomites represent a significant risk for indirect transmission between herds.

positive: 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.

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: Sampling methods for recovery of human enteric viruses from environmental surfaces Abstract Acute gastroenteritis causes the second highest infectious disease burden worldwide. Human enteric viruses have been identified as leading causative agents of acute gastroenteritis as well as foodborne illnesses in the U.S. and are generally transmitted by fecal-oral contamination. There is growing evidence of transmission occurring via contaminated fomite including food contact surfaces. Additionally, human enteric viruses have been shown to remain infectious on fomites over prolonged periods of time. To better understand viral persistence, there is a need for more studies to investigate this phenomenon. Therefore, optimization of surface sampling methods is essential to aid in understanding environmental contamination to ensure proper preventative measures are being applied. In general, surface sampling studies are limited and highly variable among recovery efficiencies and research parameters used (e.g., virus type/density, surface type, elution buffers, tools). This review aims to discuss the various factors impacting surface sampling of viruses from fomites and to explore how researchers could move towards a more sensitive and standard sampling method.

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: Characterization of a novel, low-cost, scalable ozone gas system for sterilization of N95 respirators and other COVID-19 related use cases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an elusive and highly pathogenic agent, has resulted in the ongoing COVID-19 pandemic affecting numerous populations worldwide. New studies investigating the tenacity of SARS-CoV-2 have highlighted its ability to persist on a myriad of surfaces for several days, including gowns and shoes. As a result, there is a global need for sterilization of a variety of potentially-contaminated items, ranging from clothing to personal protective equipment like face coverings. To this end, we have designed and constructed a cost-effective, scalable, and sustainable sterilization system that uses ozone gas to inactivate viral particles. We sought to determine the efficacy of the system in the sterilization of viral particles as well as its ability to sterilize N95 respirators for reuse. N95 respirators inoculated with P22 bacteriophage and sterilized in the ozone system showed a 6-log10 reduction in viral load when treated at 25 ppm for 150 minutes. Further, N95 respirators treated with five 150-minute cycles at 35 ppm for a total concentration-time product (CT) of 26,250 ppm*min in the ozone system showed comparable filtration efficiency to untreated N95 respirators in a 50 to 200 nmr particulate challenge filtration test. Interestingly, the surgical N95 respirators tested showed complete inactivation of fluid resistance and degradation of the elasticity of polyisoprene straps after five cycles in the sterilization system. Taken together, these data suggest that while our ozone system may negatively affect certain protective aspects of surgical N95 respirators, it does effectively sterilize viral particles and can be utilized for a multitude of other use cases, including sterilizing polypropylene face coverings after potential SARS-CoV-2 contamination. In addition to providing long-term environmental benefits, deployment of this system during the ongoing pandemic reduces the risk of COVID-19 community transmission while conserving monetary resources otherwise spent on the continuous purchase of disposable face coverings.

positive: Should I be worried about carrying the virus that causes COVID‐19 home on my clothes?

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: Minimization of spreading of SARS-CoV-2 via household waste produced by subjects affected by COVID-19 or in quarantine Abstract Currently available evidence supports that the predominant route of human-to-human transmission of the SARS-CoV-2 is through respiratory droplets. Indirect hands contact with surfaces contaminated by infectious droplets subsequently touching the mouth, nose or eyes seems to be another route of an indirect contact transmission. Persistence of the virus on different surfaces and other materials has been reported in recent studies: SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard. Viable virus was detected up to 72 h after application to different surfaces, although infectivity decay was also observed. This evidence suggests the likelihood that waste generated from patients affected by COVID-19 or subjects in quarantine treated in private houses or in areas different from hospitals and medical centres could be contaminated by SARS-CoV-2. Consequently, waste streams may represent a route for viral spreading being a potential risk also for the operators directly involved in the different phases of waste management. To address this concern, a specific multidisciplinary working group was settled by the Italian National Institute of Health (ISS) during the COVID-19 emergency, in order to establish guidelines related to solid waste collection, delivering, withdrawal, transport, treatment and disposal. Temporary stop of waste sorting, instructions for the population on how to package waste, instructions for Companies and operators for the adoption of adequate personal protection equipment (PPE), the use and sanitation of proper vehicles were among the main recommendations provided to the community by publications of freely downloadable reports and infographics in layman language. Incineration, sterilization and properly managed landfills were identified as the facilities to be preferentially adopted for the treatment of this kind of waste, considering the main inactivation strategies of SARS-CoV-2 (e.g. treatment length > 9 days and temperature > 70 °C for more than 5 min).

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: Does COVID-19 Spread Through Droplets Alone?

positive: 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.

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: Management of the SARS-CoV-2 (Covid 19) coronavirus epidemic in hemodialysis units Summary The current outbreak of SARS-CoV-2 represents a special risk for renal patients due to their comorbidities and advanced age. The usual performance of hemodialysis treatment s in collective rooms increases the risk. The specific information at this time in this regard is very limited. This manuscript includes a proposal for action to prevent infection in the N ephrology S ervices, and in particular in H emodialysis U nits, with the objective of early identification of patients who meet the definition of a suspected case of infection by SARS-CoV-2 and propose circuits and mechanisms to carry out hemodialysis treatment s. They are recommendations in continuous review and can be modified if the epidemiological situation, the diagnostic and therapeutic options so require.

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: 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: COVID-19: A Risk Assessment Perspective [Image: see text] COVID-19 is a newly emerging viral respiratory disease first identified in Wuhan, China, in December 2019. The disease is caused by the coronavirus SARS-CoV-2, which is related to the viruses that cause SARS and MERS. While the case fatality ratio for COVID-19 (5%) is far lower than that for SARS (11%) and MERS (34%), COVID-19 is spreading relatively uncontrolled at this time across the globe. In contrast, SARS appears to be contained, and MERS is controlled. This paper will explore why COVID-19 is able to progress to a global pandemic that affects our daily lives to an extent not known in recent history. The COVID-19 outbreak and spread will be examined based on the current literature, using a researcher’s perspective of risk assessment and risk mitigation; this approach will be related to public health.

positive: 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.

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: Evaluation of an Electrostatic Spray Disinfectant Technology for Rapid Decontamination of Portable Equipment and Large Open Areas in the Era of SARS-CoV-2 In the setting of the coronavirus disease 2019 pandemic, efficient methods are needed to decontaminate shared portable devices and large open areas such as waiting rooms. We found that wheelchairs, portable equipment, and waiting room chairs were frequently contaminated with potential pathogens. After minimal manual pre-cleaning of areas with visible soiling, application of a dilute sodium hypochlorite disinfectant using an electrostatic sprayer provided rapid and effective decontamination and eliminated the benign virus bacteriophage MS2 from inoculated surfaces.

positive: Letter to the Editor Regarding: “An Imperative Need for Research on the Role of Environmental Factors in Transmission of Novel Coronavirus (COVID-19)” —Secondhand and Thirdhand Smoke As Potential Sources of COVID-19

positive: Experimental and numerical study of potential infection risks from exposure to bioaerosols in one BSL-3 laboratory Laboratory-acquired infections (LAIs) are defined as infections of laboratory staff by exposure to pathogenic microorganisms during an experimental procedure. For a biosafety level-3 (BSL-3) laboratory with a high potential of exposure, reducing risks and threats relevant to LAIs has become a critical concern, especially after the recent outbreak of Novel Coronavirus causing COVID-19 in Wuhan, China. This study aimed to investigate the spatial-temporal characteristics of bioaerosol dispersion and deposition of two kinds of bioaerosols (Serratia marcescens and phage ΦX174). A combination of laboratory experiment and numerical simulation was adopted to explore bioaerosol removal. Three-dimensional concentration iso-surface mapping in conjunction with flow field analysis was employed to elucidate bioaerosol migration and deposition behavior. The total deposition number and unit area deposition ratio were calculated for different surfaces. The results indicate that bioaerosol concentration remains stable for up to 400 s after release, and that almost 70% of all bioaerosol particles become deposited on the surfaces of walls and equipment. Vortex flow regions and high-concentration regions were determined, and the most severely contaminated surfaces and locations were identified. Our results could provide the scientific basis for controlling the time interval between different experiments and also provide guidelines for a laboratory disinfection routine. Furthermore, future work regarding laboratory layout optimization and high efficiency air distribution for bioaerosol removal in a BSL-3 laboratory should be emphasized.

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: SARS-CoV-2 (COVID-19) by the numbers The COVID-19 pandemic is a harsh reminder of the fact that, whether in a single human host or a wave of infection across continents, viral dynamics is often a story about the numbers. In this article we provide a one-stop, curated graphical source for the key numbers (based mostly on the peer-reviewed literature) about the SARS-CoV-2 virus that is responsible for the pandemic. The discussion is framed around two broad themes: i) the biology of the virus itself; ii) the characteristics of the infection of a single human host.

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: 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings

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: A COVID-19 epidemic model integrating direct and fomite transmission as well as household structure This paper stresses its base contribution on a new SIR-type model for COVID-19 including direct and fomite transmission as well as the effect of distinct household structures. To what extent increasing the physical-distancing-related contact radius and enhancing mass control (public curfew, lockdown, workplace clearance, and school closure) reduce the number of predicted active cases is studied via parameter estimation.

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: COVID-19 and ENT Surgery ABSTRACT In Otorhinolaryngology - Head and Neck Surgery, clinical examination and invasive procedures on the respiratory tract and on airway-connected cavities such as paranasal sinuses and the middle ear expose people to direct transmission of SARS-CoV-2 by inhalation or ocular projection of contaminated droplets, and to indirect transmission by contact with contaminated hands, objects or surfaces. Estimating an R0 of Covid-19 at around 3 justified postponing non-urgent face-to-face consultations and expanding the use of teleconsultation in order to limit the risks of SARS-CoV-2 infection of patients or health workers and comply with the lockdown. The health authority recommends cancellation of all medical or surgical activities which are not urgent as long as this does not involve a loss of chance for the patient. The purpose of this cancellation is to significantly increase critical care capacity, prioritize the reception of patients with Covid-19, prioritize the allocation of staff and provision of the equipment necessary for their medical or surgical management, and contribute to the smooth running of downstream critical care within their establishment. Another goal is to reduce the risks of patient contamination within healthcare facilities. This document provides guidance on how to proceed with and adapt ENT surgery in the current pandemic context, as well as on the management of postponed operations. This best practice advice must of course be adapted in each region according to the development of the epidemic and pre-existing arrangements. Their local application can only be decided within the framework of collaboration between the ENT teams, the operational hygiene units and all the other specialties concerned.

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: A multi-scale model of virus pandemic: Heterogeneous interactive entities in a globally connected world This paper is devoted to the multidisciplinary modelling of a pandemic initiated by an aggressive virus, specifically the so-called \textit{SARS--CoV--2 Severe Acute Respiratory Syndrome, corona virus n.2}. The study is developed within a multiscale framework accounting for the interaction of different spatial scales, from the small scale of the virus itself and cells, to the large scale of individuals and further up to the collective behaviour of populations. An interdisciplinary vision is developed thanks to the contributions of epidemiologists, immunologists and economists as well as those of mathematical modellers. The first part of the contents is devoted to understanding the complex features of the system and to the design of a modelling rationale. The modelling approach is treated in the second part of the paper by showing both how the virus propagates into infected individuals, successfully and not successfully recovered, and also the spatial patterns, which are subsequently studied by kinetic and lattice models. The third part reports the contribution of research in the fields of virology, epidemiology, immune competition, and economy focused also on social behaviours. Finally, a critical analysis is proposed looking ahead to research perspectives.

positive: Solar ultraviolet radiation sensitivity of SARS-CoV-2

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: Coronavirus SARS‐CoV‐2: filtering fact from fiction in the infodemic: Q&A with virologist Professor Urs Greber As the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) continues to spread across the world, and the associated lung disease COVID-19 remains difficult to treat, information from media and private communication flows at high speed, often through unfiltered channels. Much of this information is speculative, as it derives from preliminary and inconclusive studies, and creates confusion as well as anxiety. This phenomenon was recently labelled as "infodemic" by the World Health Organization.

positive: SARS in Hospital Emergency Room Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients.

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: Reusable and Recyclable Graphene Masks with Outstanding Superhydrophobic and Photothermal Performances The 2019 coronavirus outbreak (COVID-19) is affecting over 210 countries and territories, and it is spreading mainly by respiratory droplets. The use of disposable surgical masks is common for patients, doctors, and even the general public in highly risky areas. However, the current surgical masks cannot self-sterilize in order to reuse or be recycled for other applications. The resulting high economic and environmental costs are further damaging societies worldwide. Herein, we reported a unique method for functionalizing commercially available surgical masks with outstanding self-cleaning and photothermal properties. A dual-mode laser-induced forward transfer method was developed for depositing few-layer graphene onto low-melting temperature nonwoven masks. Superhydrophobic states were observed on the treated masks' surfaces, which can cause the incoming aqueous droplets to bounce off. Under sunlight illumination, the surface temperature of the functional mask can quickly increase to over 80 °C, making the masks reusable after sunlight sterilization. In addition, this graphene-coated mask can be recycled directly for use in solar-driven desalination with outstanding salt-rejection performance for long-term use. These roll-to-roll production-line-compatible masks can provide us with better protection against this severe virus. The environment can also benefit from the direct recycling of these masks, which can be used for desalinating seawater.

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: 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.

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: 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.

positive: Surface Alterations to Impart Antiviral Properties to Combat COVID-19 Transmission A global epidemic caused by highly transmittable COVID-19 is causing severe loss of human life. In this study, two aspects of reducing transmission of COVID-19 virus, due to surface contact, are discussed: first refers to the effect of nanocarbon fullerene C(60) coating on surface, that causes lipid peroxidation on the phospholipid layer present in the outer envelope of COVID-19; the second aspect refers to creating hydrophobic surfaces by texturing them, so that the contact area between virus and surface is minimized due to the presence of entrapped air between the topographies. These can be similar to micro-/nano-multiscale textured surfaces that have anti-biofouling properties. Fullerene-coated surfaces can be seen as a possible solution to decrease the adhesion of virus on the surface, as they will be hydrophobic as well as toxic to the envelope.

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: 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: Absence of contamination of personal protective equipment (PPE) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

positive: Prevention of nosocomial COVID-19: Another challenge of the pandemic

positive: Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020 To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.

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

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

positive: Can N95 Respirators Be Reused after Disinfection? How Many Times? [Image: see text] The coronavirus disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which are essential for protecting healthcare professionals and the general public who may come into contact with the virus. Thus, it is essential to determine how we can reuse respirators and other personal protective equipment in these urgent times. We investigated multiple commonly used disinfection schemes on media with particle filtration efficiency of 95%. Heating was recently found to inactivate the virus in solution within 5 min at 70 °C and is among the most scalable, user-friendly methods for viral disinfection. We found that heat (≤85 °C) under various humidities (≤100% relative humidity, RH) was the most promising, nondestructive method for the preservation of filtration properties in meltblown fabrics as well as N95-grade respirators. At 85 °C, 30% RH, we were able to perform 50 cycles of heat treatment without significant changes in the filtration efficiency. At low humidity or dry conditions, temperatures up to 100 °C were not found to alter the filtration efficiency significantly within 20 cycles of treatment. Ultraviolet (UV) irradiation was a secondary choice, which was able to withstand 10 cycles of treatment and showed small degradation by 20 cycles. However, UV can potentially impact the material strength and subsequent sealing of respirators. Finally, treatments involving liquids and vapors require caution, as steam, alcohol, and household bleach all may lead to degradation of the filtration efficiency, leaving the user vulnerable to the viral aerosols.

positive: Environmental surface testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during prolonged isolation of an asymptomatic carrier Environmental surface testing was performed to search for evidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) environmental contamination by an asymptomatic SARS-CoV-2 carrier with persistently high viral loads under isolation. No evidence of environmental contamination was found. Further studies are needed to measure environmental contamination by SARS-CoV-2 carriers and to determine reasonable isolation periods.

positive: Prolonged presence of SARS-CoV-2 in feces of pediatric patients during the convalescent phase Background: Severe acute respiratory coronavirus 2 (SARS-CoV-2) is a newly identified virus which mainly spreads from person-to-person. Fecal shedding of SARS-CoV-2 has been constantly reported in patients with coronavirus disease 2019 (COVID-19). Most published studies focus on adult populations, whereas data concerning pediatric patients is relatively scarce. Methods: From January 17, 2020 to March 6, 2020, three pediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data of these children were collected. Real-time fluorescence reverse-transcriptase-polymerase-chain reaction (RT-PCR) was performed to detect SARS-CoV-2 RNA in throat swabs and fecal specimens. Results: All the three pediatric cases were household contacts of adults whose symptoms developed earlier. There has been no evidence showing the virus was transmitted from the children to others. Severity of disease of these children was mild to moderate and fever was the most consistent and predominant symptom at onset of illness (two cases had body temperature higher than 38.5 Celsius). All children showed increased lymphocytes (>4.4*109/L) with normal white blood cell counts on admission. One child had elevated serum levels of procalcitonin and C-reaction protein. Radiological changes were not typical for COVID-19. All children showed good response to supportive treatment. Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas persistent presence of viral RNA was found in stools of all children. One case had fecal SARS-CoV-2 turned negative 8 days after throat swabs showing negative, while that of another child lagged behind for 20 days. At the time of writing, one child still had positive results for RT-PCR analysis in stools after negative conversion of viral RNA in respiratory samples (over 19 days behind). Conclusions: Pediatric patients with COVID-19 are very different from adult patients in regards to epidemiological, clinical, laboratory, and radiological characteristics. Prolonged shedding of SARS-CoV-2 in stools of infected children indicates the potential for the virus to be transmitted through fecal excretion. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.

positive: 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.

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, Staphylococcus aureus, 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, 12 hours) 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: Are Quaternary Ammonium Compounds, the Workhorse Disinfectants, Effective against Severe Acute Respiratory Syndrome-Coronavirus-2? A novel virus named Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) emerged from Wuhan, China in late 2019. Since then, the virus has quickly spread worldwide, leading the World Health Organization to declare it as a pandemic; by the end of April 2020, the number of cases exceeded 3 million. Due to the high infectivity rate, SARS-CoV-2 is difficult to contain, making disinfectant protocols vital, especially for essential, highly trafficked areas such as hospitals, grocery stores, and delivery centers. According to the Centers for Disease Control and Prevention, best practices to slow the spread rely on good hand hygiene, including proper handwashing practices as well as the use of alcohol-based hand sanitizers. However, they provide warning against sanitizing products containing benzalkonium chloride (BAC), which has sparked concern in both the scientific community as well as the general public as BAC, a common quaternary ammonium compound (QAC), is ubiquitous in soaps and cleaning wipes as well as hospital sanitation kits. This viewpoint aims to highlight the outdated and incongruous data in the evaluation of BAC against the family of known coronaviruses and points to the need for further evaluation of the efficacy of QACs against coronaviruses.

positive: 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.

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: Preventive and Control Measures for the Coronavirus Pandemic in Clinical Dentistry. A severe public health crisis has been declared worldwide since coronavirus disease 2019 (COVID-19) was classified as a pandemic of acute respiratory infectious disease by the World Health Organisation (WHO). China has taken strict measures to curb the spread of the disease to save lives, and has managed to control the outbreak. COVID-19 is mainly transmitted through respiratory droplets and close physical contact, so it is challenging to prevent nosocomial infection and possible spread during dental treatment. Since the initial phase of the COVID-19 outbreak, a disease prevention and control strategy based on the new concept of population risk classification and rational use of personal protective equipment has been implemented by the Peking University Hospital of Stomatology. Nosocomial infection prevention and control concepts and measures relating to dental diagnosis and treatment are critically checked in the hospital. Our experiences in handling this situation are shared here and may have wide-ranging implications for infection prevention and control (IPC) for COVID-19 in dental practices worldwide.

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: 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: 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.

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: Se préparer pour la pandémie de COVID-19: revue des moyens déployés dans un bloc opératoire d'un grand hôpital tertiaire au Singapour./ Preparing for a COVID-19 pandemic: a review of operating room outbreak response measures in a large tertiary hospital in Singapore The coronavirus disease 2019 (COVID-19) outbreak has been designated a public health emergency of international concern. To prepare for a pandemic, hospitals need a strategy to manage their space, staff, and supplies so that optimum care is provided to patients. In addition, infection prevention measures need to be implemented to reduce in-hospital transmission. In the operating room, these preparations involve multiple stakeholders and can present a significant challenge. Here, we describe the outbreak response measures of the anesthetic department staffing the largest (1,700-bed) academic tertiary level acute care hospital in Singapore (Singapore General Hospital) and a smaller regional hospital (Sengkang General Hospital). These include engineering controls such as identification and preparation of an isolation operating room, administrative measures such as modification of workflow and processes, introduction of personal protective equipment for staff, and formulation of clinical guidelines for anesthetic management. Simulation was valuable in evaluating the feasibility of new operating room set-ups or workflow. We also discuss how the hierarchy of controls can be used as a framework to plan the necessary measures during each phase of a pandemic, and review the evidence for the measures taken. These containment measures are necessary to optimize the quality of care provided to COVID-19 patients and to reduce the risk of viral transmission to other patients or healthcare workers.

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: 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: 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: Efficient and quick inactivation of SARS coronavirus and other microbes exposed to the surfaces of some metal catalysts. OBJECTIVE To study the two metal catalysts Ag/Al2O3 and Cu/Al2O3 that interdict the transmission pathway for SARS and other respiratory infectious diseases. METHODS Two metal catalysts Ag/Al2O3 and Cu/Al2O3 were pressed into wafers. One hundred microL 10(6) TCID50/mL SARS-CoV, 100 microL 10(6) PFU/mL recombinant baculovirus expressing hamster's prion protein (haPrP) protein and roughly 10(6) E. coli were slowly dropped onto the surfaces of the catalyst wafers and exposed for 5 and 20 min, respectively. After eluted from the surfaces of wafers, the infectivity of viruses and propagation of bacteria were measured. The expression of PrP protein was determined by Western blot. The morphological changes of bacteria were observed by electronic microscopy. RESULTS After exposure to the catalysts surfaces for 5 and 20 min, the infectivity of SARS-CoV in Vero cells and baculovirus in Sf9 cells dropped down to a very low and undetectable level, and no colony was detected using bacteria culture method. The expression of haPrP protein reduced to 21.8% in the preparation of Sf9 cells infected with recombinant baculovirus exposed for 5 min and was undetectable exposed for 20 min. Bacterial membranes seemed to be cracked and the cytoplasm seemed to be effluent from cell bodies. CONCLUSION Exposures to the surfaces of Ag/Al2O3 and Cu/Al2O3 destroy the replication and propagation abilities of SARS-CoV, baculovirus and E. coli. Inactivation ability of metal catalysts needs to interact with air, utilizing oxygen molecules in air. Efficiently killing viruses and bacteria on the surfaces of the two metal catalysts has a promising potential for air-disinfection in hospitals, communities, and households.

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: The COVID‐19 Pandemic: An Epidemiologic, Public Health, and Clinical Brief

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: Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020 To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.

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: 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: 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.

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: Masks and closed-loop ventilators prevent environmental contamination by COVID-19 patients in negative-pressure environments Abstract Herein, we report that nosocomial infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be mitigated by using surgical masks and closed looped ventilation for both non-critical and critical patients. These preventive measures resulted in no viral contamination of surfaces in negative pressure environments.

positive: How Ophthalmologists Should Understand and Respond to the Current Epidemic of Novel Coronavirus Pneumonia (COVID-19) The new coronavirus pneumonia that first appeared in Wuhan, China, in December 2019 has attracted great attention from both the Chinese government and the international community The International Committee on Viral Classification named the virus &quot;Severe Acute Respiratory Syndrome Coronavirus 2&quot;(SARS-CoV-2), and the WHO named the pneumonia it causes &quot;Coronavirus Disease 2019&quot;(COVID-19) At present, the disease is centered in Wuhan City and is spreading rapidly to all parts of China, as well as twenty other countries About 20% of the people infected during the SARS epidemic in 2003 were employees in hospital environments COVID-19 has infected an even greater number of heath care workers Therefore, ophthalmologists need to understand the disease and recognize the importance of taking preventive measures Although ophthalmologists do not work on the front lines of the outbreak, due to their area of expertise, a variety of situations, such as infection consultations or ophthalmic emergency treatments, can lead to the exposure of ophthalmologists to high-risk environments This risk will only increase as the number of infected patients continues to increase When dealing with seemingly normal ophthalmic patients, the vigilance of ophthalmologists and associated staff tends to be significantly reduced To better protect patients, families, and health care workers, it is strongly recommended that in addition to the standard precautions for the care of all patients, strict contact precautions and droplet precautions need to be taken by ophthalmologists These measures include 1) wearing an efficient mask (an N95 mask);2) always performing hand hygiene before and after examining a patient;(3) wearing sterile gloves when entering a patient’s room and touching a patient;(4) wearing a gown when contact is expected with items and environmental surfaces surrounding a patient or when the patient is incontinent or has diarrhea or a surgical or other invasive wound with oozing fluid;5) cleaning and disinfecting ophthalmic equipment and correctly handling medical waste after examination to prevent transmission to patients who are subsequently examined;6) wearing goggles and a disposable mask to cover the front and sides of the face before touching a patient, as the virus could spread through the ocular surface;7) performing the relevant screening for novel coronavirus pneumonia for regular patients who have conjunctivitis and respiratory symptoms at the same time;8) prohibiting the use of infected patients as potential donors for corneal transplants and temporarily adding donor SARS-CoV-2 screening to the medical standard of the eye bank during the outbreak;and 9) for the purposes of scientific research, diagnosis, and other special needs, packing, shipping, and transporting collected specimens according to the relevant dangerous biological goods regulations

positive: Catalytic inactivation of SARS coronavirus, Escherichia coli and yeast on solid surface Catalytic oxidation is a potential way to disinfect air through a air-condition system. We find that the SARS coronavirus, bacteria and yeast are completely inactivated in 5 min on Ag catalyst surface and in 20 min on Cu catalyst surface at room temperature in air. Scanning electron microscopy (SEM) images show that the yeast cells are dramatically destructed on the Ag/Al(2)O(3) and Cu/Al(2)O(3) surfaces, which indicates that the inactivation is caused by catalytic oxidation rather than by toxicity of heavy metals.

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: 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: [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: Spatial spread of an epidemic through public transportation systems with a hub Abstract This article investigates an epidemic spreading among several locations through a transportation system, with a hub connecting these locations. Public transportation is not only a bridge through which infections travel from one location to another but also a place where infections occur since individuals are typically in close proximity to each other due to the limited space in these systems. A mathematical model is constructed to study the spread of an infectious disease through such systems. A variant of the next generation method is proposed and used to provide upper and lower bounds of the basic reproduction number for the model. Our investigation indicates that increasing transportation efficiency, and improving sanitation and ventilation of the public transportation system decrease the chance of an outbreak occurring. Moreover, discouraging unnecessary travel during an epidemic also decreases the chance of an outbreak. However, reducing travel by infectives while allowing susceptibles to travel may not be enough to avoid an outbreak.

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

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: World Federation for Ultrasound in Medicine and Biology Position Statement: How to Perform a Safe Ultrasound Examination and Clean Equipment in the Context of COVID-19

positive: Impact of the Coronavirus (COVID-19) pandemic on surgical practice - Part 1 (Review Article) The Coronavirus (COVID-19) pandemic has resulted in over 2.3 million confirmed cases and over 160,000 deaths. The impact of COVID-19 on surgical practice is widespread ranging from workforce and staffing issues, procedural prioritisation, viral transmission risk intraoperatively, changes to perioperative practice and ways of working alongside the impact on surgical education and training. Whilst there has been a growing literature base describing the early clinical course of COVID-19 and on aspects of critical care related to treating these patients, there has been a dearth of evidence on how this pandemic will affect surgical practice. This paper seeks to review the current evidence and offers recommendations for changes to surgical practice to minimise the effect of the COVID-19 pandemic.

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: The emergence of novel coronavirus disease (COVID-19) in Bangladesh: Present status, challenges, and future management Immediate after the official declaration of COVID-19 in Bangladesh on 8 March 2020, it has created public panic which results in price plummeting of the capital market and price hike of many essential commodities. Worldwide, the outbreak of COVID-19 has declared a pandemic. In response, the Government of Bangladesh has initiated some strict measures such as stopping the entry of passengers from Europe, stopping on-arrival visas and self-quarantine for 2 weeks for all passengers return from abroad. Still, many loopholes exist at the entry points of Bangladesh. Most of the people of Bangladesh are yet to aware of the consequences of COVID-19. In this backdrop, this article has attempted to create public awareness about COVID-19, providing some guidelines to restrict this deadly disease, enlisting current challenges of this disease in Bangladesh. This review would be helpful to undertake future management practices against the fearsome COVID-19 in Bangladesh.

positive: Detection of SARS-CoV-2 RNA on public surfaces in a densely populated urban area of Brazil Importance: The COVID-19 pandemic has resulted in more than 3.5 million cases and 245 thousand deaths worldwide as of May 6, 2020. Determining the extent of the presence of the virus on public surfaces is critical for understanding the potential risk of infection in these areas. Objective: To evaluate the presence of SARS-CoV-2 RNA on public surfaces in a densely populated urban area in Brazil. Design and Setting: A total of 101 samples were collected from different surfaces in public places in the region of Belo Horizonte with the highest number of COVID-19 cases. Samples were collected near the hospital and public transportation areas using sterile swabs, and then submitted to nucleic acid extraction and genomic detection and quantification by one-step qPCR. Results: Seventeen of the 101 samples tested positive (16.8%) for SARS-CoV-2 RNA, including samples from bus stations/terminals, public squares, and sidewalks, including those near hospitals. Conclusions and Relevance: Our data indicated the contamination of public surfaces by SARS-CoV-2, especially near hospital areas, highlighting the risk of infection for the population. Constant monitoring of the virus in urban areas is required as a strategy to fight the pandemic and prevent further infections.

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: High-touch surfaces: microbial neighbours at hand Despite considerable efforts, healthcare-associated infections (HAIs) continue to be globally responsible for serious morbidity, increased costs and prolonged length of stay. Among potentially preventable sources of microbial pathogens causing HAIs, patient care items and environmental surfaces frequently touched play an important role in the chain of transmission. Microorganisms contaminating such high-touch surfaces include Gram-positive and Gram-negative bacteria, viruses, yeasts and parasites, with improved cleaning and disinfection effectively decreasing the rate of HAIs. Manual and automated surface cleaning strategies used in the control of infectious outbreaks are discussed and current trends concerning the prevention of contamination by the use of antimicrobial surfaces are taken into consideration in this manuscript.

positive: Respiratory Viruses Abstract This article is an overview of the most clinically important respiratory viruses including the recently emerged highly pathogenic coronaviruses and other viruses that are transmitted via the respiratory tract. In this article, we highlight a description of the agent, its life cycle, epidemiology, pathogenesis, clinical features, diagnosis and management of the infection. The viruses in this article are respiratory syncytial virus, parainfluenza virus, human metapneumovirus, rhinovirus, seasonal and emerging coronaviruses, adenovirus, bocavirus and other viruses associated with the respiratory tract for their life cycle.

positive: The COVID-19 pandemic: considerations for the waste and wastewater services sector Abstract This article discusses the potential ramifications of the COVID-19 pandemic on waste and wastewater services, focusing on critical points where alternative operating procedures or additional mitigation measures may be advisable. Key concerns are (i) the long half-life of the virus on materials such as waste containers, bags, and in wastewater, and (ii) possible transmission via contaminated waste surfaces and aerosols from wastewater systems. There are opportunities to further the science of wastewater-based epidemiology by monitoring viral RNA in wastewater to assess disease prevalence and spread in defined populations, which may prove beneficial for informing COVID-19 related public health policy.

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: Environmental contamination by SARS-CoV-2 of an imported case during incubation period We collected environmental surface samples prior to and after disinfection of a quarantine room to evaluate the stability of SARS-CoV-2 during the incubation period of an imported case traveling to Qingdao, China. Overall, 11 of 23 (47.8%) of the first batch of environmental surface samples (within 4 h after case confirmation) were tested positive for SARS-CoV-2. Whereas only 2 of 23 (8.7%) of the second batch of environmental samples (after first disinfection) were tested positive for SARS-CoV-2. The majority of samples from the bedroom (70%) were positive for SARS-CoV-2, followed by 50% of samples from the bathroom and that of 33% from the corridor. The inner walls of toilet bowl and sewer inlet were the most contaminated sites with the highest viral loads. SARS-CoV-2 was widely distributed on object surfaces in a quarantine room of a later diagnosed COVID-19 case during the incubation period. Proper disinfection is crucial to minimize community transmission of this highly contagious virus.

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: Strengthening ICU health security for a coronavirus epidemic

positive: The severe acute respiratory syndrome (SARS) The world was shocked in early 2003 when a pandemic of severe acute respiratory syndrome (SARS) was imminent. The outbreak of this novel disease, caused by a novel coronavirus (the SARS-coronavirus), hit hardest in the Asian Pacific region, though eventually it spread to five continents. The speed of the spread of the SARS epidemic was unprecedented due to the highly efficient intercontinental transportation. An international collaborative effort through the World Health Organization (WHO) has helped to identify the aetiological agent about 1 month after the onset of the epidemic. The power of molecular biology and bioinformatics has enabled the complete decoding of the viral genome within weeks. Over 1000 publications on the phylogeny, epidemiology, genomics, laboratory diagnostics, antiviral, immunization, pathogenesis, clinical disease, and management accumulated within just 1 year. Although the exact animal reservoir of virus and how it evolved into a human pathogen are still obscure, accurate diagnosis and epidemiological control of the disease are now possible. This article reviews what is currently known about the virus and the disease.

positive: PrivyTRAC: Privacy and Security Preserving Contact Tracing System Smartphone location-based methods have been proposed and implemented as an effective alternative to traditional labor intensive contact tracing methods. However, there are serious privacy and security concerns that may impede wide-spread adoption in many societies. Furthermore, these methods rely solely on proximity to patients, based on Bluetooth or GPS signal for example, ignoring lingering effects of virus, including COVID-19, present in the environment. This results in inaccurate risk assessment and incomplete contact tracing. A new system concept, called PrivyTRAC, preserves user privacy, increases security and improves accuracy of smartphone contact tracing. PrivyTRAC enhances users' and patients' privacy by letting users conduct self-evaluation based on the risk maps download to their smartphones. No user information is transmitted to external locations or devices, and no personally identifiable patient information is embedded in the risk maps as they are processed anonymized and aggregated locations of confirmed patients. The risk maps consider both spatial proximity and temporal effects to improve the accuracy of the infection risk estimation. Experiments conducted in the paper illustrate improvement of PrivyTRAC over proximity based methods in terms of true and false positives. An approach to further improve infection risk estimation by incorporating both positive and negative local test results from contacts of confirmed cases is also described.

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: 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.

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: 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: Clinical characteristics of 2019 novel coronavirus infection in China Background: Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods: We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29th, 2020. Results: The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P<0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions: The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.

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: Minimization of spreading of SARS-CoV-2 via household waste produced by subjects affected by COVID-19 or in quarantine Currently available evidence supports that the predominant route of human-to-human transmission of the SARS-CoV-2 is through respiratory droplets. Indirect hands contact with surfaces contaminated by infectious droplets subsequently touching the mouth, nose or eyes seems to be another route of an indirect contact transmission. Persistence of the virus on different surfaces and other materials has been reported in recent studies: SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard. Viable virus was detected up to 72 h after application to different surfaces, although infectivity decay was also observed. This evidence suggests the likelihood that waste generated from patients affected by COVID-19 or subjects in quarantine treated in private houses or in areas different from hospitals and medical centres could be contaminated by SARS-CoV-2. Consequently, waste streams may represent a route for viral spreading being a potential risk also for the operators directly involved in the different phases of waste management. To address this concern, a specific multidisciplinary working group was settled by the Italian National Institute of Health (ISS) during the COVID-19 emergency, in order to establish guidelines related to solid waste collection, delivering, withdrawal, transport, treatment and disposal. Temporary stop of waste sorting, instructions for the population on how to package waste, instructions for Companies and operators for the adoption of adequate personal protection equipment (PPE), the use and sanitation of proper vehicles were among the main recommendations provided to the community by publications of freely downloadable reports and infographics in layman language. Incineration, sterilization and properly managed landfills were identified as the facilities to be preferentially adopted for the treatment of this kind of waste, considering the main inactivation strategies of SARS-CoV-2 (e.g. treatment length > 9 days and temperature > 70 °C for more than 5 min).

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: Environmental Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) from Medical Equipment in Long-Term Care Facilities undergoing COVID-19 Outbreaks We conducted environmental sampling at long-term care facilities to determine the extent of surface contamination with SARS-CoV-2 virus. Medical equipment used throughout the facility was determined to be contaminated.

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

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: 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: Saliva—Friend and Foe in the COVID-19 Outbreak The coronavirus disease 2019 (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global ongoing pandemic. Timely, accurate and non-invasive SARS-CoV-2 detection in both symptomatic and asymptomatic patients, as well as determination of their immune status, will facilitate effective large-scale pandemic control measures to prevent the spread of COVID-19. Saliva is a biofluid whose anatomical source and location is of particularly strategic relevance to COVID-19 transmission and monitoring. This review focuses on the role of saliva as both a foe (a common mode of viral transmission via salivary droplets and potentially aerosols) and a friend (as a non-invasive diagnostic tool for viral detection and immune status surveillance) in combating COVID-19.

positive: Concerns for activated breathing control (ABC) with breast cancer in the era of COVID-19: Maximizing infection control while minimizing heart dose

positive: Luminore CopperTouchâ¢ surface coating effectively inactivates SARS-CoV-2, Ebola and Marburg viruses in vitro We investigated the ability of Luminore CopperTouch copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, we compared viral titers in Vero cells from viral droplets exposed to copper surfaces for 30 min. The copper and copper-nickel surfaces inactivated 99.9% of the viral titer of both Ebola and Marburg viruses. The copper surfaces also inactivated 99% of SARS-CoV-2 titers in 2 hours to close to the limit of detection. These data add Ebolavirus, Marburgvirus, and SARS-CoV-2 (COVID-19) to the list of pathogens that can be inactivated by exposure to copper ions, validating Luminore CopperTouch technology (currently the only Environmental Protection Agency [EPA]-registered cold spray antimicrobial surface technology) as an efficacious, cost-friendly tool to improve infection control in hospitals, long-term care facilities, schools, hotels, buses, trains, airports, and other highly trafficked areas.

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: 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.

positive: Hand touches on the surfaces of a healthcare waiting area

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: 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: Persistance du SARS-CoV-2 infectieux sur les surfaces inertes et transmission par les mains./ Persistence of infectious SARS-CoV-2 on inert surfaces and hand-mediated transmission

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: COVID-19: Special Precautions in Ophthalmic Practice and FAQs on Personal Protection and Mask Selection The Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory coronavirus-2, was first reported in December 2019. The World Health Organization declared COVID-19 a pandemic on March 11, 2020 and as of April 17, 2020, 210 countries are affected with >2,000,000 infected and 140,000 deaths. The estimated case fatality rate is around 6.7%. We need to step up our infection control measures immediately or else it may be too late to contain or control the spread of COVID-19. In case of local outbreaks, the risk of infection to healthcare workers and patients is high. Ophthalmic practice carries some unique risks and therefore high vigilance and special precautions are needed. We share our protocols and experiences in the prevention of infection in the current COVID-19 outbreak and the previous severe acute respiratory syndrome epidemic in Hong Kong. We also endeavor to answer the key frequently asked questions in areas of the coronaviruses, COVID-19, disease transmission, personal protection, mask selection, and special measures in ophthalmic practices. COVID-19 is highly infectious and could be life-threatening. Using our protocol and measures, we have achieved zero infection in our ophthalmic practices in Hong Kong and China. Preventing spread of COVID-19 is possible and achievable.

positive: Lung cancer management challenges amidst COVID-19 pandemic: hope lives here

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: Infection control in non‐clinical areas during the COVID‐19 pandemic Large numbers of healthcare workers have acquired coronavirus disease (COVID-19) in the workplace [1]. SARS-CoV-2 is easily transmissible as each person with COVID-19 infects approximately 2.2 close contacts, and asymptomatic transmission has been reported [2,3]. SARS-CoV-2 survives in aerosols and on surfaces from hours to days, respectively [4]. Therefore, we believe non-clinical areas are potentially high-risk for transmission between healthcare workers, and often neglected by infection prevention and control protocols. To alert others to this risk and how it may be reduced, we describe our non-clinical workplace infection prevention and control measures that have been modified from those originally developed during the 2003 severe acute respiratory syndrome epidemic [5].

positive: COVID-19 Outbreak: An Overview on Dentistry Coronavirus disease 2019, also called COVID-19, is the latest infectious disease to rapidly develop worldwide [...].

positive: An Evaluation of Cleaning Practices at a Teaching Hospital BACKGROUND: The COVID-19 outbreak has highlighted the role of hospital-acquired infections in spreading epidemics. Adequately cleaning surfaces in patient rooms is an essential part of this fight to reduce the spread. Traditional audits, however, are insufficient. This study assesses surface cleaning practices using UV marker technology and the extent to which this technology can help improve cleaning audits and practices. METHODS: 144 audits (1,235 surfaces) were retrieved. UV marker cleaning audits conducted at a major teaching hospital in 2018 after implementing a new cleaning protocol. In addition, semi-structured interviews were conducted with cleaning staff and supervisors. RESULTS: On average, 63% of surfaces were appropriately cleaned. Toilet handles (80%) and toilet seats underside (83%) scored highest while main room sink fixtures (54%), light switch (55%) and bedrails (56%) scored lowest. Training, staffing and time constraints may play a role in low cleaning rates. DISCUSSION: The high-touch patient surfaces in the bedroom remain neglected and a potential source of infections. UV marker audits provided an objective measure of cleaning practices that managers and staff were unaware of. CONCLUSION: UV markers audits can play a key role in revealing deficiencies in cleaning practices and help in raising awareness of these deficiencies and improving cleaning practices.

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: 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: 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: Safety during crisis: Rapid on‐site evaluation at the time of COVID‐19 pandemic The COVID‐19 pandemic is posing a worldwide challenge to control and contain. SARS‐CoV‐2 is a highly infectious virus. Health care providers at the front lines are at high risk of getting the infection and the risk applies also to laboratory personnel as they deal with specimens that might be contaminated with infectious materiel. Cytopathology teams specifically are at high risk of dealing with contaminated material because of patients encounter during fine‐needle aspiration biopsies or Rapid On‐Site Evaluation (ROSE) for adequacy. In our article, we discuss alternative safer staining methods to the widely used Diff–Quick stain that can be utilized for ROSE to decrease the risk of viral exposure during the current COVID‐19 pandemic.

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: 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: 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: 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.

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: Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children.

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: 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: 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: Response to Letters to the Editor about the Safe Handling of Containers of Expressed Human Milk in all Settings During the SARS-CoV-2 (COVID-19) Pandemic.

positive: 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.

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: Hygiene at home: A bulwark against COVID-19 to be protect from SARS-CoV-2

positive: SARS-CoV-2 RNA detection of hospital isolation wards hygiene monitoring during the Coronavirus Disease 2019 outbreak in a Chinese hospital OBJECTIVES: The aim of this paper was to monitor the presence of SARS-Cov-2 among hospital environment surfaces, sewage, and personal protective equipment (PPE) of staffs in isolation wards in the First Affiliated Hospital of Zhejiang University, China. METHODS: Surfaces of objects were routinely wiped with 1000mg/L chlorine containing disinfectant. Air and sewage disinfection was proceeded routinely and strictly. Hospital environmental surfaces and PPE of staffs in isolation wards were sampled using swabs. The sewage from various inlet and outlets were sampled. The respiratory and stool specimens of patients were collected. The respiratory specimens of staffs in the isolation wards were also sampled once a week. Quantitative real-time reverse transcription PCR (qRT-PCR) methods were used to confirm the existence of SARS-Cov-2 RNA. Viral culture was done for the samples positive for SARS-Cov-2 RNA. RESULTS: During the study period, 33 laboratory-confirmed patients were hospitalized in isolation wards in the hospital. None of SARS-Cov-2 RNA was detected among the 36 objects surface samples and 9 staffs PPE samples in isolation wards. Though the 3 sewage samples from the inlet of preprocessing disinfection pool were positive for SARS-CoV-2 RNA and the sample from the outlet of preprocessing disinfection pool was weakly positive, the sewage sample from the outlet of the last disinfection pool was negative. All of the 5 sewage samples from various points were negative by viral culture of SARS-Cov-2. None of the respiratory specimens of staffs in the isolation wards were positive. CONCLUSIONS: Though SARS-Cov-2 RNA of the sewage samples were positive from inlets of the sewage disinfection pool and negative from the outlet of the last sewage disinfection pool, no viable virus was detected by culture. The monitoring data in this study suggested that the strict disinfection and hand hygiene could decrease the hospital-associated COVID-19 infection risk of the staffs in isolation wards.

positive: Modeling the Stability of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on Skin, Currency, and Clothing A new coronavirus (SARS-CoV-2) emerged in the winter of 2019 in Wuhan, China, and rapidly spread around the world. The extent and efficiency of SARS-CoV-2 pandemic is far greater than previous coronaviruses that emerged in the 21st Century. Here, we modeled stability of SARS-CoV-2 on skin, paper currency, and clothing to determine if these surfaces may factor in the fomite transmission dynamics of SARS-CoV-2. Skin, currency, and clothing samples were exposed to SARS-CoV-2 under laboratory conditions and incubated at three different temperatures (4C, 22C, and 37C). Stability was evaluated at 0 hours (h), 4 h, 8 h, 24 h, 72 h, 96 h, 7 days, and 14 days post-exposure. SARS-CoV-2 was shown to be stable on skin through the duration of the experiment at 4C (14 days). Virus remained stable on skin for at least 96 h at 22C and for at least 8h at 37C. There were minimal differences between the tested currency samples. The virus remained stable on the $1 U.S.A. Bank Note for at least 96 h at 4C while viable virus was not detected on the $20 U.S.A. Bank Note samples beyond 72 h. The virus remained stable on both Bank Notes for at least 8 h at 22C and 4 h at 37C. Clothing samples were similar in stability to the currency with the virus being detected for at least 96 h at 4C and at least 4 h at 22C. No viable virus was detected on clothing samples at 37C after initial exposure. This study confirms the inverse relationship between virus stability and temperature. Furthermore, virus stability on skin demonstrates the need for continued hand hygiene practices to minimize fomite transmission both in the general population as well as workplaces where close contact is common.

positive: Precautions and recommendations for orthodontic settings during the COVID-19 outbreak: A review Abstract Introduction Coronavirus disease 2019 (COVID-19) is contagious disease caused by the SARS-CoV-2 virus. It emerged as a global pandemic early in 2020, affecting more than 2000 countries and territories. The infection is highly contagious with disease transmission reported from asymptomatic carriers, including children. It spreads through person-to-person contact, via aerosol and droplets. The practice of social distancing – maintaining a distance of 1 – 2 meters or 6 feet -- between people has been widely recommended to slow or halt the spread. This places orthodontists at high risk of acquiring and transmitting the infection. The objective of this review is to report to orthodontists on the emergence, epidemiology, risks, and precautions during disease crisis. This should help increase awareness, reinforce infection control and prevent cross-transmission within the orthodontic facility. Methods A comprehensive literature review of English and non-English articles was performed in March, 2020 using (CORD-19 2020) dataset, PubMed, MEDLINE, Scopus, and Google Scholar to search for infection control and disease transmission in orthodontics. Results This review emphasizes minimizing aerosol production and reinforcing strict infection control measures. Compliance with highest level of personal protection and restriction of treatment to emergency cases is recommended during the outbreak. Surface disinfection, adequate ventilation, and decontamination of instruments and supplies following the guidelines is required. Conclusion Reinforcing strict infection control measures and minimizing personal contact and aerosol production are keys to prevent contamination within the orthodontic settings. Although no cases of COVID-19 cross-transmission within a dental facility have been reported, the risk exists and the disease is still emerging. Further studies are required.

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: 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: Environmental sampling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during a coronavirus disease (COVID-19) outbreak aboard a commercial cruise ship Background A COVID-19 outbreak occurred in a cruise ship with 3711 passengers and crew in 2020. This study is to test the hypothesis that environmental surfaces played important roles in transmission for SARS-CoV-2 during this outbreak. Methods We sampled environmental surfaces including air from common areas in the cruise ship and cabins in which confirmed COVID-19 cases and non-cases had stayed after they left the cabins. We tested the samples for SARS-CoV-2 by rt-PCR and conducted viral isolation. Findings Of 601 samples tested, SARS-CoV-2 RNA was detected from 58 samples (10%) from case-cabins from which they left 1-17 days before sampling, but not from non-case-cabins. Except for one sample from an air hood in a corridor, SARS-CoV-2 RNA was not detected from samples in common areas. SARS-CoV-2 RNA was not detected from all 14 air samples. RNA was most often detected on the floor around toilet in the bathroom (39%, 13/33, cycle quantification (Cq): 26.21-37.62) and bed pillow (34%, 11/32, Cq: 34.61-38.99). There was no difference in the detection proportion between cabins for symptomatic (15%, 28/189, Cq: 29.79-38.86) and asymptomatic cases (21%, 28/131, Cq: 26.21-38.99). No SARS-CoV-2 virus was isolated from any of the samples. Interpretation The environment around the COVID-19 cases was extensively contaminated from SARS-CoV-2 during COVID-19 outbreak in the cruise ship. Transmission risk of SARS-CoV-2 from symptomatic and asymptomatic patients seems to be similar and the environmental surface could involve viral transmission through direct contact.

positive: Homegrown Ultraviolet Germicidal Irradiation for Hospital-Based N95 Decontamination during the COVID-19 Pandemic Coronavirus disease (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is responsible for the 2020 global pandemic and characterized by high transmissibility and morbidity. Healthcare workers (HCWs) are at risk of contracting COVID-19, and this risk is mitigated through the use of personal protective equipment such as N95 Filtering Facepiece Respirators (FFRs). The high demand for FFRs is not currently met by global supply chains, potentially placing HCWs at increased exposure risk. Effective FFR decontamination modalities exist, which could maintain respiratory protection for HCWs in the midst of the current pandemic, through the decontamination and re-use of FFRs. Here, we present a locally-implemented ultraviolet-C germicidal irradiation (UVGI)-based FFR decontamination pathway, utilizing a home-built UVGI array assembled entirely with previously existing components available at our institution. We provide recommendations on the construction of similar systems, as well as guidance and strategies towards successful institutional implementation of FFR decontamination.

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: 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.

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.

positive: Coronaviruses in wastewater processes: source, fate and potential risks Abstract The last 17 years have seen three major outbreaks caused by coronaviruses, with the latest outbreak, COVID-19, declared a pandemic by the World Health Organization. The frequency of these outbreaks, their mortality and associated disruption to normal life calls for concerted efforts to understand their occurrence and fate in different environments. There is an increased interest in the occurrence of coronaviruses in wastewater from the perspective of wastewater-based epidemiology. However, there is no comprehensive review of the knowledge on coronavirus occurrence, fate and potential transmission in wastewater. This paper, provides a review of the literature on the occurrence of coronaviruses in wastewater treatment processes. We discuss the presence of viral RNA in feces as a result of gastrointestinal infections resulting in diarrhoea. We also review the literature on their presence, survival and potential removal in common wastewater treatment processes. The detection of infectious viral particles in feces of patients raises questions on the potential risks of infection for people exposed to untreated sewage/wastewater. We, therefore, discuss the potential risk of infection with coronaviruses for workers in wastewater treatment plants and the public that may be exposed through faulty plumbing or burst sewer networks. The disruption of life and mortalities warrants a much more focused research on the role of environments, such as wastewater and surface water, in disease transmission. The current wealth of knowledge on coronaviruses in wastewater based on the reviewed literature is scant and therefore calls for further studies.

negative: Prevalence and genetic diversity analysis of human coronaviruses among cross-border children BACKGROUND: More than a decade after the outbreak of human coronaviruses (HCoVs) SARS in Guangdong province and Hong Kong SAR of China in 2002, there is still no reoccurrence, but the evolution and recombination of the coronaviruses in this region are still unknown. Therefore, surveillance on the prevalence and the virus variation of HCoVs circulation in this region is conducted. METHODS: A total of 3298 nasopharyngeal swabs samples were collected from cross-border children (<6 years, crossing border between Southern China and Hong Kong SAR) showing symptoms of respiratory tract infection, such as fever (body temperature > 37.5 °C), from 2014 May to 2015 Dec. Viral nucleic acids were analyzed and sequenced to study the prevalence and genetic diversity of the four human coronaviruses. The statistical significance of the data was evaluated with Fisher chi-square test. RESULTS: 78 (2.37%; 95%CI 1.8-2.8%) out of 3298 nasopharyngeal swabs specimens were found to be positive for OC43 (36;1.09%), HKU1 (34; 1.03%), NL63 (6; 0.18%) and 229E (2;0.01%). None of SARS or MERS was detected. The HCoVs predominant circulating season was in transition of winter to spring, especially January and February and NL63 detected only in summer and fall. Complex population with an abundant genetic diversity of coronaviruses was circulating and they shared homology with the published strains (99-100%). Besides, phylogenetic evolutionary analysis indicated that OC43 coronaviruses were clustered into three clades (B,D,E), HKU1 clustered into two clades(A,B) and NL63 clustered into two clades(A,B). Moreover, several novel mutations including nucleotides substitution and the insertion of spike of the glycoprotein on the viral surface were discovered. CONCLUSIONS: The detection rate and epidemic trend of coronaviruses were stable and no obvious fluctuations were found. The detected coronaviruses shared a conserved gene sequences in S and RdRp. However, mutants of the epidemic strains were detected, suggesting continuous monitoring of the human coronaviruses is in need among cross-border children, who are more likely to get infected and transmit the viruses across the border easily, in addition to the general public.

negative: Monophyletic Relationship between Severe Acute Respiratory Syndrome Coronavirus and Group 2 Coronaviruses Although primary genomic analysis has revealed that severe acute respiratory syndrome coronavirus (SARS CoV) is a new type of coronavirus, the different protein trees published in previous reports have provided no conclusive evidence indicating the phylogenetic position of SARS CoV. To clarify the phylogenetic relationship between SARS CoV and other coronaviruses, we compiled a large data set composed of 7 concatenated protein sequences and performed comprehensive analyses, using the maximum-likelihood, Bayesian-inference, and maximum-parsimony methods. All resulting phylogenetic trees displayed an identical topology and supported the hypothesis that the relationship between SARS CoV and group 2 CoVs is monophyletic. Relationships among all major groups were well resolved and were supported by all statistical analyses.

negative: Management of ophthalmic perioperative period during 2019 novel coronavirus disease outbreak/ 新型冠状病毒肺炎疫情下眼科患者围手术期管理实践 Objective: To explore the perioperative management and infection prevention methods for acute eye diseases during the outbreak of 2019 novel coronavirus disease (COVID-19). Methods: Since the COVID-19 was included in the Class B infectious diseases and was managed according to Class A infectious diseases in China, 127 patients who underwent ophthalmic surgery were enrolled in First Affiliated Hospital of Army Military Medical University from January 20 to February 19, 2020.The perioperative management according to the national epidemic prevention and control requirements was summarized, and the perioperative clinical management that should be taken during the epidemic prevention period were discussed. Results: One hundred and twenty-seven patients underwent ophthalmic surgeries, including emergency surgery, daytime surgery and other surgeries for sight-threatening diseases.The methods of anesthesia included general anesthesia, local anesthesia and ocular superficial anesthesia.According to the national epidemic prevention and control requirements, epidemic screening for these patients and infectious managing measures were performed during the perioperative period, including the sterilization of relevant environment and equipments, the personal medical prevention and protection for medical staffs and patients, which made sure all the operations went smoothly and safely.There were no 2019-nCoV infection, surgical-relative infection, crossing infection and operation-related complications occurred.Meanwhile, there were not COVID-19-related infection events of medical staffs.The air sampling compliance rate in the operating room, ward, examination room and other areas was 100%. Conclusions: During the prevention and control period of the epidemic of COVID-19, strict adherence to the prevention and control measures can effectively ensure the smooth implementation of the operation and the perioperative safety of medical staff and patients.

negative: Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models. Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.

negative: Evaluation of the clinical characteristics of suspected or confirmed cases of COVID-19 during home care with isolation: A new retrospective analysis based on O2O Summary Background The recent outbreak of the novel coronavirus in December 2019 (COVID-19) has activated top-level response nationwide. We developed a new treatment model based on the online-to-offline (O2O) model for the home isolated patients, because in the early stages the medical staff were insufficient to cope with so many patients. Methods In this single-centered, retrospective study, we enrolled 48 confirmed/suspected COVID-19 patients who underwent home isolation in Wuhan between January 6 and January 31, 2020. By WeChat and online document editing all patients were treated with medical observation scale. The clinical indications such as Fever, Muscle soreness, Dyspnea and Lack of strength were collected with this system led by medical staff in management, medicine, nursing, rehabilitation and psychology. Findings The mean(SD) age of 48 patients was 39.08(13.88) years, 35(72.9%) were women. Compared with non-hospitalized patients, inpatients were older(≥8805;70years, 2.4% vs 33.3%, P<0.04). All inpatients had fever, 50% inpatients had coughs and showed infiltration in both lungs at the time of diagnosis. 33.3% inpatients exhibited negative changes in their CT results at initial diagnosis. The body temperature of non-hospitalized patients with mild symptoms returned to normal by day 4-5. While dyspnea peaked on day 6 for non-hospitalized patients with mild symptoms, it persisted in hospitalized patients and exacerbated over time. The lack of strength and muscle soreness were both back to normal by day 4 for non-hospitalized patients. Interpretation Monitoring the trends of symptoms is more important for identifying severe cases. Excessive laboratory data and physical examination are not necessary for the evaluation of patients with mild symptoms. The system we developed is the first to convert the subjective symptoms of patients into objective scores. This type of O2O, subjective-to-objective strategy may be used in regions with similar highly infectious diseases to minimize the possibility of infection among medical staff.

negative: Evolution of Viruses The study of virus evolution has historically been concerned with disease and its emergence and has not been integrated into the general study of evolution. Yet viruses dominate our planet and their evolution is a broad and applied field that can be studied in the real time (such HIV in human disease) and can also be applied to biotechnological problems. Virus evolution is very similar, but not identical, to host evolution. Darwinian principles apply, such as with Fisher population genetics, but other features, such as reticulated and quasispecies-based evolution, distinguish virus evolution. In RNA viruses, high error rates have led to the quasispecies concept in which collective populations are the basis of evolution. These populations provide viruses with high capacities for adaptation. Yet some RNA viruses show remarkable evolutionary stability. With DNA viruses, especially of bacteria, extensive recombination defines vast dynamic and ancient genetic pools. Temperate viruses can directly affect host gene pools by stable colonization. DNA viruses can be genetically complex and have evolved many unique viral genes. The retroviruses show both quasispecies-based rapid evolution and host-linked slow coevolution (e.g., endogenous retroviruses). Thus, virus evolution impacts all life and viral emergence continues to threaten human health.

negative: Italian pediatric respiratory society recommendations on pediatric pulmonary function testing during COVID-19 pandemic BACKGROUND: Effective prevention and control strategies are mandatory to prevent SARS-CoV-2 infection. MAIN TEXT: The Italian Pediatric Respiratory Society promotes a series of new recommendations that should be followed in pulmonary function testing laboratories during the COVID-19 pandemic. CONCLUSION: Pulmonary function testing should be performed in children with chronic lung disease only if it is needed to guide management and limited to the necessary tests, namely spirometry. When performed, strict infection control measures should be followed due to the potential risk of transmitting SARS-CoV-2.

negative: Dermatological procedures amidst Covid‐19: when and how to resume The pandemic of covid‐19 has captivated more than 3 Million people across the globe affecting the dermatology practice as well. Due to the novel nature of the virus and concomitant lack of research, standard guidelines have not been set in place regarding the procedures. Currently, due to fear and spread of coronavirus aesthetic practice has taken a seat back. Dermatologic surgeon/aesthetician have to be prepared for the forthcoming alterations in the practice and adjust to the necessary precautionary methods. This articles aims to prepare dermatologist for the upcoming difficulties and precautions to be taken for conducting procedures in amidst of coronavirus. This article is protected by copyright. All rights reserved.

negative: Recombinant Tula hantavirus shows reduced fitness but is able to survive in the presence of a parental virus: analysis of consecutive passages in a cell culture Tula hantavirus carrying recombinant S RNA segment (recTULV) grew in a cell culture to the same titers as the original cell adapted variant but presented no real match to the parental virus. Our data showed that the lower competitiveness of recTULV could not be increased by pre-passaging in the cell culture. Nevertheless, the recombinant virus was able to survive in the presence of the parental virus during five consecutive passages. The observed survival time seems to be sufficient for transmission of newly formed recombinant hantaviruses in nature.

negative: Entry and release of transmissible gastroenteritis coronavirus are restricted to apical surfaces of polarized epithelial cells. The transmissible gastroenteritis coronavirus (TGEV) infects the epithelial cells of the intestinal tract of pigs, resulting in a high mortality rate in piglets. This study shows the interaction of TGEV with a porcine epithelial cell line. To determine the site of viral entry, LLC-PK1 cells were grown on permeable filter supports and infected with TGEV from the apical or basolateral side. Initially after plating, the virus was found to enter the cells from both sides. During further development of cell polarity, however, the entry became restricted to the apical membrane. Viral entry could be blocked by a monoclonal antibody to the viral receptor aminopeptidase N. Confocal laser scanning microscopy showed that this receptor protein was present at both the apical and basolateral plasma membrane domains just after plating of the cells but that it became restricted to the apical plasma membrane during culture. To establish the site of viral release, the viral content of the apical and basolateral media of apically infected LLC-PK1 cells was measured by determining the amount of radioactively labelled viral proteins and infectious viral particles. We found that TGEV was preferentially released from the apical plasma membrane. This conclusion was confirmed by electron microscopy, which demonstrated that newly synthesized viral particles attached to the apical membrane. The results support the idea that the rapid lateral spread of TGEV infection over the intestinal epithelia occurs by the preferential release of virus from infected epithelial cells into the gut lumen followed by efficient infection of nearby cells through the apical domain.

negative: The capacity of goat epidermal adult stem cells to reconstruct the damaged ocular surface of total LSCD and activate corneal genetic programs. Epidermal adult stem cells (EpiASCs) have the potential for unlimited proliferation and differentiation, however, the ability of these stem cells to activate corneal genetic programs in response to corneal stroma stimulation needs to be further validated. Herein, a feasible strategy was developed to reconstruct the damaged corneal surface in a goat model with total limbal stem cell deficiency (LSCD) by transplanting EpiASCs, which had been explanted and cultured from the skin of an adult ram goat and were then purified by selecting single cell-derived clones and cultivating them on a denuded human amniotic membrane (HAM). These artificial tissues were then successfully transplanted into ewe goats with total LSCD. Binding of EpiASCs to the base membrane of an EpiASCs-HAM-Sheet (EHS) indicated their proliferating status. After transplantation, the EpiASCs could survive in the host tissue and they reconstructed the damaged ocular surface of total LSCD. The crystal reconstructed corneal epithelium expressed CK3 and Pax-6 similar to normal corneal epithelium and expressed the Sry gene after transplantation. These results demonstrated that EpiASCs could be induced to differentiate into corneal epithelial cell types in a corneal microenvironment and had the ability to activate corneal genetic programs. This work offer a foundation for promoting tissue-engineered cornea into clinical application.

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

negative: Hospital outbreak of Middle East respiratory syndrome coronavirus. BACKGROUND In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections. METHODS Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. RESULTS Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). CONCLUSIONS Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.

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: Chapter 12 Coronaviridae Publisher Summary Coronaviruses are spherical, lipid-containing, enveloped particles with tear-dropshaped surface projections or peplomers. The genome is one molecule of ssRNA and the virions characteristically contain three major structural protein classes. The antigenic relationships of coronaviruses present a complex pattern. The geographic distribution of many coronaviruses is worldwide. Biological vectors of coronaviruses have not been reported, and the natural hosts form the major reservoirs for further infection. Coronavirus particles contain three major protein classes, within which the polypeptides vary in number and molecular weight between species. The apparent size and shapes of coronaviruses can vary considerably. Coronavirus particles are spherical, although negatively stained air-dried particles are often pleomorphic. The morphology of coronavirus surface projections can vary considerably between different strains. The conventional structure on negative staining consists of tear-drop-shaped projections, although cone-shaped projections are also observed. In all these cases, the projections have the same length of about 20 nm. Other coronaviruses have short as well as 20-nm projections. Projections with blebs on thin stalks have been reported for other coronaviruses.

negative: Response to Letters to the Editor about the Safe Handling of Containers of Expressed Human Milk in all Settings During the SARS-CoV-2 (COVID-19) Pandemic

negative: Commentary on: The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? A One Health approach to coronaviruses

negative: An emerging cyberinfrastructure for biodefense pathogen and pathogen–host data The NIAID-funded Biodefense Proteomics Resource Center (RC) provides storage, dissemination, visualization and analysis capabilities for the experimental data deposited by seven Proteomics Research Centers (PRCs). The data and its publication is to support researchers working to discover candidates for the next generation of vaccines, therapeutics and diagnostics against NIAID's Category A, B and C priority pathogens. The data includes transcriptional profiles, protein profiles, protein structural data and host–pathogen protein interactions, in the context of the pathogen life cycle in vivo and in vitro. The database has stored and supported host or pathogen data derived from Bacillus, Brucella, Cryptosporidium, Salmonella, SARS, Toxoplasma, Vibrio and Yersinia, human tissue libraries, and mouse macrophages. These publicly available data cover diverse data types such as mass spectrometry, yeast two-hybrid (Y2H), gene expression profiles, X-ray and NMR determined protein structures and protein expression clones. The growing database covers over 23 000 unique genes/proteins from different experiments and organisms. All of the genes/proteins are annotated and integrated across experiments using UniProt Knowledgebase (UniProtKB) accession numbers. The web-interface for the database enables searching, querying and downloading at the level of experiment, group and individual gene(s)/protein(s) via UniProtKB accession numbers or protein function keywords. The system is accessible at http://www.proteomicsresource.org/.

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: Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI.

negative: Interleukin-6 blockade for severe COVID-19 In the context of COVID-19 pandemic and growing tensions worldwide regarding healthcare facilities, there is an urgent need for effective treatments likely to reduce the crunch of ICU beds. Following the assumption by Mehta and colleagues who exhorted physicians to screen patients with severe COVID-19 for hyperinflammation and investigate immunomodulatory drugs in this setting, we relate our short-term - yet promising - experience regarding IL6 blockade with tocilizumab in 30 selected patients of less than 80 years of age, >5 days of prior disease duration, severe (i.e. requiring strictly over 6L/min of oxygen therapy) rapidly deteriorating (i.e. increase by more than 3L/min of oxygen flow within the previous 12 hours) COVID-19-related pneumonia. By comparison with a control group of patients (matched for age, gender and disease severity using the inverse probability of treatment weighted methodology) that did not receive tocilizumab. We demonstrate that, in highly selected patients, IL6 blockade could curb the "cytokine storm", prevent ICU admission and the requirement for mechanical ventilation. Notwithstanding the shortcomings of this retrospective small sample-size study, we believe that these preliminary findings support the fostering of research efforts in the fight against COVID-19-induced inflammation, especially before patients require admission to the ICU.

negative: Whole-Genome Sequence of Human Rhinovirus C47, Isolated from an Adult Respiratory Illness Outbreak in Butte County, California, 2017 Here, we report the full coding sequence of rhinovirus C47 (RV-C47), obtained from a patient respiratory sample collected during an acute respiratory illness investigation in Butte County, California, in January 2017. This is the first whole-genome sequence of RV-C47 to be reported.

negative: Living with the enemy or uninvited guests: Functional genomics approaches to investigating host resistance or tolerance traits to a protozoan parasite, Theileria annulata, in cattle Abstract Many breeds of cattle with long histories of living in areas of endemic disease have evolved mechanisms that enable them to co-exist with specific pathogens. Understanding the genes that control tolerance and resistance could provide new strategies to improve the health and welfare of livestock. Around one sixth of the world cattle population is estimated to be at risk from one of the most debilitating tick-borne diseases of cattle, caused by the protozoan parasite, Theileria annulata. The parasite mainly infects cells of the myeloid lineage which are also the main producers of inflammatory cytokines. If an infectious or inflammatory insult is sufficiently great, inflammatory cytokines produced by macrophages enter the circulation and induce an acute phase proteins (APP) response. The Bos taurus Holstein breed produces higher and more prolonged levels of inflammatory cytokine induced APP than the Bos indicus Sahiwal breed in response to experimental infection with T. annulata. The Sahiwal exhibits significantly less pathology and survives infection, unlike the Holstein breed. Therefore, we hypothesised that the causal genes were likely to be expressed in macrophages and control the production of inflammatory cytokines. A functional genomics approach revealed that the transcriptome profile of the B. taurus macrophages was more associated with an inflammatory programme than the B. indicus macrophages. In particular the most differentially expressed gene was a member of the signal regulatory protein (SIRP) family. These are mainly expressed on myeloid cell surfaces and control inflammatory responses. Other differentially expressed genes included bovine major histocompatibility complex (MHC) (BoLA) class II genes, particularly BoLA DQ, and transforming growth factor (TGF)B2. We are now exploring whether sequence and functional differences in the bovine SIRP family may underlie the resistance or tolerance to T. annulata between the breeds. Potentially, our research may also have more general implications for the control of inflammatory processes against other pathogens. Genes controlling the balance between pathology and protection may determine how livestock can survive in the face of infectious onslaught. Next generation sequencing and RNAi methodologies for livestock species will bring new opportunities to link diversity at the genome level to functional differences in health traits in livestock species.

negative: Diseases of the Liver and Hepatobiliary System

negative: 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.

negative: 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.

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: Trends and Prediction in Daily New Cases and Deaths of COVID-19 in the United States: An Internet Search-Interest Based Model BACKGROUND AND OBJECTIVES: The daily incidence and deaths of coronavirus disease 2019 (COVID-19) in the USA are poorly understood. Internet search interest was found to be correlated with COVID-19 daily incidence in China, but has not yet been applied to the USA. Therefore, we examined the association of internet search-interest with COVID-19 daily incidence and deaths in the USA. METHODS: We extracted COVID-19 daily new cases and deaths in the USA from two population-based datasets, namely 1-point-3-acres.com and the Johns Hopkins COVID-19 data repository. The internet search-interest of COVID-19-related terms was obtained using Google Trends. The Pearson correlation test and general linear model were used to examine correlations and predict trends, respectively. RESULTS: There were 636,282 new cases and,325 deaths of COVID-19 in the USA from March 1 to April 15, 2020, with a crude mortality of 4.45%. The daily new cases peaked at 35,098 cases on April 10, 2020 and the daily deaths peaked at 2,494 on April 15, 2020. The search interest of COVID, “COVID pneumonia” and “COVID heart” were correlated with COVID-19 daily incidence, with 12 or 14 days of delay (Pearson’s r = 0.978, 0.978 and 0.979, respectively) and deaths with 19 days of delay (Pearson’s r = 0.963, 0.958 and 0.970, respectively). The 7-day follow-up with prospectively collected data showed no significant correlations of the observed data with the predicted daily new cases or daily deaths, using search interest of COVID, COVID heart, and COVID pneumonia. CONCLUSIONS: Search terms related to COVID-19 are highly correlated with the COVID-19 daily new cases and deaths in the USA.

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: Three Emerging Coronaviruses in Two Decades: The Story of SARS, MERS, and Now COVID-19

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: Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers RNA viruses pose a threat to public health that is exacerbated by the dearth of antiviral therapeutics. The RNA-dependent RNA polymerase (RdRp) holds promise as a broad-spectrum, therapeutic target because of the conserved nature of the nucleotide-substrate-binding and catalytic sites. Conventional, quantitative, kinetic analysis of antiviral ribonucleotides monitors one or a few incorporation events. Here, we use a high-throughput magnetic tweezers platform to monitor the elongation dynamics of a prototypical RdRp over thousands of nucleotide-addition cycles in the absence and presence of a suite of nucleotide analog inhibitors. We observe multiple RdRp-RNA elongation complexes; only a subset of which are competent for analog utilization. Incorporation of a pyrazine-carboxamide nucleotide analog, T-1106, leads to RdRp backtracking. This analysis reveals a mechanism of action for this antiviral ribonucleotide that is corroborated by cellular studies. We propose that induced backtracking represents a distinct mechanistic class of antiviral ribonucleotides.

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: Crystal Structure of the C-Terminal Cytoplasmic Domain of Non-Structural Protein 4 from Mouse Hepatitis Virus A59 BACKGROUND: The replication of coronaviruses takes place on cytoplasmic double membrane vesicles (DMVs) originating in the endoplasmic reticulum (ER). Three trans-membrane non-structural proteins, nsp3, nsp4 and nsp6, are understood to be membrane anchors of the coronavirus replication complex. Nsp4 is localized to the ER membrane when expressed alone but is recruited into the replication complex in infected cells. It is revealed to contain four trans-membrane regions and its N- and C-termini are exposed to the cytosol. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structures of the C-terminal hydrophilic domain of nsp4 (nsp4C) from MHV strain A59 and a C425S site-directed mutant. The highly conserved 89 amino acid region from T408 to Q496 is shown to possess a new fold. The wild-type (WT) structure features two monomers linked by a Cys425-Cys425 disulfide bond in one asymmetric unit. The monomers are arranged with their N- and C-termini in opposite orientations to form an “open” conformation. Mutation of Cys425 to Ser did not affect the monomer structure, although the mutant dimer adopts strikingly different conformations by crystal packing, with the cross-linked C-termini and parallel N-termini of two monomers forming a “closed” conformation. The WT nsp4C exists as a dimer in solution and can dissociate easily into monomers in a reducing environment. CONCLUSIONS/SIGNIFICANCE: As nsp4C is exposed in the reducing cytosol, the monomer of nsp4C should be physiological. This structure may serve as a basis for further functional studies of nsp4.

negative: Escherichia coli heat-stable enterotoxin in feces and intestines of calves with diarrhea. Two experiments were conducted to evaluate detection of Escherichia coli heat-stable enterotoxin (ST) in the feces of calves as a method for implicating E coli in neonatal calf diarrhea. The first experiment evaluated the use of the infant mouse test for detection of ST in the feces of calves with naturally occurring diarrhea. Simultaneous identification of bovine enteropathogenic strains of E coli (EEC) and of other infective agents implicated in neonatal calf diarrhea was attempted in these samples. The ST was detected with certainty in only 7 of 41 samples from calves less than or equal to 3 weeks old. Enteropathogenic E coli, however, was detected in 27 samples. In 23 of these 27 samples, EEC was the only recognizable diarrheagenic agent. In a small percentage of the samples, Salmonella, rotavirus, coronavirus, and cryptosporidium were recognized alone, in combination with each other, or with EEC. In the second experiment, 6 calves were fed colostrum from cows inoculated with the bovine EEC strain B44; 6 were given colostrum from cows vaccinated with non-EEC strain 28F, and 4 were given milk from nonvaccinated heifers. Two of the calves that were given colostrum from cows inoculated with strain B44 were challenge exposed with the non-EEC strain 28F. The remaining calves were challenge exposed with the EEc strain B44. Fecal samples were taken from these calves at intervals and were examined for the presence of ST and of the challenge-exposure organism. The ST was detected in approximately one half of the fecal samples obtained, and it was most often detected in the early stages of the induced diarrhea. Calves were observed to shed the challenge-exposure EEC strain for long periods in the absence of diarrhea or detectable amounts of ST in the feces. The ST was detectable in fecal samples when the diarrhea was severe and when the dry matter content of the fecal samples was low.

negative: 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.

negative: Acute Management and Long-Term Survival Among Subjects With Severe Middle East Respiratory Syndrome Coronavirus Pneumonia and ARDS. BACKGROUND Data on the management, clinical course, and outcome of critical patients with Middle East Respiratory Syndrome coronavirus are scarce. We report here our experience and long-term outcome of such patients. METHODS Subjects intubated for management of ARDS from Middle East Respiratory Syndrome coronavirus pneumonia and ARDS during the April-May 2014 outbreak were included. Their characteristics, ICU course, management, and outcome were evaluated. RESULTS Fourteen subjects, including 3 health-care workers, met study criteria. Besides 2 health-care workers, all subjects had comorbidities. Predominant symptoms were fever, cough, and dyspnea. The worst median PaO2 /FIO2 ratio of 118 post-intubation was seen on the third day, and median APACHE II score was 27. All subjects received lung-protective ventilation and 1 mg/kg/d methylprednisolone infusion for ARDS. Eleven subjects received ribavirin and peginterferon α-2a. Subjects had a critical ICU course and required neuromuscular blockade (n = 11; 79%), required rescue therapy for respiratory failure (n = 8; 57%), developed shock (n = 10; 71%), and required renal replacement therapy (n = 8; 57%). Declining C-reactive protein levels correlated with clinical improvement despite continued positive real-time polymerase chain reaction results. Nine subjects died in ICU. Five subjects, including 3 health-care workers, were discharged from hospital and were alive after 1 y. CONCLUSIONS Middle East Respiratory Syndrome coronavirus pneumonia with ARDS has high mortality in subjects with comorbidities. The mainstay of treatment is meticulous ARDS management. Those who survived the acute infection and its complications remained well after 1 y in our study. The role of ribavirin and interferon warrants urgent further evaluation.

negative: Isolation and trypsin-enhanced propagation of turkey enteric (bluecomb) coronaviruses in a continuous human rectal adenocarcinoma cell line. Turkey enteric coronavirus (TCV) from intestinal contents of diarrheal poults was isolated and serially propagated in HRT-18 cells, an established cell line derived from a human rectal adenocarcinoma. In these cells, TCV induced cytopathic changes, including polykaryocytosis, which depended on trypsin in the medium and incubation at 41 C. Viral antigens could be demonstrated in the cytoplasm by immunofluorescence, and extracellular virus was detected by an ELISA and negative electron microscopy. The cell-free virus had characteristics of TCV: shape, surface projections, buoyant density of 1.18 to 1.20 g/ml in sucrose, and hemagglutination of rat RBC. The one-step growth curve was complete by postinoculation hours 14 to 16, and maximal titers reached 9 to 9.5 log10 TCID50/ml during 5 passages, after which the titer remained stable. Electron microscopic examination of infected cell monolayers revealed budding of typical coronavirus particles through intracytoplasmic membranes and accumulation of complete virus in cytoplasmic vesicles. Late in the infection, aggregated progeny vial particles were detected near the outer surface of infected cells. One-day-old turkey poults inoculated orally with tissue culture-adapted TCV isolates developed mild to severe diarrhea.

negative: Viruses Associated With Foodborne Infections Abstract Foodborne pathogens cause acute and chronic health outcomes of very different durations, severity and mortality, resulting in high costs and burdens to society. The issues of food safety and food poisoning are being increasingly emphasised, particularly in developed countries. Infection/contamination with many agents i.e., bacterial, parasitic and viral entities can result in foodborne illness. This article will focus mainly on viral agents of infection. A range of different viruses can cause food poisoning/foodborne infection, and infection can result in a myriad of symptoms, ranging from mild, acute disease to chronic, debilitating disease and even death. Due to the inherent differences between bacteria and viruses, namely the fact that viruses do not replicate in food, while bacteria do, viruses are frequently difficult to detect. This is compounded by the fact that many of the viruses associated with enteric disease do not replicate in cell culture. These factors can lead to a lag between reporting, detection and analysis of foodborne viruses versus bacterial agents. Despite these constraints, it is now evident that there are both well-established and emerging viruses implicated in foodborne infections, and the role of molecular detection and characterisation is becoming increasingly important.

negative: Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter? Abstract SARS-CoV-2 is a novel virus of the Coronaviridiae family that represents a major global health issue. Mechanisms implicated in virus/host cells interaction are central for cell infection and replication that in turn lead to disease onset and local damage. To enter airway and lung epithelia, SARS-CoV-2 attaches to ACE2 receptors by spike (S) glycoproteins. Molecular mechanisms that promote interaction between SARS-CoV-2 virus and host with particular focus on virus cell entry receptor ACE2 are described. We further explore the impact of underlying medical conditions and therapies including renin-angiotensin inhibitors on modulating ACE 2, which is the major SARS-CoV-2 cell entry receptor.

negative: El síndrome respiratorio agudo grave: primera pandemia del siglo XXI

negative: The Middle East Respiratory Syndrome (MERS) The Middle East respiratory syndrome (MERS) is a novel lethal zoonotic disease of humans caused by the MERS coronavirus (MERS-CoV). Although MERS is endemic to the Middle East, travelers have exported MERS-CoV on return to their home countries. Clinical manifestations range from mild to severe acute respiratory disease and death. The elderly, immunocompromised, and those with chronic comorbid liver, lung, and hepatic conditions have a high mortality rate. There is no specific treatment. Person-to-person spread causes hospital and household outbreaks, and thus improved compliance with internationally recommended infection control protocols and rapid implementation of infection control measures are required.

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: Chapter 6 The immunosuppressed traveler: infection risks with autoimmunity and immunosuppression, vaccinations, and general travel advice Abstract The travel-related infection risks in the significantly immunocompromised traveler are complex and comprise vaccine preventable, vector-borne, and other nonvaccine preventable infections. A thorough risk assessment should be performed before travel and advice sought from relevant specialists. Immunosuppression used to treat autoimmune diseases and their mechanisms of action need particular consideration.This risk assessment needs to take the patient's beliefs and preferences into account. It is also important not to neglect noninfectious travel considerations.

negative: Fixed-cell immunoperoxidase technique for the study of surface antigens induced by the coronavirus of transmissible gastroenteritis (TGEV) Abstract An immunoperoxidase technique performed on the TGEV-infected cells was developed for detection of virus-induced antigens. The presence of M antigen of TGEV on the surface of infected cells was demonstrated by this technique. This finding is in contrast to the M protein of murine hepatitis coronavirus which migrates to the Golgi apparatus but is not transported to the plasma membrane. The time course of appearance M and S antigens on the surface of TGEV-infected cell can be studied by this technique.

negative: 20 Infection Prevention and Control in the Tropics Abstract Tropical settings present unique challenges to the practice of infection prevention and control. These are multi-faceted due to differences in the climate, culture, social, and political milieu of low- and middle-income countries situated in the tropics, as well as the lack of resources. The emergence of communicable diseases and low vaccination coverage also lead to nosocomial augmentation of community outbreaks, further increasing the economic burden of hospital management. Addressing these challenges requires innovative, low-cost, and tailored solutions suited to the tropical environment.

negative: Severe Childhood Respiratory Viral Infections

negative: Acute effects of viral respiratory tract infections on sputum bacterial density during CF pulmonary exacerbations Abstract Background Airway proliferation of Pseudomonas aeruginosa bacteria is thought to trigger CF exacerbations and may be affected by the presence of viral infections. Methods A 2-year prospective study was conducted on 35 adults with CF. P. aeruginosa sputum density was analyzed during stable, exacerbation and post exacerbation assessments. Upon exacerbation, samples were sent for PCR detection of respiratory viruses and the sputum density of P. aeruginosa in patients with a viral infection versus those without was compared. Results Twenty-two patients experienced 30 exacerbations during the study period; 50% were associated with a viral infection. There was no change in sputum density of P. aeruginosa from the stable to exacerbation state when measured by quantitative culture or by PCR. Virus-associated exacerbations did not result in significant increases in P. aeruginosa sputum density compared to non-viral exacerbations. Conclusion Sputum density of P. aeruginosa was not increased at the time of CF exacerbation and was not influenced by the presence of viral infection.

negative: Global trends in air travel: implications for connectivity and resilience to infectious disease threats Background: Increased connectivity via air travel can facilitate the geographic spread of infectious diseases. The number of travelers alone does not explain risk; passenger origin and destination will also influence risk of disease introduction and spread. We described trends in international air passenger numbers and connectivity between countries with different capacities to detect and respond to infectious disease threats. Methods: We used the Fragile States Index (FSI) as an annual measure of country-level resilience and capacity to respond to infectious disease events. Countries are categorized as: Sustainable, Stable, Warning, or Alert, in order of increasing fragility. We included data for 177 sovereign states for the years 2007 to 2016. Annual inbound and outbound international air passengers for each country were obtained for the same time period. We examined trends in FSI score, trends in worldwide air travel, and the association between a state's FSI score and air travel. Results: Among countries included in the FSI rankings, the total number of passengers increased from 0.791 billion to 1.28 billion between 2007 and 2016. Increasing fragility was associated with a decrease in travel volumes, with a 2.9% (95% CI: 2.3-3.5%) reduction in passengers per 1-unit increase in FSI score. Overall, travel between countries of different FSI categories either increased or remained stable. The greatest increase was observed for travel to Warning countries from Warning countries, with an annual increase of 8,967,623 passengers (95%CI: 6,546,494 to 11,388,753) over the study period. Conclusions: The world's connectivity via air travel has increased dramatically over the past decade. There has been notable growth in travel from Warning and Stable countries, which comprise more than three-quarters of international air travel passengers. These countries may have suboptimal capacity to detect and respond to infectious disease threats that emerge within their borders.

negative: The Lebanese Society of Medical Oncology (LSMO) statement on the care of patients with cancer during the COVID-19 pandemic

negative: Transmission of colds Rhinorrhea, nasal congestion, and sore throat herald the beginning of the cold season for both children and adults. Although the common cold is a self-limited infection, there are no effective treatments presently available and complications, missed time from work and school, and overall discomfort are not insignificant. Understanding how infections are transmitted may lead to interventions to reduce rates of infection. In order to establish a route of transmission, certain conditions must be met. The virus must be produced and shed at the site of infection. The virus must be deposited in the environment and be able to survive there. The virus must then be able to reach the portal of entry. Finally, interruption of the proposed route of transmission must reduce the incidence of infection under natural conditions. Applying this framework, there is clear evidence in both experimental and home settings that colds can be transmitted via self-inoculation. A small amount of evidence is available relating to large and small particle aerosol transmission. Because rhinovirus is responsible for half of all colds, it has been used as the model to understand how virus is transmitted from one person to another in experimental settings. Rhinovirus has been shown to infect via self-inoculation following hand-to-hand contact with contaminated hands or hand-to-surface contact with contaminated objects in the environment. Similarly, there is convincing evidence that the self-inoculation method of cold virus transmission occurs in the home environment, where colds arre most often transmitted. Aerosol transmission has been studied in the experimental setting and may provide another, albeit less common method for transmission of rhinovirus infection. As more is understood about the transmission of cold viruses, effective methods to interrupt transmission may be devised.

negative: Dissection of the Fusion Machine of Sars-Coronavirus

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: Influence of temporary migration on the transmission of infectious diseases in a migrants' home village Abstract The number of temporary migrant workers from rural areas to urban areas in emerging market economies like China has increased dramatically since the early 1980s. Temporary migrant workers have been labeled as the major driving force for the rising incidence of infectious diseases in cities. However, it has not been well recognized that temporary migration indeed may have tremendous impacts on the spread of infectious diseases in migrants' home villages. In this paper, by proposing a delay differential equation model, we provide a framework to study the influence of temporary migration on the transmission of infectious diseases in a migrant workers' home village. The model is shown to admit a unique positive equilibrium which is locally asymptotically stable and is globally asymptotically stable under certain conditions. This implies that the disease always persists at a constant level. Considering tuberculosis as an example, we explore various disease prevention and control strategies numerically to demonstrate how migration related parameters affect the early outbreak of the disease. We find that a single control strategy, such as reducing the migration time period alone, has little effect on reducing the disease endemic level. For disease prevention and control, temporary migrant workers should be identified as the top target group, and a combination of several prevention strategies should be implemented.

negative: 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.

negative: 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).

negative: First Mildly Ill, Non-Hospitalized Case of Coronavirus Disease 2019 (COVID-19) Without Viral Transmission in the United States — Maricopa County, Arizona, 2020 BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, non-hospitalized COVID-19 case who traveled to China. METHODS: The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive specimens collected on January 22, 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥10 minutes within 2 meters). Medium-risk contacts wore all U.S. Centers for Disease Control and Prevention (CDC)-recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. RESULTS: Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. CONCLUSIONS: This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.

negative: Chapter 22 Environmentally Transmitted Pathogens This chapter describes a variety of pathogens found in the environment that are capable of infecting humans and causing disease. Different classes of pathogens are discussed including bacteria, parasites and viruses. For each pathogen, data are provided on the incidence of the organism in a particular environmental matrix such as water, food or municipal waste. In addition, we discuss: the disease caused by the particular microbe; the mode of transmission; the incubation time needed within the host prior to the onset of disease; and the duration of illness. Fate and transport of pathogens in the environment are also described. A variety of bacterial pathogens are discussed including waterborne and waterbased bacteria. Parasites discussed include protozoa, nematodes, cestodes and trematodes. For viruses, both enteric and respiratory viruses are included.

negative: The importance of continuing breastfeeding during COVID-19: in support to the WHO statement on breastfeeding during the pandemic

negative: Selection and Characterization of Monoclonal Antibodies Targeting Middle East Respiratory Syndrome Coronavirus through a Human Synthetic Fab Phage Display Library Panning Since its first report in the Middle East in 2012, the Middle East respiratory syndrome-coronavirus (MERS-CoV) has become a global concern due to the high morbidity and mortality of individuals infected with the virus. Although the majority of MERS-CoV cases have been reported in Saudi Arabia, the overall risk in areas outside the Middle East remains significant as inside Saudi Arabia. Additional pandemics of MERS-CoV are expected, and thus novel tools and reagents for therapy and diagnosis are urgently needed. Here, we used phage display to develop novel monoclonal antibodies (mAbs) that target MERS-CoV. A human Fab phage display library was panned against the S2 subunit of the MERS-CoV spike protein (MERS-S2P), yielding three unique Fabs (S2A3, S2A6, and S2D5). The Fabs had moderate apparent affinities (Half maximal effective concentration (EC(50) = 123–421 nM) for MERS-S2P, showed no cross-reactivity to spike proteins from other CoVs, and were non-aggregating and thermostable (T(m) = 61.5–80.4 °C). Reformatting the Fabs into IgGs (Immunoglobulin Gs) greatly increased their apparent affinities (K(D) = 0.17–1.2 nM), presumably due to the effects of avidity. These apparent affinities were notably higher than that of a previously reported anti-MERS-CoV S2 reference mAb (K(D) = 8.7 nM). Furthermore, two of the three mAbs (S2A3 and S2D5) bound only MERS-CoV (Erasmus Medical Center (EMC)) and not other CoVs, reflecting their high binding specificity. However, the mAbs lacked MERS-CoV neutralizing activity. Given their high affinity, specificity, and desirable stabilities, we anticipate that these anti-MERS-CoV mAbs would be suitable reagents for developing antibody-based diagnostics in laboratory or hospital settings for point-of-care testing.

negative: Priority plan for invasive cardiac electrophysiology procedures during the coronavirus disease 2019 (COVID‐19) pandemic

negative: Global rheumatology in the time of COVID-19

negative: Infection control in paediatric office settings Transmission of infection in the paediatric office is of increasing concern. The present 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 (eg, 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: Contact lens wear during the COVID-19 pandemic

negative: Severe Acute Respiratory Syndrome (SARS) This article reviews the virology, history, pathology, epidemiology, clinical presentations, complications, radiology, laboratory testing, diagnosis, treatment, and prevention of severe respiratory distress syndrome, with reference to documented outbreaks of the disease.

negative: 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.

negative: Inactivation of Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus faecium (VRE) on Various Environmental Surfaces by Mist Application of a Stabilized Chlorine Dioxide and Quaternary Ammonium Compound-Based Disinfectant Contaminated environmental surfaces are important reservoirs in the transmission of many human pathogens. Although several options exist for disinfecting contaminated environmental surfaces, few are compatible with use on both hard smooth non-porous (hard) and soft porous surfaces (soft) while still offering significant disinfection of the contaminating organisms. This study evaluated the efficacy of mist application of a stabilized chlorine dioxide and quaternary ammonium compound-based disinfectant (Cryocide20) for inactivation of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) on various environmental surfaces. MRSA and VRE were applied to hard and soft surfaces (glass, steel, tile, carpet, and cotton fabric), allowed to dry, and exposed to a uniform mist application of the disinfectant solution. After 1 hr of contact time, the residual disinfectant was neutralized, and the bacteria were recovered and enumerated on brain heart infusion (BHI) agar. Reduction of both test bacteria was observed on most of the hard and soft surfaces tested. Log(10) reduction of the organisms tended to be higher on steel, tile, and carpet than glass or cotton. Overall, these results suggest that mist application of Cryocide20 disinfectant may be an effective option for reduction of low levels of infectious bacterial pathogens from contaminated environmental surfaces.

negative: Sialic acids as receptor determinants for coronaviruses Among coronaviruses, several members are able to interact with sialic acids. For bovine coronavirus (BCoV) and related viruses, binding to cell surface components containing N-acetyl-9- O-acetylneuraminic acid is essential for initiation of an infection. These viruses resemble influenza C viruses because they share not only the receptor determinant, but also the presence of an acetylesterase that releases the 9- O-acetyl group from sialic acid and thus abolishes the ability of the respective sialoglycoconjugate to function as a receptor for BCoV. As in the case of influenza viruses, the receptor-destroying enzyme of BCoV is believed to facilitate the spread of virus infection by removing receptor determinants from the surface of infected cells and by preventing the formation of virus aggregates. Another coronavirus, porcine transmissible gastroenteritis virus (TGEV) preferentially recognizes N-glycolylneuraminic acid. TGEV does not contain a receptor-destroying enzyme and does not depend on the sialic acid binding activity for infection of cultured cells. However, binding to sialic acids is required for the enteropathogenicity of TGEV. Interaction with sialoglycoconjugates may help the virus to pass through the sialic acid-rich mucus layer that covers the viral target cells in the epithelium of the small intestine. We discuss that the BCoV group of viruses may have evolved from a TGEV-like ancestor by acquiring an acetylesterase gene through heterologous recombination.

negative: First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany over 140,000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital of Münster (UHM). METHODS: Single-step real-time RT-PCR from nasopharyngeal swaps was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and chart reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Threshold cycle (C(t)) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory confirmed COVID-19 infections. Two SARS-CoV-2 positive cases remained clinically asymptomatic. Eleven cases reported flu-like symptoms without positive results. C(t) values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (p =0.007). CONCLUSION: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at the UHM. Semi quantitative real-time RT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2 infected HCWs in order to prevent COVID-19 outbreaks in the hospital setting.

negative: Canine coronavirus inactivation with physical and chemical agents Abstract Canine coronavirus (CCoV) is responsible for mild or moderate enteritis in puppies. The virus is highly contagious and avoiding contact with infected dogs and their excretions is the only way to ensure disease prevention. Since no studies have yet focused on the sensitivity of CCoV to chemical biocides the present investigation examined the efficiency of physical and chemical methods of viral inactivation. CCoV infectivity was stable at +56°C for up to 30min, but tended to decrease rapidly at +65°C and +75°C. Germicidal ultra-violet (UV–C) light exposure demonstrated no significant effects on virus inactivation for up to 3 days. CCoV was observed to be more stable at pH 6.0–6.5 while extreme acidic conditions inactivated the virus. Two tested aldehydes inactivated the virus but their action was temperature- and time-dependent. The methods for CCoV inactivation could be applied as animal models to study human coronavirus infection, reducing the risk of accidental exposure of researchers to pathogens during routine laboratory procedures.

negative: Virus shedding and environmental deposition of novel A (H1N1) pandemic influenza virus: interim findings. BACKGROUND The relative importance of different routes of influenza transmission, including the role of bioaerosols, and ability of masks and/or hand hygiene to prevent transmission, remains poorly understood. Current evidence suggests that infectious virus is not typically released from adults after 5 days of illness, however, little is known about the extent to which virus is deposited by infected individuals into the environment and whether deposited virus has the ability to infect new hosts. Further information about the deposition of viable influenza virus in the immediate vicinity of patients with pandemic influenza is fundamental to our understanding of the routes and mechanisms of transmission. OBJECTIVES To collect data on patients infected with pandemic H1N1 2009 (swine flu). Primary objectives were to correlate the amount of virus detected in a patient's nose with that recovered from his/her immediate environment, and with symptom duration and severity. Secondary objectives were to describe virus shedding and duration according to major patient characteristics: adults versus children, and those with mild illness (community patients) versus those with more severe disease (hospitalised patients). METHODS Adults and children, both in hospital and from the community, who had symptoms of pandemic H1N1 infection, were enrolled and visited every day during follow-up for a maximum of 12 days. Symptom data was collected and samples were taken, including nose swabs and swabs from surfaces and objects around patients. Samples of air were obtained using validated sampling equipment. The samples were tested for the presence of pandemic H1N1 virus, using polymerase chain reaction (PCR) to detect virus genome and an immunofluorescence technique to detect viable virus. RESULTS Forty-three subjects were followed up, and 19 of them were subsequently proven to be infected with pandemic H1N1 virus. The median duration of virus shedding from the 19 infected cases was 6 days when detection was performed by PCR, and 3 days when detection was performed by a culture technique. Over 30% of cases remained potentially infectious for at least 5 days. Only 0.5% of all community and none of the hospital swabs taken revealed virus on surfaces. Five subjects had samples of the air around them collected and virus was detected by PCR from four; some of the air particles in which virus was detected were small enough to be inhaled and deposited deep in the lungs. LIMITATION Small number of subjects recruited. CONCLUSIONS The finding that over 30% of infected individuals have infectious virus in their noses for 5 days or more has infection control implications. The data suggest that contact transmission of pandemic influenza via fomites may be less important than previously thought, but transmission via bioaerosols at short range may be possible, meaning that high-level personal protective equipment may be needed by health-care workers when attending patients with pandemic influenza. Further work is being undertaken to consolidate these findings, as they have important potential implications for the protection of health-care workers and the formulation of advice to households, nationally and internationally.

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: Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory CD8(+) T Cells Respiratory virus infections, such as those mediated by influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for substantial morbidity and mortality, especially in children and older adults. Furthermore, the potential emergence of highly pathogenic strains of influenza virus poses a significant public health threat. Thus, the development of vaccines capable of eliciting long-lasting protective immunity to those pathogens is a major public health priority. CD8(+) Tissue-resident memory T (T(RM)) cells are a newly defined population that resides permanently in the nonlymphoid tissues including the lung. These cells are capable of providing local protection immediately after infection, thereby promoting rapid host recovery. Recent studies have offered new insights into the anatomical niches that harbor lung CD8(+) T(RM) cells, and also identified the requirement and limitations of T(RM) maintenance. However, it remains controversial whether lung CD8(+) T(RM) cells are continuously replenished by new cells from the circulation or permanently lodged in this site. A better understanding of how lung CD8(+) T(RM) cells are generated and maintained and the tissue-specific factors that drive local T(RM) formation is required for optimal vaccine development. This review focuses on recent advance in our understanding of CD8(+) T(RM) cell establishment and maintenance in the lung, and describes how those processes are uniquely regulated in this tissue.

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

negative: BMT Settings, Infection and Infection Control Despite improvements over the past several decades, infection remains a significant risk to all haematological patients receiving therapy. Those requiring allogeneic transplant and especially those that have HLA disparity or T-cell-depleted grafts have an even higher risk of infective complications due to delayed recovery of T- and B-cell function. Early identification with prompt effective treatment is paramount to improve all patients’ survival. Patient safety through robust adherence to hand hygiene and maintenance of the environment with cleaning and disinfection are the backbone of an effective preventative program. Basic nursing care and a sound knowledge base of the risks, presentation, diagnosis and treatment will improve patient care.

negative: Chloroquine: A Potential Drug in the COVID-19 Scenario Today, the whole world is fighting a public health emergency called ‘COVID-19’ caused by a new infectious virus called SARS-CoV2. Any person can catch COVID-19 from an infected person via aerosol droplets when the person coughs, sneezes, or speaks. To limit such a transmission, World Health Organization (WHO) has recommended people to wear masks and physically distance themselves by staying at least 1 m (3 feet) away from others. As aerosol droplets (by cough or sneeze) land on objects and surfaces around the person such as tables, doorknobs and handrails, and remain active on these surfaces for hours to days, people are advised to use soaps for at least 20 s. and alcohol-based sanitizers as well. As the public made efforts, clinicians and researchers investigated and found that drugs which were initially used to treat other diseases may work as a treatment option for COVID-19. One of those drugs was Chloroquine and its related derivative called hydroxychloroquine. In this review article, we have systematically searched for details of COVID-19 pandemic till May 2020 and assembled few data pertaining to (i) Corona viruses; (ii) SARS-CoV2, the virus that causes COVID-19’ and (iii) How chloroquine and hydroxychloroquine mediates anti-viral effect in both prophylactic and therapeutic setting. These data have been acquired mostly from PubMed and websites of WHO and Indian Council for Medical Research (ICMR). We did a systematic search and found that the properties of chloroquine are very much essential for the COVID-19 scenario. We also bring to you some evidence that the anti-lysosomal activity of chloroquine may be increased by botanicals like betulinic acid.

negative: COVID-19: Preliminary Clinical Guidelines for Ophthalmology Practices The zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant human coronavirus disease (COVID-19) recently appeared as a global health threat that can cause severe respiratory infection and terminal respiratory distress. By the first week of April, more than 1.3 million people had been globally infected and more than 70,000 had lost their lives to this contagious virus. Clinical manifestations occur shortly after exposure, or a few days later. There is controversy regarding the transmission of the virus through the tear and conjunctiva; however, there are reports that the ocular surface might be a potential target for COVID-19. The ease of transmission of this virus at close proximity presents a risk to eyecare workers. Several recommendations have been issued by local and national organizations to address the issue of safe ophthalmic practice during the ongoing COVID-19 pandemic. These guidelines have numerous similarities; however, subtle differences exist. The purpose of this paper was to discuss measures, with a specific focus on standard precautions, to prevent further dissemination of COVID-19 at Eye Clinics. We have proposed procedures to triage suspected cases of COVID-19, considering emergency conditions.

negative: Machine learning-based CT radiomics model for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection: A multicenter study Abstract Objectives To develop and test machine learning-based CT radiomics models for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection. Design Cross-sectional Setting Multicenter Participants A total of 52 patients with laboratory-confirmed SARS-CoV-2 infection and their initial CT images were enrolled from 5 designated hospitals in Ankang, Lishui, Zhenjiang, Lanzhou, and Linxia between January 23, 2020 and February 8, 2020. As of February 20, patients remained in hospital or with non-findings in CT were excluded. Therefore, 31 patients with 72 lesion segments were included in the final analysis. Intervention CT radiomics models based on logistic regression (LR) and random forest (RF) were developed on features extracted from pneumonia lesions in training and inter-validation datasets. The predictive performance was further evaluated in test dataset on lung lobe- and patients-level. Main outcomes Short-term hospital stay (≤10 days) and long-term hospital stay (>10 days). Results The CT radiomics models based on 6 second-order features were effective in discriminating short- and long-term hospital stay in patients with pneumonia associated with SARS-CoV-2 infection, with areas under the curves of 0.97 (95%CI 0.83-1.0) and 0.92 (95%CI 0.67-1.0) by LR and RF, respectively, in the test dataset. The LR model showed a sensitivity and specificity of 1.0 and 0.89, and the RF model showed similar performance with sensitivity and specificity of 0.75 and 1.0 in test dataset. Conclusions The machine learning-based CT radiomics models showed feasibility and accuracy for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection.

negative: Membrane protein molecules of transmissible gastroenteritis coronavirus also expose the carboxy-terminal region on the external surface of the virion. The binding domains of four monoclonal antibodies (MAbs) specific for the M protein of the PUR46-MAD strain of transmissible gastroenteritis coronavirus (TGEV) have been located in the 46 carboxy-terminal amino acids of the protein by studying the binding of MAbs to recombinant M protein fragments. Immunoelectron microscopy using these MAbs demonstrated that in a significant proportion of the M protein molecules, the carboxy terminus is exposed on the external surface both in purified viruses and in nascent TGEV virions that recently exited infected swine testis cells. The same MAbs specifically neutralized the infectivity of the PUR46-MAD strain, indicating that the C-terminal domain of M protein is exposed on infectious viruses. This topology of TGEV M protein probably coexists with the structure currently described for the M protein of coronaviruses, which consists of an exposed amino terminus and an intravirion carboxy-terminal domain. The presence of a detectable number of M protein molecules with their carboxy termini exposed on the surface of the virion has relevance for viral function, since it has been shown that the carboxy terminus of M protein is immunodominant and that antibodies specific for this domain both neutralize TGEV and mediate the complement-dependent lysis of TGEV-infected cells.

negative: 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.

negative: Viability of Pseudomonas aeruginosa in cough aerosols generated by persons with cystic fibrosis BACKGROUND: Person-to-person transmission of respiratory pathogens, including Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres. Viable P aeruginosa are contained in aerosols produced during coughing, raising the possibility of airborne transmission. METHODS: Using purpose-built equipment, we measured viable P aeruginosa in cough aerosols at 1, 2 and 4 m from the subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a slowly rotating drum to minimise gravitational settling and inertial impaction (duration). Aerosol particles were captured and sized employing an Anderson Impactor and cultured using conventional microbiology. Sputum was also cultured and lung function and respiratory muscle strength measured. RESULTS: Nineteen patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with P aeruginosa, and 10 healthy controls, 26.5 (8.7) years, participated. Viable P aeruginosa were detected in cough aerosols from all patients with CF, but not from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18 (78%) of the CF group. Marked inter-subject heterogeneity of P aeruginosa aerosol colony counts was seen and correlated strongly (r=0.73–0.90) with sputum bacterial loads. Modelling decay of viable P aeruginosa in a clinic room suggested that at the recommended ventilation rate of two air changes per hour almost 50 min were required for 90% to be removed after an infected patient left the room. CONCLUSIONS: Viable P aeruginosa in cough aerosols travel further and last longer than recognised previously, providing additional evidence of airborne transmission between patients with CF.

negative: Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches Coronavirus disease 2019 (COVID-19) associated pneumonia caused by severe acute respiratory coronavirus 2 (SARS-COV-2) was first reported in Wuhan, China in December 2019. Till date, no vaccine or completely effective drug is available for the cure of COVID-19. Therefore, an effective vaccine against SARS-COV-2 is needed to be design. This study was conducted to design an effective multi-epitope vaccine (MEV) against SARS-COV-2. Seven antigenic proteins were taken as a target and epitopes (B cell, IFN-γ and T cell) were predicted. Highly antigenic and overlapping epitopes were shortlisted. Selected T cell epitopes indicated significant interactions with the HLA-binding alleles and 99.29% coverage of the world’s population. Finally, 505 amino acids long MEV was designed by connecting sixteen MHC class I and twelve MHC class II epitopes with suitable linkers and adjuvant. Linkers and adjuvant were added to enhance the immunogenicity response of the vaccine. The allergenicity, physiochemical properties, antigenicity and structural details of MEV were analyzed in order to ensure safety and immunogenicity. MEV construct was non-allergenic and antigenic. Molecular docking demonstrated a stable and strong binding affinity of MEV with TLR3 and TLR8. Codon optimization and in silico cloning ensured increased expression in the Escherichia coli K-12 system. However, to ensure its safety and immunogenic profile, the proposed vaccine needs to be experimentally validated.

negative: Les virus des eaux usées et leur élimination au cours des traitements des effluents pollués Abstract Viruses are a biological pollution in wastewaters. Their elimination results from treatment processes of polluted effluents in the sewage treatment plant or in the lagooning pilot plant. Bacteriophages are regarded as viruses models and as indicators of faecal contamination. In an expiremental study, two pilot plants laboratories have been used (natural lagooning and activated sludge pilot) to follow and evaluate the elimination rate of somatic coliphage X-174 or the ARN F-specific one MS2. The two phages removal, ranging to 99 % in the two systems, are related with previous values on enteric viruses. The main factors of viral removal and inactivation (adsorption to solid matters, microbial activities, solar radiations, dissolved matters) have been studied too. Adsorption of infectious particles to solid matters is a very significant process. This was obtained in the pilot plant laboratory experiment and in in vitro study (X-174 or MS2 in the presence of the kaolinite or the montmorillonite). Otherwise, 12 hours of solar rays exposition were efficient ro inactivate nearly the whole phagic suspension. The ciliate protozoan Tetrahymena pyriformis does not seem to have an important role for elimination of phages (X-174 and MS2.

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

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: Aerosols and splatter in dentistry A brief review of the literature and infection control implications ABSTRACT Background Aerosols and droplets are produced during many dental procedures. With the advent of the droplet-spread disease severe acute respiratory syndrome, or SARS, a review of the infection control procedures for aerosols is warranted. Types of Studies Reviewed The authors reviewed representative medical and dental literature for studies and reports that documented the spread of disease through an airborne route. They also reviewed the dental literature for representative studies of contamination from various dental procedures and methods of reducing airborne contamination from those procedures. Results The airborne spread of measles, tuberculosis and SARS is well-documented in the medical literature. The dental literature shows that many dental procedures produce aerosols and droplets that are contaminated with bacteria and blood. These aerosols represent a potential route for disease transmission. The literature also documents that airborne contamination can be minimized easily and inexpensively by layering several infection control steps into the routine precautions used during all dental procedures. Clinical Implications In addition to the routine use of standard barriers such as masks and gloves, the universal use of pre-procedural rinses and high-volume evacuation is recommended.

negative: Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface Human adenovirus infection of the ocular surface is associated with severe keratoconjunctivitis and the formation of subepithelial corneal infiltrates, which may persist and impair vision for months to years following infection. Long term pathology persists well beyond the resolution of viral replication, indicating that the prolonged immune response is not virus-mediated. However, it is not clear how these responses are sustained or even initiated following infection. This review discusses recent work from our laboratory and others which demonstrates different entry pathways specific to both adenovirus and cell type. These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface.

negative: SARS-CoV-2 infection does not significantly cause acute renal injury: an analysis of 116 hospitalized patients with COVID-19 in a single hospital, Wuhan, China Summary Background Whether the patients with COVID-19 infected by SARS-CoV-2 would commonly develop acute renal function damage is a problem worthy of clinical attention. This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients. Methods 116 hospitalized COVID-19-confirmed patients enrolled in this study were hospitalized in the Department of Infectious Diseases, Renmin Hospital of Wuhan University from January 14 to February 13, 2020. The recorded information includes demographic data, medical history, contact history, potential comorbidities, symptoms, signs, laboratory test results, chest computer tomography (CT) scans, and treatment measures. SARS-CoV-2 RNA in 53 urine sediments of enrolled patients was examined by real-time RT-PCR. Findings 12 (10.8%) and 8 (7.2%) patients showed mild elevation of blood urea nitrogen or creatinine, and trace or 1+ albuminuria respectively in 111 COVID-19-confirmed patients without basic kidney disease. In addition, 5 patients with chronic renal failure (CRF) were undergone regular continuous renal replacement therapy (CRRT) were confirmed infection of SARS-CoV-2, and diagnosed as COVID-19. Beside the treatment of COVID-19, CRRT was also applied three times weekly. The course of treatment, the renal function indicators showed stable, without exacerbation of CRF, and pulmonary inflammation was gradually absorbed. All 5 patients with CRF were survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without renal illness before, and one patient had a positive for SARS-CoV-2 ORF 1ab from 5 cases with CRF. Interpretation Acute renal impairment was uncommon in COVID-19. SARS-CoV-2 infection does not significantly cause obvious acute renal injury, or aggravate CRF in the COVID-19 patients.

negative: Chapter 13 Viral Disease Abstract This chapter discusses infections of rats with viruses in the following 14 virus families: Adenoviridae, Arenaviridae, Coronaviridae, Flaviviridae, Hantaviridae, Hepeviridae, Herpesviridae, Paramyxoviridae, Parvoviridae, Picornaviridae, Pneumoviridae, Polyomaviridae, Poxviridae, and Reoviridae. Serological surveys indicate that parvoviruses, coronaviruses, cardioviruses, and pneumoviruses are the most prevalent in laboratory rats. A new polyomavirus and a new cardiovirus that cause disease in laboratory rats are described. Metagenomic analyses of feces or intestinal contents from wild rats have detected viruses from an additional nine virus families that could potentially cause infections in laboratory rats.

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: Antigenic relationship of the feline infectious peritonitis virus to coronaviruses of other species Utilizing the direct and indirect fluorescent antibody procedure, the antigenic relationship of the feline infectious peritonitis virus (FIPV) to 7 other human and animal coronaviruses was studied. FIPV was found to be closely related to transmissible gastroenteritis virus (TGEV) of swine. Transmissible gastroenteritis virus and FIPV were in turn antigenically related to human coronavirus 229E (HCV-229E) and canine coronavirus (CCV). An interesting finding in the study was that the 8 coronaviruses selected for this study fell into one of two antigenically distinct groups. Viruses in each group were antigenically related to each other to varying degrees, but were antigenically unrelated to coronaviruses of the second group. The first antigenically related group was comprised of mouse hepatitis virus, type 3 (MHV-3), hemeagglutinating encephalomyelitis virus 67N (HEV-67N) of swine, calf diarrhea coronavirus (CDCV), and human coronavirus OC43 (HCV-OC43). The second antigenically related group was comprised of FIPV, TGEV, HCV-229E and CCV.

negative: 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.

negative: 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.

negative: 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.

negative: A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short α-HCoV and long β-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.

negative: The expression level of angiotensin-converting enzyme 2 determines the severity of COVID-19: lung and heart tissue as targets Researchers have reported some useful information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to CoV disease 2019 (COVID-19). Several studies have been performed in order to develop antiviral drugs, from which a few have been prescribed to patients. Also, several diagnostic tests have been designed to accelerate the process of identifying and treating COVID-19. It has been well-documented that the surface of host cells is covered by some receptors, known as angiotensin-converting enzyme 2 (ACE2), which mediates the binding and entry of CoV. After entering, the viral RNA interrupts the cell proliferation system to activate self-proliferation. However, having all the information about the outbreakof the SARS-COV-2, it is not still clear which factors determine the severity of lung and heart function impairment induced by COVID-19. A major step in exploring SARS-COV-2 pathogenesis is to determine the distribution of ACE2 in different tissues . In this review, the structure and origin of CoV, the role of ACE2 as a receptor of SARS-COV-2 on the surface of host cells, and the ACE2 distribution in different tissues with a focus on lung and cardiovascular system have been discussed. It was also revealed that acute and chronic cardiovascular diseases (CVDs) may result in the clinical severity of COVID-19. In conclusion, this review may provide useful information in developing some promising strategies to end up with a worldwide COVID-19 pandemic. Communicated by Ramaswamy H. Sarma

negative: [Clinical consideration and management of coronavirus disease 2019] Coronavirus disease 2019 (COVID-19) outbreak in Wuhan city, Hubei province in December 2019 and the epidemic so rapidly happened within the whole country and abroad, raising serious problems and urgent concerns, such as: how to control most effectively human-to-human transmission? When does infection rate rise to its peak? What will eventually be the number of infected patients? How to make early diagnosis? What effective antiviral drugs are available? How to use the existing drugs to achieve the best effect? Can available drugs effectively improve the survival rate of critical patients? In view of the above questions, this article now puts forwards the corresponding suggestions and considerations from the perspective of clinical infectious diseases physician.

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: On the utility of cloth facemasks for controlling ejecta during respiratory events The utility of wearing simple cloth face masks is analyzed using computational fluid dynamics simulations. We simulate the aerodynamic flow through the mask and the spatial spread of droplet ejecta resulting from respiratory events such as coughing or sneezing. Without a mask, a turbulent jet forms, and droplets with a broad size distribution are ejected. Large droplets (greater than about 125 {\mu}m in diameter) fall to the ground within about 2 m, while turbulent clouds transport a mist of small aerosolized droplets over significant distances (~ 5 m), consistent with reported experimental findings. A loosely fitted simple cotton cloth mask (with a pore size ~ 4 microns) qualitatively changes the propagation of the high velocity jet, and largely eliminates the turbulent cloud downstream of the mask. About 12\% of the airflow leaks around the sides of a mask, considering a uniform gap of only 1 mm all around, between the face and the mask. The spread of ejecta is also changed, with most large droplets trapped at the mask surface. We present the viral load in the air and deposited around the person, and show that wearing even a simple cloth mask substantially decreases the extent of spatial spread of virus particles when an infected person coughs or sneezes.

negative: RNA structure interactions and ribonucleoprotein processes of the influenza A virus In one more years, we will ‘celebrate’ an exact centenary of the Spanish flu pandemic. With the rapid evolution of the influenza virus, the possibility of novel pandemic remains ever a concern. This review covers our current knowledge of the influenza A virus: on the role of RNA in translation, replication, what is known of the expressed proteins and the protein products generated from alternative splicing, and on the role of base pairing in RNA structure. We highlight the main events associated with viral entry into the cell, the transcription and replication process, an export of the viral genetic material from the nucleus and the final release of the virus. We discuss the observed potential roles of RNA secondary structure (the RNA base-pairing arrangement) and RNA/RNA interactions in this scheme.

negative: Ultra-fast and onsite interrogation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in environmental specimens via surface enhanced Raman scattering (SERS) The outbreak of coronavirus infectious disease-2019 (COVID-19) pneumonia challenges the rapid interrogation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human and environmental specimens. In this study, we developed an assay using surface enhanced Raman scattering (SERS) coupled with multivariate analysis to diagnose SARS-CoV-2 in an ultra-fast manner without any pretreatment (e.g., RNA extraction). Using silver-nanorod SERS array functionalized with cellular receptor angiotensin-converting enzyme 2 (ACE2), we obtained strong SERS signals of ACE2 at 1032, 1051, 1089, 1189, 1447 and 1527 cm-1. The recognition and binding of receptor binding domain (RBD) of SARS-CoV-2 spike protein on SERS assay significantly quenched the spectral intensities of most peaks and exhibited a shift from 1189 to 1182 cm-1. On-site tests on 17 water samples with a portable Raman spectrometer proved its accuracy and easy-operation for spot diagnosis of SARS-CoV-2 to evaluate disinfection performance, explore viral survival in environmental media, assess viral decay in wastewater treatment plant and track SARS-CoV-2 in pipe network. Our findings raise a state-of-the-art spectroscopic tool to screen and interrogate viruses with RBD for human cell entry, proving its feasibility and potential as an ultra-fast diagnostic tool for public health.

negative: Life in a post-pandemic world: What to expect of anxiety-related conditions and their treatment

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

negative: Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 transmission

negative: The Human Coronaviruses The human coronaviruses have been shown to be a major player in clinical microbiology and frequently occur as pathogens responsible for mild to severe respiratory infections. Moreover, two of the most dangerous viral respiratory infections are caused by novel coronaviruses, namely, the SARS and the MERS coronavirus. This chapter briefly summarizes the most important facts and knowledge required for the appropriate laboratory diagnostics of infections caused by the human coronaviruses.

negative: Long-Term Outcomes After Open Repair for Ruptured Abdominal Aortic Aneurysm BACKGROUND: Early mortality in ruptured abdominal aneurysm (rAAA) is high, but data on long-term outcome are scarce. The aim of this study was to investigate the long-term outcome in survivors after open surgery for rAAA in well-defined population. METHODS: This is a population-based, observational long-term follow-up (beyond 30-day mortality) study of patients surgically treated for rAAA from 2000 through 2014. Long-term survival was analysed using Kaplan–Meier estimates and compared to the general population by analyses of relative survival. RESULTS: Out of 178 patients operated for rAAA, 95 patients (55%) either died in the perioperative period, were referred from other hospitals or were lost to follow-up (two patients). Altogether 83 patients were eligible for long-term outcomes: 72 men and 11 women. Estimated median crude survival time was 6.5 years [95% confidence interval (CI) 4.8–8.2]. Men had a median survival of 7.3 years (95% CI 5.1–9.4) versus 5.4 years in females (95% CI 3.5–7.3) (P = 0.082). Reinterventions during follow-up occurred in 31 (37%). Relative survival demonstrated a slightly higher risk of death in the rAAA population compared to the general age- and gender-matched population. Age, but not comorbidities, had a significant influence on long-term survival. CONCLUSION: For survivors beyond 30 days after surgery for rAAA, long-term survival compares well to that of an age- and sex-matched population. A high frequency of cardiovascular comorbidities did not seem to affect long-term survival.

negative: Coronavirus as a possible cause of severe acute respiratory syndrome Summary Background An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. Methods We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. Findings Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. Interpretation A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

negative: Comparison of the morphology of three coronaviruses The morphology of three coronaviruses; avian infectious bronchitis virus strain Connecticut (IBV Conn), human coronavirus strain 229E (HCV 229E) and mouse hepatitis virus strain 3 (MHV3), were examined by negative staining. Significant differences were found in the sizes of the three coronaviruses. Furthermore, three types of surface projection of the same lengths, but varying widths and morphology, were observed. Both IBV Conn and HCV 229E had bulbous projections characteristic of coronaviruses, although the projections of HCV 229E were somewhat thinner than those of IBV Conn. On the other hand, MHV3 particles had thin, cone-shaped surface projections, that were completely unlike typical coronavirus projections. The significance of these results is discussed.

negative: Current laboratory diagnostics of coronavirus disease 2019 (COVID-19) Laboratory medicine provides an almost irreplaceable contribution to the diagnostic reasoning and managed care of most human pathologies. The novel coronavirus disease 2019 (COVID-19) is not an exception to this paradigm. Although the relatively recent emergence does not allow to draw definitive conclusions on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics, some standpoints can be conveyed. First and foremost, it seems now clear that we will be living together with this virus for quite a long time, so that our vigilance and responsiveness against the emergence of new local outbreaks shall be maintained at the highest possible levels. The etiological diagnosis of COVID-19 is, and will remain for the foreseeable future, deeply based on direct identification of viral RNA by means of molecular biology techniques in biological materials, especially upper and lower respiratory tract specimens. Whether other materials, such as blood, urine, stools, saliva and throat washing, will become valid alternatives has not been unequivocally defined so far. As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Whether these antibodies will have persistent neutralizing activity against the virus is still to be elucidated on individual and general basis. The availability of rapid tests for detecting either viral antigens or anti-SARS-CoV-2 antibodies are a potentially viable opportunity for purposes of epidemiologic surveillance, though more information is needed on accuracy and reliability of these portable immunoassays.

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: 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.

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 suggest 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: Susceptibility to Upper Respiratory Tract Infection and Touching of the Eyes or Nose: A Cross‐sectional Study of Japanese Workers Susceptibility to Upper Respiratory Tract Infection and Touching of the Eyes or Nose: A Cross‐sectional Study of Japanese Workers: Yasushi FUKUNAKA, et al. Department of Safety and Health, Tokyo Gas Co., Ltd.— OBJECTIVES: This study was a cross‐sectional survey of Japanese workers regarding the relationship between touching the eyes or nose and susceptibility to URTI in workers. METHODS: The survey respondents were 4,663 Japanese workers. Subjects were surveyed via a self‐administered questionnaire regarding their susceptibility to URTI and how often they touched their eyes or nose. In addition, subjects were surveyed regarding their preventive behaviors and routine behaviors thought to be associated with URTIs. A multiple logistic regression model was used to assess the relationship between susceptibility to URTI and how often the eyes or nose are touched. RESULTS: Responses from 3,663 individuals who answered the self‐administered questionnaire were analyzed. There were 1,590 individuals (42.9%) with a “frequent incidence of URTIs”, defined as URTIs more than once a year. In terms of how often the eyes or nose are touched, the odds ratios (95% CI) for a frequent incidence of URTIs among the groups responding “sometimes” and “often” were 1.41 (1.21−1.63) and 1.96 (1.59−2.42) (trend test: p<0.001) compared with the groups responding “never” and “almost never”. Multivariate‐adjusted odds ratios adjusted for confounding factors, i.e., behaviors to prevent URTIs, routine behaviors associated with URTIs, age, sex and BMI, were 1.33 (1.14−1.54) and 1.69 (1.36−2.09) (trend test: p<0.001). CONCLUSIONS: The present cross‐sectional study indicates that susceptibility to URTI and how often the eyes or nose are touched are significantly associated in Japanese workers, independent of preventive behaviors and routine behaviors associated with URTIs.

negative: Nanoyeast and Other Cell Envelope Compositions for Protein Studies and Biosensor Applications [Image: see text] Rapid progress in disease biomarker discovery has increased the need for robust detection technologies. In the past several years, the designs of many immunoaffinity reagents have focused on lowering costs and improving specificity while also promoting stability. Antibody fragments (scFvs) have long been displayed on the surface of yeast and phage libraries for selection; however, the stable production of such fragments presents challenges that hamper their widespread use in diagnostics. Membrane and cell wall proteins similarly suffer from stability problems when solubilized from their native environment. Recently, cell envelope compositions that maintain membrane proteins in native or native-like lipid environment to improve their stability have been developed. This cell envelope composition approach has now been adapted toward stabilizing antibody fragments by retaining their native cell wall environment. A new class of immunoaffinity reagents has been developed that maintains antibody fragment attachment to yeast cell wall. Herein, we review recent strategies that incorporate cell wall fragments with functional scFvs, which are designed for easy production while maintaining specificity and stability when in use with simple detection platforms. These cell wall based antibody fragments are globular in structure, and heterogeneous in size, with fragments ranging from tens to hundreds of nanometers in size. These fragments appear to retain activity once immobilized onto biosensor surfaces for the specific and sensitive detection of pathogen antigens. They can be quickly and economically generated from a yeast display library and stored lyophilized, at room temperature, for up to a year with little effect on stability. This new format of scFvs provides stability, in a simple and low-cost manner toward the use of scFvs in biosensor applications. The production and “panning” of such antibody cell wall composites are also extremely facile, enabling the rapid adoption of stable and inexpensive affinity reagents for emerging infectious threats.

negative: Biosecurity for neonatal gastrointestinal diseases Infectious diarrhea is an important cause of neonatal calf morbidity and mortality that results in significant economic losses in the beef and dairy industries. Although numerous risk factors related to the occurrence of neonatal diarrhea have been identified, they can all be categorized into those that are related to the calf, the pathogens involved, or the environment of the calf. The immune status of calves, specifically the level of passively acquired immunity through colostrum, is the major risk factor related to the calf and the occurrence of diarrhea. Although numerous pathogens have been implicated in the occurrence of neonatal diarrhea, only a relatively limited number are commonly involved. Most should be viewed as secondary opportunists rather than primary pathogens, because none are extraordinarily virulent, and with the exception of Salmonella spp., most are present within the gastrointestinal tract of many healthy, mature cattle. Important risk factors related to pathogens involved in neonatal calf diarrhea involve the size of the inoculum and the occurrence of multiple infections. Finally, when considering the environment and housing conditions in which beef and dairy calves may reside, it is clear that tremendous variations exist. Despite these variations, the risk factors associated with the environment of the calf are also those that are the most amenable to the implementation of general environmental control and monitoring strategies as well as specific biosecurity measures.

negative: Pause, Persist, Pivot: Key Decisions Health Professions Education Researchers Must Make About Conducting Studies During Extreme Events When extreme events occur, some research becomes a clear priority, but what becomes of all other research? Does it stop indefinitely, or can it be paused with plans to resume, persist with modifications, or pivot to address new priorities? Facing this dilemma and witnessing it among their fellow health professions education researchers, the authors recognized a need for guidance. This Invited Commentary presents a framework, organized as key questions related to the research stage and process, to assist health professions education researchers in making decisions about how to proceed with research that was planned or in progress when an extreme event occurred. Although at the time of this writing, the COVID-19 pandemic was the extreme event at hand, the authors intentionally created questions and discussed considerations that can be helpful for thinking through decisions in a variety of disruptions in health professions education research—many of which require similar difficult decisions and creative solutions to carry important research forward and maintain high quality.

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

negative: Identification of COVID-19 can be quicker through artificial intelligence framework using a mobile phone–based survey when cities and towns are under quarantine We propose the use of a machine learning algorithm to improve possible COVID-19 case identification more quickly using a mobile phone–based web survey. This method could reduce the spread of the virus in susceptible populations under quarantine.

negative: Persistent viral RNA positivity during recovery period of a patient with SARS‐CoV‐2 infection As an emerging infectious disease, the clinical course and virological course of SARS‐CoV‐2 infection remain to be further investigated. In this case report, we described a case of SARS‐CoV‐2 infection with clinical course more than two months. This patient had recovered from the pneumonia after treatment. The viral RNA of throat swabs became negative and the viral specific antibodies were produced during recovery period. However, the viral RNA reappeared and additionally persisted in throat swabs for more than 40 days. In addition, the viral RNA was detected in multiple types of specimens with extremely high titers in the saliva. In conclusion, these findings indicate that SARS‐CoV‐2 can cause a long clinical course. The coexistence of viral RNA and viral specific antibodies may imply an immune evasion of SARAS‐CoV‐2 from host's immune system. This article is protected by copyright. All rights reserved.

negative: Phosphatidylinositol 3-kinase-, actin-, and microtubule-dependent transport of Semliki Forest Virus replication complexes from the plasma membrane to modified lysosomes. Like other positive-strand RNA viruses, alphaviruses replicate their genomes in association with modified intracellular membranes. Alphavirus replication sites consist of numerous bulb-shaped membrane invaginations (spherules), which contain the double-stranded replication intermediates. Time course studies with Semliki Forest virus (SFV)-infected cells were combined with live-cell imaging and electron microscopy to reveal that the replication complex spherules of SFV undergo an unprecedented large-scale movement between cellular compartments. The spherules first accumulated at the plasma membrane and were then internalized using an endocytic process that required a functional actin-myosin network, as shown by blebbistatin treatment. Wortmannin and other inhibitors indicated that the internalization of spherules also required the activity of phosphatidylinositol 3-kinase. The spherules therefore represent an unusual type of endocytic cargo. After endocytosis, spherule-containing vesicles were highly dynamic and had a neutral pH. These primary carriers fused with acidic endosomes and moved long distances on microtubules, in a manner prevented by nocodazole. The result of the large-scale migration was the formation of a very stable compartment, where the spherules were accumulated on the outer surfaces of unusually large and static acidic vacuoles localized in the pericentriolar region. Our work highlights both fundamental similarities and important differences in the processes that lead to the modified membrane compartments in cells infected by distinct groups of positive-sense RNA viruses.

negative: Influence of viral infection on expression of cell surface antigens in human retinal pigment epithelial cells • Background: Subacute viral infection is known to change the phenotype of infected cells, thereby causing immune-mediated tissue damage. The aim of this study was to investigate the expression of different cell surface molecules on human retinal pigment epithelial cells (RPEC) following viral infection, with special emphasis on those having immuneregulatory functions. • Methods: Cultured RPEC were infected with cytomegalovirus (CMV), coxsackievirus B3 (CVB) or herpes simplex virus type I (HSV). Double-staining fluorescence technique was used for visualization of virus infection and cell surface markers in the same cells by laser microscopy. • Results: CMV down-regulated MHC class I antigens on RPEC, whereas CVB and HSV did not alter MHC class I antigen expression. No induction of class 11 antigens was observed in RPEC infected with CVB, HSV or CMV. The intercellular adhesion molecule ICAM-1 (CD54) was strongly expressed in uninfected RPEC, and a slight increase was observed after virus infection. Vascular cell adhesion molecule 1 (VCAM-1) was expressed in low amounts in both uninfected and infected RPEC. No expression of intercellular adhesion molecule 2 (ICAM-2), E-selectin ELAM-1 or lymphocyte-function-associated antigen 1 (LFA-1) was observed on RPEC before or after virus infection. • Conclusion: Down-modulation of immune-regulating cell surface antigens has been suggested to provide a means of long-term survival of viruses in the infected cell, favoring establishment of persistent infection. Our observation in cultured human RPEC indicates that this mechanism might indeed contribute to the development of disease affecting retinal tissue.

negative: COVID-19 and Laparoscopic Surgery: Scoping Review of Current Literature and Local Expertise BACKGROUND: The current coronavirus disease (COVID-19) pandemic is holding the world in its grip. Epidemiologists have shown that the mortality risks are higher when the health care system is subjected to pressure from COVID-19. It is therefore of great importance to maintain the health of health care providers and prevent contamination. An important group who will be required to treat patients with COVID-19 are health care providers during semiacute surgery. There are concerns that laparoscopic surgery increases the risk of contamination more than open surgery; therefore, balancing the safety of health care providers with the benefit of laparoscopic surgery for the patient is vital. OBJECTIVE: We aimed to provide an overview of potential contamination routes and possible risks for health care providers; we also aimed to propose research questions based on current literature and expert opinions about performing laparoscopic surgery on patients with COVID-19. METHODS: We performed a scoping review, adding five additional questions concerning possible contaminating routes. A systematic search was performed on the PubMed, CINAHL, and Embase databases, adding results from gray literature as well. The search not only included COVID-19 but was extended to virus contamination in general. We excluded society and professional association statements about COVID-19 if they did not add new insights to the available literature. RESULTS: The initial search provided 2007 records, after which 267 full-text papers were considered. Finally, we used 84 papers, of which 14 discussed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Eight papers discussed the added value of performing intubation in a low-pressure operating room, mainly based on the SARS outbreak experience in 2003. Thirteen papers elaborated on the risks of intubation for health care providers and SARS-CoV-2, and 19 papers discussed this situation with other viruses. They conclude that there is significant evidence that intubation and extubation is a high-risk aerosol-producing procedure. No papers were found on the risk of SARS-CoV-2 and surgical smoke, although 25 papers did provide conflicting evidence on the infection risk of human papillomavirus, hepatitis B, polio, and rabies. No papers were found discussing tissue extraction or the deflation risk of the pneumoperitoneum after laparoscopic surgery. CONCLUSIONS: There seems to be consensus in the literature that intubation and extubation are high-risk procedures for health care providers and that maximum protective equipment is needed. On the other hand, minimal evidence is available of the actual risk of contamination of health care providers during laparoscopy itself, nor of operating room pressure, surgical smoke, tissue extraction, or CO2 deflation. However, new studies are being published daily from current experiences, and society statements are continuously updated. There seems to be no reason to abandon laparoscopic surgery in favor of open surgery. However, the risks should not be underestimated, surgery should be performed on patients with COVID-19 only when necessary, and health care providers should use logic and common sense to protect themselves and others by performing surgery in a safe and protected environment.

negative: Defence in Depth Against Human Extinction: Prevention, Response, Resilience, and Why They All Matter We look at classifying extinction risks in three different ways, which affect how we can intervene to reduce risk. First, how does it start causing damage? Second, how does it reach the scale of a global catastrophe? Third, how does it reach everyone? In all of these three phases there is a defence layer that blocks most risks: First, we can prevent catastrophes from occurring. Second, we can respond to catastrophes before they reach a global scale. Third, humanity is resilient against extinction even in the face of global catastrophes. The largest probability of extinction is posed when all of these defences are weak, that is, by risks we are unlikely to prevent, unlikely to successfully respond to, and unlikely to be resilient against. We find that it’s usually best to invest significantly into strengthening all three defence layers. We also suggest ways to do so tailored to the classes of risk we identify. Lastly, we discuss the importance of underlying risk factors – events or structural conditions that may weaken the defence layers even without posing a risk of immediate extinction themselves.

negative: Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung BACKGROUND: Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative bacterium that causes serious life threatening and nosocomial infections including pneumonia. PA has the ability to alter host genome to facilitate its invasion, thus increasing the virulence of the organism. Sphingosine-1- phosphate (S1P), a bioactive lipid, is known to play a key role in facilitating infection. Sphingosine kinases (SPHK) 1&2 phosphorylate sphingosine to generate S1P in mammalian cells. We reported earlier that Sphk2(−/−) mice offered significant protection against lung inflammation, compared to wild type (WT) animals. Therefore, we profiled the differential expression of genes between the protected group of Sphk2(−/−) and the wild type controls to better understand the underlying protective mechanisms related to the Sphk2 deletion in lung inflammatory injury. Whole transcriptome shotgun sequencing (RNA-Seq) was performed on mouse lung tissue using NextSeq 500 sequencing system. RESULTS: Two-way analysis of variance (ANOVA) analysis was performed and differentially expressed genes following PA infection were identified using whole transcriptome of Sphk2(−/−) mice and their WT counterparts. Pathway (PW) enrichment analyses of the RNA seq data identified several signaling pathways that are likely to play a crucial role in pneumonia caused by PA such as those involved in: 1. Immune response to PA infection and NF-κB signal transduction; 2. PKC signal transduction; 3. Impact on epigenetic regulation; 4. Epithelial sodium channel pathway; 5. Mucin expression; and 6. Bacterial infection related pathways. Our genomic data suggests a potential role for SPHK2 in PA-induced pneumonia through elevated expression of inflammatory genes in lung tissue. Further, validation by RT-PCR on 10 differentially expressed genes showed 100% concordance in terms of vectoral changes as well as significant fold change. CONCLUSION: Using Sphk2(−/−) mice and differential gene expression analysis, we have shown here that S1P/SPHK2 signaling could play a key role in promoting PA pneumonia. The identified genes promote inflammation and suppress others that naturally inhibit inflammation and host defense. Thus, targeting SPHK2/S1P signaling in PA-induced lung inflammation could serve as a potential therapy to combat PA-induced pneumonia.

negative: Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020 On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged ≥65 years and particularly those aged ≥85 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.

negative: Effect of Polyprenyl Immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis Feline infectious peritonitis (FIP) is considered a fatal disease. Three cats with dry form FIP were treated with Polyprenyl Immunostimulant. Two of the three cats are still on treatment and are alive and well 2 years after diagnosis. The third cat survived 14 months but was treated for only 4.5 months. Further studies are necessary to assess the potential of the Polyprenyl Immunostimulant.

negative: Approaches to the management of patients in oral and maxillofacial surgery during COVID-19 pandemic Oral and maxillofacial surgery is correlated with a high risk of SARS-CoV-2 transmission. Therefore, the aim of the review is to collect and discuss aspects of the management of patients in oral and maxillofacial surgery during the COVID-19 pandemic. In order to save resources and to avoid unnecessary exposure to infected patients, there is the need to schedule interventions depending on their priority. During the peak of the pandemic, no elective surgery should be performed. Even urgent procedures might be postponed if there is a view to recovery of a COVID-19 patient within a few days. Emergency procedures do not allow any delay. Specialties with overlap in therapies should have well defined arrangements among each other concerning the treatment spectra in order to avoid redundancy and loss of resources. Inpatient and outpatient units have to be organized in such a way that the risk of cross-infection among patients is reduced to a minimum. Especially, testing of patients for SARS-CoV-2 is important to detect the infected patients at an early stage. When surgery is performed on COVID-19 patients, adequate personal protective equipment is crucial. There must be negative pressure in the operating room, and aerosol formation must be reduced to a minimum. In order to address the COVID-19 challenge adequately, significant changes in the infrastructure of outpatient units, inpatient units, and operating rooms are needed. In addition, the demands concerning personal protective equipment increase significantly. The major aim is to protect patients as well as the medical staff from unnecessary infection, and to keep the healthcare system running effectively. Therefore, every effort should be taken to make the necessary investments.

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: The Prevalence of Human Parainfluenza Virus 1 on Indoor Office Fomites The objective of this study was to evaluate the potential role of fomites in human parainfluenza virus 1 (HPIV1) transmission by assessing the occurrence of HPIV1 on surfaces in an adult setting (office). In 2004, a total of 328 fomites from 12 different office buildings in five different cities were evaluated for HPIV1 viral RNA. HPIV1 was isolated using reverse transcriptase–polymerase chain reaction (RT–PCR) and detected on 37% of all office fomites. HPIV1 RNA was frequently isolated on desk tops (47%), and infrequently isolated on light switches (19%). Data revealed a statistically significant difference between the percentage of HPIV1 positive fomites in office cubicles and conference rooms (Chi-square P < 0.011, Fisher’s Exact P = 0.054). A statistically significant difference was also found among positive fomites in different buildings (Chi-square P < 0.011). HPIV1 was consistently isolated on various indoor fomites in the 12 office buildings assessed during 2004, a low HPIV incident year.

negative: [Clinical consideration and management of coronavirus disease 2019]. Coronavirus disease 2019 (COVID-19) outbreak in Wuhan city, Hubei province in December 2019 and the epidemic so rapidly happened within the whole country and abroad, raising serious problems and urgent concerns, such as: how to control most effectively human-to-human transmission? When does infection rate rise to its peak? What will eventually be the number of infected patients? How to make early diagnosis? What effective antiviral drugs are available? How to use the existing drugs to achieve the best effect? Can available drugs effectively improve the survival rate of critical patients? In view of the above questions, this article now puts forwards the corresponding suggestions and considerations from the perspective of clinical infectious diseases physician.

negative: Upper airway symptoms in coronavirus disease 2019 (COVID-19)

negative: Natural Products as Antiviral Agents Since the ancient times, natural products have served as a major source of drugs. About fifty percent of today's pharmaceutical drugs are derived from natural origin. Interest in natural products as a source of new drugs is growing due to many factors that will be discussed in this article. Viruses have been resistant to therapy or prophylaxis longer than any other form of life. Currently, there are only few drugs available for the cure of viral diseases including acyclovir which is modeled on a natural product parent. In order to combat viruses which have devastating effects on humans, animals, insects, crop plants, fungi and bacteria, many research efforts have been devoted for the discovery of new antiviral natural products. Recent analysis of the number and sources of antiviral agents reported mainly in the annual reports of medicinal chemistry from 1984 to 1995 indicated that seven out of ten synthetic agents approved by FDA between 1983-1994, are modeled on a natural product parent. It has been estimated that only 5-15% of the approximately 250,000 species of higher plants have been systematically investigated for the presence of bioactive compounds while the potential of the marine environment has barely been tapped. The aim of this review is to provide an overview on the central role of natural products in the discovery and development of new antiviral drugs by displaying 340 structures of plant, marine and microbial origin that show promising in vitro antiviral activity.

negative: How does the outbreak of 2019-nCoV spread in mainland China? A retrospective analysis of the dynamic transmission routes The fourth outbreak of the Coronaviruses, known as the 2019-nCoV, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dyamic transmission routes of this outbreak in mainland China over January 31 - February 19, 2020. Our results demonstrate that the influential inter-province routes from Hubei have become unidentifiable since February 4, whereas the self-transmission in each province was accelerating over February 4-15. From February 16, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in provinces with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of 2019-nCoV.

negative: Potential for evolution of complex defense strategies in a multi-scale model of virus-host coevolution BACKGROUND: Host resistance and viral pathogenicity are determined by molecular interactions that are part of the evolutionary arms race between viruses and their hosts. Viruses are obligate intracellular parasites and entry to the host cell is the first step of any virus infection. Commonly, viruses enter host cells by binding cell surface receptors. We adopt a computational modeling approach to study the evolution of the first infection step, where we consider two possible levels of resistance mechanism: at the level of the binding interaction between the host receptor and a virus binding protein, and at the level of receptor protein expression where we use a standard gene regulatory network model. At the population level we adopted the Susceptible-Infected-Susceptible (SIS) model. We used our multi-scale model to understand what conditions might determine the balance between use of resistance mechanisms at the two different levels. RESULTS: We explored a range of different conditions (model parameters) that affect host evolutionary dynamics and, in particular, the balance between the use of different resistance mechanisms. These conditions include the complexity of the receptor binding protein-protein interaction, selection pressure on the host population (pathogenicity), and the number of expressed cell-surface receptors. In particular, we found that as the receptor binding complexity (understood as the number of amino acids involved in the interaction between the virus entry protein and the host receptor) increases, viruses tend to become specialists and target one specific receptor. At the same time, on the host side, the potential for resistance shifts from the changes at the level of receptor binding (protein-protein) interaction towards changes at the level of gene regulation, suggesting a mechanism for increased biological complexity. CONCLUSIONS: Host resistance and viral pathogenicity depend on quite different evolutionary conditions. Viruses may evolve cell entry strategies that use small receptor binding regions, represented by low complexity binding in our model. Our modeling results suggest that if the virus adopts a strategy based on binding to low complexity sites on the host receptor, the host will select a defense strategy at the protein (receptor) level, rather than at the level of the regulatory network - a virus-host strategy that appears to have been selected most often in nature. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-016-0804-z) contains supplementary material, which is available to authorized users.

negative: 'No touch' technologies for environmental decontamination: focus on ultraviolet devices and hydrogen peroxide systems. PURPOSE OF REVIEW This article reviews 'no touch' methods for disinfection of the contaminated surface environment of hospitalized patients' rooms. The focus is on studies that assessed the effectiveness of ultraviolet (UV) light devices, hydrogen peroxide systems, and self-disinfecting surfaces to reduce healthcare-associated infections (HAIs). RECENT FINDINGS The contaminated surface environment in hospitals plays an important role in the transmission of several key nosocomial pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., Clostridium difficile, Acinetobacter spp., and norovirus. Multiple clinical trials have now demonstrated the effectiveness of UV light devices and hydrogen peroxide systems to reduce HAIs. A limited number of studies have suggested that 'self-disinfecting' surfaces may also decrease HAIs. SUMMARY Many studies have demonstrated that terminal cleaning and disinfection with germicides is often inadequate and leaves environmental surfaces contaminated with important nosocomial pathogens. 'No touch' methods of room decontamination (i.e., UV devices and hydrogen peroxide systems) have been demonstrated to reduce key nosocomial pathogens on inoculated test surfaces and on environmental surfaces in actual patient rooms. Further UV devices and hydrogen peroxide systems have been demonstrated to reduce HAI. A validated 'no touch' device or system should be used for terminal room disinfection following discharge of patients on contact precautions. The use of a 'self-disinfecting' surface to reduce HAI has not been convincingly demonstrated.

negative: Rethinking Smallpox The potential consequences of a competently executed smallpox attack have not been adequately considered by policy makers. The possibility of release of an aerosolized and/or bioengineered virus must be anticipated and planned for. The transmission and infectivity of variola virus are examined. Arguments for and against pre-event vaccination are offered. The likely morbidity and mortality that would ensue from implementation of a mass pre-event vaccination program, within reasonable boundaries, are known. The extent of contagion that could result from an aerosolized release of virus is unknown and may have been underestimated. Pre-event vaccination of first responders is urged, and voluntary vaccination programs should be offered to the public. Two defenses against a vaccine-resistant, engineered variola virus are proposed for consideration. Methisazone, an overlooked drug, is reported to be effective for prophylaxis only. The extent of reduction in the incidence of smallpox with use of this agent is uncertain. It is useless for treatment of clinical smallpox. N-100 respirators (face masks) worn by uninfected members of the public may prevent transmission of the virus.

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: 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.

negative: Household transmission of SARS-CoV-2 BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic in China and many other countries. Many infected clusters have been found within familial households, but the data about secondary transmission among household contacts is limited. METHODS: In this retrospective case series, we enrolled 85 patients infected with SARS-CoV-2 and their household members in Wuhan. Patients were confirmed infected with SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) assays on throat swabs. Epidemiological, clinical and laboratory data of the household members were collected. RESULTS: There were 155 close contacts in total. 104 contacts received RT-PCR assays, with 47 (30%) positive cases and 57 (37%) negative cases. 51 (33%) cases did not received RT-PCR tests for they showed no symptoms of pneumonia during the 2 weeks of quarantine. The infection rate of close contacts was 38% for households with 1 contact, 50% for households with 2 contacts, and 31% for households with 3 contacts. CONCLUSIONS: The rate of secondary transmission among household contacts of patients with SARS-CoV-2 infection was 30%. Our data provide insight into the rate of secondary transmission of SARS-CoV-2 in home.

negative: Estimating unobserved SARS-CoV-2 infections in the United States By March 2020, COVID-19 led to thousands of deaths and disrupted economic activity worldwide. As a result of narrow case definitions and limited capacity for testing, the number of unobserved SARS-CoV-2 infections during its initial invasion of the US remains unknown. We developed an approach for estimating the number of unobserved infections based on data that are commonly available shortly after the emergence of a new infectious disease. The logic of our approach is, in essence, that there are bounds on the amount of exponential growth of new infections that can occur during the first few weeks after imported cases start appearing. Applying that logic to data on imported cases and local deaths in the US through March 12, we estimated that 22,876 (95% posterior predictive interval: 7,451 - 53,044) infections occurred in the US by this date. By comparing the model's predictions of symptomatic infections to local cases reported over time, we obtained daily estimates of the proportion of symptomatic infections detected by surveillance. This revealed that detection of symptomatic infections decreased throughout February as exponential growth of infections outpaced increases in testing. Between February 21 and March 12, we estimated an increase in detection of symptomatic infections, which was strongly correlated (median: 0.97, 95% PPI: 0.85 - 0.98) with increases in testing. These results suggest that testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion of the US.

negative: National Institute for the Infectious Diseases “L. Spallanzani”, IRCCS. Recommendations for COVID-19 clinical management On January 9 2020, the World Health Organization (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a disease (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The “L. Spallanzani” National Institute for the Infectious Diseases, IRCCS, Rome, Italy, has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; they should be considered as expert opinions, which may be modified according to newly produced literature data.

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: 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: Transmission risk of SARS-CoV-2 to healthcare workers -observational results of a primary care hospital contact tracing BACKGROUND: The coronavirus disease (COVID)-19 epidemic is evolving rapidly. Healthcare workers are at increased risk for infection, and specific requirements for their protection are advisable to ensure the functioning of the basic healthcare system, including the availability of general practitioners (GPs). Understanding the transmission risk is particularly important for guiding evidence-based protective measures in the primary healthcare setting. METHODS: Healthcare worker contacts of an initially undiagnosed COVID-19 case, who were without personal protective equipment, in particular not wearing facemasks, were screened with nasopharyngeal swabs and polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), irrespective of respiratory symptoms or fever seven days after initial contact. The details of exposure to the index case were obtained during routine contact investigation after unintentional pathogen exposure. RESULTS: Twenty-one healthcare workers reported contacts with the index case. Three healthcare workers reported respiratory symptoms (cough) or low-grade fever within 4 days. None of them tested positive for SARS-CoV-2 at the time of symptom onset. All 21 healthcare workers tested SARS-CoV-2 negative 7 days after initial index case contact, including the three healthcare workers with previous symptoms. Ten of the 21 healthcare workers reported a cumulative exposure time of >15 minutes. Longer cumulative contact times were associated with more individual contacts, reduced contact time per contact and activities with physical patient contact. The closest relative of the index patient tested SARS-CoV-2 positive 2 days after the index case presented at the hospital emergency department. CONCLUSION: We found a low risk of SARS-CoV-2 transmission in a primary care setting. These findings are compatible with previous reports of the highest transmission probability in household settings with prolonged close contacts. The current protective measures for healthcare workers, including strict adherence to basic standard hygiene and facemasks, offer considerable protection during short periods of contact with symptomatic COVID-19 cases by diminishing the risk of direct and indirect transmission.

negative: Increased litter survival rates, reduced clinical illness and better lactogenic immunity against TGEV in gilts that were primed as neonates with porcine respiratory coronavirus (PRCV) Abstract Establishing immunological memory in female piglets at a young age with PRCV was effective in inducing a secondary immune response to a limiting dose of virulent TGEV given orally 13–18 days prior to farrowing. Subsequently, because of passive antibody transfer, the offspring of these primed gilts were more efficient in surviving a lethal TGEV challenge. An average survival rate of 89% occurred in 6 litters of piglets from primed gilts that were boosted with 2.8×106 plaque forming units (PFU) of TGEV whereas 76% of the piglets survived in three litters that suckled primed gilts boosted with 3.0×105 PFU of TGEV. Non-primed gilts given identical pre-farrowing doses of TGEV had litter survival rates of 63 and 55%, respectively. Moreover, both groups of litters from primed gilts suffered less clinical illness (as measured by the extent of weight loss post-challenge) than control litters. Priming of the piglets as neonates and boosting the pregnant gilts produced an anamnestic systemic immune response and correspondingly higher milk titers in the primed gilts compared to control animals. Thus, priming piglets with PRCV was beneficial in providing resistance to TGEV and could be incorporated into a vaccine strategy that yields better protection against TGEV.

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

negative: A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs) The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs–Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.

negative: Utilising Media and Text-Based Sources An often-underestimated, valuable source of naturally occurring data is that of media sources, such as television programmes, documentaries, newspapers, and magazines. Often in traditional textbooks these are positioned as secondary sources. We argue that they can be considered primary data, as well as naturally occurring data. This type of naturally occurring data is of interest for qualitative research, and in this chapter, we focus on the use of policy documents, medical notes, health guidelines, as well as other data sources such as police transcripts, court transcripts, and social care reports whereby health is invoked, to illustrate the value of analysing texts that occur naturally in the field of health.

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: Protecting healthcare workers from SARS-CoV-2 infection: practical indications The World Health Organization has recently defined the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a pandemic. The infection, that may cause a potentially very severe respiratory disease, now called coronavirus disease 2019 (COVID-19), has airborne transmission via droplets. The rate of transmission is quite high, higher than common influenza. Healthcare workers are at high risk of contracting the infection particularly when applying respiratory devices such as oxygen cannulas or noninvasive ventilation. The aim of this article is to provide evidence-based recommendations for the correct use of “respiratory devices” in the COVID-19 emergency and protect healthcare workers from contracting the SARS-CoV-2 infection.

negative: Characterisation of the RNA binding properties of the coronavirus infectious bronchitis virus nucleocapsid protein amino-terminal region Abstract The coronavirus nucleocapsid (N) protein binds viral RNA to form the ribonucleocapsid and regulate RNA synthesis. The interaction of N protein with viral RNA was investigated using circular dichroism and surface plasmon resonance. N protein underwent a conformational change upon binding viral RNA and the data indicated electrostatic interactions were involved in the binding of the protein to RNA. Kinetic analysis suggested the amino-terminal region facilitates long-range non-specific interactions between N protein and viral RNA, thus bringing the RNA into close proximity to N protein allowing specific contacts to form via a ‘lure’ and ‘lock’ mechanism.

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: Detection of SARS Coronavirus in Patients with Suspected SARS Cases of severe acute respiratory syndrome (SARS) were investigated for SARS coronavirus (SARS-CoV) through RNA tests, serologic response, and viral culture. Of 537 specimens from patients in whom SARS was clinically diagnosed, 332 (60%) had SARS-CoV RNA in one or more clinical specimens, compared with 1 (0.3%) of 332 samples from controls. Of 417 patients with clinical SARS from whom paired serum samples were available, 92% had an antibody response. Rates of viral RNA positivity increased progressively and peaked at day 11 after onset of illness. Although viral RNA remained detectable in respiratory secretions and stool and urine specimens for >30 days in some patients, virus could not be cultured after week 3 of illness. Nasopharyngeal aspirates, throat swabs, or sputum samples were the most useful clinical specimens in the first 5 days of illness, but later in the illness viral RNA could be detected more readily in stool specimens.

negative: An artificial intelligence-based first-line defence against COVID-19: digitally screening citizens for risks via a chatbot To combat the pandemic of the coronavirus disease (COVID-19), numerous governments have established phone hotlines to prescreen potential cases. These hotlines have struggled with the volume of callers, leading to wait times of hours or, even, an inability to contact health authorities. Symptoma is a symptom-to-disease digital health assistant that can differentiate more than 20,000 diseases with an accuracy of more than 90%. We tested the accuracy of Symptoma to identify COVID-19 using a set of diverse clinical cases combined with case reports of COVID-19. We showed that Symptoma can accurately distinguish COVID-19 in 96.32% of clinical cases. When considering only COVID-19 symptoms and risk factors, Symptoma identified 100% of those infected when presented with only three signs. Lastly, we showed that Symptoma’s accuracy far exceeds that of simple “yes-no” questionnaires widely available online. In summary, Symptoma provides unparalleled accuracy in systematically identifying cases of COVID-19 while also considering over 20,000 other diseases. Furthermore, Symptoma allows free text input, furthered with disease-specific follow up questions, in 36 languages. Combined, these results and accessibility give Symptoma the potential to be a key tool in the global fight against COVID-19. The Symptoma predictor is freely available online at https://www.symptoma.com.

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: Developing approaches to control SARS-CoV-2 in a public hospital

negative: Abstracts from the 37th Annual Meeting of the Society of General Internal Medicine

negative: Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two Betacoronaviruses, the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations.

negative: Avian metapneumoviruses expressing Infectious Bronchitis virus genes are stable and induce protection Abstract The study investigates the ability of subtype A Avian metapneumovirus (AMPV) to accept foreign genes and be used as a vector for delivery of Infectious bronchitis virus (IBV) QX genes to chickens. Initially the GFP gene was added to AMPV at all gene junctions in conjunction with the development of cassetted full length DNA AMPV copies. After recombinant virus had been recovered by reverse genetics, GFP positions supporting gene expression while maintaining virus viability in vitro, were determined. Subsequently, either S1 or nucleocapsid (N) genes of IBV were positioned between AMPV M and F genes, while later a bivalent recombinant was prepared by inserting S1 and N at AMPV MF and GL junctions respectively. Immunofluorescent antibody staining showed that all recombinants expressed the inserted IBV genes in vitro and furthermore, all recombinant viruses were found to be highly stable during serial passage. Eyedrop inoculation of chickens with some AMPV-IBV recombinants at one-day-old induced protection against virulent IBV QX challenge 3 weeks later, as assessed by greater motility of tracheal cilia from chickens receiving the recombinants. Nonetheless evidence of AMPV/IBV seroconversion, or major recombinant tracheal replication, were largely absent.

negative: Elucidation of the stability and functional regions of the human coronavirus OC43 nucleocapsid protein Human coronavirus OC43 (HCoV-OC43) is one of the causes of the “common cold” in human during seasons of cold weather. The primary function of the HCoV-OC43 nucleocapsid protein (N protein) is to recognize viral genomic RNA, which leads to ribonucleocapsid formation. Here, we characterized the stability and identified the functional regions of the recombinant HCoV-OC43 N protein. Circular dichroism and fluorescence measurements revealed that the HCoV-OC43 N protein is more highly ordered and stabler than the SARS-CoV N protein previously studied. Surface plasmon resonance (SPR) experiments showed that the affinity of HCoV-OC43 N protein for RNA was approximately fivefold higher than that of N protein for DNA. Moreover, we found that the HCoV-OC43 N protein contains three RNA-binding regions in its N-terminal region (residues 1–173) and central-linker region (residues 174–232 and 233–300). The binding affinities of the truncated N proteins and RNA follow the order: residues 1–173–residues 233–300 > residues 174–232. SPR experiments demonstrated that the C-terminal region (residues 301–448) of HCoV-OC43 N protein lacks RNA-binding activity, while crosslinking and gel filtration analyses revealed that the C-terminal region is mainly involved in the oligomerization of the HCoV-OC43 N protein. This study may benefit the understanding of the mechanism of HCoV-OC43 nucleocapsid formation.

negative: Immunoinformatics‐aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019‐nCoV The 2019 novel coronavirus (2019‐nCoV) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide, especially in East Asia. This study took an immunoinformatics approach to identify significant cytotoxic T lymphocyte (CTL) and B cell epitopes in the 2019‐nCoV surface glycoprotein. Also, interactions between identified CTL epitopes and their corresponding major histocompatibility complex (MHC) class I supertype representatives prevalent in China were studied by molecular dynamics simulations. We identified five CTL epitopes, three sequential B cell epitopes and five discontinuous B cell epitopes in the viral surface glycoprotein. Also, during simulations, the CTL epitopes were observed to be binding MHC class I peptide‐binding grooves via multiple contacts, with continuous hydrogen bonds and salt bridge anchors, indicating their potential in generating immune responses. Some of these identified epitopes can be potential candidates for the development of 2019‐nCoV vaccines.

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: 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: An engineered stable mini-protein to plug SARS-Cov-2 Spikes The novel betacoronavirus SARS-CoV-2 is the etiological agent of the current pandemic COVID-19. Like other coronaviruses, this novel virus relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2). Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2 have a great potential to inhibit viral entry. Starting from the available structural data on the interaction between SARS-CoV-2 Spike protein and the host ACE2 receptor, we here engineered a mini-protein with the aim of creating a soluble and stable Spike interactor. This mini-protein, which was recombinantly produced in high yields, possesses a stable α helical conformation and is able to interact with the RBD of glycosylated Spike protein from SARS-CoV-2 with nanomolar affinity, as measured by microscale thermophoresis. By plugging the Spike protein, our mini-protein constitutes a valid tool for the development of treatments against different types of coronavirus.

negative: The current state of COVID-19 in Australia: importation and spread Background: The rapid global spread of coronavirus disease (COVID-19) is unprecedented. The outbreak has quickly spread to more than 100 countries reporting over 100,000 confirmed cases. Australia reported its first case of COVID-19 on 25th January 2020 and has since implemented travel restrictions to stop further introduction of the virus. Methods: We analysed daily global COVID-19 data published by the World Health Organisation to investigate the spread of the virus thus far. To assess the current risk of COVID-19 importation and local spread in Australia we predict international passenger flows into Australia during 2020. Findings: Our analysis of global data shows that Australia can expect a similar growth rate of reported cases as observed in France and the United States. We identify travel patterns of Australian citizens/residents and foreign travellers that can inform the implementation of new and the alteration of existing travel restrictions related to COVID-19. Interpretation: Our findings identify the risk reduction potential of current travel bans, based on the proportion of returning travellers to Australia that are residents or visitors. The similarity of the exponential growth in the epidemic curve in Australia to other countries guides forecasts of COVID-19 growth in Australia, and opportunities for drawing lessons from other countries with more advanced outbreaks.

negative: WILDLIFE This chapter deals with the issue of veterinary participation in managing sick and injured wild animals. There are many financial, ethical, and emotional issues for veterinarians to consider when deciding whether to accept wildlife cases to their practice. Wildlife is not owned and, therefore, does not come with paying caretakers. In many cases, the hospital will be expected to absorb the cost of treatment, although avenues for monetary compensation, including grants and public donations, do exist. Accepting wildlife cases is often perceived by (prospective) clients as a positive reinforcement of a veterinarian's compassion toward animals and can serve, directly or indirectly, as a method of increasing a veterinarian's domestic and exotic pet caseload. One ethical consideration to make with these cases is deciding when intervention may interfere with a natural process occurring in a population. The potential costs of accepting wildlife cases usually include expenses associated with captivity, treatment, release, and failure to reestablish the animal in the wild, as well as the welfare risks to conspeciﬁcs and other species through the possible introduction of infection or competition for resources and the upset in natural selection (for example, treating animals that have increased susceptibility to disease may inadvertently select for less ﬁt animals). The potential benefits associated with working with these animals include the emotional pleasure humans derive from helping a “lesser” species, the potential to educate the public, and the opportunities this type of medicine provides for monitoring threats to wildlife and human populations.

negative: B-cell restriction – an alternative piece to the puzzle Effective vaccination is based on three critical aspects of the B-cell response towards infectious agents: (i) that B-cells can generate specific antibodies towards a vast molecular diversity of antigens; proteins, sugars, DNA and lipids. There seems to be no limit to the ability to raise antibodies to everything. (ii) once stimulated, B-cells can perfect their antibodies through affinity maturation to complement every nook and cranny of the epitope and (iii) that the pathogen remains genetically stable and does not change to any great extent. Thus, antibodies produced against the vaccine and subsequent boosts recognize the viral virulent field isolates in future encounters and effectively knock them out. However, some vaccine targets, such as flu virus and HIV, are extremely genetically dynamic. The rapid genetic drift of these viruses renders them moving targets which assist in their ability to evade immune surveillance. Here we postulate that in the case of hyper-variable pathogens the B-cell response actually might be “too good”. We propose that restricting B-cell activities may prove effective in counteracting the genetic diversity of variant viruses such as flu and HIV. We suggest two levels of “B-cell restriction”: (i) to focus the B-cell response exclusively towards neutralizing epitopes by creating epitope-based immunogens; (ii) to restrict affinity maturation of B-cells to prevent the production of overly optimized exquisitely specific antibodies. Together, these “B-cell restrictions” provide a new modality for vaccine design.

negative: Droplets and Aerosols in the Transmission of SARS-CoV-2

negative: 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.

negative: Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated aerosol The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It infects the cells binding to the angiotensin-converting enzyme 2 receptor (ACE2) which is expressed by cells throughout the airways as targets for cellular entry. Although the majority of persons infected with SARS-CoV-2 experience symptoms of mild upper respiratory tract infection, in some people infections of the peripheral airways result in severe, potentially fatal pneumonia. However, the induction of COVID-19 pneumonia requires that SARS-CoV-2 reaches the peripheral airways. While huge efforts have been made to understand the spread of the disease as well as the pathogenesis following cellular entry, much less attention is paid how SARS-CoV-2 from the environment reach the receptors of the target cells. The aim of the present study is to characterize the deposition distribution of SARS-CoV-2 in the airways upon exposure to cough-generated aerosol. For this purpose, the Stochastic Lung Deposition Model has been applied. Aerosol size distribution and breathing parameters were taken from the literature supposing normal breathing through the nose. We found that the probability of direct infection of the peripheral airways due to inhalation of aerosol generated by a bystander cough is very low. As the number of pathogens deposited in the extrathoracic airways is ~10 times higher than in the peripheral airways, we concluded that in most cases COVID-19 pneumonia must be preceded by SARS-CoV-2 infection of the upper airways. Our results suggest that without the enhancement of viral load in the upper airways, COVID-19 would be much less dangerous...

negative: Virus entry: molecular mechanisms and biomedical applications Viruses have evolved to enter cells from all three domains of life — Bacteria, Archaea and Eukaryotes. Of more than 3,600 known viruses, hundreds can infect human cells and most of those are associated with disease. To gain access to the cell interior, animal viruses attach to host-cell receptors. Advances in our understanding of how viral entry proteins interact with their host-cell receptors and undergo conformational changes that lead to entry offer unprecedented opportunities for the development of novel therapeutics and vaccines.

negative: 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.

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: Optimal COVID-19 epidemic control until vaccine deployment Since Dec 2019, the COVID-19 epidemic has spread over the globe creating one of the greatest pandemics ever witnessed. This epidemic wave will only begin to roll back once a critical proportion of the population is immunised, either by mounting natural immunity following infection, or by vaccination. The latter option can minimise the cost in terms of human lives but it requires to wait until a safe and efficient vaccine is developed, a period estimated to last at least 18 months. In this work, we use optimal control theory to explore the best strategy to implement while waiting for the vaccine. We seek a solution minimizing deaths and costs due to the implementation of the control strategy itself. We find that such a solution leads to an increasing level of control with a maximum reached near the fourth month of the epidemics and a steady decrease until vaccine deployment. This strategy strongly outperforms others with constant or cycling allocations of the same amount of resources to control the outbreak. This work opens new perspectives to mitigate the effects of the ongoing COVID-19 pandemics, and be used as a proof-of-concept in using mathematical modelling techniques to enlighten decision ma

negative: Identification of information types and sources by the public for promoting awareness of Middle East respiratory syndrome coronavirus in Saudi Arabia Middle East Respiratory Syndrome (MERS) is a viral respiratory disease of serious consequences caused by MERS Coronavirus (MERS-CoV). Saudi communities still lack awareness of available protective measures to prevent the transmission of the virus. It is necessary to explore the current information-seeking strategies and preferences for communication tools among the Saudi population to promote dissemination of accurate information. Guided by McGuire’s Input–Output Persuasion Model and focusing on input variables (receiver characteristics, sources, message, channel and destination), we explored the current information-seeking strategies and preferences for different communication tools among residents of Riyadh (n = 658). Preferred and sought-after information sources on MERS. Most participants in the sample were female (61.7%), and the majority (98.2%) had internet access at home. The internet was the most commonly used source of information (39.5%) and the most endorsed channel for a MERS awareness campaign. Physicians were the preferred source of information (45.6%), followed by other health care providers (31.3%). In univariate multinomial logistic regression models, males and individuals aged ≤27 years were more likely to seek information from the internet than from physicians. Residents of southern and western Riyadh preferred physicians as a credible source of information over the Ministry of Health. The results of this survey provide valuable information on how to reach this population and for understanding how to launch an effective MERS risk communication campaign in a Saudi population.

negative: Chapter 24 Coronaviridae Publisher Summary Coronavirus and coronavirus-like infections are described in swine, cattle, horses, cats, dogs, rats, birds, bats, rabbits, ferrets, mink, and various wildlife species, although many coronavirus infections are subclinical or asymptomatic. In humans, coronaviruses are included in the spectrum of viruses that cause the common cold and, recently, severe acute respiratory syndrome (SARS), which is a zoonosis. This chapter explains that the family Coronaviridae is included with the families Arteriviridae and Roniviridae in the order nidovirales; viruses in these three families share a distinctive replication strategy. The genus Coronavirus contains a substantial number of pathogens of mammals and birds that individually cause a remarkable variety of diseases, including pneumonia, reproductive disease, enteritis, polyserositis, sialodacryoadenitis, hepatitis, encephalomyelitis, nephritis, and various other disorders. The genus Coronavirus can be subdivided into at least three cluster groups on the basis of genetic and serologic properties, with subgroups in two of these. Group 1a includes transmissible gastroenteritis virus of swine, porcine respiratory coronavirus, canine coronavirus, feline enteric coronavirus, ferret and mink coronaviruses, and spotted hyena coronavirus. Group 1b includes certain human coronaviruses, porcine epidemic diarrhea virus, and bat coronavirus. Group 2a includes mouse hepatitis virus, bovine coronavirus, sialodacryoadenitis virus of rats, porcine hemagglutinating encephalomyelitis virus, canine respiratory coronavirus, and other human coronaviruses. Group 2b includes human SARS coronavirus and civet cat, raccoon dog, and horseshoe bat coronaviruses. Group 3 includes avian infectious bronchitis virus, turkey coronavirus, and several potential but still largely uncharacterized new species from ducks, geese, and pigeons.

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: Coronavirus Disease 2019: In-Home Isolation Room Construction Patient care duties will expose health care workers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many are concerned about subsequent household exposure to their families, particularly those family members with high risk of complications or mortality, potentiating additional community spread. Herein is described a temporary isolation room that can be created within a home, thereby decreasing bioburden exposure to family members. The design is simple, expedient, and can be built with locally sourced inexpensive supplies. A viewing and access window facilitates safe family interaction and decreases the emotional costs of isolation while providing a route to pass items as necessary.

negative: Immunoinformatics study to search epitopes of spike glycoprotein from SARS-CoV-2 as potential vaccine The Coronavirus disease named COVID-19 is caused by the virus reported in 2019 first identified in China. The cases of this disease have increased and as of June 1(st), 2020 there are more than 216 countries affected. Pharmacological treatments have been proposed based on the resemblance of the HIV virus. With regard to prevention there is no vaccine, thus, we proposed to explore the spike protein due to its presence on the viral surface, and it also contains the putative viral entry receptor as well as the fusion peptide (important in the genome release). In this work we have employed In Silico techniques such as immunoinformatics tools which permit the identification of potential immunogenic regions on the viral surface (spike glycoprotein). From these analyses, we identified four epitopes E332-370, E627-651, E440-464 and E694-715 that accomplish essential features such as promiscuity, conservation grade, exposure and universality, and they also form stable complexes with MHCII molecule. We suggest that these epitopes could generate a specific immune response, and thus, they could be used for future applications such as the design of new epitope vaccines against the SARS-CoV-2. Communicated by Ramaswamy H. Sarma

negative: Adhesion of Microdroplets on Water-Repellent Surfaces toward the Prevention of Surface Fouling and Pathogen Spreading by Respiratory Droplets. Biofouling caused by the adhesion of respiratory microdroplets generated in sneezing and coughing plays an important role in the spread of many infectious diseases. Although water-repellent surfaces are widely used for the long-term repellency of aqueous solutions, their repellency to pathogen-containing microdroplets is elusive. In this work, microdroplets from picoliter to nanoliter were successfully generated in a controlled manner to mimic the exhaled microdroplets in sneezing and coughing, which allowed us to evaluate the adhesion of microdroplets on both superhydrophobic and lubricant-infused "slippery" surfaces for the first time. The impact and retention of water microdroplets on the two water-repellent surfaces are compared and investigated. Microdroplet-mediated surface biofouling and pathogen transmission were also demonstrated. Our results suggested that the adhesion of microdroplets should be duly considered in the design and application of water-repellent surfaces on biofouling prevention.

negative: Occupational and Environmental Exposures to Waterborne Microbial Diseases

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

negative: Analysis of meteorological conditions and prediction of epidemic trend of 2019-nCoV infection in 2020 Objective: To investigate the meteorological condition for incidence and spread of 2019-nCoV infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease. Methods: The meteorological factors during the outbreak period of the novel coronavirus pneumonia in Wuhan in 2019 were collected and analyzed, and were confirmed with those of Severe Acute Respiratory Syndrome (SARS) in China in 2003. Data of patients infected with 2019-nCoV and SARS coronavirus were collected from WHO website and other public sources. Results: This study found that the suitable temperature range for 2019-nCoV coronavirus survival is (13-24 degree Celsius), among which 19 degree Celsius lasting about 60 days is conducive to the spread between the vector and humans; the humidity range is 50%-80%, of which about 75% humidity is conducive to the survival of the coronavirus; the suitable precipitation range is below 30 mm/ month. Cold air and continuous low temperature over one week are helpful for the elimination of the virus. The prediction results show that with the approach of spring, the temperature in north China gradually rises, and the coronavirus spreads to middle and high latitudes along the temperature line of 13-18 degree Celsius. The population of new coronavirus infections is concentrated in Beijing, Tianjin, Hebei, Jiangsu, Zhejiang, Shanghai and other urban agglomerations. Starting from May 2020, the Beijing-Tianjin-Hebei urban agglomeration, the Central China Zhengzhou-Wuhan urban agglomeration, the eastern Jiangsu-Zhejiang-Shanghai urban agglomeration, and the southern Pearl River Delta urban agglomeration are all under a high temperature above 24 degree Celsius, which is not conducive to the survival and reproduction of coronaviruses, so the epidemic is expected to end. Conclusions: A wide range of continuous warm and dry weather is conducive to the survival of 2019-nCoV. The coming of spring, in addition to the original Wuhan-Zhengzhou urban agglomeration in central China, means that the prevention and control measures in big cities located in mid-latitude should be strengthened, especially the monitoring of transportation hubs. The Pearl River Delta urban agglomeration is a concentrated area of population in south China, with a faster temperature rise than those in mid-high latitudes, and thus the prevention in this area should be prioritized. From a global perspective, cities with a mean temperature below 24 degree Celsius are all high-risk cities for 2019-nCoV transmission before June.

negative: 25 Hepatitis viruses and emerging viruses Abstract: This chapter describes viruses that are enterically transmitted and cause systemic disease. These are recognized as important food and waterborne pathogens. The chapter first summarizes the general characteristics of the viruses, then describes their typical epidemiological patterns. The chapter then discusses methods to detect and to inactivate the viruses, with an emphasis on strategies that can be implemented for food safety.

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: Chapter 14 Viral Diseases This chapter reviews the naturally occurring viral diseases and asymptomatic viral infections of rabbits and hares. The principal emphasis is on virus infections of domestic rabbits of the genus Oryctolagus. Included are Myxoma virus and other Poxviruses, Herpesviruses, Papilloma, and Polyoma viruses, Adenovirus, Parvovirus, Rotavirus, Caliciviruses, including rabbit hemorrhagic disease virus and European brown hare disease virus, Bunyaviruses, Togaviruses, Flaviviruses, Picobirnavirus, and Rabies virus. Each virus is discussed under the following topics, history, etiology, epidemiology, clinical signs, pathology, diagnosis, and control.

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: Quarantine for SARS, Taiwan During the 2003 outbreak of severe acute respiratory syndrome (SARS) in Taiwan, >150,000 persons were quarantined, 24 of whom were later found to have laboratory-confirmed SARS-coronavirus (SARS-CoV) infection. Since no evidence exists that SARS-CoV is infective before the onset of symptoms and the quarantined persons were exposed but not symptomatic, we thought the quarantine's effectiveness should be investigated. Using the Taiwan quarantine data, we found that the onset-to-diagnosis time of previously quarantined confirmed case-patients was significantly shortened compared to that for those who had not been quarantined. Thus, quarantine for SARS in Taiwan screened potentially infective persons for swift diagnosis and hospitalization after onset, thereby indirectly reducing infections. Full-scale quarantine measures implemented on April 28 led to a significant improvement in onset-to-diagnosis time of all SARS patients, regardless of previous quarantine status. We discuss the temporal effects of quarantine measures and other interventions on detection and isolation as well as the potential usefulness of quarantine in faster identification of persons with SARS and in improving isolation measures.

negative: Rapid diagnostic tests for infectious diseases in the emergency department Abstract Background Rapid diagnostic tests (RDTs) for infectious diseases, with a turn-around time <2 hours, are promising tools that could improve patient care, antimicrobial stewardship and infection prevention in the emergency department (ED) setting. Numerous RDTs have been developed but not necessarily for the ED environment. Their successful implementation in the ED relies on their performance and impact on patient management. Objectives The aim of this narrative review is to provide an overview of currently available RDTs for infectious diseases in the ED. Sources PubMed was searched through August 2019 for available studies on RDTs for infectious diseases. Inclusion criteria included: commercial tests approved by the FDA or CE-IVD with data on clinical samples, ability to run on fully-automated systems and result delivery within 2 hours. Content A non-exhaustive list of representative commercially available FDA or CE approved assays was categorized by clinical syndrome: pharyngitis and upper respiratory tract infection, lower respiratory tract infection, gastrointestinal infection, meningitis and encephalitis, fever in the returning traveler and sexually-transmitted infection including HIV. The performance of tests was described based on clinical validation studies. Further, their impact on clinical outcomes and anti-infective use was discussed with a focus on ED-based studies. Implications Clinicians should be familiar with the distinctive features of each RDT and individual performance characteristics for each target. Their integration into ED workflow should be pre-planned considering local constraints of given settings. Additional clinical studies are needed to further evaluate their clinical and cost effectiveness.

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: 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: Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective

negative: Severe acute respiratory syndrome coronavirus spike protein counteracts BST2‐mediated restriction of virus‐like particle release BST2/tetherin, an interferon‐inducible antiviral factor, can block the cellular release of various enveloped viruses. We previously reported that human coronavirus 229E (HCoV‐229E) infection can alleviate the BST2 tethering of HIV‐1 virions by downregulating cell surface BST2, suggesting that coronaviruses are capable of encoding anti‐BST2 factors. Here we report our new finding that severe acute respiratory syndrome coronavirus (SARS‐CoV) spike (S) glycoprotein, similar to Vpu, is capable of antagonizing the BST2 tethering of SARS‐CoV, HCoV‐229E, and HIV‐1 virus‐like particles via BST2 downregulation. However, unlike Vpu (which downmodulates BST2 by means of proteasomal and lysosomal degradation pathways), BST2 downregulation is apparently mediated by SARS‐CoV S through the lysosomal degradation pathway only. We found that SARS‐CoV S colocalized with both BST2 and reduced cell surface BST2, suggesting an association between SARS‐CoV S and BST2 that targets the lysosomal degradation pathway. According to one recent report, SARS‐CoV ORF7a antagonizes BST2 by interfering with BST2 glycosylation(1). Our data provide support for the proposal that SARS‐CoV and other enveloped viruses are capable of evolving supplementary anti‐BST2 factors in a manner that requires virus replication. Further experiments are required to determine whether the BST2‐mediated restriction of authentic SARS‐CoV virions is alleviated by the SARS‐CoV spike protein.

negative: 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.

negative: Outcomes of slit mesh in laparoscopic totally extraperitoneal inguinal hernia repair: Does it affect recurrence? INTRODUCTION The aim of this study was to compare outcomes between slit and non-slit mesh placement in laparoscopic totally extraperitoneal inguinal hernia repair. METHODS This is a retrospective study of 113 patients who underwent laparoscopic totally extraperitoneal inguinal hernia repair with Ultrapro mesh between January 2010 and December 2011. Sixty-two and 82 hernias were operated on in the slit mesh and non-slit mesh groups, respectively. Postoperative complications, recurrence, and patient satisfaction levels were evaluated. RESULTS One hernia in the slit mesh group (1/62, 1.6%) and one in the non-slit mesh group (1/82, 1.2%) developed recurrence (P = 1.00). The incidence of postoperative neuralgia was 4/62 (6.5%) and 7/82 (8.5%) in the slit mesh and non-slit mesh groups, respectively (P = 0.76). Satisfaction rates in the slit mesh and non-slit mesh groups were similar at 60/62 (96.8%) and 80/82 (97.6%), respectively (P = 1.00). CONCLUSION No significant differences in outcomes were found between slit and non-slit mesh placement. Both have low complication rates, low recurrence rates, and high satisfaction levels.

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: Guidelines for dental care provision during the COVID-19 pandemic Abstract Since the coronavirus disease 2019 (COVID-19) outbreak was declared a pandemic on 11 March 2020. Several dental care facilities in affected countries have been completely closed or have been only providing minimal treatment for emergency cases. However, several facilities in some affected countries are still providing regular dental treatment. This can in part be a result of the lack of universal protocol or guidelines regulating the dental care provision during such a pandemic. This lack of guidelines can on one hand increase the nosocomial COVID-19 spread through dental health care facilities, and on the other hand deprive patients’ in need of the required urgent dental care. Moreover, ceasing dental care provision during such a period will incense the burden on hospitals emergency departments already struggle with the pandemic. This work aimed to develop guidelines for dental patients’ management during and after the COVID-19 pandemic. Guidelines for dental care provision during the COVID-19 pandemic were developed after considering the nature of COVID-19 pandemic, and were based on grouping the patients according to condition and need, and considering the procedures according to risk and benefit. It is hoped that the guidelines proposed in this work will help in the management of dental care around the world during and after this COVID-19 pandemic.

negative: Effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with COVID-19 • Initiation of IVIG as adjuvant treatment for COVID-19 pneumonia within 48 hours of admission to the ICU can reduce the use of mechanical ventilation . • Initiation of IVIG as adjuvant treatment for COVID-19 pneumonia within 48 hours of admission to the ICU can reduce hospital length of stay and length of stay in ICU. • Initiation of IVIG as adjuvant treatment for COVID-19 pneumonia within 48 hours of admission to the ICU can reduce 28-day mortality of patients with severe COVID-19 pneumonia.

negative: The eye as the discrete but defensible portal of coronavirus infection Oculo-centric factors may provide a key to understanding invasion success by SARS-CoV-2, a highly contagious, potentially lethal, virus with ocular tropism. Respiratory infection transmission via the eye and lacrimal-nasal pathway elucidated during the 1918 influenza pandemic, remains to be explored in this crisis. The eye and its adnexae represent a large surface area directly exposed to airborne viral particles and hand contact. The virus may bind to corneal and conjunctival angiotensin converting enzyme 2 (ACE2) receptors and potentially to the lipophilic periocular skin and superficial tear film with downstream carriage into the nasopharynx and subsequent access to the lungs and gut. Adenoviruses and influenza viruses share this ocular tropism and despite differing ocular and systemic manifestations and disease patterns, common lessons, particularly in management, emerge. Slit lamp usage places ophthalmologists at particular risk of exposure to high viral loads (and poor prognosis) and as for adenoviral epidemics, this may be a setting for disease transmission. Local, rather than systemic treatments blocking virus binding in this pathway (advocated for adenovirus) are worth considering. This pathway is accessible with eye drops or aerosols containing drugs which appear efficacious via systemic administration. A combination such as hydroxychloroquine, azithromycin and zinc, all of which have previously been used topically in the eye and which work at least in part by blocking ACE2 receptors, may offer a safe, cost-effective and resource-sparing intervention.

negative: Transmission and Control of Respiratory Viral Infections in the Healthcare Setting PURPOSE OF THE REVIEW: Viral respiratory infections have been recognized as a cause of severe illness in immunocompromised and non-immunocompromised hosts. This acknowledgement is a consequence of improvement in diagnosis and better understanding of transmission. Available vaccines and antiviral drugs for prophylaxis and treatment have been developed accordingly. Viral respiratory pathogens are increasingly recognized as nosocomial pathogens as well. The purpose of this review is to describe the most frequent and relevant nosocomial viral respiratory infections, their mechanisms of transmission and the infection control measures to prevent their spread in the healthcare setting. RECENT FINDINGS: Although most mechanisms of transmission and control measures of nosocomial viral infections are already known, improved diagnostic tools allow better characterization of these infections and also lead to the discovery of new viruses such as the coronavirus, which is the cause of the Middle East Respiratory Syndrome, or the human bocavirus. Also, the ability to understand better the impact, dissemination and prevention of these viruses, allows us to improve the measures to prevent these infections. SUMMARY: Healthcare viral respiratory infections increase patient morbidity. Each virus has a different mechanism of transmission; therefore, early detection and prompt implementation of infection control measures are very important in order to avoid their transmission in the hospital setting.

negative: Epidemiological Concepts Epidemiology is the study of the distribution and determinants of health-related states, conditions, or events in specified populations and the application of the results of this study to the control of health problems.(1) It is a quantitative science concerned in infectious diseases with the circumstances under which disease processes occur, the factors that affect their incidence and the host response to the infectious agent, and the use of this knowledge for control and prevention.(2) It includes the pathogenesis of disease in both the community and the individual. For infectious diseases, one must study the circumstances under which both infection and disease occur, for these may be different. Infection is the consequence of an encounter of a potentially pathogenic microorganism with a susceptible human host through an appropriate portal of entry and usually involves a demonstrable host response to the agent. Exposure is the key factor, and the sources of infection lie mostly outside the individual human host, within the environment, or in other infected hosts. Disease represents one of the possible consequences of infection, and the factors important in its development are mostly intrinsic to the host, although the dosage and virulence of the infecting microbe play a role. These intrinsic factors include the age at the time of infection, the portal of entry, the presence or absence of immunity, the vigor of the primary defense system, the efficiency and nature of humoral and cell-mediated immune responses, the genetic makeup of the host, the state of nutrition, the presence of other diseases, and psychosocial influences. These factors that result in the occurrence of clinical illness among those infected have been called the “clinical illness-promotion factors,”(3) and many of them remain unknown. The host responses can include death, the classic clinical features of the disease, mild or atypical forms, subclinical and inapparent infections, and the carrier state, which may exist in the absence of a detectable host response. While the clinician is primarily concerned with disease, the epidemiologist is interested in both infection and disease. Infection without disease is a common phenomenon, so that a study limited to clinical illness alone would give an incomplete epidemiological picture and would be a poor basis for control and prevention.(4) A full understanding involves the pathogenesis of the process leading to clinical disease both in the community and in the individual.

negative: Low-dose Interferon-α Treatment Improves Survival and Inflammatory Responses in a Mouse Model of Fulminant Acute Respiratory Distress Syndrome Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of symptoms, therapeutic strategies for this pathologic condition are still poorly developed. Interferon (IFN)-α is well known as an antiviral cytokine and low-dose IFN-α has been reported to show antiinflammatory effects. Therefore, we investigated how this cytokine affected ARDS in a mouse model. C57BL/6 mice received sequential intratracheal administration of α-galactosylceramide (α-GalCer) and lipopolysaccharide (LPS), which resulted in the development of fulminant ARDS. These mice were then treated intranasally with IFN-α and their survival, lung weight, pathological findings, and cytokine production were evaluated. Administration of low-dose IFN-α prolonged survival of fulminant ARDS mice, but higher doses of IFN-α did not. Histological analysis showed that low-dose IFN-α treatment improved findings of diffuse alveolar damage in fulminant ARDS mice, which was associated with reduction in the wet/dry (W/D) lung weight ratio. Furthermore, IFN-γ production in the lungs was significantly reduced in IFN-α-treated mice, compared with control mice, but tumor necrosis factor (TNF)-α production was almost equivalent for both groups. Low-dose IFN-α shows antiinflammatory and therapeutic effects in a mouse model of fulminant ARDS, and reduced production of IFN-γ in the lung may be involved in the beneficial effect of this treatment.

negative: Alignment using genetic programming with causal trees for identification of protein functions Abstract A hybrid evolutionary model is used to propose a hierarchical homology of protein sequences to identify protein functions systematically. The proposed model offers considerable potentials, considering the inconsistency of existing methods for predicting novel proteins. Because some novel proteins might align without meaningful conserved domains, maximizing the score of sequence alignment is not the best criterion for predicting protein functions. This work presents a decision model that can minimize the cost of making a decision for predicting protein functions using the hierarchical homologies. Particularly, the model has three characteristics: (i) it is a hybrid evolutionary model with multiple fitness functions that uses genetic programming to predict protein functions on a distantly related protein family, (ii) it incorporates modified robust point matching to accurately compare all feature points using the moment invariant and thin-plate spline theorems, and (iii) the hierarchical homologies holding up a novel protein sequence in the form of a causal tree can effectively demonstrate the relationship between proteins. This work describes the comparisons of nucleocapsid proteins from the putative polyprotein SARS virus and other coronaviruses in other hosts using the model.

negative: Respiratory virus infections: Understanding COVID-19 Respiratory viruses affect us throughout our lives, from infancy to old age, causing illnesses ranging from a common cold to severe pneumonia. They belong to several virus families, and although many features of infection with these diverse viruses are shared, some have unique characteristics. Here we explain what happens when we are infected by respiratory viruses, including SARS-CoV-2, which causes COVID-19.

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: Conduite à tenir devant une diarrhée aiguë. Étiologies Résumé Les diarrhées aiguës constituent un problème de santé publique du fait de leur grande fréquence. Leur origine est presque toujours infectieuse et leur évolution spontanément résolutive, le plus souvent en moins de 3 jours. Seul 1 % des diarrhées nécessite d'emblée des explorations complémentaires, notamment des examens de selles, car leur présentation clinique évoque une colite aiguë sous-jacente (selles sanglantes, douleurs abdominales circonscrites), du fait d'un terrain fragile sous-jacent avec un risque immédiat pour le malade, ou d'un contexte particulier (séjour sous les tropiques…). Ces examens de selles doivent être orientés afin de guider le biologiste et améliorer la rentabilité des prélèvements, qui s'avère sinon très faible et coûteuse à l'échelle d'une population. Une antibiothérapie empirique basée essentiellement sur les fluoroquinolones est ensuite licite dans ces cas sélectionnés, en attendant les résultats des examens. Ces explorations sont aussi justifiées lorsque la diarrhée persiste au-delà de 3 jours. Enfin, lorsque l'épisode se prolonge au-delà de 5 jours, avec des prélèvements de selles négatifs, un avis spécialisé est nécessaire. Ainsi, seule une petite proportion de ces diarrhées aiguës va nécessiter une endoscopie, permettant de parler ainsi de colite ou de rectocolite. Au plan thérapeutique, la réhydratation précoce chez l'enfant reste d'actualité car elle a prouvé son efficacité en termes de mortalité depuis plus de deux décennies, principalement dans les pays en voie de développement. Abstract Acute diarrheas are a common disease, and their high frequency constitutes an important problem in terms of public health. Most of the time, they have an infectious origin and spontaneous complete recovery is achieved within less than three days. In practice, history of diarrhea, physical examination and environmental identification are the main points for selecting patients who will need medical explorations. Only 1% of patients need immediate laboratory complementary investigations, i.e., stool analysis, either because their symptomatology indicates potential underlying acute colitis (bloody stools, localized abdominal pain), or when there is an underlying frail condition associated with an immediate risk for the patient, or in case of a particular context such a stay in a tropical area. The practitioner has to inform the biologist on all symptoms and relevant information so as to optimize the analysis and its cost-effectiveness. Until the laboratory results are available, such selected patients require antibiotic treatment (quinolones). These investigations are also needed in case of >3-day persistent diarrhea. When stool samples are free of bacteria or parasite, and when acute diarrhea persists more than 5 days, a specialist should be visited. Thus, only a small proportion of patients with acute diarrhea will undergo endoscopy, probably cases of colitis or recto colitis. Early re-hydration remains the preferential treatment of acute diarrhea in children since, for more than two decades, it has demonstrated its efficacy in reducing mortality, particularly in developing countries.

negative: 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.

negative: Caffeine for the Treatment of Apnea in Bronchiolitis: A Randomized Trial Objective To evaluate the efficacy and safety of caffeine citrate in the treatment of apnea in bronchiolitis. Study design Eligible infants aged ≤4 months presenting to the main pediatric emergency service with apnea associated bronchiolitis were stratified by gestational age (<34 weeks or longer) and randomized to receive a single dose of intravenous 25 mg/kg caffeine citrate or saline placebo. The primary efficacy outcome was a 24-hour apnea-free period beginning after completion of the blinded study drug infusion. Secondary outcomes were frequency of apnea by 24, 48, and 72 hours after study medication, need for noninvasive/invasive ventilation, and length of stay in the hospital's pediatric intensive care/step-down unit. Results A total of 90 infants diagnosed with viral bronchiolitis associated with apnea (median age, 38 days) were enrolled. The rate of respiratory virus panel positivity was similar in the 2 groups (78% for the placebo group vs 84% for the caffeine group). The geometric mean duration to a 24-hour apnea-free period was 28.1 hours (95% CI, 25.6-32.3 hours) for the caffeine group and 29.1 hours (95% CI, 25.7-32.9 hours) for the placebo group (P = .88; OR, 0.99; 95% CI, 0.83-1.17). The frequency of apnea at 24 hours, 24-48 hours, and 48-72 hours after enrollment and the need for noninvasive and invasive ventilation were similar in the 2 groups. No safety issues were reported. Conclusions A single dose of caffeine citrate did not significantly reduce apnea episodes associated with bronchiolitis. Trial registration Clinicaltrials.gov: NCT01435486.

negative: 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.

negative: Quantitative proteomics identifies serum response factor binding protein 1 as a host factor for hepatitis C virus entry Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection as indicated by RNA interference. We further characterized serum response factor binding protein 1 (SRFBP1), which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.

negative: Viable supply chain model: integrating agility, resilience and sustainability perspectives—lessons from and thinking beyond the COVID-19 pandemic Viability is the ability of a supply chain (SC) to maintain itself and survive in a changing environment through a redesign of structures and replanning of performance with long-term impacts. In this paper, we theorize a new notion—the viable supply chain (VSC). In our approach, viability is considered as an underlying SC property spanning three perspectives, i.e., agility, resilience, and sustainability. The principal ideas of the VSC model are adaptable structural SC designs for supply–demand allocations and, most importantly, establishment and control of adaptive mechanisms for transitions between the structural designs. Further, we demonstrate how the VSC components can be categorized across organizational, informational, process-functional, technological, and financial structures. Moreover, our study offers a VSC framework within an SC ecosystem. We discuss the relations between resilience and viability. Through the lens and guidance of dynamic systems theory, we illustrate the VSC model at the technical level. The VSC model can be of value for decision-makers to design SCs that can react adaptively to both positive changes (i.e., the agility angle) and be able to absorb negative disturbances, recover and survive during short-term disruptions and long-term, global shocks with societal and economical transformations (i.e., the resilience and sustainability angles). The VSC model can help firms in guiding their decisions on recovery and re-building of their SCs after global, long-term crises such as the COVID-19 pandemic. We emphasize that resilience is the central perspective in the VSC guaranteeing viability of the SCs of the future. Emerging directions in VSC research are discussed.

negative: Detection of 2019 novel coronavirus in semen and testicular biopsy specimen of COVID-19 patients Background: As of March 11, 2020, the COVID-19 outbreak was declared as a pandemic. Expending our understanding of the transmission routes of the viral infection is crucial in controlling the outbreak. It is unclear whether the 2019 novel coronavirus (2019-nCoV) can directly infect the testes or male genital tract and be sexually transmitted from males. Methods: From January 31 to March 14, 2020, 12 patients in recovery and one patient died of COVID-19 were included in this descriptive study. The clinical characteristics, laboratory findings, chest CT scans and outcome data were recorded. To examine whether there is sexual transmission from male, we employed realtime polymerase chain reaction testing (RT-PCR) to detect 2019-nCov in semen or testicular biopsy specimen. Findings: The age range of the 12 patients in recovery was 22-38 years. None of the patients developed severe COVID-19 pneumonia. As of March 14, 2020, ten patients discharged from the hospital while the rest 2 had developed into recovery stage. All of the patients in recovery tested negative for 2019-nCoV RNA in semen samples. Another died patient was 67 years old, who died in March 10, 2020 and tissue sample via testicular biopsy was tested negative for viral RNA. Conclusion: No positive RT-PCR result was found in the semen or testicular biopsy specimen. The results from this study show no evidence of sexual transmission of 2019-nCov from males.

negative: Airflow Dynamics of Coughing in Healthy Human Volunteers by Shadowgraph Imaging: An Aid to Aerosol Infection Control Cough airflow dynamics have been previously studied using a variety of experimental methods. In this study, real-time, non-invasive shadowgraph imaging was applied to obtain additional analyses of cough airflows produced by healthy volunteers. Twenty healthy volunteers (10 women, mean age 32.2±12.9 years; 10 men, mean age 25.3±2.5 years) were asked to cough freely, then into their sleeves (as per current US CDC recommendations) in this study to analyze cough airflow dynamics. For the 10 females (cases 1–10), their maximum detectable cough propagation distances ranged from 0.16–0.55 m, with maximum derived velocities of 2.2–5.0 m/s, and their maximum detectable 2-D projected areas ranged from 0.010–0.11 m(2), with maximum derived expansion rates of 0.15–0.55 m(2)/s. For the 10 males (cases 11–20), their maximum detectable cough propagation distances ranged from 0.31–0.64 m, with maximum derived velocities of 3.2–14 m/s, and their maximum detectable 2-D projected areas ranged from 0.04–0.14 m(2), with maximum derived expansion rates of 0.25–1.4 m(2)/s. These peak velocities were measured when the visibility of the exhaled airflows was optimal and compare favorably with those reported previously using other methods, and may be seen as a validation of these previous approaches in a more natural setting. However, the propagation distances can only represent a lower limit due to the inability of the shadowgraph method to visualize these cough airflows once their temperature cools to that of the ambient air, which is an important limitation of this methodology. The qualitative high-speed video footage of these volunteers coughing into their sleeves demonstrates that although this method rarely completely blocks the cough airflow, it decelerates, splits and redirects the airflow, eventually reducing its propagation. The effectiveness of this intervention depends on optimum positioning of the arm over the nose and mouth during coughing, though unsightly stains on sleeves may make it unacceptable to some.

negative: Polymorphism of SARS-CoV Genomes Abstract In this work, severe acute respiratory syndrome associated coronavirus (SARS-CoV) genome BJ202 (AY864806) was completely sequenced. The genome was directly accessed from the stool sample of a patient in Beijing. Comparative genomics methods were used to analyze the sequence variations of 116 SARS-CoV genomes (including BJ202) available in the NCBI Gen-Bank. With the genome sequence of GZ02 as the reference, there were 41 polymorphic sites identified in BJ202 and a total of 278 polymorphic sites present in at least two of the 116 genomes. The distribution of the polymorphic sites was biased over the whole genome. Nearly half of the variations (50.4%, 140/278) clustered in the one third of the whole genome at the 3′ end (19.0 kb-29.7 kb). Regions encoding Orf10–11, Orf3/4, E, M and S protein had the highest mutation rates. A total of 15 PCR products (about 6.0 kb of the genome) including 11 fragments containing 12 known polymorphic sites and 4 fragments without identified polymorphic sites were cloned and sequenced. Results showed that 3 unique polymorphic sites of BJ202 (positions 13 804, 15 031 and 20 792) along with 3 other polymorphic sites (26 428, 26 477 and 27 243) all contained 2 kinds of nucleotides. It is interesting to find that position 18379 which has not been identified to be polymorphic in any of the other 115 published SARS-CoV genomes is actually a polymorphic site. The nucleotide composition of this site is A (8) to G (6). Among 116 SARS-CoV genomes, 18 types of deletions and 2 insertions were identified. Most of them were related to a 300 bp region (27 700–28 000) which encodes parts of the putative ORF9 and ORF10–11. A phylogenetic tree illustrating the divergence of whole BJ202 genome from 115 other completely sequenced SARS-CoVs was also constructed. BJ202 was phylogeneticly closer to BJ01 and LLJ-2004.

negative: Diagnosis and clinical management of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2.0): Working Group of 2019 Novel Coronavirus, Peking Union Medical College Hospital Since December 2019, China has been experiencing an outbreak of a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical features include fever, coughing, shortness of breath, and inflammatory lung infiltration. China rapidly listed SARS-CoV-2-related pneumonia as a statutory infectious disease. To standardize the diagnosis and treatment of this new infectious disease, an operational recommendation for the diagnosis and management of SARS-CoV-2 infection is developed by Peking Union Medical College Hospital.

negative: Echo in Pandemic: Front Line Perspective, Expanding Role of Ultrasound and Ethics of Resource Allocation Abstract The grave clinical context of the pandemic must be understood. Italy is immersed in COVID-19. Most of the world will soon follow. The United States currently has the most documented cases of COVID-19 of any nation. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) associated acute cardiomyopathy is common in critical care patients and is associated with a high mortality. COVID-19 patients frequently require mechanical support for adequate oxygenation. A severe shortfall of ventilators is predicted. Of equal concern is the projected shortage of trained professionals required to care for patients on mechanical ventilation. Ultrasonography is proving to be a valuable tool for identifying the pulmonary manifestations and progression of COVID-19. Lung ultrasound also facilitates successful weaning from mechanical ventilation. Ultrasonography of the lung, pleura and diaphragm are easily mastered by experienced echocardiographers. Echocardiography has an established role for optimal fluid management and recognition of cardiac disease including SARS-CoV-2 associated acute cardiomyopathy. Cardiologists, anesthesiologists, sonographers, and all providers should be prepared to commit their full spectrum of skills to mitigate the consequences of the pandemic. We should also be prepared to collaborate and cross-train to expand professional services as necessary. During a declared health care crisis, providers must be familiar with the ethical principles, organizational structure, practical application, and gravity of limited resource allocation.

negative: 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.

negative: Survival of Enteric Viruses in the Environment and Food Enteric viruses are those human viruses that are primarily transmitted by the fecal-oral route, either by person-to-person contact or by ingestion of contaminated food or water. The importance of viral foodborne diseases is increasingly being recognized, and several international organizations have found that there is an upward trend in their incidence. Thus, in this review, state-of-the-art information regarding virus persistence in food and the environment is compiled.

negative: Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. The distribution of the severe acute respiratory syndrome coronavirus (SARS-CoV) receptor, an angiotensin-converting enzyme 2 (ACE2), does not strictly correlate with SARS-CoV cell tropism in lungs; therefore, other cellular factors have been predicted to be required for activation of virus infection. In the present study, we identified transmembrane protease serine 2 (TMPRSS2), whose expression does correlate with SARS-CoV infection in the upper lobe of the lung. In Vero cells expressing TMPRSS2, large syncytia were induced by SARS-CoV infection. Further, the lysosome-tropic reagents failed to inhibit, whereas the heptad repeat peptide efficiently inhibited viral entry into cells, suggesting that TMPRSS2 affects the S protein at the cell surface and induces virus-plasma membrane fusion. On the other hand, production of virus in TMPRSS2-expressing cells did not result in S-protein cleavage or increased infectivity of the resulting virus. Thus, TMPRSS2 affects the entry of virus but not other phases of virus replication. We hypothesized that the spatial orientation of TMPRSS2 vis-a-vis S protein is a key mechanism underling this phenomenon. To test this, the TMPRSS2 and S proteins were expressed in cells labeled with fluorescent probes of different colors, and the cell-cell fusion between these cells was tested. Results indicate that TMPRSS2 needs to be expressed in the opposing (target) cell membrane to activate S protein rather than in the producer cell, as found for influenza A virus and metapneumoviruses. This is the first report of TMPRSS2 being required in the target cell for activation of a viral fusion protein but not for the S protein synthesized in and transported to the surface of cells. Our findings suggest that the TMPRSS2 expressed in lung tissues may be a determinant of viral tropism and pathogenicity at the initial site of SARS-CoV infection.

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: 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.

negative: Operation Department: Infection Control Infection control in the operation department is the result of many single factors and routines, based on experience, documentation and expert panels through more than a hundred years. Many factors and routines in surgery are evidence-based, but most of them are still lacking evidence and can probably never be investigated because of ethical problems. Consequently, consensus and guidance are used to a great extent. Surgery opens into sterile tissues for hours, where there is massive tissue damage by knife, diathermy, clogging of vessels, pressure against and drying of tissues, decreased blood supply, impaired phagocytosis and impaired infection defence. Microbes deposited in this devitalized tissues may find a good basis for growth and proliferation if there is lack of infection control and sterility. For patients with ongoing infections and who need surgery, special routines are made to prevent the spread of infections in the operation department. This chapter is a practical description of many important preventive procedures that may protect the surgical patient against surgical site infection (SSI).

negative: ACE2 fragment as a decoy for novel SARS-Cov-2 virus Novel SARS-Cov-2 enters human cells via interaction between the surface spike (S) glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). Using a combination of comparative structural analyses of the binding surface of the S protein to ACE2, docking experiments, and molecular dynamics simulations we computationally identified a minimal, stable fragment of ACE2. This fragment binds to the S protein, is soluble, and appears not to bind to the physiological ligand angiotensinII. These results suggest a possible use of the ACE2 fragment as a decoy that could interfere with viral binding by competition.

negative: Ultra-Low-Cost Integrated Silicon-based Transducer for On-Site, Genetic Detection of Pathogens Rapid screening and low-cost diagnosis play a crucial role in choosing the correct course of intervention e.g., drug therapy, quarantine, no action etc. when dealing with highly infectious pathogens. This is especially important if the disease-causing agent has no effective treatment, such as the novel coronavirus SARS-CoV-2 (the pathogen causing COVID-19), and shows no or similar symptoms to other common infections. We report a silicon-based integrated Point-of-Need (PoN) transducer (TriSilix) that can chemically-amplify and detect pathogen-specific sequences of nucleic acids (NA) quantitatively in real-time. Unlike other silicon-based technologies, TriSilix can be produced at wafer-scale in a standard laboratory; we have developed a series of methodologies based on metal-assisted chemical (wet) etching, electroplating, thermal bonding and laser-cutting to enable a cleanroom-free low-cost fabrication that does not require processing in an advanced semiconductor foundry. TriSilix is, therefore, resilient to disruptions in the global supply chain as the devices can be produced anywhere in the world. To create an ultra-low-cost device, the architecture proposed exploits the intrinsic properties of silicon and integrates three modes of operation in a single chip: i) electrical (Joule) heater, ii) temperature sensor (i.e. thermistor) with a negative temperature coefficient that can provide the precise temperature of the sample solution during reaction and iii) electrochemical sensor for detecting target NA. Using TriSilix, the sample solution can be maintained at a single, specific temperature (needed for isothermal amplification of NA such as Recombinase Polymerase Amplification (RPA) or cycled between different temperatures (with a precision of ±1.3°C) for Polymerase Chain Reaction (PCR) while the exact concentration of amplicons is measured quantitatively and in real-time electrochemically. A single 4-inch Si wafer yields 37 TriSilix chips of 10×10×0.65 mm in size and can be produced in 7 hours, costing ~US $0.35 per device. The system is operated digitally, portable and low power – capable of running up to 35 tests with a 4000 mAh battery (a typical battery capacity of a modern smartphone). We were able to quantitatively detect a 563-bp fragment (Insertion Sequence IS900) of the genomic DNA of M. avium subsp. paratuberculosis (extracted from cultured field samples) through PCR in real-time with a Limit-of-Detection of 20 fg, equivalent to a single bacterium, at the 30th cycle. Using TriSilix, we also detected the cDNA from SARS-CoV-2 (1 pg), through PCR, with high specificity against SARS-CoV (2003).

negative: Necessitating repeated chest CT in COVID-19 pneumonia

negative: Resistance of livestock to viruses: mechanisms and strategies for genetic engineering

negative: SARS: un Coronavirus formellement impliqué

negative: 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.

negative: Insulin Degrading Enzyme Induces a Conformational Change in Varicella-Zoster Virus gE, and Enhances Virus Infectivity and Stability Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines.

negative: Development of a Laboratory-safe and Low-cost Detection Protocol for SARS-CoV-2 of the Coronavirus Disease 2019 (COVID-19) The severe acute respiratory coronavirus 2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, has spread rapidly to over a dozen countries. Especially, the spike of case numbers in South Korea sparks pandemic worries. This virus is reported to spread mainly through person-to-person contact via respiratory droplets generated by coughing and sneezing, or possibly through surface contaminated by people coughing or sneezing on them. More critically, there have been reports about the possibility of this virus to transmit even before a virus-carrying person to show symptoms. Therefore, a low-cost, easy-access protocol for early detection of this virus is desperately needed. Here, we have established a real-time reverse-transcription PCR (rtPCR)-based assay protocol composed of easy specimen self-collection from a subject via pharyngeal swab, Trizol-based RNA purification, and SYBR Green-based rtPCR. This protocol shows an accuracy and sensitivity limit of 1-10 virus particles as we tested with a known lentivirus. The cost for each sample is estimated to be less than 15 US dollars. Overall time it takes for an entire protocol is estimated to be less than 4 hours. We propose a cost-effective, quick-and-easy method for early detection of SARS-CoV-2 at any conventional Biosafety Level II laboratories that are equipped with a rtPCR machine. Our newly developed protocol should be helpful for a first-hand screening of the asymptomatic virus-carriers for further prevention of transmission and early intervention and treatment for the rapidly propagating virus.

negative: The airborne transmission of infection between flats in high-rise residential buildings: Particle simulation Abstract Several case clusters occurred in high-rise residential buildings in Hong Kong in the 2003 SARS (the severe acute respiratory syndrome) epidemic, which motivated a series of engineering investigations into the possible airborne transport routes. It is suspected that, driven by buoyancy force, the polluted air that exits the window of the lower floor may re-enter the immediate upper floor through the window on the same side. This cascade effect has been quantified and reported in a previous paper, and it is found that, by tracer gas concentration analysis, the room in the adjacent upstairs may contain up to 7% of the air directly from the downstairs room. In this study, after validation against the experimental data from literatures, Eulerian and Lagrangian approaches are both adopted to numerically investigate the dispersion of expiratory aerosols between two vertically adjacent flats. It is found that the particle concentration in the upper floor is two to three orders of magnitude lower than in the source floor. 1.0μm particles disperse like gaseous pollutants. For coarse particles larger than 20.0μm, strong deposition on solid surfaces and gravitational settling effect greatly limit their upward transport.

negative: Cell-Surface Peptidases∗ ∗ Dedicated to Professor Dr. Eberhard Heymann on the occasion of his 65th birthday. Abstract The cell surface has various functions: communicating with other cells, integrating into the tissue, and interacting with the extracellular matrix. Proteases play a key role in these processes. This review focuses on cell-surface peptidases (ectopeptidases, oligopeptidases) that are involved in the inactivation or activation of extracellular regulatory peptides, hormones, paracrine peptides, cytokines, and neuropeptides. The nomenclature of cell-surface peptidases is explained in relation to other proteases, and information is provided on membrane anchoring, catalytic sites, regulation, and, in particular, on their physiological and pharmacological importance. Furthermore, nonenzymatic (binding) functions and participation in intracellular signal transduction of cell surfaces peptidases are described. An overview on the different cell-surface peptidases is given, and their divergent functions are explained in detail. An example of actual pharmacological importance, dipeptidyl-peptidase IV (CD26), is discussed.

negative: Four Cultural Narratives for Managing Social-ecological Complexity in Public Natural Resource Management Public Natural Resource Management (NRM) agencies operate in complex social-ecological domains. These complexities proliferate unpredictably therefore investigating and supporting the ability of public agencies to respond effectively is increasingly important. However, understanding how public NRM agencies innovate and restructure to negotiate the range of particular complexities they face is an under researched field. One particular conceptualisation of the social-ecological complexities facing NRM agencies that is of growing influence is the Water–Energy–Food (WEF) nexus. Yet, as a tool to frame and understand those complexities it has limitations. Specifically, it overlooks how NRMs respond institutionally to these social-ecological complexities in the context of economic and organisational challenges—thus creating a gap in the literature. Current debates in public administration can be brought to bear here. Using an organisational cultures approach, this paper reports on a case study with a national NRM agency to investigate how they are attempting to transform institutionally to respond to complexity in challenging times. The research involved 12 elite interviews with senior leaders from Natural Resources Wales, (NRW) and investigated how cultural narratives are being explicitly and implicitly constructed and mobilised to this end. The research identified four distinct and sequential cultural narratives: collaboration, communication, trust, and empowerment where each narrative supported the delivery of different dimensions of NRW’s social-ecological complexity mandate. Counter to the current managerialist approaches in public administration, these results suggest that the empowerment of expert bureaucrats is important in responding effectively to complexity.

negative: Sizes of Long RNA Molecules Are Determined by the Branching Patterns of Their Secondary Structures Long RNA molecules are at the core of gene regulation across all kingdoms of life, while also serving as genomes in RNA viruses. Few studies have addressed the basic physical properties of long single-stranded RNAs. Long RNAs with nonrepeating sequences usually adopt highly ramified secondary structures and are better described as branched polymers. To test whether a branched polymer model can estimate the overall sizes of large RNAs, we employed fluorescence correlation spectroscopy to examine the hydrodynamic radii of a broad spectrum of biologically important RNAs, ranging from viral genomes to long noncoding regulatory RNAs. The relative sizes of long RNAs measured at low ionic strength correspond well to those predicted by two theoretical approaches that treat the effective branching associated with secondary structure formation—one employing the Kramers theorem for calculating radii of gyration, and the other featuring the metric of maximum ladder distance. Upon addition of multivalent cations, most RNAs are found to be compacted as compared with their original, low ionic-strength sizes. These results suggest that sizes of long RNA molecules are determined by the branching pattern of their secondary structures. We also experimentally validate the proposed computational approaches for estimating hydrodynamic radii of single-stranded RNAs, which use generic RNA structure prediction tools and thus can be universally applied to a wide range of long RNAs.

negative: Microstructure, evolution, and ontogeny of scale surfaces in cordylid and gerrhosaurid lizards The distal oberhautchen and proximal beta layer of 41 species and every genus of cordylid and gerrhosaurid lizard were examined with a scanning electron microscope. Scale organs in these families are concentrated on the face, and scale organs occur singly or in pairs below the keel on the dorsals of cordylids but not gerrhosaurids. Most species examined possess primitive, lenticular scale organs. Unique and previously unknown, projecting scale organs occur in two species of Cordylus. Scale organs appear to be absent in species of Chamaesaura. The scale surfaces of cordylids are covered in macrohoneycomb. Individual compartments of cordylid macrohoneycomb are not intracellular structures but may be overlain by apparent oberhautchen cells. In some cordylid species, part of each cell is free and projects away from the scale surface as a pointed flap. Gerrhosaurids lack macrohoneycomb. Instead, their scale surfaces are covered in lamellae without dentate borders, 50–100 times as long as wide. The epidermis of Platysaurus is unique among cordylids in possessing lamellae 1–8 times as wide as long that overlap macrohoneycomb in some regions of the body. The scale surfaces of Cordylus cordylus undergo an ontogenetic change similar to that recently described for the xenosaurid genus Shinisaurus. Phylogenetic analysis of scale surface features allows the partitioning of Cordylus into three species groups and Chamaesaura into two species groups. Synapomorphies of the species of Chamaesaura, the species of Platysaurus, and the genera of the gerrhosaurids are also described. © 1995 Wiley‐Liss, Inc.

negative: Staying Home, Staying Safe? A Short-Term Analysis of COVID-19 on Dallas Domestic Violence Abstract COVID-19 has wreaked havoc on the lives of persons around the world and social scientists are just beginning to understand its consequences on human behavior. One policy that public health officials put in place to help stop the spread of the virus were stay-at-home/shelter-in-place lockdown-style orders. While designed to protect people from the coronavirus, one potential and unintended consequence of such orders could be an increase in domestic violence – including abuse of partners, elders or children. Stay-at-home orders result in perpetrators and victims being confined in close quarters for long periods of time. In this study, we use data from Dallas, Texas to examine the extent to which a local order was associated with an increase in domestic violence. Our results provide some evidence for a short-term spike in the 2 weeks after the lockdown was instituted but a decrease thereafter. We note that it is difficult to determine just how much the lockdown was the cause of this increase as the domestic violence trend was increasing prior to the order.

negative: Canine Respiratory Coronavirus: An Emerging Pathogen in the Canine Infectious Respiratory Disease Complex Infectious respiratory disease in dogs is a constant challenge because of the involvement of several pathogens and environmental factors. Canine respiratory coronavirus (CRCoV) is a new coronavirus of dogs, which is widespread in North America, Japan, and several European countries. CRCoV has been associated with respiratory disease, particularly in kenneled dog populations. The virus is genetically and antigenically distinct from enteric canine coronavirus; therefore, specific tests are required for diagnosis.

negative: Antiviral B cell and T cell immunity in the lungs Respiratory viruses are frequent causes of repeated common colds, bronchitis and pneumonia, which often occur unpredictably as epidemics and pandemics. Despite those decimating effects on health and decades of intensive research, treatments remain largely supportive. The only commonly available vaccines are against influenza virus, and even these need improvement. The lung shares some features with other mucosal sites, but preservation of its especially delicate anatomical structures necessitates a fine balance of pro- and anti-inflammatory responses; well-timed, appropriately placed and tightly regulated T cell and B cell responses are essential for protection from infection and limitation of symptoms, whereas poorly regulated inflammation contributes to tissue damage and disease. Recent advances in understanding adaptive immunity should facilitate vaccine development and reduce the global effect of respiratory viruses.

negative: Applications of ultraviolet germicidal irradiation disinfection in health care facilities: Effective adjunct, but not stand-alone technology This review evaluates the applicability and relative contribution of ultraviolet germicidal irradiation (UVGI) to disinfection of air in health care facilities. A section addressing the use of UVGI for environmental surfaces is also included. The germicidal susceptibility of biologic agents is addressed, but with emphasis on application in health care facilities. The balance of scientific evidence indicates that UVGI should be considered as a disinfection application in a health care setting only in conjunction with other well-established elements, such as appropriate heating, ventilating, and air-conditioning (HVAC) systems; dynamic removal of contaminants from the air; and preventive maintenance in combination with through cleaning of the care environment. We conclude that although UVGI is microbiocidal, it is not “ready for prime time” as a primary intervention to kill or inactivate infectious microorganisms; rather, it should be considered an adjunct. Other factors, such as careful design of the built environment, installation and effective operation of the HVAC system, and a high level of attention to traditional cleaning and disinfection, must be assessed before a health care facility can decide to rely solely on UVGI to meet indoor air quality requirements for health care facilities. More targeted and multiparameter studies are needed to evaluate the efficacy, safety, and incremental benefit of UVGI for mitigating reservoirs of microorganisms and ultimately preventing cross-transmission of pathogens that lead to health care-associated infections.

negative: Infections Associated with Group Childcare

negative: Chapter 19 Current and New Approaches for Mucosal Vaccine Delivery Abstract Mucosal surfaces are the interface between the host’s internal milieu and the external environment, and they have dual functions, serving as physical barriers to foreign antigens and as accepting sites for vital materials. Mucosal vaccines are more favored to prevent mucosal infections from the portal of entry. Although mucosal vaccination has many advantages, licensed mucosal vaccines are scarce. The most widely studied mucosal routes are oral and intranasal. Licensed oral and intranasal vaccines are composed mostly of whole cell killed or live attenuated microorganisms serving as both delivery systems and built-in adjuvants. Future mucosal vaccines should be made with more purified antigen components, which will be relatively less immunogenic. To induce robust protective immune responses against well-purified vaccine antigens, an effective mucosal delivery system is an essential requisite. Recent developments in biomaterials and nanotechnology have enabled many innovative mucosal vaccine trials. For oral vaccination, the vaccine delivery system should be able to stably carry antigens and adjuvants and resist harsh physicochemical conditions in the stomach and intestinal tract. Besides many nano/microcarrier tools generated by using natural and chemical materials, the development of oral vaccine delivery systems using food materials should be more robustly researched to expand vaccine coverage of gastrointestinal infections in developing countries. For intranasal vaccination, the vaccine delivery system should survive the very active mucociliary clearance mechanisms and prove safety because of the anatomical location of nasal cavity separated by a thin barrier. Future mucosal vaccine carriers, regardless of administration routes, should have certain common characteristics. They should maintain stability in given environments, be mucoadhesive, and have the ability to target specific tissues and cells.

negative: Emerging viruses set to soar The emergence rate of novel viruses, such as the coronavirus that sparked SARS, could well be on the rise.Researchers now think that the SARS virus split from group 2 coronaviruses, and that this happened relatively recently on the scale of coronavirus evolution.

negative: Long-Term Persistence of IgG Antibodies in SARS-CoV Infected Healthcare Workers BACKGROUND: The ongoing worldwide outbreak of the 2019-nCoV is markedly similar to the severe acute respiratory syndrome (SARS) outbreak 17 years ago. During the 2002-2003 SARS outbreak, healthcare workers formed a special population of patients. Although virus-specific IgG play important roles in virus neutralization and prevention against future infection, limited information is available regarding the long term persistence of IgG after infection with SARS-like coronavirus. METHODS: A long-term prospective cohort study followed 34 SARS-CoV-infected healthcare workers from a hospital with clustered infected cases during the 2002-2003 SARS outbreak in Guangzhou, China, with a 13-year follow-up. Serum samples were collected annually from 2003-2015. Twenty SARS-CoV-infected and 40 non-infected healthcare workers were enrolled in 2015, and their serum samples were collected. All sera were tested for IgG antibodies with ELISA using whole virus and a recombinant nucleocapsid protein of SARS-CoV, as a diagnostic antigen. RESULTS: Anti SARS-CoV IgG was found to persist for up to 12 years. IgG titers typically peaked in 2004, declining rapidly from 2004-2006, and then continued to decline at a slower rate. IgG titers in SARS-CoV-infected healthcare workers remained at a significantly high level until 2015. Patients treated with corticosteroids at the time of infection were found to have lower IgG titers than those without. CONCLUSIONS: IgG antibodies against SARS-CoV can persist for at least 12 years. The presence of SARS-CoV IgG might provide protection against SARS-CoV and other betacoronavirus. This study provides valuable information regarding humoral immune responses against SARS-CoV and the 2019-nCoV.

negative: Vitrification after multiple rounds of sample application and blotting improves particle density on cryo-electron microscopy grids Single particle cryo-electron microscopy (cryoEM) is becoming widely adopted as a tool for structural characterization of biomolecules at near-atomic resolution. Vitrification of the sample to obtain a dense distribution of particles within a single field of view remains a major bottleneck for the success of such experiments. Here, we describe a simple and cost-effective method to increase the density of frozen-hydrated particles on grids with holey carbon support films. It relies on performing multiple rounds of sample application and blotting prior to plunge freezing in liquid ethane. We show that this approach is generally applicable and significantly increases particle density for a range of samples, such as small protein complexes, viruses and filamentous assemblies. The method is versatile, easy to implement, minimizes sample requirements and can enable characterization of samples that would otherwise resist structural studies using single particle cryoEM.

negative: Intermediate compartment (IC): from pre-Golgi vacuoles to a semi-autonomous membrane system Despite its discovery more than three decades ago and well-established role in protein sorting and trafficking in the early secretory pathway, the intermediate compartment (IC) has remained enigmatic. The prevailing view is that the IC evolved as a specialized organelle to mediate long-distance endoplasmic reticulum (ER)–Golgi communication in metazoan cells, but is lacking in other eukaryotes, such as plants and fungi. However, this distinction is difficult to reconcile with the high conservation of the core machineries that regulate early secretory trafficking from yeast to man. Also, it has remained unclear whether the pleiomorphic IC components—vacuoles, tubules and vesicles—represent transient transport carriers or building blocks of a permanent pre-Golgi organelle. Interestingly, recent studies have revealed that the IC maintains its compositional, structural and spatial properties throughout the cell cycle, supporting a model that combines the dynamic and stable aspects of the organelle. Moreover, the IC has been assigned novel functions, such as cell signaling, Golgi-independent trafficking and autophagy. The emerging permanent nature of the IC and its connections with the centrosome and the endocytic recycling system encourage reconsideration of its relationship with the Golgi ribbon, role in Golgi biogenesis and ubiquitous presence in eukaryotic cells.

negative: Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection BACKGROUND: Mortality is high among patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. We aimed to determine hospital mortality and the factors associated with it in a cohort of MERS-CoV patients. METHODS: We reviewed hospital records of confirmed cases (detection of virus by polymerase chain reaction from respiratory tract samples) of MERS-CoV patients (n = 63) admitted to Buraidah Central Hospital in Al-Qassim, Saudi Arabia between 2014 and 2017. We abstracted data on demography, vital signs, associated conditions presented on admission, pre-existing chronic diseases, treatment, and vital status. Bi-variate comparisons and multiple logistic regressions were the choice of data analyses. RESULTS: The mean age was 60 years (SD = 18.2); most patients were male (74.6%) and Saudi citizens (81%). All but two patients were treated with Ribavirin plus Interferon. Hospital mortality was 25.4%. Patients who were admitted with septic shock and/or organ failure were significantly more likely to die than patients who were admitted with pneumonia and/or acute respiratory distress syndrome (OR = 47.9, 95% CI = 3.9, 585.5, p-value 0.002). Age, sex, and presence of chronic conditions were not significantly associated with mortality. CONCLUSION: Hospital mortality was 25%; septic shock/organ failure at admittance was a significant predictor of mortality.

negative: The effects of renin-angiotensin system inhibitors (RASI) in Corona Virus Disease (COVID-19) with Hypertension: A retrospective, single-center trial Abstract Introduction and objective: A recent outbreak of Coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin-angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with Hypertension. Patients and method: In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. Results: Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. Conclusions: Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanisms.

negative: 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.

negative: A study on infectivity of asymptomatic SARS-CoV-2 carriers. BACKGROUND An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers. MATERIAL AND METHODS 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules. RESULTS The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test. CONCLUSION In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.

negative: The Epidemiology of Viral Infections in Dogs and Cats Understanding the epidemiology of an infectious disease is a prerequisite to be being able to suggest the most appropriate methods for prevention and control of the disease. This article reviews some important epidemiologic concepts.

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: Mass Air Medical Repatriation of Coronavirus Disease 2019 Patients Abstract Recent coronavirus disease 2019 (COVID-19) events have presented challenges to health care systems worldwide. Air medical movement of individuals with potential infectious disease poses unique challenges and threats to crews and receiving personnel. The US Department of Health and Human Services air medical evacuation teams of the National Disaster Medical System directly supported 39 flights, moving over 2,000 individuals. Infection control precautions focused on source and engineering controls, personal protective equipment, safe work practices to limit contamination, and containment of the area of potential contamination. Source control to limit transmission distance was used by requiring all passengers to wear masks (surgical masks for persons under investigation and N95 for known positives). Engineering controls used plastic sheeting to segregate and treat patients who developed symptoms while airborne. Crews used Tyvek (Dupont Richmond, VA) suits with booties and a hood, a double layer of gloves, and either a powered air-purifying respirator or an N95 mask with a face shield. For those outside the 6-ft range, an N95 mask and gloves were worn. Safe work practices were used, which included mandatory aircraft surface decontamination, airflow exchanges, and designated lavatories. Although most patients transported were stable, to the best of our knowledge, this represents the largest repatriation of potentially contagious patients in history without infection of any transporting US Department of Health and Human Services air medical evacuation crews.

negative: Reusable and Recyclable Graphene Masks with Outstanding Superhydrophobic and Photothermal Performances. The 2019 coronavirus outbreak (COVID-19) is affecting over 210 countries and territories, and it is spreading mainly by respiratory droplets. The use of disposable surgical masks is common for patients, doctors, and even the general public in highly risky areas. However, the current surgical masks cannot self-sterilize in order to reuse or be recycled for other applications. The resulting high economic and environmental costs are further damaging societies worldwide. Herein, we reported a unique method for functionalizing commercially available surgical masks with outstanding self-cleaning and photothermal properties. A dual-mode laser-induced forward transfer method was developed for depositing few-layer graphene onto low-melting temperature nonwoven masks. Superhydrophobic states were observed on the treated masks' surfaces, which can cause the incoming aqueous droplets to bounce off. Under sunlight illumination, the surface temperature of the functional mask can quickly increase to over 80 °C, making the masks reusable after sunlight sterilization. In addition, this graphene-coated mask can be recycled directly for use in solar-driven desalination with outstanding salt-rejection performance for long-term use. These roll-to-roll production-line-compatible masks can provide us with better protection against this severe virus. The environment can also benefit from the direct recycling of these masks, which can be used for desalinating seawater.

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 SARS-CoV-2 mutational profile, spike protein stability and viral transmission The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has a capability of gaining rapid mutations as the virus spreads. Whole genome sequencing data offers a wide range of opportunities to study the mutation dynamics. The advantage of increasing amount of whole genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity and to investigate the implications of those mutations in protein stability and viral transmission. Four proteins, surface glycoprotein, nucleocapsid, ORF1ab and ORF8 showed frequent mutations, while envelop, membrane, ORF6 and ORF7a proteins showed conservation in terms of amino acid substitutions. Some of the mutations across different proteins showed co-occurrence, suggesting their functional cooperation in stability, transmission and adaptability. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Analysis of protein structure stability of surface glycoprotein mutants indicated viability of specific variants and are more prone to be temporally and spatially distributed across the globe. Similar empirical analysis of other proteins indicated existence of important functional implications of several variants. Analysis of co-occurred mutants indicated their structural and/or functional interaction among different SARS-COV-2 proteins. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing and containment of the disease.

negative: Medical masks and Respirators for the Protection of Healthcare Workers from SARS-CoV-2 and other viruses Abstract The use of medical masks and respirators as personal protective equipment is pivotal to reducing the level of biological hazard to which healthcare workers are exposed during the outbreak of highly diffusible pathogens, such as the recent novel coronavirus SARS-CoV-2. Unfortunately, during this pandemic, supplies are rapidly running out worldwide, with potential consequences for the rate of occupational infections. Also, knowledge about specific characteristics of respirators is of utmost importance to select the proper type according to the clinical setting. A wide variety of literature is available on the topic, but mostly based on Influenza viruses infection models. Clinical evidence on the use of respirators is poor and interest in the topic has not been constant over time. A better understanding of SARS-CoV-2 transmission is needed, together with high-quality clinical data on the use of respirators or alternative devices. Moreover, healthcare workers, regardless of their level of experience, should receive specific training. This review aims to summarize the available evidence on the use of medical masks and respirators in the context of viral infections, especially the current coronavirus disease 2019 (COVID-19).

negative: Hydroxychloroquine and chloroquine in COVID-19: should they be used as standard therapy? The pandemic of the new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has urged the nations to an unprecedented world-wide reaction, including an accelerated exploration of therapeutic options. In the absence of a vaccine and specifically designed antivirals, the medical community has proposed the use of various previously available medications in order to reduce the number of patients requiring prolonged hospitalizations, oxygen therapy, and mechanical ventilation and to decrease mortality from coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine are among the proposed drugs and are the most widely used so far, despite the lack of robust evidence on their usefulness. The objective of this article is to review and discuss the possible role of these drugs in the therapy of COVID-19.

negative: Genomic diversity of SARS-CoV-2 in Coronavirus Disease 2019 patients BACKGROUND: A novel coronavirus (SARS-CoV-2) has infected more than 75,000 individuals and spread to over 20 countries. It is still unclear how fast the virus evolved and how the virus interacts with other microorganisms in the lung. METHODS: We have conducted metatranscriptome sequencing for the bronchoalveolar lavage fluid of eight SARS-CoV-2 patients, 25 community-acquired pneumonia (CAP) patients, and 20 healthy controls. RESULTS: The median number of intra-host variants was 1-4 in SARS-CoV-2 infected patients, which ranged between 0 and 51 in different samples. The distribution of variants on genes was similar to those observed in the population data (110 sequences). However, very few intra-host variants were observed in the population as polymorphism, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intra-host variants in a person-to-person spread, the risk should not be overlooked. The microbiota in SARS-CoV-2 infected patients was similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria. CONCLUSION: SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intra-host variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.

negative: Protective effect of OK‐432 (streptococcal preparation) on murine fulminant hepatitis following mouse hepatitis virus infection The effects of OK‐432 (streptococcal preparation) on murine fulminant hepatitis were investigated. Hepatitis was induced by injection of mouse hepatitis virus type 2 (MHV‐2) at a strength of either 1 times 10(3) or 1 times 10(4) plaque‐forming units (PFU). Mice without OK‐432 treatment died within 5 days, whereas mice pre‐inoculated with OK‐432 showed survival rates of 50% (1 times 10(3)PFU) or 10% (1 times 10(4)PFU) after 60 days. Survival time was not prolonged if OK‐432 was injected after MHV‐2. Examined histologically, mice not treated with OK‐432 showed severe haemorrhagic necrosis of the liver, often panlobular. Treated mice showed less necrosis; the least necrosis was observed in those injected with OK‐432 before MHV‐2. In those mice injected first with OK‐432 and then with 1 times 10(3)PFU of MHV‐2 that survived 7 days, autopsy showed a very slight and focal hepatic necrosis, with follicular infiltration by lymphocytes and macrophages. Mitogenic reaction of spleen cells was remarkably less than normal in mice with MHV‐2 injection. However, mice injected with OK‐432 before MHV‐2 (same treatment as mice showing high survival rates) showed relatively high reactivity in comparison with mice not treated with OK‐432.

negative: Prevalence of novel coronavirus pneumonia in the early stage of transmission and responding strategies in Japan/ 上海预防医学 Novel coronavirus pneumonia disease (COVID-19) caused by SARS-CoV-2 began to emerge in Wuhan, Hubei, China in December 2019. It is currently spreading globally including Japan. The COVID-19 case in Japan began to appear in middle January 2020 and continued to increase over time. The period from middle January to the end of February is considered to be the initial stage of domestic transmission in Japan. This article described the spread of 935 COVID-19 cases related to Japan by the end of February 2020, including the 15 infected Japanese returned from Wuhan, the 696 infected individuals in the large-scale cruise ship 'Diamond Princess' and the 224 infected individuals in Japan. This paper summarizes the measures to control the spread of SARS-CoV-2 in Japan, such as limiting RT-PCR detection for SARS-CoV-2, reducing the number of patients with mild illness who go to medical institutions unnecessarily, formulating guidelines for SARS-CoV-2 infection consultation, canceling large gatherings and temporarily closing schools. This paper further points out the problems encountered in the prevention and control of the spread of SARS-CoV-2 in Japan, such as the slow detection of RT-PCR, the risk of infection faced by medical staff, the regional differences in the domestic health care service system, the confusion of information disclosure and management. The above introduction as allows us to acquire a better understanding of the new coronavirus pneumonia in Japan and the world and may provide reference for the control the epidemic of COVID-19 in worldwide.

negative: Telehealth: Helping your patients and practice survive and thrive during the COVID-19 crisis with rapid quality implementation

negative: Mechanisms that determine plasma cell lifespan and the duration of humoral immunity Summary: Humoral immunity following vaccination or infection is mainly derived from two types of cells: memory B cells and plasma cells. Memory B cells do not actively secrete antibody but instead maintain their immunoglobulin in the membrane‐bound form that serves as the antigen‐specific B‐cell receptor. In contrast, plasma cells are terminally differentiated cells that no longer express surface‐bound immunoglobulin but continuously secrete antibody without requiring further antigenic stimulation. Pre‐existing serum or mucosal antibody elicited by plasma cells (or other intermediate antibody‐secreting cells) represents the first line of defense against reinfection and is critical for protection against many microbial diseases. However, the mechanisms involved with maintaining long‐term antibody production are not fully understood. Here, we examine several models of long‐term humoral immunity and present a new model, described as the ‘Imprinted Lifespan’ model of plasma cell longevity. The foundation of this model is that plasma cells are imprinted with a predetermined lifespan based on the magnitude of B‐cell signaling that occurs during the induction of an antigen‐specific humoral immune response. This represents a testable hypothesis and may explain why some antigen‐specific antibody responses fade over time whereas others are maintained essentially for life.

negative: Rethinking the role of blood pressure drugs in COVID-19 All it takes is a simple cough: a sharp intake of breath, the compression of air in the lungs, and the throat flying open to spew air, spit, and mucus If the person coughing is infected with the novel coronavirus, it comes along for the ride on droplets, which can travel up to 50 miles per hour When someone breathes those droplets in, the virus can get into the lungs Once inside, it uses a spike protein on its surface to target an enzyme—ACE2—scattered over the outsides of the airway’s cells If the spike protein connects with its target, the coronavirus uses ACE2 as a door to slip inside the cell Thus begins an infection During the early days of the coronavirus outbreak, researchers hypothesized that the likelihood of contracting COVID-19, the disease caused by the novel coronavirus, could be related to the amount of ACE2 on someone’s cells—the more doors for the virus to enter through, the higher the risk That idea prompted doctors around the world in March to warn the millions of people taking two classes of blood pressure medications, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), of a potential danger: these medications appear to increase ACE2 levels in cells, at least in some studies, so the drugs may make their users more susceptible to the novel coronavirus, SARS-CoV-2

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: 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: Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV) caused substantial morbidity and mortality in 2002–2003. Deletion of the envelope (E) protein modestly diminished virus growth in tissue culture but abrogated virulence in animals. Here, we show that immunization with rSARS-CoV-ΔE or SARS-CoV-Δ[E,6-9b] (deleted in accessory proteins (6, 7a, 7b, 8a, 8b, 9b) in addition to E) nearly completely protected BALB/c mice from fatal respiratory disease caused by mouse-adapted SARS-CoV and partly protected hACE2 Tg mice from lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-ΔE and rSARS-CoV-Δ[E,6-9b] induced anti-virus T cell and antibody responses. Further, the E-deleted viruses were stable after 16 blind passages through tissue culture cells, with only a single mutation in the surface glycoprotein detected. The passaged virus remained avirulent in mice. These results suggest that rSARS-CoV-ΔE is an efficacious vaccine candidate that might be useful if SARS recurred.

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: Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients A global health emergency has been declared by the World Health Organization as the 2019-nCoV outbreak spreads across the world, with confirmed patients in Canada. Patients infected with 2019-nCoV are at risk for developing respiratory failure and requiring admission to critical care units. While providing optimal treatment for these patients, careful execution of infection control measures is necessary to prevent nosocomial transmission to other patients and to healthcare workers providing care. Although the exact mechanisms of transmission are currently unclear, human-to-human transmission can occur, and the risk of airborne spread during aerosol-generating medical procedures remains a concern in specific circumstances. This paper summarizes important considerations regarding patient screening, environmental controls, personal protective equipment, resuscitation measures (including intubation), and critical care unit operations planning as we prepare for the possibility of new imported cases or local outbreaks of 2019-nCoV. Although understanding of the 2019-nCoV virus is evolving, lessons learned from prior infectious disease challenges such as Severe Acute Respiratory Syndrome will hopefully improve our state of readiness regardless of the number of cases we eventually manage in Canada.

negative: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19? INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.

negative: 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.

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

negative: Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors of this article suggest that there is convincing evidence to support this recommendation.

negative: Molecular targets for the rational design of drugs to inhibit SARS coronavirus Despite years of research, the precise determinants of coronavirus replication and pathogenesis remain unidentified. What is known of the pathogenesis of the severe acute respiratory syndrome coronavirus (SARS-CoV) is limited, but clinical observations suggest that both viral-induced cytotoxicity and host immune-mediated destruction contribute to the severity of disease. This summary discusses recent advances in coronavirus research that will facilitate the identification of crucial molecular targets for the rational design of SARS therapeutics. Section Editor: Anne Moscona – Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1198, New York, NY 10029, USA When the SARS coronavirus came dramatically to attention as a fatal and potentially pandemic respiratory disease, the scientific response was swift and effective. The etiological agent was identified, the genome was cloned and sequenced, and large strides have been made in understanding key points in the viral life cycle, including recent identification of a functional host cell receptor and solution of the three-dimensional structure of the viral attachment protein. Much of this progress was possible only because a foundation of basic coronavirus biology existed. The Denison laboratory has been at the forefront of the small group of investigators who have dissected the basic features of coronaviruses. Denison has discovered critical mechanisms in the life cycle of the coronaviruses and is a key figure in the effective and urgent application of this knowledge to SARS.

negative: Copper Alloy Touch Surfaces in Healthcare Facilities: An Effective Solution to Prevent Bacterial Spreading In the healthcare environment, microorganisms’ cross-transmission between inanimate surfaces and patients or healthcare workers can lead to healthcare-associated infections. A recent interest has grown to create antimicrobial copper touch surfaces, in order to counteract microbial spread in the healthcare environment. For the first time, five French long-term care facilities were at 50% fitted with copper alloys door handles and handrails. Related to the environmental bacterial contamination, 1400 samples were carried out on copper and control surfaces over three years after copper installation. In addition, some copper door handles were taken from the different facilities, and their specific activity against methicillin-resistant S. aureus (MRSA) was tested in vitro. In comparison to control surfaces, copper door handles and handrails revealed significantly lower contamination levels. This difference was observed in the five long-term care facilities and it persists through the three years of the study. High and extreme levels of bacterial contamination were less frequent on copper surfaces. Although, the antibacterial activity of copper surfaces against MRSA was lowered after three years of regular use, it was still significant as compared to inert control surfaces. Therefore, copper containing surfaces are promising actors in the non-spreading of environmental bacterial contamination in healthcare facilities.

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: Prevention and Treatment of Yeast and Endemic Fungal Infections Invasive fungal infections (IFIs) remain an important complication of solid organ transplantation owing to their significant morbidity and mortality and include infections due to Candida, Cryptococcus, endemic mycosis, and other rare yeasts and molds. IFIs occur in different intervals posttransplantation and depend on a number of extrinsic and intrinsic risk factors, some of which are specific to the type of organs transplanted, surgical techniques, and type of immunosuppressive medications. Donor-derived IFIs and emergence of new multidrug-resistant yeasts have been reported in various healthcare settings. Clinical manifestations of yeast and endemic fungal infections vary in different types of organ transplants. Diagnosis of IFIs in SOT recipients is challenging due to their nonspecific signs and symptoms owing to the impaired inflammatory responses as a result of immunosuppression and the lack of highly sensitive and specific diagnostic modalities. Early diagnosis is key to successful therapy, and physicians should have a high index of suspicion based on risk factors and epidemiology of these pathogens. Antifungal treatment strategies for yeast infections have been outlined in various society guidelines. Management of complications that arise before or during antifungal therapy is critical for optimizing clinical response.

negative: 2019-novel Coronavirus (2019-nCoV): estimating the case fatality rate - a word of caution.

negative: 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.

negative: Persistence of Antibodies against Middle East Respiratory Syndrome Coronavirus To determine how long antibodies against Middle East respiratory syndrome coronavirus persist, we measured long-term antibody responses among persons serologically positive or indeterminate after a 2012 outbreak in Jordan. Antibodies, including neutralizing antibodies, were detectable in 6 (86%) of 7 persons for at least 34 months after the outbreak.

negative: 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.

negative: The Importance of the Clinical Environment in the Transmission of Health Care-Associated Infections

negative: How best to use limited tests? Improving COVID-19 surveillance in long-term care Background: Long-term care facilities (LTCFs) are particularly vulnerable to nosocomial outbreaks of coronavirus disease 2019 (COVID-19), with high rates of transmission and mortality. Timely epidemiological surveillance is essential to detect and respond to outbreaks, but testing resources are highly limited in the current pandemic context. Methods: We used an individual-based transmission model to simulate COVID-19 spread along inter-individual contact networks in the LTCF setting. A range of surveillance strategies were evaluated for their ability to detect simulated outbreaks, assuming limited availability of standard RT-PCR tests. Various epidemiological scenarios were considered, including COVID-19 importation from patient transfers or staff members infected in the community. Findings: We estimated a median delay of 7 (95% uncertainty interval: 2-15) days from importation of an asymptomatic COVID-19-infected patient to first presentation of COVID-19 symptoms among any patients or staff, at which point an additional 7 (0-25) individuals were infected but did not (yet) show symptoms. Across a range of scenarios, the reference surveillance strategy (testing individuals with COVID-like symptoms with signs of severity) took a median 11-21 days to detect an outbreak. Group testing (pooling specimens from multiple individuals for a single RT-PCR test) patients and staff with any COVID-like symptoms was both the most timely and efficient strategy, detecting outbreaks up to twice as quickly as the reference, and more quickly than other considered strategies while using fewer tests. Maximizing use of available tests via testing cascades was more effective than group testing only when substantial testing resources were available (on the order of 1 test/20 beds/day). Including not merely those with symptoms but also newly admitted patients in group tests and testing cascades reduced delays in outbreak detection for LTCFs actively admitting patients potentially already infected with COVID-19. Interpretation: Improving COVID-19 surveillance can alert healthcare institutions to emerging outbreaks before they escalate, informing a need for urgent public health intervention in settings with ongoing nosocomial transmission.

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: Recommendations from workshops of the second international feline coronavirus/feline infectious peritonitis symposium Abstract In August 2002, scientists and veterinarians from all over the world met in Scotland to discuss feline coronavirus (FCoV) and feline infectious peritonitis (FIP). The conference ended with delegates dividing into three workshops to draw up recommendations for FCoV control, diagnosis and treatment and future research. The workshops were chaired by the three authors and the recommendations are presented in this paper.

negative: Understanding the COVID19 Outbreak: A Comparative Data Analytics and Study The Coronavirus, also known as the COVID-19 virus, has emerged in Wuhan China since late November 2019. Since that time, it has been spreading at large-scale until today all around the world. It is currently recognized as the world's most viral and severe epidemic spread in the last twenty years, as compared to Ebola 2014, MERS 2012, and SARS 2003. Despite being still in the middle of the outbreak, there is an urgent need to understand the impact of COVID-19. The objective is to clarify how it was spread so fast in a short time worldwide in unprecedented fashion. This paper represents a first initiative to achieve this goal, and it provides a comprehensive analytical study about the Coronavirus. The contribution of this paper consists in providing descriptive and predictive models that give insights into COVID-19 impact through the analysis of extensive data updated daily for the outbreak in all countries. We aim at answering several open questions: How does COVID-19 spread around the world? What is its impact in terms of confirmed and death cases at the continent, region, and country levels? How does its severity compare with other epidemic outbreaks, including Ebola 2014, MERS 2012, and SARS 2003? Is there a correlation between the number of confirmed cases and death cases? We present a comprehensive analytics visualization to address the questions mentioned above. To the best of our knowledge, this is the first systematic analytical papers that pave the way towards a better understanding of COVID-19. The analytical dashboards and collected data of this study are available online [1].

negative: Complete Genome Sequences of Two Genetically Distinct Variants of Porcine Epidemic Diarrhea Virus in the Eastern Region of Thailand Porcine epidemic diarrhea virus (PEDV) has continued to cause sporadic outbreaks in Thailand since 2007. Previously, PEDV in Thailand was a new variant containing an insertion and deletion in the spike gene. Herein, full-length genome sequences are reported for two variants of PEDV isolates from pigs displaying diarrhea in Thailand.

negative: OX40:OX40L axis: emerging targets for improving poxvirus-based CD8(+) T-cell vaccines against respiratory viruses The human respiratory tract is the entry point for over 200 known viruses that collectively contribute to millions of annual deaths worldwide. Consequently the World Health Organization has designated respiratory viral infections as a priority for vaccine development. Despite enormous advances in understanding the attributes of a protective mucosal antiviral immune response, current vaccines continue to fail in effectively generating long-lived protective CD8(+) T-cell immunity. To date, the majority of licensed human vaccines afford protection against infectious pathogens through the generation of specific immunoglobulin responses. In recent years, the selective manipulation of specific costimulatory pathways, which are critical in regulating T-cell-mediated immune responses, has generated increasing interest. Impressive results in animal models have shown that the tumor necrosis factor receptor (TNFR) family member OX40 (CD134) and its binding partner OX40L (CD252) are key costimulatory molecules involved in the generation of protective CD8(+) T-cell responses at mucosal surfaces such as the lung. In this review, we highlight these new findings with a particular emphasis on their potential as immunological adjuvants to enhance poxvirus-based CD8(+) T-cell vaccines.

negative: Genome Sequences of Rhinovirus Genotype C56 Detected in Three Patients with Acute Respiratory Illness, California, 2016 to 2017 We report here two genome sequences of a newly designated rhinovirus genotype, RV-C56, which were obtained from respiratory specimens of three patients with acute respiratory illness in 2016 and 2017. To our knowledge, these sequences represent the first near-complete genomes for RV-C56 strains.

negative: 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.

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: Effectiveness of bacterial disinfectants on surfaces of mechanical ventilator systems. BACKGROUND Pathogens in healthcare settings can be transmitted via skin contact and environmental media. This study investigates bacterial contamination rate on surfaces of mechanical ventilator systems and bedside equipment. An experimental study evaluates the effectiveness of 75% alcohol in killing bacteria on surfaces. METHODS Surface swab sampling was conducted on ventilator systems and patient bedside equipment for detection of bacterial contamination. Surfaces of ventilator systems, such as faceplates, Y-pieces, and water traps, were swab sampled at 0.5, 8, and 24 hours after initial disinfection using a solution containing 0.5% sodium hypochlorite and pasteurization. The 75% alcohol aerosol was sprayed on the surfaces of faceplates, Y-pieces, and water traps on ventilator systems at 24 hours after initial disinfection, and then bacterial levels on the surfaces were evaluated. RESULTS Detection rates of Staphylococcus aureus were measured on the handrails of mechanical ventilators (64.7%), Y-pieces of breathing circuits (86.7%), and resuscitators (60.0%). Pseudomonas aeruginosa was identified on the surfaces of Y-pieces (6.7%) and water traps (13.3%) of breathing circuits, and also on suction systems (6.7%) and resuscitators (13.3%). The positive rate for total bacterial count was clearly increased on the surfaces of faceplates, Y-pieces, and water traps at 8 hour following disinfection by 0.5% sodium hypochlorite solution and pasteurization. Concentrations of S. aureus on surfaces decreased following treatment with 75% alcohol. However, considerable P. aeruginosa growth on water trap surfaces was observed after treatment with 75% alcohol. CONCLUSIONS The surfaces of ventilator systems, including faceplates, Y-pieces, and water traps, must be disinfected frequently (at least every 8 h) to control bacterial growth. Disinfection using 75% alcohol spray with air drying effectively decreased S. aureus on ventilator system surfaces.

negative: Prolonged SARS‐CoV‐2 RNA shedding: Not a rare phenomenon A few studies have reported the long shedding of SARS-CoV-2 RNA. However, the duration of RNA shedding in Wuhan is rarely known and the meaning of the prolonged shedding is still under investigation. Almost 10% patients diagnosed of COVID-19 had a RNA shedding longer than 30 days even if the symptom elimination. The IgM was in a high level in the 9th week after symptom onset in these prolonged-RNA-shedding patients. Further study should be conducted to know the infectivity of the virus and the relationship between RNA shedding and antibody expression. This article is protected by copyright. All rights reserved.

negative: 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.

negative: Diagnostic methods and potential portable biosensors for coronavirus disease 2019 Timely detection and diagnosis are urgently needed to guide epidemiological measures, infection control, antiviral treatment, and vaccine research. In this review, biomarkers/indicators for diagnosis of coronavirus disease 2019 (COVID-19) or detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the environment are summarized and discussed. It is concluded that the detection methods targeting antibodies are not suitable for screening of early and asymptomatic cases since most patients had an antibody response at about 10 days after onset of symptoms. However, antibody detection methods can be combined with quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) to significantly improve the sensitivity and specificity of diagnosis, and boost vaccine research. Fast, sensitive and accurate detection methods targeting antigens need to be developed urgently. Various specimens for diagnosis or detection are compared and analyzed. Among them, deep throat saliva and induced sputum are desired for RT-qPCR test or other early detection technologies. Chest computerized tomography (CT) scan, RT-qPCR, lateral flow immunochromatographic strip (LFICS) for diagnosis of COVID-19 are summarized and compared. Specially, potential electrochemical biosensor, surface enhanced Raman scattering (SERS)-based biosensor, and artificial intelligence (AI) assisted diagnosis of COVID-19 are emphasized. Finally, some commercialized portable detection device, current challenges and future directions are discussed.

negative: Levels of feline infectious peritonitis virus in blood, effusions, and various tissues and the role of lymphopenia in disease outcome following experimental infection Abstract Twenty specific pathogen free cats were experimentally infected with a virulent cat-passaged type I field strain of FIPV. Eighteen cats succumbed within 2–4 weeks to effusive abdominal FIP, one survived for 6 weeks, and one seroconverted without outward signs of disease. A profound drop in the absolute count of blood lymphocytes occurred around 2 weeks post-infection (p.i.) in cats with rapid disease, while the decrease was delayed in the one cat that survived for 6 weeks. The absolute lymphocyte count of the surviving cat remained within normal range. Serum antibodies as measured by indirect immunofluorescence appeared after 2 weeks p.i. and correlated with the onset of disease signs. Viral genomic RNA was either not detectable by reverse transcription quantitative real-time PCR (RT-qPCR) or detectable only at very low levels in terminal tissues not involved directly in the infection, including hepatic and renal parenchyma, cardiac muscle, lung or popliteal lymph node. High tissue virus loads were measured in severely affected tissues such as the omentum, mesenteric lymph nodes and spleen. High levels of viral genomic RNA were also detected in whole ascitic fluid, with the cellular fraction containing 10–1000 times more viral RNA than the supernatant. Replicating virus was strongly associated with macrophages by immunohistochemistry. Virus was usually detected at relatively low levels in feces and there was no evidence of enterocyte infection. Viral genomic RNA was not detected at the level of test sensitivity in whole blood, plasma, or the white cell fraction in terminal samples from the 19 cats that succumbed or in the single survivor. These studies reconfirmed the effect of lymphopenia on disease outcome. FIPV genomic RNA was also found to be highly macrophage associated within diseased tissues and effusions as determined by RT-qPCR and immunohistochemistry but was not present in blood.

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: 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.

negative: Cell-surface proteolysis, growth factor activation and intercellular communication in the progression of melanoma Abstract Normal skin architecture and melanocyte function is maintained by a dynamic interplay between the melanocytes themselves, the epithelial cells between which they are interspersed, and their microenvironment. The microenvironment consists of the extracellular matrix, fibroblasts, migratory immune cells, and neural elements supported by a vascular network, all within a milieu of cytokines, growth factors, and bioactive peptides as well as proteolytic enzymes. Cells interact with the microenvironment via complex autocrine and paracrine mechanisms. Proteolytic enzymes in melanoma may activate or release growth factors from the microenvironment or act directly on the microenvironment itself, thereby facilitating angiogenesis or tumor cell migration. This review summarizes recent findings regarding the expression, structure and function of proteolytic enzymes at or near the cell surface in cell–cell and cell–stroma interactions during melanoma progression. Cell-surface (membrane) peptidases are a multi-functional group of ectoenzymes that have been implicated in the control of growth and differentiation of many cellular systems. The potential, but yet speculative, role of other membrane-bound molecules, such as multifunctional surface proteins with adhesion and protease activity (ADAM gene family) or the ephrin/Eph receptor protein kinases in the pathogenesis of melanoma are discussed.

negative: Development of a Laboratory-safe and Low-cost Detection Protocol for SARS-CoV-2 of the Coronavirus Disease 2019 (COVID-19) The severe acute respiratory coronavirus 2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, has spread rapidly to over a dozen countries. Especially, the spike of case numbers in South Korea sparks pandemic worries. This virus is reported to spread mainly through personto- person contact via respiratory droplets generated by coughing and sneezing, or possibly through surface contaminated by people coughing or sneezing on them. More critically, there have been reports about the possibility of this virus to transmit even before a virus-carrying person to show symptoms. Therefore, a low-cost, easy-access protocol for early detection of this virus is desperately needed. Here, we have established a real-time reverse-transcription PCR (rtPCR)-based assay protocol composed of easy specimen self-collection from a subject via pharyngeal swab, Trizolbased RNA purification, and SYBR Green-based rtPCR. This protocol shows an accuracy and sensitivity limit of 1-10 virus particles as we tested with a known lentivirus. The cost for each sample is estimated to be less than 15 US dollars. Overall time it takes for an entire protocol is estimated to be less than 4 hours. We propose a cost-effective, quick-and-easy method for early detection of SARS-CoV-2 at any conventional Biosafety Level II laboratories that are equipped with a rtPCR machine. Our newly developed protocol should be helpful for a first-hand screening of the asymptomatic virus-carriers for further prevention of transmission and early intervention and treatment for the rapidly propagating virus.

negative: Outbreak of Novel Coronavirus (SARS-CoV-2): First Evidences From International Scientific Literature and Pending Questions On 31 December, 2019, a cluster of 27 pneumonia cases of unknown etiology was reported by Chinese health authorities in Wuhan City (China) [ ]

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: Tobacco use and vaping in the COVID‐19 era Health crises have become a popular topic of discussion. In the wave of the ongoing pandemic, experts have suggested the role of vaping and other tobacco product use exemplifying the vulnerability of the population to contract the COVID‐19. We discuss some of the events that led up to these conclusions and also offer a unique insight into another form of tobacco use that is potentially propagating its spread especially in the South Asian region—chewed tobacco. Both of these have been a perennial issue that head and neck cancer surgeons have been dealing with. Governments and head and neck cancer care providers now have an opportunity to deal with a common enemy in the midst of this pandemic.

negative: The dissemination of COVID-19: an expectant and preventive role in global health Backgroung: Coronaviruses (CoV) make up a large family of viruses, known since the mid-1960s, which received this name due to the spikes on its surface, which resemble a crown (from the Latin corona). CoV infections can cause everything from a common cold to severe respiratory syndromes, such as severe acute respiratory syndrome (SARS-CoV) and Middle Eastern respiratory syndrome (MERS-CoV).COVID-19 (SARS-CoV2) is a new variant of the coronavirus, and its isolation occurred in China on January 7th, 2020. COVID-19 has stood out with a high impact on public health due to the high number of cases with infection in a short period of time. However, it is possible to observe that 17% of patients confirmed with COVID-19 have severe infections and about 2.5% of these patients die. Current studies have shown that the number of mild and asymptomatic cases may be even greater. Thus, the challenges for controlling unreported cases of patients with mild symptoms that are spreading the virus and interfering with the magnitude and real data of the cases stand out. The transmission of the coronavirus occurs between humans, and it can occur from person to person through the air, through coughing or sneezing, by touching or shaking hands or by contact with contaminated objects or surfaces, followed by contact with the mouth, nose or eyes. Given the fluctuation in the incidence and the lethality rate, it is essential to stand out the precepts of health promotion in search of reorienting hygiene practices, considering that there is validity in health care models, still with a curative approach and the current situation experienced by the world population requires a preventive stance.(AU)

negative: Two-step conformational changes in a coronavirus envelope glycoprotein mediated by receptor binding and proteolysis. The coronaviruses mouse hepatitis virus type 2 (MHV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) utilize proteases to enter host cells. Upon receptor binding, the spike (S) proteins of both viruses are activated for membrane fusion by proteases, such as trypsin, present in the environment, facilitating virus entry from the cell surface. In contrast, in the absence of extracellular proteases, these viruses can enter cells via an endosomal pathway and utilize endosomal cathepsins for S protein activation. We demonstrate that the MHV-2 S protein uses multistep conformational changes for membrane fusion. After interaction with a soluble form of the MHV receptor (CEACAM1a), the metastable form of S protein is converted to a stable trimer, as revealed by mildly denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Liposome-binding assays indicate that the receptor-bound virions are associated with the target membrane through hydrophobic interactions. The exposure of receptor-bound S protein to trypsin or cathepsin L (CPL) induces the formation of six-helix bundles (6HB), the final conformation. This trypsin- or CPL-mediated conversion to 6HB can be blocked by a heptad repeat peptide known to block the formation of 6HB. Although trypsin treatment enabled receptor-bound MHV-2 to enter from the cell surface, CPL failed to do so. Interestingly, consecutive treatment with CPL and then chlorpromazine enabled a portion of the virus to enter from cell surface. These results suggest that trypsin suffices for the induction of membrane fusion of receptor-primed S protein, but an additional unidentified cellular factor is required to trigger membrane fusion by CPL.

negative: A future for transgenic livestock The techniques that are used to generate transgenic livestock are inefficient and expensive. This, coupled with the fact that most agriculturally relevant traits are complex and controlled by more than one gene, has restricted the use of transgenic technology. New methods for modifying the genome will underpin a resurgence of research using transgenic livestock. This will not only increase our understanding of basic biology in commercial species, but might also lead to the generation of animals that are more resistant to infectious disease.

negative: Novel Coronavirus COVID-19 Strike on Arab Countries and Territories: A Situation Report I The novel Coronavirus (COVID-19) is an infectious disease caused by a new virus called COVID-19 or 2019-nCoV that first identified in Wuhan, China. The disease causes respiratory illness (such as the flu) with other symptoms such as a cough, fever, and in more severe cases, difficulty breathing. This new Coronavirus seems to be very infectious and has spread quickly and globally. In this work, information about COVID-19 is provided and the situation in Arab countries and territories regarding the COVID-19 strike is presented. The next few weeks main expectations is also given.

negative: SARS-associated Coronavirus Transmission, United States To better assess the risk for transmission of the severe acute respiratory syndrome–associated coronavirus (SARS-CoV), we obtained serial specimens and clinical and exposure data from seven confirmed U.S. SARS patients and their 10 household contacts. SARS-CoV was detected in a day-14 sputum specimen from one case-patient and in five stool specimens from two case-patients. In one case-patient, SARS-CoV persisted in stool for at least 26 days after symptom onset. The highest amounts of virus were in the day-14 sputum sample and a day-14 stool sample. Residual respiratory symptoms were still present in recovered SARS case-patients 2 months after illness onset. Possible transmission of SARS-CoV occurred in one household contact, but this person had also traveled to a SARS-affected area. The data suggest that SARS-CoV is not always transmitted efficiently. Laboratory diagnosis of SARS-CoV infection is difficult; thus, sputum and stool specimens should be included in the diagnostic work-up for SARS-CoV infection.

negative: 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.

negative: COVID-19 in a patient with long-term use of glucocorticoids: A study of a familial cluster Abstract Clusters of patients with novel coronavirus disease 2019 (COVID-19) have been successively reported globally. Studies show clear person-to-person transmission. The average incubation period is 2–14 days, and mostly 3–7 days. However, in some patients, this period may be longer. Here, we report a familial cluster of COVID-19 where a 47-year-old woman with long-term use of glucocorticoids did not develop any symptoms within the 14-day quarantine period but was confirmed with COVID-19 by tested positive of antibody on day 40 after she left Wuhan. Almost at the same time, her father and sister were diagnosed with COVID-19. The results suggest that the long-term use of glucocorticoids might cause atypical infections, a long incubation period, and extra transmission of COVID-19.

negative: 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.

negative: Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study Summary Background Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures. Methods From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk. Findings Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20–22). Cases were isolated on average 4·6 days (95% CI 4·1–5·0) after developing symptoms; contact tracing reduced this by 1·9 days (95% CI 1·1–2·7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6·27 [95% CI 1·49–26·33] for household contacts and 7·06 [1·43–34·91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11·2% (95% CI 9·1–13·8), and children were as likely to be infected as adults (infection rate 7·4% in children <10 years vs population average of 6·6%). The observed reproductive number (R) was 0·4 (95% CI 0·3–0·5), with a mean serial interval of 6·3 days (95% CI 5·2–7·6). Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control. Funding Emergency Response Program of Harbin Institute of Technology, Emergency Response Program of Peng Cheng Laboratory, US Centers for Disease Control and Prevention.

negative: The role of community-wide wearing of face mask for control of coronavirus disease 2019 (COVID-19) epidemic due to SARS-CoV-2 Abstract Background Face mask usage by the healthy population in the community to reduce risk of transmission of respiratory viruses remains controversial. We assessed the effect of community-wide mask usage to control coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region (HKSAR). Methods Patients presenting with respiratory symptoms at outpatient clinics or hospital wards were screened for COVID-19 per protocol. Epidemiological analysis was performed for confirmed cases, especially persons acquiring COVID-19 during mask-off and mask-on settings. The incidence of COVID-19 per-million-population in HKSAR with community-wide masking was compared to that of non-mask-wearing countries which are comparable with HKSAR in terms of population density, healthcare system, BCG vaccination and social distancing measures but not community-wide masking. Compliance of face mask usage in the HKSAR community was monitored. Findings Within first 100 days (31 December 2019 to 8 April 2020), 961 COVID-19 patients were diagnosed in HKSAR. The COVID-19 incidence in HKSAR (129.0 per-million-population) was significantly lower (p<0.001) than that of Spain (2983.2), Italy (2250.8), Germany (1241.5), France (1151.6), U.S. (1102.8), U.K. (831.5), Singapore (259.8), and South Korea (200.5). The compliance of face mask usage by HKSAR general public was 96.6% (range: 95.7% to 97.2%). We observed 11 COVID-19 clusters in recreational ‘mask-off’ settings compared to only 3 in workplace ‘mask-on’ settings (p = 0.036 by Chi square test of goodness-of-fit). Conclusion Community-wide mask wearing may contribute to the control of COVID-19 by reducing virus shedding in saliva and respiratory droplets from individuals with subclinical or mild COVID-19.

negative: [Management and clinical thinking of Coronavirus Disease 2019]. In December 2019, the 2019 novel coronavirus pneumonia (NCP, officially named Coronavirus Disease 2019(COVID-19) by the World Health Organization) broke out in Wuhan, Hubei, and it quickly spread to the whole country and abroad. The situation was at stake. The sudden and serious COVID-19 epidemic has brought us a lot of urgent problems. How to effectively control the spread of COVID-19? When does the population infection rate rise to its peak? What will eventually be the number of infected patients? How to make early diagnosis? What effective antiviral drugs are available? How to effectively treat with existing drugs? Can it successfully improve the survival rate of critically patients? In response to the above questions, we put forward corresponding suggestions and reflections from the perspective of the infectious clinician.

negative: 1.13 The Role of Small- or Medium-Sized Enterprises in Drug Discovery The past 10 years has seen the rise of large numbers of small- and medium-size enterprises (SMEs) engaging in some or many of the aspects of drug research. Few of these companies have been able to take candidate drugs to market due to development costs not being met by funding opportunities, but those companies that have been able to challenge traditional big pharma in the marketplace. Most SMEs have instead supplied traditional pharma with pipeline candidate drugs, either by licensing them or by the large companies actually acquiring the whole of the SME which owns the intellectual property. Many other companies engage in providing traditional big pharma or other SMEs with technologies and services. Hundreds of such companies have arisen, many clustered around centres of academic excellence on the coasts of the USA, or in certain regions in Europe and Asia – such clustering of scientific prowess has changed the location of where even big pharma tends to perform its research. By 2006, a large proportion (but generally less than 50%) of new drugs could be track to an origin in an SME, trends indicate that the proportion will rise even though the common prediction that large pharma will abandon internal research in favour of in-licensing from SMEs remains far from reality.

negative: 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.

negative: 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.

negative: Oligomerized transferrin receptors are selectively retained by a lumenal sorting signal in a long-lived endocytic recycling compartment Cross-linking of surface receptors results in altered receptor trafficking in the endocytic system. To better understand the cellular and molecular mechanisms by which receptor cross-linking affects the intracellular trafficking of both ligand and receptor, we studied the intracellular trafficking of the transferrin receptor (TfR) bound to multivalent-transferrin (Tf10) which was prepared by chemical cross- linking of transferrin (Tf). Tf10 was internalized about two times slower than Tf and was retained four times longer than Tf, without being degraded in CHO cells. The intracellular localization of Tf10 was investigated using fluorescence and electron microscopy. Tf10 was not delivered to the lysosomal pathway followed by low density lipoprotein but remained accessible to Tf in the pericentriolar endocytic recycling compartment for at least 60 min. The retained Tf10 was TfR-associated as demonstrated by a reduction in surface TfR number when cells were incubated with Tf10. The presence of Tf10 within the recycling compartment did not affect trafficking of subsequently endocytosed Tf. Retention of Tf10 within the recycling compartment did not require the cytoplasmic domain of the TfR since Tf10 exited cells with the same rate when bound to the wild-type TfR or a mutated receptor with only four amino acids in the cytoplasmic tail. Thus, cross-linking of surface receptors by a multivalent ligand acts as a lumenal retention signal within the recycling compartment. The data presented here show that the recycling compartment labeled by Tf10 is a long-lived organelle along the early endosome recycling pathway that remains fusion accessible to subsequently endocytosed Tf.

negative: Virus and virus-like particles observed in the intestinal contents of the possum,Trichosurus vulpecula Intestinal contents derived from the Australian brush-tailed possum,Trichosurus vulpecula, were examined by negative stain electron microscopy for the presence of viruses. Out of 100 samples, 23 contained at least one type of vertebrate virus or virus-like particle. Adenovirus was identified in six samples, herpesvirus in two samples, coronavirus in four samples, and coronavirus-like particles in 14 samples. To date no viruses of the brush-tailed possum have been isolated in tissue culture but these results indicate that this species is probably host to several viral species.

negative: Toxicogenomics analysis of mouse lung responses following exposure to titanium dioxide nanomaterials reveal their disease potential at high doses Titanium dioxide nanoparticles (TiO(2)NPs) induce lung inflammation in experimental animals. In this study, we conducted a comprehensive toxicogenomic analysis of lung responses in mice exposed to six individual TiO(2)NPs exhibiting different sizes (8, 20 and 300nm), crystalline structure (anatase, rutile or anatase/rutile) and surface modifications (hydrophobic or hydrophilic) to investigate whether the mechanisms leading to TiO(2)NP-induced lung inflammation are property specific. A detailed histopathological analysis was conducted to investigate the long-term disease implications of acute exposure to TiO(2)NPs. C57BL/6 mice were exposed to 18, 54, 162 or 486 µg of TiO(2)NPs/mouse via single intratracheal instillation. Controls were exposed to dispersion medium only. Bronchoalveolar lavage fluid (BALF) and lung tissue were sampled on 1, 28 and 90 days post-exposure. Although all TiO(2)NPs induced lung inflammation as measured by the neutrophil influx in BALF, rutile-type TiO(2)NPs induced higher inflammation with the hydrophilic rutile TiO(2)NP showing the maximum increase. Accordingly, the rutile TiO(2)NPs induced higher number of differentially expressed genes. Histopathological analysis of lung sections on Day 90 post-exposure showed increased collagen staining and fibrosis-like changes following exposure to the rutile TiO(2)NPs at the highest dose tested. Among the anatase, the smallest TiO(2)NP of 8nm showed the maximum response. The anatase TiO(2)NP of 300nm was the least responsive of all. The results suggest that the severity of lung inflammation is property specific; however, the underlying mechanisms (genes and pathways perturbed) leading to inflammation were the same for all particle types. While the particle size clearly influenced the overall acute lung responses, a combination of small size, crystalline structure and hydrophilic surface contributed to the long-term pathological effects observed at the highest dose (486 µg/mouse). Although the dose at which the pathological changes were observed is considered physiologically high, the study highlights the disease potential of certain TiO(2)NPs of specific properties.

negative: Likelihood of survival of coronavirus disease 2019

negative: Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations The novel coronavirus (nCOV-2019) outbreak has put the world on edge, causing millions of cases and hundreds of thousands of deaths all around the world, as of June 2020, let alone the societal and economic impacts of the crisis. The spike protein of nCOV-2019 resides on the virion’s surface mediating coronavirus entry into host cells by binding its receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2). Our goal is to provide a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier coronavirus SARS-COV in 2002 via extensive molecular dynamics (MD) simulations. Numerous mutations have been identified in the RBD of nCOV-2019 strains isolated from humans in different parts of the world. In this study, we investigated the effect of these mutations as well as other Ala-scanning mutations on the stability of RBD/ACE2 complex. It is found that most of the naturally-occurring mutations to the RBD either strengthen or have the same binding affinity to ACE2 as the wild-type nCOV-2019. This may have implications for high human-to-human transmission of coronavirus in regions where these mutations have been found as well as any vaccine design endeavors since these mutations could act as antibody escape mutants. Furthermore, in-silico Ala-scanning and long-timescale MD simulations, highlight the crucial role of the residues at the interface of RBD and ACE2 that may be used as potential pharmacophores for any drug development endeavors. From an evolutional perspective, this study also identifies how the virus has evolved from its predecessor SARS-COV and how it could further evolve to become more infectious.

negative: Adaptive surface variation in mycoplasmas Mycoplasmas excel as infectious agents, despite their very small genomes. In one mycoplasma species, adaptive flexibility is enhanced by an elegant genetic system that diversifies the membrane surface through a set of variable lipoproteins (Vlps). A family of vlp genes supplies divergent coding sequences and undergoes high-frequency mutations, thus creating large repertoires of surface mosaics and structural variants.

negative: 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.

negative: The effects of glass surfaces and probe GC content on signal intensities of a 60-mer diagnostic microarray The effects of glass surfaces and probe GC content on signal intensities of a 60-mer diagnostic microarray were studied. Twelve virus-specific oligonucleotide probes for severe acute respiratory syndrome coronavirus (SARS-CoV) were divided into a high GC content group (≥ 50%) and a low GC content group (< 50%), and spotted onto four different chemically-modified glass surfaces: a poly-amine coating activated by 1,4-phenylene diisothiocyanate (Poly-Amine surface), an acrylic acid-co-acrylamide copolymer coating activated by 1-(3-dimethylamino propyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide (AACA-Copolymer surface), a commercial Corning CMT-GAPS amino surface, and a Telechem SuperAmine amino surface. RNA samples from cultured SARS-CoV strain were labelled using direct cDNA labelling with restriction display in a single colour format. The background-subtracted signal intensities were analysed using two-way analysis of variance. The effects of glass surfaces on background-subtracted signal intensities were significant (p=0.003). Multiple comparisons showed that differences existed mainly between the AACA-Copolymer surface and the other glass surfaces, and that the AACA-Copolymer surface had the highest background-subtracted signal intensity. The probe GC content had no significant effect on signal intensities in the narrow range of GC content represented (p=0.07). The results suggested that the AACA-Copolymer surface may be a novel choice of microorganism survey based on long oligonucleotide microarray.

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: Could injured skin be a reservoir for SARS-COV2 virus spread? Abstract The current corona virus disease 2019 (COVID-19) outbreak which is caused by SARS-COV2 is still expanding. The authors tried to focus a spotlight on the injured skin as a reservoir of SARS-COV2 to decrease the infection rate.

negative: 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.

negative: The human coronavirus HCoV-229E S-protein structure and receptor binding The coronavirus S-protein mediates receptor binding and fusion of the viral and host cell membranes. In HCoV-229E, its receptor binding domain (RBD) shows extensive sequence variation but how S-protein function is maintained is not understood. Reported are the X-ray crystal structures of Class III-V RBDs in complex with human aminopeptidase N (hAPN), as well as the electron cryomicroscopy structure of the 229E S-protein. The structures show that common core interactions define the specificity for hAPN and that the peripheral RBD sequence variation is accommodated by loop plasticity. The results provide insight into immune evasion and the cross-species transmission of 229E and related coronaviruses. We also find that the 229E S-protein can expose a portion of its helical core to solvent. This is undoubtedly facilitated by hydrophilic subunit interfaces that we show are conserved among coronaviruses. These interfaces likely play a role in the S-protein conformational changes associated with membrane fusion.

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: A 21(st) century view of infection control in everyday settings: moving from the Germ Theory of Disease to the Microbial Theory of Health Background: The growing understanding of the importance of a healthy microbiome is challenging traditional thinking that resulted in the general acceptance of the germ theory of disease. We propose a more encompassing Microbial Theory of Health that will have implications for the way that we address our relationship with microbes, including hygiene policy and community-based infection control practices. Methods: This paper considers theories over the last 30 years that have impacted hygiene policy and consumer practice, from the Germ Theory of Disease and the Hygiene Hypothesis, to the Microbial Theory of Health, including the concept of Bidirectional Hygiene. Here we present a high-level review of the literature on pathogen transmission and the cycle of infection in the home and everyday settings. Results: Targeted hygiene is an evidence-based hygiene policy that is employed to prevent transmission of pathogens and the transmission of infectious diseases through targeting only sites, surfaces, and practices that are considered high risk for pathogen transmission. Targeted hygiene also discourages the indiscriminate use of broad-spectrum microbicides for lower-risk activities and surfaces. Conclusions: The Microbial Theory of Health, including age-appropriate and health-appropriate hygiene practices for home and everyday life, should usher in a new era in which pathogen reduction can be accomplished without indiscriminate elimination of potentially beneficial microbes from the human and environmental microbiomes.

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: News and Perspectives Is There an Association Between Oral Health and Severity of COVID-19 Complications? Most patients with severe complications from COVID-19 have underlying conditions such as obesity, diabetes, and hypertension. In parallel, there is growing evidence for a link between periodontitis and non-oral systemic diseases. The oral cavity is also a reservoir for respiratory pathogens, and patients with periodontal disease are more likely to develop hospital-acquired pneumonia than healthy individuals. We therefore hypothesize that improving oral health could decrease the severity of COVID-19 symptoms and reduce the associated morbidity.

negative: Coronavirus nucleocapsid protein is an RNA chaperone Abstract RNA chaperones are nonspecific nucleic acid binding proteins with long disordered regions that help RNA molecules to adopt its functional conformation. Coronavirus nucleoproteins (N) are nonspecific RNA-binding proteins with long disordered regions. Therefore, we investigated whether transmissible gastroenteritis coronavirus (TGEV) N protein was an RNA chaperone. Purified N protein enhanced hammerhead ribozyme self-cleavage and nucleic acids annealing, which are properties that define RNA chaperones. In contrast, another RNA-binding protein, PTB, did not show these activities. N protein chaperone activity was blocked by specific monoclonal antibodies. Therefore, it was concluded that TGEV N protein is an RNA chaperone. In addition, we have shown that purified severe acute respiratory syndrome (SARS)-CoV N protein also has RNA chaperone activity. In silico predictions of disordered domains showed a similar pattern for all coronavirus N proteins evaluated. Altogether, these data led us to suggest that all coronavirus N proteins might be RNA chaperones.

negative: The evidence of SARS-CoV-2 infection on ocular surface This is a cross-sectional study of patients who received a COVID-19 diagnosis between December 30, 2019 and February 7, 2020 at Tongji Hospital. A total of 102 patients (48 Male [47%] and 54 Female [53%]) 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) were confirmed to have COVID-19 by laboratory diagnosis with a SARS-CoV-2 RT-PCR assay. Only two patients (2.78%) with conjunctivitis were identified from 72 patients with a laboratory confirmed COVID-19. Of those two patients, SARS-CoV-2 RNA fragments were found in ocular discharges by SARS-CoV-2 RT-PCR in only one patient. Our findings suspect the incidence of SARS-CoV-2 infection through the ocular surface is extremely low, while the nosocomial infection of SARS-CoV-2 through the eyes after occupational exposure is a potential route. To lower the SARS-CoV-2 nosocomial infection, all health care professionals should wear protective goggles. The inefficient diagnostic method and the sampling time lag may contribute to the lower positive rate of conjunctival swab samples of SARS-CoV-2.

negative: Numerical investigation of gaseous pollutant cross-transmission for single-sided natural ventilation driven by buoyancy and wind Abstract Single-sided natural ventilation was numerically investigated to determine the impact of buoyancy and wind on the cross-transmission of pollution by considering six window types commonly found in multistory buildings. The goal of this study was to predict the gaseous pollutant transmission using computational fluid dynamics based on the Reynolds-averaged Navier-Stokes equations and baseline k-ω turbulence equations. The results indicated that ventilation rates generally increased with increasing wind speeds if the effects of buoyancy and wind were not suppressed; however, the re-entry ratio representing the proportion of expelled air re-entering other floors and the corresponding risk of infection decreased. If the source of the virus was on a central floor, the risk of infection was the highest on the floors closest to the source. Different window types were also considered for determining their effectiveness in controlling cross-transmission and infection risk, depending on the source location and driving force (e.g., buoyancy and wind).

negative: Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion Abstract The SARS-coronavirus (SARS-CoV) is the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. To delineate functional domains of the SARS-CoV S glycoprotein, single point mutations, cluster-to-lysine and cluster-to-alanine mutations, as well as carboxyl-terminal truncations were investigated in transient expression experiments. Mutagenesis of either the coiled-coil domain of the S glycoprotein amino terminal heptad repeat, the predicted fusion peptide, or an adjacent but distinct region, severely compromised S-mediated cell-to-cell fusion, while intracellular transport and cell-surface expression were not adversely affected. Surprisingly, a carboxyl-terminal truncation of 17 amino acids substantially increased S glycoprotein-mediated cell-to-cell fusion suggesting that the terminal 17 amino acids regulated the S fusogenic properties. In contrast, truncation of 26 or 39 amino acids eliminating either one or both of the two endodomain cysteine-rich motifs, respectively, inhibited cell fusion in comparison to the wild-type S. The 17 and 26 amino-acid deletions did not adversely affect S cell-surface expression, while the 39 amino-acid truncation inhibited S cell-surface expression suggesting that the membrane proximal cysteine-rich motif plays an essential role in S cell-surface expression. Mutagenesis of the acidic amino-acid cluster in the carboxyl terminus of the S glycoprotein as well as modification of a predicted phosphorylation site within the acidic cluster revealed that this amino-acid motif may play a functional role in the retention of S at cell surfaces. This genetic analysis reveals that the SARS-CoV S glycoprotein contains extracellular domains that regulate cell fusion as well as distinct endodomains that function in intracellular transport, cell-surface expression, and cell fusion.

negative: Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a Public Health Emergency of International Concern. However, so far, there are still controversies about the source of the virus and its intermediate host. Here, we found the novel coronavirus was closely related to coronaviruses derived from five wild animals, including Paguma larvata, Paradoxurus hermaphroditus, Civet, Aselliscus stoliczkanus and Rhinolophus sinicus, and was in the same branch of the phylogenetic tree. However, genome and ORF1a homology show that the virus is not the same coronavirus as the coronavirus derived from these five animals, whereas the virus has the highest homology with Bat coronavirus isolate RaTG13.

negative: Current and emergent strategies for disinfection of hospital environments A significant number of hospital-acquired infections occur due to inefficient disinfection of hospital surfaces, instruments and rooms. The emergence and wide spread of multiresistant forms of several microorganisms has led to a situation where few compounds are able to inhibit or kill the infectious agents. Several strategies to disinfect both clinical equipment and the environment are available, often involving the use of antimicrobial chemicals. More recently, investigations into gas plasma, antimicrobial surfaces and vapour systems have gained interest as promising alternatives to conventional disinfectants. This review provides updated information on the current and emergent disinfection strategies for clinical environments.

negative: Bovine coronavirus antigen in the host cell plasmalemma Abstract Expression of bovine coronavirus (BCV) antigen in the plasmalemma of epithelioid human rectal tumor (HRT-18) and fibroblastic bovine fetal spleen (BFS) cell lines was traced by immunofluorescence and immunoelectron microscopy facilitated by colloidal gold. Cytoplasmic fluorescence was first observed at 12 hr postinfection (h.p.i) in infected HRT-18 cultures. This fluorescence coincided with the appearance of cell surface antigen reacting with colloidal gold-labeled antibodies to BCV antigens. At 24 h.p.i the amount of viral antigens at the surface of HRT-18 had increased, although cytoplasmic fluorescence remained constant. Infected BFS cells but not HRT-18 cells formed polykaryons when incubated in the presence of trypsin. One viral antigen in the plasma membrane of BFS cells was thus identified as the S glycoprotein with a fusion domain. In contrast to HRT-18 cells, the overall amount of BCV antigens at the surface of BFS cells remained constant after the onset of fusion. Analysis of the labeling characteristics established that the goldmarked-sites represented de novo expression of BCV antigen in the plasma membrane of infected cells.

negative: Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines Enveloped viruses enter cells by inducing fusion of viral and cellular membranes, a process catalyzed by a specialized membrane-fusion protein expressed on their surface. This review focuses on recent structural studies of viral fusion proteins with an emphasis on their metastable prefusion form and on interactions with neutralizing antibodies. The fusion glycoproteins have been difficult to study because they are present in a labile, metastable form at the surface of infectious virions. Such metastability is a functional requirement, allowing these proteins to refold into a lower energy conformation while transferring the difference in energy to catalyze the membrane fusion reaction. Structural studies have shown that stable immunogens presenting the same antigenic sites as the labile wild-type proteins efficiently elicit potently neutralizing antibodies, providing a framework with which to engineer the antigens for stability, as well as identifying key vulnerability sites that can be used in next-generation subunit vaccine design.

negative: Bats and Emerging Infections: An Ecological and Virological Puzzle More than 200 viruses have been detected in bats. Some unique bat characteristics can explain the roles played in the maintenance and transmission of viruses: long phylogenetic history can have originated coevolution processes, great number of species are adapted to live in different environments, big mobility, long lifespan and gregarious behaviour of many species. To analyse zoonoses long longitudinal studies are needed with a multidisciplinary approximation to obtain the following eco-epidemiological data: colony size, number of bats per species, population structure, behaviour of each species, degree of contact between bats, social structure, remaining time of bats in the colony, colony type, foraging area, turnover rate of individuals, shelter temperature, relationship with other colonies and co-infection processes. These data allows assessing the epidemiological risk and which preventive measures are necessary to take. The structure and functionality of ecosystems are changing worldwide at an unprecedented rate and can modify the interactions between humans and infected bats. There are more or less local factors that can affect the emergence and spread of diseases (environmental alterations, changes in land use, human population growth, changes in human socioeconomic behavior or social structure, people mobility increase, trade increase, forest fires, extreme weather events, wars, breakdown in public health infrastructure, etc.). Twenty-three percent of all bat species in the world are decreasing. How does the regression of bat species affect the dynamic of viruses? The dichotomy between health risk and bat preservation is compatible with a preventive task based on more information and training.

negative: Physical interventions to interrupt or reduce the spread of respiratory viruses. BACKGROUND Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a global threat. Antiviral drugs and vaccinations may be insufficient to prevent their spread. OBJECTIVES To review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. SEARCH STRATEGY We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL 2010, Issue 3), which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to October 2010), OLDMEDLINE (1950 to 1965), EMBASE (1990 to October 2010), CINAHL (1982 to October 2010), LILACS (2008 to October 2010), Indian MEDLARS (2008 to October 2010) and IMSEAR (2008 to October 2010). SELECTION CRITERIA In this update, two review authors independently applied the inclusion criteria to all identified and retrieved articles and extracted data. We scanned 3775 titles, excluded 3560 and retrieved full papers of 215 studies, to include 66 papers of 67 studies. We included physical interventions (screening at entry ports, isolation, quarantine, social distancing, barriers, personal protection, hand hygiene) to prevent respiratory virus transmission. We included randomised controlled trials (RCTs), cohorts, case-controls, before-after and time series studies. DATA COLLECTION AND ANALYSIS We used a standardised form to assess trial eligibility. We assessed RCTs by randomisation method, allocation generation, concealment, blinding and follow up. We assessed non-RCTs for potential confounders and classified them as low, medium and high risk of bias. MAIN RESULTS We included 67 studies including randomised controlled trials and observational studies with a mixed risk of bias. A total number of participants is not included as the total would be made up of a heterogenous set of observations (participant people, observations on participants and countries (object of some studies)). The risk of bias for five RCTs and most cluster-RCTs was high. Observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis. The highest quality cluster-RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Benefit from reduced transmission from children to household members is broadly supported also in other study designs where the potential for confounding is greater. Nine case-control studies suggested implementing transmission barriers, isolation and hygienic measures are effective at containing respiratory virus epidemics. Surgical masks or N95 respirators were the most consistent and comprehensive supportive measures. N95 respirators were non-inferior to simple surgical masks but more expensive, uncomfortable and irritating to skin. Adding virucidals or antiseptics to normal handwashing to decrease respiratory disease transmission remains uncertain. Global measures, such as screening at entry ports, led to a non-significant marginal delay in spread. There was limited evidence that social distancing was effective, especially if related to the risk of exposure. AUTHORS' CONCLUSIONS Simple and low-cost interventions would be useful for reducing transmission of epidemic respiratory viruses. Routine long-term implementation of some measures assessed might be difficult without the threat of an epidemic.

negative: Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells The N-terminal domain of the coronavirus nucleocapsid (N) protein adopts a fold resembling a right hand with a flexible, positively charged β-hairpin and a hydrophobic palm. This domain was shown to interact with the genomic RNA for coronavirus infectious bronchitis virus (IBV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Based on its 3D structure, we used site-directed mutagenesis to identify residues essential for the RNA-binding activity of the IBV N protein and viral infectivity. Alanine substitution of either Arg-76 or Tyr-94 in the N-terminal domain of IBV N protein led to a significant decrease in its RNA-binding activity and a total loss of the infectivity of the viral RNA to Vero cells. In contrast, mutation of amino acid Gln-74 to an alanine, which does not affect the binding activity of the N-terminal domain, showed minimal, if any, detrimental effect on the infectivity of IBV. This study thus identifies residues critical for RNA binding on the nucleocapsid surface, and presents biochemical and genetic evidence that directly links the RNA binding capacity of the coronavirus N protein to the viral infectivity in cultured cells. This information would be useful in development of preventive and treatment approaches against coronavirus infection.

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: COVID-19 in older adults The advent of the SARS-CoV-2 and COVID-19 pandemic has generated a lot of publications at a rapid pace. We know that older adults disproportionately suffer the most severe of COVID outcomes. Here we attempt to coalesce the key knowledge of SARS-CoV-2 biology to the disease and clinical care concepts in the context of older adults.

negative: The Role of the Environment and Colonization in Healthcare-Associated Infections Healthcare-associated infections (HAIs) can be caused by endogenous host microbial flora or by exogenous microbes, including those found in the hospital environment. Efforts to decrease endogenous pathogens via decolonization and skin antisepsis may decrease the risk of infection in some settings. Controlling the spread of potential pathogens from the environment requires meticulous attention to cleaning and disinfection practices. In addition to selection of the appropriate cleaning agent, use of tools that assess the adequacy of cleaning and addition of no-touch cleaning technology may decrease environmental contamination. Hand hygiene is also a critical component of preventing transmission of pathogens from the environment to patients via healthcare worker hands.

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: Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses classified within the Nidovirales order. This coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (SARS-CoV). This review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses the newly described human emerging pathogen, SARS-CoV. The coronavirus part covers (i) a description of a group of coronaviruses and the diseases they cause, including the prototype coronavirus, murine hepatitis virus, which is one of the recognized animal models for multiple sclerosis, as well as viruses of veterinary importance that infect the pig, chicken, and cat and a summary of the human viruses; (ii) a short summary of the replication cycle of coronaviruses in cell culture; (iii) the development and application of reverse genetics systems; and (iv) the roles of individual coronavirus proteins in replication and pathogenesis. The SARS-CoV part covers the pathogenesis of SARS, the developing animal models for infection, and the progress in vaccine development and antiviral therapies. The data gathered on the animal coronaviruses continue to be helpful in understanding SARS-CoV.

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: Role of respirators in controlling the spread of novel coronavirus (COVID‐19) amongst dental healthcare providers: a review During the ongoing COVID‐19 pandemic, healthcare professionals are at the forefront of managing the highly infectious coronavirus. As the most common route of transmission is via aerosols and droplet inhalation, it is critical for healthcare workers to have the correct personal protective equipment (PPE) including gowns, masks and goggles. Surgical masks are not effective in preventing the influenza and SARS, so they are unlikely to be able to resist contaminated aerosols from entering the respiratory system. Therefore, it is vital to use respirators which have been proven to offer better protection against droplets, aerosols and fluid penetration and which form a tight seal around the mouth and nose. Various types of respirators are used in healthcare settings, such as half‐mask filtering facepiece respirators (FFRs) and powered air‐purifying respirators (PAPRs). The most commonly used FFR is the N95 disposable respirator, which is tight fitting and has a 95% or above particle filtering efficiency for a median particle size of 0.3 µm. This review discusses respirators, their purpose, types, clinical efficiency and proper donning and doffing techniques.

negative: Outbreak analysis with a logistic growth model shows COVID-19 suppression dynamics in China China experienced an outbreak of a novel coronavirus, SARS-CoV2, from mid-January till mid-March 2020. Here we review the curves of epidemic growth and decline of the virus in China using a phenomenological logistic growth model to summarize the dynamics of the outbreak using three parameters that characterize the epidemic's timing, rate and peak. During the initial phase, the number of cases doubled every 2.7 (range 2.2 - 4.4) days. The rate of increase in the number of reported cases peaked approximately 10 days after suppression measures were started on 23-25 January 2020. The peak in the number of reported sick cases occurred on average 18 days after the start of measures. From the time of starting measures till the peak, the number of cases increased by a factor 38.5 in the province Hubei, and by a factor 9.5 for all of China (range: 6.2-20.4 in the other provinces). Complete suppression took up to 2 months (range: 23-57d.), during which period severe restrictions, social distancing measures, testing and isolation of cases were in place. The suppression of the disease in China has been successful, acting as a beacon of hope for countries outside China where the epidemic is still in a phase of increase and authorities need to decide their course of action.

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: Implications of gastrointestinal manifestations of COVID-19

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: What is the importance of zoonotic trichomonads for human health? Trichomonads are common parasites of many vertebrate and invertebrate species, with four species classically recognized as human parasites: Dientamoeba fragilis, Pentatrichomonas hominis, Trichomonas vaginalis, and Trichomonas tenax. The latter two species are considered human-specific; by contrast, D. fragilis and P. hominis have been isolated from domestic and farm mammals, demonstrating a wide host range and potential zoonotic origin. Several new studies have highlighted the zoonotic dimension of trichomonads. First, species typically known to infect birds and domestic mammals have been identified in human clinical samples. Second, several phylogenetic analyses have identified animal-derived trichomonads as close sister taxa of the two human-specific species. It is our opinion, therefore, that these observations prompt further investigation into the importance of zoonotic trichomonads for human health.

negative: Envelope glycoprotein interactions in coronavirus assembly Coronaviruses are assembled by budding into smooth membranes of the intermediate ER-to-Golgi compartment. We have studied the association of the viral membrane glycoproteins M and S in the formation of the virion envelope. Using coimmunoprecipitation analysis we demonstrated that the M and S proteins of mouse hepatitis virus (MHV) interact specifically forming heteromultimeric complexes in infected cells. These could be detected only when the detergents used for their solubilization from cells or virions were carefully chosen: a combination of nonionic (NP-40) and ionic (deoxycholic acid) detergents proved to be optimal. Pulse-chase experiments revealed that newly made M and S proteins engaged in complex formation with different kinetics. Whereas the M protein appeared in complexes immediately after its synthesis, newly synthesized S protein did so only after a lag phase of > 20 min. Newly made M was incorporated into virus particles faster than S, which suggests that it associates with preexisting S molecules. Using the vaccinia virus T7-driven coexpression of M and S we also demonstrate formation of M/S complexes in the absence of other coronaviral proteins. Pulse-chase labelings and coimmunoprecipitation analyses revealed that M and S associate in pre-Golgi membranes because the unglycosylated form of M appeared in M/S complexes rapidly. Since no association of M and S was detected when protein export from the ER was blocked by brefeldin A, stable complexes most likely arise in the ER-to-Golgi intermediate compartment. Sucrose velocity gradient analysis showed the M/S complexes to be heterogeneous and of higher order, suggesting that they are maintained by homo- and heterotypic interactions. M/S complexes colocalized with alpha-mannosidase II, a resident Golgi protein. They acquired Golgi-specific oligosaccharide modifications but were not detected at the cell surface. Thus, the S protein, which on itself was transported to the plasma membrane, was retained in the Golgi complex by its association with the M protein. Because coronaviruses bud at pre-Golgi membranes, this result implies that the envelope glycoprotein complexes do not determine the site of budding. Yet, the self-association of the MHV envelope glycoproteins into higher order complexes is indicative of its role in the sorting of the viral membrane proteins and in driving the formation of the viral lipoprotein coat in virus assembly.

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: Map of SARS-CoV-2 spike epitopes not shielded by glycans The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping.

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: Comparisons of substitution, insertion and deletion probes for resequencing and mutational analysis using oligonucleotide microarrays Although oligonucleotide probes complementary to single nucleotide substitutions are commonly used in microarray-based screens for genetic variation, little is known about the hybridization properties of probes complementary to small insertions and deletions. It is necessary to define the hybridization properties of these latter probes in order to improve the specificity and sensitivity of oligonucleotide microarray-based mutational analysis of disease-related genes. Here, we compare and contrast the hybridization properties of oligonucleotide microarrays consisting of 25mer probes complementary to all possible single nucleotide substitutions and insertions, and one and two base deletions in the 9168 bp coding region of the ATM (ataxia telangiectasia mutated) gene. Over 68 different dye-labeled single-stranded nucleic acid targets representing all ATM coding exons were applied to these microarrays. We assess hybridization specificity by comparing the relative hybridization signals from probes perfectly matched to ATM sequences to those containing mismatches. Probes complementary to two base substitutions displayed the highest average specificity followed by those complementary to single base substitutions, single base deletions and single base insertions. In all the cases, hybridization specificity was strongly influenced by sequence context and possible intra- and intermolecular probe and/or target structure. Furthermore, single nucleotide substitution probes displayed the most consistent hybridization specificity data followed by single base deletions, two base deletions and single nucleotide insertions. Overall, these studies provide valuable empirical data that can be used to more accurately model the hybridization properties of insertion and deletion probes and improve the design and interpretation of oligonucleotide microarray-based resequencing and mutational analysis.

negative: New coronavirus pneumonia COVID-19 and ocular surface transmission/ 国际眼科杂志(Guoji Yanke Zazhi) @#Since the end of 2019, the novel coronavirus pneumonia(COVID-19)has rapidly spread in Wuhan City, Hubei Province of China. This has aroused great concern of the Chinese government and the international community. There have been unconfirmed threads of COVID-19 patients with conjunctivitis as the first symptom. Therefore, the issue that whether and how the novel coronavirus strain SARS-CoV-2 infection is transmitted through the ocular surface has become a new concern. In the absence of clinical and experimental evidence of COVID-19 in ocular infection, we have conducted a retrospective literature analysis of viral pathogens that simultaneously trigger ocular lesions during the onset of epidemic diseases. The purpose of this paper is to provide some reference and suggestions for appropriately understanding of ocular protection in the prevention and control of the COVID-19.

negative: Persistence pays: how viruses promote host group survival Recently, we have realized that viruses numerically dominate all life. Although viruses are known to affect host survival in populations, this has not been previously evaluated in the context of host group selection. Group selection per se is not a currently accepted idea and its apparent occurrence is explained by statistical gene frequency models of kin selection. Viruses were not considered in such models. Prevalent views associate viruses and disease. Yet many viruses establish species-specific persistent, inapparent infections that are stable on an evolutionary time scale. Such persistent infections can have large effects on relative reproductive fitness of competing host populations. In this essay, I present arguments on how persistent infections can promote population survival. Mouse hepatitis virus is used as well studied examplar to re-evaluate the theoretical basis of the mouse haystack model of M Smith. This virus-centric re-examination concludes that viruses can indeed affect and promote relative group selection.

negative: The Role of the Lung’s Microbiome in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease that commonly affects older adults and is associated with the histopathological and/or radiological patterns of usual interstitial pneumonia (UIP). Despite significant advances in our understanding of disease pathobiology and natural history, what causes IPF remains unknown. A potential role for infection in the disease’s pathogenesis and progression or as a trigger of acute exacerbation has long been postulated, but initial studies based on traditional culture methods have yielded inconsistent results. The recent application to IPF of culture-independent techniques for microbiological analysis has revealed previously unappreciated alterations of the lung microbiome, as well as an increased bacterial burden in the bronchoalveolar lavage (BAL) of IPF patients, although correlation does not necessarily entail causation. In addition, the lung microbiome remains only partially characterized and further research should investigate organisms other than bacteria and viruses, including fungi. The clarification of the role of the microbiome in the pathogenesis and progression of IPF may potentially allow its manipulation, providing an opportunity for targeted therapeutic intervention.

negative: Antagonism of dsRNA-Induced Innate Immune Pathways by NS4a and NS4b Accessory Proteins during MERS Coronavirus Infection Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in 2012 as a novel etiological agent of severe respiratory disease in humans. As during infection by other viruses, host sensing of viral double-stranded RNA (dsRNA) induces several antiviral pathways. These include interferon (IFN), oligoadenylate synthetase (OAS)-RNase L, and protein kinase R (PKR). Coronaviruses, including MERS-CoV, potently suppress the activation of these pathways, inducing only modest host responses. Our study describes the functions of two accessory proteins unique to MERS-CoV and related viruses, NS4a and NS4b, during infection in human airway epithelium-derived A549 cells. NS4a has been previously characterized as a dsRNA binding protein, while NS4b is a 2′,5′-phosphodiesterase with structural and enzymatic similarity to NS2 encoded by mouse hepatitis virus (MHV). We found that deletion of NS4a results in increased interferon lambda (IFNL1) expression, as does mutation of either the catalytic site or nuclear localization sequence of NS4b. All of the mutant viruses we tested exhibited slight decreases in replication. We previously reported that, like MHV NS2, NS4b antagonizes OAS-RNase L, but suppression of IFN is a previously unidentified function for viral phosphodiesterases. Unexpectedly, deletion of NS4a does not result in robust activation of the PKR or OAS-RNase L pathways. Therefore, MERS-CoV likely encodes other proteins that contribute to suppression or evasion of these antiviral innate immune pathways that should be an important focus of future work. This study provides additional insight into the complex interactions between MERS-CoV and the host immune response.

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

negative: Myocyte Specific Upregulation of ACE2 in Cardiovascular Disease: Implications for SARS-CoV-2 mediated myocarditis Coronavirus disease 2019 (COVID-19) is a global pandemic caused by a novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 infection of host cells occurs predominantly via binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor. Hypertension and pre-existing cardiovascular disease are risk factors for morbidity from COVID-19, and it remains uncertain whether the use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) impacts infection and disease. Here, we aim to shed light on this question by assessing ACE2 expression in normal and diseased human myocardial samples profiled by bulk and single nucleus RNA-seq.

negative: The calendar of epidemics: Seasonal cycles of infectious diseases

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: Physico-chemical properties of murine hepatitis virus, strain A59 The infectivity of murine hepatitis virus (MHV-A59) was optimally stable at pH 6.0 and was unaffected by ionic strength or at least 15 cycles of freezing and thawing. It was completely inactivated within 25 minutes at 56° C, but was protected by 1m magnesium chloride or magnesium sulphate. It was completely inactivated within 14 days at 37 and 22°C, but was relatively stable for as long as 72 days at 4°C and optimal pH.

negative: Commentary Considerations for Recommending Extended Use and Limited Reuse of Filtering Facepiece Respirators in Health Care Settings Public health organizations, such as the Centers for Disease Control and Prevention (CDC), are increasingly recommending the use of N95 filtering facepiece respirators (FFRs) in health care settings. For infection control purposes, the usual practice is to discard FFRs after close contact with a patient (“single use”). However, in some situations, such as during contact with tuberculosis patients, limited FFR reuse (i.e., repeated donning and doffing of the same FFR by the same person) is practiced. A related practice, extended use, involves wearing the same FFR for multiple patient encounters without doffing. Extended use and limited FFR reuse have been recommended during infectious disease outbreaks and pandemics to conserve FFR supplies. This commentary examines CDC recommendations related to FFR extended use and limited reuse and analyzes available data from the literature to provide a relative estimate of the risks of these practices compared to single use. Analysis of the available data and the use of disease transmission models indicate that decisions regarding whether FFR extended use or reuse should be recommended should continue to be pathogen- and event-specific. Factors to be included in developing the recommendations are the potential for the pathogen to spread via contact transmission, the potential that the event could result in or is currently causing a FFR shortage, the protection provided by FFR use, human factors, potential for self-inoculation, the potential for secondary exposures, and government policies and regulations. While recent findings largely support the previous recommendations for extended use and limited reuse in certain situations, some new cautions and limitations should be considered before issuing recommendations in the future. In general, extended use of FFRs is preferred over limited FFR reuse. Limited FFR reuse would allow the user a brief respite from extended wear times, but increases the risk of self-inoculation and preliminary data from one study suggest that some FFR models may begin to lose effectiveness after multiple donnings.

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: Structure-based antigen design: a strategy for next generation vaccines Vaccine design is progressing from empiricism towards the increasingly rational presentation of the targets of protective immunity. Nevertheless, most current vaccine antigens are essentially the native macromolecules of pathogens. These molecules are adapted to evade, not induce, immunity. High resolution structures reveal the electrostatic surfaces recognized by neutralizing antibodies and the architectures underlying these surfaces, thereby identifying which substructures must be left intact and which can be changed to optimize biochemical and immunologic performance. Armed with detailed structural information, we can engineer optimized antigens that are more stable, homogeneous, and efficiently produced, making immunization more practical and affordable. Understanding the structural basis for immunogenicity and immunodominance will allow us to improve vaccine efficacy and broaden the range of vaccine-preventable diseases.

negative: 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.

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: Coronaviridae, pathogenetic and clinical aspects: An update Abstract A review is given about pathogenetic and clinical aspects of the well-known as well as of recently detected members of the family Coronaviridae. Special attention is paid to coronavirus infections of domestic cattle and pets, whereas avian, murine, rat and human coronaviruses are summarized briefly.

negative: Purification and Electron Cryomicroscopy of Coronavirus Particles Intact, enveloped coronavirus particles vary widely in size and contour, and are thus refractory to study by traditional structural means such as X-ray crystallography. Electron microscopy (EM) overcomes some problems associated with particle variability and has been an important tool for investigating coronavirus ultrastructure. However, EM sample preparation requires that the specimen be dried onto a carbon support film before imaging, collapsing internal particle structure in the case of coronaviruses. Moreover, conventional EM achieves image contrast by immersing the specimen briefly in heavy-metal-containing stain, which reveals some features while obscuring others. Electron cryomicroscopy (cryo-EM) instead employs a porous support film, to which the specimen is adsorbed and flash-frozen. Specimens preserved in vitreous ice over holes in the support film can then be imaged without additional staining. Cryo-EM, coupled with single-particle image analysis techniques, makes it possible to examine the size, structure and arrangement of coronavirus structural components in fully hydrated, native virions. Two virus purification procedures are described.

negative: Respiratory viruses in airline travellers with influenza symptoms: Results of an airport screening study Abstract Background There is very little known about the prevalence and distribution of respiratory viruses, other than influenza, in international air travellers and whether symptom screening would aid in the prediction of which travellers are more likely to be infected with specific respiratory viruses. Objectives In this study, we investigate whether, the use of a respiratory symptom screening tool at the border would aid in predicting which travellers are more likely to be infected with specific respiratory viruses. Study design Data were collected from travellers arriving at Christchurch International Airport, New Zealand, during the winter 2008, via a symptom questionnaire, temperature testing, and respiratory sampling. Results Respiratory viruses were detected in 342 (26.0%) of 1313 samples obtained from 2714 symptomatic travellers. The most frequently identified viruses were rhinoviruses (128), enteroviruses (77) and influenza B (48). The most frequently reported symptoms were stuffy or runny nose (60%), cough (47%), sore throat (27%) and sneezing (24%). Influenza B infections were associated with the highest number of symptoms (mean of 3.4) followed by rhinoviruses (mean of 2.2) and enteroviruses (mean of 1.9). The positive predictive value (PPV) of any symptom for any respiratory virus infection was low at 26%. Conclusions The high prevalence of respiratory virus infections caused by viruses other than influenza in this study, many with overlapping symptotology to influenza, has important implications for any screening strategies for the prediction of influenza in airline travellers.

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: The American College of Nuclear Medicine Guidance on Operating Procedures for a Nuclear Medicine Facility During COVID-19 Pandemic The novel coronavirus 2 pandemic is causing widespread disruption in everyday life necessitating urgent and radical adaptations in operating procedures at Nuclear Medicine facilities. The potential for causing severe illness, COVID-19, calls for strict observance of preventive measures aimed to mitigate the spread of the virus. The threat of COVID-19 is particularly serious as there is no vaccine and no specific antiviral therapy. Further complications are introduced by shortages of personal protective equipment for healthcare workers who have direct contact with patients and effective testing to identify infected patients, raising the need for delaying some testing and therapies. Certain vulnerable segments of the general population have been identified (advanced age and certain comorbidities), which should heighten further their preventive efforts. Therefore, this guidance is intended to be operationalized depending on a facility’s specific needs and local disease prevalence.

negative: 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.

negative: Lessons from Operations Management to Combat the COVID-19 Pandemic

negative: Western Cold and Flu (WeCoF) aerosol study – preliminary results BACKGROUND: Influenza virus is responsible for annual deaths due to seasonal epidemics and is the cause of major pandemics which have claimed millions of human lives over the last century. Knowledge about respiratory virus transmission is advancing. Spread is likely through the air, but much work remains to be done to characterize the aerosols produced by infected individuals, including viral particle survival and infectivity. Although coughs have been characterized, little work has been done to examine coughs from infected individuals. The WeCoF project aims at providing evidence to support prevention measures to mitigate person-to-person influenza transmission in critical locations, such as hospitals, and during pandemics. FINDINGS: A novel experimental cough chamber facility – the FLUGIE – has been developed to study the far-field aerodynamics and aerosol transport of droplets produced by the coughs from humans naturally-infected with influenza. The flow field of each cough is measured using Particle Image Velocimetry (PIV). A preliminary study involving 12 healthy individuals has been carried out in order to quantify the strengths of their coughs at a distance of 1 m from the mouth. The spatially averaged maximum velocity was determined and the average value was 0.41 m/s across 27 coughs of good data quality. The peak value of velocity was also extracted and compared with the average velocity. CONCLUSIONS: Preliminary results show that there is significant air motion associated with a cough (on the order of 0.5 m/s) as far away as 1 m from the mouth of the healthy person who coughs. The results from this pilot study provide the framework for a more extensive participant recruitment campaign that will encompass a statistically-significant cohort.

negative: 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.

negative: Natural protection of ocular surface from viral infections – a hypothesis A pandemic outbreak of a viral respiratory infection (COVID-19) caused by a coronavirus (SARS-CoV-2) prompted a multitude of research focused on various aspects of this disease. One of the interesting aspects of the clinical manifestation of the infection is an accompanying ocular surface viral infection, viral conjunctivitis. Although occasional reports of viral conjunctivitis caused by this and the related SARS-CoV virus (causing the SARS outbreak in the early 2000s) are available, the prevalence of this complication among infected people appears low (∼1%). This is surprising, considering the recent discovery of the presence of viral receptors (ACE2 and TMPRSS2) in ocular surface tissue. The discrepancy between the theoretically expected high rate of concurrence of viral ocular surface inflammation and the observed relatively low occurrence can be explained by several factors. In this work, we discuss the significance of natural protective factors related to anatomical and physiological properties of the eyes and preventing the deposition of large number of virus-loaded particles on the ocular surface. Specifically, we advance the hypothesis that the standing potential of the eye plays an important role in repelling aerosol particles (microdroplets) from the surface of the eye and discuss factors associated with this hypothesis, possible ways to test it and its implications in terms of prevention of ocular infections.

negative: The outbreak of COVID-19: An overview In late December 2019, a previous unidentified coronavirus, currently named as the 2019 novel coronavirus#, emerged from Wuhan, China, and resulted in a formidable outbreak in many cities in China and expanded globally, including Thailand, Republic of Korea, Japan, United States, Philippines, Viet Nam, and our country (as of 2/6/2020 at least 25 countries). The disease is officially named as Coronavirus Disease-2019 (COVID-19, by WHO on February 11, 2020). It is also named as Severe Pneumonia with Novel Pathogens on January 15, 2019 by the Taiwan CDC, the Ministry of Health and is a notifiable communicable disease of the fifth category. COVID-19 is a potential zoonotic disease with low to moderate (estimated 2%–5%) mortality rate. Person-to-person transmission may occur through droplet or contact transmission and if there is a lack of stringent infection control or if no proper personal protective equipment available, it may jeopardize the first-line healthcare workers. Currently, there is no definite treatment for COVID-19 although some drugs are under investigation. To promptly identify patients and prevent further spreading, physicians should be aware of the travel or contact history of the patient with compatible symptoms.

negative: The role of asymptomatic SARS-CoV-2 infections: rapid living systematic review and meta-analysis Background: There is substantial disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a population. The disagreement results, in part, from the interpretation of studies that report a proportion of asymptomatic people with SARS-CoV-2 detected at a single point. Review questions: 1. Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? 2. Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? 3. What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection, or pre-symptomatic? Methods: Rapid living systematic review (protocol https://osf.io/9ewys/). We searched Pubmed, Embase, bioRxiv and medRxiv using a living evidence database of SARS-CoV-2 literature on 25.03.2020. We included studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up and modelling studies. Study selection, data extraction and bias assessment were done by one reviewer and verified by a second, with disagreement resolved by discussion or a third reviewer. We used a common-effect model to synthesise proportions from comparable studies. Results: We screened 89 studies and included 11. We estimated an upper bound for the proportion of asymptomatic SARS-CoV-2 infections of 29% (95% confidence interval 23 to 37%) in eight studies. Selection bias and likely publication bias affected the family case investigation studies. One statistical modelling study estimated the true proportion of asymptomatic infections at 18% (95% credibility interval 16 to 20%). Estimates of the proportions of pre-symptomatic individual in four studies were too heterogeneous to combine. In modelling studies, 40-60% of all SARS-CoV-2 infections are the result of transmission from pre-symptomatic individuals, with a smaller contribution from asymptomatic individuals. Conclusions: An intermediate contribution of pre-symptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention, with enhanced hand and respiratory hygiene, testing tracing and isolation strategies and social distancing, will continue to be needed. The findings of this systematic review of publications early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection.

negative: Early events of SARS coronavirus infection in vero cells An isolate from a patient in the recent severe acute respiratory syndrome (SARS) outbreak in Singapore was used to infect Vero E6 cells. This study concentrated on the first 30 min of infection. It was discovered that the SARS coronavirus attached, entered, and uncoated the nucleocapsids, all within a 30‐min period. At 5 min after infection, several virus particles lined the Vero cell plasma membrane. Virus particles were at various stages of fusion at the cell surface, since entry was not a synchronised process. After entry (10 and 15 min), spherical core particles moved into the cytoplasm within large vacuoles. Quite surprising at such early stages of infection (20 min), a virus‐induced change in the infected cells was evident. The induction of myelin‐like membrane whorls was obvious within the same vacuoles as the core particles. The significance of this virus‐induced change is unknown at this stage. By 25–30 min postinfection (p.i.), the spherical core particles appeared to be disassociating and, in their place, doughnut‐shaped electron‐dense structures were observed. These could be the virus genomes together with the helical nucleocapsids. They were no longer in large vacuoles but packaged into smaller vacuoles in the cytoplasm, and occasionally in small groups. J. Med. Virol. 71:323–331, 2003. © 2003 Wiley‐Liss, Inc.

negative: Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI-RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials.

negative: Comprehensive in-vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms SARS-CoV-2 is the positive-sense RNA virus that causes COVID-19, a disease that has triggered a major human health and economic crisis. The genome of SARS-CoV-2 is unique among viral RNAs in its vast potential to form stable RNA structures and yet, as much as 97% of its 30 kilobases have not been structurally explored in the context of a viral infection. Our limited knowledge of SARS-CoV-2 genomic architecture is a fundamental limitation to both our mechanistic understanding of coronavirus life cycle and the development of COVID-19 RNA-based therapeutics. Here, we apply a novel long amplicon strategy to determine for the first time the secondary structure of the SARS-CoV-2 RNA genome probed in infected cells. In addition to the conserved structural motifs at the viral termini, we report new structural features like a conformationally flexible programmed ribosomal frameshifting pseudoknot, and a host of novel RNA structures, each of which highlights the importance of studying viral structures in their native genomic context. Our in-depth structural analysis reveals extensive networks of well-folded RNA structures throughout Orf1ab and reveals new aspects of SARS-CoV-2 genome architecture that distinguish it from other single-stranded, positive-sense RNA viruses. Evolutionary analysis of RNA structures in SARS-CoV-2 shows that several features of its genomic structure are conserved across beta coronaviruses and we pinpoint individual regions of well-folded RNA structure that merit downstream functional analysis. The native, complete secondary structure of SAR-CoV-2 presented here is a roadmap that will facilitate focused studies on mechanisms of replication, translation and packaging, and guide the identification of new RNA drug targets against COVID-19.

negative: RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses As the COVID-19 outbreak spreads, there is a growing need for a compilation of conserved RNA genome regions in the SARS-CoV-2 virus along with their structural propensities to guide development of antivirals and diagnostics. Using sequence alignments spanning a range of betacoronaviruses, we rank genomic regions by RNA sequence conservation, identifying 79 regions of length at least 15 nucleotides as exactly conserved over SARS-related complete genome sequences available near the beginning of the COVID-19 outbreak. We then confirm the conservation of the majority of these genome regions across 739 SARS-CoV-2 sequences reported to date from the current COVID-19 outbreak, and we present a curated list of 30 ‘SARS-related-conserved’ regions. We find that known RNA structured elements curated as Rfam families and in prior literature are enriched in these conserved genome regions, and we predict additional conserved, stable secondary structures across the viral genome. We provide 106 ‘SARS-CoV-2-conserved-structured’ regions as potential targets for antivirals that bind to structured RNA. We further provide detailed secondary structure models for the 5’ UTR, frame-shifting element, and 3’ UTR. Last, we predict regions of the SARS-CoV-2 viral genome have low propensity for RNA secondary structure and are conserved within SARS-CoV-2 strains. These 59 ‘SARS-CoV-2-conserved-unstructured’ genomic regions may be most easily targeted in primer-based diagnostic and oligonucleotide-based therapeutic strategies.

negative: A Preliminary Assessment of Novel Coronavirus (COVID-19) Knowledge and Perceptions in Nigeria This study assessed knowledge and perceptions about COVID-19 among the general public in Nigeria during the initial week of the pandemic lockdown in the country. From March 28 to April 4, 2020, this cross-sectional survey used an anonymous online questionnaire to collect data from respondents within Nigeria. Purposive and snowball sampling techniques were used to recruit 1357 respondents, aged 15-70 years, from 180 cities and towns within Nigeria. Study data were analyzed using descriptive statistics. Approximately more than half (57.02%) of the respondents were male with a high level of education (48.86% bachelor degree or higher). Approximately half of the respondents (46.94%) opined that COVID-19 was a biological weapon designed by the Chinese government. About 94% of the respondents identified contact with airborne droplets via breathing, sneezing, or coughing as the most common mode of transmission; most respondents associated COVID-19 with coughing (81.13%), shortness of breath (73.47%) and fever (62.79%). Regular hand washing and social distancing were selected by most respondents (94.25%) as a way of preventing infection whereas 11.86% reported consuming gins, garlic, ginger, herbal mixtures and African foods/soups as preventive measures against COVID-19. The majority of the respondents (91.73%) thought COVID-19 is deadly, and most respondents (84.3%) got 4 or more answers correctly. It was also observed that the traditional media (TV/Radio) is the most common source of health information about COVID-19 (93.5%). Findings revealed that Nigerians have relatively high knowledge, mostly derived from traditional media, about COVID-19. Their perceptions of COVID-19 bear implications across public health initiatives, compliance with precautionary behavior as well as bilateral relations with foreign nations. Evidence-based campaign should be intensified to remove misconceptions and promote precautionary measures.

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: 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.

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: Cellular composition, coronavirus antigen expression and production of specific antibodies in lesions in feline infectious peritonitis Abstract Twenty-three cats with spontaneous feline infectious peritonitis (FIP) were examined by light microscopy including immunohistology and histochemistry in order to determine the cellular composition and the expression of viral antigen in lesions in FIP. Furthermore, the presence of plasma-cells producing coronavirus-specific antibodies was evaluated in situ. Macrophages and neutrophils were demonstrated by an antibody against calprotectin (leukocyte protein L1, myeloid/histiocyte antigen), neutrophils were recognized due to their chloroacetate esterase activity, and B- and T-lymphocytes were identified by antibodies against the CD3 antigen and the CD45R antigen, respectively. Expression of viral antigen was immunohistologically demonstrated by a monoclonal antibody (mAb) against coronavirus while coronavirus-specific antibodies in situ were identified by the application of feline coronavirus prior to the coronavirus antibody. Lesions were classified as diffuse alterations at serosal surfaces, granulomas with areas of necrosis, granulomas without extended necrosis, focal and perivascular lymphoplasmocytic infiltrates, and granulomatous-necrotizing vasculitis. Diffuse alterations on serosal surfaces were represented either by activated mesothelial cells with single coronavirus antigen-bearing macrophages or by layers of precipitated exudate containing single to numerous granulomas with areas of necrosis. In liver and spleen, the exudate was often underlaid by a small band of subcapsular B-cells with an occasional plasma-cell producing coronavirus-specific antibodies. In other locations, a variably broad band of B-cells and plasma-cells, often infiltrating between underlying muscle fibers, separated the exudate from the unaltered tissue. Some of these plasma-cells were positive for coronavirus-specific antibodies. In granulomas with areas of necrosis, the central necrosis was surrounded by macrophages usually expressing considerable amounts of viral antigen. Few B-cells and plasma-cells were found in the periphery. In granulomas without extended necrosis, the number of macrophages were lower. Only few macrophages expressing low amounts of viral antigen were present. B-cells and plasma-cells formed a broad rim. Few plasma-cells stained positive for coronavirus-specific antibodies. In both types of granulomas, few neutrophils were found between macrophages. Few T-cells were seen scattered throughout the lesions. Focal and perivascular lymphoplasmocytic infiltrates were mainly seen in omentum and leptomeninx. B-cells were the predominant cells; some plasma-cells were positive for coronavirus-specific antibodies. Viral antigen was not readily detected in these alterations. Granulomatous-necrotizing vasculitis was occasionally found in kidneys and leptomeninx. It was dominated by macrophages which often stained strongly positive for coronavirus antigen. Different types of alteration were often seen in the same animal and even the same tissue. There was no obvious correlation between the cat's age, gross pathological changes, and the histological types of alteration. Single plasma-cells positive for coronavirus-specific antibodies were found around blood vessels distant from inflammatory alterations, within the lung parenchyma, as infiltrating cells in the mucosa of the small intestine, and in spleen and mesenteric lymph node. Results show that alterations in FIP are heterogeneous concerning cellular composition and expression of viral antigen. The dominance of B-cells in part of the lesions together with the presence of plasma-cells positive for coronavirus-specific antibodies indicate that these cells may play a role in the maintenance of inflammatory processes in FIP.

negative: Chapter 20 Vaccines the tugboat for prevention-based animal production Abstract The world population is growing at a faster rate day-by-day and the demands for animal products are also increasing to meet the food security worldwide. For sustained production of animals products, healthy livestock and poultry farming are the major concerns as animals are susceptible to various infectious agents viz. bacteria, virus, and parasites leading to huge economical losses in the form of livestock’s morbidity and mortality. Besides, zoonotic nature of some infectious pathogens of animals is also raising concern for human safety. Vaccination of animals against various diseases present in different geographical regions is a best known strategy for prevention of different disease outbreaks both in organized and unorganized livestock and poultry sectors. Vaccines had played a major role in eradication of different dreaded diseases of livestock sectors globally. In this article we have discussed different vaccine types, various vaccine strategies used for the development of more efficacious and safe vaccines and commercially available vaccines for livestock and poultry.

negative: Alterations in Pulmonary Function Following Respiratory Viral Infection Respiratory viral illness is a major cause of morbidity in both adults and children. This report focuses on both the acute and chronic effects on respiratory function of these ubiquitous infections. Infant airways are particularly vulnerable due to the relatively low conductance in immature peripheral airways. Bronchiolitis, caused predominantly by respiratory syncytial virus, is the most important of these viral illnesses and is emerging as a major risk factor for the subsequent development of obstructive airway disease in adults, possibly by interference with normal alveolar proliferation. The basic pathogenic mechanism involved in adult respiratory viral infection is bronchial hyperreactivity, presumably secondary to epithelial damage and resultant sensitization of rapidly adapting airway receptors. In addition, there may be virus-related alterations in the autonomic and humoral regulation of airway tone. Viral infections may alter the effects of common air pollutants on respiratory function.

negative: An interactome map of the nucleocapsid protein from a highly pathogenic North American porcine reproductive and respiratory syndrome virus strain generated using SILAC‐based quantitative proteomics Positive strand RNA viruses replicate in the cytoplasm of an infected cell and encode nucleocapsid proteins. These proteins function to promote encapsidation of the RNA genome and virus particle assembly as well as playing potential roles in viral RNA synthesis. Nucleocapsid proteins can also associate with cellular proteins and signaling cascades. The arterivirus nucleocapsid (N) protein is no exception and localizes to both the cytoplasm and the nucleolus in virus‐infected cells. This study generated an interactome map of the N protein from a highly virulent North American strain of porcine reproductive and respiratory syndrome virus (PRRSV). This is a major pathogen of swine resulting in significant morbidity and mortality. Crucial to the study was the use of SILAC coupled to affinity purification using GFP‐traps and LC‐MS/MS. This approach has not been applied before to the investigation of host/viral protein interactomes and this study revealed that the PRRSV N protein interacts with the host cell protein synthesis machinery especially at the level of translation initiation as well as with the RNA post‐transcriptional modification machinery. Applications of the dataset can include studies of virus/host interactions and the design of live attenuated recombinant vaccines.

negative: Declining Public Health Protections within Autocratic Regimes: Impact on Global Public Health Security, Infectious Disease Outbreaks, Epidemics, and Pandemics Public health emergencies of international concern, in the form of infectious disease outbreaks, epidemics, and pandemics, represent an increasing risk to the worldʼs population. Management requires coordinated responses, across many disciplines and nations, and the capacity to muster proper national and global public health education, infrastructure, and prevention measures. Unfortunately, increasing numbers of nations are ruled by autocratic regimes which have characteristically failed to adopt investments in public health infrastructure, education, and prevention measures to keep pace with population growth and density. Autocratic leaders have a direct impact on health security, a direct negative impact on health, and create adverse political and economic conditions that only complicate the crisis further. This is most evident in autocratic regimes where health protections have been seriously and purposely curtailed. All autocratic regimes define public health along economic and political imperatives that are similar across borders and cultures. Autocratic regimes are seriously handicapped by sociopathic narcissistic leaders who are incapable of understanding the health consequences of infectious diseases or the impact on their population. A cross section of autocratic nations currently experiencing the impact of COVID-19 (coronavirus disease 2019) are reviewed to demonstrate the manner where self-serving regimes fail to manage health crises and place the rest of the world at increasing risk. It is time to re-address the pre-SARS (severe acute respiratory syndrome) global agendas calling for stronger strategic capacity, legal authority, support, and institutional status under World Health Organization (WHO) leadership granted by an International Health Regulations Treaty. Treaties remain the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world. “Honesty is worth a lot more than hope…” The Economist, February 17, 2020.

negative: Infection Control Programs for Dogs and Cats

negative: 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.

negative: Trunk extensor fatigue decreases jump height similarly under stable and unstable conditions with experienced jumpers. PURPOSE The purpose of this study was to investigate the effects of back extensor fatigue on performance measures and electromyographic (EMG) activity of leg and trunk muscles during jumping on stable and unstable surfaces. METHODS Before and after a modified Biering-Sorensen fatigue protocol for the back extensors, countermovement (CMJ) and lateral jumps (LJ) were performed on a force plate under stable and unstable (balance pad on the force plate) conditions. Performance measures for LJ (contact time) and CMJ height and leg and trunk muscles EMG activity were tested in 14 male experienced jumpers during 2 time intervals for CMJ (braking phase, push-off phase) and 5 intervals for LJ (-30 to 0, 0-30, 30-60, 60-90, and 90-120 ms) in non-fatigued and fatigued conditions. RESULTS A significant main effect of test (fatigue) (p = 0.007, f = 0.57) was observed for CMJ height. EMG analysis showed a significant fatigue-induced decrease in biceps femoris and gastrocnemius activity with CMJ (p = 0.008, f = 0.58 andp = 0.04, f = 0.422, respectively). LJ contact time was not affected by fatigue or surface interaction. EMG activity was significantly lower in the tibialis anterior with LJ following fatigue (p = 0.05, f = 0.405). A test x surface (p = 0.04, f = 0.438) interaction revealed that the non-fatigued unstable CMJ gastrocnemius EMG activity was lower than the non-fatigued stable condition during the onset-of-force phase. CONCLUSION The findings revealed that fatiguing the trunk negatively impacts CMJ height and muscle activity during the performance of CMJs. However, skilled jumpers are not additionally affected by a moderately unstable surface as compared to a stable surface.

negative: Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? PURPOSE: To evaluate the diagnostic value of computed tomography (CT) and real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) for COVID-19 pneumonia. METHODS: This retrospective study included all patients with COVID-19 pneumonia suspicion, who were examined by both CT and rRT-PCR at initial presentation. The sensitivities of both tests were then compared. For patients with a final confirmed diagnosis, clinical and laboratory data, in addition to CT imaging findings were evaluated. RESULTS: A total of 36 patients were finally diagnosed with COVID-19 pneumonia. Thirty-five patients had abnormal CT findings at presentation, whereas one patient had a normal CT. Using rRT-PCR, 30 patients were tested positive, with 6 cases initially missed. Amongst these 6 patients, 3 became positive in the second rRT-PCR assay(after 2 days, 2 days and 3 days respectively), and the other 3 became positive only in the third round of rRT-PCR tests(after 5 days, 6 days and 8 days respectively). At presentation, CT sensitivity was therefore 97.2%, whereas the sensitivity of initial rRT-PCR was only 83.3%. CONCLUSION: rRT-PCR may produce initial false negative results. We suggest that patients with typical CT findings but negative rRT-PCR results should be isolated, and rRT-PCR should be repeated to avoid misdiagnosis.

negative: Clearance and persistence of SARS-CoV-2 RNA in patients with COVID-19 Patients with coronavirus disease-2019 may be discharged based on clinical resolution of symptoms, and evidence for viral RNA clearance from the upper respiratory tract. Understanding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral clearance profile is crucial to establish a re-testing plan on discharge and ending isolation of patients. We aimed to evaluate the number of days that a patient needed to achieve undetectable levels of SARS-CoV-2 in upper respiratory tract specimens (nasopharyngeal swab and/or an oropharyngeal swab). The clearance and persistence of viral RNA was evaluated in two groups of positive patients: those who achieved two negative reverse transcription-polymerase chain reaction (RT-PCR) tests and those who kept testing positive. Patients were organized thereafter in two subgroups, mild illness patients discharged home and inpatients who had moderate to severe illness. Results from RT-PCR tests were then correlated with results from the evaluation of the immune response. The study evidenced that most patients tested positive for more than 2 weeks and that persistence of viral RNA is not necessarily associated with severe disease but may result from a weaker immune response instead.

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: Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents. METHODS: We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic. RESULTS: Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. CONCLUSIONS: Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

negative: Model-based estimation of the link between the daily survival probability and a time-varying covariate, application to mosquitofish survival data Abstract The survival probability in a group of individuals may evolve in time due to the influence of a time-varying covariate. In this paper we present a model-based approach allowing the estimation of the functional link between the survival probability and a time-varying covariate when data are grouped and time-period censored. The approach is based on an underlying model consisting in non-stationary Markov processes and describing the survival of individuals. The underlying model is aggregated in time and at the group level to handle the group structure of data and the censoring. The aggregation yields a generalized non-linear mixed model. Then, a Bayesian procedure allows the estimation of the model parameters and the description of the link between the survival probability and the time-varying covariate. This approach is applied in order to explore the relationship between the daily survival probability of mosquitofish (Gambusia holbrooki) and their time-varying lengths (small mosquitofish die with a higher rate than large ones because they are more affected by predation, cannibalism and environmental stress).

negative: Estimating Variability in the Transmission of Severe Acute Respiratory Syndrome to Household Contacts in Hong Kong, China The extensive data collection and contact tracing that occurred during the 2003 outbreak of severe acute respiratory syndrome (SARS) in Hong Kong, China, allowed the authors to examine how the probability of transmission varied from the date of symptom onset to the date of hospitalization for household contacts of SARS patients. Using a discrete-time likelihood model, the authors estimated the transmission probability per contact for each day following the onset of symptoms. The results suggested that there may be two peaks in the probability of SARS transmission, the first occurring around day 2 after symptom onset and the second occurring approximately 10 days after symptom onset. Index patients who were aged 60 years or older or whose lactate dehydrogenase level was elevated upon admission to the hospital (indicating higher viral loads) were more likely to transmit SARS to their contacts. There was little variation in the daily transmission probabilities before versus after the introduction of public health interventions on or around March 26, 2003. This study suggests that the probability of transmission of SARS is dependent upon characteristics of the index patients and does not simply reflect temporal variability in the viral load of SARS cases.

negative: A possible strategy to fight COVID-19: Interfering with spike glycoprotein trimerization Abstract The recent release of COVID-19 spike glycoprotein allows detailed analysis of the structural features that are required for stabilizing the infective form of its quaternary assembly. Trying to disassemble the trimeric structure of COVID-19 spike glycoprotein, we analyzed single protomer surfaces searching for concave moieties that are located at the three protomer-protomer interfaces. The presence of some druggable pockets at these interfaces suggested that some of the available drugs in Drug Bank could destabilize the quaternary spike glycoprotein formation by binding to these pockets, therefore interfering with COVID-19 life cycle. The approach we propose here can be an additional strategy to fight against the deadly virus. Ligands of COVID-19 spike glycoprotein that we have predicted in the present computational investigation, might be the basis for new experimental studies in vitro and in vivo.

negative: The CD200–CD200R1 Inhibitory Signaling Pathway: Immune Regulation and Host–Pathogen Interactions The CD200:CD200R1 inhibitory signaling pathway has been implicated in playing a prominent role in limiting inflammation in a wide range of inflammatory diseases. CD200R1 signaling inhibits the expression of proinflammatory molecules including tumor necrosis factor, interferons, and inducible nitric oxide synthase in response to selected stimuli. Unsurprisingly, due to the regulatory role that CD200R1 plays in multiple inflammatory pathways, an increasing number of parasitic, bacterial, and viral pathogens exploit this pathway to suppress host defenses. A complete understanding of the pathways regulated by CD200R1 signaling and the diverse mechanisms that pathogens have evolved to manipulate the CD200:CD200R1 pathway can help identify clinical situations where targeting this interaction can be of therapeutic benefit. In this review, we compare CD200R1 to other pathogen-targeted inhibitory receptors and highlight how this signaling pathway is utilized by a diverse number of pathogens and, therefore, may represent a novel targeting strategy for the treatment of infectious diseases.

negative: 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.

negative: Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Summary Background Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities. Methods We abstracted and analysed epidemiological, demographic, clinical, and laboratory data from confirmed cases of sporadic, household, community, and health-care-associated MERS-CoV infections reported from Saudi Arabia between Sept 1, 2012, and June 15, 2013. Cases were confirmed as having MERS-CoV by real-time RT-PCR. Findings 47 individuals (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying comorbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]). Common symptoms at presentation were fever (46 [98%]), fever with chills or rigors (41 [87%]), cough (39 [83%]), shortness of breath (34 [72%]), and myalgia (15 [32%]). Gastrointestinal symptoms were also frequent, including diarrhoea (12 [26%]), vomiting (ten [21%]), and abdominal pain (eight [17%]). All patients had abnormal findings on chest radiography, ranging from subtle to extensive unilateral and bilateral abnormalities. Laboratory analyses showed raised concentrations of lactate dehydrogenase (23 [49%]) and aspartate aminotransferase (seven [15%]) and thrombocytopenia (17 [36%]) and lymphopenia (16 [34%]). Interpretation Disease caused by MERS-CoV presents with a wide range of clinical manifestations and is associated with substantial mortality in admitted patients who have medical comorbidities. Major gaps in our knowledge of the epidemiology, community prevalence, and clinical spectrum of infection and disease need urgent definition. Funding None.

negative: Structure, Function, and Evolution of Coronavirus Spike Proteins. The coronavirus spike protein is a multifunctional molecular machine that mediates coronavirus entry into host cells. It first binds to a receptor on the host cell surface through its S1 subunit and then fuses viral and host membranes through its S2 subunit. Two domains in S1 from different coronaviruses recognize a variety of host receptors, leading to viral attachment. The spike protein exists in two structurally distinct conformations, prefusion and postfusion. The transition from prefusion to postfusion conformation of the spike protein must be triggered, leading to membrane fusion. This article reviews current knowledge about the structures and functions of coronavirus spike proteins, illustrating how the two S1 domains recognize different receptors and how the spike proteins are regulated to undergo conformational transitions. I further discuss the evolution of these two critical functions of coronavirus spike proteins, receptor recognition and membrane fusion, in the context of the corresponding functions from other viruses and host cells.

negative: The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations Viral entry into the host cell is the first step of virus infection; however, its dynamic process via endocytosis remains largely elusive. Here, the force tracing technique and single particle simulation are combined to investigate the invagination of single human enterovirus 71 (HEV71, a positive single‐stranded RNA virus that is associated with hand, foot, and mouth disease) via cell membranes during its host cell entry. The experimental results reveal that the HEV71 invaginates in membrane vesicles at a force of 58 ± 16 pN, a duration time of 278 ± 68 ms. The simulation further shows that the virus can reach a partially wrapped state very fast, then the upper surface of the virus is covered by the membrane traveling over a long period of time. Combining the experiment with the simulation, the mechanism of membrane wrapping of virus is uncovered, which provides new insights into how the cell is operated to initiate the endocytosis of virus.

negative: Émergence de virus nouveaux en Asie : les changements climatiques sont-ils en cause ? Résumé L’Afrique tropicale n’est pas la seule région du monde où des virus dangereux pour l’homme aient récemment émergé. L’Asie, en particulier la Chine et le Sud-est asiatique, a également connu l’émergence de viroses humaines graves, telles que la dengue hémorragique (les Philippines, 1954) ou plusieurs pandémies grippales, la grippe asiatique (N2H2) en 1957, la grippe de Hong-Kong (H3N2) en 1968, et la grippe russe (H1N1) en 1977. Mais, c’est surtout au cours des dix dernières années que les émergences virales s’y sont multipliées avec l’apparition de la fièvre hémorragique à virus Alkhurma en Arabie Saoudite (1995), de la grippe aviaire H5N1 à Hong-Kong, en 1997, de l’encéphalite à virus Nipah en Malaisie, en 1998, et surtout du SRAS, en Chine du sud en 2002. Les facteurs climatiques n’ont probablement joué qu’un rôle réduit dans le succès émergentiel de ces viroses, favorisé plutôt par des facteurs humains : le développement d’élevages industriels d’animaux de basse cour augmentant les risques d’épizooties, les habitudes alimentaires, les pressions économiques et démographiques, les négligences dans la surveillance épidémiologique et la déclaration des premiers cas. Abstract Tropical Africa is not the only area where deadly viruses have recently emerged. In South-East Asia severe epidemics of dengue hemorrhagic fever started in 1954 and flu pandemics have originated from China such as the Asian flu (H2N2) in 1957, the Hong-Kong flu (H3N2) in 1968, and the Russian flu (H1N1) in 1977. However, it is especially during the last ten years that very dangerous viruses for mankind have repeatedly developed in Asia, with the occurrence of Alkhurma hemorrhagic fever in Saudi Arabia (1995), avian flu (H5N1) in Hong-Kong (1997), Nipah virus encephalitis in Malaysia (1998,) and, above all, the SARS pandemic fever from Southern China (2002). The evolution of these viral diseases was probably not directly affected by climate change. In fact, their emergential success may be better explained by the development of large industry poultry flocks increasing the risks of epizootics, dietary habits, economic and demographic constraints, and negligence in the surveillance and reporting of the first cases.

negative: The local stability of a modified multi-strain SIR model for emerging viral strains We study a novel multi-strain SIR epidemic model with selective immunity by vaccination. A newer strain is made to emerge in the population when a preexisting strain has reached equilibrium. We assume that this newer strain does not exhibit cross-immunity with the original strain, hence those who are vaccinated and recovered from the original strain become susceptible to the newer strain. Recent events involving the COVID-19 virus demonstrates that it is possible for a viral strain to emerge from a population at a time when the influenza virus, a well-known virus with a vaccine readily available for some of its strains, is active in a population. We solved for four different equilibrium points and investigated the conditions for existence and local stability. The reproduction number was also determined for the epidemiological model and found to be consistent with the local stability condition for the disease-free equilibrium.

negative: Chapter 20 Design of genomic signatures for pathogen identification and characterization Abstract Once the genome of a microbial organism has been sequenced, it becomes possible to utilize portions of the genome, known as “signatures” to identify when that organism is present in a complex clinical or environmental sample. Genomic signatures can be at multiple levels of resolution depending on the questions being asked. (“Is this white powder anthrax?”; “Does this white powder match any of the anthrax samples taken from every laboratory in the United States that possesses anthrax?”) Multiple technologies exist to turn abstract genomic signatures into assays that can interrogate complex samples with varying degrees of speed, sensitivity, specificity, and cost. The recent flood of microbial genomic data has complicated the task of designing genomic signatures.

negative: Effect of 24 hours light on circadian rhythms of secretory enzymes and morphology of rat von Ebner’s glands Abstract Von Ebner’s glands of the rat are minor salivary serous glands in the posterior portion of the tongue. They secrete two digestive enzymes, lingual lipase and amylase. In this investigation, circadian rhythm in feeding was established under a normal 12 h light/12 h dark cycle, with the rats eating primarily during the dark period. At lights on, the size of the acinar cells and the area of the inclusive secretory granules, and the amount of digestive enzyme activity (lingual lipase and amylase) remaining in the gland was significantly less than in the mid-afternoon, after very little daylight food consumption. However, after 7 days of continuous light the circadian rhythm was altered: the food consumption during the normal night-time hours (5 p.m. to 8 a.m.) went from 88% of total 24 h food consumption to 45%, and during normal daylight hours (8 a.m. to 5 p.m.) from 12% to 55%. These changes were correlated with histometric findings of a near reversal of the areas of acinar cells and secretory granules of a.m. and p.m. samples under continuous light. Lingual lipase activity in the glands went from 35% under 12 h light to 61% under continuous light in the a.m. and from 65% to 39% in the p.m. Amylase activity also showed nearly a reversal in activity remaining in the gland, from 36% at 12 h light to 58% at 24 h light in the a.m. and 64% to 41% for the p.m. samples. These results indicate that the von Ebner’s glands of the rat have a circadian rhythm of secretion and storage of secretory proteins that is subject to light entrainment similar to that seen in other exocrine glands such as the parotid and pancreas.

negative: Binding of the 5′-untranslated region of coronavirus RNA to zinc finger CCHC-type and RNA-binding motif 1 enhances viral replication and transcription Coronaviruses RNA synthesis occurs in the cytoplasm and is regulated by host cell proteins. In a screen based on a yeast three-hybrid system using the 5′-untranslated region (5′-UTR) of SARS coronavirus (SARS-CoV) RNA as bait against a human cDNA library derived from HeLa cells, we found a positive candidate cellular protein, zinc finger CCHC-type and RNA-binding motif 1 (MADP1), to be able to interact with this region of the SARS-CoV genome. This interaction was subsequently confirmed in coronavirus infectious bronchitis virus (IBV). The specificity of the interaction between MADP1 and the 5′-UTR of IBV was investigated and confirmed by using an RNA pull-down assay. The RNA-binding domain was mapped to the N-terminal region of MADP1 and the protein binding sequence to stem–loop I of IBV 5′-UTR. MADP1 was found to be translocated to the cytoplasm and partially co-localized with the viral replicase/transcriptase complexes (RTCs) in IBV-infected cells, deviating from its usual nuclear localization in a normal cell using indirect immunofluorescence. Using small interfering RNA (siRNA) against MADP1, defective viral RNA synthesis was observed in the knockdown cells, therefore indicating the importance of the protein in coronaviral RNA synthesis.

negative: New Approaches to Preventing, Diagnosing, and Treating Neonatal Sepsis Karen Edmond and Anita Zaidi highlight new approaches that could reduce the burden of neonatal sepsis worldwide.

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: Hand sanitisers amid CoViD-19: A critical review of alcohol-based products on the market and formulation approaches to respond to increasing demand. The world is facing a medical crisis amid the CoViD-19 pandemic and the role of adequate hygiene and hand sanitisers is inevitable in controlling the spread of infection in public places and healthcare institutions. There has been a great surge in demand for hand sanitisation products leading to shortages in their supply. A consequent increase of substandard products in the market has raised safety concerns. This article, therefore, presents a critical review of hand sanitation approaches and products available on the market in light of the scientific evidence available to date. This review also provides a range of hand sanitisation product formulations, and manufacturing instructions to allow for extemporaneous preparations at the community and hospital pharmacies during this urgent crisis. In addition, this emergent situation is expected to continue, hence hand sanitisers will be in demand for an extended time, and the availability and purchase of substandard products on the market create an ongoing safety concern. Therefore, this article shall also provide various commercial organisations, interested in stepping forward the production and marketing of hand sanitisers, with a guide on the development of products of standardised ingredients and formulations.

negative: The Curious Case of the Nidovirus Exoribonuclease: Its Role in RNA Synthesis and Replication Fidelity Among RNA viruses, the order Nidovirales stands out for including viruses with the largest RNA genomes currently known. Nidoviruses employ a complex RNA-synthesizing machinery comprising a variety of non-structural proteins (nsps). One of the postulated drivers of the expansion of nidovirus genomes is the presence of a proofreading 3′-to-5′ exoribonuclease (ExoN) belonging to the DEDDh family. ExoN may enhance the fidelity of RNA synthesis by correcting nucleotide incorporation errors made by the RNA-dependent RNA polymerase. Here, we review our current understanding of ExoN evolution, structure, and function. Most experimental data are derived from studies of the ExoN domain of coronaviruses (CoVs), which were triggered by the bioinformatics-based identification of ExoN in the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) and its relatives in 2003. Although convincing data supporting the proofreading hypothesis have been obtained, from biochemical assays and studies with CoV mutants lacking ExoN functionality, the features of ExoN from most other nidovirus families remain to be characterized. Remarkably, viable ExoN knockout mutants were obtained only for two CoVs, mouse hepatitis virus (MHV) and SARS-CoV, whose RNA synthesis and replication kinetics were mildly affected by the lack of ExoN function. In several other CoV species, ExoN inactivation was not tolerated, and knockout mutants could not be rescued when launched using a reverse genetics system. This suggests that ExoN is also critical for primary viral RNA synthesis, a property that poorly matches the profile of an enzyme that would merely boost long-term replication fidelity. In CoVs, ExoN resides in a bifunctional replicase subunit (nsp14) whose C-terminal part has (N7-guanine)-methyltransferase activity. The crystal structure of SARS-CoV nsp14 has shed light on the interplay between these two domains, and on nsp14’s interactions with nsp10, a co-factor that strongly enhances ExoN activity in vitro assays. Further elucidation of the structure-function relationships of ExoN and its interactions with other (viral and/or host) members of the CoV replication machinery will be key to understanding the enzyme’s role in viral RNA synthesis and pathogenesis, and may contribute to the design of new approaches to combat emerging nidoviruses.

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: Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.

negative: The Covid19Impact Survey: Assessing the Pulse of the COVID-19 Pandemic in Spain via 24 questions In this paper, we describe the results of analyzing a large-scale survey, called the Covid19Impact survey, to assess citizens feedback on four areas related to the COVID-19 pandemic in Spain: social contact behavior, financial impact, working situation and health status. A total of 24 questions cover the areas of demographics, their home situation, social contact behavior, personal economic impact, their workplace situation and their health. The survey was responded to by 156,614 participants between the evening of March 28th and April 2nd, 2020. Such a large response enables us to gain new insights, as well as an unprecedented glimpse at respondents personal experiences and concerns during the current COVID-19 pandemic. From the analysis, we draw several implications for the design of public policies related to the management of the COVID-19 pandemic.

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: A randomized controlled feasibility trial comparing safety and effectiveness of prehospital pacing versus conventional treatment: ‘PrePACE’()() OBJECTIVE: To evaluate the feasibility of a prehospital randomized controlled trial comparing transcutaneous pacing (TCP) with dopamine for unstable bradycardia. METHODS: Unstable bradycardic patients who failed to respond to a fluid bolus and up to 3 mg atropine were enrolled. The intervention was dopamine or TCP with crossover to dopamine if TCP failed. The primary outcome was survival to discharge or 30 days. Randomization compliance, safety, follow-up rates, primary outcome, and sample size requirements were assessed. RESULTS: Of 383 patients with unstable bradycardia, 151 (39%) failed to respond to atropine or fluid and were eligible for enrolment and 82 (55%) were correctly enrolled. Fifty-five (36%) of eligible patients could not be enrolled for practical reasons; 3 had advance directives, 32 met inclusion criteria on arrival at hospital and in 20 cases, paramedics chose not to enroll based on the circumstances of the case. The remaining 13 were missed cases; 8 were missing randomization envelopes and in 5, the paramedic forgot. Randomization compliance was 95% (78/82). Forty-two (51%) patients were randomized to TCP and seven of these crossed over to dopamine. Two cases were randomized but did not receive the intervention; either due to lack of time or loss of IV access. Three adverse events occurred in each group. Survival to discharge or 30 days in hospital was 70% (28/40) and 69% (29/42) in the dopamine and TCP groups, respectively with 100% follow up. To detect a 10% relative difference in 30 days survival between treatment arms, a sample size of 690 per group would be required. CONCLUSIONS: It is feasible to conduct a prehospital randomized controlled trial of TCP for unstable bradycardia and a definitive trial would require a multi-centre study.

negative: Atypical presentation of SARS-CoV-2 infection: A case report. BACKGROUND The first case of pneumonia subsequently attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province on December 8, 2019. The symptoms included fever, coughing, and breathing difficulties. A few patients with this infection may only have atypical symptoms, which could lead to a misdiagnosis and subsequently further facilitate the spread of the virus. CASE SUMMARY A 74-year-old female patient complained of severe diarrhea. She did not have fever, coughing, or breathing difficulties. A physical examination revealed no obvious positive signs. The patient had been hypertensive for more than 10 years. Her blood pressure was well controlled. On January 9, 2020, the patient's son visited a colleague who was later confirmed positive for SARS-CoV-2 and his first close contact with our patient was on January 17. The patient was first diagnosed with gastrointestinal dysfunction. However, considering her indirect contact with a SARS-CoV-2-infected individual, we suggested that an atypical pneumonia virus infection should be ruled out. A computed tomography scan was performed on January 26, and showed ground-glass nodules scattered along the two lungs, suggestive of viral pneumonia. Given the clinical characteristics, epidemiological history, and examination, the patient was diagnosed with coronavirus disease-2019 (COVID-19). CONCLUSION Our patient had atypical symptoms of COVID-19. Careful acquisition of an epidemiological history is necessary to make a correct diagnosis and strategize a treatment plan.

negative: Meeting abstracts from International Conference on Prevention & Infection Control (ICPIC 2017): Geneva, Switzerland. 20-23 June 2017

negative: Molecular analysis of cerebrospinal fluid in viral diseases of the central nervous system The use of nucleic acid (NA) amplification techniques has transformed the diagnosis of viral infections of the central nervous system (CNS). Because of their enhanced sensitivity, these methods enable detection of even low amounts of viral genomes in cerebrospinal fluid. Following more than 10 years of experience, the polymerase chain reaction or other NA-based amplification techniques are nowadays performed in most diagnostic laboratories and have become the test of choice for the diagnosis of several viral CNS infections, such as herpes encephalitis, enterovirus meningitis and other viral infections occurring in human immunodeficiency virus-infected persons. Furthermore, they have been useful to establish a viral etiology in neurological syndromes of dubious origin and to recognise unusual or poorly characterised CNS diseases. Quantitative methods have provided a valuable additional tool for clinical management of these diseases, whereas post-amplification techniques have enabled precise genome characterisation. Current efforts are aiming at further improvement of the diagnostic efficiency of molecular techniques, their speed and standardisation, and to reduce the costs. The most relevant NA amplification strategies and clinical applications of to date will be the object of this review.

negative: Exacerbation of Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease (COPD) is a disease with high prevalence and substantial associated economical burden. A significant determinant of quality of life, long-term survival, and health care costs is an acute exacerbation of COPD. Acute exacerbations are provoked by respiratory viruses, altered airway microbiome, and environmental factors. The current treatment options are limited. In order to develop specific therapeutic measures, it is important to understand how acute exacerbations evolve. This review focuses on pathophysiology of stable and exacerbated COPD.

negative: Is a 14-day quarantine period optimal for effectively controlling coronavirus disease 2019 (COVID-19)? Background The outbreak of a new coronavirus (SARS-CoV-2) disease (Covid-19) has become pandemic. To be more effectively controlling the disease, it is critical to set up an optimal quarantine period so that about 95% of the cases developing symptoms will be retained for isolation. At the moment, the WHO-established quarantine period is 14 days based on previous reports which had studied small sizes of hospitalized cases (10 and ~100, respectively), however, over 80% of adult- and 95% of child-cases were not necessary to stay in hospitals, and therefore, had not been hospitalized. Therefore, we are questioning if the current-inferred median incubation time is representative for the whole Covid-19 population, and if the current quarantine period is optimal. Methods We compiled and analyzed the patient-level information of 2015 laboratory-confirmed Covid-19 cases including 99 children in 28 Chinese provinces. This cohort represents a wide-range spectrum of Covid-19 disease with both hospitalized and non-hospitalized cases. Results The full range of incubation periods of the Covid-19 cases ranged from 0 to 33 days among 2015 cases. There were 6 (0.13%) symptom-free cases including 4 females with a median age of 25.5 years and 2 males with a median age of 36 years. The median incubation period of both male and female adults was similar (7-day) but significantly shorter than that (9-day) of child cases (P=0.02). This cohort contained 4 transmission generations, and incubation periods of the cases between generations were not significantly different, suggesting that the virus has not been rapidly adapted to human beings. Interestingly, incubation periods of 233 cases (11.6%) were longer than the WHO-established quarantine period (14 days). Data modeling suggested that if adults take an extra 4-day or 7-day of isolation (i.e., a quarantine period of 18 or 21 days), 96.2% or 98.3%, respectively, of the people who are developing symptoms will be more effectively quarantined. Patients transmitted via lunch/dinner parties (i.e., gastrointestinal tract infection through oral transmission) had a significantly longer incubation period (9-day) than other adults transmitted via respiratory droplets or contaminated surfaces and objects (P<0.004). Conclusions The whole Covid-19 population including both hospitalized and non-hospitalized cases had a median incubation period of 7-day for adults, which is 1.8-day longer than the hospitalized cases reported previously. An extension of the adult quarantine period to 18 days or 21 days could be more effective in preventing virus-spreading and controlling the disease. The cases transmitted by lunch/dinner parties could be infected first in the gastrointestinal tract through oral transmission and then infected in the respiratory system so that they had a longer incubation period.

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: Persistent detection of SARS-CoV-2 RNA in patients and healthcare workers with COVID-19 BACKGROUND: Current guidelines for returning health care workers (HCW) to service after a positive SARS-CoV-2 RT-PCR test and ceasing of transmission precautions for patients is based on two general strategies. A test-based strategy that requires negative respiratory RT-PCR tests obtained after the resolution of symptoms. Alternatively, due to the limited availability of testing, many sites employ a symptom-based strategy that recommends excluding HCW from the workforce and keeping patients on contact precautions until a fixed period of time has elapsed from symptom recovery. The underlying assumption of the symptom-based strategy is that waiting for a fixed period of time is a surrogate for negative RT-PCR testing, which itself is a surrogate for the absence of shedding infectious virus. OBJECTIVES: To better understand the appropriate length of symptom based return to work and contact precaution strategies. STUDY DESIGN: We performed an observational analysis of 150 patients and HCW that transitioned from RT-PCR SARS-CoV-2 positive to negative over the course of 2 months at a US academic medical center. RESULTS: We found that the average time to transition from RT-PCR positive to negative was 24 days after symptom onset and 10 % remained positive even 33 days after symptom onset. No difference was seen in HCW and patients. CONCLUSIONS: These findings suggest until definitive evidence of the length of infective viral shedding is obtained that the fixed length of time before returning to work or ceasing contract precautions be revised to over one-month.

negative: Nucleic acid amplification-based techniques for pathogen detection and identification Abstract Nucleic acid amplification techniques have revolutionised diagnostic and research industries. Current technologies that allow the detection of amplification in real-time are fast becoming industry standards, particularly in a diagnostic context. In this review, we describe and explore the application of numerous real-time detection chemistries and amplification techniques for pathogen detection and identification, including the polymerase chain reaction, nucleic acid sequence-based amplification, strand displacement amplification and the ligase chain reaction. The emergence of newer technologies, such as lab-on-a-chip devices and photo-cleavable linkers, is also discussed.

negative: Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.

negative: Occurrence and Distribution of Hexavalent Chromium in Ground and Surface Waters in Cyprus. The origin and distribution of hexavalent chromium, Cr (VI) over four seasonal cycles was investigated through a conceptual model that included three aquifer systems in Cyprus. An extensive water sampling grid covered two sea water intruded coastal aquifers, namely the Kokkinochoria (A1) and Kiti-Pervolia (A2) aquifers and the Troodos massif (A3). Analytical results give a first insight to the presence of Cr (VI) in Cyprus ground and surface waters. The highest Cr (VI) value of 26 μg L-1 is observed in the Troodos area (A3) where Cr(VI) is detected in all sampled water systems (surface and ground/spring). Nonetheless, the highest median values of 4.6 and 4.5 μg L-1 are observed in the Kokkinochoria (A1) and Kiti-Pervolia (A2) study areas respectively, where the local aquifers are under increased pressure from agriculture, urbanization and seawater intrusion. Stable isotopes were used to discern the effect of return irrigation and seawater intrusion. Stable isotope analyses from Troodos samples show two distinct groups of meteoric and near meteoric waters whereas isotopically enriched water is shown to correspond to the Kiti and Kokkinochoria area.

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: Abstracts of Papers Presented at the Session of the Virology Section of the Deutsche Gesellschaft für Hygiene und Mikrobiologie, Martinsried, March 25–28, 1987

negative: Art of prevention: Life in the time of coronavirus Abstract The novel coronavirus disease 2019 (COVID-19) has continued to progress since its discovery in December 2019. A cluster of patients with atypical pneumonia identified in Wuhan, China, served as the epicenter of this recent epidemic. This family of viruses is responsible for the common cold along with the infamous severe acute respiratory syndrome epidemic in 2002 and Middle East respiratory syndrome in 2012. The Southern China Wholesale Market reportedly has connections to the original 27 cases in Wuhan, China. The worldwide confirmed case total has eclipsed 1,450,000, with more than 83,000 deaths. Patient presentation ranges from mild respiratory illness to acute respiratory distress syndrome and subsequent death. Early epidemiologic studies of viral spread support the hypothesis that COVID-19 can remain latent with an extended and infectious incubation period. The U.S. government has issued level 3 precautions for most international travel, along with prohibiting entry to foreign nationals traveling from China, Iran, the United Kingdom, the Republic of Ireland, and the European Schengen area (e.g., France, Italy, Germany). Prevention remains the mainstay in treating and defeating the COVID-19 epidemic. Anyone infected or suspected of being infected should self-quarantine at home or admit themselves to a specified hospital with infrastructure to handle the situation. The combination of prevention and containment provides the best opportunity to stall the spread of COVID-19.

negative: Should, and how can, exercise be done during a coronavirus outbreak? An interview with Dr. Jeffrey A. Woods

negative: 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.

negative: Respiratory Viruses Respiratory viruses are the most frequent causative agents of disease in humans, with significant impact on morbidity and mortality worldwide. Common respiratory agents from several virus families are well adapted to efficient person-to-person transmission and circulate in a global scale, and community-based studies conducted over the past five decades or so confirm that these viruses are the predominant etiological agents of acute respiratory infections (ARIs). The respiratory viruses that most commonly circulate in all continents as endemic or epidemic agents are influenza virus, respiratory syncytial virus, parainfluenza viruses, metapneumovirus, rhinovirus, coronaviruses, adenoviruses, and bocaviruses. Although vaccines and effective antiviral drugs are not yet available for most of these viruses, much progress has been made in the understanding of their biology and fundamental issues of host–parasite relationship. This article is a summary of the current knowledge about these viruses.

negative: The Severe Acute Respiratory Syndrome (SARS)-coronavirus 3a protein may function as a modulator of the trafficking properties of the spike protein BACKGROUND: A recent publication reported that a tyrosine-dependent sorting signal, present in cytoplasmic tail of the spike protein of most coronaviruses, mediates the intracellular retention of the spike protein. This motif is missing from the spike protein of the severe acute respiratory syndrome-coronavirus (SARS-CoV), resulting in high level of surface expression of the spike protein when it is expressed on its own in vitro. PRESENTATION OF THE HYPOTHESIS: It has been shown that the severe acute respiratory syndrome-coronavirus genome contains open reading frames that encode for proteins with no homologue in other coronaviruses. One of them is the 3a protein, which is expressed during infection in vitro and in vivo. The 3a protein, which contains a tyrosine-dependent sorting signal in its cytoplasmic domain, is expressed on the cell surface and can undergo internalization. In addition, 3a can bind to the spike protein and through this interaction, it may be able to cause the spike protein to become internalized, resulting in a decrease in its surface expression. TESTING THE HYPOTHESIS: The effects of 3a on the internalization of cell surface spike protein can be examined biochemically and the significance of the interplay between these two viral proteins during viral infection can be studied using reverse genetics methodology. IMPLICATION OF THE HYPOTHESIS: If this hypothesis is proven, it will indicate that the severe acute respiratory syndrome-coronavirus modulates the surface expression of the spike protein via a different mechanism from other coronaviruses. The interaction between 3a and S, which are expressed from separate subgenomic RNA, would be important for controlling the trafficking properties of S. The cell surface expression of S in infected cells significantly impacts viral assembly, viral spread and viral pathogenesis. Modulation by this unique pathway could confer certain advantages during the replication of the severe acute respiratory syndrome-coronavirus.

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: Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2 The outbreak of the 2019 novel coronavirus (SARS-CoV-2) has infected thousands of people with a large number of deaths across 26 countries. The sudden appearance of the virus leads to the limited existing therapies for SARS-CoV-2. Therefore, vaccines and antiviral medicines are in desperate need. This study took immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein (S) of SARS-CoV-2, followed by estimating their antigenicity and interactions with the human leukocyte antigen (HLA) alleles. We identified four B cell epitopes, two MHC class-I and nine MHC class-II binding T-cell epitopes, which showed highly antigenic features. Allergenicity, toxicity and physiochemical properties analysis confirmed the specificity and selectivity of epitopes. The stability and safety of epitopes were confirmed by digestion analysis. No mutations were observed in all the selected B- and T-cell epitopes across all isolates from different locations worldwide. Epitopes were thus identified and some of them can be potential candidates for vaccine development.

negative: Murine Olfactory Bulb Interneurons Survive Infection with a Neurotropic Coronavirus. Viral infection of the central nervous system (CNS) is complicated by the mostly irreplaceable nature of neurons, as the loss of neurons has the potential to result in permanent damage to brain function. However, whether neurons or other cells in the CNS sometimes survive infection and the effects of infection on neuronal function is largely unknown. To address this question, we used the rJHM strain (rJ) of mouse hepatitis virus (MHV), a neurotropic coronavirus that causes acute encephalitis in susceptible strains of mice. To determine whether neurons or other CNS cells survive acute infection with this virulent virus, we developed a recombinant JHMV that expresses Cre recombinase (rJ-Cre) and infected mice that universally expressed a silent (floxed) version of tdTomato. Infection of these mice with rJ-Cre resulted in expression of tdTomato in host cells. The results showed that some cells were able to survive the infection, as demonstrated by continued tdTomato expression after virus antigen could no longer be detected. Most notably, interneurons in the olfactory bulb, which are known to be inhibitory, represented a large fraction of the surviving cells. In conclusion, our results indicated that some neurons are resistant to virus-mediated cell death and provide a framework for studying the effects of prior coronavirus infection on neuron function.IMPORTANCE We developed a novel recombinant virus that allows the study of cells that survive an infection by a central nervous system-specific strain of murine coronavirus. Using this virus, we identified neurons and, to a lesser extent, nonneuronal cells in the brain that were infected during the acute phase of the infection and survived for approximately 2 weeks until the mice succumbed to the infection. We focused on neurons and glial cells within the olfactory bulb because the virus enters the brain at this site. Our results show that interneurons of the olfactory bulb were the primary cell type able to survive infection. Further, these results indicate that this system will be useful for functional and gene expression studies of cells in the brain that survive acute infection.

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: Answering the right questions for policymakers on COVID-19

negative: A specific transmembrane domain of a coronavirus E1 glycoprotein is required for its retention in the Golgi region The E1 glycoprotein of the avian coronavirus infectious bronchitis virus contains a short, glycosylated amino-terminal domain, three membrane-spanning domains, and a long carboxy-terminal cytoplasmic domain. We show that E1 expressed from cDNA is targeted to the Golgi region, as it is in infected cells. E1 proteins with precise deletions of the first and second or the second and third membrane-spanning domains were glycosylated, thus suggesting that either the first or third transmembrane domain can function as an internal signal sequence. The mutant protein with only the first transmembrane domain accumulated intracellularly like the wild-type protein, but the mutant protein with only the third transmembrane domain was transported to the cell surface. This result suggests that information specifying accumulation in the Golgi region resides in the first transmembrane domain, and provides the first example of an intracellular membrane protein that is transported to the plasma membrane after deletion of a specific domain.

negative: Perception of emergent epidemic of COVID-2019 / SARS CoV-2 on the Polish Internet Problem: Due to the spread of SARS CoV-2 virus infection and COVID-2019 disease, there is an urgent need to analyze COVID-2019 epidemic perception in Poland. This would enable authorities for preparation of specific actions minimizing public health and economic risks. Methods: We study the perception of COVID-2019 epidemic in Polish society using quantitative analysis of its digital footprints on the Internet (on Twitter, Google, YouTube, Wikipedia and electronic media represented by Event Registry) from January 2020 to 12.03.2020 (before and after official introduction to Poland on 04.03.2020). To this end we utilize data mining, social network analysis, natural language processing techniques. Each examined internet platform was analyzed for representativeness and composition of the target group. Results: We identified three major cluster of the interest before disease introduction on the topic COVID-2019: China- and Italy-related peaks on all platforms, as well as a peak on social media related to the recent special law on combating COVID-2019. Besides, there was a peak in interest on the day of officially confirmed introduction as well as an exponential increase of interest when the Polish government declared war against disease with a massive mitigation program. From sociolingistic perspective, we found that concepts and issues of threat, fear and prevention prevailed before introduction. After introduction, practical concepts about disease and epidemic dominate. Twitter reflected the clear, structural division of the Polish political sphere. We were able to identify potential sources of misinformation as well as key actors (especially early adopters) and influencers. Conclusions: Traditional and social media not only reflect reality, but also create it. Polish authorities, having a reliable analysis of the perception of the problem, could optimally prepare and manage the social dimension of the current epidemic and future ones. Due to filter bubbles observed on Twitter, public information campaigns might have less impact on society than expected. For greater penetration, it might be necessary to diversify information channels to reach as many people as possible which might already be happening. Moreover, it might be necessary to prevent the spread of disinformation, which is now possible due to the special law on combating COVID-2019.

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: HexaPrime: A novel method for detection of coronaviruses Abstract Despite intense efforts to develop novel and better tools to identify known viruses and to discover new viruses, establishing etiological roles for viruses in human disease is challenging. In large part, this may be attributed to the high variability of viral species and the difficulties in developing broad-spectrum, yet specific, diagnostic assays. To overcome this problem, a novel method for the detection of viruses is described in the current manuscript. The technique relies on the addition of synthetic oligonucleotides to both termini of RNA fragments in a sequence-dependent manner during first- and second-strand DNA synthesis; these oligonucleotides are used subsequently for amplification of the viral nucleic acids of interest. The recognition of the target sequence by the oligonucleotides is mediated by short (6–8nt) conserved regions, which facilitates development of broad–spectrum assays. The method has been tested for coronaviruses, although it may be also adopted for other RNA viruses.

negative: NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion The lethal Coronaviruses (CoVs), Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) and most recently Middle East Respiratory Syndrome Coronavirus, (MERS-CoV) are serious human health hazard. A successful viral infection requires fusion between virus and host cells carried out by the surface spike glycoprotein or S protein of CoV. Current models propose that the S2 subunit of S protein assembled into a hexameric helical bundle exposing hydrophobic fusogenic peptides or fusion peptides (FPs) for membrane insertion. The N-terminus of S2 subunit of SARS-CoV reported to be active in cell fusion whereby FPs have been identified. Atomic-resolution structure of FPs derived either in model membranes or in membrane mimic environment would glean insights toward viral cell fusion mechanism. Here, we have solved 3D structure, dynamics and micelle localization of a 64-residue long fusion peptide or LFP in DPC detergent micelles by NMR methods. Micelle bound structure of LFP is elucidated by the presence of discretely folded helical and intervening loops. The C-terminus region, residues F42-Y62, displays a long hydrophobic helix, whereas the N-terminus is defined by a short amphipathic helix, residues R4-Q12. The intervening residues of LFP assume stretches of loops and helical turns. The N-terminal helix is sustained by close aromatic and aliphatic sidechain packing interactions at the non-polar face. (15)N{(1)H}NOE studies indicated dynamical motion, at ps-ns timescale, of the helices of LFP in DPC micelles. PRE NMR showed that insertion of several regions of LFP into DPC micelle core. Together, the current study provides insights toward fusion mechanism of SARS-CoV.

negative: Review and analysis of current responses to COVID-19 in Indonesia: Period of January to March 2020 Abstract The world is under pressure from the novel COVID-19 pandemic. Indonesia is the fourth most populous country in the world and predicted to be affected significantly over a longer time period. Our paper aims to provide detailed reporting and analyses of the present rapid responses to COVID-19, between January and March 2020, in Indonesia. We particularly highlight responses taken by the governments, non-government organisations and the community. We outline gaps and limitations in the responses, based on our rapid analysis of media contents, from government speeches and reports, social and mass media platforms. We present five recommendations toward more rapid, effective, and comprehensive responses.

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: Detection of Group 1 Coronaviruses in Bats Using Universal Coronavirus Reverse Transcription Polymerase Chain Reactions The zoonotic transmission of SARS coronavirus from animals to humans revealed the potential impact of coronaviruses on mankind. This incident also triggered several surveillance programs to hunt for novel coronaviruses in human and wildlife populations. Using classical RT-PCR assays that target a highly conserved sequence among coronaviruses, we identified the first coronaviruses in bats. These assays and the cloning and sequencing of the PCR products are described in this chapter. Using the same approach in our subsequent studies, we further detected several novel coronaviruses in bats. These findings highlighted the fact that bats are important reservoirs for coronaviruses.

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: 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: Respiratory mucus and persistence of virus on surfaces

negative: Dermatologists and SARS‐CoV‐2: The impact of the pandemic on daily practice Since the first case of “pneumonia of unknown aetiology” was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognised thereafter as “severe acute respiratory syndrome coronavirus 2” (SARS‐CoV‐2) has spread over the four continents, causing the respiratory manifestations of Coronavirus disease‐19 (COVID‐ 19) and satisfying the epidemiological criteria for a label of “pandemic.” The ongoing SARS‐CoV‐2 pandemic is having a huge impact on dermatological practice including the marked reduction of face‐to‐face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID‐19 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID‐19 care for patients assistance and new research needs to be addressed. It is not known yet, if skin lesions and derangement of the skin barrier could make it easier for SARS‐CoV‐2 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS‐CoV‐2 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS‐CoV‐2 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID‐19 disaster. Learning from experience may help to cope with future major societal changes.

negative: Immortalization of Human B Cells: Analysis of B Cell Repertoire and Production of Human Monoclonal Antibodies One of the major challenges in human B cell immunology field has been the objective to establish stable monoclonal cells lines that express the B cell receptor (BCR) on their cell surface and secrete antibodies. Such a system is extremely attractive not only for studying various aspect of BCR signaling but also for the generation of human monoclonal antibody and the analysis of the human B cell repertoire. This chapter describes an efficient method to immortalize and clone human B cells by Epstein–Barr Virus (EBV) transformation.

negative: Coronavirus receptor switch explained from the stereochemistry of protein-carbohydrate interactions and a single mutation. Hemagglutinin-esterases (HEs) are bimodular envelope proteins of orthomyxoviruses, toroviruses, and coronaviruses with a carbohydrate-binding "lectin" domain appended to a receptor-destroying sialate-O-acetylesterase ("esterase"). In concert, these domains facilitate dynamic virion attachment to cell-surface sialoglycans. Most HEs (type I) target 9-O-acetylated sialic acids (9-O-Ac-Sias), but one group of coronaviruses switched to using 4-O-Ac-Sias instead (type II). This specificity shift required quasisynchronous adaptations in the Sia-binding sites of both lectin and esterase domains. Previously, a partially disordered crystal structure of a type II HE revealed how the shift in lectin ligand specificity was achieved. How the switch in esterase substrate specificity was realized remained unresolved, however. Here, we present a complete structure of a type II HE with a receptor analog in the catalytic site and identify the mutations underlying the 9-O- to 4-O-Ac-Sia substrate switch. We show that (i) common principles pertaining to the stereochemistry of protein-carbohydrate interactions were at the core of the transition in lectin ligand and esterase substrate specificity; (ii) in consequence, the switch in O-Ac-Sia specificity could be readily accomplished via convergent intramolecular coevolution with only modest architectural changes in lectin and esterase domains; and (iii) a single, inconspicuous Ala-to-Ser substitution in the catalytic site was key to the emergence of the type II HEs. Our findings provide fundamental insights into how proteins "see" sugars and how this affects protein and virus evolution.

negative: Are Powered Air Purifying Respirators a Solution for Protecting Healthcare Workers from Emerging Aerosol-Transmissible Diseases?

negative: Quantifying the prevalence of SARS-CoV-2 long-term shedding among non-hospitalized COVID-19 patients With anecdotal reports of viral shedding from COVID-19 patients for several weeks, there is a need to quantify the prevalence of long-term SARS-CoV-2 shedding. Here, we characterize the temporal distribution of diagnostic SARS-CoV-2 PCR outcomes from nasopharyngeal swabs and associated EHR-derived features over two months for 874 COVID-19 patients with longitudinal data. Among a cohort of 379 COVID-19 patients with at least one positive follow-up SARS-CoV-2 PCR test, 53 patients remain SARS-CoV-2-positive after four weeks of initial diagnosis. Surprisingly, a majority of COVID-19 patients with long-term viral shedding are not hospitalized (40 of 53 patients), and have no enrichments among symptoms, demographics, or medical history. In a cohort of 370 COVID-19 patients that transition to a confirmed negative status, the upper bound of viral shedding duration has a mean of 21.2 days with standard deviation of 9.3 days. Of the 81 PCR-confirmed COVIDpos patients who have undergone serologic testing, 68 patients have developed anti-SARS-CoV-2 IgG to date, with a mean upper bound of time to seroconversion of 38.1 days (95% C.I. = 35.2-41.1 days). Given that SARS-CoV-2 PCR testing may detect replication incompetent virus and that serologic tests do not imply neutralizing immunity, we suggest that the development of novel assays for measuring infectious viral load in non-hospitalized long-term shedders may help mitigate community transmission. This study motivates a platform that can link longitudinal diagnostic and serologic testing with real-time epidemiological data, towards proactively identifying and managing emerging hotspots of COVID-19.

negative: Aberrant Expression of Syndecan-1 in Cervical Cancers Syndecan-1, is a transmembrane heparan/chondroitin sulfate proteoglycan necessary for cell-cell and cell-matrix interactions. Its decreased level on the cell surface correlates with poor prognosis in several tumor types. Aberrant stromal localization of syndecan-1 is also considered an unfavorable prognostic factor in various human malignancies. In the presented work the question was addressed if changes in syndecan-1 expression are related to the prognosis of cervical cancer. Immunohistochemistry for syndecan-1 extracellular domain was performed on surgical specimens of primary cervical cancer. To follow the communication between tumor cells and stromal fibroblasts, their mono-and co-cultures were studied, detecting the expression of syndecan-1, smooth muscle actin, vimentin, and desmin. Immunohistochemistry of tumorous specimens revealed that while cell surface syndecan-1 expression was reduced on cancer cells, it appeared on the surface of tumor-associated fibroblasts. Until year 7, the cohort with high cell surface syndecan-1 expression had significantly longer survival. No difference in the same time-period could be detected when stromal syndecan-1 expression was analyzed. In vitro analysis revealed, that tumor cells can induce syndecan-1 expression on fibroblast, and fibroblasts showed that fibroblast-like cells are built by two cell types: (a) syndecan-1 positive, cytokeratin negative real fibroblasts, and (b) syndecan-1 and cytokeratin positive epithelial-mesenchymal transformed tumor cells. Syndecan-1 on the surface of cancer cells appears to be a positive prognostic marker. Although syndecan-1 positive fibroblasts promote tumor cell proliferation in vitro, we failed to detect their cancer promoting effect in vivo.

negative: A Computational Approach to Design Potential siRNA Molecules as a Prospective Tool for Silencing Nucleocapsid Phosphoprotein and Surface Glycoprotein Gene of SARS-CoV-2 An outbreak, caused by a RNA virus, SARS-CoV-2 named COVID-19 has become pandemic with a magnitude which is daunting to all public health institutions in the absence of specific antiviral treatment. Surface glycoprotein and nucleocapsid phosphoprotein are two important proteins of this virus facilitating its entry into host cell and genome replication. Small interfering RNA (siRNA) is a prospective tool of the RNA interference (RNAi) pathway for the control of human viral infections by suppressing viral gene expression through hybridization and neutralization of target complementary mRNA. So, in this study, the power of RNA interference technology was harnessed to develop siRNA molecules against specific target genes namely, nucleocapsid phosphoprotein gene and surface glycoprotein gene. Conserved sequence from 139 SARS-CoV-2 strains from around the globe was collected to construct 78 siRNA that can inactivate nucleocapsid phosphoprotein and surface glycoprotein genes. Finally, based on GC content, free energy of folding, free energy of binding, melting temperature and efficacy prediction process 8 siRNA molecules were selected which are proposed to exerts the best action. These predicted siRNAs should effectively silence the genes of SARS-CoV-2 during siRNA mediated treatment assisting in the response against SARS-CoV-2

negative: COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up Abstract Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

negative: 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.

negative: Recent increase of surface particulate matter concentrations in the Seoul Metropolitan Area, Korea Recent changes of surface particulate matter (PM) concentration in the Seoul Metropolitan Area (SMA), South Korea, are puzzling. The long-term trend of surface PM concentration in the SMA declined in the 2000s, but since 2012 its concentrations have tended to incline, which is coincident with frequent severe hazes in South Korea. This increase puts the Korean government’s emission reduction efforts in jeopardy. This study reports that interannual variation of surface PM concentration in South Korea is closely linked with the interannual variations of wind speed. A 12-year (2004–2015) regional air quality simulation was conducted over East Asia (27-km) and over South Korea (9-km) to assess the impact of meteorology under constant anthropogenic emissions. Simulated PM concentrations show a strong negative correlation (i.e. R = −0.86) with regional wind speed, implying that reduced regional ventilation is likely associated with more stagnant conditions that cause severe pollutant episodes in South Korea. We conclude that the current PM concentration trend in South Korea is a combination of long-term decline by emission control efforts and short-term fluctuation of regional wind speed interannual variability. When the meteorology-driven variations are removed, PM concentrations in South Korea have declined continuously even after 2012.

negative: Evolutionary dynamics of HIV at multiple spatial and temporal scales Infectious diseases remain a formidable challenge to human health, and understanding pathogen evolution is crucial to designing effective therapeutics and control strategies. Here, we review important evolutionary aspects of HIV infection, highlighting the concept of selection at multiple spatial and temporal scales. At the smallest scale, a single cell may be infected by multiple virions competing for intracellular resources. Recombination and phenotypic mixing introduce novel evolutionary dynamics. As the virus spreads between cells in an infected individual, it continually evolves to circumvent the immune system. We discuss evolutionary mechanisms of HIV pathogenesis and progression to AIDS. Viral spread throughout the human population can lead to changes in virulence and the transmission of immune-evading variation. HIV emerged as a human pathogen due to selection occurring between different species, adapting from related viruses of primates. HIV also evolves resistance to antiretroviral drugs within a single infected host, and we explore the possibility for the spread of these strains between hosts, leading to a drug-resistant epidemic. We investigate the role of latency, drug-protected compartments, and direct cell-to-cell transmission on viral evolution. The introduction of an HIV vaccine may select for viral variants that escape vaccine control, both within an individual and throughout the population. Due to the strong selective pressure exerted by HIV-induced morbidity and mortality in many parts of the world, the human population itself may be co-evolving in response to the HIV pandemic. Throughout the paper, we focus on trade-offs between costs and benefits that constrain viral evolution and accentuate how selection pressures differ at different levels of selection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-012-0892-1) contains supplementary material, which is available to authorized users.

negative: Severe Acute Respiratory Syndrome (SARS) and the GDP. Part II: Implications for GDPs The transmission modes of SARS-coronavirus appear to be through droplet spread, close contact and fomites although air borne transmission has not been ruled out. This clearly places dental personnel at risks as they work in close proximity to their patients employing droplet and aerosol generating procedures. Although the principle of universal precautions is widely advocated and followed throughout the dental community, additional precautionary measures — termed standard precaution may be necessary to help control the spread of this highly contagious disease. Patient assessment should include questions on recent travel to SARS infected areas and, contacts of patients, fever and symptoms of respiratory infections. Special management protocols and modified measures that regulate droplet and aerosol contamination in a dental setting have to be introduced and may include the reduction or avoidance of droplet/aerosol generation, the disinfection of the treatment field, application of rubber dam, pre-procedural antiseptic mouthrinse and the dilution and efficient removal of contaminated ambient air. The gag, cough or vomiting reflexes that lead to the generation of aerosols should also be prevented.

negative: The SCHOOL of nature: IV. Learning from viruses. During the co-evolution of viruses and their hosts, the latter have equipped themselves with an elaborate immune system to defend themselves from the invading viruses. In order to establish a successful infection, replicate and persist in the host, viruses have evolved numerous strategies to counter and evade host antiviral immune responses as well as exploit them for productive viral replication. These strategies include those that modulate signaling mediated by cell surface receptors. Despite tremendous advancement in recent years, the exact molecular mechanisms underlying these critical points in viral pathogenesis remain unknown. In this work, based on a novel platform of receptor signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) platform, I suggest specific mechanisms used by different viruses such as human immunodeficiency virus (HIV), cytomegalovirus (CMV), severe acute respiratory syndrome coronavirus, human herpesvirus 6 and others, to modulate receptor signaling. I also use the example of HIV and CMV to illustrate how two unrelated enveloped viruses use a similar SCHOOL mechanism to modulate the host immune response mediated by two functionally different receptors: T cell antigen receptor and natural killer cell receptor, NKp30. This suggests that it is very likely that similar general mechanisms can be or are used by other viral and possibly non-viral pathogens. Learning from viruses how to target cell surface receptors not only helps us understand viral strategies to escape from the host immune surveillance, but also provides novel avenues in rational drug design and the development of new therapies for immune disorders.

negative: Knowledge and attitude towards COVID-19 in Bangladesh: Population-level estimation and a comparison of data obtained by phone and online survey methods Adherence of people to the guidelines and measures suggested in fighting the ongoing COVID-19 pandemic is partly determined by the Knowledge, Attitude, and Practices (KAP) of the population. In this cross-sectional study, we primarily addressed two key issues. First, we tried to determine whether there is a significant difference in the estimated COVID-19 knowledge level from the online and phone survey methods. Second, we tried to quantify the knowledge and attitude of COVID-19 in Bangladeshi adult population. Data were collected through phone calls (April 14-23, 2020) and online survey (April 18-19, 2020) in Bangladesh. The questionnaire had 20 knowledge questions with each correct response getting one point and incorrect/do not know response getting no point (maximum total knowledge score 20). Participants scoring >17 were categorized as having good knowledge. The percentages of good knowledge holders were 57.6%, 75.1%, and 95.8% in the phone (n=1426), online non-medical (n=1097), and online medical participants (n=382), respectively. Comparison between phone and online survey showed that, overall, online survey might overestimate knowledge level than that of phone survey, although there was no difference for elderly, poor, and rural people. Male gender, higher education, living in town/urban areas, good financial condition, and use of internet were positively associated with good knowledge. However, higher knowledge was associated with having less confidence in the final control of COVID-19. Our adult population-level estimates showed that only 32.6% (95% CI 30.1-35.2%) had good knowledge. This study provides crucial information that could be useful for the researchers and policymakers to develop effective strategies.

negative: Asymptomatic carriage and transmission of SARS-CoV-2: What do we know? PURPOSE: Risk to healthcare workers treating asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the operating room depends on multiple factors. This review examines the evidence for asymptomatic or pre-symptomatic carriage of SARS-CoV-2, the risk of transmission from asymptomatic patients, and the specific risks associated with aerosol-generating procedures. Protective measures, such as minimization of aerosols and use of personal protective equipment in the setting of treating asymptomatic patients, are also reviewed. SOURCE: We examined the published literature as well as Societal guidelines. PRINCIPAL FINDINGS: There is evidence that a proportion of those infected with SARS-CoV-2 have detectable viral loads prior to exhibiting symptoms, or without ever developing symptoms. The degree of risk of transmission from asymptomatic patients to healthcare providers will depend on the prevalence of disease in the population, which is difficult to assess without widespread population screening. Aerosol-generating procedures increase the odds of viral transmission from infected symptomatic patients to healthcare providers, but transmission from asymptomatic patients has not been reported. Techniques to minimize aerosolization and appropriate personal protective equipment may help reduce the risk to healthcare workers in the operating room. Some societal guidelines recommend the use of airborne precautions during aerosol-generating procedures on asymptomatic patients during the coronavirus disease pandemic, although evidence supporting this practice is limited. CONCLUSION: Viral transmission from patients exhibiting no symptoms in the operating room is plausible and efforts to reduce risk to healthcare providers include reducing aerosolization and wearing appropriate personal protective equipment, the feasibility of which will vary based on geographic risk and equipment availability.

negative: Computational Design of ACE2-Based Peptide Inhibitors of SARS-CoV-2 [Image: see text] Peptide inhibitors against the SARS-CoV-2 coronavirus, currently causing a worldwide pandemic, are designed and simulated. The inhibitors are mostly formed by two sequential self-supporting α-helices (bundle) extracted from the protease domain (PD) of angiotensin-converting enzyme 2 (ACE2), which bind to the SARS-CoV-2 receptor binding domains. Molecular dynamics simulations revealed that the α-helical peptides maintain their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. To provide a multivalent binding to the SARS-CoV-2 receptors, many such peptides could be attached to the surfaces of nanoparticle carriers. The proposed peptide inhibitors could provide simple and efficient therapeutics against the COVID-19 disease.

negative: Povidone-iodine gargle as a prophylactic intervention to interrupt the transmission of SARS-CoV-2

negative: 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.

negative: Visualising the expansion and spread of coronavirus disease 2019 by cartograms Coronavirus disease 2019 (COVID-19) has emerged as a growing focus of global attention and a critical factor in public-health decision making. Towards fighting the COVID-19 outbreak, countries worldwide and international organisations have taken various actions, including promoting the transparency of and public access to disease data. In such public communications, maps have played an important role in that a map is worth a thousand words. Most of these have taken the form of a choropleth map. Here, we propose employing cartograms to visualise both the expansion and spread of COVID-19. We designed a combination of six circular cartograms containing the data of confirmed cases every 48 hours from 24 January to 3 February 2020. Such a design conveys both spatial and temporal information more intuitively and efficiently, so it can be expected to facilitate better public participation in the fight against COVID-19.

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: Ghosts A travel barrier to tourism recovery Abstract This study aims to assess whether or not beliefs in ghosts really deter tourists from traveling to disaster-hit destinations. To many it may appear that cultural differences do play a role in travel decision making between Asian and Western tourists. However, it is vital to provide empirical evidence of the impact of cultural differences in beliefs through a case study of the tsunami-hit destinations. Thus, this study aims to examine tourist barriers associated with tsunami-hit destinations, and also to assess cultural differences regarding such beliefs between Asians tourists from China and Thailand and Western tourists from Britain, Germany, and the United States and also across demographic profile.

negative: Population Wellness: Keeping Cats Physically and Behaviorally Healthy

negative: Development of a heat-stable and orally delivered recombinant M2e-expressing B. subtilis spore-based influenza vaccine. Highly conserved ectodomain of influenza virus M2 protein (M2e) is an important target for the development of universal influenza vaccines. Today, the use of chemical or genetic fusion constructs have been undertaken to overcome the low immunogenicity of M2e in vaccine formulation. However, current M2e vaccines are neither orally delivered nor heat-stable. In this study, we evaluated the immune efficacy of an orally delivered recombinant M2e vaccine containing 3 molcules of M2e consensus sequence of influenza A viruses, termed RSM2e3. To accomplish this, CotB, a spore coat of Bacillus subtilis (B. subtilis), was used as a fusion partner, and heat-stable nonpathogenic B. subtilis spores were used as the carrier. Our results showed that CotB-M2e3 fusion had no effect on spore structure or function in the resultant recombinant RSM2e3 strain and that heterologous influenza virus M2e protein was successfully displayed on the surface of the recombinant RSM2e3 spore. Importantly, recombinant RSM2e3 spores elicited strong and long-term M2e-specific systemic and mucosal immune responses, completely protecting immunized mice from lethal challenge of A/PR/8/34(H1N1) influenza virus. Taken together, our study forms a solid basis for the development of a novel orally delivered and heat-stable influenza vaccine based on B. subtilis spore surface display.

negative: Adaptive evolution of bat dipeptidyl peptidase 4 (dpp4): implications for the origin and emergence of Middle East respiratory syndrome coronavirus BACKGROUND: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) that first appeared in Saudi Arabia during the summer of 2012 has to date (20th September 2013) caused 58 human deaths. MERS-CoV utilizes the dipeptidyl peptidase 4 (DPP4) host cell receptor, and analysis of the long-term interaction between virus and receptor provides key information on the evolutionary events that lead to the viral emergence. FINDINGS: We show that bat DPP4 genes have been subject to significant adaptive evolution, suggestive of a long-term arms-race between bats and MERS related CoVs. In particular, we identify three positively selected residues in DPP4 that directly interact with the viral surface glycoprotein. CONCLUSIONS: Our study suggests that the evolutionary lineage leading to MERS-CoV may have circulated in bats for a substantial time period.

negative: CFD investigation on the effects of wind and thermal wall-flow on pollutant transmission in a high-rise building Abstract The solar radiation can heat the building outer surface, and then cause the upward natural convection flows adjacent to the wall. This phenomenon is especially obvious on a windless sunny day. The near wall thermal plume can drive gaseous pollutants released from lower floors to upper floors. Combined with the effect of ambient approaching wind, the transmission routes will be very complicated. The paper aims to investigate the airflow patterns and pollutant transmission within a building under the effects of wind and thermal forces. A hypothetical twenty-storey slab-shape high-rise building in Shanghai with single-sided natural ventilation is set as the research object in the present study. The intensity of solar radiation on a typical day during transition season is theoretically analysed. The temperature difference between the heated building envelope and the ambient air is calculated by a simplified heat balance model. Finally, the tracer gas method is employed in the numerical simulation to analyse the influence of the wind and wall thermal plume flow on the inter-flat pollutant transmission characteristics. The results show that, the temperature difference between sunward and shady side wall is about 10 K at noon on the designate day. When the source is set as a point with steady intensity and the buoyancy is stronger than or approximately equivalent to the wind, the reentry ratio of the flat immediately above the source can be around 25%.

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: Chapter 4 Structure and Genotypes of Noroviruses Abstract Human noroviruses are structurally very simple, but how this correlates with their highly infectious nature, environmental stability, and the fact that they survive commonly used food sterilization processes remains elusive. Noroviruses are genetically very diverse, and new genogroups and genotypes are continuously being discovered. Some norovirus genotypes are more commonly found in foodborne outbreaks, suggesting that virological factors may determine virus adsorption characteristics to food surfaces and the efficiency of food-to-person transmission. Noroviruses can be found in a wide range of mammalian species, including pigs and cows that are extensively farmed for human consumption. The zoonotic potential of animal noroviruses via the food chain cannot be ignored.

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: An approach to the photocatalytic mechanism in the TiO(2)-nanomaterials microorganism interface for the control of infectious processes The approach of this timely review considers the current literature that is focused on the interface nanostructure/cell-wall microorganism to understand the annihilation mechanism. Morphological studies use optical and electronic microscopes to determine the physical damage on the cell-wall and the possible cell lysis that confirms the viability and microorganism death. The key parameters of the tailoring the surface of the photoactive nanostructures such as the metal functionalization with bacteriostatic properties, hydrophilicity, textural porosity, morphology and the formation of heterojunction systems, can achieve the effective eradication of the microorganisms under natural conditions, ranging from practical to applications in environment, agriculture, and so on. However, to our knowledge, a comprehensive review of the microorganism/nanomaterial interface approach has rarely been conducted. The final remarks point the ideal photocatalytic way for the effective prevention/eradication of microorganisms, considering the resistance that the microorganism could develop without the appropriate regulatory aspects for human and ecosystem safety.

negative: Illuminating pathogen–host intimacy through optogenetics The birth and subsequent evolution of optogenetics has resulted in an unprecedented advancement in our understanding of the brain. Its outstanding success does usher wider applications; however, the tool remains still largely relegated to neuroscience. Here, we introduce selected aspects of optogenetics with potential applications in infection biology that will not only answer long-standing questions about intracellular pathogens (parasites, bacteria, viruses) but also broaden the dimension of current research in entwined models. In this essay, we illustrate how a judicious integration of optogenetics with routine methods can illuminate the host–pathogen interactions in a way that has not been feasible otherwise.

negative: Monoclonal Antibody to the Receptor for Murine Coronavirus MHV-A59 Inhibits Viral Replication In Vivo Because many strains of mouse hepatitis virus (MHV) infect laboratory mice, no effective vaccine has yet been developed. An alternative approach to control MHV disease is the use of a host cell receptor-targeted ligand. Toaddress the potential usefulness of this approach, a monoclonal antibody directed against the host cell receptor for the coronavirus MHV-A59 was administered to infant mice that were then challenged oronasally with 10(4) intracerebral infant mouse median lethal doses of MHV-A59. Antibody treatment of virus-challenged mice resulted in lower proportions of mice with MHV-A59 in target organs and markedly reduced viral titers in these organs compared with mock-treated infected mice. Some antibody-treated infected mice survived for 7 days after viral challenge, whereas no mock-treated, infected mice survived beyond day 3 after viral inoculation. These results support a receptor-targeted approach to intervention in coronavirus disease.

negative: Epidemiology and Control: Principles, Practice and Programs Infectious disease epidemiology is concerned with the occurrence of both infection and disease in populations and the factors that determine their frequency, spread, expression and distribution. Viruses show characteristic infectivity, virulence and pathogenicity. The most well established host factors are age, sex and race, but other host biological and behavioral factors affect acquisition of viral infection and/or its course and manifestations. The physical, chemical and biological environment operates on the virus itself and may also alter the host biological or behavioral response. Viral infections have incubation periods lasting days or weeks, while their pathologic sequelae may not manifest for years or decades. Likewise the degree or intensity of host response and clinical expression may range from largely inapparent to highly lethal. The degree of cell, tissue and organ specificity is high. Common syndromes involve the respiratory, gastrointestinal, and central nervous systems, the liver, and mucocutaneous surfaces. Vertical transmission may produce a variety of congenital and perinatal conditions. Viruses spread by multiple modes, using nearly every bodily surface or fluid as a route of exit or entry, either by direct contact or indirectly through an animal vector or other inanimate vehicle. Different viral Infections occur nearly ubiquitously or sporadically; they may be present continuously throughout a population (endemic) or occur in seasonal rhythm or in unexpectedly explosive form (epidemic). Many viruses are refractory to all known therapeutic agents, while for a few, the increasing number of highly effective agents holds great promise. Vaccines have produced many historical successes including the ultimate goal of eradication, but many viral infections continue to elude effective vaccine development. Major government and private sector programs for treatment and prevention have raised expectations of successful control for certain widespread and serious viral diseases; however, in every case a unique set of scientific, socioeconomic, political and behavioral barriers remains to be overcome.

negative: Simple and label-free pathogen enrichment via homobifunctional imidoesters using a microfluidic (SLIM) system for ultrasensitive pathogen detection in various clinical specimens Abstract Diseases caused by pathogenic microorganisms including bacteria and viruses can cause serious medical issues including death and result in huge economic losses. Despite the myriad of recent advances in the rapid and accurate detection of pathogens, large volume clinical samples with a low concentration of pathogens continue to present challenges for diagnosis and surveillance. We here report a simple and label-free approach via homobifunctional imidoesters (HIs) with a microfluidic platform (SLIM) to efficiently enrich and extract pathogens at low concentrations from clinical samples. The SLIM system consists of an assembled double microfluidic chip for streamlining large volume processing and HIs for capturing pathogens and isolating nucleic acids by both electrostatic and covalent interaction without a chaotropic detergent or bulky instruments. The SLIM system significantly increases the enrichment and extraction rate of pathogens (up to 80% at 10 CFU (colony forming unit) in a 1 mL volume within 50 min). We demonstrated its clinical utility in large sample volumes from 46 clinical specimens including environmental swabs, saliva, and blood plasma. The SLIM system showed higher sensitivity with these samples and could detect pathogens that were below the threshold of detection with other methods. Finally, by combining our SLIM approach with an isothermal optical sensor, pathogens could be detected at a very high sensitivity in blood plasma samples within 80 min via enrichment, extraction and detection steps. Our SLIM system thus provides a simple, reliable, cost-effective and ultrasensitive pathogen diagnosis platform for use with large volume clinical samples and would thus have significant utility for various infectious diseases.

negative: Going global – Travel and the 2019 novel coronavirus

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: Possible role of an animal vector in the SARS outbreak at Amoy Gardens Summary A mass outbreak of severe acute respiratory syndrome (SARS) in the Amoy Gardens housing complex in Hong Kong at the end of March, 2003, affected more than 300 residents in less than a month, and has epidemiologists all over the world puzzled about the mode of transmission of this new disease, which until then was thought to be transmitted solely by respiratory droplets. The source of the outbreak was later traced to an individual with SARS who spent two nights at Amoy Gardens. Official explanations failed to account for the large number of residents infected over a wide area within a short time. A powerful environmental mechanism that efficiently amplified and distributed the causal agent must have been at work to cause this outbreak. One such mechanism could be an animal vector, most probably roof rats, that was infected by the index patient and subsequently spread the disease to more than 150 households.

negative: Pandemic Politics: Timing State-Level Social Distancing Responses to COVID-19 Social distancing policies are critical but economically painful measures to flatten the curve against emergent infectious diseases. As the novel coronavirus that causes COVID-19 spread throughout the United States in early 2020, the federal government issued social distancing recommendations but left to the states the most difficult and consequential decisions restricting behavior, such as canceling events, closing schools and businesses, and issuing stay-at-home orders. We present an original dataset of state-level social distancing policy responses to the epidemic and explore how political partisanship, COVID-19 caseload, and policy diffusion explain the timing of governors' decisions to mandate social distancing. An event history analysis of five social distancing policies across all fifty states reveals the most important predictors are political: all else equal, Republican governors and governors from states with more Trump supporters were slower to adopt social distancing policies. These delays are likely to produce significant, on-going harm to public health.

negative: Air and environmental sampling for SARS-CoV-2 around hospitalized patients with coronavirus disease 2019 (COVID-19) BACKGROUND: The role of severe respiratory coronavirus virus 2 (SARS-CoV-2)-laden aerosols in the transmission of coronavirus disease 2019 (COVID-19) remains uncertain. Discordant findings of SARS-CoV-2 RNA in air samples were noted in early reports. METHODS: Sampling of air close to 6 asymptomatic and symptomatic COVID-19 patients with and without surgical masks was performed with sampling devices using sterile gelatin filters. Frequently touched environmental surfaces near 21 patients were swabbed before daily environmental disinfection. The correlation between the viral loads of patients' clinical samples and environmental samples was analyzed. RESULTS: All air samples were negative for SARS-CoV-2 RNA in the 6 patients singly isolated inside airborne infection isolation rooms (AIIRs) with 12 air changes per hour. Of 377 environmental samples near 21 patients, 19 (5.0%) were positive by reverse-transcription polymerase chain reaction (RT-PCR) assay, with a median viral load of 9.2 × 102 copies/mL (range, 1.1 × 102 to 9.4 × 104 copies/mL). The contamination rate was highest on patients' mobile phones (6 of 77, 7.8%), followed by bed rails (4 of 74, 5.4%) and toilet door handles (4 of 76, 5.3%). We detected a significant correlation between viral load ranges in clinical samples and positivity rate of environmental samples (P < .001). CONCLUSION: SARS-CoV-2 RNA was not detectable by air samplers, which suggests that the airborne route is not the predominant mode of transmission of SARS-CoV-2. Wearing a surgical mask, appropriate hand hygiene, and thorough environmental disinfection are sufficient infection control measures for COVID-19 patients isolated singly in AIIRs. However, this conclusion may not apply during aerosol-generating procedures or in cohort wards with large numbers of COVID-19 patients.

negative: Mucins in the mucosal barrier to infection The mucosal tissues of the gastrointestinal, respiratory, reproductive, and urinary tracts, and the surface of the eye present an enormous surface area to the exterior environment. All of these tissues are covered with resident microbial flora, which vary considerably in composition and complexity. Mucosal tissues represent the site of infection or route of access for the majority of viruses, bacteria, yeast, protozoa, and multicellular parasites that cause human disease. Mucin glycoproteins are secreted in large quantities by mucosal epithelia, and cell surface mucins are a prominent feature of the apical glycocalyx of all mucosal epithelia. In this review, we highlight the central role played by mucins in accommodating the resident commensal flora and limiting infectious disease, interplay between underlying innate and adaptive immunity and mucins, and the strategies used by successful mucosal pathogens to subvert or avoid the mucin barrier, with a particular focus on bacteria. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/mi.2008.5) contains supplementary material, which is available to authorized users.

negative: NMR spectroscopy of basic/aromatic amino acid clusters in membrane proteins

negative: Virus recognition of glycan receptors Attachment of viruses to cell-surface receptors is the initial step in infection. Many mammalian viruses have evolved to recognize receptors that are glycans on cell-surface glycoproteins or glycolipids. Although glycans are a ubiquitous component of mammalian cells, the types of terminal structures expressed vary among different cell-types and tissues, and even between comparable cells and tissues from different species, frequently leading to specific tissue and species tropisms as a direct consequence of glycan receptor recognition. Covering the majority of known virus families, this review provides an overview of mammalian viruses that use glycans as receptors, and their roles in determining in host recognition and tropism.

negative: Global Public Health Security National public health institutes will play a key role in implementation of the revised International Health Regulations.

negative: Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes Background. The threat of contagious infectious diseases is constantly evolving, as demographic explosion, travel globalization and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results. PubMed electronic database was requested for relevant articles linking TB, influenza and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (with a focus on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from the past outbreaks (other coronaviruses), as well as influenza pandemic / seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions. Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their harmful synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead.

negative: Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated aerosol The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It infects the cells binding to the angiotensin-converting enzyme 2 receptor (ACE2) which is expressed by cells throughout the airways as targets for cellular entry. Although the majority of persons infected with SARS-CoV-2 experience symptoms of mild upper respiratory tract infection, in some people infections of the peripheral airways result in severe, potentially fatal pneumonia. However, the induction of COVID-19 pneumonia requires that SARS-CoV-2 reaches the peripheral airways. While huge efforts have been made to understand the spread of the disease as well as the pathogenesis following cellular entry, much less attention is paid how SARS-CoV-2 from the environment reach the receptors of the target cells. The aim of the present study is to characterize the deposition distribution of SARS-CoV-2 in the airways upon exposure to cough-generated aerosol. For this purpose, the Stochastic Lung Deposition Model has been applied. Aerosol size distribution and breathing parameters were taken from the literature supposing normal breathing through the nose. We found that the probability of direct infection of the peripheral airways due to inhalation of aerosol generated by a bystander cough is very low. As the number of pathogens deposited in the extrathoracic airways is ~10 times higher than in the peripheral airways, we concluded that in most cases COVID-19 pneumonia must be preceded by SARS-CoV-2 infection of the upper airways. Our results suggest that without the enhancement of viral load in the upper airways, COVID-19 would be much less dangerous. The period between the onset of initial symptoms and the potential clinical deterioration could provide an opportunity for prevention of pneumonia by blocking or significantly reducing the transport of viruses towards the peripheral airways. Coughing into a tissue or cloth even at home in order to absorb the emitted aerosol is highly recommended to avoid the continuous re-inhalation of own cough.

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: CIRD-F: Spread and Influence of COVID-19 in China The outbreak of coronavirus disease 2019 (COVID-19) has been spreading rapidly in China and the Chinese government took a series of policies to control the epidemic. Therefore, it will be helpful to predict the tendency of the epidemic and analyze the influence of official policies. Existing models for prediction, such as cabin models and individual-based models, are either oversimplified or too meticulous, and the influence of the epidemic was studied much more than that of official policies. To predict the epidemic tendency, we consider four groups of people, and establish a propagation dynamics model. We also create a negative feedback to quantify the public vigilance to the epidemic. We evaluate the tendency of epidemic in Hubei and China except Hubei separately to predict the situation of the whole country. Experiments show that the epidemic will terminate around 17 March 2020 and the final number of cumulative infections will be about 78 191 (prediction interval, 74 872 to 82 474). By changing the parameters of the model accordingly, we demonstrate the control effect of the policies of the government on the epidemic situation, which can reduce about 68% possible infections. At the same time, we use the capital asset pricing model with dummy variable to evaluate the effects of the epidemic and official policies on the revenue of multiple industries.

negative: How long does a lockdown need to be? Social distancing, often in the form of lockdown, has been adopted by many countries as a way to contrast the spreading of COVID-19. We discuss the temporal aspects of social distancing in contrasting an epidemic diffusion. We argue that a strategy based uniquely on social distancing requires to maintain the relative measures for a very long time, while a more articulate strategy, which also uses early detection and prompt isolation, can be both more efficient on reducing the epidemic peak and allow to relax the social distancing measures after a much shorter time. We consider in more detail the situation in Italy, simulating the effect of different strategies through a recently introduced SIR-type epidemiological model. The short answer to the question in the title is:"it depends on what else you do".

negative: Effectiveness of Masks and Respirators Against Respiratory Infections in Healthcare Workers: A Systematic Review and Meta-Analysis This systematic review and meta-analysis quantified the protective effect of facemasks and respirators against respiratory infections among healthcare workers. Relevant articles were retrieved from Pubmed, EMBASE, and Web of Science. Meta-analyses were conducted to calculate pooled estimates. Meta-analysis of randomized controlled trials (RCTs) indicated a protective effect of masks and respirators against clinical respiratory illness (CRI) (risk ratio [RR] = 0.59; 95% confidence interval [CI]:0.46–0.77) and influenza-like illness (ILI) (RR = 0.34; 95% CI:0.14–0.82). Compared to masks, N95 respirators conferred superior protection against CRI (RR = 0.47; 95% CI: 0.36–0.62) and laboratory-confirmed bacterial (RR = 0.46; 95% CI: 0.34–0.62), but not viral infections or ILI. Meta-analysis of observational studies provided evidence of a protective effect of masks (OR = 0.13; 95% CI: 0.03–0.62) and respirators (OR = 0.12; 95% CI: 0.06–0.26) against severe acute respiratory syndrome (SARS). This systematic review and meta-analysis supports the use of respiratory protection. However, the existing evidence is sparse and findings are inconsistent within and across studies. Multicentre RCTs with standardized protocols conducted outside epidemic periods would help to clarify the circumstances under which the use of masks or respirators is most warranted.

negative: Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation BACKGROUND: An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology. METHODS: We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization. RESULTS: Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive. CONCLUSIONS: The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.

negative: CHAPTER 7 CELL-SURFACE ANTIGENS Publisher Summary The cell surface is covered with protein molecules that are held in the membrane by hydrophobic transmembrane segments or glycosyl–phosphatidylinositol (GPI) anchors. Antigens found on cell surfaces comprise not only those encoded by the cell itself but also the products of intracellular parasites. Soluble ligands may be bound to receptor structures on the cell membrane or lectin-like molecules bound to cell-surface carbohydrate structures. The molecules that form an integral part of the cell surface may be proteins, glycoproteins, or glycolipids. They subserve one of three major functions: adhesion, antigen recognition, or receptors for soluble mediators. However, many cell-surface molecules possess more than one function—for example, molecules involved in cell–cell or cell–extracellular matrix adhesion can also themselves be involved in signal transduction. The cell-surface antigens of leukocytes have been intensively studied because of ease of access to this cellular compartment.

negative: Superinfection and cell regeneration can lead to chronic viral coinfections Abstract Molecular diagnostic techniques have revealed that approximately 43% of the patients hospitalized with influenza-like illness are infected by more than one viral pathogen, sometimes leading to long-lasting infections. It is not clear how the heterologous viruses interact within the respiratory tract of the infected host to lengthen the duration of what are usually short, self-limiting infections. We develop a mathematical model which allows for single cells to be infected simultaneously with two different respiratory viruses (superinfection) to investigate the possibility of chronic coinfections. We find that a model with superinfection and cell regeneration has a stable chronic coinfection fixed point, while superinfection without cell regeneration produces only acute infections. This analysis suggests that both superinfection and cell regeneration are required to sustain chronic coinfection via this mechanism since coinfection is maintained by superinfected cells that allow slow-growing infections a chance to infect cells and continue replicating. This model provides a possible mechanism for chronic coinfection independent of any viral interactions via the immune response.

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: Standing your Ground to Exoribonucleases: Function of Flavivirus Long Non-coding RNAs Members of the Flaviviridae (e.g. Dengue virus, West Nile virus, and Hepatitis C virus) contain a positive-sense RNA genome that encodes a large polyprotein. It is now also clear most if not all of these viruses also produce an abundant subgenomic long non-coding RNA. These non-coding RNAs, which are called subgenomicflavivirus RNAs (sfRNAs) or Xrn1-resistant RNAs (xrRNAs), are stable decay intermediates generated from the viral genomic RNA through the stalling of the cellular exoribonuclease Xrn1 at highly structured regions. Several functions of these flavivirus long non-coding RNAs have been revealed in recent years. The generation of these sfRNAs/xrRNAs from viral transcripts results in the repression of Xrn1 and the dysregulation of cellular mRNA stability. The abundant sfRNAs also serve directly as a decoy for important cellular protein regulators of the interferon and RNA interference antiviral pathways. Thus the generation of long non-coding RNAs from flaviviruses, hepaciviruses and pestiviruses likely disrupts aspects of innate immunity and may directly contribute to viral replication, cytopathology and pathogenesis.

negative: Analysis of Microorganisms in Hospital Environments and Potential Risks This report provides information on indoor air quality and on associated potential risks in hospitals. Spread and persistence of microbial communities in hospital environments are of huge interest to public health. Hospitals are characterized by high infective risk, firstly cause of the compromised immunologic conditions of the patients that make them vulnerable to bacterial, viral, parasitological and fungal opportunistic infections. Evidence suggests that microbial agents spread through air, surfaces, aerosol and hands. If surfaces may act as a reservoir for some pathogens, hands are an important transmission route. Airborne and aerosolized waterborne microorganisms are taken into consideration, and their presence into the hospital environments is reviewed.

negative: Four ways researchers are responding to the COVID-19 outbreak How did researchers react so quickly to the SARS-CoV-2 epidemic? Nature Medicine has asked some key experts How did researchers react so quickly to the SARS-CoV-2 epidemic? Nature Medicine has asked some key experts

negative: Thermally stable and uniform DNA amplification with picosecond laser ablated graphene rapid thermal cycling device Abstract Rapid thermal cycling (RTC) in an on-chip device can perform DNA amplification in vitro through precise thermal control at each step of the polymerase chain reaction (PCR). This study reports a straightforward fabrication technique for patterning an on-chip graphene-based device with hole arrays, in which the mechanism of surface structures can achieve stable and uniform thermal control for the amplification of DNA fragments. A thin-film based PCR device was fabricated using picosecond laser (PS-laser) ablation of the multilayer graphene (MLG). Under the optimal fluence of 4.72 J/cm2 with a pulse overlap of 66%, the MLG can be patterned with arrays of 250 μm2 hole surface structures. A 354-bp DNA fragment of VP1, an effective marker for diagnosing the BK virus, was amplified on an on-chip device in less than 60 min. A thin-film electrode with the aforementioned MLG as the heater was demonstrated to significantly enhance temperature stability for each stage of the thermal cycle. The temperature control of the heater was performed by means of a developed programmable PCR apparatus. Our results demonstrated that the proposed integration of a graphene-based device and a laser-pulse ablation process to form a thin-film PCR device has cost benefits in a small-volume reagent and holds great promise for practical medical use of DNA amplification.

negative: The Molecular Biology of Coronaviruses Publisher Summary This chapter discusses the manipulation of clones of coronavirus and of complementary DNAs (cDNAs) of defective-interfering (DI) RNAs to study coronavirus RNA replication, transcription, recombination, processing and transport of proteins, virion assembly, identification of cell receptors for coronaviruses, and processing of the polymerase. The nature of the coronavirus genome is nonsegmented, single-stranded, and positive-sense RNA. Its size ranges from 27 to 32 kb, which is significantly larger when compared with other RNA viruses. The gene encoding the large surface glycoprotein is up to 4.4 kb, encoding an imposing trimeric, highly glycosylated protein. This soars some 20 nm above the virion envelope, giving the virus the appearance-with a little imagination-of a crown or coronet. Coronavirus research has contributed to the understanding of many aspects of molecular biology in general, such as the mechanism of RNA synthesis, translational control, and protein transport and processing. It remains a treasure capable of generating unexpected insights.

negative: Re-purposing a face tent as a disposable aerosol evacuation system to reduce contamination in COVID-19 patients: a simulated demonstration

negative: Generalists and Specialists: A New View of How MHC Class I Molecules Fight Infectious Pathogens In comparison with the major histocompatibility complexes (MHCs) of typical mammals, the chicken MHC is simple and compact with a single dominantly expressed class I molecule that can determine the immune response. In addition to providing useful information for the poultry industry and allowing insights into the evolution of the adaptive immune system, the simplicity of the chicken MHC has allowed the discovery of phenomena that are more difficult to discern in the more complicated mammalian systems. This review discusses the new concept that poorly expressed promiscuous class I alleles act as generalists to protect against a wide variety of infectious pathogens, while highly expressed fastidious class I alleles can act as specialists to protect against new and dangerous pathogens.

negative: Acute kidney injury in COVID-19; A review on current knowledge Coronaviruses are a large family of viruses that can cause a variety of diseases in humans. Some coronaviruses cause only mild illnesses like the common cold. While, some coronaviruses such as SARS-CoV (SARS-associated coronavirus) and Middle East respiratory syndrome coronavirus (MERS-CoV) have, in recent years, been able to cause severe respiratory involvement (pneumonia), leading to death in several patients. By identifying the genomic sequence of the new human coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) it has been revealed that it belongs to the beta coronavirus genus. COVID-19 appears to be transmitted by a mechanism similar to the influenza virus via person to person, sneezing coughing, or contact with the secretions of infected patients. Early symptoms of these respiratory viruses include fever, cough, and shortness of breath, with an incubation period of 2-14 days. SARS-CoV-2 is an acute respiratory disease that initially causes lung damage. SARS-CoV-2 can affect other organs, including the kidneys. Kidney damage may be caused by alterations that occur during coronavirus infection. It seems that low-oxygen delivery to tissues like the kidney in the setting of this disease may lead to ischemic damage of the kidney. Considering the importance of the kidneys, as one, this review study aimed to investigate the effect of the new coronavirus on the kidneys and its role in the development of renal failure.

negative: Emerging infectious diseases and biological invasions: a call for a One Health collaboration in science and management The study and management of emerging infectious diseases (EIDs) and of biological invasions both address the ecology of human-associated biological phenomena in a rapidly changing world. However, the two fields work mostly in parallel rather than in concert. This review explores how the general phenomenon of an organism rapidly increasing in range or abundance is caused, highlights the similarities and differences between research on EIDs and invasions, and discusses shared management insights and approaches. EIDs can arise by: (i) crossing geographical barriers due to human-mediated dispersal, (ii) crossing compatibility barriers due to evolution, and (iii) lifting of environmental barriers due to environmental change. All these processes can be implicated in biological invasions, but only the first defines them. Research on EIDs is embedded within the One Health concept—the notion that human, animal and ecosystem health are interrelated and that holistic approaches encompassing all three components are needed to respond to threats to human well-being. We argue that for sustainable development, biological invasions should be explicitly considered within One Health. Management goals for the fields are the same, and direct collaborations between invasion scientists, disease ecologists and epidemiologists on modelling, risk assessment, monitoring and management would be mutually beneficial.

negative: Longitudinally Profiling Neutralizing Antibody Response to SARS Coronavirus with Pseudotypes The severe acute respiratory syndrome–associated coronavirus (SARS-CoV) spike protein (S) is a major target for neutralizing antibodies. Retroviral SARS-CoV S pseudotypes have been constructed and used to develop an in vitro microneutralization assay that is both sensitive and specific for SARS-CoV neutralizing antibodies. Neutralization titers measured by this assay are highly correlated to those measured by an assay using replication-competent SARS-CoV. No cross-neutralization occurred with human sera known to contain antibodies to coronavirus strains OC43 and 229E. The pseudotype assay was used to profile neutralizing antibody responses against SARS-CoV S in sequential serum samples taken from 41 confirmed SARS patients during the 2003 outbreak in Hong Kong and shows long-lasting immunity in most recovered patients. The pseudotype assay does not require handling live SARS virus; it is a useful tool to determine neutralizing titers during natural infection and the preclinical evaluation of candidate vaccines.

negative: Computer simulations of protein–membrane systems The interactions between proteins and membranes play critical roles in signal transduction, cell motility, and transport, and they are involved in many types of diseases. Molecular dynamics (MD) simulations have greatly contributed to our understanding of protein–membrane interactions, promoted by a dramatic development of MD-related software, increasingly accurate force fields, and available computer power. In this chapter, we present available methods for studying protein–membrane systems with MD simulations, including an overview about the various all-atom and coarse-grained force fields for lipids, and useful software for membrane simulation setup and analysis. A large set of case studies is discussed.

negative: Ranking hazards pertaining to human health concerns from land application of anaerobic digestate Abstract Anaerobic digestion (AD) has been identified as one of the cleanest producers of green energy. AD typically uses organic materials as feedstock and, through a series of biological processes, produces methane. Farmyard manure and slurry (FYM&S) are important AD feedstock and are typically mixed with agricultural waste, grass and/or food wastes. The feedstock may contain many different pathogens which can survive the AD process and hence also possibly be present in the final digestate. In this study, a semi-quantitative screening tool was developed to rank pathogens of potential health concern emerging from AD digestate. A scoring system was used to categorise likely inactivation during AD, hazard pathways and finally, severity as determined from reported human mortality rates, number of global human-deaths and infections per 100,000 populations. Five different conditions including mesophilic and thermophilic AD and three different pasteurisation conditions were assessed in terms of specific pathogen inactivation. In addition, a number of scenarios were assessed to consider foodborne incidence data from Ireland and Europe and to investigate the impact of raw FYM&S application (without AD and pasteurisation). A sensitivity analysis revealed that the score for the mortality rate (S3) was the most sensitive parameter (rank coefficient 0.49) to influence the final score S; followed by thermal inactivation score (S1, 0.25) and potential contamination pathways (S2, 0.16). Across all the scenarios considered, the screening tool prioritised Cryptosporidium parvum, Salmonella spp., norovirus, Streptococcus pyogenes, enteropathogenic E. coli (EPEC), Mycobacterium spp., Salmonella typhi (followed by S. paratyphi), Clostridium spp., Listeria monocytogenes and Campylobacter coli as the highest-ranking pathogens of human health concern resulting from AD digestate in Ireland. This tool prioritises potentially harmful pathogens which can emerge from AD digestate and highlights where regulation and intervention may be required.

negative: Safety management of nasopharyngeal specimen collection from suspected cases of coronavirus disease 2019 Abstract This article introduces safety management strategies of nasopharyngeal specimen collection from suspected cases of coronavirus disease 2019 in a tertiary designated hospital. The key points includes establishing a special sampling room, strict sterilization of the entire environment, training of professional nurses, enhancement of personal protection, standardization of methods and processes for swab collection, and a timely and safety sample submission. More than 11,000 nasopharyngeal specimens were collected by eight nurses, with an average of 1375 specimen swab collections each nurse, and no one was infected.

negative: Coronavirus disease 2019 and ophthalmologists: introducing a simple protective shield for slitlamp biomicroscopic examination

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: COVID-19 therapeutic options for patients with kidney disease

negative: A follow-up study of children infected with SARS-CoV-2 from Western China Background: To clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children. Methods: A total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in Western China were enrolled in this study and followed up until discharge and quarantine 14 days later. Results: Eleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD=7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test. Conclusions: Children with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.

negative: Successful Environmental Disinfection to Prevention Transmission of Candida Auris BACKGROUND: Candida auris is a globally-emerging, multidrug-resistant yeast causing invasive infections and can persist on environmental surfaces if not adequately disinfected. Last summer, two patients with C. Auris infections were admitted at University of Chicago Medicine (UCM). Environmental samples were collected to assess environmental contamination before and after cleaning. METHODS: Environmental samples were collected using 3M Sponge Sticks with neutralizing Buffer during one patientÕs stay, weeks after another patientÕs stay, and after enhanced terminal cleaning. Samples were cultured directly and yeast was identified using MALDI. The following surfaces were sampled: Bathroom sink drain, bedside table, bedrail, mattress, chair and window ledge. Routine terminal cleaning includes 10% sodium hypochlorite solution applied high touch surfaces of both room and bathroom. The enhanced terminal cleaning process used for these rooms included: (1) 10% sodium hypochlorite solution applied to all high touch surfaces and walls; (2) privacy curtains removed and replaced; (3) supervision by environmental services manager; and (4) single UV disinfection cycle in room and bathroom. RESULTS: Because of delay in identification of C auris for the first patient, pre-clean samples were taken >2 weeks after the patient had been discharged. During the intervening weeks, multiple patients had occupied the room and there had been >3 routine terminal cleanings. None of these samples were positive for C auris. Pre-clean, in-residence samples indicated C auris contamination of multiple surfaces for the second patient. Because of transfers within the institution, there are three sets of post-cleaning cultures for the second patient. All post-clean environmental cultures were negative for both patients. Results are shown in Figure 1. CONCLUSION: Candida auris can contaminate environmental surfaces. While routine terminal cleaning may have been effective in removing C auris from surfaces in one patientÕs room, the enhanced terminal cleaning strategy used here was effective in our facility. DISCLOSURES: J. P. Ridgway, Gilead FOCUS: Grant Investigator, Grant recipient

negative: Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2 To date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called “cytokine storm”, clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.

negative: Cross-Country Comparison of Case Fatality Rates of COVID-19/SARS-COV-2 OBJECTIVES: Case fatality rates (CFR) and recovery rates are important readouts during epidemics and pandemics. In this article, an international analysis was performed on the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: Data were retrieved from accurate databases according to the user’s guide of data sources for patient registries, CFR and recovery rates were calculated for each country. A comparison of CFR between countries with total cases ≥ 1,000 was observed for 12(th) and 23(rd) March. RESULTS: Italy’s CFR was the highest of all countries studied for both time points (12(th) March, 6.22% versus 23(rd) March, 9.26%). The data showed that even though Italy was the only European country reported on 12(rd) March, Spain and France had the highest CFR of 6.16 and 4.21%, respectively, on 23(rd) March, which was strikingly higher than the overall CFR of 3.61%. CONCLUSION: Obtaining detailed and accurate medical history from COVID-19 patients, and analyzing CFR alongside the recovery rate, may enable the identification of the highest risk areas so that efficient medical care may be provided. This may lead to the development of point-of-care tools to help clinicians in stratifying patients based on possible requirements in the level of care, to increase the probabilities of survival from COVID-19 disease.

negative: The role of growth factor receptors in viral infections: An opportunity for drug repurposing against emerging viral diseases such as COVID‐19? Growth factor receptors are known to be involved in the process of viral infection. Many viruses not only use growth factor receptors to physically attach to the cell surface and internalize, but also divert receptor tyrosine kinase signaling in order to replicate. Thus, repurposing drugs that have initially been developed to target growth factor receptors and their signaling in cancer may prove to be a fast track to effective therapies against emerging new viral infections, including the coronavirus disease 19 (COVID‐19).

negative: Oral Mutian®X stopped faecal feline coronavirus shedding by naturally infected cats Abstract Feline coronavirus (FCoV) is common among cats living indoors in groups. In about 10% of infected cats, a potentially lethal disease, feline infectious peritonitis (FIP) occurs. Virus transmission is faecal-oral. Mutian® Xraphconn (Mutian X) is a product marketed to treat cats with FIP but is also being used to stop virus shedding, although no clear guidelines exist for its use for this purpose. The aim of this study was to establish the minimum dose and treatment duration required to ensure viral clearance from the faeces of asymptomatic virus-shedding cats. In five multicat households, 29 cats naturally infected with FCoV and actively shedding virus in the faeces were given Mutian X pills. Virus shedding was monitored using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) controlled for faecal inhibitors to ensure sensitivity. Mutian X given orally cleared the virus in 29 cats; although four cats required a repeated course to finally stop virus shedding. A dose of 4 mg/kg q24 h for four days was found to be the optimal treatment protocol: 2 mg/kg cleared only 80% of cats. Post-treatment using a sensitive RT-qPCR test was essential to ensure that virus clearance had been achieved, since failure to clear even one cat can result in re-infection of the others. Records of virus shedding by cats before treatment provided a retrospective control: significantly more cats stopped shedding virus after Mutian X than recovered from infection during the control period (p < .00001). This is the first report of the successful elimination of faecal FCoV shedding in chronically infected cats.

negative: Complete Genome Sequence of Human Coronavirus NL63 CN0601/14, First Isolated in South Korea We report here the complete genome sequence of the human coronavirus NL63 CN0601/14 strain, first isolated from South Korea. It contains 18-nucleotide discontinuous deletions of the open reading frame 1a (ORF1a) and spike regions. This study will aid in our understanding of the complete genome sequences of isolated coronaviruses in South Korea.

negative: Understanding the B and T cell epitopes of spike protein of severe acute respiratory syndrome coronavirus-2: A computational way to predict the immunogens The 2019 novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak has caused a large number of deaths, with thousands of confirmed cases worldwide. The present study followed computational approaches to identify B- and T-cell epitopes for the spike (S) glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We identified 24 peptide stretches on the SARS-CoV-2 S protein that are well conserved among the reported strains. The S protein structure further validated the presence of predicted peptides on the surface, of which 20 are surface exposed and predicted to have reasonable epitope binding efficiency. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics. Also, identified T-cell epitopes might be considered for incorporation in vaccine designs.

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: Coronavirus Disease 2019 and the Pediatric Gastroenterologist

negative: What are we doing in the dermatology outpatient department amidst the raging of the 2019 novel coronavirus?

negative: Modern veterinary vaccines and the Shaman's apprentice Abstract This paper is an overview and assessment of new, commercially available veterinary vaccines placed in a historical context. The authors critically evaluate the current state of the field of veterinary vaccines in both food and companion animals and the promises for future vaccine development. The authors maintain that there is considerable variability in safety and sustained efficacy among veterinary vaccines, especially those developed for companion animals. It is proposed that establishment of an international vaccine advisory committee be supported which would function to apprise the veterinary profession of the current status of vaccines and their use.

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: 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.

negative: Response to: Safe Handling of Containers of Expressed Human Milk in all Settings During the SARS-CoV-2 (COVID-19) Pandemic (Marinelli and Lawrence, 2020).

negative: Management and clinical thinking of Coronavirus Disease 2019/ 中华肝脏病杂志 In December 2019, the 2019 novel coronavirus pneumonia (NCP, officially named Coronavirus Disease 2019(COVID-19) by the World Health Organization) broke out in Wuhan, Hubei, and it quickly spread to the whole country and abroad. The situation was at stake. The sudden and serious COVID-19 epidemic has brought us a lot of urgent problems. How to effectively control the spread of COVID-19? When does the population infection rate rise to its peak? What will eventually be the number of infected patients? How to make early diagnosis? What effective antiviral drugs are available? How to effectively treat with existing drugs? Can it successfully improve the survival rate of critically patients? In response to the above questions, we put forward corresponding suggestions and reflections from the perspective of the infectious clinician.

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: Survival of Enveloped and Non-Enveloped Viruses on Inanimate Surfaces In the present study, we evaluated the viability of non-enveloped viruses, minute virus of mice (MVM) and coxsackievirus B4 (CVB4), and enveloped-viruses, influenza A virus (H1N1) and herpes simplex virus type 1 (HSV-1), on surfaces. We also investigated the impact of the initial concentration of proteins and sodium chloride on the persistence of infectious CVB4 on surfaces. Viral suspensions (>10(4.5) TCID(50)) were applied to petri dish lids and dried under the air flow of a biosafety cabinet. The recovered viral preparations were titered on appropriate cell lines. Enveloped viruses persisted for less than 5 days while CVB4 and MVM persisted for weeks. However, repetitive cycles of drying and resuspension had a stronger virucidal effect on CVB4 than on H1N1 and HSV-1. These repetitive cycles had no effect on the infectious titer of MVM. When exposed to drying, the initial concentrations of bovine serum albumin (from 0 to 90 mg mL(−1)), fetal calf serum (from 0 to 100%), and sodium chloride (from 0 to 300 mg mL(−1)) affected the viability of CVB4. CVB4 was more likely to be inactivated by drying in a protein-rich medium, whereas the impact of drying was reduced in the presence of sodium chloride. The results of the present study demonstrated that the resistance of viruses to drying, as suggested by iterative drying, was not due to the heterogeneity of viral subpopulations, but was influenced by media compositions and component concentrations, as illustrated in the model of CVB4.

negative: Le nouveau Coronavirus Covid-19 : quels risques ophtalmiques ?

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: Inbred Strain Variant Database (ISVdb): A Repository for Probabilistically Informed Sequence Differences Among the Collaborative Cross Strains and Their Founders The Collaborative Cross (CC) is a panel of recently established multiparental recombinant inbred mouse strains. For the CC, as for any multiparental population (MPP), effective experimental design and analysis benefit from detailed knowledge of the genetic differences between strains. Such differences can be directly determined by sequencing, but until now whole-genome sequencing was not publicly available for individual CC strains. An alternative and complementary approach is to infer genetic differences by combining two pieces of information: probabilistic estimates of the CC haplotype mosaic from a custom genotyping array, and probabilistic variant calls from sequencing of the CC founders. The computation for this inference, especially when performed genome-wide, can be intricate and time-consuming, requiring the researcher to generate nontrivial and potentially error-prone scripts. To provide standardized, easy-to-access CC sequence information, we have developed the Inbred Strain Variant Database (ISVdb). The ISVdb provides, for all the exonic variants from the Sanger Institute mouse sequencing dataset, direct sequence information for CC founders and, critically, the imputed sequence information for CC strains. Notably, the ISVdb also: (1) provides predicted variant consequence metadata; (2) allows rapid simulation of F1 populations; and (3) preserves imputation uncertainty, which will allow imputed data to be refined in the future as additional sequencing and genotyping data are collected. The ISVdb information is housed in an SQL database and is easily accessible through a custom online interface (http://isvdb.unc.edu), reducing the analytic burden on any researcher using the CC.

negative: Chapter 4 Interaction of virus populations with their hosts Abstract Viral population numbers are extremely large compared with those of their host species. Population bottlenecks are frequent during the life cycle of viruses and can reduce viral populations transiently to very few individuals. Viruses have to confront several types of constraints that can be divided into basal, cell-dependent, and organism-dependent constraints. Viruses overcome them exploiting a number of molecular mechanisms, with an important contribution of population numbers and genome variation. The adaptive potential of viruses is reflected in modifications of cell tropism and host range, escape to components of the host immune response, and capacity to alternate among different host species, among other phenotypic changes. Despite a fitness cost of most mutations required to overcome a selective constraint, viruses can find evolutionary pathways that ensure their survival in equilibrium with their hosts.

negative: Deliberate release: Plague – A review Yersinia pestis is the causative agent of plague and is considered one of the most likely pathogens to be used as a bioweapon. In humans, plague is a severe clinical infection that can rapidly progress with a high mortality despite antibiotic therapy. Therefore, early treatment of Y. pestis infection is crucial. This review provides an overview of its clinical manifestations, diagnosis, treatment, prophylaxis, and protection requirements for the use of clinicians. We discuss the likelihood of a deliberate release of plague and the feasibility of obtaining, isolating, culturing, transporting and dispersing plague in the context of an attack aimed at a westernized country. The current threat status and the medical and public health responses are reviewed. We also provide a brief review of the potential prehospital treatment strategy and vaccination against Y. pestis. Further, we discuss the plausibility of antibiotic resistant plague bacterium, F1-negative Y. pestis, and also the possibility of a plague mimic along with potential strategies of defense against these. An extensive literature search on the MEDLINE, EMBASE, and Web of Science databases was conducted to collate papers relevant to plague and its deliberate release. Our review concluded that the deliberate release of plague is feasible but unlikely to occur, and that a robust public health response and early treatment would rapidly halt the transmission of plague in the population. Front-line clinicians should be aware of the potential of a deliberate release of plague and prepared to instigate early isolation of patients. Moreover, front-line clinicians should be weary of the possibility of suicide attackers and mindful of the early escalation to public health organizations.

negative: Reducing risks from coronavirus transmission in the home-the role of viral load.

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: Conformational change of the coronavirus peplomer glycoprotein at pH 8.0 and 37 degrees C correlates with virus aggregation and virus-induced cell fusion. We have obtained biochemical and electron microscopic evidence of conformational changes at pH 8.0 and 37 degrees C in the coronavirus spike glycoprotein E2 (S). The importance of these changes is reflected in the loss of virus infectivity, the aggregation of virions, and increased virus-induced cell fusion at the same pH. Coronavirus (MHV-A59) infectivity is exquisitely sensitive to pH. The virus was quite stable at pH 6.0 and 37 degrees C (half-life, approximately 24 h) but was rapidly and irreversibly inactivated by brief treatment at pH 8.0 and 37 degrees C (half-life, approximately 30 min). Virions treated at pH 8.0 and 37 degrees C formed clumps and large aggregates. With virions treated at pH 8.0 and 37 degrees C, the amino-terminal peptide E2N (or S1) was released from virions and the remaining peptide, E2C (S2), was aggregated. Viral spikes isolated from detergent-treated virions also aggregated at pH 8.0 and 37 degrees C. Loss of virus infectivity and E2 (S) aggregation at pH 8.0 and 37 degrees C were markedly enhanced in the presence of dithiothreitol. On the basis of the effects of dithiothreitol on the reactions of the peplomer, we propose that release of E2N (S1) and aggregation of E2C (S2) may be triggered by rearrangement of intramolecular disulfide bonds. The aggregation of virions and the isolated E2 (S) glycoprotein at pH 8.0 and 37 degrees C or following treatment with guanidine and urea at pH 6.0 and 37 degrees C indicate that an irreversible conformational change has been induced in the peplomer glycoprotein by these conditions. It is interesting that coronavirus-induced cell fusion also occurred under mildly alkaline conditions and at 37 degrees C. Some enveloped viruses, including influenza viruses and alphaviruses, show conformational changes of spike glycoproteins at a low pH, which correlates with fusion and penetration of those viruses in acidified endocytic vesicles. For coronavirus MHV-A59, comparable conformational change of the spike glycoprotein E2 (S) and cell fusion occurred at a mildly alkaline condition, suggesting that coronavirus infection-penetration, like that of paramyxoviruses and lentiviruses, may occur at the plasma membrane, rather than within endocytic vesicles.

negative: The HIV-1 Envelope Glycoprotein Structure: Nailing down a Moving Target Structure determination of the HIV-1 envelope glycoprotein (Env) presented a number of challenges, but several high-resolution structures have now become available. In 2013, cryo-EM and x-ray structures of soluble, cleaved SOSIP Env trimers from the clade A BG505 strain provided the first glimpses into the Env trimer fold as well as more the variable regions. A recent cryo-EM structure of a native full-length trimer without any stabilizing mutations had the same core structure, but revealed new insights and features. A more comprehensive and higher resolution understanding of the glycan shield has also emerged, enabling a more complete representation of the Env glycoprotein structure. Complexes of Env trimers with broadly neutralizing antibodies have surprisingly illustrated that most of the Env surface can be targeted in natural infection and that the neutralizing epitopes are almost all composed of both peptide and glycan components. These structures have also provided further evidence of the inherent plasticity of Env and how antibodies can exploit this flexibility by perturbing or even stabilizing the trimer to facilitate neutralization. These breakthroughs have stimulated further design and stabilization of Env trimers as well as other platforms to generate trimers that now span multiple subtypes The Env trimers as immunogens have led to the first vaccine-induced neutralizing antibodies for structural and functional analyses.

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: What Role Is There for Antithymocyte Globulin in Allogeneic Nonmyeloablative Canine Hematopoietic Cell Transplantation? We investigated whether pretransplantation immunosuppression with canine-specific rabbit antithymocyte globulin (ATG), combined with a suboptimal dose of 1 Gy of total body irradiation (TBI), would permit engraftment of canine dog leukocyte antigen-identical marrow. Cumulative ATG doses of 2 to 5 mg/kg produced a T-cell depletion of 1 log in the peripheral blood and 50% in the lymph nodes. Serum levels of ATG peaked on days 4 to 6 after initiation of therapy and became undetectable by day 13 as a result of canine antibody responses to ATG. ATG prolonged allogeneic skin graft survival to 14 days (n = 5), compared with 8 days in control dogs (P = .0003). Five dogs were given marrow transplants after ATG (3.5–5 mg/kg) and 1 Gy of TBI. Posttransplantation immunosuppression consisted of mycophenolate mofetil and cyclosporine. All dogs showed initial engraftment, with maximum donor chimerism levels of 25%. However, only 1 dog achieved sustained engraftment, and 4 rejected their grafts. The duration of engraftment ranged from 8 to ≥36 weeks (median, 11 weeks), and this is comparable to that in 6 historical controls not given ATG (range, 3–12 weeks; median, 10 weeks; P = .20). The total nucleated cell doses in the marrow grafts had the highest correlation coefficient with the duration of engraftment: 0.82 (P = .09). We concluded that administering ATG before an otherwise suboptimal conditioning dose of 1 Gy of TBI failed to secure uniform stable hematopoietic engraftment.

negative: Novel SARS-like Betacoronaviruses in Bats, China, 2011 To clarify the evolutionary relationships among betavoronaviruses that infect bats, we analyzed samples collected during 2010–2011 from 14 insectivorous bat species in China. We identified complete genomes of 2 novel betacoronaviruses in Rhinolophus pusillus and Chaerephon plicata bats, which showed close genetic relationships with severe acute respiratory syndrome coronaviruses.

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: Molecular Characterization of Transmissible Gastroenteritis Coronavirus Defective Interfering Genomes: Packaging and Heterogeneity Abstract Three transmissible gastroenteritis virus (TGEV) defective RNAs were selected by serial undiluted passage of the PUR46 strain in ST cells. These RNAs of 22, 10.6, and 9.7 kb (DI-A, DI-B, and DI-C, respectively) were detected at passage 30, remained stable upon further passage in cell culture, and significantly interfered with helper mRNA synthesis. RNA analysis from purified virions showed that the three defective RNAs were efficiently packaged. Virions of different densities containing either full-length or defective RNAs were sorted in sucrose gradients, indicating that defective and full-length genomes were independently encapsidated. DI-B and DI-C RNAs were amplified by the reverse transcription-polymerase chain reaction, cloned, and sequenced. DI-B and DI-C genomes are formed by three and four discontinuous regions of the wild-type genome, respectively. DI-C contains 2144 nucleotides (nt) from the 5′-end of the genome, two fragments of 4540 and 2531 nt mostly from gene 1b, and 493 nt from the 3′ end of the genome. DI-B and DI-C RNAs include sequences with the pseudoknot motif and encoding the polymerase, metal ion binding, and helicase motifs. DI-B RNA has a structure closely related to DI-C RNA with two main differences: it maintains the entire ORF 1b and shows heterogeneity in the size of the 3′ end deletion. This heterogeneity maps at the beginning of the S gene, where other natural TGEV recombination events have been observed, suggesting that either a process of template switching occurs with high frequency at this point or that the derived genomes have a selective advantage.

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: Skin cancer plastic surgery during the COVID-19 pandemic

negative: Low serum 25-hydroxyvitamin D levels are associated with increased risk of viral coinfections in wheezing children

negative: Contamination of hospital surfaces with respiratory pathogens in Bangladesh With limited infection control practices in overcrowded Bangladeshi hospitals, surfaces may play an important role in the transmission of respiratory pathogens in hospital wards and pose a serious risk of infection for patients, health care workers, caregivers and visitors. In this study, we aimed to identify if surfaces near hospitalized patients with respiratory infections were contaminated with respiratory pathogens and to identify which surfaces were most commonly contaminated. Between September-November 2013, we collected respiratory (nasopharyngeal and oropharyngeal) swabs from patients hospitalized with respiratory illness in adult medicine and paediatric medicine wards at two public tertiary care hospitals in Bangladesh. We collected surface swabs from up to five surfaces near each case-patient including: the wall, bed rail, bed sheet, clinical file, and multipurpose towel used for care giving purposes. We tested swabs using real-time multiplex PCR for 19 viral and 12 bacterial pathogens. Case-patients with at least one pathogen detected had corresponding surface swabs tested for those same pathogens. Of 104 patients tested, 79 had a laboratory-confirmed respiratory pathogen. Of the 287 swabs collected from surfaces near these patients, 133 (46%) had evidence of contamination with at least one pathogen. The most commonly contaminated surfaces were the bed sheet and the towel. Sixty-two percent of patients with a laboratory-confirmed respiratory pathgen (49/79) had detectable viral or bacterial nucleic acid on at least one surface. Klebsiella pneumoniae was the most frequently detected pathogen on both respiratory swabs (32%, 33/104) and on surfaces near patients positive for this organism (97%, 32/33). Surfaces near patients hospitalized with respiratory infections were frequently contaminated by pathogens, with Klebsiella pneumoniae being most common, highlighting the potential for transmission of respiratory pathogens via surfaces. Efforts to introduce routine cleaning in wards may be a feasible strategy to improve infection control, given that severe space constraints prohibit cohorting patients with respiratory illness.

negative: Coronavirus: Hotspot on coronavirus disease 2019 in India The novel coronavirus disease (COVID-19) or also known as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been recognized as the cause of respiratory infection in Wuhan, Hubei Province, China, in late December 2019. As of April 5, 2020, this epidemic had spread to worldwide with 12,03,485 confirmed cases, including 62,000 deaths. The World Health Organization has declared it a Global Public Health Crisis. Coronavirus causes respiratory illness coughing, sneezing, breathlessness, and fever including pneumonia. The disease is transmitted person to person through infected droplets. At present, the research on novel coronavirus is still in the primary stage. Based on the published study, we thoroughly summarize the history and origin, microbiology and taxonomy, mode of transmissions, target receptor, clinical features, diagnosis, prevention, and treatment about COVID-19. This short report writes in hope for providing platform to community and researcher dealings against with the novel coronavirus and providing a reference for further studies.

negative: 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.

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: Observations on disinfectant performance

negative: Epidemiology of severe acute respiratory syndrome (SARS): adults and children Summary Severe acute respiratory syndrome (SARS) is a newly described respiratory infection with pandemic potential. The causative agent is a new strain of coronavirus most likely originating from wild animals. This disease first emerged in November 2002 in Guangdong Province, China. Early in the outbreak the infection had been transmitted primarily via household contacts and healthcare settings. In late February 2003 the infection was transmitted to Hong Kong when an infected doctor from the mainland visited there. During his stay in Hong Kong at least 17 guests and visitors were infected at the hotel at which he stayed. By modern day air travel, the infection was rapidly spread to other countries including Vietnam, Singapore and Canada by these infected guests. With the implementation of effective control strategies including early isolation of suspected cases, strict infection control measures in the hospital setting, meticulous contact tracing and quarantine, the outbreak was finally brought under control by July 2003. In addition, there were another two events of SARS in China between the end of December 2003 and January 2004 and from March to May 2004; both were readily controlled without significant patient spread.

negative: In Vitro Efficacy of Povidone-Iodine Nasal And Oral Antiseptic Preparations Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) Introduction:Improved antisepsis of human and non-human surfaces has been identified as a key feature of transmission reduction. There are no previous studies of povidone-iodine (PVP-I) against SARS-CoV-2. This study evaluated nasal and oral antiseptic formulations of povidone-iodine (PVP-I) for virucidal activity against SARS-CoV-2. This is the first report on the efficacy of PVP-I against the virus that causes COVID-19. Methods: PVP-I nasal antiseptic formulations and PVP-I oral rinse antiseptic formulations from 1-5% concentrations as well as controls were studied for virucidal efficacy against the SARS-CoV-2 virus. Test compounds were evaluated for ability to inactivate SARS-CoV-2 as measured in a virucidal assay. SARS-CoV-2 was exposed directly to the test compound for 60 seconds, compounds were then neutralized and surviving virus was quantified. Results: All concentrations of nasal antiseptics and oral rinse antiseptics evaluated completely inactivated the SARS-CoV-2 virus. Conclusions: Nasal and oral PVP-I antiseptic solutions are effective at inactivating the SARS-CoV-2 virus at a variety of concentrations after 60s exposure times. The formulations tested may help to reduce the transmission of SARS-CoV-2 if used for nasal decontamination, oral decontamination or surface decontamination in known or suspected cases of COVID-19.

negative: Disposable DNA Amplification Chips with Integrated Low-Cost Heaters † Fast point-of-use detection of, for example, early-stage zoonoses, e.g., Q-fever, bovine tuberculosis, or the Covid-19 coronavirus, is beneficial for both humans and animal husbandry as it can save lives and livestock. The latter prevents farmers from going bankrupt after a zoonoses outbreak. This paper describes the development of a fabrication process and the proof-of-principle of a disposable DNA amplification chip with an integrated heater. Based on the analysis of the milling process, metal adhesion studies, and COMSOL MultiPhysics heat transfer simulations, the first batch of chips has been fabricated and successful multiple displacement amplification reactions are performed inside these chips. This research is the first step towards the development of an early-stage zoonoses detection device. Tests with real zoonoses and DNA specific amplification reactions still need to be done.

negative: Nosocomial amplification of MERS-coronavirus in South Korea, 2015 BACKGROUND: Nosocomial amplification resulted in nearly 200 cases of Middle East respiratory syndrome (MERS) during the 2015 South Korean MERS-coronavirus outbreak. It remains unclear whether certain types of cases were more likely to cause secondary infections than others, and if so, why. METHODS: Publicly available demographic and transmission network data for all cases were collected from the Ministry of Health and Welfare. Statistical analyses were conducted to determine the relationship between demographic characteristics and the likelihood of human-to-human transmission. Findings from the statistical analyses were used to inform a hypothesis-directed literature review, through which mechanistic explanations for nosocomial amplification were developed. RESULTS: Cases that failed to recover from MERS were more likely to cause secondary infections than those that did. Increased probability of direct, human-to-human transmission due to clinical manifestations associated with death, as well as indirect transmission via environmental contamination (e.g., fomites and indoor ventilation systems), may serve as mechanistic explanations for nosocomial amplification of MERS-coronavirus in South Korea. CONCLUSIONS: In addition to closely monitoring contacts of MERS cases that fail to recover during future nosocomial outbreaks, potential fomites with which they may have had contact should be sanitized. Furthermore, indoor ventilation systems that minimize recirculation of pathogen-bearing droplets should be implemented whenever possible.

negative: Worrying decrease in hospital admissions for myocardial infarction during the COVID-19 pandemic Summary Background: How coronavirus 2019 (COVID-19) is affecting management of myocardial infarction is a matter of concern, as medical resources have been massively reorientated and the population has been in lockdown since 17 March 2020 in France. Aims: To describe how lockdown has affected the evolution of the weekly rate of myocardial infarctions (non–ST-segment and ST-segment elevation) hospital admissions in Lyon, the second largest city in France. To verify the trend observed, the same analysis was conducted for an identical time window during 2018–2019 and for an unavoidable emergency, i.e. birth. Methods: Based on the national hospitalization database (Programme de médicalisation des systèmes d'information [PMSI]), all patients admitted to the main public hospitals for a principal diagnosis of myocardial infarction or birth during the 2nd to the 14th week of 2020 were included. These were compared with the average number of patients admitted for the same diagnosis during the same time window in 2018 and 2019. Results: Before lockdown, the number of admissions for myocardial infarction in 2020 differed from that in 2018–2019 by less than 10%; after the start of lockdown, it decreased by 31% compared with the corresponding time window in 2018–2019. Conversely, the numbers of births remained stable across years and before and after the start of lockdown. Conclusion: This study strongly suggests a decrease in the number of admissions for myocardial infarction during lockdown. Although we do not have a long follow-up to determine whether this trend will endure, this is an important warning for the medical community and health authorities.

negative: Effect of single- versus double-gloving on virus transfer to health care workers’ skin and clothing during removal of personal protective equipment BACKGROUND: The removal of personal protective equipment (PPE) after patient care may result in transfer of virus to hands and clothing of health care workers (HCWs). The risk of transfer can be modeled using harmless viruses to obtain quantitative data. To determine whether double-gloving reduces virus transfer to HCWs’ hands and clothing during removal of contaminated PPE, we conducted a human challenge study using bacteriophages to compare the frequency and quantity of virus transfer to hands and clothes during PPE removal with single-gloving and double-gloving technique. METHODS: Each experiment had a double-gloving phase and a single-gloving phase. Participants donned PPE (ie, contact isolation gown, N95 respirator, eye protection, latex gloves). The gown, respirator, eye protection, and dominant glove were contaminated with bacteriophage. Participants then removed the PPE, and their hands, face, and scrubs were sampled for virus. RESULTS: Transfer of virus to hands during PPE removal was significantly more frequent with single-gloving than with double-gloving. Transfer to scrubs was similar during single-gloving and double-gloving. The amount of virus transfer to hands ranged from 0.15 to 2.5 log(10) most probable number. Significantly more virus was transferred to participants’ hands after single-gloving than after double-gloving. CONCLUSIONS: Our comparison of double-gloving and single-gloving using a simulation system with MS2 and a most-probable number method suggests that double gloving can reduce the risk of viral contamination of HCWs’ hands during PPE removal. If incorporated into practice when full PPE is worn, this practice may reduce the risk of viral contamination of HCWs’ hands during PPE removal. The use of double gloves should be explored in larger controlled studies.

negative: Recognition of aerosol transmission of infectious agents: a commentary Although short-range large-droplet transmission is possible for most respiratory infectious agents, deciding on whether the same agent is also airborne has a potentially huge impact on the types (and costs) of infection control interventions that are required. The concept and definition of aerosols is also discussed, as is the concept of large droplet transmission, and airborne transmission which is meant by most authors to be synonymous with aerosol transmission, although some use the term to mean either large droplet or aerosol transmission. However, these terms are often used confusingly when discussing specific infection control interventions for individual pathogens that are accepted to be mostly transmitted by the airborne (aerosol) route (e.g. tuberculosis, measles and chickenpox). It is therefore important to clarify such terminology, where a particular intervention, like the type of personal protective equipment (PPE) to be used, is deemed adequate to intervene for this potential mode of transmission, i.e. at an N95 rather than surgical mask level requirement. With this in mind, this review considers the commonly used term of ‘aerosol transmission’ in the context of some infectious agents that are well-recognized to be transmissible via the airborne route. It also discusses other agents, like influenza virus, where the potential for airborne transmission is much more dependent on various host, viral and environmental factors, and where its potential for aerosol transmission may be underestimated.

negative: Synergistic effect of modified Pd-based cobalt chromite and manganese oxide system towards NO-CO redox detoxification reaction. Surface architecting of the catalyst is a hopeful method to expand the surface property of the impetus material for upgrading their response towards the chemical reaction. In the present study, designing of the catalyst was carried out using specific transition metals to boost the simultaneous NO-CO conversion reaction catalytically. These metal oxide systems have been prepared using the combustion and wet impregnation method. Prepared oxides were characterized using XRD, BET, XPS, SEM, and TEM. Further, the surface phenomenon of the catalyst was monitored through H2-TPR, O2-TPO, NO-TPD, and CO-TPD studies. The highly remarkable activity was perceived by Pd-based modified manganese oxide-cobalt chromite system as compared with simple Pd-based manganese oxide and Pd-based cobalt chromite. The catalyst showed the highest activity for NO-CO redox reaction with T100 at 170 °C. Also, good stability was observed with a runtime of 7 h.

negative: Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019 Abstract Objective To investigate the diagnostic value of serological testing and dynamic variance of serum antibody in coronavirus disease 2019 (COVID-19). Methods This study retrospectively included 43 patients with a laboratory-confirmed infection and 33 patients with a suspected infection, in whom the disease was eventually excluded. The IgM/IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was measured by chemiluminescence immunoassay analysis. Results Compared to molecular detection, the sensitivities of serum IgM and IgG antibodies to diagnose COVID-19 were 48.1% and 88.9%, and the specificities were 100% and 90.9%, respectively.In the COVID-19 group, the IgM-positive rate increased slightly at first and then decreased over time; in contrast, the IgG-positive rate increased to 100% and was higher than IgM at all times. The IgM-positive rate and titer were not significantly different before and after conversion to virus-negative. The IgG-positive rate was up to 90% and not significantly different before and after conversion to virus-negative. However, the median IgG titer after conversion to virus-negative was double that before, and the difference was significant. Conclusions Viral serological testing is an effective means of diagnosis for SARS-CoV-2 infection. The positive rate and titer variance of IgG are higher than those of IgM in COVID-19.

negative: Virus adsorption of water-stable quaternized chitosan nanofibers Abstract The burden of unsafe drinking water is responsible for millions of deaths each year. To relieve this burden, we are in search of an inexpensive material that can adsorb pathogens from drinking water. In this pursuit, we have studied the natural carbohydrate, chitosan. To impart virus removal features, chitosan has been functionalized with a quaternary amine to form quaternized chitosan N-[(2-hydroxyl-3-trimethylammonium) propyl] chitosan (HTCC). HTCC can be electrospun into nanofibers with the non-ionogenic polyvinyl alcohol (PVA), creating a high surface area mat. High surface area is a major requirement for effective adsorption processes. HTCC is antiviral and antimicrobial, making it a good material for water purification. However, HTCC dissolves in water. We have explored the parameters to crosslink the nanofibers with glutaraldehyde. We have imparted water stability so there is a maximum of 30% swelling of the fibers after 6h in water. The water stable fibers retain their ability to adsorb virus, as shown for an enveloped and nonenveloped virus. HTCC now has the potential to be incorporated into a microfiltration membrane that can remove viruses. This could create an inexpensive, low pressure filtration membrane for drinking water purification.

negative: COVID-19: A Call for Physical Scientists and Engineers [Image: see text] The COVID-19 pandemic is one of those global challenges that transcends territorial, political, ideological, religious, cultural, and certainly academic boundaries. Public health and healthcare workers are at the frontline, working to contain and to mitigate the spread of this disease. Although intervening biological and immunological responses against viral infection may seem far from the physical sciences and engineering that typically work with inanimate objects, there actually is much that can—and should—be done to help in this global crisis. In this Perspective, we convert the basics of infectious respiratory diseases and viruses into physical sciences and engineering intuitions, and through this exercise, we present examples of questions, hypotheses, and research needs identified based on clinicians’ experiences. We hope researchers in the physical sciences and engineering will proactively study these challenges, develop new hypotheses, define new research areas, and work with biological researchers, healthcare, and public health professionals to create user-centered solutions and to inform the general public, so that we can better address the many challenges associated with the transmission and spread of infectious respiratory diseases.

negative: Procedures to Investigate Waterborne Illness Humanity could not survive without a reliably clean, safe, and steady flow of drinking water. Since the early 1900s when typhoid fever and cholera were frequently causes of waterborne illness in developed countries, drinking water supplies have been protected and treated to ensure water safety, quality, and quantity. Having access to safe drinking water has always been one of the cornerstones of good public health. Not only safe water is limited to drinking water, but recreational water can also be a source for waterborne illness—both from treated waters such as in swimming pools, whirlpools, or splash pads and from non-treated surface waters such as lakes, rivers, streams and ponds. Recreational waters may cause illness not only from ingestion of pathogens, but also when in contact with eyes, ears, or skin. Some pathogens in water can be acquired by inhalation of aerosols from water that is agitated or sprayed such as in humidifiers, fountains, or misting of produce. This poses a potential risk to those exposed, particularly if they are immunocompromised.

negative: A Continuously Active Antimicrobial Coating effective against Human Coronavirus 229E The disinfection of high-contact surfaces is seen as an infection control practice to prevent the spread of pathogens by fomites. Unfortunately, recontamination of these surfaces can occur any time after the use of common disinfectants. We recently reported on a novel continuously active antimicrobial coating which was shown to reduce the spread of healthcare acquired infections in hospitals. We evaluated a modified coating that demonstrated a residual efficacy against viruses. The coated surfaces were found to be effective against human coronavirus (HCoV) 229E, reducing the concentration of these viruses by greater than 90% in 10 minutes and by greater than 99.9% after two hours of contact. The coating formulation when tested in suspension yielded a greater than 99.99% reduction of HCoV 229E within ten minutes of contact. This outcome presents an opportunity for controlling the transmission of COVID-19 from contaminated fomites.

negative: Comparative features of a coronavirus isolated from a cheetah with feline infectious peritonitis Abstract A coronavirus which was isolated from a cheetah (Acinonyx jubatus) that succumbed to feline infectious peritonitis was characterized in vitro. The virus was determined to be highly cell-associated with Crandell feline kidney (CrFK) cells and was routinely maintained as a persistent infection (CrFK 83–4497). The cheetah coronavirus was compared with other members of the feline coronavirus group including the feline enteric coronavirus (FECV) 79–1683 and the feline infectious peritonitis viruses (FIPV), 79–1146, and UCD-1. The cheetah coronavirus was demonstrated to have a restricted host-cell range with limited cytopathic effect. Indirect immunofluorescence with antisera to FIPV UCD-1 revealed the concentration of viral antigens in the perinuclear region of cells infected with the cheetah coronavirus. Ultrastructural studies of the cheetah coronavirus indicated a limited number of immature viral particles within cytoplasmic vesicles and at the cell surface. This was in contrast to electron microscopy results of FECV 79–1683 and FIPV 79–1146, which had numerous mature virus particles within the cytoplasmic vesicles, as well as at the cell surface. The cheetah coronavirus was tentatively placed in the feline coronavirus family based upon its antigenic reactivity by immunofluorescence; however, the possibility that it represents a unique coronavirus of cheetahs should not be dismissed without further analyses at the host and genomic levels.

negative: Harmonizing the COVID-19 cacophony: People need guidance

negative: Effectiveness of ultraviolet devices and hydrogen peroxide systems for terminal room decontamination: Focus on clinical trials Over the last decade, substantial scientific evidence has accumulated that indicates contamination of environmental surfaces in hospital rooms plays an important role in the transmission of key health care–associated pathogens (eg, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Clostridium difficile, Acinetobacter spp). For example, a patient admitted to a room previously occupied by a patient colonized or infected with one of these pathogens has a higher risk for acquiring one of these pathogens than a patient admitted to a room whose previous occupant was not colonized or infected. This risk is not surprising because multiple studies have demonstrated that surfaces in hospital rooms are poorly cleaned during terminal cleaning. To reduce surface contamination after terminal cleaning, no touch methods of room disinfection have been developed. This article will review the no touch methods, ultraviolet light devices, and hydrogen peroxide systems, with a focus on clinical trials which have used patient colonization or infection as an outcome. Multiple studies have demonstrated that ultraviolet light devices and hydrogen peroxide systems have been shown to inactivate microbes experimentally plated on carrier materials and placed in hospital rooms and to decontaminate surfaces in hospital rooms naturally contaminated with multidrug-resistant pathogens. A growing number of clinical studies have demonstrated that ultraviolet devices and hydrogen peroxide systems when used for terminal disinfection can reduce colonization or health care–associated infections in patients admitted to these hospital rooms.

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: Preventive measures and management of COVID-19 in pregnancy

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: Grundlagen der Replikation und der Immunologie von SARS-CoV-2./ [Basic principles of replication and immunology of SARS-CoV-2] Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ Tcell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.

negative: Mechanisms of Cell and Tissue Damage Cell damage has profound effects if it is the endothelial cells of small blood vessels that are involved. When bacteria invade tissues, they almost inevitably cause some damage, and this is also true for fungi and protozoa. Cell and tissue damage are sometimes due to the direct local action of the microorganism and microbial toxins. They either interfere with the transcription, translation, and DNA synthesis or change the permeability of the cell membrane. Some of the indirect damage brought about by these microbes is through inflammation and immune responses. Host cells are destroyed or blood vessels injured as a direct result of the action of microbes or their toxins. Inflammatory materials are liberated from necrotic cells, whatever the cause of the necrosis. Also many bacteria themselves liberate inflammatory products and certain viruses cause living infected cells to release inflammatory mediators. The expression of the immune response necessarily involves a certain amount of inflammation, cell infiltration, lymph node swelling, even tissue destruction. Sometimes they are very severe, leading to serious disease or death, but at other times they play a minimal part in the pathogenesis of disease. Other indirect mechanisms of damage include stress, hemorrhage, placental infection, and tumors.

negative: Quantitation, biological and physicochemical properties of cell culture-adapted porcine epidemic diarrhea coronavirus (PEDV) Abstract The porcine epidemic coronavirus (PEDV), tentatively classified as a coronavirus, was adapted to Vero cells and a plaque test developed for infectivity titration, allowing us to test the biological and biophysical properties of the virus. Growth kinetics showed peak titers of 105.5 plaque-forming units ml−1 15 h after infection. Filtration experiments and electron microscopy revealed a particle diameter between 100 and 200 nm. The bouyant density of the virus was 1.18. The particle lost its infectivity on treatment with lipid solvents. Virus replication could not be inhibited by 5-iodo-2′-deoxyuridine. PEDV was moderately stable at 50°C, but heat sensitivity was not altered by divalent cations. At 4°C, the virus was stable between pH 5.0 and 9.0, but at 37°C stability was restricted to the pH range 6.5–7.5. Viral infectivity was not impaired by ultrasonication or by multiple freezing and thawing. PEDV was not neutralized by transmissible gastroenteritis virus antiserum. On the basis of the tests carried out, PEDV is a pleomorphic, enveloped RNA virus with a particle diameter of ∼ 150 nm and a bouyant density of 1.18. Infectivity depends on the presence of trypsin, and infected cells show a tendency to fuse and to form syncytia. All of these properties, as well as its physicochemical characteristics, allow PEDV to be classified as a coronavirus.

negative: Disorders of the Gastrointestinal System

negative: The sialic acid binding activity of the S protein facilitates infection by porcine transmissible gastroenteritis coronavirus BACKGROUND: Transmissible gastroenteritis virus (TGEV) has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity. METHODS: The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min. Prior to infection, cultured cells were either treated with neuraminidase to deplete sialic acids from the cell surface, or mock-treated. In a second approach, pre-treatment of the virus with porcine intestinal mucin was performed, followed by the plaque assay after a 5 min adsorption time. A student's t-test was used to verify the significance of the results. RESULTS: Desialylation of cells only had a minor effect on the infection by TGEV strain Purdue 46 when an adsorption period of 60 min was allowed for initiation of infection. However, when the adsorption time was reduced to 5 min the infectivity on desialylated cells decreased by more than 60%. A TGEV PUR46 mutant (HAD3) deficient in sialic acid binding showed a 77% lower titer than the parental virus after a 5 min adsorption time. After an adsorption time of 60 min the titer of HAD3 was 58% lower than that of TGEV PUR46. Another TGEV strain, TGEV Miller, and IBV Beaudette showed a reduction in infectivity after neuraminidase treatment of the cultured cells irrespective of the virion adsorption time. CONCLUSIONS: Our results suggest that the sialic acid binding activity facilitates the infection by TGEV under unfavorable environmental conditions. The dependence on the sialic acid binding activity for an efficient infection differs in the analyzed TGEV strains.

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: Reactive Polymer Targeting dsRNA as Universal Virus Detection Platform with Enhanced Sensitivity Reactive poly(pentafluorophenyl acrylate) (PPFPA)-grafted surfaces offer a versatile platform to immobilize biomolecules. Here, we utilize PPFPA-grafted surface and double-stranded RNA (dsRNA) recognizing J2 antibody to construct a universal virus detection platform with enhanced sensitivity. PPFPA on silicon substrates is prepared, and surface hydrophilicity is modulated by partial substitution of the pentafluorophenyl units with poly(ethylene glycol). Following dsRNA antibody immobilization, the prepared surfaces can distinguish long dsRNAs from single-stranded RNAs of the same length and short dsRNAs. As long dsRNAs are common byproducts of viral transcription/replication, these surfaces can detect the presence of different kinds of viruses without prior knowledge of their genomic sequences. To increase dsRNA detection sensitivity, a two-step method is devised where the captured dsRNAs are visualized with multiple fluorophore-tagged J2 antibodies. We show that the developed platform can differentiate foreign long dsRNAs from cellular dsRNAs and other biomolecules present in the cell lysate. Moreover, when tested against cells infected with hepatitis A or C viruses, both viruses are successfully detected using a single platform. Our study shows that the developed PPFPA platform immobilized with J2 antibody can serve as a primary diagnostic tool to determine the infection status for a wide range of viruses.

negative: Culturing the unculturable: human coronavirus HKU1 infects, replicates, and produces progeny virions in human ciliated airway epithelial cell cultures. Culturing newly identified human lung pathogens from clinical sample isolates can represent a daunting task, with problems ranging from low levels of pathogens to the presence of growth suppressive factors in the specimens, compounded by the lack of a suitable tissue culture system. However, it is critical to develop suitable in vitro platforms to isolate and characterize the replication kinetics and pathogenesis of recently identified human pathogens. HCoV-HKU1, a human coronavirus identified in a clinical sample from a patient with severe pneumonia, has been a major challenge for successful propagation on all immortalized cells tested to date. To determine if HCoV-HKU1 could replicate in in vitro models of human ciliated airway epithelial cell cultures (HAE) that recapitulate the morphology, biochemistry, and physiology of the human airway epithelium, the apical surfaces of HAE were inoculated with a clinical sample of HCoV-HKU1 (Cean1 strain). High virus yields were found for several days postinoculation and electron micrograph, Northern blot, and immunofluorescence data confirmed that HCoV-HKU1 replicated efficiently within ciliated cells, demonstrating that this cell type is infected by all human coronaviruses identified to date. Antiserum directed against human leukocyte antigen C (HLA-C) failed to attenuate HCoV-HKU1 infection and replication in HAE, suggesting that HLA-C is not required for HCoV-HKU1 infection of the human ciliated airway epithelium. We propose that the HAE model provides a ready platform for molecular studies and characterization of HCoV-HKU1 and in general serves as a robust technology for the recovery, amplification, adaptation, and characterization of novel coronaviruses and other respiratory viruses from clinical material.

negative: 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.

negative: Pulmonary embolism in COVID-19. When nothing is what it seems

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: The COVID-19 pandemic: a live class on medical professionalism

negative: 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.

negative: Comparing Metapopulation Dynamics of Infectious Diseases under Different Models of Human Movement Newly available data sets present an exciting opportunity to investigate how human population movement contributes to the spread of infectious diseases across large geographical distances. It is now possible to construct realistic models of infectious disease dynamics for the purposes of understanding global-scale epidemics. Nevertheless, a remaining unanswered question is how best to leverage the new data to parameterize models of movement, and whether one's choice of movement model impacts modeled disease outcomes. We adapt three well-studied models of infectious disease dynamics, the SIR model; the SIS model; and the Ross-Macdonald model, to incorporate either of two candidate movement models. We describe the effect that the choice of movement model has on each disease model's results, finding that in all cases there are parameter regimes where choosing one movement model instead of another has a profound impact on epidemiological outcomes. We further demonstrate the importance of choosing an appropriate movement model using the applied case of malaria transmission and importation on Bioko Island, Equatorial Guinea, finding that one model produces intelligible predictions of R0 while the other produces nonsensical results.

negative: A view from the common cold unit Abstract I have been asked to stand back and describe in broad terms the view I have had of common colds — probably the most frequent of acute human diseases and a long-lasting scientific problem — and in particular our recent work on antivirals. I should be able to do this for two reasons. Like everyone else I have suffered from colds, but in addition I have been studying the problem from the virological and clinical point of view for over 35 years — for the last 31 at the Common Cold Unit, Salisbury. As a result I may have problems with perspective — it is not possible to give a personal view and at the same time to describe something from every possible angle, and quite impossible to be comprehensive, but I have done my best and readers will make their own judgements and corrections.

negative: A Rare Case of Human Coronavirus 229E Associated with Acute Respiratory Distress Syndrome in a Healthy Adult Human coronavirus 229E (HCoV-229E) is one of the first coronavirus strains being described. It is linked to common cold symptoms in healthy adults. Younger children and the elderly are considered vulnerable to developing lower respiratory tract infections (LRTIs). In particular, immunocompromised patients have been reported with severe and life-threatening LRTIs attributed to HCoV-229E. We report for the first time a case of LRTI and acute respiratory distress syndrome developed in a healthy adult with no comorbidities and HCoV-229E strain identified as the only causative agent. A 45-year-old female with a clear medical history presented with fever, cough, and headache. Respiratory tract infection was diagnosed, and empirical antibiotics were started. Within two days, she developed bilateral pleural effusions, diffuse consolidations, and ground glass opacities involving all lung fields. She needed immediate oxygen supply, while ABGs deteriorated and chest imaging and PaO(2)/FiO(2) indicated ARDS. Early administration of systemic corticosteroids led to gradual clinical improvement. Multiplex PCR from nasal secretions was positive only for HCoV-229E and negative for multiple other pathogens. It remains to be elucidated how an immunocompetent adult developed a life-threatening LRTI caused by a “benign considered” coronavirus strain, the HCoV-229E.

negative: Are identity badges and lanyards in pediatrics potentially contaminated with viral pathogens? Identity (ID) badges and lanyards worn by pediatric health care workers (HCWs) have been shown to be potential vectors of nosocomial bacterial infections. This cross-sectional study determined the contamination of ID badges and lanyards worn by pediatric HCWs with common respiratory and gastrointestinal viruses. The results showed that ID badges and lanyards are not significantly contaminated with common respiratory or gastrointestinal viruses and are unlikely to be a significant vector for nosocomial infection.

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: Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development. METHOD: Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded. RESULTS: Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development (P = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment. CONCLUSIONS: This study suggests that VRTI during the first year after lung transplantation is associated with long-term CLAD development and that coronavirus infections in particular might be a risk factor.

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: 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.

negative: Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens BACKGROUND: Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues. METHODS: We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search. RESULTS: Based on parameter estimates from the literature the reproductive number ([Formula: see text] ) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, [Formula: see text] for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding. CONCLUSIONS: Fomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower [Formula: see text] for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious ([Formula: see text] ) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3425-x) contains supplementary material, which is available to authorized users.

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: 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.

negative: Purpose by design or disaster: Preserving a sense of purpose amid environmental uncertainty Abstract Psychological research suggests a sense of purpose in life is a coveted asset, with well-established linkages to well-being and healthy functioning. But how do individuals preserve this sense when previously reliable settings – and the opportunities they afford – are profoundly disrupted? The current moment provides a formidable test of this question, as widespread transmission of Covid-19 and intense efforts to slow it drastically transform our environment. Here, we consider how the experience of purpose may be impacted by disruptions in three key person-environment interactions: how we engage with work, how we engage in education, and how we manage physical proximity. We hope to motivate critical thinking about how this pandemic, and our collective responses to it, influence the experience of purpose and delineate a research agenda that may inform how individuals’ can preserve a sense of engagement and contribution.

negative: Characteristics of COVID-19 infection in Beijing Abstract Background Since the first case of a novel coronavirus (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Beijing. We analyzed the data of 262 confirmed cases to determine the clinical and epidemiological characteristics of COVID-19 in Beijing. Methods We collected patients who were transferred by Beijing Emergency Medical Service to the designated hospitals. The information on demographic, epidemiological, clinical, laboratory test for the COVID-19 virus, diagnostic classification, cluster case and outcome were obtained. Furthermore we compared the characteristics between severe and common confirmed cases which including mild cases, no-pneumonia cases and asymptomatic cases, and we also compared the features between COVID-19 and 2003 SARS. Findings By Feb 10, 2020, 262 patients were transferred from the hospitals across Beijing to the designated hospitals for special treatment of the COVID-19 infected by Beijing emergency medical service. Among of 262 patients, 46 (17.6%) were severe cases, 216 (82.4%) were common cases, which including 192 (73.3%) mild cases, 11(4.2%) non-pneumonia cases and 13 (5.0%) asymptomatic cases respectively. The median age of patients was 47.5 years old and 48.5% were male. 192 (73.3%) patients were residents of Beijing, 50 (26.0%) of which had been to Wuhan, 116 (60.4%) had close contact with confirmed cases, 21 (10.9%) had no contact history. The most common symptoms at the onset of illness were fever (82.1%), cough (45.8%), fatigue (26.3%), dyspnea (6.9%) and headache (6.5%). The median incubation period was 6.7 days, the interval time from between illness onset and seeing a doctor was 4.5 days. As of Feb 10, 17.2% patients have discharged and 81.7% patients remain in hospital in our study, the fatality of COVID-19 infection in Beijing was 0.9%. Interpretation On the basis of this study, we provided the ratio of the COVID-19 infection on the severe cases to the mild, asymptomatic and non-pneumonia cases in Beijing. Population was generally susceptible, and with a relatively low fatality rate. The measures to prevent transmission was very successful at early stage, the next steps on the COVID-19 infection should be focused on early isolation of patients and quarantine for close contacts in families and communities in Beijing. Funding Beijing Municipal Science and Technology Commission and Ministry of Science and Technology.

negative: 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.

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: 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.

negative: Human and Animal Viruses in Food (Including Taxonomy of Enteric Viruses) In recent years, there has been an increase in the incidence of foodborne diseases worldwide, with viruses now being recognized as a major cause of these illnesses. The most common viruses implicated in foodborne disease are enteric viruses, which are found in the human gastrointestinal tract, excreted in human feces and transmitted by the fecal-oral route. Many different viruses are found in the gastrointestinal tract but not all are recognized as foodborne pathogens. The diseases caused by enteric viruses fall into three main types: gastroenteritis, enterically transmitted hepatitis, and illnesses that can affect other parts of the body such as the eye, the respiratory system and the central nervous system leading to conjunctivitis, poliomyelitis, meningitis and encephalitis. Viral pathogens excreted in human feces include noroviruses, sapoviruses, enteroviruses, adenoviruses, hepatitis A virus (HAV), hepatitis E virus (HEV), rotaviruses, and astroviruses. Most of these viruses have been associated with foodborne disease outbreaks. Noroviruses and HAV are commonly identified as foodborne causes of gastroenteritis and acute hepatitis, respectively.

negative: Structure of alphacoronavirus transmissible gastroenteritis virus nsp1 has implications for coronavirus nsp1 function and evolution. Coronavirus nsp1 has been shown to induce suppression of host gene expression and to interfere with the host immune response. However, the mechanism is currently unknown. The only available structural information on coronavirus nsp1 is the nuclear magnetic resonance (NMR) structure of the N-terminal domain of nsp1 from severe acute respiratory syndrome coronavirus (SARS-CoV) from the betacoronavirus genus. Here we present the first nsp1 structure from an alphacoronavirus, transmissible gastroenteritis virus (TGEV) nsp1. It displays a six-stranded β-barrel fold with a long alpha helix on the rim of the barrel, a fold shared with SARS-CoV nsp1(13-128). Contrary to previous speculation, the TGEV nsp1 structure suggests that coronavirus nsp1s have a common origin, despite the lack of sequence homology. However, comparisons of surface electrostatics, shape, and amino acid conservation between the alpha- and betacoronaviruses lead us to speculate that the mechanism for nsp1-induced suppression of host gene expression might be different in these two genera.

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: Guidance for otolaryngology health care workers performing aerosol generating medical procedures during the COVID-19 pandemic BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for Coronavirus disease 2019 (COVID-19) has a predilection for infecting the mucosa of the upper and lower airways. Otolaryngologists and supporting health care workers (HCWs) are particularly at high risk of becoming infected while treating patients as many in-office procedures and surgeries are Aerosol Generating Medical Procedures (AGMP). Based on a review of the literature and various guidelines, recommendations are made to mitigate the risk to health care workers of becoming infected with SARS-CoV-2 while providing clinical care. RECOMMENDATIONS: During the COVID-19 pandemic all elective and non-time sensitive Otolaryngology procedures should be deferred to mitigate the risk of transmission of infection to HCWs. For non-AGMPs in all patients, even COVID-19 positive patients Level 1 PPE (surgical mask, gown, gloves and face shield or goggles) is sufficient. If local prevalence is favourable and patients are asymptomatic and test negative for SARS-CoV-2, Level 1 PPE can be used during short duration AGMPs, with limited risk of infected aerosol spread. For AGMPs in patients who test positive for SARS-CoV-2 a minimum of Level 2 PPE, with adequate protection of mucosal surfaces, is recommended (N95/FFP2 respirator, gown, double gloves, goggles or face shield and head cover). For long duration AGMPs that are deemed high-risk in COVID-19 positive patients, Level 3 PPE can provide a higher level of protection and be more comfortable during long duration surgeries if surgical hoods or PAPRs are used. It is recommended that these procedures are performed in negative pressure rooms, if available. It is essential to follow strict donning and doffing protocols to minimize the risk of contamination. CONCLUSIONS: By following strict infection prevention recommendations, the risk of HCWs becoming infected with SARS-CoV-2 while treating patients can be minimized. As the COVID-19 pandemic evolves rapidly, these recommendations should serve as guidance and need to be interpreted based on local factors and availability of healthcare resources.

negative: First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. METHODS: Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. FINDINGS: Patient 1—a woman in her 60s—returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. INTERPRETATION: Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected. FUNDING: None.

negative: What infection control measures will people carry out to reduce transmission of pandemic influenza? A focus group study BACKGROUND: Pandemic influenza poses a future health threat against which infection control behaviours may be an important defence. However, there is little qualitative research examining perceptions of infection control measures in the context of pandemic influenza. METHODS: Eight focus groups and one interview were conducted with a purposive sample of 31 participants. Participants were invited to discuss their perceptions of infection transmission and likely adherence to infection control measures in both non-pandemic and pandemic contexts. Infection control measures discussed included handwashing, social distancing and cough hygiene (e.g. covering mouth, disposing of tissues immediately etc.). RESULTS: Thematic analysis revealed that although participants were knowledgeable about infection transmission, most expressed unfavourable attitudes toward control behaviours in non-pandemic situations. However, with the provision of adequate education about control measures and appropriate practical support (e.g. memory aids, access to facilities), most individuals report that they are likely to adhere to infection control protocols in the event of a pandemic. Of the behaviours likely to influence infection transmission, handwashing was regarded by our participants as more feasible than cough and sneeze hygiene and more acceptable than social distancing. CONCLUSION: Handwashing could prove a useful target for health promotion, but interventions to promote infection control may need to address a number of factors identified within this study as potential barriers to carrying out infection control behaviours.

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: Household Secondary Attack Rate of COVID-19 and Associated Determinants BACKGROUND: As of April 2, 2020, the global reported number of COVID-19 cases has crossed over 1 million with more than 55,000 deaths. The household transmissibility of SARS-CoV-2, the causative pathogen, remains elusive. METHODS: Based on a comprehensive contact-tracing dataset from Guangzhou, we estimated both the population-level effective reproductive number and individual-level secondary attack rate (SAR) in the household setting. We assessed age effects on transmissibility and the infectivity of COVID-19 cases during their incubation period. RESULTS: A total of 195 unrelated clusters with 212 primary cases, 137 nonprimary (secondary or tertiary) cases and 1938 uninfected close contacts were traced. We estimated the household SAR to be 13.8% (95% CI: 11.1–17.0%) if household contacts are defined as all close relatives and 19.3% (95% CI: 15.5–23.9%) if household contacts only include those at the same residential address as the cases, assuming a mean incubation period of 4 days and a maximum infectious period of 13 days. The odds of infection among children (<20 years old) was only 0.26 (95% CI: 0.13–0.54) times of that among the elderly (≥60 years old). There was no gender difference in the risk of infection. COVID-19 cases were at least as infectious during their incubation period as during their illness. On average, a COVID-19 case infected 0.48 (95% CI: 0.39–0.58) close contacts. Had isolation not been implemented, this number increases to 0.62 (95% CI: 0.51–0.75). The effective reproductive number in Guangzhou dropped from above 1 to below 0.5 in about 1 week. CONCLUSION: SARS-CoV-2 is more transmissible in households than SARS-CoV and MERS-CoV, and the elderly ≥60 years old are the most vulnerable to household transmission. Case finding and isolation alone may be inadequate to contain the pandemic and need to be used in conjunction with heightened restriction of human movement as implemented in Guangzhou.

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: Persistent viral RNA shedding after COVID‐19 symptom resolution in older convalescent plasma donors INTRODUCTION: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is responsible for a worldwide pandemic. While the medical community understands the mode of viral transmission, less is known about how long viral shedding occurs once viral symptoms have resolved. Our objective was to determine how long the SARS‐CoV‐2 remains detectable following self‐reporting of viral symptom resolution. METHODS: This study was approved by the University of Wisconsin Institutional Review Board. A cohort of patients who were previously SARS‐CoV‐2 positive less than 28 days after self‐reported symptom resolution were retested for proof of viral recovery by nasal swab reverse transcriptase polymerase chain reaction for SARS‐CoV‐2 RNA. RESULTS: A total of 152 potential participants were screened, of which 5 declined, 54 were ineligible, and 93 were recruited; 86 of 93 completed testing. Eleven of 86 (13%) were still positive at a median of 19 days (range, 12‐24 days) after symptom resolution. Positive participants were significantly older than negative participants (mean, 54 years; 95% confidence interval [CI], 44‐63 vs 42 years; 95% CI, 38‐46; P = .024). C (T) values were significantly, inversely associated with age (β = −.04; r (2) = 0.389; P = .04). The number of days since symptom recovery was not apparently different between positive and negative participants. CONCLUSION: We found evidence of persistent viral shedding in nasopharyngeal secretions more than 2 weeks after resolution of symptoms from confirmed COVID‐19 infection. Persistent shedding was more common in older participants, and viral load was higher among older positive participants. These results underscore the necessity of testing COVID‐19 convalescent plasma donors less than 28 days after symptom resolution.

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: 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: Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

negative: Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division. The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001), indicating that nucleolar localization of the N protein is a common feature of the coronavirus family and is possibly of functional significance. Nucleolar localization signals were identified in the domain III region of the N protein from all three coronavirus groups, and this suggested that transport of N protein to the nucleus might be an active process. In addition, our results suggest that the N protein might function to disrupt cell division. Thus, we observed that approximately 30% of cells transfected with the N protein appeared to be undergoing cell division. The most likely explanation for this is that the N protein induced a cell cycle delay or arrest, most likely in the G(2)/M phase. In a fraction of transfected cells expressing coronavirus N proteins, we observed multinucleate cells and dividing cells with nucleoli (which are only present during interphase). These findings are consistent with the possible inhibition of cytokinesis in these cells.

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: Asymptomatic COVID-19 Patients Can Contaminate Their Surroundings: an Environment Sampling Study The contamination of patients’ surroundings by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains understudied. We sampled the surroundings and the air of six negative-pressure non-intensive care unit (non-ICU) rooms in a designated isolation ward in Chengdu, China, that were occupied by 13 laboratory-confirmed coronavirus disease 2019 (COVID-19) patients who had returned from overseas travel, including 2 asymptomatic patients. A total of 44 of 112 (39.3%) surface samples were positive for SARS-CoV-2 as detected by real-time PCR, suggesting extensive contamination, although all of the air samples were negative. In particular, in a single room occupied by an asymptomatic patient, four sites were SARS-CoV-2 positive, highlighting that asymptomatic COVID-19 patients do contaminate their surroundings and impose risks for others with close contact. Placement of COVID-19 patients in rooms with negative pressure may bring a false feeling of safety, and the importance of rigorous environment cleaning should be emphasized. IMPORTANCE Although it has been well recognized that the virus SARS-CoV-2, the causative agent of COVID-19, can be acquired by exposure to fomites, surprisingly, the contamination of patients’ surroundings by SARS-CoV-2 is largely unknown, as there have been few studies. We performed an environmental sampling study for 13 laboratory-confirmed COVID-19 patients and found extensive contamination of patients’ surroundings. In particular, we found that asymptomatic COVID-19 patients contaminated their surroundings and therefore imposed risks for other people. Environment cleaning should be emphasized in negative-pressure rooms. The findings may be useful to guide infection control practice to protect health care workers.

negative: COVID-19 pneumonia manifestations at the admission on chest ultrasound, radiographs, and CT: single-center study and comprehensive radiologic literature review PURPOSE: To investigate the imaging features of emerging COVID-19 pneumonia on chest ultrasound (US), radiographs (CXR) and computed tomography (CT) examinations performed at admission and to provide a comprehensive radiological literature review on ongoing radiological data from recent publications. MATERIALS AND METHODS: In this retrospective single-center study, we enrolled consecutive patients from February 15, 2020, to March 15, 2020, with laboratory-confirmed SARS-CoV-2 hospitalized in Valduce Hospital (Como, Italy). Multi-modality imaging findings were evaluated and compared. Literature research was conducted through a methodical search on Pubmed and Embase databases. RESULTS: Fifty-eight patients (36 men, 22 women; age range, 18–98 years) were included in the study. Among these, chest US, CXR, and CT were performed respectively in twenty-two, thirty-two and forty-two patients. Lung US findings were consistent with diffuse B lines (100%) and subpleural consolidations (27.3%). CXR showed prevalent manifestations of consolidations (46.9%) and hazy increased opacities (37.5%). Typical CT features included bilateral and multilobar ground-glass opacities (GGO) with (59.5%) and without (35.7%) consolidations having a predominantly peripheral distribution (64.3%). Other imaging features included crazy paving pattern (57.1%), fibrous stripes (50%), subpleural lines (35.7%), architectural distortion (28.6%), air bronchogram sign (26.2%), vascular thickening (23.8%) and nodules (2.4%). Also, enlarged lymph nodes (14.3 %) and pleural effusion (7.1%) were observed. The literature review identified twenty-six original studies supporting our imaging chest findings. CONCLUSION: The spectrum of chest imaging manifestations of COVID-19 pneumonia upon admission includes B-lines and consolidations on US, consolidations and hazy increased opacities on CXR, and multifocal GGO with consolidations on CT.

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: Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.

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: Symptoms and immunoglobulin development in hospital staff exposed to a SARS-CoV-2 outbreak. BACKGROUND Worldwide, the number of SARS-CoV-2 infections is increasing. Serological immunoglobulin tests may help to better understand the development of immune mechanisms against SARS-CoV-2 in COVID-19 cases and exposed but asymptomatic individuals. The aim of this study was to investigate exposure to SARS-CoV-2, symptoms and antibody responses in a large sample of health care workers following a COVID-19 outbreak. METHODS A COVID-19 outbreak among staff members of a major German children's and women's hospital was followed by massive RT-PCR SARS-CoV-2 tests and provided the opportunity to study symptoms, chains of infection and SARS-CoV-2 specific antibody responses (IgG and IgA) by ELISA. Study participants were classified as COVID-19 cases, and persons with close, moderate or no exposure to SARS-CoV-2 in the clinical setting, respectively. RESULTS Out of 201 study participants, 31 were COVID-19 cases. While most study participants experienced many symptoms indicative for SARS-CoV-2 infection, anosmia and coughing were remarkably more frequent in COVID-19 cases. Approximately 80% of COVID-19 cases developed some specific antibody response (IgA and IgG) approximately 3 weeks after onset of symptoms. Subjects in the non COVID-19 groups had also elevated IgG (1.8%) and IgA values (7.6%) irrespective of contact history with cases. CONCLUSION We found that a significant number of diseased did not develop relevant antibody responses three weeks after symptom onset. Our data also suggests that exposure to COVID-19 positive co-workers in a hospital setting is not leading to the development of measurable immune responses in a significant proportion of asymptomatic contact-persons.

negative: Cell entry mechanisms of SARS-CoV-2 A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Here we investigated receptor binding and protease activation of SARS-CoV-2 spike using biochemical and pseudovirus entry assays. Our findings have identified key cell entry mechanisms of SARS-CoV-2. First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. Third, unlike SARS-CoV, cell entry of SARS-CoV-2 is preactivated by proprotein convertase furin, reducing its dependence on target cell proteases for entry. The high hACE2 binding affinity of the RBD, furin preactivation of the spike, and hidden RBD in the spike potentially allow SARS-CoV-2 to maintain efficient cell entry while evading immune surveillance. These features may contribute to the wide spread of the virus. Successful intervention strategies must target both the potency of SARS-CoV-2 and its evasiveness.

negative: Review of Hygiene and Disinfection Recommendations for Outpatient Glaucoma Care: A COVID Era Update This review focuses on best practices and recommendations for hygiene and disinfection to limit exposure and transmission of infection in outpatient glaucoma clinics during the current COVID-19 pandemic.

negative: Infectious disease transmission: survey of contacts between hospital-based healthcare workers and working adults from the general population Summary Background Healthcare workers (HCWs) may be the inadvertent interface between the healthcare setting and the community for infectious diseases transmission. Aim To investigate HCWs' contacts during a work day and compare these against working adults from the general population. Methods Prospective survey of contacts through 24 h self-reported diary in three public sector tertiary care hospitals and community-based working adults in Singapore. Participants were HCWs and working adults from the community. Findings In all, 211 HCWs and 1028 working adults reported a total of 4066 and 9206 contacts. HCWs reported more work-related contacts than community-based working adults (median of 13 versus 4), and more contacts that were neither household nor work-related (1 versus 0) but fewer household contacts (2 versus 3). HCWs reported more work-related contacts involving physical contacts, and more new contacts particularly with short duration (≤15 min) compared to community-based working adults. Among different HCW types, doctors reported the highest whereas ward-based nurses reported the lowest total work-related contacts. Around half of ward-based and clinic-based nurses' contacts involved physical touch. Work-related contacts reported by clinic-based nurses, doctors, and assorted HCWs were shorter than in ward-based nurses, with a substantial number effectively occurring with new contacts. Institutional effects significant on univariate analyses were much reduced and non-significant after adjusting for confounding by HCW type. Conclusion HCWs' contacts differ substantially from those of community-based working adults. HCWs may thus be at higher risk of acquiring and spreading contact-transmissible and respiratory infections due to the nature of their work. Whereas total number of contacts was fairly similar between HCW types, the characteristics of their contacts differed substantively.

negative: Severe human infection with a novel avian-origin influenza A(H7N4) virus Abstract Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient. We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient’s backyard, neighborhood, local live poultry markets (LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry (chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.

negative: The great balancing act: regulation and fate of antiviral T-cell interactions The fate of T lymphocytes revolves around a continuous stream of interactions between the T-cell receptor (TCR) and peptide-major histocompatibility complex (MHC) molecules. Beginning in the thymus and continuing into the periphery, these interactions, refined by accessory molecules, direct the expansion, differentiation, and function of T-cell subsets. The cellular context of T-cell engagement with antigen-presenting cells, either in lymphoid or nonlymphoid tissues, plays an important role in determining how these cells respond to antigen encounters. CD8(+) T cells are essential for clearance of a lymphocytic choriomeningitis virus (LCMV) infection, but the virus can present a number of unique challenges that antiviral T cells must overcome. Peripheral LCMV infection can lead to rapid cytolytic clearance or chronic viral persistence; central nervous system infection can result in T-cell-dependent fatal meningitis or an asymptomatic carrier state amenable to immunotherapeutic clearance. These diverse outcomes all depend upon interactions that require TCR engagement of cognate peptide-MHC complexes. In this review, we explore the diversity in antiviral T-cell behaviors resulting from TCR engagement, beginning with an overview of the immunological synapse and progressing to regulators of TCR signaling that shape the delicate balance between immunopathology and viral clearance.

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: 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.

negative: Long period dynamics of viral load and antibodies for SARS-CoV-2 infection: an observational cohort study ABSTRACT OBJECTIVE To investigate the dynamics of viral RNA, IgM, and IgG and their relationships in patients with SARS-CoV-2 pneumonia over an 8-week period. DESIGN Retrospective, observational case series. SETTING Wenzhou Sixth Peoples Hospital PARTICIPANTS Thirty-three patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to hospital. Data were collected from January 27 to April 10, 2020. MAIN OUTCOME MEASURES Throat swabs, sputum, stool, and blood samples were collected, and viral load was measured by reverse transcription PCR (RT-PCR). Specific IgM and IgG against spike protein (S), spike protein receptor binding domain (RBD), and nucleocapsid (N) were analyzed. RESULTS At the early stages of symptom onset, SARS-CoV-2 viral load is higher in throat swabs and sputum, but lower in stool. The median (IQR) time of undetectable viral RNA in throat swab, sputum, and stool was 18.5 (13.25-22) days, 22 (18.5-27.5) days, and 17 (11.5-32) days, respectively. In sputum, 17 patients (51.5%) had undetectable viral RNA within 22 days (short persistence), and 16 (48.5%) had persistent viral RNA more than 22 days (long persistence). Three patients (9.1%) had a detectable relapse of viral RNA in sputum within two weeks of their discharge from the hospital. One patient had persistent viral RNA for 59 days or longer. The median (IQR) seroconversion time of anti-S IgM, anti-RBD IgM, and anti-N IgM was 10.5 (7.75-15.5) days, 14 (9-24) days, and 10 (7-14) days, respectively. The median (IQR) seroconversion time of anti-S IgG, anti-RBD IgG, and anti-N IgG was 10 (7.25-16.5) days, 13 (9-17) days, and 10 (7-14) days, respectively. By week 8 after symptom onset, IgM were negative in many of the previously positive patients, and IgG levels remained less than 50% of the peak levels in more than 20% of the patients. In about 40% of the patients, anti-RBD IgG levels were 4-times higher in convalescence than in acute phase. SARS-CoV-2 RNA coexisted with antibodies for more than 50 days. Anti-RBD IgM and IgG levels, including anti-RBD IgM levels at presentation and peak time, were significantly higher in viral RNA short persistence patients than in long persistence patients. CONCLUSION This study adds important new information about the features of viral load and antibody dynamics of SARS-CoV-2. It is clear from these results that the viral RNA persists in sputum and stool specimens for a relatively long time in many patients. Anti-RBD may also serve as a potential protective antibody against SARS-CoV-2 infection, as viral persistence appears to be related to anti-RBD levels. Earlier treatment intervention also appears to be a factor in viral persistence.

negative: Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells BACKGROUND AND OBJECTIVE: Coronavirus disease (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the incessant spread of the disease with substantial morbidity and mortality rates, there is an urgent demand for effective therapeutics and vaccines to control and diminish this pandemic. A critical step in the crosstalk between the virus and the host cell is the binding of SARS-CoV-2 spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of the host cells. Hence, inhibition of this interaction could be a promising strategy to combat the SARS-CoV-2 infection. METHODS: Docking and Molecular Dynamics (MD) simulation studies revealed that designed peptide maintains their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. RESULTS: We have designed a novel peptide that could inhibit SARS-CoV-2 spike protein interaction with ACE2, thereby blocking the cellular entry of the virus. CONCLUSION: Our findings suggest that computationally developed inhibitory peptide may be developed as an anti-SARS-CoV-2 agent for the treatment of SARS-CoV-2 infection. We further plan to pursue the peptide in cell-based assays and eventually for clinical trials.

negative: Hand Hygiene: A Frequently Missed Lifesaving Opportunity During Patient Care Health care-associated infections constitute one of the greatest challenges of modern medicine. Despite compelling evidence that proper hand washing can reduce the transmission of pathogens to patients and the spread of antimicrobial resistance, the adherence of health care workers to recommended hand-hygiene practices has remained unacceptably low. One of the key elements in improving hand-hygiene practice is the use of an alcohol-based hand rub instead of washing with soap and water. An alcohol-based hand rub requires less time, is microbiologically more effective, and is less irritating to skin than traditional hand washing with soap and water. Therefore, alcohol-based hand rubs should replace hand washing as the standard for hand hygiene in health care settings in all situations in which the hands are not visibly soiled. It is also important to change gloves between each patient contact and to use hand-hygiene procedures after glove removal. Reducing health care-associated infections requires that health care workers take responsibility for ensuring that hand hygiene becomes an everyday part of patient care.

negative: Aberrant Expression of Syndecan-1 in Cervical Cancers. Syndecan-1, is a transmembrane heparan/chondroitin sulfate proteoglycan necessary for cell-cell and cell-matrix interactions. Its decreased level on the cell surface correlates with poor prognosis in several tumor types. Aberrant stromal localization of syndecan-1 is also considered an unfavorable prognostic factor in various human malignancies. In the presented work the question was addressed if changes in syndecan-1 expression are related to the prognosis of cervical cancer. Immunohistochemistry for syndecan-1 extracellular domain was performed on surgical specimens of primary cervical cancer. To follow the communication between tumor cells and stromal fibroblasts, their mono-and co-cultures were studied, detecting the expression of syndecan-1, smooth muscle actin, vimentin, and desmin. Immunohistochemistry of tumorous specimens revealed that while cell surface syndecan-1 expression was reduced on cancer cells, it appeared on the surface of tumor-associated fibroblasts. Until year 7, the cohort with high cell surface syndecan-1 expression had significantly longer survival. No difference in the same time-period could be detected when stromal syndecan-1 expression was analyzed. In vitro analysis revealed, that tumor cells can induce syndecan-1 expression on fibroblast, and fibroblasts showed that fibroblast-like cells are built by two cell types: (a) syndecan-1 positive, cytokeratin negative real fibroblasts, and (b) syndecan-1 and cytokeratin positive epithelial-mesenchymal transformed tumor cells. Syndecan-1 on the surface of cancer cells appears to be a positive prognostic marker. Although syndecan-1 positive fibroblasts promote tumor cell proliferation in vitro, we failed to detect their cancer promoting effect in vivo.

negative: Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by the SARS-coronavirus (SARS-CoV). SARS-CoV entry is facilitated by the spike protein (S), which consists of an N-terminal domain (S1) responsible for cellular attachment and a C-terminal domain (S2) that mediates viral and host cell membrane fusion. The SARS-CoV S2 is a potential drug target, as peptidomimetics against S2 act as potent fusion inhibitors. In this study, site-directed mutagenesis and thermal stability experiments on electrostatic, hydrophobic, and polar residues to dissect their roles in stabilizing the S2 postfusion conformation was performed. It was shown that unlike the pH-independent retroviral fusion proteins, SARS-CoV S2 is stable over a wide pH range, supporting its ability to fuse at both the plasma membrane and endosome. A comprehensive SARS-CoV S2 analysis showed that specific hydrophobic positions at the C-terminal end of the HR2, rather than electrostatics are critical for fusion protein stabilization. Disruption of the conserved C-terminal hydrophobic residues destabilized the fusion core and reduced the melting temperature by 30°C. The importance of the C-terminal hydrophobic residues led us to identify a 42-residue substructure on the central core that is structurally conserved in all existing CoV S2 fusion proteins (root mean squared deviation = 0.4 Å). This is the first study to identify such a conserved substructure and likely represents a common foundation to facilitate viral fusion. We have discussed the role of key residues in the design of fusion inhibitors and the potential of the substructure as a general target for the development of novel therapeutics against CoV infections.

negative: COVID-19: How can a department of general surgery survive in a pandemic?

negative: Assessment of the Antiviral Properties of Zeolites Containing Metal Ions The antiviral properties of zeolite (sodium aluminosilicate) powders amended with metal ions were assessed using human coronavirus 229E, feline infectious peritonitis virus (FIPV), and feline calicivirus F-9. Zeolites containing silver and silver/copper caused significant reductions of coronavirus 229E after 1 h in suspension. The silver/copper combination yielded a >5.13-log(10) reduction within 24 h. It was also the most effective (>3.18-log(10)) against FIPV after 4 h. Other formulations were ineffective against FIPV. On plastic coupons with incorporated silver/copper-zeolites, >1.7-log(10) and >3.8-log(10) reductions were achieved for coronavirus 229E and feline calicivirus within 24 h, respectively. Silver/copper zeolite reduced titers of all viruses tested, suggesting that it may be effective against related pathogens of interest [i.e., SARS coronavirus, other coronaviruses, human norovirus (calicivirus)]. Of note, it was effective against both enveloped and nonenveloped viruses. Metal-zeolites could therefore possibly be used in applications to reduce virus contamination of fomites and thus the spread of viral diseases.

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: COVID-19, an opportunity to reevaluate the correlation between long-term effects of anthropogenic pollutants on viral epidemic/pandemic events and prevalence Occupational, residential, dietary and environmental exposures to mixtures of synthetic anthropogenic chemicals after World War II have a strong relationship with the increase of chronic diseases, health cost and environmental pollution. The link between environment and immunity is particularly intriguing as it is known that chemicals and drugs can cause immunotoxicity (e.g., allergies and autoimmune diseases). In this review, we emphasize the relationship between long-term exposure to xenobiotic mixtures and immune deficiency inherent to chronic diseases and epidemics/pandemics. We also address the immunotoxicologic risk of vulnerable groups, taking into account biochemical and biophysical properties of SARS-CoV-2 and its immunopathological implications. We particularly underline the common mechanisms by which xenobiotics and SARS-CoV-2 act at the cellular and molecular level. We discuss how long-term exposure to thousand chemicals in mixtures, mostly fossil fuel derivatives, exposure toparticle matters, metals, ultraviolet (UV)–B radiation, ionizing radiation and lifestyle contribute to immunodeficiency observed in the contemporary pandemic, such as COVID-19, and thus threaten global public health, human prosperity and achievements, and global economy. Finally, we propose metrics which are needed to address the diverse health effects of anthropogenic COVID-19 crisis at present and those required to prevent similar future pandemics.

negative: Transmission of infectious diseases through breast milk and breastfeeding

negative: Major receptor-binding and neutralization determinants are located within the same domain of the transmissible gastroenteritis virus (coronavirus) spike protein. The spike glycoprotein (S) of coronavirus, the major target for virus-neutralizing antibodies, is assumed to mediate the attachment of virions to the host cell. A 26-kilodalton fragment proteolytically cleaved from transmissible gastroenteritis virus (TGEV) S protein was previously shown to bear two adjacent antigenic sites, A and B, both defined by high-titer neutralizing antibodies. Recombinant baculoviruses expressing C-terminal truncations of the 26-kilodalton region were used to localize functionally important determinants in the S protein primary structure. Two overlapping 223- and 150-amino-acid-long products with serine 506 as a common N terminus expressed all of the site A and B epitopes and induced virus-binding antibodies. Coexpression of one of these truncated protein S derivatives with aminopeptidase N (APN), a cell surface molecule acting as a receptor for TGEV, led to the formation of a complex which could be immunoprecipitated by anti-S antibodies. These data provide evidence that major neutralization-mediating and receptor-binding determinants reside together within a domain of the S protein which behaves like an independent module. In spite of their ability to prevent S-APN interaction, the neutralizing antibodies appeared to recognize a preformed complex, thus indicating that antibody- and receptor-binding determinants should be essentially distinct. Together these findings bring new insight into the molecular mechanism of TGEV neutralization.

negative: Viability of intertwined supply networks: extending the supply chain resilience angles towards survivability. A position paper motivated by COVID-19 outbreak An intertwined supply network (ISN) is an entirety of interconnected supply chains (SC) which, in their integrity secure the provision of society and markets with goods and services. The ISNs are open systems with structural dynamics since the firms may exhibit multiple behaviours by changing the buyer-supplier roles in interconnected or even competing SCs. From the positions of resilience, the ISNs as a whole provide services to society (e.g. food service, mobility service or communication service) which are required to ensure a long-term survival. The analysis of survivability at the level of ISN requires a consideration at a large scale as resilience of individual SCs. The recent example of coronavirus COVID-19 outbreak clearly shows the necessity of this new perspective. Our study introduces a new angle in SC resilience research when a resistance to extraordinary disruptions needs to be considered at the scale of viability. We elaborate on the integrity of the ISN and viability. The contribution of our position study lies in a conceptualisation of a novel decision-making environment of ISN viability. We illustrate the viability formation through a dynamic game-theoretic modelling of a biological system that resembles the ISN. We discuss some future research areas.

negative: Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes Novel SARS coronavirus (SARS-CoV-2) has caused a pandemic condition world-wide and has been declared as public health emergency of International concern by WHO in a very short span of time. The community transmission of this highly infectious virus has severely affected various parts of China, Italy, Spain and USA among others. The prophylactic solution against SARS-CoV-2 infection is challenging due to the high mutation rate of its RNA genome. Herein, we exploited a next generation vaccinology approach to construct a multi-epitope vaccine candidate against SARS-CoV-2 with high antigenicity, safety and efficacy to combat this deadly infectious agent. The whole proteome was scrutinized for the screening of highly conserved, antigenic, non-allergen and non-toxic epitopes having high population coverage that can elicit both humoral and cellular mediated immune response against COVID-19 infection. These epitopes along with four different adjuvants were utilized to construct a multi-epitope vaccine candidate that can generate strong immunological memory response having high efficacy in humans. Various physiochemical analyses revealed the formation of a stable vaccine product having a high propensity to form a protective solution against the detrimental SARS-CoV-2 strain with high efficacy. The vaccine candidate interacted with immunological receptor TLR3 with high affinity depicting the generation of innate immunity. Further, the codon optimization and in silico expression show the plausibility of the high expression and easy purification of the vaccine product. Thus, this present study provides an initial platform of the rapid generation of an efficacious protective vaccine for combating COVID-19.

negative: The Common Missed Handwashing Instances and Areas after 15 Years of Hand-Hygiene Education The outbreak of severe acute respiratory syndrome (SARS) claimed the lives of 286 Hong Kong people in 2003. Since then, the Hong Kong government has been promoting the benefits of proper hand hygiene. There are few studies that explore the general quality of handwashing and the hand-hygiene practices of the public of Hong Kong; given this, the aim of this study is to explore this neglected topic. This study is a quantitative study that was conducted in January 2018. The results show that the majority of participants only wash their hands after using the toilet (87%) or handling vomitus or faecal matter (91%). The mean duration of handwashing was 36.54 seconds (SD = 18.57). The areas of the hand most neglected during handwashing were the fingertips (48.1%), medial area (30.5%), and back of the hand (28%). A multiple logistic regression shows that participants who have reached third-level education or higher often tend to be more hand hygienic than those who have not reached third-level education (p ≤ 0.001, B = 1.003). Thus, participants aged 30 and above tend to neglect 5 more areas of the hand than those aged below 30 (p=0.001, B = 4.933).

negative: Rapid community-driven development of a SARS-CoV-2 tissue simulator The 2019 novel coronavirus, SARS-CoV-2, is an emerging pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors like diabetes. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable “choke points” for pharmacologic interactions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving rapid refinements with a two-to-four week release cycle. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health.

negative: Variational-LSTM Autoencoder to forecast the spread of coronavirus across the globe Modelling the spread of coronavirus globally while learning trends at global and country levels remains crucial for tackling the pandemic. We introduce a novel variational LSTM-Autoencoder model to predict the spread of coronavirus for each country across the globe. This deep spatio-temporal model does not only rely on historical data of the virus spread but also includes factors related to urban characteristics represented in locational and demographic data (such as population density, urban population, and fertility rate), an index that represent the governmental measures and response amid toward mitigating the outbreak (includes 13 measures such as: 1) school closing, 2) workplace closing, 3) cancelling public events, 4) close public transport, 5) public information campaigns, 6) restrictions on internal movements, 7) international travel controls, 8) fiscal measures, 9) monetary measures, 10) emergency investment in health care, 11) investment in vaccines, 12) virus testing framework, and 13) contact tracing). In addition, the introduced method learns to generate graph to adjust the spatial dependences among different countries while forecasting the spread. We trained two models for short and long-term forecasts. The first one is trained to output one step in future with three previous timestamps of all features across the globe, whereas the second model is trained to output 10 steps in future. Overall, the trained models show high validation for forecasting the spread for each country for short and long-term forecasts, which makes the introduce method a useful tool to assist decision and policymaking for the different corners of the globe.

negative: A preoperative hernia symptom score predicts inguinal hernia anatomy and outcomes after TEP repair. BACKGROUND The Carolinas comfort scale (CCS) is an ideal tool for assessing patients’ quality-of-life post hernia repair, but its use has been barely investigated preoperatively. The aim was to quantify preoperative symptoms and assess their relevance in predicting postoperative clinical outcomes following totally extraperitoneal (TEP) inguinal hernia repair. METHODS The CCS was modified for preoperative use (modified or MCCS) by omitting mesh sensation questioning. Data collection was prospective over a 16 months period. (M)CCS questionnaires were completed preoperatively and at 2 then 6 weeks post repair. Intraoperative findings were also recorded. One hundred and four consecutive patients consented for TEP repair were included using a fibrin glue mesh fixation technique. RESULTS All three questionnaires were completed by 88 patients (84.6 %). Preoperative MCCS scores did not differ with age, obesity, the presence of bilateral or recurrent inguinal herniae or hernia type. Higher MCCS grouping [OR 4.3 (95 % CI 1.5–12.6)] and the presence of bilateral herniae [OR 8.5 (1.2–61.8)] were predictors of persisting discomfort at 6 weeks, with lower scores on MCCS [OR 16.4 (3.9–67.6), obesity (OR 9.9 91.6–63.2)] and recurrent hernia repair [OR 11.4 (1.4–91.0)] predicting increased discomfort at 2 weeks versus preoperatively. MCCS scores were inversely correlated with the size of a direct defect (r −0.42, p = 0.011) but did not differ with the intraoperative finding of an incidental femoral and/or obturator hernia. Female sex was strongly associated with recognition of a synchronous incidental hernia (5 vs 57 %, p = 0.001). CONCLUSIONS Pre- and post-operative scoring of hernia specific symptoms should be considered as part of routine surgical practice, to counsel patients on their expectations of pain and discomfort post repair and to select those who might be more appropriate for a watchful waiting approach. Females with inguinal hernia warrant complete assessment of their groin hernial orifices intraoperatively due to a high rate of synchronous incidental hernia.

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: The Rapid Deployment of a 3D Printed Latticed Nasopharyngeal Swab for COVID-19 Testing Made Using Digital Light Synthesis The novel coronavirus disease (COVID-19) has caused a pandemic that has disrupted supply chains globally. This black swan event is challenging industries from all sectors of the economy including those industries directly needed to produce items that safeguard us from the disease itself, especially personal protection equipment (N95 masks, face shields) and much needed consumables associated with testing and vaccine delivery (swabs, vials and viral transfer medium). Digital manufacturing, especially 3D printing, has been promulgated as an important approach for the rapid development of new products as well as a replacement manufacturing technique for many traditional manufacturing methods, including injection molding, when supply chains are disrupted. Herein we report the use of Digital Light Synthesis (DLS) for the design and large-scale deployment of nasopharyngeal (NP) swabs for testing of coronavirus SARS-CoV-2 infections in humans. NP swabs have been one of society's essential products hardest hit by the supply chain disruptions caused by COVID-19. A latticed tip NP swab was designed and fabricated by DLS from a liquid resin previously developed and approved for use to make dental night guard devices. These latticed NP swabs demonstrated non-inferiority in a human clinical study of patients suspected of being infected with SARS-CoV-2.

negative: Forum: Technology, Ecology, and Human Health Since 1850

negative: Modeling the spread of bird flu and predicting outbreak diversity Abstract Avian influenza, commonly known as bird flu, is an epidemic caused by H5N1 virus that primarily affects birds like chickens, wild water birds, etc. On rare occasions, these can infect other species including pigs and humans. In the span of less than a year, the lethal strain of bird flu is spreading very fast across the globe mainly in South East Asia, parts of Central Asia, Africa and Europe. In order to study the patterns of spread of epidemic, we made an investigation of outbreaks of the epidemic in one week, that is from February 13–18, 2006, when the deadly virus surfaced in India. We have designed a statistical transmission model of bird flu taking into account the factors that affect the epidemic transmission such as source of infection, social and natural factors and various control measures are suggested. For modeling the general intensity coefficient f ( r ) , we have implemented the recent ideas given in the article Fitting the Bill, Nature [R. Howlett, Fitting the bill, Nature 439 (2006) 402], which describes the geographical spread of epidemics due to transportation of poultry products. Our aim is to study the spread of avian influenza, both in time and space, to gain a better understanding of transmission mechanism. Our model yields satisfactory results as evidenced by the simulations and may be used for the prediction of future situations of epidemic for longer periods. We utilize real data at these various scales and our model allows one to generalize our predictions and make better suggestions for the control of this epidemic.

negative: The effectiveness of hand hygiene procedures in reducing the risks of infections in home and community settings including handwashing and alcohol-based hand sanitizers Infectious diseases (ID) circulating in the home and community remain a significant concern. Several demographic, environmental, and health care trends, as reviewed in this report, are combining to make it likely that the threat of ID will increase in coming years. Two factors are largely responsible for this trend: first, the constantly changing nature and range of pathogens to which we are exposed and, secondly, the demographic changes occurring in the community, which affect our resistance to infection. This report reviews the evidence base related to the impact of hand hygiene in reducing transmission of ID in the home and community. The report focuses on developed countries, most particularly North America and Europe. It also evaluates the use of alcohol-based hygiene procedures as an alternative to, or in conjunction with, handwashing. The report compiles data from intervention studies and considers it alongside risk modeling approaches (both qualitative and quantitative) based on microbiologic data. The main conclusions are as follows: (1) Hand hygiene is a key component of good hygiene practice in the home and community and can produce significant benefits in terms of reducing the incidence of infection, most particularly gastrointestinal infections but also respiratory tract and skin infections. (2) Decontamination of hands can be carried out either by handwashing with soap or by use of waterless hand sanitizers, which reduce contamination on hands by removal or by killing the organisms in situ. The health impact of hand hygiene within a given community can be increased by using products and procedures, either alone or in sequence, that maximize the log reduction of both bacteria and viruses on hands. (3) The impact of hand hygiene in reducing ID risks could be increased by convincing people to apply hand hygiene procedures correctly (eg, wash their hands correctly) and at the correct time. (4) To optimize health benefits, promotion of hand hygiene should be accompanied by hygiene education and should also involve promotion of other aspects of hygiene.

negative: Declining winter survival and fitness implications associated with latitudinal distribution in Norwegian Greylag Geese Anser anser The Norwegian Greylag Goose Anser anser population has been increasing steadily over the past few decades, causing increasing nuisance in terms of agricultural crop damage. This, in combination with the importance of Greylags as a hunting target, has called for demographic estimates for the population to assist in management decisions. To this end, we analysed long‐term mark–recapture data using Cormack–Jolly‐Seber models embedded in program MARK to obtain survival estimates for the population. No sex‐specific difference, or age effect on survival after juveniles had completed their first migration (3 months of age), was evident. Mean first‐year survival was reported as 0.485 and annual survival of older birds as 0.700. On a monthly basis, survival in Greylags during summer and winter was very similar over the study period. A significant linear decline in winter survival from 0.909 to 0.807 was, however, apparent during the study period. Over the second half of the study (1994–2002), summer survival was about 3% lower than in the first half (1986–94) but no linear relationship was evident. We found a significant inverse relationship between Greylag survival during summer and latitudinal distribution in Norway. A similar relationship was evident between survival and annual bag numbers. The changes in adult survival observed in this study are likely to have had a substantial impact on the growth rate of the Norwegian Greylag population.

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: [Management and clinical thinking of Coronavirus Disease 2019] In December 2019, the 2019 novel coronavirus pneumonia (NCP, officially named Coronavirus Disease 2019(COVID-19) by the World Health Organization) broke out in Wuhan, Hubei, and it quickly spread to the whole country and abroad. The situation was at stake. The sudden and serious COVID-19 epidemic has brought us a lot of urgent problems. How to effectively control the spread of COVID-19? When does the population infection rate rise to its peak? What will eventually be the number of infected patients? How to make early diagnosis? What effective antiviral drugs are available? How to effectively treat with existing drugs? Can it successfully improve the survival rate of critically patients? In response to the above questions, we put forward corresponding suggestions and reflections from the perspective of the infectious clinician.

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: Genetic polymorphisms in mouse genes regulating age-sensitive and age-stable T cell subsets To see whether genetic polymorphisms regulate inter-individual differences in T cell subset levels, we have conducted a genome scan in two populations of mice, bred as the progeny of a cross between CB6F1 females and C3D2F1 males. The data document quantitative trait loci (QTL) with statistically significant effects on CD4, CD8, and CD8 memory T cells, and on subsets of CD4 and CD8 T cells that express P-glycoprotein. Some of the loci detected were robust, in the sense that they produced effects of similar size both in mated female mice, and in a population that included male and female virgin animals. Some of the effects were stable, in that they were apparent at both 8 and 18 months of age, but others were age-specific, showing effects either at 8 or at 18 months but not at both ages. Genes that had an effect on the same T cell subset were in almost all cases additive rather than epistatic, and their combined effects could produce large overall effects, leading in the most dramatic case to a two-fold difference in CD8 memory cells. The analysis also documented two QTL, on chromosomes 4 and 13, that regulate an age-sensitive composite index of T cell subset pattern which has been shown previously to be a predictor of life expectancy in these mice. The analysis thus reveals both subset-specific genes and others which modulate the overall pattern of age-sensitive changes in T cell subset distributions.

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: SARS-CoV-2 Vaccines: Status Report SARS-CoV-2, the causal agent of COVID-19, first emerged in late 2019 in China. It has since infected more than 870,000 individuals and caused more than 43,000 deaths globally. Here, we discuss therapeutic and prophylactic interventions for SARS-CoV-2 with a focus on vaccine development and its challenges. Vaccines are being rapidly developed but will likely come too late to affect the first wave of a potential pandemic. Nevertheless, critical lessons can be learned for the development of vaccines against rapidly emerging viruses. Importantly, SARS-CoV-2 vaccines will be essential to reducing morbidity and mortality if the virus establishes itself in the population.

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: Role of air changes per hour (ACH) in possible transmission of airborne infections The cost of nosocomial infections in the United States is estimated to be $4 billion to $5 billion annually. Applying a scientifically based analysis to disease transmission and performing a site specific risk analysis to determine the design of the ventilation system can provide real and long term cost savings. Using a scientific approach and convincing data, this paper hypothetically illustrates how a ventilation system design can be optimized to potentially reduce infection risk to occupants in an isolation room based on a thorough risk assessment without necessarily increasing ventilation airflow rate. A computational fluid dynamics (CFD) analysis was performed to examine the transport mechanism, particle path and a suggested control strategy for reducing airborne infectious disease agents. Most studies on the transmission of infectious disease particles have concentrated primarily on air changes per hour (ACH) and how ACH provides a dilution factor for possible infectious agents. Although increasing ventilation airflow rate does dilute concentrations better when the contaminant source is constant, it does not increase ventilation effectiveness. Furthermore, an extensive literature review indicates that not every exposure to an infectious agent will necessarily cause a recipient infection. The results of this study suggest a hypothesis that in an enclosed and mechanically ventilated room (e.g., an isolation room), the dominant factor that affects the transmission and control of contaminants is the path between the contaminant source and exhaust. Contaminants are better controlled when this path is uninterrupted by an air stream. This study illustrates that the ventilation system design, i.e., when it conforms with the hypothesized path principle, may be a more important factor than flow rate (i.e., ACH). A secondary factor includes the distance from the contaminant source. This study provides evidence and supports previous studies that moving away from the patient generally reduces the infection risk in a transient (coughing) situation, although the effect is more pronounced under higher flow rate. It is noted that future research is needed to determine the exact mode of transmission for most recently identified organisms.

negative: Lifting the lid on toilet plume aerosol: A literature review with suggestions for future research BACKGROUND: The potential risks associated with “toilet plume” aerosols produced by flush toilets is a subject of continuing study. This review examines the evidence regarding toilet plume bioaerosol generation and infectious disease transmission. METHODS: The peer-reviewed scientific literature was searched to identify articles related to aerosol production during toilet flushing, as well as epidemiologic studies examining the potential role of toilets in infectious disease outbreaks. RESULTS: The studies demonstrate that potentially infectious aerosols may be produced in substantial quantities during flushing. Aerosolization can continue through multiple flushes to expose subsequent toilet users. Some of the aerosols desiccate to become droplet nuclei and remain adrift in the air currents. However, no studies have yet clearly demonstrated or refuted toilet plume-related disease transmission, and the significance of the risk remains largely uncharacterized. CONCLUSION: Research suggests that toilet plume could play a contributory role in the transmission of infectious diseases. Additional research in multiple areas is warranted to assess the risks posed by toilet plume, especially within health care facilities.

negative: First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany over 140,000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital of Münster (UHM). METHODS: Single-step real-time RT-PCR from nasopharyngeal swaps was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and chart reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Threshold cycle (Ct) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory confirmed COVID-19 infections. Two SARS-CoV-2 positive cases remained clinically asymptomatic. Eleven cases reported flu-like symptoms without positive results. Ct values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (p =0.007). CONCLUSION: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at the UHM. Semi quantitative real-time RT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2 infected HCWs in order to prevent COVID-19 outbreaks in the hospital setting.

negative: Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms [Image: see text] The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host–virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement.

negative: In Preparation for Outdoor Pharming: Griffithsin Can Be Expressed in Nicotiana excelsiana and Retains Activity After Storage as Silage Griffithsin is an algae-derived lectin with strong anti-viral activity against HIV and a positive safety profile. Multiple clinical studies are investigating griffithsin's utility as topical HIV microbicide. HIV microbicides are an extremely cost-sensitive market and plant-based griffithsin protein expression has the potential to meet those demands. The griffithsin product used in the clinic has been expressed and purified in N. benthamiana, using a TMV-based viral vector system, Geneware®. Outdoor pharming of biopharmaceuticals would further alleviate startup costs for biotechnology firms and may allow broader product accessibility. Therefore, this study assessed expression in a hybrid tobacco line, N. excelsiana, that is susceptible to TMV-based viral vectors and can be grown outdoors. In addition to using this hybrid line we expand on methods for in planta storage of griffithsin in leafy plants by ensiling kilogram quantities of griffithsin. The ensiling process allows year-round biomanufacturing, minimal environmental-controlled storage, and reduces the industry need for multiple growth areas to maintain multi-product manufacturing of plant-based pharmaceuticals. This study shows that griffithsin can be expressed in N. excelsiana and is stable, recoverable, and active from ensiled tissue. These studies can pave the way for future plant-based pharmaceuticals to be expressed and stored in this manner.

negative: 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.

negative: Challenges presented by MERS corona virus, and SARS corona virus to global health Numerous viral infections have arisen and affected global healthcare facilities. Millions of people are at severe risk of acquiring several evolving viral infections through several factors. In the present article we have described about risk factors, chance of infection, and prevention methods of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV), human coronaviruses (CoVs) frequently cause a normal cold which is mild and self-restricting. Zoonotic transmission of CoVs such as the newly discovered MERS-CoV and SARS-CoV, may be associated with severe lower respiratory tract infection. The present review provides the recent clinical and pathological information on MERS and SARS. The task is to transform these discoveries about MERS and SARS pathogenesis and to develop intervention methods that will eventually allow the effective control of these recently arising severe viral infections. Global health sector has learnt many lessons through the recent outbreak of MERS and SARS, but the need for identifying new antiviral treatment was not learned. In the present article we have reviewed the literature on the several facets like transmission, precautions and effectiveness of treatments used in patients with MERS-CoV and SARS infections.

negative: Influence of Community and Culture in the Ethical Allocation of Scarce Medical Resources in a Pandemic Situation: Deliberative Democracy Study BACKGROUND: Stark gaps exist between projected health needs in a pandemic situation and the current capacity of health care and medical countermeasure systems. Existing pandemic ethics discussions have advocated to engage the public in scarcity dilemmas and attend the local contexts and cultural perspectives that shape responses to a global health threat. This public engagement study thus considers the role of community and culture in the ethical apportionment of scarce health resources, specifically ventilators, during an influenza pandemic. It builds upon a previous exploration of the values and preferences of Maryland residents regarding how a finite supply of mechanical ventilators ought to be allocated during a severe global outbreak of influenza. An important finding of this earlier research was that local history and place within the state engendered different ways of thinking about scarcity. OBJECTIVE: Given the intrastate variation in the themes expressed by Maryland participants, the project team sought to examine interstate differences by implementing the same protocol elsewhere to answer the following questions. Does variation in ethical frames of reference exist within different regions of the United States? What practical implications does evidence of sameness and difference possess for pandemic planners and policymakers at local and national levels? METHODS: Research using the same deliberative democracy process from the Maryland study was conducted in Central Texas in March 2018 among 30 diverse participants, half of whom identified as Hispanic or Latino. Deliberative democracy provides a moderated process through which community members can learn facts about a public policy matter from experts and explore their own and others’ views. RESULTS: Participants proposed that by evenly distributing supplies of ventilators and applying clear eligibility criteria consistently, health authorities could enable fair allocation of scarce lifesaving equipment. The strong identification, attachment, and obligation of persons toward their nuclear and extended families emerged as a distinctive regional and ethnic core value that has practical implications for the substance, administration, and communication of allocation frameworks. CONCLUSIONS: Maryland and Central Texas residents expressed a common, overriding concern about the fairness of allocation decisions. Central Texas deliberants, however, more readily expounded upon family as a central consideration. In Central Texas, family is a principal, culturally inflected lens through which life and death matters are often viewed. Conveners of other pandemic-related public engagement exercises in the United States have advocated the benefits of transparency and inclusivity in developing an ethical allocation framework; this study demonstrates cultural competence as a further advantage.

negative: Three‐dimensional Sequential Study of the Intestinal Surface in Experimental Porcine CV 777 Coronavirus Enteritis SUMMARY: The intestinal surface of piglets, experimentally infected with the CV777 coronavirus, was studied at different time intervals using stereo‐microscopy, histology and scanning electron microscopy. Desquamation of epithelial cells was most severe on jejunal villi at the time of onset of clinical signs. It was also seen at 6h after the onset of clinical signs in the ileum. Duodenum and colon remained normal. From 24h after the first clinical signs onwards, villous fusion was seen. The alterations of the mucosal surface are compared to those seen in other enteropathogenic conditions of pigs. ZUSAMMENFASSUNG: Rasterelektronen‐ und stereomikroskopische Untersuchung der Darmoberfläche nach experimenteller Infektion mit dem porcinen Coronavirus CV777 Die Darmoberfläche von experimentell mit CV 777 infizierten Ferkeln wurde nach bestimmten Zeitintervallen mit Hilfe der Stereo‐ und einfachen Lichtmikroskopie sowie mit dem Raster‐Elektronenmikroskop untersucht. Bei Auftreten der ersten klinischen Symptome sowie sechs Stunden danach war die Desquamation der Epithelzellen des Jejunums am ausgeprägtesten. Ab 24 Stunden nach der Infektion wurde eine Verschmelzung der Zotten untereinander beobachtet. Die Veränderungen der Schleimhautoberfläche werden mit denen bei anderen enteropathogenen Prozessen verglichen. RÉSUMÉ: Recherche au microscope électronique à balayage et au stéréomicroscope de la surface intestinale après une infection expérimentale avec le Coronavirus CV 777 du porc On a examiné la surface intestinale chez des porcelets infectés avec CV 777 à intervalles déterminés au stéréomicroscope, au microscope optique et au microscope électronique à balayage. La desquamation des cellules épithéliales du Jejunum fut la plus marquée au début des premiers symptômes cliniques et six heures après. On a observé un amalgame des villosités dès 24 heures suivant l'infection. Les modifications de la surface de la muqueuse sont comparées à celles recontrées dans d'autres processus entéropathogènes. RESUMEN: Estudios con el microscopio electrónico de trazados y con el estereo de la superficie intestinal tras la infección experimental con el virus corona porcino CV 777 Se examinó la superficie intestinal de lechones infectados experimental‐mente con CV 777 tras ciertos intervalos de tiempo con ayuda de la estereo‐microscopía y del microscopio óptico simple, así como con el microscopio electrónico de trazados. Al aparecer los síntomas clínicos primeros y seis horas después era muy manifiesta la descamación de las células epiteliales en el yeyuno. A partir de las 24 horas tras la infección se observó una coalescencia de las vellosidades entre sí. Las modificaciones en la superficie mucosa se comparan con las de los otros procesos enteropatógenos.

negative: Surface analysis of long-term hemodialysis catheters made of carbothane (poly(carbonate)urethane) before and after implantation in the patients' bodies. PURPOSE The vascular cannulation is associated with a number of complications. The aim of this work was to study the composition and distribution of the film covering the surfaces of Mahurkar Maxid and Palindrome catheters, which were removed from the body of long-term hemodialysis patients. Moreover, the roughness and contact angle of the catheters were evaluated. METHODS Two brand new (as a reference) and thirty used catheters were the subject of the study. Their implantation period lasted from 4 months to a year and the reason for removal was the production of another vascular access or obstruction. Surfaces were analyzed by scanning electron microscope, atomic force microscope and goniometer. RESULTS The inner surfaces of the used catheters were covered with a film of various complexity which includes a plurality of protein, blood cell counts and the crystals. The closer to the distal part the film becomes more complex and multi-layered. Even the surfaces of brand new catheter were not completely smooth. The only significant difference between analyzed models was the presence of thrombus in the distal part of Mahurkar Maxid catheters, not in the Palindrome. CONCLUSIONS The distal part of the catheters is the place most exposed to obstruction and infection, which may be due to not reaching the anticoagulant agent into this part. Not only the occurrence of side holes affects the formation of thrombus, but also their quantity, geometry and distribution which effect on fluid mechanics. The surface of the catheters needs to improvement to minimize the occurrence of defects and cracks.

negative: Transmissible gastroenteritis coronavirus: surface antigens induced by virulent and attenuated strains Summary Three strains of the transmissible gastroenteritis virus (TGEV) possessing different degrees of pathogenicity for piglets were examined for their capacity to express M and S glycoproteins on the infected cell surface using a microwell immunoperoxidase test. These two viral glycoproteins were easily detected on the plasma membrane of 0.1 % paraformaldehyde-fixed swine testis (ST) or pig kidney (RP.D) cells which were infected with high-passaged Purdue-115 and low-passaged D-52 strains and a high-passaged attenuated (188-SG) mutant of TGEV. No significant differences were found between attenuated and virulent strains with regard to the viral antigen expression on the membrane of infected cells over a 14-h period.

negative: Public perception and attitudes to disaster risks in a coastal metropolis of Saudi Arabia Abstract Disaster risk reduction is an increasingly important policy issue, especially in developing countries that suffer most of the global human and economic losses associated with disasters. Indeed, public awareness and attitudes can help in disaster risk reduction and management efforts toward reducing mortality and economic losses. In Saudi Arabia, many cities have been recently experiencing incidences of disasters, such as floods, disease epidemics, and sandstorms. However, studies on public perception of disaster risk in the country are few and nascent. Therefore, based on a questionnaire survey (n = 683), this paper explores public perception and attitudes to disaster risks in Dammam, a coastal metropolis in Saudi Arabia. The findings indicate that although almost two-thirds (64.7%) of the participants are aware of disasters, and 81% are concerned about disaster risks, less than half (47.3%) believe that their settlements could be at risk. While 37% opine that disasters are caused by both natural factors and human activities, about half (54%) indicate that they can personally contribute to reducing disaster risks. Chi-square analysis indicates a significant positive relationship between place of residence and perception of disaster risks (χ2 (6) = 56.18, p < 0.05), and between place of residence and concern about disaster risks (χ2 (12) = 68.47, p < 0.05). The paper recommends raising public awareness and encouraging positive behaviors in reducing disaster risks in the study area and similar environments.

negative: pH stability studies with avian infectious bronchitis virus (coronavirus) strains. A comparison of 17 infectious bronchitis virus strains, using the same test procedure and assay system, demonstrated that stability at an acid pH is a variable characteristic of the avian coronaviruses.

negative: Chapter 19 Advances in structure-assisted antiviral discovery for animal viral diseases Abstract The latest advancements in drug development are structure-assisted and computer-aided identification, design, and synthesis of target-specific antiviral. Structural virology of animal viruses has made valuable contribution to our understanding of viruses in general, replication, evolution, and interaction with the host. Structure–function relation studies are definitely the need of the hour for rational design of drugs and vaccines to effectively treat animal viral diseases. These studies are important for economical, veterinary, and human medical perspectives. X-ray crystallography, nuclear magnetic resonance and cryo-electron microscopy techniques elaborate the structure–function relation studies by utilizing various computational approaches for structure-assisted designing of drug molecules and antiviral against viruses. Availability of protein three-dimensional structures, high-performance computing, data management software, and internet are enhancing the modern day drug discovery process. Computational tools offer the advantage of delivering new drug candidates more quickly and at a lower cost. Various viral proteins that are necessary for the survival of the virus inside the host are discussed in this chapter such as viral polymerase, helicase, protease, etc. Various antiviral drug molecules identified and designed on the basis of the structure of viral proteins which are highlighted, and disclosed details of the available inhibitors and potential antiviral are discussed. Further improvement in identified inhibitors, the need of novel structure-based drugs and their clinical testing is emphasized. This chapter describes briefly the structural techniques and advances made in animal virology toward structure-based identification and development of antiviral for treatment of animal viruses. In the future, the studies discussed may serve as the basis for development of potential antiviral against animal viral diseases.

negative: Microbial contamination in kitchens and bathrooms of rural Cambodian village households Aims: To quantify microbial contamination on kitchen and bathroom surfaces (fomites) in rural Cambodian homes and to compare these concentrations to similar data from the United States and Japan. Methods and Results: This study monitored the numbers of faecal coliforms (i.e. thermotolerant coliforms), total coliforms, Escherichia coli and heterotrophic plate count bacteria on household surfaces in a rural village of Cambodia. Faecal coliform levels in Cambodia were highest on moist locations such as the plastic ladle used for sink water, the toilet seat surface and the cutting board surface with 100‐fold higher levels of faecal coliform bacteria than E. coli and 100‐fold higher levels of faecal coliforms than the US and Japanese studies. Conclusions: A single public health intervention barrier, such as an improved latrine, is only partially effective for household sanitation. For complete sanitation, multiple environmental barriers may be necessary. These barriers occur in a house constructed with easily washable surfaces, a chlorinated water distribution system, house climate control and cleaning product availability. Significance and Impact of the Study: Results of this study can be used to emphasize the importance of increasing household environmental sanitation barriers.

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: Chapter 10 Bioaugmentation for the treatment of waterborne pathogen contamination water Abstract Bioaugmentation is an eco-friendly and economically viable approach for enhanced degradation of pollutants and pathogens by addition of pregrown microbe or microbial cocultures in the medium. Microorganisms from different ecological conditions and engineered microbes capable to produce versatile enzymes and bioproducts are added to native microbial population for in situ treatment of wastewater. Bacterial pathogen borne in wastewater is an important concern for public health because they are not only associated with environmental damage, morbidity, and mortality but also cause economic loss connected with physical and chemical methods in wastewater treatment. Bacteriophages are natural killer of bacteria; they can be used as an alternative, cost-effective, biological method for waterborne bacterial pathogen control. Legionella pneumophila is the most tracked waterborne pathogen requiring specific treatment conditions because despite of biocides use, they are able to persist in water supplies with the help of multispecies biofilms and phagocytic protists. This type of pathogens can be biologically controlled through native complex communities fight for nutrients by means of antagonistic molecules as war weapons. Bioinoculation of heterotrophic bacterial strains in different wastewater treatment systems improves the process of pathogenic bacteria removal. The antagonist substances produced by the inoculated strains are responsible for bacterial pathogen inactivation.

negative: The potential impact of COVID-19-related disruption on tuberculosis burden

negative: A study of non-prescription usage of antibiotics in the upper respiratory tract infections in the urban population

negative: Severe acute respiratory syndrome (SARS)—paradigm of an emerging viral infection Abstract An acute and often severe respiratory illness emerged in southern China in late 2002 and rapidly spread to different areas of the Far East as well as several countries around the globe. When the outbreak of this apparently novel infectious disease termed severe acute respiratory syndrome (SARS) came to an end in July 2003, it had caused over 8000 probable cases worldwide and more than 700 deaths. Starting in March 2003, the World Health Organization (WHO) organised an unprecedented international effort by leading laboratories working together to find the causative agent. Little more than one week later, three research groups from this WHO-coordinated network simultaneously found evidence of a hitherto unknown coronavirus in SARS patients, using different approaches. After Koch’s postulates had been fulfilled, WHO officially declared on 16 April 2003 that this virus never before seen in humans is the cause of SARS. Ever since, progress around SARS-associated coronavirus (SARS-CoV) has been swift. Within weeks of the first isolate being obtained, its complete genome was sequenced. Diagnostic tests based on the detection of SARS-CoV RNA were developed and made available freely and widely; nevertheless the SARS case definition still remains based on clinical and epidemiological criteria. The agent’s environmental stability, methods suitable for inactivation and disinfection, and potential antiviral compounds have been studied, and development of vaccines and immunotherapeutics is ongoing. Despite its grave consequences in humanitarian, political and economic terms, SARS may serve as an example of how much can be achieved through a well-coordinated international approach, combining the latest technological advances of molecular virology with more “traditional” techniques carried out to an excellent standard.

negative: Thoracoscopic pulmonary wedge resection without post-operative chest drain: an observational study. OBJECTIVE Chest drains are used routinely after wedge resection by video-assisted thoracoscopic surgery (VATS), although this practice is based largely on tradition rather than evidence. Chest drains may furthermore cause pain, infections, and prolonged length of stay. The aim of this prospective observational study was to assess the feasibility of avoiding chest drains following VATS wedge resection for pulmonary nodules. METHODS Between 1 February and 25 August 2015 166 consecutive patients planned for VATS wedge resection of pulmonary nodules were screened for inclusion using the following criteria: Forced expiratory volume in 1 s (FEV1) ≥60 % of expected, FEV1/forced vital capacity ≥70 %, tumour diameter ≤2 cm, distance from tumour to visceral pleura ≤3 cm, ≤2 separate wedges, no air leak on an intraoperative air leakage test and absence of severe adhesions, bullous/emphysematous disease, pleural effusion and coagulopathy. Chest X-rays were done twice on the day of surgery. 30-day complications were compiled from patient records. RESULTS 49 patients underwent 51 unilateral VATS wedge resections without using a post-operative chest drain. No patient required reinsertion of a chest drain. 30 (59 %) patients had a pneumothorax of mean size 12 ± 12 mm on supine 8-h post-operative X-ray for which the majority resolved spontaneously within 2-week control. There were no complications on 30-day follow-up. Median length of stay was 1 day. CONCLUSIONS The results support that VATS wedge resection for pulmonary nodules without a post-operative chest drain may be safe in a selected group of patients.

negative: Palivizumab use during respiratory syncytial virus outbreak in the neonatal intensive care unit

negative: Chapter 7 Long-term virus evolution in nature Abstract Viruses spread to give rise to epidemics and pandemics, and some key parameters that include virus and host population numbers determine virus persistence or extinction in nature. Viruses evolve at different rates depending on the polymerase copying fidelity during genome replication and a number of environmental influences. Calculated rates of evolution in nature vary depending on the time interval between virus isolations. In particular, intrahost evolution is generally more rapid that interhost evolution, and several possible mechanisms for this difference are considered. The mechanisms by which the error-prone viruses evolve are very unlikely to render the operation of a molecular clock (constant rate of incorporation of mutations in the evolving genomes), although a clock is assumed in many calculations. Several computational tools permit the alignment of viral sequences and the establishment of phylogenetic relationships among viruses. The evolution of the virus in the form of dynamic mutant clouds in each infected individual, together with multiple environmental parameters renders the emergence and reemergence of viral pathogens an unpredictable event, another facet of biological complexity.

negative: Fundamental principles of epidemic spread highlight the immediate need for large-scale serological surveys to assess the stage of the SARS-CoV-2 epidemic The spread of a novel pathogenic infectious agent eliciting protective immunity is typically characterised by three distinct phases: (I) an initial phase of slow accumulation of new infections (often undetectable), (II) a second phase of rapid growth in cases of infection, disease and death, and (III) an eventual slow down of transmission due to the depletion of susceptible individuals, typically leading to the termination of the (first) epidemic wave. Before the implementation of control measures (e.g. social distancing, travel bans, etc) and under the assumption that infection elicits protective immunity, epidemiological theory indicates that the ongoing epidemic of SARS-CoV-2 will conform to this pattern. Here, we calibrate a susceptible-infected-recovered (SIR) model to data on cumulative reported SARS-CoV-2 associated deaths from the United Kingdom (UK) and Italy under the assumption that such deaths are well reported events that occur only in a vulnerable fraction of the population. We focus on model solutions which take into consideration previous estimates of critical epidemiological parameters such as the basic reproduction number (R0), probability of death in the vulnerable fraction of the population, infectious period and time from infection to death, with the intention of exploring the sensitivity of the system to the actual fraction of the population vulnerable to severe disease and death. Our simulations are in agreement with other studies that the current epidemic wave in the UK and Italy in the absence of interventions should have an approximate duration of 2-3 months, with numbers of deaths lagging behind in time relative to overall infections. Importantly, the results we present here suggest the ongoing epidemics in the UK and Italy started at least a month before the first reported death and have already led to the accumulation of significant levels of herd immunity in both countries. There is an inverse relationship between the proportion currently immune and the fraction of the population vulnerable to severe disease. This relationship can be used to determine how many people will require hospitalisation (and possibly die) in the coming weeks if we are able to accurately determine current levels of herd immunity. There is thus an urgent need for investment in technologies such as virus (or viral pseudotype) neutralization assays and other robust assays which provide reliable read-outs of protective immunity, and for the provision of open access to valuable data sources such as blood banks and paired samples of acute and convalescent sera from confirmed cases of SARS-CoV-2 to validate these. Urgent development and assessment of such tests should be followed by rapid implementation at scale to provide real-time data. These data will be critical to the proper assessment of the effects of social distancing and other measures currently being adopted to slow down the case incidence and for informing future policy direction.

negative: Emergency Medical Services Utilization during an Outbreak of Severe Acute Respiratory Syndrome (SARS) and the Incidence of SARS‐associated Coronavirus Infection among Emergency Medical Technicians Objectives: This was a study to evaluate the utilization of emergency medical services (EMS) systems during the outbreak of severe acute respiratory syndrome (SARS), and to assess the incidence of infection among emergency medical technicians (EMTs). Methods:This was a prospective, observational study conducted in the EMS system of Taipei, Taiwan. Probable/suspect cases of SARS were defined by World Health Organization criteria. SARS‐related transports were categorized into 1) requests from hospitals for probable/suspect cases of SARS, 2) quarantined individuals, and 3) febrile persons. City ambulances were organized into teams A, B, and C for transports of different perceived risks. Data on the EMS volume, the transport category, the final SARS status of patients, and the EMT responsible for the transports were collected. The EMS projected volume was computed by previous years' data and compared with that collected. The SARS incidence among EMTs was assessed by investigating probable SARS (P‐SARS) and by surveying the seroprevalence of SARS‐associated coronavirus (SARS‐CoV) antibody. Results: From March 18 to June 19, 2003, there were 7,961 EMS transports, similar to the volume projected from previous years (7,506) (95% CI = 6,688 to 8,324). Of these, 1,760 (22.1%) were SARS‐related. When SARS‐related transports were excluded, there was a 12.2% decrease (95% CI = 11.4% to 12.9%) in EMS activities. Requests from hospitals, quarantined individuals, and febrile citizens accounted for 23%, 18%, and 59% of SARS‐related transports. Among the 397 P‐SARS cases in the city of 2.65 million people (incidence 0.01%, 95% CI = 0.01% to 0.02%), 138 (35%) required EMS transports. Two EMTs working in team C, the team with the lowest risk, developed P‐SARS. One of them died soon thereafter. The incidence of P‐SARS was 0.6% (95% CI = 0.2% to 2.2%), or 0.1% (95% CI = 0.03% to 0.4%) per transport. SARS‐CoV serology was available in 74.1% of EMTs who were alive. In addition to the surviving P‐SARS EMT, one EMT from team A, the team with the highest risk, was seropositive. Combining P‐SARS and the seropositive case, three EMTs were infected (incidence 1.3%, 95% CI = 0.4% to 3.6%). No patient transported by the infected EMTs developed SARS. The hospitals serving EMS by the infected EMTs had been involved in a clustered outbreak prior to the EMTs' infections. Conclusions: During the outbreak of SARS, the overall EMS volume did not change significantly, but the non‐SARS EMS activities decreased. Compared with the general population, EMS providers are at higher risk of contracting the SARS virus regardless of different perceived levels of risk. Standard protections and procedures for infection control should be strictly followed during transport and within the hospital environment.

negative: Features, Evaluation and Treatment Coronavirus (COVID-19) According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019 Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019 As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology " The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019" In the past twenty years, two additional coronavirus epidemics have occurred SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be very contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated

negative: Ventilation-Induced Modulation of Pulse Oximeter Waveforms: A Method for the Assessment of Early Changes in Intravascular Volume During Spinal Fusion Surgery in Pediatric Patients. BACKGROUND Scoliosis surgery is often associated with substantial blood loss, requiring fluid resuscitation and blood transfusions. In adults, dynamic preload indices have been shown to be more reliable for guiding fluid resuscitation, but these indices have not been useful in children undergoing surgery. The aim of this study was to introduce frequency-analyzed photoplethysmogram (PPG) and arterial pressure waveform variables and to study the ability of these parameters to detect early bleeding in children during surgery. METHODS We studied 20 children undergoing spinal fusion. Electrocardiogram, arterial pressure, finger pulse oximetry (finger PPG), and airway pressure waveforms were analyzed using time domain and frequency domain methods of analysis. Frequency domain analysis consisted of calculating the amplitude density of PPG and arterial pressure waveforms at the respiratory and cardiac frequencies using Fourier analysis. This generated 2 measurements: The first is related to slow mean arterial pressure modulation induced by ventilation (also known as DC modulation when referring to the PPG), and the second corresponds to pulse pressure modulation (AC modulation or changes in the amplitude of pulse oximeter plethysmograph when referring to the PPG). Both PPG and arterial pressure measurements were divided by their respective cardiac pulse amplitude to generate DC% and AC% (normalized values). Standard hemodynamic data were also recorded. Data at baseline and after bleeding (estimated blood loss about 9% of blood volume) were presented as median and interquartile range and compared using Wilcoxon signed-rank tests; a Bonferroni-corrected P value <0.05 was considered statistically significant. RESULTS There were significant increases in PPG DC% (median [interquartile range] = 359% [210 to 541], P = 0.002), PPG AC% (160% [87 to 251], P = 0.003), and arterial DC% (44% [19 to 84], P = 0.012) modulations, respectively, whereas arterial AC% modulations showed nonsignificant increase (41% [1 to 85], P = 0.12). The change in PPG DC% was significantly higher than that in PPG AC%, arterial DC%, arterial AC%, and systolic blood pressure with P values of 0.008, 0.002, 0.003, and 0.002, respectively. Only systolic blood pressure showed significant changes (11% [4 to 21], P = 0.003) between bleeding phase and baseline. CONCLUSIONS Finger PPG and arterial waveform parameters (using frequency analysis) can track changes in blood volume during the bleeding phase, suggesting the potential for a noninvasive monitor for tracking changes in blood volume in pediatric patients. PPG waveform baseline modulation (PPG DC%) was more sensitive to changes in venous blood volume when compared with respiration-induced modulation seen in the arterial pressure waveform.

negative: Spread and prevention of some common viral infections in community facilities and domestic homes

negative: Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity The SARS 3C-like proteinase (SARS-3CLpro), which is the main proteinase of the SARS coronavirus, is essential to the virus life cycle. This enzyme has been shown to be active as a dimer in which only one protomer is active. However, it remains unknown how the dimer structure maintains an active monomer conformation. It has been observed that the Ser139-Leu141 loop forms a short 3(10)-helix that disrupts the catalytic machinery in the inactive monomer structure. We have tried to disrupt this helical conformation by mutating L141 to T in the stable inactive monomer G11A/R298A/Q299A. The resulting tetra-mutant G11A/L141T/R298A/Q299A is indeed enzymatically active as a monomer. Molecular dynamics simulations revealed that the L141T mutation disrupts the 3(10)-helix and helps to stabilize the active conformation. The coil-3(10)-helix conformational transition of the Ser139-Leu141 loop serves as an enzyme activity switch. Our study therefore indicates that the dimer structure can stabilize the active conformation but is not a required structure in the evolution of the active enzyme, which can also arise through simple mutations.

negative: A surface plasmon resonance-based assay for small molecule inhibitors of human cyclophilin A Abstract A simple protocol for generating a highly stable and active surface plasmon resonance (SPR) sensor surface of recombinant human hexahistidine cyclophilin A (His-CypA) is described. The sensor surface was sensitive and stable enough to allow, for the first time, the screening and ranking of several novel small-molecule (M r ∼250–500Da) ligands in a competition binding assay with cyclosporin A (CsA). It also allowed us to accurately determine the kinetic rate constants for the interaction between His-CypA and CsA. His-CypA was first captured on a Ni2+–nitrilotriacetic acid (NTA) sensor chip and was then briefly covalently stabilized, coupling via primary amines. The significant baseline drift observed due to dissociation of weakly bound His-CypA from the Ni2+–NTA moiety was eliminated, resulting in a surface that was stable for at least 36h. In addition, immobilized protein activity levels were high, typically between 85 and 95%, assayed by the interaction between His-CypA and CsA. The mean equilibrium dissociation constant for CsA (K dCsA) binding to the immobilized His-CypA was 23±6nM, with on and off rates of 0.53±0.1μM−1 s−1 and 1.2±0.1 (×10−2) s−1, respectively. These values agree well with the values for the corresponding binding constants determined from steady-state and kinetic fluorescence titrations in solution.

negative: Literature-related discovery: Potential treatments and preventatives for SARS Abstract Literature-related discovery (LRD) is the linking of two or more previously disjoint concepts in order to produce novel, interesting, plausible, and intelligible connections (i.e., potential discovery). LRD has been used to identify potential treatments or preventative actions for challenging medical problems, among myriad other applications. Severe acute respiratory syndrome (SARS) was the first pandemic of the 21st century. SARS was eventually controlled through increased hygienic measures (e.g., face mask protection, frequent hand washing, living quarter disinfection), travel restrictions, and quarantine. According to recent reviews of SARS, none of the drugs that were used during the pandemic worked. For the present paper, SARS was selected as the first application of LRD to an infectious disease. The main goal of this research was to identify non-drug non-surgical treatments that would 1) prevent the occurrence, or 2) reduce the progression rate, or 3) stop/reverse the progression of SARS. The MeSH taxonomy of Medline was used to restrict potential discoveries to selected semantic classes, and to identify potential discoveries efficiently. To enhance the volume of potential discovery, databases were used in addition to Medline. These included the Science Citation Index (SCI) and, in contrast to previous work, a full text database. Because of the richness of the full text, ‘surgical’ queries were developed that targeted the exact types of potential discovery of interest while eliminating clutter more efficiently.

negative: Apparent discontinuous transcription of Trypanosoma brucei variant surface antigen genes The repeated mini-exon sequence that encodes the first 35 base pairs of all variant surface antigen mRNAs of Trypanosoma brucei directs the synthesis of a discrete 137-nucleotide transcript. It thus seems that variant surface antigen mRNAs are transcribed discontinuously, and we present two alternative models for how this might occur.

negative: Unprecedented nationwide blood studies seek to track U.S. coronavirus spread We still don’t know how many people have been infected with the novel coronavirus, SARS-CoV-2 Not only have countries struggled to roll out wide-scale testing for the virus, those efforts inevitably will miss people who have recovered from an infection The best way to figure out how far and wide the virus has spread in a population is to look at blood Antibodies, blood proteins that the immune system produces to attack pathogens, are viral fingerprints that remain long after infections are cleared Sensitive tests can detect them even in people who never felt a single symptom of COVID-19 The World Health Organization has announced an ambitious global effort, called Solidarity II, of so-called serosurveys, studies that look for antibodies to SARS-CoV-2 in the population

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: A Novel Loading Method for Doxycycline Liposomes for Intracellular Drug Delivery: Characterization of In Vitro and In Vivo Release Kinetics and Efficacy in a J774A.1 Cell Line Model of Mycobacterium smegmatis Infection. Doxycycline (doxy) is used in treating intracellular and extracellular infections. Liposomal (LE) antibiotics allow low-frequency dosing and extended efficacy compared with standard (STD) formulations. We developed a novel sulfuric acid-loading method for doxycycline liposomes (LE-doxy). We hypothesized that a single s.c. injection of LE-doxy would be detectable in serum for at least 2 weeks at concentrations equal to or better than STD-doxy and would be bactericidal in an in vitro Mycobacterium smegmatis infection of J774A.1 macrophage cells. Liposomes were encapsulated by sulfuric acid gradient loading, and release kinetics were performed in vitro and in vivo. LE-doxy made using 8.25 mg/ml doxycycline loaded for 24 hours achieved 97.77% capture in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 43.87% in sphingomyelin (sphing). Rats were injected s.c. with 50 mg/kg LE-doxy or 5 mg/kg STD-doxy, and serial blood samples were collected. Pharmacokinetics were analyzed using high-performance liquid chromatography. Liver and injection site skin samples were collected at euthanasia (4 weeks postinjection). Minimal histologic tissue reactions occurred after injection of STD (nonliposomal), DPPC, or sphing-doxy. DPPC-doxy had slightly faster in vitro leakage than sphing liposomes, although both were detectable at 264 hours. The mean residence time for DPPC was the highest (111.78 hours), followed by sphing (56.00 hours) and STD (6.86 hours). DPPC and sphing-doxy were detectable at 0.2 μg/ml in serum at 336 hours postadministration. LE-doxy was not toxic to J774A.1 cells in vitro and produced inhibition of viable Mycobacterium smegmatis at 24 and 48 hours. LE-doxy will require further testing in in vivo infection models.

negative: Using Google Trends to Examine the Spatio-Temporal Incidence and Behavioral Patterns of Dengue Disease: A Case Study in Metropolitan Manila, Philippines Dengue is a major public health concern and an economic burden in the Philippines. Despite the country’s improved dengue surveillance, it still suffers from various setbacks and needs to be complemented with alternative approaches. Previous studies have demonstrated the potential of Internet-based surveillance such as Google Dengue Trends (GDT) in supplementing current epidemiological methods for predicting future dengue outbreaks and patterns. With this, our study has two objectives: (1) assess the temporal relationship of weekly GDT and dengue incidence in Metropolitan Manila from 2009–2014; and (2) examine the health-seeking behavior based on dengue-related search queries of the population. The study collated the population statistics and reported dengue cases in Metropolitan Manila from respective government agencies to calculate the dengue incidence (DI) on a weekly basis for the entire region and annually per city. Data processing of GDT and dengue incidence was performed by conducting an ‘adjustment’ and scaling procedures, respectively, and further analyzed for correlation and cross-correlation analyses using Pearson’s correlation. The relative search volume of the term ‘dengue’ and top dengue-related search queries in Metropolitan Manila were obtained and organized from the Google Trends platform. Afterwards, a thematic analysis was employed, and word clouds were generated to examine the health behavior of the population. Results showed that weekly temporal GDT pattern are closely similar to the weekly DI pattern in Metropolitan Manila. Further analysis showed that GDT has a moderate and positive association with DI when adjusted or scaled, respectively. Cross-correlation analysis revealed a delayed effect where GDT leads DI by 1–2 weeks. Thematic analysis of dengue-related search queries indicated 5 categories namely; (a) dengue, (b) sign and symptoms of dengue, (c) treatment and prevention, (d) mosquito, and (e) other diseases. The majority of the search queries were classified in ‘signs and symptoms’ which indicate the health-seeking behavior of the population towards the disease. Therefore, GDT can be utilized to complement traditional disease surveillance methods combined with other factors that could potentially identify dengue hotspots and help in public health decisions.

negative: Media impact switching surface during an infectious disease outbreak There are many challenges to quantifying and evaluating the media impact on the control of emerging infectious diseases. We modeled such media impacts using a piecewise smooth function depending on both the case number and its rate of change. The proposed model was then converted into a switching system, with the switching surface determined by a functional relationship between susceptible populations and different subgroups of infectives. By parameterizing the proposed model with the 2009 A/H1N1 influenza outbreak data in the Shaanxi province of China, we observed that media impact switched off almost as the epidemic peaked. Our analysis implies that media coverage significantly delayed the epidemic's peak and decreased the severity of the outbreak. Moreover, media impacts are not always effective in lowering the disease transmission during the entire outbreak, but switch on and off in a highly nonlinear fashion with the greatest effect during the early stage of the outbreak. The finding draws the attention to the important role of informing the public about ‘the rate of change of case numbers' rather than ‘the absolute number of cases' to alter behavioral changes, through a self-adaptive media impact switching on and off, for better control of disease transmission.

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: Analysis of the mitigation strategies for COVID-19: from mathematical modelling perspective In this article, a mathematical model for the transmission of COVID-19 disease is formulated and analysed. It is shown that the model exhibits a backward bifurcation at [Formula: see text] when recovered individuals do not develop a permanent immunity for the disease. In the absence of reinfection, it is proved that the model is without backward bifurcation and the disease free equilibrium is globally asymptotically stable for [Formula: see text]. By using available data, the model is validated and parameter values are estimated. The sensitivity of the value of [Formula: see text] to changes in any of the parameter values involved in its formula is analysed. Moreover, various mitigation strategies are investigated using the proposed model and it is observed that the asymptomatic infectious group of individuals may play the major role in the re-emergence of the disease in the future. Therefore, it is recommended that in the absence of vaccination, countries need to develop capacities to detect and isolate at least 30% of the asymptomatic infectious group of individuals while treating in isolation at least 50% of symptomatic patients to control the disease.

negative: Projecting the Spread of COVID19 for Germany We model the evolution of the number of individuals that are reported to be sick with COVID-19 in Germany. Our theoretical framework builds on a continuous time Markov chain with four states: healthy without infection, sick, healthy after recovery or after infection but without symptoms and dead. Our quantitative solution matches the number of sick individuals up to the most recent observation and ends with a share of sick individuals following from infection rates and sickness probabilities. We employ this framework to study inter alia the expected peak of the number of sick individuals in a scenario without public regulation of social contacts. We also study the effects of public regulations. For all scenarios we report the expected end of the CoV-2 epidemic. We have four general findings: First, current epidemiological thinking implies that the long-run effects of the epidemic only depend on the aggregate long-run infection rate and on the individual risk to turn sick after an infection. Any measures by individuals and the public therefore only influence the dynamics of spread of CoV-2. Second, predictions about the duration and level of the epidemic must strongly distinguish between the officially reported numbers (Robert Koch Institut, RKI) and actual numbers of sick individuals. Third, given the current (scarce) medical knowledge about long-run infection rate and individual risks to turn sick, any prediction on the length (duration in months) and strength (e.g. maximum numbers of sick individuals on a given day) is subject to a lot of uncertainty. Our predictions therefore offer robustness analyses that provide ranges on how long the epidemic will last and how strong it will be. Fourth, public interventions that are already in place and that are being discussed can lead to more and less severe outcomes of the epidemic. If an intervention takes place too early, the epidemic can actually be stronger than with an intervention that starts later. Interventions should therefore be contingent on current infection rates in regions or countries. Concerning predictions about COVID-19 in Germany, we find that the long-run number of sick individuals (that are reported to the RKI), once the epidemic is over, will lie between 500 thousand and 5 million individuals. While this seems to be an absurdly large range for a precise projection, this reflects the uncertainty about the long-run infection rate in Germany. If we assume that Germany will follow the good scenario of Hubei (and we are even a bit more conservative given discussions about data quality), we will end up with 500 thousand sick individuals over the entire epidemic. If by contrast we believe (as many argue) that once the epidemic is over 70% of the population will have been infected (and thereby immune), we will end up at 5 million cases. Defining the end of the epidemic by less than 100 newly reported sick individuals per day, we find a large variation depending on the effectiveness of governmental pleas and regulations to reduce social contacts. An epidemic that is not influenced by public health measures would end mid June 2020. With public health measures lasting for few weeks, the end is delayed by around one month or two. The advantage of the delay, however, is to reduce the peak number of individuals that are simultaneously sick. When we believe in long-run infection rates of 70%, this number is equally high for all scenarios we went through and well above 1 million. When we can hope for the Hubei-scenario, the maximum number of sick individuals will be around 200 thousand only. Whatever value of the range of long-run infection rates we want to assume, the epidemic will last at least until June, with extensive and potentially future public health measures, it will last until July. In the worst case, it will last until end of August. We emphasize that all projections are subject to uncertainty and permanent monitoring of observed incidences are taken into account to update the projection. The most recent projections are available at https://www.macro.economics.uni-mainz.de/corona-blog/.

negative: Low transmission rate of 2009 H1N1 Influenza during a long-distance bus trip BACKGROUND: Current data on the risk of transmission of 2009 H1N1 Influenza in public transportation systems (e.g., public trains, busses, airplanes) are conflicting. The main transmission route of this virus is thought to be via droplets, but airborne transmission has not been completely ruled out. METHODS: This is a contact tracing investigation of a young woman subsequently diagnosed with the 2009 H1N1 Influenza virus who was symptomatic during a long-distance bus trip from Spain to Switzerland. Fever and cough had begun 24 h earlier, 2 h before she stepped onto a bus for a long-distance trip. After the 2009 H1N1 virus had been confirmed in the patient, the other bus travellers were contacted by telephone on day 7 and 10 after the bus trip. RESULTS: Of the 72 individuals travelling on the bus with the H1N1-infected young woman, 52 (72%) could be contacted. Only one of these 52 developed fever, with onset of symptoms 3 days after the bus trip, and rRT-PCR analysis of the nasopharyngeal swab showed the infection to be caused by the 2009 H1N1 virus. One other person complained of coughing 1 day after the bus trip, but without fever, and no further investigation was carried out. All other passengers remained without fever, coughing, or arthralgia. The risk of transmission was calculated as 1.96% (95% confidence interval 0–5.76%). CONCLUSION: The transmission rate of 2009 H1N1 Influenza was low on a long-distance bus trip. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s15010-011-0084-x) contains supplementary material, which is available to authorized users.

negative: Complete Genome Sequencing of a Novel Strain of Sapelovirus A Circulating in Vietnam Sapelovirus A (SV-A) is currently spreading as an enteric pathogen of pigs worldwide. We isolated SV-A strain XTND/2018 from the small intestine of a dead pig with severe diarrhea in the north of Vietnam and determined the genomic sequence. This is the first report of the genomic sequence of SV-A circulating in Vietnam.

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: Long-term humoral immunity against viruses: revisiting the issue of plasma cell longevity Despite extensive documentation of prolonged antibody responses following vaccination or acute viral infection, the mechanisms behind long-term antibody production are not fully understood. We propose the hypothesis that long-lived plasma cells are an important, yet largely overlooked, component of long-term humoral immunity.

negative: Resilience resistance: The challenges and implications of urban resilience implementation Growing concern about major threats, including climate change, environmental disasters, and other hazards, is matched with the increased interest and appeal of the concept of urban resilience. Much scholarly attention has focused on how to define urban resilience, in addition to raising questions about its applicability and usefulness. But those debates typically overlook questions of implementation. Implementation is important not only for how cities respond to threats but also because it can influence how urban resilience is perceived, discussed, and understood. The policy literature suggests that implementation is rarely straightforward and has ideological and normative perspectives embedded within it. Building on this literature, this paper argues that urban resilience implementation raises its own conceptual questions for both theory and practice. Further, implementing urban resilience entails its own unique challenges, such as extensive coordination, maintaining adaptability, divergent time horizons, and diverse outcomes. The paper also introduces the idea of resilience resistance as a new challenge for urban resilience. Resistance refers to the condition in which governance systems inherently develop barriers to change, flexibility, and adaptability through implementation. Several aspects of resistance are highlighted, including fatigue, complacency, and overconfidence. However, the implementation process can also have unintended positive effects on a city's capacity to prepare for and respond to shocks.

negative: SARS-Coronavirus (SARS-CoV) Humanes SARS-Coronavirus

negative: SARS-coronavirus replicates in mononuclear cells of peripheral blood (PBMCs) from SARS patients Abstract Background: The etiologic agent of severe acute respiratory syndrome (SARS) is a recently identified, positive single-stranded RNA (ssRNA) coronavirus (SARS-CoV). Little is known about the dynamic changes of the viral replicative form in SARS cases. Objectives: Evaluate whether SARS-CoV can infect and replicate in peripheral blood mononuclear cells (PBMCs) of infected persons and reveal any dynamic changes to the virus during the course of the disease. Study design: Peripheral blood mononuclear cells collected from SARS cases infected by the same infectious source were tested for both negative-stranded RNA (minus-RNA, “replicative intermediates”) and positive-stranded RNA (genomic RNA) of SARS-CoV during the course of hospitalization by reverse transcription-polymerase chain reaction (RT-PCR). Results: SARS-CoV minus-RNA was detected in PBMCs from SARS patients. The viral replicative forms in PBMCs were detectable during a period of 6 days post-onset of the disease, while the plus-RNA were detectable for a longer period (8–12 days post-onset). Conclusions: SARS-coronavirus can infect and replicate within PBMCs of SARS patients, but viral replication in PBMCs seems subject to self-limitation.

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: The use of comb-type copolymers to sustain the surface bactericidal effect of highly water-soluble cationic biocides A series of free radical comb-type acrylic copolymers was prepared in a solution incorporating charged and/or neutral stabilising species on the backbone. The polymer solutions were formulated with cationic biocides to give physically stable formulations with a long shelf life. Furthermore, through the control of polymer architecture of both the side-chain and the backbone, hydrophobicity, a controlled release of a biocide could be achieved. This technology has resulted in the design of temporary coatings demonstrating a sustained surface disinfecting effect. In laboratory trials, coated surfaces with polymeric/biocidal formulations continued to show a disinfection effect after several washes.

negative: Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations Statistical and epidemiological data imply temperature sensitivity of the SARS-CoV-2 coronavirus. However, the molecular level understanding of the virus structure at different temperature is still not clear. Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the solvent exposed domain of Spike protein, namely S1, is more mobile than the transmembrane domain, S2. Structural studies implied the presence of several charged residues on the surface of N-terminal Domain of S1 which are optimally oriented at 10-30 °C. Bioinformatics analyses indicated that it is capable of binding to other human receptors and should not be disregarded. Additionally, we found that receptor binding motif (RBM), present on the receptor binding domain (RBD) of S1, begins to close around temperature of 40 °C and attains a completely closed conformation at 50 °C. The closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues. Our results clearly show that there are active and inactive states of the protein at different temperatures. This would not only prove beneficial for understanding the fundamental nature of the virus, but would be also useful in the development of vaccines and therapeutics. Graphical Abstract Highlights Statistical and epidemiological evidence show that external climatic conditions influence the SARS-CoV infectivity, but we still lack a molecular level understanding of the same. Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2. Results show that the Spike’s S1 domain is very sensitive to external atmospheric conditions compared to the S2 transmembrane domain. The N-terminal domain comprises of several solvent exposed charged residues that are capable of binding to human proteins. The region is specifically stable at temperatures ranging around 10-30° C. The Receptor Binding Motif adopts a closed conformation at 40°C and completely closes at higher temperatures making it unsuitable of binding to human receptors

negative: Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19 COVID-19 is a complex disease phenotype where the underlying microbiome could influence morbidity and mortality. Amplicon and metagenomic MinION based sequencing was used to rapidly (within 8 hours) identify SARS-CoV-2 and assess the microbiome in nasopharyngeal swabs obtained from patients with COVID-19 by the ISARIC 4C consortium.

negative: Finding the Dose for Hydroxychloroquine Prophylaxis for COVID‐19: The Desperate Search for Effectiveness Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID‐19) pandemic caused by the severe acute respiratory syndrome coronavirus 2. Although the efficacy of hydroxychloroquine for COVID‐19 remains uncertain, it may serve as a potential prophylactic agent especially in those at high risk, such as healthcare workers, household contacts of infected patients, and the immunocompromised. Our aim was to identify possible hydroxychloroquine dosing regimens through simulation in those at high risk of infections by optimizing exposures above the in vitro generated half maximal effective concentration (EC(50)) and to help guide researchers in dose‐selection for COVID‐19 prophylactic studies. To maintain weekly troughs above EC(50) in > 50% of subjects at steady‐state in a pre‐exposure prophylaxis setting, an 800 mg loading dose followed by 400 mg twice or 3 times weekly is required. In an exposure driven, post‐exposure prophylaxis setting, 800 mg loading dose followed in 6 hours by 600 mg, then 600 mg daily for 4 more days achieved daily troughs above EC(50) in > 50% subjects. These doses are higher than recommended for malaria chemoprophylaxis, and clinical trials are needed to establish safety and efficacy.

negative: 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.

negative: Emerging virus diseases: can we ever expect the unexpected? Emerging virus diseases are a major threat to human and veterinary public health. With new examples occurring approximately one each year, the majority are viruses originating from an animal host. Of the many factors responsible, changes to local ecosystems that perturb the balance between pathogen and principal host species is one of the major drivers, together with increasing urbanization of mankind and changes in human behavior. Many emerging viruses have RNA genomes and as such are capable of rapid mutation and selection of new variants in the face of environmental changes in host numbers and available target species. This review summarizes recent work on aspects of virus emergence and the current understanding of the molecular and immunological basis whereby viruses may cross between species and become established in new ecological niches. Emergence is hard to predict, although mathematical modeling and spatial epidemiology have done much to improve the prediction of where emergence may occur. However, much needs to be done to ensure adequate surveillance is maintained of animal species known to present the greatest risk thus increasing general alertness among physicians, veterinarians and those responsible for formulating public health policy.

negative: Lessons from Walking the Medical Distancing Tightrope

negative: Vanadium compounds in medicine Abstract Vanadium is a transition metal that, being ubiquitously distributed in soil, crude oil, water and air, also found roles in biological systems and is an essential element in most living beings. There are also several groups of organisms which accumulate vanadium, employing it in their biological processes. Vanadium being a biological relevant element, it is not surprising that many vanadium based therapeutic drugs have been proposed for the treatment of several types of diseases. Namely, vanadium compounds, in particular organic derivatives, have been proposed for the treatment of diabetes, of cancer and of diseases caused by parasites. In this work we review the medicinal applications proposed for vanadium compounds with particular emphasis on the more recent publications. In cells, partly due to the similarity of vanadate and phosphate, vanadium compounds activate numerous signaling pathways and transcription factors; this by itself potentiates application of vanadium-based therapeutics. Nevertheless, this non-specific bio-activity may also introduce several deleterious side effects as in addition, due to Fenton's type reactions or of the reaction with atmospheric O2, VCs may also generate reactive oxygen species, thereby introducing oxidative stress with consequences presently not well evaluated, particularly for long-term administration of vanadium to humans. Notwithstanding, the potential of vanadium compounds to treat type 2 diabetes is still an open question and therapies using vanadium compounds for e.g. antitumor and anti-parasitic related diseases remain promising.

negative: 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.

negative: Understanding the Experience of an Extreme Event: A Personal Reflection Mental models, which include our assumptions about how the world works, influence how we experience extreme events, such as the Australian bushfires. In turn, they can be altered by those experiences. Understanding (changes to) our mental models can help communities plan for, and recover from, extreme events.

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: VIRUSES | Introduction Abstract Several virus types can contaminate food, with the consequent possibility of human infection. The most common foodborne virus is norovirus, with hepatitis A and hepatitis E viruses also being prominent. Food can be directly contaminated with viruses by infected handlers, and also indirectly by, for example, polluted water used for irrigation or washing. Routine screening of foodstuffs for virus contamination is seldom performed, and may not be wholly cost-effective. Prevention of contamination through risk management of critical control points is more realistic, but physical means of virus elimination will always be required in case of failure of procedural controls. Much research remains necessary before the global challenge of foodborne viruses will be met.

negative: Human respiratory coronavirus OC43: genetic stability and neuroinvasion. The complete genome sequences of the human coronavirus OC43 (HCoV-OC43) laboratory strain from the American Type Culture Collection (ATCC), and a HCoV-OC43 clinical isolate, designated Paris, were obtained. Both genomes are 30,713 nucleotides long, excluding the poly(A) tail, and only differ by 6 nucleotides. These six mutations are scattered throughout the genome and give rise to only two amino acid substitutions: one in the spike protein gene (I958F) and the other in the nucleocapsid protein gene (V81A). Furthermore, the two variants were shown to reach the central nervous system (CNS) after intranasal inoculation in BALB/c mice, demonstrating neuroinvasive properties. Even though the ATCC strain could penetrate the CNS more effectively than the Paris 2001 isolate, these results suggest that intrinsic neuroinvasive properties already existed for the HCoV-OC43 ATCC human respiratory isolate from the 1960s before it was propagated in newborn mouse brains. It also demonstrates that the molecular structure of HCoV-OC43 is very stable in the environment (the two variants were isolated ca. 40 years apart) despite virus shedding and chances of persistence in the host. The genomes of the two HCoV-OC43 variants display 71, 53.1, and 51.2% identity with those of mouse hepatitis virus A59, severe acute respiratory syndrome human coronavirus Tor2 strain (SARS-HCoV Tor2), and human coronavirus 229E (HCoV-229E), respectively. HCoV-OC43 also possesses well-conserved motifs with regard to the genome sequence of the SARS-HCoV Tor2, especially in open reading frame 1b. These results suggest that HCoV-OC43 and SARS-HCoV may share several important functional properties and that HCoV-OC43 may be used as a model to study the biology of SARS-HCoV without the need for level three biological facilities.

negative: Structural analysis of the SARS-CoV-2 methyltransferase complex involved in coronaviral RNA cap creation COVID-19 pandemic is caused by the SARS-CoV-2 virus that has several enzymes that could be targeted by antivirals including a 2’-O RNA methyltransferase (MTase) that is involved in the viral RNA cap formation; an essential process for RNA stability. This MTase is composed of two nonstructural proteins, the nsp16 catalytic subunit and the activating nsp10 protein. We have solved the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site. Based on the structural data we built a model of the MTase in complex with RNA that illustrates the catalytic reaction. A structural comparison to the Zika MTase revealed low conservation of the catalytic site between these two RNA viruses suggesting preparation of inhibitors targeting both these viruses will be very difficult. Together, our data will provide the information needed for structure-based drug design.

negative: Exploring Conformational Transition of 2019 Novel Coronavirus Spike Glycoprotein Between Its Closed and Open States Using Molecular Dynamics Simulations Since its first recorded appearance in December 2019, a novel coronavirus (SARS-CoV-2) causing the disease COVID-19 has resulted in more than 2,000,000 infections and 128,000 deaths. Currently there is no proven treatment for COVID-19 and there is an urgent need for the development of vaccines and therapeutics. Coronavirus spike glycoproteins play a critical role in coronavirus entry into the host cells, as they provide host cell recognition and membrane fusion between virus and host cell. Thus, they emerged as popular and promising drug targets. Crystal structures of spike protein in its closed and open states were resolved very recently in March 2020. These structures comprise 77% of the sequence and provide almost the complete protein structure. Based on down and up positions of receptor binding domain (RBD), spike protein can be in a receptor inaccessible closed or receptor accessible open state, respectively. Starting from closed and open state crystal structures, and also 16 intermediate conformations, an extensive set of all-atom molecular dynamics (MD) simulations in the presence of explicit water and ions were performed. Simulations show that in its down position, RBD has significantly lower mobility compared to its up position; probably caused by the 6 interdomain salt bridges of RBD in down position compared to 3 in up position. Free energy landscapes based on MD simulations revealed a semi-open state located between closed and open states. Minimum energy pathway between down and up positions comprised a gradual salt bridge switching mechanism. Furthermore, although significantly lower than open state, ACE2 binding surface of RBD contained a partial solvent accessibility in its closed state.

negative: Worrying decrease in hospital admissions for myocardial infarction during the COVID-19 pandemic BACKGROUND: How coronavirus 2019 (COVID-19) is affecting management of myocardial infarction is a matter of concern, as medical resources have been massively reorientated and the population has been in lockdown since 17 March 2020 in France. AIMS: To describe how lockdown has affected the evolution of the weekly rate of myocardial infarctions (non-ST-segment and ST-segment elevation) hospital admissions in Lyon, the second largest city in France. To verify the trend observed, the same analysis was conducted for an identical time window during 2018-2019 and for an unavoidable emergency, i.e. birth. METHODS: Based on the national hospitalisation database [Programme de médicalisation des systèmes d'information (PMSI)], all patients admitted to the main public hospitals for a principal diagnosis of myocardial infarction or birth during the 2nd to the 14th week of 2020 were included. These were compared with the average number of patients admitted for the same diagnosis during the same time window in 2018 and 2019. RESULTS: Before lockdown, the number of admissions for myocardial infarction in 2020 differed from that in 2018-2019 by less than 10%; after the start of lockdown, it decreased by 31% compared to the corresponding time window in 2018-2019. Conversely, the numbers of births remained stable across years and before and after the start of lockdown. CONCLUSION: This study strongly suggests a decrease in the number of admissions for myocardial infarction during lockdown. Although we do not have a long follow-up to determine whether this trend will endure, this is an important warning for the medical community and health authorities.

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: The use of nucleic acid hybridization to detect human coronaviruses We have applied an RNA: RNA hybridization test for the detection of human coronavirus 229E. This test is undergoing further development but already allows a diagnosis of HCV 229E infection within 48 hours.

negative: Effect of Heat Moisture Exchanger on Aerosol Drug Delivery and Airway Resistance in Simulated Ventilator-Dependent Adults Using Jet and Mesh Nebulizers. BACKGROUND Placement of a heat moisture exchanger (HME) between aerosol generator and patient has been associated with greatly reduced drug delivery. The purpose of this study was to evaluate the effect of filtered and nonfiltered HMEs placed between nebulizer and patient on aerosol deposition and airway resistance (Raw) in simulated ventilator-dependent adults. METHODS An in vitro lung model was developed to simulate a mechanically ventilated adult (Vt 500 mL, RR 15/min, and PEEP 5 cmH2O, using two inspiratory flow rates 40 and 50 L/min) using an intubated adult manikin with an endotracheal tube (8 mmID). The bronchi of the manikin were connected to a Y-adapter through a collecting filter (Respirgard II) attached to a test lung through a heated humidifier (37°C producing 100% relative humidity) to simulate exhaled humidity. For treatment conditions, a nonfiltered HME (ThermoFlo™ 6070; ARC Medical) and filtered HMEs (ThermoFlo™ Filter; ARC Medical and PALL Ultipor; Pall Medical) were placed between the ventilator circuit at the endotracheal tube and allowed to acclimate to the exhaled heat and humidity for 30 minutes before aerosol administration. Airway resistance (cmH2O/L/s) was taken at 0, 10, 20, and 30 minutes after HME placement and after each of four aerosol treatments. Albuterol sulfate (2.5 mg/3 mL) was administered with jet (Misty Max 10; Airlife) and mesh (Aerogen Solo; Aerogen) nebulizers positioned in the inspiratory limb proximal to the Y-adapter. Control consisted of nebulization with no HME. Drug was eluted from filter at the end of the trachea and measured using spectrophotometry (276 nm). RESULTS Greater than 60% of the control dose was delivered through the ThermoFlo. No significant difference was found between the first four treatments given by the jet (p = 0.825) and the mesh (p = 0.753) nebulizers. There is a small increase in Raw between pre- and post-four treatments with the jet (p = 0.001) and mesh (p = 0.015) nebulizers. Aerosol delivery through filtered HMEs was similar (<0.5%) across the four treatments. Airway resistance was similar using the ThermoFlo Filter. With the PALL Ultipor, changes in Raw increased with mesh nebulizer after treatment (p = 0.005). Changes in resistance pre- and post-treatment were similar with both filtered HMEs. CONCLUSION The ThermoFlo™ nonfilter HME allowed the majority of the control dose to be delivered to the airway. Increases in Raw would likely not be outside of a tolerable range in ventilated patients. In contrast, filtered HMEs should not be placed between nebulizers and patient airways. Further research with other HMEs and materials is warranted.

negative: Dissecting racial disparities in multiple myeloma-clues from differential immunoglobulin levels.

negative: Chapter 16 Dengue Virus Abstract Dengue virus (DENV) belongs to the family Flaviviridae, genus Flavivirus. It is a single-stranded positive-sense ribonucleic acid virus with 10,700 bases. The genus Flavivirus includes other arthropod borne viruses such as yellow fever virus, West Nile virus, Zika virus, tick-borne encephalitis virus. It infects ~50–200 million people annually, putting over 3.6 billion people living in tropical regions at risk and causing ~20,000 deaths annually. The expansion of dengue is attributed to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement, and also viral evolution. There are four antigenically different serotypes of DENV based on the differences in their viral structural and nonstructural proteins. DENV infection causes a spectrum of illness ranging from asymptomatic to dengue fever to severe dengue shock syndrome. Infection with one serotype confers lifelong immunity against that serotype, but heterologus infection leads to severe dengue hemorrhagic fever due to antibody-dependent enhancement. Diagnosis of dengue infections is based mainly on serological detection of either antigen in acute cases or antibodies in both acute and chronic infection. Viral detection and real-time PCR detection though helpful is not feasible in resource poor setup. Treatment of dengue depends on symptomatic management along with fluid resuscitation and may require platelet transfusion. Although vaccine development is in late stages of development, developing a single vaccine against four serotypes often causes serious challenges to researchers; hence, the main stay of prevention is vector control and management.

negative: Effects of Surface Material, Ventilation, and Human Behavior on Indirect Contact Transmission Risk of Respiratory Infection Infectious particles can be deposited on surfaces. Susceptible persons who contacted these contaminated surfaces may transfer the pathogens to their mucous membranes via hands, leading to a risk of respiratory infection. The exposure and infection risk contributed by this transmission route depend on indoor surface material, ventilation, and human behavior. In this study, quantitative infection risk assessments were used to compare the significances of these factors. The risks of three pathogens, influenza A virus, respiratory syncytial virus (RSV), and rhinovirus, in an aircraft cabin and in a hospital ward were assessed. Results showed that reducing the contact rate is relatively more effective than increasing the ventilation rate to lower the infection risk. Nonfabric surface materials were found to be much more favorable in the indirect contact transmission for RSV and rhinovirus than fabric surface materials. In the cases considered in this study, halving the ventilation rate and doubling the hand contact rate to surfaces and the hand contact rate to mucous membranes would increase the risk by 3.7–16.2%, 34.4–94.2%, and 24.1–117.7%, respectively. Contacting contaminated nonfabric surfaces may pose an indirect contact risk up to three orders of magnitude higher than that of contacting contaminated fabric surfaces. These findings provide more consideration for infection control and building environmental design.

negative: Chapter 15 Application of Microbial Cleaning Technology for Removal of Surface Contamination Abstract Microbial cleaning takes advantage of naturally-occurring microbes to remove a wide variety of contaminants from various surfaces. The method is based on the affinity of microbes for hydrocarbons that are digested, producing harmless carbon dioxide, water, and soluble fatty acids. The microbes are nonpathogenic and are safe to handle and dispose. The process is environmentally-friendly and is less expensive than solvent cleaning, but it is not applicable to high precision cleaning applications. Typical applications include parts washing; oil and grease removal from concrete and other floor surfaces, and from drains and grease traps; cleaning and disinfection in healthcare facilities; cleaning of historical artworks and structures; and household and institutional cleaning applications.

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: A Novel Method for the Estimation of a Dynamic Effective Reproduction Number (Dynamic-R) in the CoViD-19 Outbreak The CoViD-19 outbreak has escalated to a pandemic in the last few weeks, with no signs of stopping. Pharmaceutical solutions based upon virologic studies, at this point, remain inconclusive. In contrast, this paper looks towards epidemiological models during this phase of viral growth, in particular, by providing a responsive, timely model of the R value based on the previous few days' results. Such an R value, although bearing less statistical precision due to limited sampling, could allow R to become a more effective, responsive standalone measure of infectious transmission. It demonstrates that the R value can be used as a dynamic, time-dependent indicator without the use of curve-fitting, and also estimates the most recent R-value of the CoViD-19 outbreak to be about 4.29, based on the data from the previous 3 days.

negative: Induction of a systemic antiviral state in vivo in the domestic cat with a class A CpG oligonucleotide Abstract The evolution of cats as a solitary species has pressured feline viruses to develop highly efficient transmission strategies, the ability to persist within the host for long periods of time and the aptitude to adapt to natural and vaccine-induced immunological pressures. These characteristics render feline viruses particularly dangerous in catteries, shelters and rescue homes, were cats from different backgrounds live in close proximity. The possibility to induce short-term resistance of newcomer cats to a broad variety of viruses could help prevent the dissemination of viruses both within and outside such facilities. Oligonucleotides (ODN) containing unmethylated cytosine phosphate guanosine (CpG) motifs stimulate innate immune responses in mammals. We have previously shown that ODN 2216, a class A CpG ODN, promotes the expression by feline immune cells of potent antiviral molecules that increase resistance of feline fibroblastic and epithelial cell lines to five common feline viruses. With the aim to test the safety and extent of the biological effects of ODN 2216 in the domestic cat, we performed an initial in vivo experiment in which two cats were injected the molecule once subcutaneously and two additional cats received control treatments. No side effects to administration of ODN 2216 were observed. Moreover, this molecule induced the expression of the myxovirus resistance (Mx) gene, a marker for the instigation of innate antiviral processes, in blood as well as in oral, conjunctival and rectal mucosa cells, indicating systemic biological activity of the molecule with protective potential at viral entry sites. Mx mRNA levels were already elevated in blood 6h post injection of ODN 2216, reached peak levels within 24h and returned to basal values by 96–192h after administration of the molecule. Similar induction patterns were observed in all analyzed mucosal cells. Plasma collected from treated cats at regular intervals until 96–192h could moreover induce Mx mRNA expression in fcwf-4 cells and increase resistance of these cells to feline calicivirus inoculation. Finally, Mx mRNA levels measured in blood correlated with the degree of viral inhibition that was induced by plasma from the same cat and the same experimental time point. Our results altogether underline the promising potential of ODN 2216 in promoting antiviral defense mechanisms and inducing temporary resistance to viral infections in vivo in the domestic cat.

negative: The immune responses of HLA-A*0201 restricted SARS-CoV S peptide-specific CD8+ T cells are augmented in varying degrees by CpG ODN, PolyI:C and R848 Abstract The induction of antigen specific memory CD8+ T cells in vivo is very important to new vaccines against infectious diseases. In the present study, we aimed to evaluate the immune responses of peptide-specific CD8+ T cells induced by HLA-A*0201 restricted severe acute respiratory syndrome-associated coronavirus (SARS-CoV) S epitopes plus CpG oligodeoxynucleotide (CpG ODN), PolyI:C and R848 as adjuvants. Furthermore, the generation, distribution and phenotype of long-lasting peptide-specific memory CD8+ T cells were assessed by ELISA, ELISPOT and flow cytometry. Our results showed that antigen specific CD8+ T cells were elicited by HLA-A*0201 restricted SARS-CoV S epitopes. Furthermore, the frequency of peptide-specific CD8+ T cells was dramatically increased after both prime and boost immunization with peptides plus CpG ODN, whereas slight enhancements were induced following boost vaccination with peptides plus PolyI:C or R848. SARS-CoV S peptide-specific IFN-γ+CD8+ T cells were distributed throughout the lymphoid and non-lymphoid tissues. Results also demonstrated that the HLA-A*0201 restricted peptide-specific CD8+ T cells induced by peptides plus CpG ODN carried a memory cell phenotype with CD45RB+ and CD62L− and possessed long-term survival ability in vivo. Taken together, our results implied that HLA-A*0201 restricted SARS-CoV S epitopes plus CpG ODN might be the superior candidates for SARS vaccine.

negative: Selection of homemade mask materials for preventing transmission of COVID-19: a laboratory study The Coronavirus Disease 2019 (COVID-19) has swept the whole world with high mortality. Since droplet transmission is the main route of transmission, wearing a mask serves as a crucial preventive measure. However, the virus has spread quite quickly, causing severe mask shortage. Finding alternative materials for homemade masks while ensuring the significant performance indicators will help alleviate the shortage of masks. Referring to the national standard for the "Surgical Mask" of China, 17 materials to be selected for homemade masks were tested in four key indicators: pressure difference, particle filtration efficiency, bacterial filtration efficiency and resistance to surface wetting. Eleven single-layer materials met the standard of pressure difference ([≤]49 Pa), of which 3 met the standard of resistance to surface wetting ([≥]3), 1 met the standard of particle filtration efficiency ([≥]30%), but none met the standard of bacterial filtration efficiency ([≥]95%). Based on the testing results of single-layer materials, fifteen combinations of paired materials were tested. The results showed that three double-layer materials including double-layer medical non-woven fabric, medical non-woven fabric plus non-woven shopping bag, and medical non-woven fabric plus granular tea towel could meet all the standards of pressure difference, particle filtration efficiency, and resistance to surface wetting, and were close to the standard of the bacterial filtration efficiency. In conclusion, if resources are severely lacking and medical masks cannot be obtained, homemade masks using available materials, based on the results of this study, can minimize the chance of infection to the maximum extent.

negative: Chapter 6 Conservation Genetics of the Cheetah: Genetic History and Implications for Conservation Abstract From allozymes in 1983 to whole genomes in 2015, genetic studies of the cheetah have been extensive. In this chapter we provide an overview of the available literature. Overall, patterns of genetic variation provided evidence of low variability and suggest this loss occurred thousands of years ago. Differences between published subspecies were supported genetically. At a local scale, populations were generally considered panmictic with minor genetic structure. Although cheetahs have persisted despite low genetic variability, important questions arise from these findings: Does the cheetah have the ability to adapt to and evolve with future changes in environmental and infectious pressure? How would cheetahs cope with further loss of genetic diversity? Connectivity in the wild should be maintained via prevention of habitat loss, while management of small isolated populations may require reestablishing gene flow. Genetics could assist captive-breeding decisions and provide forensic evidence as to the geographical origin of illegally traded animals.

negative: Is the ultrasonic scalpel recommended in head and neck surgery during the COVID‐19 pandemic? State‐of‐the‐art review BACKGROUND: Guidelines for ultrasonic devices use are imperative because infectious aerosols arising from airway procedures were a key etiologic factor in prior coronavirus outbreaks. This manuscript aims to summarize the available recommendations and the most relevant concepts about the use of ultrasonic scalpel during the SARS‐CoV‐2 pandemic. METHODS: Literature review of manuscripts with patients, animal models, or in vitro studies where the ultrasonic scalpel was used and the plume produced was analyzed in a quantitative and/ or qualitative way. DISCUSSION: Activated devices with tissue produce a biphasic bioaerosol composed (size 68.3‐994 nm) of tissue particles, blood, intact and no viable cells, and carcinogenic or irritant hydrocarbons (benzene, ethylbenzene, styrene, toluene, heptene, and methylpropene). CONCLUSION: It is imperative to use an active smoke evacuator, to avoid ultrasonic scalpel use in COVID‐19 positive patients and in upper airway surgery, as well as to follow the protection recommendations of the guidelines for management this type of patients.

negative: Does mRNA structure contain genetic information for regulating co-translational protein folding? Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model with supports of genomic data is still lacking. Recent technological advances have enabled much needed genome-wide experiments. While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of mRNA structure in the regulation of protein folding by modulating translational elongation rate. In conjunctions with previous theories, this mechanistic model of protein folding guided by mRNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.

negative: CHAPTER 14 RABBITS Publisher Summary This chapter provides an overview of the biology and medical care of rabbits. There are about 50 different breeds of domestic rabbits. Rabbits have very thin and delicate skin that is covered with fine fur comprised of both a soft undercoat and stiff guard hairs. Care must be taken when clipping fur because the skin is prone to tearing. A rabbit enclosure should be large enough to provide a sleeping space, eating space, and latrine. Animals housed for long periods of time should also have ample room to exercise. The enclosure should be tall enough to allow the rabbit to sit up and not have its ears touch the top of the cage. Because rabbits are prone to heatstroke, they should be housed in temperatures ranging from 60°F to 75°F. If rabbits are housed outdoors, they must have access to shade and clean water, and the shelter should protect them from the elements as well as from predators. The ideal substrate for rabbits is grass hay; however, for indoor, caged rabbits, a foam rubber pad or a towel covered with newspaper and a thick layer of timothy hay can also be used.

negative: Assessment of N95 respirator decontamination and re-use for SARS-CoV-2 The unprecedented pandemic of SARS-CoV-2 has created worldwide shortages of personal protective equipment, in particular respiratory protection such as N95 respirators. SARS-CoV-2 transmission is frequently occurring in hospital settings, with numerous reported cases of nosocomial transmission highlighting the vulnerability of healthcare workers. In general, N95 respirators are designed for single use prior to disposal. Here, we have analyzed four readily available and often used decontamination methods: UV, 70% ethanol, 70C heat and vaporized hydrogen peroxide for inactivation of SARS-CoV-2 on N95 respirators. Equally important we assessed the function of the N95 respirators after multiple wear and decontamination sessions.

negative: In-Silico evidence for two receptors based strategy of SARS-CoV-2 We propose a novel numerical method able to determine efficiently and effectively the relationship of complementarity between portions of protein surfaces. This innovative and general procedure, based on the representation of the molecular iso-electron density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, that was unfeasible with previous methods. We first tested the method with a large dataset of known protein complexes obtaining an overall area under the ROC curve of 0.76 in the blind recognition of binding sites and then applied it to investigate the features of the interaction between the Spike protein of SARS-CoV-2 and human cellular receptors. Our results indicate that SARS-CoV-2 uses a dual strategy: its spike protein could also interact with sialic acid receptors of the cells in the upper airways, in addition to the known interaction with Angiotensin-converting enzyme 2.

negative: Estimated effectiveness of symptom and risk screening to prevent the spread of COVID-19 Traveller screening is being used to limit further spread of COVID-19 following its recent emergence, and symptom screening has become a ubiquitous tool in the global response. Previously, we developed a mathematical model to understand factors governing the effectiveness of traveller screening to prevent spread of emerging pathogens (Gostic et al., 2015). Here, we estimate the impact of different screening programs given current knowledge of key COVID-19 life history and epidemiological parameters. Even under best-case assumptions, we estimate that screening will miss more than half of infected people. Breaking down the factors leading to screening successes and failures, we find that most cases missed by screening are fundamentally undetectable, because they have not yet developed symptoms and are unaware they were exposed. Our work underscores the need for measures to limit transmission by individuals who become ill after being missed by a screening program. These findings can support evidence-based policy to combat the spread of COVID-19, and prospective planning to mitigate future emerging pathogens.

negative: #SendHelpNow: Mental wellness and virtual connection in the age of coronavirus Coronavirus, coronavirus disease (COVID‐19) and social/physical distancing are among the words that have become household names amidst this pandemic. Not only has our vocabulary changed, but also the ways we connect with others. We have become even more reliant on technological advances for business, education, pleasure and other activities. In fact, 93% of Americans report that an outage in internet or cellular service during the outbreak would cause problems in their daily lives (Pew Research Center, 2020).

negative: Inactivation of SARS Coronavirus by Means of Povidone-Iodine, Physical Conditions and Chemical Reagents The efficacy of several povidone-iodine (PVP-I) products, a number of other chemical agents and various physical conditions were evaluated for their ability to inactivate the severe acute respiratory syndrome coronavirus (SARS-CoV). Treatment of SARS-CoV with PVP-I products for 2 min reduced the virus infectivity from 1.17 × 10(6) TCID(50)/ml to below the detectable level. The efficacy of 70% ethanol was equivalent to that of PVP-I products. Fixation of SARS-CoV-infected Vero E6 cells with a fixative including formalin, glutaraldehyde, methanol and acetone for 5 min or longer eliminated all infectivity. Heating the virus at 56°C for 60 min or longer reduced the infectivity of the virus from 2.6 × 10(7) to undetectable levels. Irradiation with ultraviolet light at 134 μW/cm(2) for 15 min reduced the infectivity from 3.8 × 10(7) to 180 TCID(50)/ml; however, prolonged irradiation (60 min) failed to eliminate the remaining virus, leaving 18.8 TCID(50)/ml.

negative: A 24-month evaluation of a percutaneous osseointegrated limb-skin interface in an ovine amputation model. Percutaneous osseointegrated (OI) prostheses directly connect an artificial limb to the residual appendicular skeleton via a permanently implanted endoprosthesis with a bridging connector that protrudes through the skin. The resulting stoma produces unique medical and biological challenges. Previously, a study using a large animal amputation model indicated that infection could be largely prevented, for at least a 12-month period, but the terminal epithelium continued to downgrow. The current study was undertaken to test the longer-term efficacy of this implant construct to maintain a stable skin-implant interface for 24 months. Using the previously successful amputation and implantation surgical procedure, a total of eight sheep were fitted with a percutaneous OI prosthesis. Two animals were removed from the study due to early complications. Of the remaining six sheep, one (16.7%) became infected at 15-months post-implantation and five remained infection-free for the intended 24 months. The histological data of the remaining animals further confirmed the grossly observable epithelial downgrowth. Albeit a receding interface, it was clear that all animals that survived to the end of the study had residual fibrous soft-tissue ingrowth into, and debris within, the exposed titanium porous-coated surface. Overall, the data demonstrated that the porous coated subdermal barrier offered initial protection against infection. However, the fibrous skin attachment was continuously lysed over time by the down-growing epithelium.

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: 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.

negative: 36 Viral Febrile Illnesses and Emerging Pathogens Abstract Emerging or emerged diseases and viral pathogens are responsible historically and currently for large epidemics, global pandemics, and significant morbidity and mortality. Our civilization will continue to face the emergence of new pathogens and viruses: viruses will continue to evolve and adapt to new environments at a high rate; our population continues to grow through birth rate, land development, and migration; climate change will continue to increase the vector burden and spread and change the migratory pattern of animals; and our societal mobility will continue to increase through rapid transportation. The clinical evaluation of the febrile patient with a potential emerging viral pathogen involves documenting the likelihood for an infection by a detailed travel history, calculation of an incubation time by exposure, and an understanding of the disease progression though the clinical illness, which drives the differential diagnosis and the type of diagnostics ordered. Ultimately, the proper identification and diagnosis of a patient with a viral febrile illness due to an emerging pathogen will elicit the appropriate precautions to protect health care providers and communities, deliver appropriate therapeutic interventions, and initiate a targeted public health response.

negative: Post-mortem histology in transient receptor potential cation channel subfamily V member 6 (TRPV6) under-mineralising skeletal dysplasia suggests postnatal skeletal recovery: a case report BACKGROUND: The calcium-selective channel TRPV6 (transient receptor potential cation channel subfamily V member 6) is crucial for maternal-fetal calcium transport across the placenta. TRPV6 mutations have recently been associated with an antenatally severe under-mineralising skeletal dysplasia accompanied by postnatal biochemical abnormalities. This is the first post-mortem report in a patient with TRPV6 skeletal dysplasia. CASE PRESENTATION: The female infant had severe antenatal and postnatal skeletal abnormalities by 20 weeks gestation and was ventilator-dependent from birth. These skeletal abnormalities were apparent at an earlier gestational age than in previous reported cases and a more severe clinical course ensued. Biochemical and skeletal abnormalities, including bone density, improved postnatally but cardiac arrest at 4 months of age led to withdrawal of intensive care. Compound heterozygous TRPV6 variants (c.1978G > C p.(Gly660Arg) and c.1528C > T p.(Arg510Ter)) were identified on exome sequencing. Post-mortem identified skeletal abnormalities but no specific abnormalities in other organ systems. No placental pathology was found, multi-organ histological features reflected prolonged intensive care only. Post-mortem macroscopic examination indicated reduced thoracic size and short, pale and pliable ribs. Histological examination identified reduced number of trabeculae in the diaphyses (away from the growth plates), whereas metaphyses showed adequate mineralisation and normal number of trabeculae, but with slightly enlarged reactive chondrocytes, indicating post-natal skeletal growth recovery. Post-mortem radiological findings demonstrated improved bone density, improved rib width, healed fractures, although ribs were still shorter than normal. Long bones (especially humerus and femur) had improved from initial poorly defined metaphyses and reduced bone density to sharply defined metaphyses, prominent growth restart lines in distal diaphyses and bone-in-bone appearance along diaphyses. CONCLUSIONS: This case provide bone histological confirmation that human skeletal development is compromised in the presence of TRPV6 pathogenic variants. Post-mortem findings were consistent with abnormal in utero skeletal mineralisation due to severe calcium deficit from compromised placental calcium transfer, followed by subsequent phenotypic improvement with adequate postnatal calcium availability. Significant skeletal recovery occurs in the early weeks of postnatal life in TRPV6 skeletal dysplasia.

negative: The Battle Against COVID-19: Where Do We Stand Now?

negative: Household Transmission of SARS-CoV-2, Zhuhai, China, 2020 BACKGROUND: To illustrate the extent of transmission, identify affecting risk factors and estimate epidemiological modeling parameters of SARS-CoV-2 in household setting. METHODS: We enrolled 35 confirmed index cases and their 148 household contacts, January 2020–February 2020, in Zhuhai, China. All participants were interviewed and asked to complete questionnaires. Household contacts were then prospectively followed active symptom monitoring through the 21-day period and nasopharyngeal and/or oropharyngeal swabs were collected at 3-7 days intervals. Epidemiological, demographic and clinical data (when available) were collected. RESULTS: Assuming that all these secondary cases were infected by their index cases, the second infection rate (SIR) in household context is 32.4% (95% confidence interval [CI] 22.4%-44.4%), with 10.4% of secondary cases being asymptomatic. Multivariate analysis showed that household contacts with underlying medical conditions, a history of direct exposure to Wuhan and its surrounding areas, and shared vehicle with an index patient were associated with higher susceptibility. Household members without protective measures after illness onset of the index patient seem to increase the risk for SARS-CoV-2 infection. The median incubation period and serial interval within household were estimated to be 4.3 days (95% CI; 3.4 to 5.3 days) and 5.1 days (95% CI; 4.3 to 6.2 days), respectively. CONCLUSION: Early isolation of patients with COVID-19 and prioritizing rapid contact investigation, followed by active symptom monitoring and periodic laboratory evaluation, should be initiated immediately after confirming patients to address the underlying determinants driving the continuing pandemic.

negative: Partitioning of Viruses in Wastewater Systems and Potential for Aerosolization [Image: see text] To gain insight into the potential for aerosolization of viruses in wastewater systems, we investigated the partitioning of MS2 and Phi6 bacteriophages in synthetic sludge and anaerobically digested sludge from a wastewater treatment plant. We evaluated partitioning among the liquid, solids, and material surfaces of porcelain, concrete, polyvinyl chloride (PVC), and polypropylene. In all cases, at least 94% of the virions partitioned into the liquid fraction. In real sludge, no more than 0.8% of virions partitioned to the solids and no more than 6% to the material surface. Both MS2 and Phi6 partitioned more to the surface of concrete and polypropylene than to the surface of porcelain or PVC. Partitioning of viruses in wastewater among the liquid, biosolids, and material surface does not appear to mitigate the potential for aerosolization of virus, as most of the virus remains in the liquid phase.

negative: Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has attracted interest because of its global rapid spread, clinical severity, high mortality rate, and capacity to overwhelm healthcare systems [1, 2]. SARS-CoV-2 transmission occurs mainly through droplets, although surface contamination contributes and debate continues on aerosol transmission [3–5].

negative: Life-threatening Development of Cardiac Tamponade in the Span of 24 Hours Cardiac tamponade is a medical emergency that requires immediate treatment. Caused by the development of fluid in the pericardial space, it can result in a severe decrease in cardiac output. When encountering patients with severe hypotension and tachycardia, emergency physicians must always consider the diagnosis of tamponade to facilitate prompt and effective treatment and stabilization. We report our experience with a patient who developed life-threatening cardiac tamponade within a span of less than 24 hours.

negative: 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.

negative: Pathologies virales émergentes en pneumologie

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

negative: Palmitoylations on murine coronavirus spike proteins are essential for virion assembly and infectivity. Coronavirus spike (S) proteins are palmitoylated at several cysteine residues clustered near their transmembrane-spanning domains. This is achieved by cellular palmitoyl acyltransferases (PATs), which can modify newly synthesized S proteins before they are assembled into virion envelopes at the intermediate compartment of the exocytic pathway. To address the importance of these fatty acylations to coronavirus infection, we exposed infected cells to 2-bromopalmitate (2-BP), a specific PAT inhibitor. 2-BP profoundly reduced the specific infectivities of murine coronaviruses at very low, nontoxic doses that were inert to alphavirus and rhabdovirus infections. 2-BP effected only two- to fivefold reductions in S palmitoylation, yet this correlated with reduced S complexing with virion membrane (M) proteins and consequent exclusion of S from virions. At defined 2-BP doses, underpalmitoylated S proteins instead trafficked to infected cell surfaces and elicited cell-cell membrane fusions, suggesting that the acyl chain adducts are more critical to virion assembly than to S-induced syncytial developments. These studies involving pharmacologic inhibition of S protein palmitoylation were complemented with molecular genetic analyses in which cysteine acylation substrates were mutated. Notably, some mutations (C1347F and C1348S) did not interfere with S incorporation into virions, indicating that only a subset of the cysteine-rich region provides the essential S-assembly functions. However, the C1347F/C1348S mutant viruses exhibited relatively low specific infectivities, similar to virions secreted from 2-BP-treated cultures. Our collective results indicate that the palmitate adducts on coronavirus S proteins are necessary in assembly and also in positioning the assembled envelope proteins for maximal infectivity.

negative: How fast does the SARS-Cov-2 virus really mutate in heterogeneous populations? We introduce the problem of determining the mutational support of genes in the SARS-Cov-2 virus and estimating the distribution of mutations within different genes using small sample sizes that do not allow for accurate maximum likelihood estimation. The mutational support refers to the unknown number of sites mutated across all strains and individual samples of the SARS-Cov-2 genome; given the high cost and limited availability of real-time polymerase chain reaction (RT-PCR) test kits, especially in early stages of infections when only a small number of genomic samples (∼ 1000s) are available that do not allow for determining the exact degree of mutations in an RNA virus that comprises roughly 30, 000 nucleotides. Nevertheless, working with small sample sets is required in order to quickly predict the mutation rate of this and other viruses and get an insight into their transformational power. Furthermore, with the small number of samples available, it is hard to estimate the mutational landscape across different age/gender groups and geographical locations which may be of great importance in assessing different risk categories and factors influencing susceptibility to infection. To this end, we use our state-of-the art polynomial estimator techniques and the Good-Turing estimator to obtain estimates based on only roughly 1, 000 samples per category. Our analysis reveals an interesting finding: the mutational support appears to be statistically more significant in patients which appear to have lower infection rates and handle the exposure with milder symptoms, such as women and people of relatively young age (≤ 55).

negative: Medical Waste Management Practice during the 2019-2020 Novel Coronavirus Pandemic: Experience in a General Hospital It is currently a critical period for the prevention and control of the COVID-19 pandemic. Since the medical waste disposal could be an important way to control the source of infection, standardization and strict implementation of the management of COVID-19 related medical waste should be with careful consideration to reduce the risk of epidemic within hospitals. This study illustrates the practice of medical waste disposal responding to the 2019-2020 novel coronavirus pandemic.

negative: 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.

negative: 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.

negative: 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.

negative: Novel Coronavirus: Current Understanding of Clinical Features, Diagnosis, Pathogenesis, and Treatment Options Since December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in devastating consequences worldwide and infected more than 350,000 individuals and killed more than 16,000 people. SARS-CoV-2 is the seventh member of the coronavirus family to affect humans. Symptoms of COVID-19 include fever (88%), cough (68%), vomiting (5%) and diarrhoea (3.7%), and transmission of SARS-CoV-2 is thought to occur from human to human via respiratory secretions released by the infected individuals when coughing and sneezing. COVID-19 can be detected through computed tomography scans and confirmed through molecular diagnostics tools such as polymerase chain reaction. Currently, there are no effective treatments against SARS-CoV-2, hence antiviral drugs have been used to reduce the development of respiratory complications by reducing viral load. The purpose of this review is to provide a comprehensive update on the pathogenesis, clinical aspects, diagnosis, challenges and treatment of SARS-CoV-2 infections.

negative: Long-Term Care Facilities and the Coronavirus Epidemic: Practical Guidelines for a Population at Highest Risk

negative: A Study of Nonstructural Protein 1 of SARS Coronavirus Severe acute respiratory syndrome coronavirus (SARS-CoV) encoded nonstructural protein 1 (nsp1) orchestrates a multi-pronged mechanism to down regulate host gene expression, also known as host shutoff Nsp1 is a 180 amino acid long protein with primarily flexible structure that allows nsp1 to interact with various cellular factors during host shutoff to inhibit translation and promote mRNA decay Mutations of the surface residues of nsp1 either attenuates or augments its host shutoff function prompting the hypothesis that these residues bind cellular proteins that facilitate nsp1 during host shutoff To identify cellular proteins that interact with nsp1 and assist its function, we conducted a quantitative proteomics experiment by comparing protein complexes associated with nsp1 and its inactive mutant (K164AH165A) and computer modeling to predict structural changes By comparing protein complexes, we identified a previously undetected mechanism by which nsp1 exploits the nuclear pore complex and disrupts nuclear-cytoplasmic transport of biomolecules Expression of nsp1 in 293 cells disrupts Nup93 localization around the nuclear envelope without triggering proteolytic degradation of the protein while other nucleoporins and the nuclear lamina remain unperturbed, suggesting a significant alteration of the nuclear pore complex in the presence of nsp1 However, expression of mutant nsp1, which does not bind to Nup93, does not alter the nuclear pore complex To better understand the structural basis of this protein?s function, we have utilized computational modeling tools, more specifically, I-TASSER (Iterative Threading ASSEmbly Refinement) Structural models of various mutants of nsp1 were obtained (by using I-TASSER) in order to explore the structural impact of different mutations Our preliminary explorations show significant topological changes on nsp1?s surface for specific mutations These perturbations of surface properties can provide a steric-based mechanism of interfering with nsp1?s binding or recognition function therefore, aggravating its host shutoff function

negative: A distinct ERCC1 haplotype is associated with mRNA expression levels in prostate cancer patients Both genetic variants and messenger RNA (mRNA) expression of DNA repair and tumor suppressor genes have been investigated as molecular markers for therapy outcome. However, the phenotypic impact of genetic variants often remained unclear, thus the rationale of their use in risk prediction may be limited. We therefore analyzed genetic variants together with anthropometric and lifestyle factors to see how these affect mRNA levels of ERCC1 , MDM2 and TP53 in primary blood lymphocytes. mRNA expression was measured in 376 prostate cancer patients by quantitative real-time polymerase chain reaction after reverse transcription, and ERCC1 rs11615 T>C, ERCC1 rs3212986 C>A, MDM2 rs2279744 T>G and TP53 rs17878362 (p53PIN3) polymorphisms were determined. Considerable interindividual differences in mRNA expression were found (coefficients of variation: ERCC1 , 45%; MDM2 , 43% and TP53 , 35%). ERCC1 expression was positively correlated with plasma levels of β-carotene ( P = 0.03) and negatively correlated with canthaxanthin ( P = 0.02) and lutein ( P = 0.02). Overall, the polymorphisms affected mRNA expression only weakly. Carriers of a distinct ERCC1 haplotype (CC) showed, however, significantly lower expression values than non-carriers ( P = 0.001). Applying logistic regression, we found that CC haplotype carriers had a 1.69-fold increased odds ratio (95% confidence interval: 1.06–2.71) for reduced ERCC1 mRNA levels. This low ERCC1 expression might be associated with reduced DNA repair and better therapy response. In summary, the association we have found between ERCC1 genotype and mRNA expression supports recent clinical observations that genetic variation in ERCC1 can affect treatment outcome and prognosis. Our study further revealed a modulating effect by nutritional factors.

negative: Laparoscopic and Robotic Urology Surgery during Global Pandemic COVID19 Known laparoscopic and robotic assisted approaches and techniques for the surgical management of urological malignant and benign diseases are commonly used around the World. During the global pandemic COVID19, urology surgeons had to reorganize their daily surgical practice. A concern with the use of minimally invasive techniques arose due to a proposed risk of viral transmission of the coronavirus disease with the creation of pneumoperitoneum. Due to this, we reviewed the literature to evaluate the use of laparoscopy and robotics during the pandemic COVID19. A literature review of viral transmission in surgery and of the available literature regarding the transmission of the COVID19 virus was performed up to April 30, 2020. We additionally reviewed surgical society guidelines and recommendations regarding surgery during this pandemic. Few studies have been performed on viral transmission during surgery. No study has been made regarding this area during minimally invasive urology cases. To date there is no study that demonstrates or can suggest the ability for a virus to be transmitted during surgical treatment whether open, laparoscopic or robotic. There is no society consensus on restricting laparoscopic or robotic surgery. However, there is expert consensus on modification of standard practices to minimize any risk of transmission. During the pandemic COVID19 we recommend the use of specific personal protective equipment for the surgeon, anesthesiologist and nursing staff in the operating room. Modifications of standard practices during minimally invasive surgery such as using lowest intra-abdominal pressures possible, controlled smoke evacuation systems, and minimizing energy device usage are recommended.

negative: Response to: Safe Handling of Containers of Expressed Human Milk in all Settings During the SARS-CoV-2 (COVID-19) Pandemic (Marinelli and Lawrence, 2020)

negative: COVID‐19 diagnosis and management: a comprehensive review Severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2, a novel coronavirus from the same family as SARS‐CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS‐CoV‐2, coronavirus disease 2019 (COVID‐19), presents flu‐like symptoms which can become serious in high‐risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID‐19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: ‘COVID‐19’, ‘2019‐nCoV’, ‘coronavirus’ and ‘SARS‐CoV‐2’. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID‐19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real‐time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow‐up. To date, there is no evidence of any effective treatment for COVID‐19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence‐based treatment modality.

negative: Acute Respiratory Distress Syndrome in Cancer Patients Acute respiratory distress syndrome (ARDS) is a heterogeneous form of acute, diffuse lung injury that is characterized by dysregulated inflammation, increased alveolar-capillary interface permeability, and non-cardiogenic pulmonary edema. In the general population, the incidence and mortality associated with ARDS over the last two decades have steadily declined in parallel with optimized approaches to pneumonia and other underlying causes of ARDS as well as increased utilization of multimodal treatment strategies that include lung-protective ventilation. In the cancer settings, significant declines in the incidence and mortality of ARDS over the past two decades have also been reported, although these rates remain significantly higher than those in the general population. Epidemiologic studies identify infection, including disseminated fungal pneumonias, as a major underlying cause of ARDS in the cancer setting. More than half of cancer patients who develop ARDS will not survive to hospital discharge. Those who do survive often face a protracted and often incomplete recovery, resulting in significant long-term physical, psychological, and cognitive sequelae. The residual organ dysfunction and poor functional status after ARDS may delay or preclude subsequent cancer treatments. As such, close collaboration between the critical care physicians and oncology team is essential in identifying and reversing the underlying causes and optimizing treatments for cancer patients with ARDS. This chapter reviews the diagnosis and common causes of ARDS in cancer and gives an update on the general management principles for cancer patients with ARDS in the ICU.

negative: COVID-19: ICU delirium management during SARS-CoV-2 pandemic The novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.

negative: Visibility and transmission: complexities around promoting hand hygiene in young children – a qualitative study BACKGROUND: Effective hand hygiene practice can reduce transmission of diseases such as respiratory tract infections (RTIs) and gastrointestinal infections, especially in young children. While hand hygiene has been widely promoted within Australia, primary care providers’ (PCPs) and parents’ understanding of hand hygiene importance, and their views on hand hygiene in reducing transmission of diseases in the community are unclear. Therefore, the aim of this study was to explore the views of PCPs and parents of young children on their knowledge and practice of hand hygiene in disease transmission. METHODS: Using a cross-sectional qualitative research design, we conducted 30 in-depth interviews with PCPs and five focus groups with parents (n = 50) between June 2014 and July 2015 in Melbourne, Australia. Data were thematically analysed. RESULTS: Participants agreed that hand hygiene practice was important in reducing disease transmissions. However, barriers such as variations of hand hygiene habits, relating visibility to transmission; concerns around young children being obsessed with washing hands; children already being ‘too clean’ and the need to build their immunity through exposure to dirt; and scepticism that hand hygiene practice was achievable in young children, all hindered participants’ motivation to develop good hand hygiene behaviour in young children. CONCLUSION: Despite the established benefits of hand hygiene, sustained efforts are needed to ensure its uptake in routine care. To overcome the barriers identified in this study a multifaceted intervention is needed that includes teaching young children good hand hygiene habits, PCPs prompting parents and young children to practice hand hygiene when coming for an RTI consultation, reassuring parents that effective hand hygiene practice will not lead to abnormal psychological behaviour in their children, and community health promotion education campaigns.

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: Identification of major histocompatibility complex class I C molecule as an attachment factor that facilitates coronavirus HKU1 spike-mediated infection. Human coronavirus HKU1 (HCoV-HKU1) is a recently discovered human coronavirus associated with respiratory tract infections worldwide. In this study, we have identified the major histocompatibility complex class I C molecule (HLA-C) as an attachment factor in facilitating HCoV-HKU1 spike (S)-mediated infection. HCoV-HKU1 S pseudotyped virus was assembled using a human immunodeficiency virus type 1-derived reporter virus harboring the human codon-optimized spike of HCoV-HKU1. We identified human alveolar epithelial A549 cells as the most susceptible cell line among those tested to infection by HCoV-HKU1 S pseudotypes. A549 cells were shown to bind purified soluble HCoV-HKU1 S(1-600) glycopeptide. To search for the functional receptor for HCoV-HKU1, an A549 cDNA expression library was constructed and transduced into the nonpermissive, baby hamster kidney cells line BHK-21. Transduced cells that bind soluble HCoV-HKU1 S(1-600) glycoprotein with C-terminal FLAG were sorted. Sequencing of two independent clones revealed cDNA inserts encoding HLA-C. Inhibition of HLA-C expression or function by RNAi silencing and anti-HLA-C antibody decreased HCoV-HKU1 S pseudotyped virus infection of A549 cells by 62 to 65%, whereas pretreatment of cells with neuraminidase decreased such infection by only 13%. When HLA-C was constitutively expressed in another nonpermissive cell line, NIH-3T3, quantitative PCR showed that the binding of HCoV-HKU1 S pseudotyped virus to cell surfaces was increased by 200-fold, but the cells remained nonsusceptible to HCoV-HKU1 S pseudotyped virus infection. Our data suggest that HLA-C is involved in the attachment of HCoV-HKU1 to A549 cells and is a potential candidate to facilitate cell entry. However, other unknown surface proteins on A549 cells may be concomitantly utilized by S glycoprotein of HCoV-HKU1 during viral entry. Further studies are required to elucidate other putative receptors or coreceptors for HCoV-HKU1 and the mechanism of HCoV-HKU1 S-mediated cell entry.

negative: Does SARS‐CoV‐2 has a longer incubation period than SARS and MERS? The outbreak of a novel coronavirus (SARS‐CoV‐2) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS‐CoV‐2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS‐CoV‐2, severe acute respiratory syndrome coronavirus (SARS‐CoV), and middle east respiratory syndrome coronavirus (MERS‐CoV), highlighting the need for larger and well‐annotated datasets.

negative: Organization of two transmissible gastroenteritis coronavirus membrane protein topologies within the virion and core. The difference in membrane (M) protein compositions between the transmissible gastroenteritis coronavirus (TGEV) virion and the core has been studied. The TGEV M protein adopts two topologies in the virus envelope, a Nexo-Cendo topology (with the amino terminus exposed to the virus surface and the carboxy terminus inside the virus particle) and a Nexo-Cexo topology (with both the amino and carboxy termini exposed to the virion surface). The existence of a population of M molecules adopting a Nexo-Cexo topology in the virion envelope was demonstrated by (i) immunopurification of (35)S-labeled TGEV virions using monoclonal antibodies (MAbs) specific for the M protein carboxy terminus (this immunopurification was inhibited only by deletion mutant M proteins that maintained an intact carboxy terminus), (ii) direct binding of M-specific MAbs to the virus surface, and (iii) mass spectrometry analysis of peptides released from trypsin-treated virions. Two-thirds of the total number of M protein molecules found in the virion were associated with the cores, and one-third was lost during core purification. MAbs specific for the M protein carboxy terminus were bound to native virions through the M protein in a Nexo-Cexo conformation, and these molecules were removed when the virus envelope was disrupted with NP-40 during virus core purification. All of the M protein was susceptible to N-glycosidase F treatment of the native virions, which indicates that all the M protein molecules are exposed to the virus surface. Cores purified from glycosidase-treated virions included M protein molecules that completely or partially lost the carbohydrate moiety, which strongly suggests that the M protein found in the cores was also exposed in the virus envelope and was not present exclusively in the virus interior. A TGEV virion structure integrating all the data is proposed. According to this working model, the TGEV virion consists of an internal core, made of the nucleocapsid and the carboxy terminus of the M protein, and the envelope, containing the spike (S) protein, the envelope (E) protein, and the M protein in two conformations. The two-thirds of the molecules that are in a Nexo-Cendo conformation (with their carboxy termini embedded within the virus core) interact with the internal core, and the remaining third of the molecules, whose carboxy termini are in a Nexo-Cexo conformation, are lost during virus core purification.

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: Povidone‐iodine gargle as a prophylactic intervention to interrupt the transmission of SARS‐CoV‐2 Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, SARS-COV-2 was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in January 2020. Human-to-Human transmission occurs through close contact with an infected person or surfaces that are contaminated with droplets or secretions.

negative: Frequent Detection of Human Coronaviruses in Clinical Specimens from Patients with Respiratory Tract Infection by Use of a Novel Real-Time Reverse-Transcriptase Polymerase Chain Reaction During the past years, human coronaviruses (HCoVs) have been increasingly identified as pathogens associated with more-severe respiratory tract infection (RTI). Diagnostic tests for HCoVs are not frequently used in the routine setting. It is likely that, as a result, the precise role that HCoVs play in RTIs is greatly underestimated. We describe a rapid, sensitive, and highly specific quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for the detection of HCoV that can easily be implemented in the routine diagnostic setting. HCoV was detected in 28 (11%) of the 261 clinical specimens obtained from patients presenting with symptoms of RTI ranging from common cold to severe pneumonia. Only 1 (0.4%) of the 243 control specimens obtained from patients without symptoms of RTI showed the presence of HCoV. We conclude that HCoVs can be frequently detected in patients presenting with RTI. Real-time RT-PCR provides a tool for large-scale epidemiological studies to further clarify the role that coronavirus infection plays in RTI in humans.

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: 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.

negative: Seroprevalence of SARS Coronavirus Among Residents Near a Hospital with a Nosocomial Outbreak Background/Purpose An epidemic of severe acute respiratory syndrome (SARS) occurred in Taiwan from April to July 2003. A nosocomial outbreak of SARS occurred at Kaohsiung Chang Gung Memorial Hospital (CGMH) in May 2003. The purpose of our study was to survey the prevalence of the SARS coronavirus (CoV) in a community adjacent to Kaohsiung CGMH and collect demographic data, including basic information about health status, household, and possible risk factors for SARS-CoV infection. Methods We randomly recruited 1030 persons living in three precincts adjacent to Kaohsiung CGMH. For all subjects, we collected demographic data and measured the seroprevalence of the SARS-CoV with an enzyme-linked immunosorbent assay (ELISA) and an immunofluorescence assay (IFA). Results The ELISA was seropositive for 124 of 1030 participants (12%). The more sensitive and specific IFA confirmed SARS in only two cases (0.19%). Both confirmed cases were under 19 years of age and had no known SARS-related risk factors. Conclusion There was low post-epidemic seroprevalence of SARS-CoV in a community adjacent to a hospital which had a nosocomial SARS outbreak. The SARS outbreak in Taiwan was primarily limited to hospital settings.

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: Guidance for clinical neurophysiology examination throughout the COVID-19 pandemic. Latin American chapter of the IFCN task force – COVID-19 On 31st December 2019, China notified the World Health Organization of an outbreak of atypical pneumonia from patients at a local seafood market in Wuhan, Hubei, China, responsible for a new coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that caused COVID-19 disease, which spread rapidly around the world. WHO declared a state of pandemic (11th March, 2020), which has caused more than 1 million infected and more than 110,000 deaths; it was observed that up to 29% of those infected were health care personnel. The main route of transmission of SARS-CoV2 is through respiratory secretions and direct contact with contaminated surfaces and material. The pandemic induced an international saturation of health care services and a rupture in the supply chain of protective equipment for healthcare personnel, which poses a high occupational risk to all. Based on the different healthcare systems, human resources, infrastructure and medical emergencies that will warrant the conduct of clinical neurophysiology studies and the lack of a guide for the management of the situation, it was decided by an expert task force of the Latin American Chapter of the International Federation of Clinical Neurophysiology to carry out these guidelines for the protection of patient and healthcare professionals conducting clinical neurophysiological studies.

negative: Facemasks prevent influenza-like illness: implications for COVID-19 The coronavirus disease 2019 (COVID-19) pandemic is causing a huge toll on individuals, families, communities and societies across the world. Currently, whether wearing facemasks in public should be a measure to prevent transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains contraversial.1 This is largely because there have been no randomized controlled trials (RCTs) for coronavirus to directly support this. However, lessons may be taken from published RCTs examining influenza-like illness (ILI).2,3 Recent studies suggested that SARS-CoV-2 shares similar transmission route with influenza virus,4 and the incidence of community transmission of SARS-CoV-2 in individuals with ILI is high.5 Therefore, we undertook this meta-analysis of RCTs examining the efficacy of wearing facemasks to prevent ILI in community settings, irrespective of confirmatory testing for the causative virus. We undertook a systematic literature search for RCTs related to facemasks and ILI between 1966 and April 2020 using PUBMED, EMBASE, and Cochrane library. RCTs undertaken in community (not hospital) settings comparing wearing and not wearing facemasks for ILI were included. Incidence of ILI (e.g., fever, cough, headache, sore throat, aches or pains in muscles or joints) was estimated per group. Relative risk (RR) and 95% confidence interval (CI) were calculated. We screened 899 related abstracts and eventually included 8 RCTs (Figure S1). Basic characteristics and quality of included RCTs are listed in Supplement. Participants wearing facemasks had a significantly lower risk of developing ILI than those not wearing facemasks (pooled RR=0.81, 95% CI: 0.70-0.95) and there was no heterogeneity (Figure 1). The decreased risk of ILI was more pronounced if everyone wore facemask irrespective of whether they were infected or not (RR=0.77, 95% CI: 0.65-0.91), compared to those wearing facemasks when infected (RR=0.95, 95% CI: 0.58-1.56) or uninfected (RR=1.26, 95% CI: 0.69-2.31). This study shows that wearing facemasks, irrespective of infection status, is effective in preventing ILI spread in the community. This situation mirrors what is happening now in public settings where we do not know who has been infected and who has not. Although there are no RCTs of facemasks for SARS-CoV-2, as with other simple measures such as social distancing and handwashing, these data support the recommendation to wear facemasks in public to further reduce transmission of SARS-CoV-2 and flatten the curve of this pandemic, especially when social distancing is impractical, such as shopping, or travelling with public transport for work that cannot be done from home.

negative: Logistic approximations used to describe new outbreaks in the 2020 COVID-19 pandemic In this investigation I used the Logistic Model to fit the COVID-19 pandemic data for some countries. The data modeled is the death numbers per day in China, Iran, Italy, South Korea, Spain and United States. Considering the current growth rate of the pandemic, it was possible to show that the death toll should be between 3,277-3,327 deaths in China, 2,035-2,107 in Iran, 120-134 in South Korea, 11,227-12,793 in Italy and 6,217-7,405 in Spain. Also, with this toy model it was possible to show a clear emergence of a new outbreak within the same country (Iran, China and the United States). The growth rate of deaths found for South Korea was the lowest among the countries studied ($0.14701\pm0.00923$) and for China ($0.16667\pm0.00284$). Italy ($0.22594\pm0.00599$) and Spain ($0.31213\pm0.02337$) had the highest rates and in the second wave in Iran ($0.37893\pm0.02712$).

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: Detection of feline coronavirus using microcantilever sensors This work demonstrated the feasibility of detecting severe acute respiratory syndrome associated coronavirus (SARS-CoV) using microcantilever technology by showing that the feline coronavirus (FIP) type I virus can be detected by a microcantilever modified by feline coronavirus (FIP) type I anti-viral antiserum. A microcantilever modified by FIP type I anti-viral antiserum was developed for the detection of FIP type I virus. When the FIP type I virus positive sample is injected into the fluid cell where the microcantilever is held, the microcantilever bends upon the recognition of the FIP type I virus by the antiserum on the surface of the microcantilever. A negative control sample that does not contain FIP type I virus did not cause any bending of the microcantilever. The detection limit of the sensor was 0.1 µg ml(−1) when the assay time was <1 h.

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: Establishment of Vero E6 cell clones persistently infected with severe acute respiratory syndrome coronavirus Abstract Little information is available on persistent infection of severe acute respiratory syndrome (SARS) coronavirus (CoV). In this study, we established persistent infection of SARS-CoV in the Vero E6 cell line. Acute infection of Vero E6 with SARS-CoV produced a lytic infection with characteristic rounding cytopathic effects (CPE) and the production of a large number of infectious particles in the culture fluid within 3 days post-infection. Upon subsequent culturing of the remaining adherent cells, the cells gradually proliferated and recovered normal morphology similar to that of the parental cells, and continued to produce large numbers of infectious viral particles during the observation period of 5 months. Among a total of 87 cell clones obtained from the persistently infected Vero E6, only four cell clones (named #13, #18, #21, and #34) were positive for viral RNA. Clones #13, #18, and #34 shifted to viral RNA-negative during subsequent cultures, while #21 continuously produced infectious particles at a high rate. The SARS-CoV receptor, angiotensin-converting enzyme 2, was almost completely down regulated from the cell surface of persistently infected cells. Western blot analysis as well as electron microscopy indicated that the ratios of spike to nucleocapsid protein in clone #21 as well as its parental persistently infected cells were lower than that in the cells in the acute phase of infection. These Vero E6 cells persistently infected with SARS-CoV may be useful for clarifying the mechanism of the persistent infection and also for elucidating the possible pathophysiologic significance of such long-term maintenance of this virus.

negative: Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy - achieving global consensus and visibility for cellular host-directed therapies Abstract As of May 11th 2020, the coronavirus disease 2019 (COVID-19) pandemic, caused by the novel, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused 274,361 deaths out of 3,917,366 (7% case fatality rate). As with the two other novel coronavirus zoonotic diseases of humans, SARS and MERS, no specific treatments for reducing mortality or morbidity are yet available. Deaths from COVID-19 will continue to rise globally until effective and appropriate treatments and vaccines are found. With no specific treatments being available for treating COVID-19 patients, the global medical, scientific, pharma and funding communities have rapidly initiated over 500 COVID-19 clinical on a range of antiviral drug regimens, biologics, repurposed drugs in various combinations. We focus this editorial specifically on the background to, and the rationale for, the use and evaluation of mesenchymal stromal (Stem) cells (MSCs) in treatment trials of patients with severe COVID-19 disease. This is an area which has been eclipsed by the current emphasis the huge number of trials evaluating new anti-viral drugs, repurposed drugs and combinations thereof. MSCs should also be trialed for treatment of severe cases of MERS where mortality rates are upto 34% and MERS-CoV remains a WHO priority Blueprint pathogen. It’s about time funding agencies now invest more into development MSCs per se and other host-directed therapies in combination with other therapeutic interventions. MSC therapy could turn out to be an important contribution to bringing an end to the high COVID-19 and MERS death rates.

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: ICU-acquired weakness, diaphragm dysfunction and long-term outcomes of critically ill patients BACKGROUND: Intensive care unit (ICU)-acquired weakness and diaphragm dysfunction are frequent conditions, both associated with poor prognosis in critically ill patients. While it is well established that ICU-acquired weakness severely impairs long-term prognosis, the association of diaphragm dysfunction with this outcome has never been reported. This study investigated whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and ICU-acquired weakness has a particular association with 2-year survival and health-related quality of life (HRQOL). METHODS: This study is an ancillary study derived from an observational cohort study. Patients under mechanical ventilation were enrolled at the time of their first spontaneous breathing trial. Diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation < 11 cmH(2)O and ICU-acquired weakness was defined by Medical Research Council (MRC) score < 48. HRQOL was evaluated with the SF-36 questionnaire. RESULTS: Sixty-nine of the 76 patients enrolled in the original study were included in the survival analysis and 40 were interviewed. Overall 2-year survival was 67% (46/69): 64% (29/45) in patients with diaphragm dysfunction, 71% (17/24) in patients without diaphragm dysfunction, 46% (11/24) in patients with ICU-acquired weakness and 76% (34/45) in patients without ICU-acquired weakness. Patients with concomitant diaphragm dysfunction and ICU-acquired weakness had a poorer outcome with a 2-year survival rate of 36% (5/14) compared to patients without diaphragm function and ICU-acquired weakness [79% (11/14) (p < 0.01)]. Health-related quality of life was not influenced by the presence of ICU-acquired weakness, diaphragm dysfunction or their coexistence. CONCLUSIONS: ICU-acquired weakness but not diaphragm dysfunction was associated with a poor 2-year survival of critically ill patients.

negative: INFECTION CONTROL CHALLENGES IN CHILD-CARE CENTERS Current social and economic factors have resulted in increasing numbers of children attending child-care facilities outside of the home. In the United States over 13 million children less than 5 years of age and 60% of children less than 13 years of age are enrolled in some form of out-of-home child care.85, 108 Children attending out-of-home care settings are at increased risk for a variety of infections.25, 62, 79, 88 The incidence of respiratory tract infections, diarrheal disease, cytomegalovirus, hepatitis A, and bacterial meningitis is higher in children cared for outside of the home.54, 88 Increased rates of infections result in increased morbidity of children attending child-care facilities and significant economic impact because of loss of work and cost of medical care. These costs have been estimated at 1.8 billion dollars per year in the United States.(47) Parents of children attending child-care facilities miss from 1 to 4 weeks of work per year caring for ill children.(28) Increased risk for infections in child-care settings is of public health significance because of potential transmission to adult contacts and dissemination into the community.(88) Infections acquired in child-care settings that are mild or asymptomatic in children may be severe in adults.(85)

negative: Ethical Alternatives to Experiments with Novel Potential Pandemic Pathogens Please see later in the article for the Editors' Summary

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: Changes in implementation of personal protective measures by ordinary Japanese citizens: A longitudinal study from the early phase to the community transmission phase of the COVID-19 outbreak OBJECTIVES: To clarify changes in the implementation of personal protective measures among ordinary Japanese citizens from the early phase of the COVID-19 outbreak to the community transmission phase. METHODS: This longitudinal, internet-based survey included 2,141 people (50.8% men; 20-79 years). The baseline and follow-up surveys were conducted from February 25-27, 2020 and April 1-6, 2020, respectively. Participants were asked how often they implemented the 5 personal protective measures recommended by the World Health Organization (hand hygiene, social distancing, avoiding touching the eyes, nose and mouth, respiratory etiquette, and self-isolation) in the baseline and follow-up surveys. RESULTS: The prevalence of 3 of the 5 personal protective measures significantly improved in the community transmission phase compared to the early phase. Social distancing measures showed significant improvement, from 67.4% to 82.2%. However, the prevalence of avoiding touching the eyes, nose and mouth, which had the lowest prevalence in the early phase, showed no significant improvement (approximately 60%). Multivariate logistic regression analysis revealed, men and persons of low-income households made fewer improvements than women and persons of high-income households. CONCLUSIONS: The prevalence of personal protective measures by ordinary citizens is improving, however there is potential for improvement, especially in regard to avoiding touching eyes, nose and mouth.

negative: Diagnostic methods and potential portable biosensors for coronavirus disease 2019 Timely detection and diagnosis are urgently needed to guide epidemiological measures, infection control, antiviral treatment, and vaccine research. In this review, biomarkers/indicators for diagnosis of coronavirus disease 2019 (COVID-19) or detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the environment are summarized and discussed. It is concluded that the detection methods targeting antibodies are not suitable for screening of early and asymptomatic cases since most patients had an antibody response at about 10 days after onset of symptoms. However, antibody detection methods can be combined with quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) to significantly improve the sensitivity and specificity of diagnosis, and boost vaccine research. Fast, sensitive and accurate detection methods targeting antigens need to be developed urgently. Various specimens for diagnosis or detection are compared and analyzed. Among them, deep throat saliva and induced sputum are desired for RT-qPCR test or other early detection technologies. Chest computerized tomography (CT) scan, RT-qPCR, lateral flow immunochromatographic strip (LFICS) for diagnosis of COVID-19 are summarized and compared. Specially, potential electrochemical (EC) biosensor, surface enhanced Raman scattering (SERS)-based biosensor, field-effect transistor (FET)-based biosensor, surface plasmon resonance (SPR)-based biosensor and artificial intelligence (AI) assisted diagnosis of COVID-19 are emphasized. Finally, some commercialized portable detection device, current challenges and future directions are discussed.

negative: Surface ultrastructure of SARS coronavirus revealed by atomic force microscopy Atomic force microscopy has been used to probe the surface nanostructures of severe acute respiratory syndrome coronavirus (SARS‐CoV). Single crown‐like virion was directly visualized and quantitative measurements of the dimensions for the structural proteins were provided. A corona of large, distinctive spikes in the envelope was measured after treatment with hydroxyoctanoic acid. High‐resolution images revealed that the surface of each single SARS‐CoV was surrounded with at least 15 spherical spikes having a diameter of 7.29 ± 0.73 nm, which is in close agreement with that of S glycoproteins earlier predicted through the genomes of SARS‐CoV. This study represents the first direct characterization of the surface ultrastructures of SARS‐CoV particles at the nanometre scale and offers new prospects for mapping viral surface properties.

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: Porcine Epidemic Diarrhea Virus 3C-Like Protease Regulates Its Interferon Antagonism by Cleaving NEMO. UNLABELLED Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus causing lethal watery diarrhea in piglets. Since 2010, a PEDV variant has spread rapidly in China, and it emerged in the United States in 2013, posing significant economic and public health concerns. The ability to circumvent the interferon (IFN) antiviral response, as suggested for PEDV, promotes viral survival and regulates pathogenesis of PEDV infections, but the underlying mechanisms remain obscure. Here, we show that PEDV-encoded 3C-like protease, nsp5, is an IFN antagonist that proteolytically cleaves the nuclear transcription factor kappa B (NF-κB) essential modulator (NEMO), an essential adaptor bridging interferon-regulatory factor and NF-κB activation. NEMO is cleaved at glutamine 231 (Q231) by PEDV, and this cleavage impaired the ability of NEMO to activate downstream IFN production and to act as a signaling adaptor of the RIG-I/MDA5 pathway. Mutations specifically disrupting the cysteine protease activity of PEDV nsp5 abrogated NEMO cleavage and the inhibition of IFN induction. Structural analysis suggests that several key residues outside the catalytic sites of PEDV nsp5 probably impact NEMO cleavage by modulating potential interactions of nsp5 with their substrates. These data show that PEDV nsp5 disrupts type I IFN signaling by cleaving NEMO. Previously, we and others demonstrated that NEMO is also cleaved by 3C or 3C-like proteinases of picornavirus and artertivirus. Thus, NEMO probably represents a prime target for 3C or 3C-like proteinases of different viruses. IMPORTANCE The continued emergence and reemergence of porcine epidemic diarrhea virus (PEDV) underscore the importance of studying how this virus manipulates the immune responses of its hosts. During coevolution with its hosts, PEDV has acquired mechanisms to subvert host innate immune responses for its survival advantage. At least two proteins encoded by PEDV have been identified as interferon (IFN) antagonists, papain-like protease (PLP) and N protein. Here, we report that the PEDV nsp5 gene, which encodes the 3C-like protease of PEDV, is another IFN antagonist. Mechanistically, the cysteine protease activity of PEDV nsp5 mediates proteolysis of NEMO, the key adaptor for IFN synthesis, and NEMO is cleaved at glutamine 231 (Q231). The new molecular details and determinants impacting NEMO scission by PEDV nsp5 delineated in this study are fundamental to our understanding of critical virus-host interactions that determine PEDV pathogenesis.

negative: Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure Abstract The 3C-like protease of SARS coronavirus (SARS-CoV 3CLpro) is vital for SARS-CoV replication and is a promising drug target. It has been extensively proved that only the dimeric enzyme is active. Here we discovered that two adjacent mutations (Ser139_Ala and Phe140_Ala) on the dimer interface resulted in completely different crystal structures of the enzyme, demonstrating the distinct roles of these two residues in maintaining the active conformation of SARS-CoV 3CLpro. S139A is a monomer that is structurally similar to the two reported monomers G11A and R298A. However, this mutant still retains a small fraction of dimer in solution, which might account for its remaining activity. F140A is a dimer with the most collapsed active pocket discovered so far, well-reflecting the stabilizing role of this residue. Moreover, a plausible dimerization mechanism was also deduced from structural analysis. Our work is expected to provide insight on the dimerization–function relationship of SARS-CoV 3CLpro.

negative: Plaque assay for human coronavirus NL63 using human colon carcinoma cells BACKGROUND: Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV) NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. RESULTS: 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2) replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2). CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4(th )day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. CONCLUSION: CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.

negative: 3C protein of feline coronavirus inhibits viral replication independently of the autophagy pathway Abstract Feline coronavirus (FCoV) can cause either asymptomatic enteric infection or fatal peritonitis in cats. Although the mutation of FCoV accessory gene 3c has been suggested to be related to the occurrence of feline infectious peritonitis (FIP), how the 3C protein is involved in this phenomenon remains unknown. To investigate the role of the 3C protein, a full-length 3c gene was transiently expressed and the cytoplasmic distribution of the protein was found to be primarily in the perinuclear region. Using 3c-stable expression cells, the replication of a 3c-defective FCoV strain was titrated and a significant decrease in replication (p < 0.05) was observed. The mechanism underlying the decreased FIPV replication caused by the 3C protein was further investigated; neither the induction nor inhibition of autophagy rescued the viral replication. Taken together, our data suggest that the 3C protein might have a virulence-suppressing effect in FCoV-infected cats. Deletion of the 3c gene could therefore cause more efficient viral replication, which leads to a fatal infection.

negative: Cellular Entry of the SARS Coronavirus: Implications for Transmission, Pathogenicity and Antiviral Strategies A novel coronavirus was identified as the causative agent of the lung disease severe acute respiratory syndrome (SARS). The outbreak of SARS in 2002/2003 was associated with high morbidity and mortality and sparked international research efforts to develop antiviral strategies. Many of these efforts focussed on the viral surface protein spike (S), which facilitates the first indispensable step in the viral replication cycle, infectious entry into target cells. For infectious cellular entry to occur, the S protein must engage a cellular receptor, the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). The interface between ACE2 and S protein, which has been characterized at the structural level, constitutes a key target for vaccines and inhibitors, and is believed to be an important determinant of viral pathogenesis and interspecies transmission. In this chapter, we will discuss how SARS-S mediates cellular entry and we will review the implications of this process for SARS coronavirus (SARS-CoV) transmission, disease development and antiviral intervention.

negative: Stability of infectious human coronavirus NL63 Abstract The human coronavirus NL63 was identified in 2004 and subsequent studies showed its worldwide distribution. Infection with this pathogen is associated with upper and lower respiratory tract diseases of mild to moderate severity. Furthermore, HCoV-NL63 is the main cause of croup in children. Within this study an optimal protocol for freeze-drying that allows safe and effective preservation of HCoV-NL63 infectious material was developed. Lyophilized virus preparations can be stored either at ambient temperature or at +4°C. In the latter case samples may be stored for at least two months. Surprisingly, conducted analysis showed that HCoV-NL63 virions are exquisitely stable in liquid media and can be stored also without preservatives at ambient temperature for up to 14 days.

negative: What are the risks of COVID-19 infection in pregnant women?

negative: Identifying highly influential travellers for spreading disease on a public transport system The recent outbreak of a novel coronavirus and its rapid spread underlines the importance of understanding human mobility. Enclosed spaces, such as public transport vehicles (e.g. buses and trains), offer a suitable environment for infections to spread widely and quickly. Investigating the movement patterns and the physical encounters of individuals on public transit systems is thus critical to understand the drivers of infectious disease outbreaks. For instance previous work has explored the impact of recurring patterns inherent in human mobility on disease spread, but has not considered other dimensions such as the distance travelled or the number of encounters. Here, we consider multiple mobility dimensions simultaneously to uncover critical information for the design of effective intervention strategies. We use one month of citywide smart card travel data collected in Sydney, Australia to classify bus passengers along three dimensions, namely the degree of exploration, the distance travelled and the number of encounters. Additionally, we simulate disease spread on the transport network and trace the infection paths. We investigate in detail the transmissions between the classified groups while varying the infection probability and the suspension time of pathogens. Our results show that characterizing individuals along multiple dimensions simultaneously uncovers a complex infection interplay between the different groups of passengers, that would remain hidden when considering only a single dimension. We also identify groups that are more influential than others given specific disease characteristics, which can guide containment and vaccination efforts.

negative: Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide Sodium taurocholate cotransporting polypeptide (NTCP) is a major entry receptor of hepatitis B virus (HBV) and one of the most attractive targets for anti-HBV drugs. We developed a cell-mediated drug screening method to monitor NTCP expression on the cell surface by generating a HepG2 cell line with tetracycline-inducible expression of NTCP and a monoclonal antibody that specifically detects cell-surface NTCP. Using this system, we screened a small molecule library for compounds that protected against HBV infection by targeting NTCP. We found that glabridin, a licorice-derived isoflavane, could suppress viral infection by inducing caveolar endocytosis of cell-surface NTCP with an IC(50) of ~40 μM. We also found that glabridin could attenuate the inhibitory effect of taurocholate on type I interferon signaling by depleting the level of cell-surface NTCP. These results demonstrate that our screening system could be a powerful tool for discovering drugs targeting HBV entry.

negative: Hand hygiene and the novel coronavirus pandemic: The role of healthcare workers

negative: 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.

negative: Best practice recommendations: ENT consultations during the COVID-19 pandemic These best practice recommendations for ENT consultations during the COVID-19 pandemic have been drawn up because ENT examinations and treatments are at risk of contamination by the SARS-Cov-2 virus in certain instances. Thus, ENT specialists are among the professionals who are most exposed to this infection. During the pandemic, insofar as an asymptomatic patient may be infected and contagious, the same precautions must be employed whether the patient is ill with, suspected of having, or without any clinical evidence of COVID-19 infection. According to the scientific data available, the examinations and procedures potentially exposing to projections/aerosolizations of organic material of human origin are considered to be at risk of staff contamination. For ENT examinations and procedures without exposure to such projections/aerosolizations, the professional is advised to a long sleeve clean outfit, a surgical mask and gloves in case of contact with the patient's mucosa. ENT examinations and procedures with exposure to these projections/aerosolizations require the so-called “airborne”, “contact”, and “droplets” additional precautions: FFP2/N95 respiratory protection device, eye protection, disposable headwear and long sleeve overgown.

negative: Clinical and Immunologic Responses in Patients with Viral Keratoconjunctivitis

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: Biometric Fingerprinting for Visa Application: Device and Procedure Are Risk Factors for Infection Transmission BACKGROUND: Biometric fingerprint identity verification is currently introduced in visa application and entry screening at border control. The system implies physical contact between the skin and the surface of the fingerprint‐capturing and reading devices. AIM: To assess the risk of infection transmission through fingerprinting. METHODS: The medical literature was reviewed for the potential of microorganisms to be carried on the skin of hands in the community, to be transferred from hands to inanimate surfaces, to survive on surfaces, and to be transferred in doses exceeding the infectious dose. The fingerprinting procedures as currently applied were reviewed. RESULTS: Factors that favor transfer of microorganisms are large skin–surface contact between flat fingers (2 × 20 cm(2)) and fingerprint‐capturing device, nonporous contact surface, large overlap of contact surface and short turnaround time between successive applicants, high contact pressure, and difficulties to disinfect devices. Transmission risk exists for enteric viruses (rotavirus, norovirus, and hepatitis A virus), respiratory viruses (respiratory syncytial virus, rhinovirus, influenzavirus, etc.), and enteropathogenic bacteria with low infectious doses (Shigella dysenteriae, Enterohemorrhagic Escherichia coli, etc.). Using Monte Carlo risk analysis on US data, transmission of human rotavirus is estimated at 191 [95% credible intervals (CI) 0–289] per million fingerprint‐capturing procedures. Application of 70% isopropyl hand rub and 85% ethanol hand gel reduces the risk to 77 (95% CI 0–118) and 0.3 (95% CI 0–0.3) transmissions per million procedures, respectively. CONCLUSIONS: The fingerprinting procedure as currently used is associated with a risk of infection transmission. Simple hygienic measures can considerably reduce this transmission risk.

negative: Statistical analysis of the impact of environmental temperature on the exponential growth rate of cases infected by COVID-19 We perform a statistical analysis for understanding the effect of the environmental temperature on the exponential growth rate of the cases infected by COVID-19 for US and Italian regions. In particular, we analyze the datasets of regional infected cases, derive the growth rates for regions characterized by readable exponential growth phase in their evolution spread curve and plot them against the environmental temperatures averaged within the same regions, derive the relationship between temperature and growth rate, and evaluate its statistical confidence. The results clearly support the first reported statistically significant relationship of negative correlation between the average environmental temperature and exponential growth rates of the infected cases. The critical temperature, which eliminates the exponential growth, and thus the COVID-19 spread in US regions, is estimated to be Tc = 86.1 ± 4.3 F.

negative: 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.

negative: Outbreak dynamics of COVID-19 in China and the United States On March 11, 2020, the World Health Organization declared the coronavirus disease 2019, COVID-19, a global pandemic. In an unprecedented collective effort, massive amounts of data are now being collected worldwide to estimate the immediate and long-term impact of this pandemic on the health system and the global economy. However, the precise timeline of the disease, its transmissibility, and the effect of mitigation strategies remain incompletely understood. Here we integrate a global network model with a local epidemic SEIR model to quantify the outbreak dynamics of COVID-19 in China and the United States. For the outbreak in China, in n=30 provinces, we found a latent period of 2.56+/-0.72 days, a contact period of 1.47+/-0.32 days, and an infectious period of 17.82+/-2.95 days. We assume that the latent and infectious periods are disease-specific and the contact period is behavior-specific and can vary between different communities, states, or countries. For the early stages of the outbreak in the United States, in n=50 states, we adopted the latent and infectious periods from China, and found a contact period of 3.38+/-0.69 days. Our network model predicts that - without the massive political mitigation strategies that are in place today - the United states would have faced a basic reproduction number of 5.3+/-0.95 and a nationwide peak of the outbreak on May 10, 2020 with 3 million infections. Our results demonstrate how mathematical modeling can help estimate outbreak dynamics and provide decision guidelines for successful outbreak control. We anticipate that our model will become a valuable tool to estimate the potential of vaccination and quantify the effect of relaxing political measures including total lock down, shelter in place, and travel restrictions for low-risk subgroups of the population or for the population as a whole.

negative: Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR BACKGROUND: The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. AIM: We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. METHODS: Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. RESULTS: The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. CONCLUSION: The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.

negative: Roll-out of SARS-CoV-2 testing for healthcare workers at a large NHS Foundation Trust in the United Kingdom, March 2020 Healthcare workers (HCW) are potentially at increased risk of infection with coronavirus disease (COVID-19) and may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to vulnerable patients. We present results from staff testing at Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom. Between 16 and 29 March 2020, 1,533 symptomatic HCW were tested, of whom 282 (18%) were positive for SARS-CoV-2. Testing HCW is a crucial strategy to optimise staffing levels during this outbreak.

negative: Serodiagnostic Aids and Management Practice for Feline Retrovirus and Coronavirus Infections

negative: Current laboratory diagnostics of coronavirus disease 2019 (COVID-19). Laboratory medicine provides an almost irreplaceable contribution to the diagnostic reasoning and managed care of most human pathologies. The novel coronavirus disease 2019 (COVID-19) is not an exception to this paradigm. Although the relatively recent emergence does not allow to draw definitive conclusions on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics, some standpoints can be conveyed. First and foremost, it seems now clear that we will be living together with this virus for quite a long time, so that our vigilance and responsiveness against the emergence of new local outbreaks shall be maintained at the highest possible levels. The etiological diagnosis of COVID-19 is, and will remain for the foreseeable future, deeply based on direct identification of viral RNA by means of molecular biology techniques in biological materials, especially upper and lower respiratory tract specimens. Whether other materials, such as blood, urine, stools, saliva and throat washing, will become valid alternatives has not been unequivocally defined so far. As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Whether these antibodies will have persistent neutralizing activity against the virus is still to be elucidated on individual and general basis. The availability of rapid tests for detecting either viral antigens or anti-SARS-CoV-2 antibodies are a potentially viable opportunity for purposes of epidemiologic surveillance, though more information is needed on accuracy and reliability of these portable immunoassays.

negative: From fighting COVID-19 pandemic to tackling sustainable development goals: An opportunity for responsible information systems research The recent outbreak of the COVID-19 pandemic has posed a significant threat to the healthy lives and well-being of billions of people worldwide. As the world begins to open up from lockdowns and enters an unprecedented state of vulnerability, or what many have called “the new normal”, it makes sense to reflect on what we have learned, revisit our fundamental assumptions, and start charting the way forward to contribute to building a sustainable world. In this essay, we argue that despite its significant damage to human lives and livelihoods, the coronavirus pandemic presents an excellent opportunity for the human family to act in solidarity and turn this crisis into an impetus to achieve the United Nation’s (UN) Sustainable Development Goals (SDG). In this article, we will highlight the six relevant themes that have evolved during the pandemic and the corresponding topics that future researchers could focus on. We conclude by issuing a call for more research attention on tackling SDG through developing the concept and practice of digital sustainability.

negative: Cryo-Electron Microscopy Structure of Porcine Deltacoronavirus Spike Protein in the Prefusion State Coronavirus spike proteins from different genera are divergent, although they all mediate coronavirus entry into cells by binding to host receptors and fusing viral and cell membranes. Here, we determined the cryo-electron microscopy structure of porcine deltacoronavirus (PdCoV) spike protein at 3.3-Å resolution. The trimeric protein contains three receptor-binding S1 subunits that tightly pack into a crown-like structure and three membrane fusion S2 subunits that form a stalk. Each S1 subunit contains two domains, an N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD). PdCoV S1-NTD has the same structural fold as alpha- and betacoronavirus S1-NTDs as well as host galectins, and it recognizes sugar as its potential receptor. PdCoV S1-CTD has the same structural fold as alphacoronavirus S1-CTDs, but its structure differs from that of betacoronavirus S1-CTDs. PdCoV S1-CTD binds to an unidentified receptor on host cell surfaces. PdCoV S2 is locked in the prefusion conformation by structural restraint of S1 from a different monomeric subunit. PdCoV spike possesses several structural features that may facilitate immune evasion by the virus, such as its compact structure, concealed receptor-binding sites, and shielded critical epitopes. Overall, this study reveals that deltacoronavirus spikes are structurally and evolutionally more closely related to alphacoronavirus spikes than to betacoronavirus spikes; it also has implications for the receptor recognition, membrane fusion, and immune evasion by deltacoronaviruses as well as coronaviruses in general. IMPORTANCE In this study, we determined the cryo-electron microscopy structure of porcine deltacoronavirus (PdCoV) spike protein at a 3.3-Å resolution. This is the first atomic structure of a spike protein from the deltacoronavirus genus, which is divergent in amino acid sequences from the well-studied alpha- and betacoronavirus spike proteins. Here, we described the overall structure of the PdCoV spike and the detailed structure of each of its structural elements. Moreover, we analyzed the functions of each of the structural elements. Based on the structures and functions of these structural elements, we discussed the evolution of PdCoV spike protein in relation to the spike proteins from other coronavirus genera. This study combines the structure, function, and evolution of PdCoV spike protein and provides many insights into its receptor recognition, membrane fusion, and immune evasion.

negative: Kitchen Spectroscopy: Shining a (UV) Light on Everyday Objects Fluorescent objects often lead to a sense of joy and intrigue. While the current COVID-19 pandemic limits the synthesis of “glowy things” like quantum dots, many household objects fluoresce, providing an opportunity to brighten your day while learning fundamental chemistry.

negative: Bats, Civets and the Emergence of SARS Severe acute respiratory syndrome (SARS) was the first pandemic transmissible disease of previously unknown aetiology in the twenty-first century. Early epidemiologic investigations suggested an animal origin for SARS-CoV. Virological and serological studies indicated that masked palm civets ( Paguma larvata ), together with two other wildlife animals, sampled from a live animal market were infected with SARS-CoV or a closely related virus. Recently, horseshoe bats in the genus Rhinolophus have been identified as natural reservoir of SARS-like coronaviruses. Here, we review studies by different groups demonstrating that SARS-CoV succeeded in spillover from a wildlife reservoir (probably bats) to human population via an intermediate host(s) and that rapid virus evolution played a key role in the adaptation of SARS-CoVs in at least two nonreservoir species within a short period.

negative: Acute Type A Aortic Dissection during COVID-19 Outbreak Abstract As of April 7, 2020, approximately 1,300,000 cases and 80,000 deaths related to coronavirus disease 2019 (COVID-19) have been reported in > 180 countries/territories. Healthcare infrastructures and resources, particularly as it relates to the care of the most critically ill patients, are currently being strained globally. In this context, however, there has been little clinical guidance or information regarding life-threatening conditions requiring emergency surgery that cannot be delayed. We herein present a case of acute type A aortic dissection with COVID-19 in order to highlight the clinical implications of a true emergent procedure during the COVID-19 outbreak.

negative: Potential Hazards of Concern in the Walk-Through Screening System for the Corona Virus Disease 2019 from the Perspective of Infection Preventionists

negative: Distinct cellular functions mediated by haemopoietic cell-surface proteases

negative: Cutaneous manifestations of COVID-19: Report of three cases and a review of literature ABSTRACT Background Various cutaneous manifestations have been observed in patients with COVID-19 infection. However, overall similarities in the clinical presentation of these dermatological manifestations have not yet been summarized. Objective This review aims to provide an overview of various cutaneous manifestations in patients with COVID-19 through three case reports and a literature review. Methods A literature search was conducted using PubMed, OVID, and Google search engines for original and review articles. Studies written in the English language that mentioned cutaneous symptoms and COVID-19 were included. Results Eighteen articles and three additional cases reported in this paper were included in this review. Of these studies, 6 are case series and 12 are case report studies. The most common cutaneous manifestation of COVID-19 was found to be maculopapular exanthem (morbilliform), presenting in 36.1% (26/72) patients. The other cutaneous manifestations included: a papulovesicular rash (34.7%, 25/72), urticaria (9.7%, 7/72), painful acral red purple papules (15.3%, 11/72) of patients, livedo reticularis lesions (2.8%, 2/72) and petechiae (1.4%, 1/72). Majority of lesions were localized on the trunk (66.7%, 50/72), however, 19.4% (14/72) of patients experienced cutaneous manifestations in the hands and feet. Skin lesion development occurred after the onset of respiratory symptoms or before COVID-19 diagnosis in 12.5% (9/72) of the patients, and lesions spontaneously healed in all patients within 10 days. Majority of the studies reported no correlation between COVID-19 severity and skin lesions. Conclusion Infection with COVID-19 may result in dermatological manifestations with various clinical presentations, which may aid in the timely diagnosis of this infection.

negative: Role of meteorological temperature and relative humidity in the January-February 2020 propagation of 2019-nCoV in Wuhan, China Identified in December 2019, the 2019-nCoV emerged in Wuhan, China, and its spread increased rapidly, with cases arising across Mainland China and several other countries. By January 2020, the potential risks imposed by 2019-nCoV in human health and economical activity were promptly highlighted. Considerable efforts have been devoted for understanding the transmission mechanisms aimed to pursue public policies oriented to mitigate the number of infected and deaths. An important question requiring some attention is the role of meteorological variables (e.g., temperature and humidity) in the 2019-nCoV transmission. Correlations between meteorological temperature and relative humidity with the number of daily confirmed cases were explored in this work for the epicenter city of Wuhan, China for the period from 29 January to March 6, 2020. Long-term trend of temperature and relative humidity was obtained with a 14-days adjacent-averaging filter, and lagged correlations of the number of daily confirmed cases were explored. The analysis showed negative correlations between temperatures with the number of daily confirmed cases. Maximum correlations were found for 6-day lagged temperatures, which is likely reflecting the incubation period of the virus. It was postulated that the indoor crowding effect is responsible of the high incidence of 2019-nCoV cases, where low absolute humidity and close human contact facilitate the transport of aerosol droplets.

negative: Physics of Virus Transmission by Speaking Droplets Droplets of oral fluid emitted by speaking are a long-recognized mechanism of respiratory virus transmission. While there have been many simulations of droplet evaporation to determine whether droplets containing virions remain floating in air or rapidly fall to the ground, they typically conceal the fundamental mechanisms because of the use of numerics. To make the physics of emitted oral fluid droplets easily understood, we present simple and transparent algebraic equations that capture the essential physics of the problem. Calculations with these equations provide a straightforward way to determine the airborne lifetime of emitted droplets after accounting for the decrease in droplet size from water evaporation. At a relative humidity of 50%, droplets with initial radii larger than about 50 microns rapidly fall to the ground while smaller, potentially-virus containing droplets shrink in size and remain airborne for many minutes. Rough estimates of airborne virion emission rates while speaking support the proposal that covering the mouth can help end the pandemic more quickly.

negative: The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future The respiratory system, which includes the trachea, airways, and distal alveoli, is a complex multi-cellular organ that intimately links with the cardiovascular system to accomplish gas exchange. In this review and as members of the NIH/NHLBI-supported Progenitor Cell Translational Consortium, we discuss key aspects of lung repair and regeneration. We focus on the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung repair and regeneration. We also provide future directions for an improved understanding of the cell biology of the respiratory system, as well as new therapeutic avenues.

negative: Coronavirus envelope (E) protein remains at the site of assembly Abstract Coronaviruses (CoVs) assemble at endoplasmic reticulum Golgi intermediate compartment (ERGIC) membranes and egress from cells in cargo vesicles. Only a few molecules of the envelope (E) protein are assembled into virions. The role of E in morphogenesis is not fully understood. The cellular localization and dynamics of mouse hepatitis CoV A59 (MHV) E protein were investigated to further understanding of its role during infection. E protein localized in the ERGIC and Golgi with the amino and carboxy termini in the lumen and cytoplasm, respectively. E protein does not traffic to the cell surface. MHV was genetically engineered with a tetracysteine tag at the carboxy end of E. Fluorescence recovery after photobleaching (FRAP) showed that E is mobile in ERGIC/Golgi membranes. Correlative light electron microscopy (CLEM) confirmed the presence of E in Golgi cisternae. The results provide strong support that E proteins carry out their function(s) at the site of budding/assembly.

negative: Traditional techniques of esophagectomy. Several well described and accepted traditional techniques exist for the performance of an open esophagectomy. The rationale for selecting one of these techniques is determined by the location and histology of the disease being treated and surgeon and institutional preferences. Large retrospective studies and a limited number of prospective studies have comparatively evaluated the operative and long-term oncologic outcomes of transthoracic versus transhiatal surgical approaches, which indicate trends toward higher perioperative complications but improved long-term outcomes among patients treated with a transthoracic approach. Other retrospective studies investigated the extent of a thoracic lympadenectomy that is necessary at the time of an esophagectomy to optimize survival.

negative: 250 examens de laboratoire en pratique médicale courante

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: Biology and Diseases of Ruminants: Sheep, Goats, and Cattle

negative: 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.

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: Molecular characterization and biological activity of bovine interferon-omega3 Abstract Bovine interferon-omega3 (BoIFN-ω3) gene was amplified from bovine liver genomic DNA, which encodes a 195-amino acid protein containing a 23-amino acid signal peptide. Analysis of the molecular characteristics revealed that BoIFN-ω3 evolving from IFN-ω, contained four cysteine residues and five alpha helices, showing that BoIFN-ω3 presented the typical molecular characteristics of type I interferon. BoIFN-ω3 exhibited antiviral and antiproliferative activities, which exerted a protective effect against VSV in several mammalian cell lines, as well as against BEV, IBRV, and BVDV in MDBK cell. Moreover, BoIFN-ω3 was shown to be highly sensitive to trypsin, but remaining stable despite changes in pH and temperature. Additionally, BoIFN-ω3 induced the transcription of Mx1, ISG15, and ISG56 genes, as well as the expression of Mx1 protein in a time-dependent manner. These findings will be useful to further study BoIFN-ω in host's defence against infectious diseases, particularly viral infections. Furthermore, results will facilitate further research on the bovine interferon family.

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: The evidence of SARS-CoV-2 infection on ocular surface Abstract This is a cross-sectional study of patients who received a COVID-19 diagnosis between December 30, 2019 and February 7, 2020 at Tongji Hospital. A total of 102 patients (48 Male [47%] and 54 Female [53%]) 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) were confirmed to have COVID-19 by laboratory diagnosis with a SARS-CoV-2 RT-PCR assay. Only two patients (2.78%) with conjunctivitis were identified from 72 patients with a laboratory confirmed COVID-19. Of those two patients, SARS-CoV-2 RNA fragments were found in ocular discharges by SARS-CoV-2 RT-PCR in only one patient. Our findings suspect the incidence of SARS-CoV-2 infection through the ocular surface is extremely low, while the nosocomial infection of SARS-CoV-2 through the eyes after occupational exposure is a potential route. To lower the SARS-CoV-2 nosocomial infection, all health care professionals should wear protective goggles. The inefficient diagnostic method and the sampling time lag may contribute to the lower positive rate of conjunctival swab samples of SARS-CoV-2.

negative: Influenza A (H1N1) In March 2009, an outbreak of human infected swine influenza, first name by WHO, occurred in Mexico that rapidly spread worldwide. On Apr 30, 2009, the WHO, the United Nations Food and Agriculture Organization and the World Organization for Animal Health agreed to use the name of influenza A (H1N1), which was then used in bulletins issued by Ministry of Health in China.

negative: Lung Involvement Found on Chest CT Scan in a Pre-Symptomatic Person with SARS-CoV-2 Infection: A Case Report The novel coronavirus SARS-CoV-2 infection is spreading worldwide, and there are many reports of acute respiratory distress syndrome caused by this infection. However, asymptomatic lung involvement has not been reported. We hereby present the case of a 44-year-old health-care worker, who was found to be infected with the SARS-CoV-2 virus after a CT-scan performed for an unrelated condition revealed a lesion in the lung field compatible with COVID-19 infection. His condition deteriorated initially, but eventually improved with supportive treatment and the compassionate use of antivirals and antimalarials and is now in a stable condition.

negative: 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.

negative: Induciton of MHC class I antigens on glial cells is dependent on persistent mouse hepatitis virus infection Abstract H-2 class I antigens, but not class II antigens, were detected on the surface of glial cells persistently infected with mouse hepatitis virus strain A59 (MHV-A59) as late as 90 days post-infection. Uninfected glial cells remained negative for H-2 class I and class II surface antigens. We have previously shown that conditioned media from infected glial cell cultures (supernatants) contain a factor unrelated to infectious virus and capable of inducing H-2 class I antigens on uninfected glial cells. The synthesis of this factor appears to be dependent on production of infectious virus since the H-2 inducing activity could not be detected 3 days following the addition of neutralizing antibodies to the cultures. This suggests that H-2 inducing activity contains as unstable component, the synthesis of which is dependent on continual virus production. Persistent MHV infection and H-2 class I antigen expression may play a role in MHV-induced demyelination.

negative: Polymerase chain reaction–based detection of rhinovirus, respiratory syncytial virus, and coronavirus in otitis media with effusion Abstract Objectives: To study the association of human rhinovirus (HRV), respiratory syncytial virus (RSV), and human coronavirus infections in children aged 6 months to 12 years with otitis media with effusion (OME). To determine how long HRV RNA can be detected after HRV infection. Methods: Middle ear effusion (MEE) samples collected at the time of tympanostomy tube placement from 100 children with OME were examined. Viral RNA was detected by reverse-transcriptase polymerase chain reaction. For HRV the results were compared with virus isolation in cell culture. In vitro studies of the persistence of HRV infectivity and RNA were conducted by combining ~105 median cell culture infectious doses of HRV with pooled MEE at 37°C and assaying serial samples for 12 weeks. Results: Virus RNA was detected in 30 children. HRV was detected by reverse-transcriptase polymerase chain reaction in 19 children with OME and by virus isolation in 5 children. RSV RNA was found in 8 and HCV in 3 children with OME. No dual viral infection was found. Bacterial pathogens were isolated from 35 MEE samples and were associated with viral RNA in 11 cases, most often with HRV (9 cases). Under in vitro conditions, HRV culture positivity declined rapidly (<2 days), but RNA was detectable for up to 8 weeks. Conclusions: These results suggest that virus infection, particularly HRV infection, either alone or concurrent with bacteria, is present in a larger percentage of children with OME than previously suspected. It remains to be determined how often the presence of viral RNA in MEE represents persistent RNA, ongoing viral replication, or recurrent infection. (J Pediatr 1998;133:390-4)

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: Household transmission of SARS-CoV-2 Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic in China and many other countries. Many infected clusters have been found within familial households, but the data about secondary transmission among household contacts is limited. Methods In this retrospective case series, we enrolled 85 patients infected with SARS-CoV-2 and their household members in Wuhan. Patients were confirmed infected with SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) assays on throat swabs. Epidemiological, clinical and laboratory data of the household members were collected. Results There were 155 close contacts in total. 104 contacts received RT-PCR assays, with 47 (30%) positive cases and 57 (37%) negative cases. 51 (33%) cases did not received RT-PCR tests for they showed no symptoms of pneumonia during the 2 weeks of quarantine. The infection rate of close contacts was 38% for households with 1 contact, 50% for households with 2 contacts, and 31% for households with 3 contacts. Conclusions The rate of secondary transmission among household contacts of patients with SARS-CoV-2 infection was 30%. Our data provide insight into the rate of secondary transmission of SARS-CoV-2 in home.

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: Optimizing working space in laparoscopy: CT-measurement of the effect of neuromuscular blockade and its reversal in a porcine model. OBJECTIVE The objective of this paper was to determine the effect of neuromuscular blockade (NMB) on working space in a porcine laparoscopy model. BACKGROUND Conflicting results on the effect of NMB on laparoscopic working space are found in literature. Almost all studies are limited by absence of objective assessment of working space or use surrogate outcomes. METHODS In a standardized porcine laparoscopy model, laparoscopic working-space dimensions with and without NMB were investigated in 16 animals using computed tomography at intra-abdominal pressures of 0, 5, 10, and 15 mmHg during multiple runs of abdominal insufflation. RESULTS No statistically significant effect of NMB on abdominal dimensions and laparoscopic working-space volume was found during CO2 pneumoperitoneum. In contrast, the effect of pre-stretching of the abdominal wall by a previous abdominal insufflation was found to be significant. CONCLUSIONS This experimental study confirms the results from several clinical studies that NMB does not influence laparoscopic working space. Studies dealing with working space during laparoscopy should take note of pre-stretching bias.

negative: Vimentin Modulates Infectious Internalization of Human Papillomavirus 16 Pseudovirions Human papillomavirus (HPV) infection is the most common viral infection of the reproductive tract, with virtually all cases of cervical cancer being attributable to infection by oncogenic HPVs. However, the exact mechanism and receptors used by HPV to infect epithelial cells are controversial. The current entry model suggests that HPV initially attaches to heparan sulfate proteoglycans (HSPGs) at the cell surface, followed by conformational changes, cleavage by furin convertase, and subsequent transfer of the virus to an as-yet-unidentified high-affinity receptor. In line with this model, we established an in vitro infection system using the HSPG-deficient cell line pgsD677 together with HPV16 pseudovirions (HPV16-PsVs). While pgsD677 cells were nonpermissive for untreated HPV16-PsVs, furin cleavage of the particles led to a substantial increase in infection. Biochemical pulldown assays followed by mass spectrometry analysis showed that furin-precleaved HPV16-PsVs specifically interacted with surface-expressed vimentin on pgsD677 cells. We further demonstrated that both furin-precleaved and uncleaved HPV16-PsVs colocalized with surface-expressed vimentin on pgsD677, HeLa, HaCaT, and NIKS cells, while binding of incoming viral particles to soluble vimentin protein before infection led to a substantial decrease in viral uptake. Interestingly, decreasing cell surface vimentin by small interfering RNA (siRNA) knockdown in HeLa and NIKS cells significantly increased HPV16-PsV infectious internalization, while overexpression of vimentin had the opposite effect. The identification of vimentin as an HPV restriction factor enhances our understanding of the initial steps of HPV-host interaction and may lay the basis for the design of novel antiviral drugs preventing HPV internalization into epithelial cells. IMPORTANCE Despite HPV being a highly prevalent sexually transmitted virus causing significant disease burden worldwide, particularly cancer of the cervix, cell surface events preceding oncogenic HPV internalization are poorly understood. We herein describe the identification of surface-expressed vimentin as a novel molecule not previously implicated in the infectious internalization of HPV16. Contrary to our expectations, vimentin was found to act not as a receptor but rather as a restriction factor dampening the initial steps of HPV16 infection. These results importantly contribute to our current understanding of the molecular events during the infectious internalization of HPV16 and open a new direction in the development of alternative drugs to prevent HPV infection.

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: COVID-19 and Anosmia in Tehran, Iran Patients with acute olfactory disorders typically present to the otolaryngologist with both acute hyposmia and less often with anosmia. With the onset of COVID-19 we have noticed an increase in the number of patients who have presented with new onset of complete smell loss to the senior author’s practice in Tehran, Iran. This anosmia and the frequency with which patients present is highly unusual. Coronaviruses have been known to cause common cold symptoms. COVID-19 infections have been described as causing more severe respiratory infections and the symptoms reported by authors from Wuhan, China have not specifically included anosmia. We describe patients who have presented during a two-week period of the COVID-19 pandemic with complete loss of sense of smell. Most had either no symptoms or mild respiratory symptoms. Many had a normal otolaryngologic exam. A relationship between COVID-19 and anosmia should be considered during the pandemic. We hypothesize that the mechanism of injury is similar to that of other coronavirus infections that cause central and peripheral neurologic deficits.

negative: Survival and Transport of Enteric Viruses in the Environment

negative: Caveolin-1 and -2 in airway epithelium: expression and in situ association as detected by FRET-CLSM BACKGROUND: Caveolae are involved in diverse cellular functions such as signal transduction, cholesterol homeostasis, endo- and transcytosis, and also may serve as entry sites for microorganisms. Hence, their occurrence in epithelium of the airways might be expected but, nonetheless, has not yet been examined. METHODS: Western blotting, real-time quantitative PCR analysis of abraded tracheal epithelium and laser-assisted microdissection combined with subsequent mRNA analysis were used to examine the expression of cav-1 and cav-2, two major caveolar coat proteins, in rat tracheal epithelium. Fluorescence immunohistochemistry was performed to locate caveolae and cav-1 and -2 in the airway epithelium of rats, mice and humans. Electron-microscopic analysis was used for the identification of caveolae. CLSM-FRET analysis determined the interaction of cav-1α and cav-2 in situ. RESULTS: Western blotting and laser-assisted microdissection identified protein and transcripts, respectively, of cav-1 and cav-2 in airway epithelium. Real-time quantitative RT-PCR analysis of abraded tracheal epithelium revealed a higher expression of cav-2 than of cav-1. Immunoreactivities for cav-1 and for cav-2 were co-localized in the cell membrane of the basal cells and basolaterally in the ciliated epithelial cells of large airways of rat and human. However, no labeling for cav-1 or cav-2 was observed in the epithelial cells of small bronchi. Using conventional double-labeling indirect immunofluorescence combined with CLSM-FRET analysis, we detected an association of cav-1α and -2 in epithelial cells. The presence of caveolae was confirmed by electron microscopy. In contrast to human and rat, cav-1-immunoreactivity and caveolae were confined to basal cells in mice. Epithelial caveolae were absent in cav-1-deficient mice, implicating a requirement of this caveolar protein in epithelial caveolae formation. CONCLUSION: These results show that caveolae and caveolins are integral membrane components in basal and ciliated epithelial cells, indicating a crucial role in these cell types. In addition to their physiological role, they may be involved in airway infection.

negative: Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R 2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R 2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.

negative: 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.

negative: Complete Genome Sequence of a Divergent Human Rhinovirus C Isolate from an Infant with Severe Community-Acquired Pneumonia in Colorado, USA Here, we report the genome sequence of a divergent human rhinovirus C isolate identified from an infant with a severe community-acquired respiratory infection. RNA sequencing performed on an Illumina platform identified reads aligning to human rhinovirus species, which were de novo assembled to produce a coding-complete genome sequence.

negative: Efficacy of an automated multi-emitter whole room UV-C disinfection system against Coronaviruses MHV and MERS-CoV The virus responsible for Middle Eastern respiratory syndrome, MERS-CoV is a lineage C betacoronavirus similar to the mouse hepatitis virus type A59 (MHV-A59). The first reported case of MERS occurred in Saudi Arabia in 2012 and resulted in 76 deaths(1). Outbreaks of MERS have since occurred not only in the Middle East but South Korea as well(2). Rapid, efficient, and automated methods of disinfecting surfaces contaminated with the MERS-CoV virus may prevent the spread of the virus in the healthcare setting. Here we report on the use of an automated triple-emitter whole room disinfection system to inactivate the MHV-A59 and the MERS-CoV viruses on surfaces with a greater than 5 log(10) reduction on MERS in 5 minutes of UV-C exposure.

negative: Does SARS-CoV-2 infection cause chronic neurological complications? The current pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has created an unparalleled health crisis. Besides the acute respiratory infection, CoVs are neuroinvasive causing additional inflammation and neurodegeneration. This is likely also true of SARS-CoV-2 given reports of neurological manifestations in coronavirus disease 2019 (COVID-19) positive patients. Older adults > 65 years of age constitute a high-risk group prone to severe infection and death. Despite the higher mortality rate, a majority of cases are expected to recover and survive from this viral outbreak. But, the long-term consequences of SARS-CoV-2 neuroinfection are unknown. We discuss these potential chronic changes to the central nervous system (CNS) in relation to accelerated brain aging and age-related neurodegenerative disorders.

negative: Potential short-term outcome of an uncontrolled COVID-19 epidemic in Lombardy, Italy, February to March 2020 Sustained coronavirus disease (COVID-19) transmission is ongoing in Italy, with 7,375 reported cases and 366 deaths by 8 March 2020. We provide a model-based evaluation of patient records from Lombardy, predicting the impact of an uncontrolled epidemic on the healthcare system. It has the potential to cause more than 250,039 (95% credible interval (CrI): 147,717–459,890) cases within 3 weeks, including 37,194 (95% CrI: 22,250–67,632) patients requiring intensive care. Aggressive containment strategies are required.

negative: Protein interaction with dendrimer monolayers: Energy and surface topology Protein interaction with polymers layers is a keystone in designing bio-nano devices. Polyamidoamines (PAMAMs) are well-known polymers. Zero aromatic core dendrimers (ZAC) are molecules with no proven toxic effect in cultured cells. When coating nanodevices with enzymatic systems, active sites are disturbed by an interaction with the biosystem surface. Computational methods were used in order to simulate, characterize, and quantify protein-polymer interaction. Protein corona, i.e., surface proteins disposed on a viral membrane or nanodevice outer surface, are crucial in interactions with a potential pharmacological target or receptor. Corona symmetry has been observed in the Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndromecoronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As a protein alpha 1 antitrypsin's a crystallographic structure was chosen. Protein-mono dendrimer layer systems were generated using in silico methods in order to simulate their interaction. Interactions were quantified using topological and quantum mechanical strategies. Results showed that PAMAM and ZAC interact differently with alpha 1 antitrypsin. Energy and topological surfaces of protein vary accordingly with the dendrimer monolayer. Topological surfaces have a higher sensibility in describing the interactions.

negative: Global research trends of World Health Organization’s top eight emerging pathogens BACKGROUND: On December 8(th), 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. METHOD: Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. RESULTS: A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h-index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R. was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine – related research with Ebola vaccine being most studied. CONCLUSION: Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h-index are indicative of how international collaboration can create common health agenda among distant different countries.

negative: 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.

negative: Reducing mortality from 2019-nCoV: host-directed therapies should be an option

negative: A Chinese Case of Coronavirus Disease 2019 (COVID-19) Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey Controversy remains over whether the coronavirus disease 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period.

negative: 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.

negative: The virus crisis affects Orthopaedic surgery and scientific activities worldwide

negative: A case report of neonatal COVID-19 infection in China In December 2019, the 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 emerged in China and now has spread in many countries. Pregnant women are susceptible population of COVID-19 which are more likely to have complications and even progresse to severe illness. We report a case of neonatal COVID-19 infection in China with pharyngeal swabs tested positive by rRT-PCR assay 36 hours after birth. However, whether the case is a vertical transmission from mother to child remains to be confirmed.

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: Environmental contamination of SARS-CoV-2 in healthcare premises 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.

negative: Spatio-temporal evolution of Beijing 2003 SARS epidemic Studying spatio-temporal evolution of epidemics can uncover important aspects of interaction among people, infectious diseases, and the environment, providing useful insights and modeling support to facilitate public health response and possibly prevention measures. This paper presents an empirical spatio-temporal analysis of epidemiological data concerning 2321 SARS-infected patients in Beijing in 2003. We mapped the SARS morbidity data with the spatial data resolution at the level of street and township. Two smoothing methods, Bayesian adjustment and spatial smoothing, were applied to identify the spatial risks and spatial transmission trends. Furthermore, we explored various spatial patterns and spatio-temporal evolution of Beijing 2003 SARS epidemic using spatial statistics such as Moran’s I and LISA. Part of this study is targeted at evaluating the effectiveness of public health control measures implemented during the SARS epidemic. The main findings are as follows. (1) The diffusion speed of SARS in the northwest-southeast direction is weaker than that in northeast-southwest direction. (2) SARS’s spread risk is positively spatially associated and the strength of this spatial association has experienced changes from weak to strong and then back to weak during the lifetime of the Beijing SARS epidemic. (3) Two spatial clusters of disease cases are identified: one in the city center and the other in the eastern suburban area. These two clusters followed different evolutionary paths but interacted with each other as well. (4) Although the government missed the opportunity to contain the early outbreak of SARS in March 2003, the response strategies implemented after the mid of April were effective. These response measures not only controlled the growth of the disease cases, but also mitigated the spatial diffusion.

negative: 157 Coronaviruses, Including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)

negative: Deep learning model can predict water binding sites on the surface of proteins using limited-resolution data The surfaces of proteins are generally hydrophilic but there have been reports of sites that exhibit an exceptionally high affinity for individual water molecules. Not only do such molecules often fulfil critical biological functions, but also, they may alter the binding of newly designed drugs. In crystal structures, sites consistently occupied in each unit cell yield electron density clouds that represent water molecule presence. These are recorded in virtually all high-resolution structures obtained through X-ray diffraction. In this work, we utilized the wealth of data from the RCSB Protein Data Bank to train a residual deep learning model named ‘hotWater’ to identify sites on the surface of proteins that are most likely to bind water, the so-called water hot spots. The model can be used to score existing water molecules from a PDB file to provide their ranking according to the predicted binding strength or to scan the surface of a protein to determine the most likely water hot-spots de novo. This is computationally much more efficient than currently used molecular dynamics simulations. Based on testing the model on three example proteins, which have been resolved using both high-resolution X-ray crystallography (providing accurate positions of trapped waters) as well as low-resolution X-ray diffraction, NMR or CryoEM (where structure refinement does not yield water positions), we were able to show that the hotWater method is able to recover in the “water-free” structures many water binding sites known from the high-resolution structures. A blind test on a newly solved protein structure with waters removed from the PDB also showed good prediction of the crystal water positions. This was compared to two known algorithms that use electron density and was shown to have higher recall at resolutions >2.6 Å. We also show that the algorithm can be applied to novel proteins such as the RNA polymerase complex from SARS-CoV-2, which could be of use in drug discovery. The hotWater model is freely available at (https://pypi.org/project/hotWater/).

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: Quantitative Assessment of the Bioburden of High-Touch Environmental Surfaces in Pediatric Operating Rooms BACKGROUND: Previous studies have linked healthcare-associated infections to bacterial pathogens in the operating room (OR) environment. The purpose of this study was to determine the bioburden on OR surfaces to guide future quality improvement efforts and optimize OR cleanliness. METHODS: This study was performed in the pediatric ORs of a 200-bed, academically affiliated, children’s hospital with ~6000 general and subspecialty surgical procedures annually. Immediately after cases were finished, but prior to cleaning, the 3M Clean-Trace Clinical Hygiene Monitoring System was used to quantify bioburden (in surface ATP concentration) on 24 surfaces in each of 8 ORs. These 24 surfaces were previously identified by the Association of periOperative Registered Nurses as high-touch surfaces and various disciplines are responsible for their cleaning. Each OR was sampled 1–4 times. A surface passed the test of cleanliness if the result was <250 relative light units (RLUs). RESULTS: In all, 364 surfaces were tested. The median RLUs were <250, 250–850, and >850 RLUs for 7, 11, and 6 surfaces, respectively. Of the 24 surfaces tested, all demonstrated bioburden ≥250 at least once. Median RLUs for each surface ranged from 39-2282 and median RLUs for each OR ranged from 196 to 1534. The highest bioburden occurred following cardiac surgery (median 1534, range 24-13275 RLU) and the lowest bioburden occurred after neurosurgery (median 196, range 23-2475 RLU). The surfaces with the highest bioburden were the anesthesia keyboards (median 2282, range 347-38376 RLU) and core door handles (median 1471, range 140–6788 RLU) and those with the lowest bioburden were the Mayo stand (median 39, range 19-765 RLU) and back table (median 39, range 17-406 RLU). CONCLUSION: ATP testing demonstrated that most OR surfaces were contaminated with organic material. While OR surfaces prior to cleaning are expected to be contaminated, these data highlight the importance of cleaning/disinfection. These findings are being used to develop educational tools and interventions for the interdisciplinary OR team, which will focus on delineation of cleaning responsibilities, the use of appropriate cleaning products, and audits of end-of-case cleaning and terminal cleaning. DISCLOSURES: All authors: No reported disclosures.

negative: Structural definition of a conserved neutralization epitope on HIV-1 gp120 The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 Å resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.

negative: 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.

negative: Tabagisme et maladie à coronavirus 2019 (COVID-19)

negative: The Regulation and Maturation of Antiviral Immune Responses

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

negative: Characterization of a calf diarrheal coronavirus. A coronavirus-like agent isolated from feces of a calf with diarrhea and attenuated by consecutive passage in a fetal bovine kidney cell line was characterized as a coronavirus. Negatively stained virions were approximately circular, had a mean diameter of 120 nm, and were covered with wide-spaced, petal-shaped projections about 20 nm long. Virions in ultrathin sections of infected cell monolayers had a mean diameter of 80 nm, lacked surface projections, and were found within cytoplasmic vesicles. Viral antigen was demonstrated by immunofluorescence microscopy to occur only in cytoplasm. Growth of the virus was not inhibited by 5-iodo-2'- deoxyuridine and actinomycin D. The virus was sensitive to ether, chloroform, deoxycholate, and heat treatment. However, thermosensitivity was stabilized in the presence of 1 M MgCl2; at pH 3, the virus was stable. Hemadsorption and hemagglutination were observed with erythrocytes of hamsters, mice, and rats but not with erythrocytes of cats, dogs, goats, sheep, cattle, horses, turkeys, chickens, guinea pigs, rabbits, geese, pigs, and man (type O). However, hemadsorption and hemagglutination were shown to be virus specific, since this could be inhibited by specific antiserum. Both infectivity and hemagglutinating activity were maximal at a particle density of 1.18 g/ml by sucrose density gradient centrifugation, indicating that hemagglutinin was part of the virion.

negative: COVID-19 and surface water quality: Improved lake water quality during the lockdown Abstract Human life comes to a standstill as many countries shut themselves off from the work due to the novel coronavirus disease pandemic (COVID-19) that hit the world severely in the first quarter of 2020. All types of industries, vehicle movement, and people's activity suddenly halted, perhaps for the first time in modern history. For a long time, it has been stated in various literature that the increased industrialization and anthropogenic activities in the last two decades polluted the atmosphere, hydrosphere, and biosphere. Since the industries and people's activities have been shut off for a month or more in many parts of the world, it is expected to show some improvement in the prevailing conditions in the aforementioned spheres of environment. Here, with the help of remote sensing images, this work quantitatively demonstrated the improvement in surface water quality in terms of suspended particulate matter (SPM) in the Vembanad Lake, the longest freshwater lake in India. The SPM estimated based on established turbidity algorithm from Landsat-8 OLI images showed that the SPM concentration during the lockdown period decreased by 15.9% on average (range: −10.3% to 36.4%, up to 8 mg/l decrease) compared with the pre-lockdown period. Time series analysis of satellite image collections (April 2013 – April 2020) showed that the SPM quantified for April 2020 is the lowest for 11 out of 20 zones of the Vembanad lake. When compared with preceding years, the percentage decrease in SPM for April 2020 is up to 34% from the previous minima.

negative: A simple procedure for the derivation of electron density based surfaces of drug-receptor complexes from a combination of X-ray data and theoretical calculations Abstract To contribute to an understanding of biological recognition and interaction, an easy-to-use procedure was developed to generate and display molecular surfaces and selected electron density based surface properties. To overcome the present limitations to derive electron densities of macromolecules, the considered systems were reduced to appropriate substructures around the active centers. The combination of experimental X-ray structural information and aspherical atomic electron density data from theoretical calculations resulted in properties like the electrostatic potential and the Hirshfeld surface which allowed a study of electronic complementarity and the identification of sites and strengths of drug-receptor interactions. Applications were examined for three examples. The anilinoquinazoline gefitinib (Iressa®) belongs to a new class of anticancer drugs that inhibit the tyrosine kinase activity of the epidermal growth factor receptor (EGFR). In the second example, the interaction of epoxide inhibitors with the main protease of the SARS coronavirus was investigated. Furthermore, the progesterone receptor complex was examined. The quantitative analysis of hydrogen bonding in the chosen substructure systems follows a progression elaborated earlier on the basis of accurate small molecule crystal structures. This finding and results from modified substructures suggest that also the surface properties seem robust enough to provide stable information about the recognition of interacting biomolecular species although they are obtained from medium molecular weighted subfragments of macromolecular complexes, which consist of no more than ∼40 residues.

negative: Modelling of SARS for Hong Kong A simplified susceptible-infected-recovered (SIR) epidemic model and a small-world model are applied to analyse the spread and control of Severe Acute Respiratory Syndrome (SARS) for Hong Kong in early 2003. From data available in mid April 2003, we predict that SARS would be controlled by June and nearly 1700 persons would be infected based on the SIR model. This is consistent with the known data. A simple way to evaluate the development and efficacy of control is described and shown to provide a useful measure for the future evolution of an epidemic. This may contribute to improve strategic response from the government. The evaluation process here is universal and therefore applicable to many similar homogeneous epidemic diseases within a fixed population. A novel model consisting of map systems involving the Small-World network principle is also described. We find that this model reproduces qualitative features of the random disease propagation observed in the true data. Unlike traditional deterministic models, scale-free phenomena are observed in the epidemic network. The numerical simulations provide theoretical support for current strategies and achieve more efficient control of some epidemic diseases, including SARS.

negative: Does hand hygiene reduce SARS-CoV-2 transmission?

negative: Coronavirus, humanpathogenes Humanes Coronavirus, Gruppe 1 Coronavirus

negative: High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release Tetherin is an interferon-inducible antiviral protein that inhibits the release of a broad spectrum of enveloped viruses by retaining virions at the surface of infected cells. While the role of specific tetherin domains in antiviral activity is clearly established, the role of glycosylation in tetherin function is not clear. In this study, we carried out a detailed investigation of this question by using tetherin variants in which one or both sites of N-linked glycosylation were mutated (N65A, N92A, and N65,92A), and chemical inhibitors that prevent glycosylation at specific stages of oligosaccharide were added or modified. The single N-linked glycosylation mutants, N65A and N92A, efficiently inhibited the release of Vpu-defective human immunodeficiency virus type 1 (HIV-1). In contrast, the non-glycosylated double mutant, N65,92A, lost its ability to block HIV-1 release. The inability of the N65,92A mutant to inhibit HIV-1 release is associated with a lack of cell-surface expression. A role for glycosylation in cell-surface tetherin expression is supported by tunicamycin treatment, which inhibits the first step of N-linked glycosylation and impairs both cell-surface expression and antiviral activity. Inhibition of complex-type glycosylation with kifunensine, an inhibitor of the oligosaccharide processing enzyme mannosidase 1, had no effect on either the cell-surface expression or antiviral activity of tetherin. These results demonstrate that high-mannose modification of a single asparagine residue is necessary and sufficient, while complex-type glycosylation is dispensable, for cell-surface tetherin expression and antiviral activity.

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: A self-assembled fusion protein-based surface plasmon resonance biosensor for rapid diagnosis of severe acute respiratory syndrome Abstract A surface plasmon resonance (SPR)-based biosensor was developed for simple diagnosis of severe acute respiratory syndrome (SARS) using a protein created by genetically fusing gold binding polypeptides (GBPs) to a SARS coronaviral surface antigen (SCVme). The GBP domain of the fusion protein serves as an anchoring component onto the gold surface, exploiting the gold binding affinity of the domain, whereas the SCVme domain is a recognition element for anti-SCVme antibody, the target analyte in this study. SPR analysis indicated the fusion protein simply and strongly self-immobilized onto the gold surface, through GBP, without surface chemical modification, offering a stable and specific sensing platform for anti-SCVme detection. AFM and SPR imaging analyses demonstrated that anti-SCVme specifically bound to the fusion protein immobilized onto the gold-micropatterned chip, implying that appropriate orientation of bound fusion protein by GBP resulted in optimal exposure of the SCVme domain to the assay solution, resulting in efficient capture of anti-SCVme antibody. The best packing density of the fusion protein onto the SPR chip was achieved at the concentration of 10μgmL−1; this density showed the highest detection response (906RU) for anti-SCVme. The fusion protein-coated SPR chip at the best packing density had a lower limit of detection of 200ngmL−1 anti-SCVme within 10min and also allowed selective detection of anti-SCVme with significantly low responses for non-specific mouse IgG at all tested concentrations. The fusion protein provides a simple and effective method for construction of SPR sensing platforms permitting sensitive and selective detection of anti-SCVme antibody.

negative: Hand disinfection in the combat against Covid‐19 The World Health Organization (WHO) has declared a global health emergency over a new coronavirus. The new corona virus (SARS‐CoV‐2) has raised global attention with raising concerns of rapid spread from human‐to‐human. Like severe acute respiratory syndrome (SARS)‐nCoV, 2019‐nCoV can be passed directly from person to person by respiratory droplets, and may also be transmitted through contact and fomites.

negative: Extracorporeal membrane oxygenation (ECMO) for pulmonary parenchymal disease in older children Extracorporeal membrane oxygenation (ECMO) for the support of children outside the newborn period who have pulmonary failure is only recently becoming accepted. It is again being applied, after earlier failures, because well-trained teams and improved equipment and techniques are available following the success of neonatal ECMO. In addition, in Europe extracorporeal CO(2) removal (ECCO(2)R) in adults has been more successful. The use of ECMO for pulmonary failure in children does not have fixed indications and has had considerably less success than neonatal ECMO. Patients who require inspired oxygen fractions of over 0.5 and positive end-expiratory pressures of over 6 cm H(2)O for more than 12 h after being treated for more than 48 h should be considered candidates, given the high mortality of children with ARDS (70%). Survival averages 50% to 60%. Circuits and patient management techniques are very similar to those for newborn ECMO, but patients usually require longer times on ECMO. There are many more options for cannulation for both venoarterial and venovenous techniques than in neonatal and cardiac ECMO. The improving results indicate that ECMO will play a part in treating children with pulmonary failure. Further studies will be required to determine which patients can benefit from ECMO as well as the exact application in each case.

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: Customs officers in relation to viral infections, tuberculosis, psittacosis and environmental health risk. Customs Service is a financial authority responsible for controlling the flow of importation and exportation goods in each country and for collecting the relevant taxes. Customs officers are considered as 'high-demand' and 'high-responsibility' governmental officials, which constitute members of multidisciplinary teams at the local, as well as international level and collaborate with different authorities, including medical officers. Despite limited data in the medical literature, customs officers are considered as a 'high-risk' occupational group for infections and environmental health risk. During the severe acute respiratory syndrome (SARS) and influenza A/H1N1 pandemic outbreaks in 2003 and 2009, respectively, customs officers had a fundamental front-line input in the establishment of the recommended at that time border measures. In Belgium in 1994, a psittacosis outbreak occurred in customs officers following their exposure to illegally imported parakeets. During the recent increased immigration proceedings, customs officers have been involved in detaining unauthorized populations for various infectious diseases, such as tuberculosis, varicella and measles. Occupational risk for customs officers also includes noise-induced hearing loss, exposure to diesel engine emission and stored tobacco and occupational stress due to their increased time-schedule and decision-making duties. In this review, we discuss customs officers' occupational risk towards environmental and infectious factors, including viral infections, tuberculosis and psittacosis.

negative: COVID-19 and the Ocular Surface: A Review of Transmission and Manifestations PURPOSE: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached pandemic proportions within an unprecedented span of time. It is controversial whether the virus can be transmitted via tears and its ocular implications have not been widely studied. In this article, the current evidence related to ocular transmission and ocular manifestations is reviewed. RESULTS: Several mechanisms for the ocular transmission of the virus are proposed with highlight on the nasolacrimal system as a conduit between the eye and the respiratory tract, and the role of the lacrimal gland in hematogenous spread. Ocular surface manifestations such as conjunctivitis are more commonly reported. CONCLUSION: The exact pathophysiology of ocular transmission of the virus remains incompletely understood, although there is preliminary evidence of SARS-CoV-2 being detected in ocular secretions. The ocular tropism of the virus and its potential to cause localized ocular disease are worth considering.

negative: Reading Comics for Citizenship This chapter offers assignments which center on reading comics. These assignments are meant to help students read comics in light of ideas and concepts related to citizenship and the social studies.

negative: Long time frames to detect the impact of changing COVID-19 control measures Background: Many countries have implemented population-wide interventions such as physical distancing measures, in efforts to control COVID-19. The extent and success of such measures has varied. Many jurisdictions with declines in reported COVID-19 cases are moving to relax measures, while others are continuing to intensify efforts to reduce transmission. Aim: We aim to determine the time frame between a change in COVID-19 measures at the population level and the observable impact of such a change on cases. Methods: We examine how long it takes for there to be a substantial difference between the cases that occur following a change in control measures and those that would have occurred at baseline. We then examine how long it takes to detect a difference, given delays and noise in reported cases. We use changes in population-level (e.g., distancing) control measures informed by data and estimates from British Columbia, Canada. Results: We find that the time frames are long: it takes three weeks or more before we might expect a substantial difference in cases given a change in population-level COVID-19 control, and it takes slightly longer to detect the impacts of the change. The time frames are shorter (11-15 days) for dramatic changes in control, and they are impacted by noise and delays in the testing and reporting process, with delays reaching up to 25-40 days. Conclusion: The time until a change in broad control measures has an observed impact is longer than is typically understood, and is longer than the mean incubation period (time between exposure than onset) and the often used 14 day time period. Policy makers and public health planners should consider this when assessing the impact of policy change, and efforts should be made to develop rapid, consistent real-time COVID-19 surveillance.

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: 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.

negative: 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.

negative: USING A BIOLOGICAL INDICATOR TO DETECT POTENTIAL SOURCES OF CROSS-CONTAMINATION IN THE DENTAL OPERATORY ABSTRACT The authors conducted a study using surveillance monitoring methodology to identify operatory contamination and to evaluate the effectiveness of infection control procedures. Viridans streptococci were evaluated as biological indicators of oral contamination. Viridans streptococci, abundant in human saliva, were detected on operatory surfaces after dental treatments were finished and surfaces were disinfected. The findings validate current concepts of infection control as demonstrated in barrier methods.

negative: Influenza D Virus Infection in Dromedary Camels, Ethiopia Influenza D virus has been found to cause respiratory diseases in livestock. We surveyed healthy dromedary camels in Ethiopia and found a high seroprevalence for this virus, in contrast to animals co-existing with the camels. Our observation implies that dromedary camels may play an important role in the circulation of influenza D virus.

negative: Corona Epidemic in Indian context: Predictive Mathematical Modelling The novel Coronavirus pathogen Covid-19 is a cause of concern across the world as the human-to-human infection caused by it is spreading at a fast pace. The virus that first manifested in Wuhan, China has travelled across continents. The increase in number of deaths in Italy, Iran, USA, and other countries has alarmed both the developed and developing countries. Scientists are working hard to develop a vaccine against the virus, but until now no breakthrough has been achieved. India, the second most populated country in the world, is working hard in all dimensions to stop the spread of community infection. Health care facilities are being updated; medical and paramedical staffs are getting trained, and many agencies are raising awareness on the issues related to this virus and its transmission. The administration is leaving no stone unturned to prepare the country to mitigate the adverse effects. However, as the number of infected patients, and those getting cured is changing differently in different states everyday it is difficult to predict the spread of the virus and its fate in Indian context. Different states have adopted measures to stop the community spread. Considering the vast size of the country, the population size and other socio-economic conditions of the states, a single uniform policy may not work to contain the disease. In this paper, we discuss a predictive mathematical model that can give us some idea of the fate of the virus, an indicative data and future projections to understand the further course this pandemic can take. The data can be used by the health care agencies, the Government Organizations and the Planning Commission to make suitable arrangements to fight the pandemic. Though the model is preliminary, it can be used at regional level to manage the health care system in the present scenario. The recommendations can be made, and advisories prepared based on the predictive results that can be implemented at regional levels.

negative: Prior and Novel Coronaviruses, COVID-19, and Human Reproduction: What Is Known? Structured Abstract Objective To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. Design Review of English publications in PubMed and Embase to April 6, 2020. Methods Manuscripts were screened for reports including coronavirus, reproduction, including pathophysiology and pregnancy. Intervention(s) None. Main Outcome Measure(s) Reproductive outcomes; effects on gametes; pregnancy outcomes; neonatal complications. Results Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. SARS-CoV-1 may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following COVID-19 infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-CoV-2 adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or MERS, but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. COVID-19 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. Conclusion COVID-19 infection may adversely affect some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.

negative: Human T-cell immunity against the emerging and re-emerging viruses Over the past decade, we have seen an alarming number of high-profile outbreaks of newly emerging and re-emerging viruses. Recent outbreaks of avian influenza viruses, Middle East respiratory syndrome coronaviruses, Zika virus and Ebola virus present great threats to global health. Considering the pivotal role of host T-cell immunity in the alleviation of symptoms and the clearance of viruses in patients, there are three issues to be primarily concerned about T-cell immunity when a new virus emerges: first, does the population possess pre-existing T-cells against the new virus through previous infections of genetically relevant viruses; second, does a proper immune response arise in the patients to provide protection through an immunopathogenic effect; lastly, how long can the virus-specific immune memory persist. Herein, we summarize the current updates on the characteristics of human T-cell immunological responses against recently emerged or re-emerged viruses, and emphasize the necessity for timely investigation on the T-cell features of these viral diseases, which may provide beneficial recommendations for clinical diagnosis and vaccine development.

negative: Effect of various decontamination procedures on disposable N95 mask integrity and SARS-CoV-2 infectivity The COVID-19 pandemic has created a high demand on personal protective equipment, including disposable N95 masks. Given the need for mask reuse, we tested the feasibility of vaporized hydrogen peroxide (VHP), ultraviolet light (UV), and ethanol decontamination strategies on N95 mask integrity and the ability to remove the infectious potential of SARS-CoV-2. FIT test data showed functional degradation by both ethanol and UV decontamination to different degrees. VHP treated masks showed no significant change in function after two treatments. We also report a single SARS-CoV-2 virucidal experiment using Vero E6 cell infection. We hope our data will guide further research for evidenced-based decisions for disposable N95 mask reuse and help protect caregivers from SARS-CoV-2 and other pathogens.

negative: Active Immunoprophylaxis and Vaccine Augmentations Mediated by a Novel Plasmid DNA Formulation Plasmid DNA (pDNA) gene delivery is a highly versatile technology that has the potential to address a multitude of unmet medical needs. Advances in pDNA delivery to host tissue with the employment of in vivo electroporation (EP) have led to significantly enhanced gene expression and the recent demonstration of clinical efficacy with the platform. Building upon this platform, this study reports that enzyme-mediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to enhance both local and systemic gene expression further. Specifically, administration of chondroitinase ABC (Cho ABC) to the site of intramuscular delivery of pDNA led to transient disruption of chondroitin sulfate scaffolding barrier, permitting enhanced gene distribution and expression across the tissue. The employment of Cho ABC in combination with CELLECTRA(®) intramuscular EP resulted in increased gene expression by 5.5-fold in mice and 17.98-fold in rabbits. The study demonstrates how this protocol can be universally applied to an active prophylaxis platform to increase the in vivo production of functional immunoglobulin G, and to DNA vaccine protocols to permit drug dose sparing. The data indicate the Cho ABC formulation to be of significant value upon combination with EP to drive enhanced gene expression levels in pDNA delivery protocols.

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: Liposome-Coupled Peptides Induce Long-Lived Memory CD8(+) T Cells Without CD4(+) T Cells CD8(+) T cells provide broad immunity to viruses, because they are able to recognize all types of viral proteins. Therefore, the development of vaccines capable of inducing long-lived memory CD8(+) T cells is desired to prevent diseases, especially those for which no vaccines currently exist. However, in designing CD8(+) T cell vaccines, the role of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells remains uncertain. In the present study, the necessity or not of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells was investigated in mice immunized with liposome-coupled CTL epitope peptides. When OVA-derived CTL epitope peptides were chemically coupled to the surfaces of liposomes and inoculated into mice, both primary and secondary CTL responses were successfully induced. The results were further confirmed in CD4(+) T cell-eliminated mice, suggesting that CD4(+) T cells were not required for the generation of memory CD8(+) T cells in the case of immunization with liposome-coupled peptides. Thus, surface-linked liposomal antigens, capable of inducing long-lived memory CD8(+) T cells without the contribution of CD4(+) T cells, might be applicable for the development of vaccines to prevent viral infection, especially for those viruses that evade humoral immunity by varying their surface proteins, such as influenza viruses, HIV, HCV, SARS coronaviruses, and Ebola viruses.

negative: A child with household transmitted COVID-19 BACKGROUND: Although people of all ages are susceptible to the novel coronavirus infection, which is presently named “Coronavirus Disease 2019” (COVID-19), there has been relatively few cases reported among children. Therefore, it is necessary to understand the clinical characteristics of COVID-19 in children and the differences from adults. CASE PRESENTATION: We report one pediatric case of COVID-19. A 14-month-old boy was admitted to the hospital with a symptom of fever, and was diagnosed with a mild form of COVID-19. The child’s mother and grandmother also tested positive for SARS-CoV-2 RNA. However, the lymphocyte counts were normal. The chest computed tomography (CT) revealed scattered ground glass opacities in the right lower lobe close to the pleura and resorption after the treatment. The patient continued to test positive for SARS-CoV-2 RNA in the nasopharyngeal swabs and stool at 17 days after the disappearance of symptoms. CONCLUSION: The present pediatric case of COVID-19 was acquired through household transmission, and the symptoms were mild. Lymphocyte counts did not significantly decrease. The RNA of SARS-CoV-2 in stool and nasopharyngeal swabs remained positive for an extended period of time after the disappearance of symptoms. This suggests that attention should be given to the potential contagiousness of pediatric COVID-19 cases after clinical recovery.

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: Structure of the SARS-CoV NSP12 polymerase bound to NSP7 and NSP8 co-factors Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (NSP) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV NSP12 polymerase bound to its essential co-factors, NSP7 and NSP8, using single particle cryo-electron microscopy. NSP12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is unexpectedly bound by two NSP8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into NSP12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.

negative: 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.

negative: Why does the coronavirus spread so easily between people? As the number of coronavirus infections approaches 100,000 people worldwide, researchers are racing to understand what makes it spread so easily A handful of genetic and structural analyses have identified a key feature of the virus — a protein on its surface — that might explain why it infects human cells so readily Other groups are investigating the doorway through which the new coronavirus enters human tissues — a receptor on cell membranes Both the cell receptor and the virus protein offer potential targets for drugs to block the pathogen, but researchers say it is too early to be sure “Understanding transmission of the virus is key to its containment and future prevention,” says David Veesler, a structural virologist at the University of Washington in Seattle, who posted his team’s findings about the virus protein on the biomedical preprint server bioRxiv on 20 February1 The new virus spreads much more readily than the one that caused severe acute respiratory syndrome, or SARS (also a coronavirus), and has infected more than ten times the number of people who contracted SARS

negative: Understanding Epidemic Data and Statistics: A case study of COVID-19 The 2019-Novel-Coronavirus (COVID-19) has affected 181 countries and out of about 1197405 confirmed cases (By April 5). Understanding the transmission dynamics of the infection in each country which affected on a daily basis and evaluating the effectiveness of control policies is critical for our further actions. To date, the statistics of COVID-19 reported cases show more than 80 percent of infected had a mild case of disease, while around 14 percent of infected experienced a severe one and about 5 percent are categorized as critical disease victims. Today's report (2020-04-05; daily updates in the prepared website) shows the confirmed cases of COVID-19 in the US, Spain, Italy, and Germany are 308850, 126168, 124632, and 96092; respectively. Calculating the total Case Fatality Rate (CFR) of Italy (2020-04-04), about 13.3% of confirmed cases passed away. Compared to South Korea's rate of 1.8% (7 times lower than Italy) and China's 4% (69% lower than Italy), the CFR of Italy is too high. There are some effective policies that yield significant changes in the trend of cases. The lockdown policy in China, Italy, and Spain (the effect observed after some days), Shutdown of all non-essential companies in Hubei (the effect observed after 5 days), combined policy in South Korea, and reducing working hours in Iran.

negative: Gender Differences in Patients With COVID-19: Focus on Severity and Mortality Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS. Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003. Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015). Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.

negative: Stability of Porcine Epidemic Diarrhea Virus on Fomite Materials at Different Temperatures Indirect transmission of porcine epidemic diarrhea virus (PEDV) ensues when susceptible animals contact PEDV-contaminated fomite materials. Although the survival of PEDV under various pHs and temperatures has been studied, virus stability on different fomite surfaces under varying temperature conditions has not been explored. Hence, we evaluated the survival of PEDV on inanimate objects routinely used on swine farms such as styrofoam, rubber, plastic, coveralls, and other equipment. The titer of infectious PEDV at 4 °C decreased by only 1 to 2 log during the first 5 days, and the virus was recoverable for up to 15 days on Styrofoam, aluminum, Tyvek(®) coverall, cloth, and plastic. However, viral titers decreased precipitously when stored at room temperature; no virus was detectable after one day on all materials tested. A more sensitive immunoplaque assay was able to detect virus from Styrofoam, metal, and plastic at 20 days post application, representing a 3-log loss of input virus on fomite materials. Recovery of infectious PEDV from Tyvek(®) coverall and rubber was above detection limit at 20 days. Our findings indicate that the type of fomite material and temperatures impact PEDV stability, which is important in understanding the nuances of indirect transmission and epidemiology of PEDV.

negative: Human Coronavirus Infections—Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and SARS-CoV-2 Three novel coronaviruses have emerged as new lethal zoonotic pathogens of humans during the past 17 years: The Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS-CoV), the Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV), and most recently SARS-CoV-2. SARS-CoV first surfaced as a human pathogen in Guangdong, China in November 2002 and rapidly spread worldwide with 8098 cases and 774 deaths before the end of the epidemic. SARS-like CoVs have been detected in horseshoe bats with high sequence homology with human or civet isolates, suggesting that bats could be a natural reservoir of a close ancestor of SARS-CoV. No cases of SARS have been reported since January 2004. MERS-CoV was first reported in September 2012, after it was isolated from respiratory samples from a patient in Jeddah, Saudi Arabia who died in June 2012. How humans acquire MERS-CoV infection is not yet known although bats and dromedary camels are intermediary reservoirs. MERS-CoV continues to circulate in the Middle East. As of May 22, 2019, 2428 cases of laboratory-confirmed MERS-CoV cases reported to the World Health Organization, including 838 deaths (34.5% mortality) have been reported from 27 countries. While the majority of MERS cases occur in the Middle East, travel related MERS cases have been reported from all continents. Large health care associated outbreaks of MERS-CoV have occurred in Saudi Arabia, United Arab Emirates, and the Republic of Korea. SARS-CoV-2 emerged from Wuhan, China in December 2019, and by March 2020 had established as a pandemic which has caused massive disruption in multiple countries. The eventual mortality caused by this virus remains to be seen. All three viruses cause a similar wide range of nonspecific clinical manifestations from mild upper respiratory tract illness to severe respiratory, gastrointestinal and other extra-pulmonary disease. Early recognition of cases, improved compliance with internationally recommended infection control protocols, and rapid implementation of infection control measures are required to prevent health care facility-associated outbreaks, and in the case of SARS-CoV-2 for control of community spread as well. Treatment is supportive and there are no specific antivirals or vaccines available for both SARS and MERS.

negative: Feline coronaviruses associated with feline infectious peritonitis have modifications to spike protein activation sites at two discrete positions Feline infectious peritonitis (FIP) is associated with mutations in the feline coronavirus (FCoV) genome that are thought to convert the subclinical feline enteric coronavirus (FECV) into the lethal feline infectious peritonitis virus (FIPV). A key feature of FIPV, not shared with FECV, is the productive infection of macrophages. Therefore mutations in proteins that govern cell tropism, such as the spike glycoprotein, may play an important role in FIP progression. In a prior study, involving a limited number of samples, we have shown an association of FIP with mutations in the protease cleavage-activation site located between the receptor-binding and fusion domains of the FCoV spike (S1/S2). Here, we extend these studies to investigate a larger sample set and to obtain a more refined analysis of the mutations at this S1/S2 site. Our larger data set more clearly shows that the mutations acquired by FIPV at S1/S2 are also accompanied by additional mutations at a second protease cleavage-activation site located in the fusion domain (S2'), adjacent to the viral fusion peptide. Overall, our data indicate a pattern of mutations across the two protease recognition sites that results in substitutions, and/or altered recognition, of critical basic/polar amino acid residues needed for virus activation in the enteric tract. Typically, FIPVs have substitutions of non-polar, aliphatic or aromatic residues in the protease recognition sites. These changes likely modulate the proteolytic activation of the virus and its ability to productively infect macrophages in vivo.

negative: A family cluster of three confirmed cases infected with avian influenza A (H7N9) virus in Zhejiang Province of China BACKGROUND: A total of 453 laboratory-confirmed cases infected with avian influenza A (H7N9) virus (including 175 deaths) have been reported till October 2,2014, of which 30.68% (139/453) of the cases were identified from Zhejiang Province. We describe the largest reported cluster of virologically confirmed H7N9 cases, comprised by a fatal Index case and two mild secondary cases. METHODS: A retrospective investigation was conducted in January of 2014. Three confirmed cases, their close contacts, and relevant environments samples were tested by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), viral culture, and sequencing. Serum samples were tested by haemagglutination inhibition (HI) assay. RESULTS: The Index case, a 49-year-old farmer with type II diabetes, who lived with his daughter (Case 2, aged 24) and wife (Case 3, aged 43) and his son-in-law (H7N9 negative). The Index case and Case 3 worked daily in a live bird market. Onset of illness in Index case occurred in January 13, 2014 and subsequently, he died of multi-organ failure on January 20. Case 2 presented with mild symptoms on January 20 following frequent unprotected bed-side care of the Index case between January 14 to 19, and exposed to live bird market on January 17. Case 3 became unwell on January 23 after providing bedside care to the Index case on January 17 to 18, and following the contact with Case 2 during January 21 to 22 at the funeral of the Index case. The two secondary cases were discharged on February 2 and 5 separately after early treatment with antiviral medication. Four virus strains were isolated and genome analyses showed 99.6 ~100% genetic homology, with two amino mutations (V192I in NS and V280A in NP). 42% (11/26) of environmental samples collected in January were H7N9 positive. Twenty-five close contacts remained well and were negative for H7N9 infection by RT-PCR and HI assay. CONCLUSIONS: In the present study, the Index case was infected from a live bird market while the two secondary cases were infected by the Index case during unprotected exposure. This family cluster is, therefore, compatible with non-sustained person-to-person transmission of avian influenza A/H7N9. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0698-6) contains supplementary material, which is available to authorized users.

negative: Chapter 40 Waterborne Transmission of Enteric Viruses and Their Impact on Public Health Abstract Viruses of human or animal origin can spread in the environment and infect people via water and food. These viruses are released into the environment by various routes including water runoffs and aerosols. Furthermore, zoonotic viruses may infect humans exposed to contaminated surface waters. Viruses are emerging pathogens and are able to adapt by mutation, recombination, and reassortment and can thus become able to infect new hosts and to adjust to new environments. Enteric viruses are among the commonest and most hazardous waterborne pathogens, causing both sporadic and outbreak-related illness. While considerable research has documented the risk of enteric viruses to human health from contact with contaminated water, the current bacterial indicator-based methods for the evaluation of water quality are often ineffectual proxies for pathogenic viruses, but no correlation was established between the enteric bacteria and viruses studied. The present chapter will focus on viral pathogens shown to be transmitted through water. It will also provide an overview of viruses that had not been a concern for waterborne transmission in the past, but that may represent potentially emerging waterborne pathogens due to their occurrence and persistence in water environments. Monitoring effluents from wastewater treatment plants is important to preventing both environmental contamination and the spread of disease.

negative: Why does COVID-19 disproportionately affect older people? The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Adults over 65 years of age represent 80% of hospitalizations and have a 23-fold greater risk of death than those under 65. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea, and from there the disease can progress to acute respiratory distress syndrome, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes and obesity increase the chances of fatal disease, but they alone do not explain why age is an independent risk factor. Here, we present the molecular differences between young, middle-aged and older people that may explain why COVID-19 is a mild illness in some but life-threatening in others. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase the survival of older people, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection and effectively regulate immune responses.

negative: Human coronavirus reinfection dynamics: lessons for SARS-CoV-2 In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.

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: The epidemiology, diagnosis and treatment of COVID-19 Abstract In December 2019, the outbreak of the novel coronavirus disease (COVID-19) in China spread worldwide, becoming an emergency of major international concern. SARS-CoV-2 infection causes clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus. Human-to-human transmission via droplets, contaminated hands or surfaces has been described, with incubation times of 2-14 days. Early diagnosis, quarantine, and supportive treatments are essential to cure patients. This paper reviews the literature on all available information about the epidemiology, diagnosis, isolation and treatments of COVID-19. Treatments, including antiviral agents, chloroquine and hydroxychloroquine, corticosteroids, antibodies, convalescent plasma transfusion and vaccines, are discussed in this article. In addition, registered trials investigating treatment options for COVID-19 infection are listed.

negative: Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein. Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1A through S1D Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1B We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia). Initially demonstrated by hemagglutination assay with human erythrocytes and intact virus, MERS-CoV Sia-binding activity was assigned to S subdomain S1A When multivalently displayed on nanoparticles, S1 or S1A bound to human erythrocytes and to human mucin in a strictly Sia-dependent fashion. Glycan array analysis revealed a preference for α2,3-linked Sias over α2,6-linked Sias, which correlates with the differential distribution of α2,3-linked Sias and the predominant sites of MERS-CoV replication in the upper and lower respiratory tracts of camels and humans, respectively. Binding is hampered by Sia modifications such as 5-N-glycolylation and (7,)9-O-acetylation. Depletion of cell surface Sia by neuraminidase treatment inhibited MERS-CoV entry of Calu-3 human airway cells, thus providing direct evidence that virus-Sia interactions may aid in virion attachment. The combined observations lead us to propose that high-specificity, low-affinity attachment of MERS-CoV to sialoglycans during the preattachment or early attachment phase may form another determinant governing the host range and tissue tropism of this zoonotic pathogen.

negative: Protect Healthcare Workers and Patients from COVID-19: The Experience of Two Tertiary Ophthalmology Care Referral Centers in Italy.

negative: Severe air pollution events not avoided by reduced anthropogenic activities during COVID-19 outbreak Abstract Due to the pandemic of coronavirus disease 2019 in China, almost all avoidable activities in China are prohibited since Wuhan announced lockdown on January 23, 2020. With reduced activities, severe air pollution events still occurred in the North China Plain, causing discussions regarding why severe air pollution was not avoided. The Community Multi-scale Air Quality model was applied during January 01 to February 12, 2020 to study PM2.5 changes under emission reduction scenarios. The estimated emission reduction case (Case 3) better reproduced PM2.5. Compared with the case without emission change (Case 1), Case 3 predicted that PM2.5 concentrations decreased by up to 20% with absolute decreases of 5.35, 6.37, 9.23, 10.25, 10.30, 12.14, 12.75, 14.41, 18.00 and 30.79 μg/m3 in Guangzhou, Shanghai, Beijing, Shijiazhuang, Tianjin, Jinan, Taiyuan, Xi'an, Zhengzhou, Wuhan, respectively. In high-pollution days with PM2.5 greater than 75 μg/m3, the reductions of PM2.5 in Case 3 were 7.78, 9.51, 11.38, 13.42, 13.64, 14.15, 14.42, 16.95 and 22.08 μg/m3 in Shanghai, Jinan, Shijiazhuang, Beijing, Taiyuan, Xi'an, Tianjin, Zhengzhou and Wuhan, respectively. The reductions in emissions of PM2.5 precursors were ~2 times of that in concentrations, indicating that meteorology was unfavorable during simulation episode. A further analysis shows that benefits of emission reductions were overwhelmed by adverse meteorology and severe air pollution events were not avoided. This study highlights that large emissions reduction in transportation and slight reduction in industrial would not help avoid severe air pollution in China, especially when meteorology is unfavorable. More efforts should be made to completely avoid severe air pollution.

negative: 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.

negative: Coronavirus Nsp10, a Critical Co-factor for Activation of Multiple Replicative Enzymes The RNA-synthesizing machinery of the severe acute respiratory syndrome Coronavirus (SARS-CoV) is composed of 16 non-structural proteins (nsp1–16) encoded by ORF1a/1b. The 148-amino acid nsp10 subunit contains two zinc fingers and is known to interact with both nsp14 and nsp16, stimulating their respective 3′-5′ exoribonuclease and 2′-O-methyltransferase activities. Using alanine-scanning mutagenesis, in cellulo bioluminescence resonance energy transfer experiments, and in vitro pulldown assays, we have now identified the key residues on the nsp10 surface that interact with nsp14. The functional consequences of mutations introduced at these positions were first evaluated biochemically by monitoring nsp14 exoribonuclease activity. Disruption of the nsp10-nsp14 interaction abrogated the nsp10-driven activation of the nsp14 exoribonuclease. We further showed that the nsp10 surface interacting with nsp14 overlaps with the surface involved in the nsp10-mediated activation of nsp16 2′-O-methyltransferase activity, suggesting that nsp10 is a major regulator of SARS-CoV replicase function. In line with this notion, reverse genetics experiments supported an essential role of the nsp10 surface that interacts with nsp14 in SARS-CoV replication, as several mutations that abolished the interaction in vitro yielded a replication-negative viral phenotype. In contrast, mutants in which the nsp10-nsp16 interaction was disturbed proved to be crippled but viable. These experiments imply that the nsp10 surface that interacts with nsp14 and nsp16 and possibly other subunits of the viral replication complex may be a target for the development of antiviral compounds against pathogenic coronaviruses.

negative: Chapter Three Climate Change and the Neglected Tropical Diseases Abstract Climate change is expected to impact across every domain of society, including health. The majority of the world's population is susceptible to pathological, infectious disease whose life cycles are sensitive to environmental factors across different physical phases including air, water and soil. Nearly all so-called neglected tropical diseases (NTDs) fall into this category, meaning that future geographic patterns of transmission of dozens of infections are likely to be affected by climate change over the short (seasonal), medium (annual) and long (decadal) term. This review offers an introduction into the terms and processes deployed in modelling climate change and reviews the state of the art in terms of research into how climate change may affect future transmission of NTDs. The 34 infections included in this chapter are drawn from the WHO NTD list and the WHO blueprint list of priority diseases. For the majority of infections, some evidence is available of which environmental factors contribute to the population biology of parasites, vectors and zoonotic hosts. There is a general paucity of published research on the potential effects of decadal climate change, with some exceptions, mainly in vector-borne diseases.

negative: Effect of temperature and relative humidity on ultraviolet (UV254) inactivation of airborne porcine respiratory and reproductive syndrome virus Abstract The objective of this research was to estimate the effects of temperature and relative humidity on the inactivation of airborne porcine reproductive and respiratory syndrome (PRRS) virus by ultraviolet light (UV254). Aerosols of PRRS virus were exposed to one of four doses of UV254 under nine combinations of temperature (n =3) and relative humidity (n =3). Inactivation constants (k), defined as the absolute value of the slope of the linear relationship between the survival fraction of the microbial population and the UV254 exposure dose, were estimated using the random coefficient model. The associated UV254 half-life dose for each combination of environmental factors was determined as (log10 2/k) and expressed as UV254 mJ per unit volume. The effects of UV254 dose, temperature, and relative humidity were all statistically significant, as were the interactions between UV254 dose×temperature and UV254 dose×relative humidity. PRRS virus was more susceptible to ultraviolet as temperature decreased; most susceptible to ultraviolet inactivation at relative humidity between 25% and 79%, less susceptible at relative humidity ≤24%, and least susceptible at ≥80% relative humidity. The current study allows for calculating the dose of UV254 required to inactivate airborne PRRS virus under various laboratory and field conditions using the inactivation constants and UV254 half-life doses reported therein.

negative: Heat inactivation of serum interferes with the immunoanalysis of antibodies to SARS-CoV-2 The detection of serum antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as a new tool for the coronavirus disease-2019 (COVID-19) diagnosis. Since many coronaviruses are sensitive to heat, heating inactivation of samples at 56 ℃ prior to testing is considered a possible method to reduce the risk of transmission, but the effect of heating on the measurement of SARS-CoV-2 antibodies is still unclear. By comparing the levels of SARS-CoV-2 antibodies before and after heat inactivation of serum at 56 ℃ for 30 minutes using a quantitative fluorescence immunochromatographic assay, we shown that heat inactivation significantly interferes with the levels of antibodies to SARS-CoV-2. The IgM levels of all the 34 serum samples (100%) from COVID-19 patients decreased by an average level of 53.56%. The IgG levels were decreased in 22 of 34 samples (64.71%) by an average level of 49.54%. Similar changes can also be observed in the non-COVID-19 diseases group (n=9). Of note, 44.12% of the detected IgM levels were dropped below the cut-off value after heating, suggesting heat inactivation can lead to false-negative results of these samples. Our results indicate that heat inactivation of serum at 56 ℃ for 30 minutes interferes with the immunoanalysis of antibodies to SARS-CoV-2. Heat inactivation prior to immunoanalysis is not recommended and the possibility of false-negative results should be considered if the sample was pre-inactivated by heating.

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: Hydroxychloroquine Versus COVID-19: A Rapid Systematic Review and Meta-Analysis Background: Coronavirus Disease 2019 (COVID-19) has become a major global issue with rising the number of infected individuals and mortality in recent months. Among all therapeutic approaches, arguments have raised about hydroxychloroquine efficacy in treatment of COVID-19. We aimed to overcome the controversies regarding effectiveness of hydroxychloroquine in treatment of COVID-19, using a systematic review and meta-analysis. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar and medRxiv pre-print database using all available MeSH terms for COVID-19 and hydroxychloroquine. Two authors selected and assessed the quality of studies independently using related checklists. Data have been extracted from included studies and analyzed using CMA v. 2.2.064. heterogeneity was also assessed using I-squared test. Results: Seven studies including four clinical trials and three observational studies have entered into the study. The results of meta-analysis of clinical trials showed that there were no significant differences between patients who received the standard treatment with HCQ regimen and the patients that received the standard treatment without HCQ (RR: 1.44, 95% CI, 0.80-2.59). CT-Scan findings improved in 59% (95% CI 0.15-0.92) and nasopharyngeal culture following RT-PCR resulted negative in 76% (95% CI 0.56-0.89) of patients received hydroxychloroquine. Meta-analysis of observational studies showed 75% (95% CI, 0.54-0.88) of patients were discharged from the hospital, 34% (95% CI, 0.07-0.14) admitted to intensive care unit and 1.5% (95% CI, 0.03-0.83) have expired. Conclusion: This study indicated no clinical benefits regarding HCQ for treatment of COVID-19 patients. However, further large clinical trials should be taken into account in order to achieve more reliable findings.

negative: Transformation of the mathematics classroom with the internet Growing use of the internet in educational contexts has been prominent in recent years. In this survey paper, we describe how the internet is transforming the mathematics classroom and mathematics teacher education. We use as references several reviews of use of the internet in mathematics education settings made in recent years to determine how the field has evolved. We identify three domains in which new approaches are being generated by mathematic educators: principles of design of new settings; social interaction and construction knowledge; and tools and resources. The papers in this issue reflect different perspectives developed in the last decade in these three domains, providing evidence of the advances in theoretical frameworks and support in the generation of new meanings for old constructs such as ‘tool’, ‘resources’ or ‘learning setting’. We firstly highlight the different ways in which the use of digital technologies generates new ways of thinking about mathematics and the settings in which it is learnt, and how mathematics teacher educators frame the new initiatives of initial training and professional development. In this survey paper, we identify trends for future research regarding theoretical and methodological aspects, and recognise new opportunities requiring further engagement.

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: Spread of infectious microbes during emergency medical response BACKGROUND: To our knowledge, no studies to date demonstrate potential spread of microbes during actual emergency medical service (EMS) activities. Our study introduces a novel approach to identification of contributors to EMS environment contamination and development of infection control strategies, using a bacteriophage surrogate for pathogenic organisms. METHODS: Bacteriophage ΦX174 was used to trace cross-contamination and evaluate current disinfection practices and a hydrogen peroxide (H(2)O(2)) wipe intervention within emergency response vehicles. Prior to EMS calls, 2 surfaces were seeded with ΦX174. On call completion, EMS vehicle and equipment surfaces were sampled before decontamination, after decontamination per current practices, and after implementation of the intervention. RESULTS: Current decontamination practices did not significantly reduce viral loads on surfaces (P = .3113), but H(2)O(2) wipe intervention did (P = .0065). Bacteriophage spread to 56% (27/48) of sites and was reduced to 54% (26/48) and 40% (19/48) with current decontamination practices and intervention practices, respectively. CONCLUSION: Results suggest firefighters' hands were the main vehicles of microbial transfer. Current practices were not consistently applied or standardized and minimally reduced prevalence and quantity of microbial contamination on EMS surfaces. Although use of a consistent protocol of H(2)O(2) wipes significantly reduced percent prevalence and concentration of viruses, training and promotion of surface disinfection should be provided.

negative: Middle East Respiratory Syndrome Coronavirus Transmission in Extended Family, Saudi Arabia, 2014 Risk factors for human-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) are largely unknown. After MERS-CoV infections occurred in an extended family in Saudi Arabia in 2014, relatives were tested by using real-time reverse transcription PCR (rRT-PCR) and serologic methods. Among 79 relatives, 19 (24%) were MERS-CoV positive; 11 were hospitalized, and 2 died. Eleven (58%) tested positive by rRT-PCR; 8 (42%) tested negative by rRT-PCR but positive by serology. Compared with MERS-CoV–negative adult relatives, MERS-CoV–positive adult relatives were older and more likely to be male and to have chronic medical conditions. Risk factors for household transmission included sleeping in an index patient’s room and touching respiratory secretions from an index patient. Casual contact and simple proximity were not associated with transmission. Serology was more sensitive than standard rRT-PCR for identifying infected relatives, highlighting the value of including serology in future investigations.

negative: Handling and Processing of Blood Specimens from Patients with COVID‐19 for Safe Studies on Cell Phenotype and Cytokine Storm The pandemic caused by severe acute respiratory syndrome coronavirus 2 heavily involves all those working in a laboratory. Samples from known infected patients or donors who are considered healthy can arrive, and a colleague might be asymptomatic but able to transmit the virus. Working in a clinical laboratory is posing several safety challenges. Few years ago, International Society for Advancement of Cytometry published guidelines to safely analyze and sort human samples that were revised in these days. We describe the procedures that we have been following since the first patient appeared in Italy, which have only slightly modified our standard one, being all human samples associated with risks. © 2020 International Society for Advancement of Cytometry

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: Letter to the Editor Regarding: "An Imperative Need for Research on the Role of Environmental Factors in Transmission of Novel Coronavirus (COVID-19)" -Secondhand and Thirdhand Smoke As Potential Sources of COVID-19

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: Building upon current knowledge and techniques of indoor microbiology to construct the next era of theory into microorganisms, health, and the built environment In the constructed habitat in which we spend up to 90% of our time, architectural design influences occupants’ behavioral patterns, interactions with objects, surfaces, rituals, the outside environment, and each other. Within this built environment, human behavior and building design contribute to the accrual and dispersal of microorganisms; it is a collection of fomites that transfer microorganisms; reservoirs that collect biomass; structures that induce human or air movement patterns; and space types that encourage proximity or isolation between humans whose personal microbial clouds disperse cells into buildings. There have been recent calls to incorporate building microbiology into occupant health and exposure research and standards, yet the built environment is largely viewed as a repository for microorganisms which are to be eliminated, instead of a habitat which is inexorably linked to the microbial influences of building inhabitants. Health sectors have re-evaluated the role of microorganisms in health, incorporating microorganisms into prevention and treatment protocols, yet no paradigm shift has occurred with respect to microbiology of the built environment, despite calls to do so. Technological and logistical constraints often preclude our ability to link health outcomes to indoor microbiology, yet sufficient study exists to inform the theory and implementation of the next era of research and intervention in the built environment. This review presents built environment characteristics in relation to human health and disease, explores some of the current experimental strategies and interventions which explore health in the built environment, and discusses an emerging model for fostering indoor microbiology rather than fearing it.

negative: Ocular manifestation as first sign of Coronavirus Disease 2019 (COVID-19): interest of telemedicine during the pandemic context Abstract We report here the case of a 27-year-old man who consulted by telemedicine during the Coronavirus Disease 2019 (COVID-19) pandemic, due to foreign body sensation and left eye redness. Examination revealed unilateral eyelid edema and moderate conjunctival hyperemia. A few hours later the patient experienced intense headache and developed fever, cough and severe dyspnea. A nasopharyngeal swab proved positive for SARS-CoV-2. This case demonstrates that conjunctivitis can be the inaugural manifestation of the COVID-19 infection. It illustrates the interest of telemedicine in ophthalmology during the COVID-19 pandemic, since moderate conjunctival hyperemia can be the first sign of a severe respiratory distress.

negative: Manipulation of the infectious bronchitis coronavirus genome for vaccine development and analysis of the accessory proteins() Infectious bronchitis coronavirus (IBV) is the cause of the single most economically costly infectious disease of domestic fowl in the UK—and probably so in many countries that have a developed poultry industry. A major reason for its continued dominance is its existence as many serotypes, determined by the surface spike protein (S), cross-protection being poor. Although controlled to some degree by live and inactivated vaccines, a new generation of IB vaccines is called for. Reverse genetic or ‘infectious clone’ systems, which allow the manipulation of the IBV genome, are key to this development. New vaccines would ideally be: genetically stable (i.e. maintain a stable attenuated phenotype); administered in ovo; and be flexible with respect to the source of the spike protein gene. Rational attenuation of IBV requires the identification of genes that are simultaneously not essential for replication and whose absence would reduce pathogenicity. Being able to modify a ‘core’ vaccine strain to make it applicable to a prevailing serotype requires a procedure for doing so, and the demonstration that ‘spike-swapping’ is sufficient to induce good immunity. We have demonstrated that four small IBV proteins, encoded by genes 3 and 5, are not essential for replication; failure to produce these proteins had little detrimental affect on the titre of virus produced. Our current molecularly cloned IBV, strain Beaudette, is non-pathogenic, so we do not know what effect the absence of these proteins would have on pathogenicity. That said, plaque size and composition of various gene 3/5 recombinant IBVs in cell culture, and reduced output and ciliostasis in tracheal organ cultures, shows that they are less aggressive than the wild-type Beaudette. Consequently these genes remain targets for rational attenuation. We have recently obtained evidence that one or more of the 15 proteins encoded by gene 1 are also determinants of pathogenicity. Hence gene 1 is also a target for rational attenuation. Replacing the S protein gene of Beaudette with that from the pathogenic M41 strain resulted in a recombinant virus that was still non-pathogenic but which did induce protection against challenge with M41. We have since made other ‘spike-swapped’ recombinants, including ones with chimaera S genes. Uniquely, our molecular clone of Beaudette is benign when administered to 18-day-old embryos, even at high doses, and induces immunity after this route of vaccination. Taken together, our results point to the creation of a new generation of IB vaccines, based on rational modification of the genome, as being a realisable objective.

negative: Selection of viral variants during persistent infection of insectivorous bat cells with Middle East respiratory syndrome coronavirus Coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are speculated to have originated in bats. The mechanisms by which these viruses are maintained in individuals or populations of reservoir bats remain an enigma. Mathematical models have predicted long-term persistent infection with low levels of periodic shedding as a likely route for virus maintenance and spillover from bats. In this study, we tested the hypothesis that bat cells and MERS coronavirus (CoV) can co-exist in vitro. To test our hypothesis, we established a long-term coronavirus infection model of bat cells that are persistently infected with MERS-CoV. We infected cells from Eptesicus fuscus with MERS-CoV and maintained them in culture for at least 126 days. We characterized the persistently infected cells by detecting virus particles, protein and transcripts. Basal levels of type I interferon in the long-term infected bat cells were higher, relative to uninfected cells, and disrupting the interferon response in persistently infected bat cells increased virus replication. By sequencing the whole genome of MERS-CoV from persistently infected bat cells, we identified that bat cells repeatedly selected for viral variants that contained mutations in the viral open reading frame 5 (ORF5) protein. Furthermore, bat cells that were persistently infected with ΔORF5 MERS-CoV were resistant to superinfection by wildtype virus, likely due to reduced levels of the virus receptor, dipeptidyl peptidase 4 (DPP4) and higher basal levels of interferon in these cells. In summary, our study provides evidence for a model of coronavirus persistence in bats, along with the establishment of a unique persistently infected cell culture model to study MERS-CoV-bat interactions.

negative: RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions.

negative: Disinfection Policies in Hospitals and the Community

negative: Finding the Dose for Hydroxychloroquine Prophylaxis for COVID-19: The Desperate Search for Effectiveness Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2. Although the efficacy of hydroxychloroquine for COVID-19 remains uncertain, it may serve as a potential prophylactic agent especially in those at high risk, such as healthcare workers, household contacts of infected patients, and the immunocompromised. Our aim was to identify possible hydroxychloroquine dosing regimens through simulation in those at high risk of infections by optimizing exposures above the in vitro generated half maximal effective concentration (EC50 ) and to help guide researchers in dose-selection for COVID-19 prophylactic studies. To maintain weekly troughs above EC50 in > 50% of subjects at steady-state in a pre-exposure prophylaxis setting, an 800 mg loading dose followed by 400 mg twice or 3 times weekly is required. In an exposure driven, post-exposure prophylaxis setting, 800 mg loading dose followed in 6 hours by 600 mg, then 600 mg daily for 4 more days achieved daily troughs above EC50 in > 50% subjects. These doses are higher than recommended for malaria chemoprophylaxis, and clinical trials are needed to establish safety and efficacy.

negative: Household transmission of COVID-19, Shenzhen, January-February 2020 Coronavirus disease 2019 has led to more than three million cases globally. Since the first family cluster of COVID-19 cases identified in Shenzhen in early January, most of the local transmission occurred within household contacts. Identifying the factors associated with household transmission is of great importance to guide preventive measures.

negative: Chapter 6 Virus population dynamics examined with experimental model systems Abstract Experimental evolution permits exploring the effect of controlled environmental variables in virus evolution. Several designs in cell culture and in vivo have established basic concepts that can assist in the interpretation of evolutionary events in the field. Important information has come from cytolytic and persistent infections in cell culture that have unveiled the power of virus-cell coevolution in virus and cell diversification. Equally informative are comparisons of the response of viral populations when subjected to different passage régimens. In particular, plaque-to-plaque transfers in cell culture have revealed unusual genotypes and phenotypes that populate minority layers of viral quasispecies. Some of these viruses display properties that contradict features established in virology textbooks. Several hypotheses and principles of population genetics have found experimental confirmation in experimental designs with viruses. The possibilities of using experimental evolution to understand virus behavior are still largely unexploited.

negative: Noninvasive ventilation in acute respiratory failure due to H1N1 influenza: A word of caution

negative: Review of Viral Testing (Polymerase Chain Reaction) and Antibody/Serology Testing for Severe Acute Respiratory Syndrome-Coronavirus-2 for the Intensivist OBJECTIVE: As the severe acute respiratory syndrome-coronavirus-2 pandemic develops, assays to detect the virus and infection caused by it are needed for diagnosis and management. To describe to clinicians how each assay is performed, what each assay detects, and the benefits and limitations of each assay. DATA SOURCES: Published literature and internet. STUDY SELECTION: As well done, relevant and recent as possible. DATA EXTRACTION: Sources were read to extract data from them. DATA SYNTHESIS: Was synthesized by all coauthors. CONCLUSIONS: Available assays test for current or previous severe acute respiratory syndrome-coronavirus-2 infection. Nucleic acid assays such as quantitative, or real-time, polymerase chain reaction and loop-mediated isothermal amplification are ideal for acute diagnosis with polymerase chain reaction testing remaining the “gold standard” to diagnose acute infection by severe acute respiratory syndrome-coronavirus-2, specifically the presence of viral RNA. Assays that detect serum antibodies can theoretically diagnose both acute and remote infection but require time for the patient to develop immunity and may detect nonspecific antibodies. Antibody assays that quantitatively measure neutralizing antibodies are needed to test efficacy of convalescent plasma therapy but are more specialized.

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: Disease Prevention: An Opportunity to Expand Edible Plant-Based Vaccines? The lethality of infectious diseases has decreased due to the implementation of crucial sanitary procedures such as vaccination. However, the resurgence of pathogenic diseases in different parts of the world has revealed the importance of identifying novel, rapid, and concrete solutions for control and prevention. Edible vaccines pose an interesting alternative that could overcome some of the constraints of traditional vaccines. The term “edible vaccine” refers to the use of edible parts of a plant that has been genetically modified to produce specific components of a particular pathogen to generate protection against a disease. The aim of this review is to present and critically examine “edible vaccines” as an option for global immunization against pathogenic diseases and their outbreaks and to discuss the necessary steps for their production and control and the list of plants that may already be used as edible vaccines. Additionally, this review discusses the required standards and ethical regulations as well as the advantages and disadvantages associated with this powerful biotechnology tool.

negative: Identification of Coronavirus Isolated from a Patient in Korea with COVID-19 OBJECTIVES: Following reports of patients with unexplained pneumonia at the end of December 2019 in Wuhan, China, the causative agent was identified as coronavirus (SARS-CoV-2), and the 2019 novel coronavirus disease was named COVID-19 by the World Health Organization. Putative patients with COVID-19 have been identified in South Korea, and attempts have been made to isolate the pathogen from these patients. METHODS: Upper and lower respiratory tract secretion samples from putative patients with COVID-19 were inoculated onto cells to isolate the virus. Full genome sequencing and electron microscopy were used to identify the virus. RESULTS: The virus replicated in Vero cells and cytopathic effects were observed. Full genome sequencing showed that the virus genome exhibited sequence homology of more than 99.9% with SARS-CoV-2 which was isolated from patients from other countries, for instance China. Sequence homology of SARS-CoV-2 with SARS-CoV, and MERS-CoV was 77.5% and 50%, respectively. Coronavirus-specific morphology was observed by electron microscopy in virus-infected Vero cells. CONCLUSION: SARS-CoV-2 was isolated from putative patients with unexplained pneumonia and intermittent coughing and fever. The isolated virus was named BetaCoV/Korea/KCDC03/2020.

negative: Factors associated with nosocomial SARS-CoV transmission among healthcare workers in Hanoi, Vietnam, 2003 BACKGROUND: In March of 2003, an outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi, initiating a serious and substantial transmission event within the hospital, and subsequent limited spread within the community. METHODS: We surveyed Hospital A personnel for exposure to the index patient and for symptoms of disease during the outbreak. Additionally, serum specimens were collected and assayed for antibody to SARS-associated coronavirus (SARS-CoV) antibody and job-specific attack rates were calculated. A nested case-control analysis was performed to assess risk factors for acquiring SARS-CoV infection. RESULTS: One hundred and fifty-three of 193 (79.3%) clinical and non-clinical staff consented to participate. Excluding job categories with <3 workers, the highest SARS attack rates occurred among nurses who worked in the outpatient and inpatient general wards (57.1, 47.4%, respectively). Nurses assigned to the operating room/intensive care unit, experienced the lowest attack rates (7.1%) among all clinical staff. Serologic evidence of SARS-CoV infection was detected in 4 individuals, including 2 non-clinical workers, who had not previously been identified as SARS cases; none reported having had fever or cough. Entering the index patient's room and having seen (viewed) the patient were the behaviors associated with highest risk for infection by univariate analysis (odds ratios 20.0, 14.0; 95% confidence intervals 4.1–97.1, 3.6–55.3, respectively). CONCLUSION: This study highlights job categories and activities associated with increased risk for SARS-CoV infection and demonstrates that a broad diversity of hospital workers may be vulnerable during an outbreak. These findings may help guide recommendations for the protection of vulnerable occupational groups and may have implications for other respiratory infections such as influenza.

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

negative: Signals of T(h)2 immune response from COVID-19 patients requiring intensive care

negative: SARS: epidemiology Severe acute respiratory syndrome (SARS) originated in Southern China in November 2002, and was brought to Hong Kong in February 2003. From Hong Kong, the disease spread rapidly worldwide but mostly to Asian countries. At the end of the epidemic in June, the global cumulative total was 8422 cases with 916 deaths (case fatality rate of 11%). People of all ages were affected, but predominantly females. Health care workers were at high risk and accounted for one‐fifth of all cases. Risk factors for death included old age and comorbid illnesses, especially diabetes. The disease is caused by a novel coronavirus and is transmitted by droplets or direct inoculation from contact with infected surfaces. Contaminated sewage was found to be responsible for the outbreak in a housing estate in Hong Kong affecting over 300 residents. The mean incubation period was 6.4 days (range 2–10). The duration between onset of symptoms and hospitalisation was from 3 to 5 days. The relatively prolonged incubation period allowed asymptomatic air travellers to spread the disease globally. The number of individuals infected by each case has been estimated to be 2.7. Effective control of nosocomial transmission included early detection of disease, strict isolation of patients, practice of droplet and contact precautions and compliance with the use of personal protective equipment. Effective control of disease spread in the community included tracing and quarantine of contacts. Development of a validated diagnostic test and an effective vaccine as well as elimination of possible animal reservoirs are measures needed to prevent another epidemic.

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: Heat inactivation of the Middle East respiratory syndrome coronavirus The culture supernatants of the emerging Middle East respiratory syndrome coronavirus (MERS-CoV) were submitted to three temperatures over time and tested for infectivity by TCID(50) method on Vero E6 cells. At 56°C, almost 25 minutes were necessary to reduce the initial titre by 4 log(10). Increasing temperature to 65°C had a strong negative effect on viral infectivity as virucidy dropped significantly to 1 minute. On the contrary, no significant decrease in titre was observed after 2 hours at 25°C. These data might be useful in establishing biosafety measures in laboratories against MERS-CoV.

negative: Environmental survey to assess viral contamination of air and surfaces in hospital settings Summary The presence of pathogenic viruses in healthcare settings represents a serious risk for both staff and patients. Direct viral detection in the environment poses significant technical problems and the indirect indicators currently in use suffer from serious limitations. The aim of this study was to monitor surfaces and air in hospital settings to reveal the presence of hepatitis C virus, human adenovirus, norovirus, human rotavirus and torque teno virus by nucleic acid assays, in parallel with measurements of total bacterial count and haemoglobin presence. In total, 114 surface and 62 air samples were collected. Bacterial contamination was very low (<1cfu/cm2) on surfaces, whereas the ‘medium’ detected value in air was 282cfu/m3. Overall, 19 (16.7%) surface samples tested positive for viral nucleic acids: one for norovirus, one for human adenovirus and 17 (14.9%) for torque teno virus (TTV). Only this latter virus was directly detected in 10 air samples (16.1%). Haemoglobin was found on two surfaces. No relationship was found between viral, biochemical or bacterial indicators. The data obtained confirm the difficulty of assessing viral contamination using bacterial indicators. The frequent detection of TTV suggests its possible use as an indicator for general viral contamination of the environment.

negative: Structure and Function of the HIV Envelope Glycoprotein as Entry Mediator, Vaccine Immunogen, and Target for Inhibitors Publisher Summary This chapter discusses the advances of the envelope glycoprotein (Env) structure as related to the interactions of conserved Env structures with receptor molecules and antibodies with implications for the design of vaccine immunogens and inhibitors. The human immunodeficiency virus (HIV) Env binds to cell surface–associated receptor (CD4) and coreceptor (CCR5 or CXCR4) by one of its two non-covalently associated subunits, gp120. The induced conformational changes activate the other subunit (gp41), which causes the fusion of the viral with the plasma cell membranes resulting in the delivery of the viral genome into the cell and the initiation of the infection cycle. As the only HIV protein exposed to the environment, the Env is also a major immunogen to which neutralizing antibodies are directed and a target that is relatively easy to access by inhibitors. A fundamental problem in the development of effective vaccines and inhibitors against HIV is the rapid generation of alterations at high levels of expression during long chronic infection and the resulting signiﬁcant heterogeneity of the Env. The preservation of the Env function as an entry mediator and limitations on size and expression impose restrictions on its variability and lead to the existence of conserved structures.

negative: Causal empirical estimates suggest COVID-19 transmission rates are highly seasonal Nearly every country is now combating the 2019 novel coronavirus (COVID-19). It has been hypothesized that if COVID-19 exhibits seasonality, changing temperatures in the coming months will shift transmission patterns around the world. Such projections, however, require an estimate of the relationship between COVID-19 and temperature at a global scale, and one that isolates the role of temperature from confounding factors, such as public health capacity. This paper provides the first plausibly causal estimates of the relationship between COVID-19 transmission and local temperature using a global sample comprising of 166,686 confirmed new COVID-19 cases from 134 countries from January 22, 2020 to March 15, 2020. We find robust statistical evidence that a 1°C increase in local temperature reduces transmission by 13% [-21%, -4%, 95%CI]. In contrast, we do not find that specific humidity or precipitation influence transmission. Our statistical approach separates effects of climate variation on COVID-19 transmission from other potentially correlated factors, such as differences in public health responses across countries and heterogeneous population densities. Using constructions of expected seasonal temperatures, we project that changing temperatures between March 2020 and July 2020 will cause COVID-19 transmission to fall by 43% on average for Northern Hemisphere countries and to rise by 71% on average for Southern Hemisphere countries. However, these patterns reverse as the boreal winter approaches, with seasonal temperatures in January 2021 increasing average COVID-19 transmission by 59% relative to March 2020 in northern countries and lowering transmission by 2% in southern countries. These findings suggest that Southern Hemisphere countries should expect greater transmission in the coming months. Moreover, Northern Hemisphere countries face a crucial window of opportunity: if contagion-containing policy interventions can dramatically reduce COVID-19 cases with the aid of the approaching warmer months, it may be possible to avoid a second wave of COVID-19 next winter.

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 Molecular Biology of Coronaviruses Publisher Summary Coronaviruses have recently emerged as an important group of animal and human pathogens that share a distinctive replicative cycle. Some of the unique characteristics in the replication of coronaviruses include generation of a 3' coterminal-nested set of five or six subgenomic mRNAs, each of which appears to direct the synthesis of one protein. Two virus-specific RNA polymerase activities have been identified. Many of the distinctive features of coronavirus infection and coronavirus-induced diseases may result from the properties of the two coronavirus glycoproteins. The intracellular budding site, which may be important in the establishment and maintenance of persistent infections, appears to be due to the restricted intracytoplasmic migration of the E1 glycoprotein, which acts as a matrix-like transmembrane glycoprotein. E1 also exhibits distinctive behavior by self-aggregating on heating at 100°C in sodium dodecyl sulfate (SDS) and by its interaction with RNA in the viral nucleocapsid. The E1 of mouse hepatitis virus (MHV) is an O-linked glycoprotein, unlike most other viral glycoproteins. Thus, the coronavirus system may be a useful model for the study of synthesis, glycosylation, and transport of O-linked cellular glycoproteins.

negative: Detecting signals of chronic shedding to explain pathogen persistence: Leptospira interrogans in California sea lions 1. Identifying mechanisms driving pathogen persistence is a vital component of wildlife disease ecology and control. Asymptomatic, chronically infected individuals are an oft‐cited potential reservoir of infection, but demonstrations of the importance of chronic shedding to pathogen persistence at the population‐level remain scarce. 2. Studying chronic shedding using commonly collected disease data is hampered by numerous challenges, including short‐term surveillance that focuses on single epidemics and acutely ill individuals, the subtle dynamical influence of chronic shedding relative to more obvious epidemic drivers, and poor ability to differentiate between the effects of population prevalence of chronic shedding vs. intensity and duration of chronic shedding in individuals. 3. We use chronic shedding of Leptospira interrogans serovar Pomona in California sea lions (Zalophus californianus) as a case study to illustrate how these challenges can be addressed. Using leptospirosis‐induced strands as a measure of disease incidence, we fit models with and without chronic shedding, and with different seasonal drivers, to determine the time‐scale over which chronic shedding is detectable and the interactions between chronic shedding and seasonal drivers needed to explain persistence and outbreak patterns. 4. Chronic shedding can enable persistence of L. interrogans within the sea lion population. However, the importance of chronic shedding was only apparent when surveillance data included at least two outbreaks and the intervening inter‐epidemic trough during which fadeout of transmission was most likely. Seasonal transmission, as opposed to seasonal recruitment of susceptibles, was the dominant driver of seasonality in this system, and both seasonal factors had limited impact on long‐term pathogen persistence. 5. We show that the temporal extent of surveillance data can have a dramatic impact on inferences about population processes, where the failure to identify both short‐ and long‐term ecological drivers can have cascading impacts on understanding higher order ecological phenomena, such as pathogen persistence.

negative: Human coronavirus 229E infects polarized airway epithelia from the apical surface. Gene transfer to differentiated airway epithelia with existing viral vectors is very inefficient when they are applied to the apical surface. This largely reflects the polarized distribution of receptors on the basolateral surface. To identify new receptor-ligand interactions that might be used to redirect vectors to the apical surface, we investigated the process of infection of airway epithelial cells by human coronavirus 229E (HCoV-229E), a common cause of respiratory tract infections. Using immunohistochemistry, we found the receptor for HCoV-229E (CD13 or aminopeptidase N) localized mainly to the apical surface of airway epithelia. When HCoV-229E was applied to the apical or basolateral surface of well-differentiated primary cultures of human airway epithelia, infection primarily occurred from the apical side. Similar results were noted when the virus was applied to cultured human tracheal explants. Newly synthesized virions were released mainly to the apical side. Thus, HCoV-229E preferentially infects human airway epithelia from the apical surface. The spike glycoprotein that mediates HCoV-229E binding and fusion to CD13 is a candidate for pseudotyping retroviral envelopes or modifying other viral vectors.

negative: Ferret Coronavirus-Associated Diseases A novel coronavirus of ferrets was first described in 1993. This coronavirus caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new systemic disease resembles the dry form of feline infectious peritonitis (FIP) and has been reported in the United States and Europe. This article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret FIP-like disease.

negative: Quantifying the relative impact of contact heterogeneity on MRSA transmission in ICUs - a modelling study BACKGROUND: An efficient surface cleaning strategy would first target cleaning to surfaces that make large contributions to the risk of infections. METHODS: In this study, we used data from the literature about methicillin-resistant Staphylococcus aureus (MRSA) and developed an ordinary differential equations based mathematical model to quantify the impact of contact heterogeneity on MRSA transmission in a hypothetical 6-bed intensive care unit (ICU). The susceptible patients are divided into two types, these who are cared by the same nurse as the MRSA infected patient (Type 1) and these who are not (Type 2). RESULTS: The results showed that the mean MRSA concentration on three kinds of susceptible patient nearby surfaces was significantly linearly associated with the hand-touch frequency (p < 0.05). The noncompliance of daily cleaning on patient nearby high-touch surfaces (HTSs) had the most impact on MRSA transmission. If the HTSs were not cleaned, the MRSA exposure to Type 1 and 2 susceptible patients would increase 118.4% (standard deviation (SD): 33.0%) and 115.4% (SD: 30.5%) respectively. The communal surfaces (CSs) had the least impact, if CSs were not cleaned, the MRSA exposure to Type 1 susceptible patient would only increase 1.7% (SD: 1.3). The impact of clinical equipment (CE) differed largely for two types of susceptible patients. If the CE was not cleaned, the exposure to Type 1 patients would only increase 8.4% (SD: 3.0%), while for Type 2 patients, it can increase 70.4% (SD: 25.4%). CONCLUSIONS: This study provided a framework to study the pathogen concentration dynamics on environmental surfaces and quantitatively showed the importance of cleaning patient nearby HTSs on controlling the nosocomial infection transmission via contact route.

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: Les zoonoses (tableaux synthétiques: animaux réservoirs de pathogènes et modes de transmission) The knowledge of animals which act as reservoirs for human pathogenic agents is essential for the understanding of the epidemiology of zoonotic diseases and for the application of relevant methods of control. In the present article, synthetic tables present the main zoonoses due to viruses, bacteria, protozoa, helminths, arthropods and fungi. A list of the main pathogenic agents, the animal reservoirs and the way of transmission to man is detailed in each table.

negative: Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial INTRODUCTION: Chou-Ling-Dan (CLD) (Laggerapterodonta) granules are an ethnic herbal medicine from Yunnan province of China. CLD granules have been used for the treatment of inflammatory conditions and feverish diseases in China, including seasonal influenza, but few evidence-based medicine (EBM) clinical studies have been conducted to assess its efficacy and safety in the treatment of influenza. Here, we performed an EBM clinical trial combining Western Chinese medicine and traditional Chinese medicine (TCM) evaluation systems to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza. METHODS AND ANALYSIS: The study is designed as a multicentre, randomised, double-blinded, double-simulation, oseltamivir-controlled and placebo-controlled, parallel-design clinical trial. Eligible subjects (n=318) will be allocated after satisfying the criteria (Western medicine). Subjects will be randomised to receive CLD granules, oseltamivir, or a placebo for 5 days of treatment and with follow-up after treatment to record symptoms and signs and to collect pharyngeal/throat swabs and serum samples for detecting the virus and antibodies. At the same time, the syndrome differentiation criteria of TCM, such as tongue body, furred tongue and type of pulse, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza based on both Western Chinese medicine and TCM evaluation systems. ETHICS AND DISSEMINATION: The CLD granules clinical trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02662426; Pre-results.

negative: A sorghum xylanase inhibitor-like protein with highly potent antifungal, antitumor and HIV-1 reverse transcriptase inhibitory activities Abstract A 25-kDa protein, with an N-terminal amino acid sequence homologous to that of xylanase inhibitor and designated as xylanase inbibitor-like protein (XILP) was purified from sorghum seeds. The isolation protocol consisted of affinity chromatography, ion exchange chromatography, and gel filtration. XILP inhibited mycelial growth in various phytopathogenic fungi. The antifungal activity was thermostable and pH-stable. XILP inhibited proliferation of various cancer cell lines but did not do so in human embryonic liver (WRL 68) cells. There was no mitogenic activity toward mouse splenocytes. XILP reduced the activity of HIV-1 reverse transcriptase with an IC50 of 11.1μM, but lacked inhibitory activity toward HIV-1 integrase and SARS coronavirus proteinase. In conclusion, sorghum XILP is thermostable and pH stable and exhibits potent antifungal, antiproliferative, and HIV-1 reverse transcriptase inhibitory activities.

negative: Heteroaggregation of an enveloped bacteriophage with colloidal sediments and effect on virus viability Abstract Four sediments in the colloidal size range: goethite, montmorillonite, illite, and kaolinite, were suspended with the bacteriophage φ6, a model enveloped virus, to determine relative rates of heteroaggregation and the effect of aggregation on virus viability. Turbidity was measured on combinations of virus and each sediment type at low concentration to determine aggregation rates. Aggregation of sediment with virus occurred regardless of mineral type, and larger fraction of virus is expected to aggregate with increasing sediment concentration leading to higher deposition rates. The negatively charged sediments, aggregated with φ6 (also negatively charged at neutral pH) at a faster rate than the positively charged sediments, yielding turbidity slopes of 4.94 × 10−3 s−1 and 7.50 × 10−4 s−1 for φ6-montmorillonite and φ6-illite aggregates, respectively, and 2.98 × 10−5 s−1 and 2.84 × 10−5 s−1, for φ6-goethite and φ6-kaolinite, respectively. This indicates that the interaction between sediments and virus is hydrophobic, rather than electrostatic. Large numbers of virions remained viable post-aggregation, despite the fragility of the viral envelope, indicating that small-sized aggregates, which may travel more readily through porous media, may pose an infection risk. The fraction of φ6 that remained viable varied with sediment type, with montmorillonite-φ6 aggregates experiencing the greatest reduction in infectivity at 35%. TEM analyses reveal that in all sediment-φ6 combinations, infectivity loss was likely due to disassembly of the viral envelope as a result of aggregation.

negative: Responding to the severe acute respiratory syndrome (SARS) outbreak: Lessons learned in a Toronto emergency department()

negative: All eyes on Coronavirus—What do we need to know as ophthalmologists

negative: Sialic acid binding activity of transmissible gastroenteritis coronavirus affects sedimentation behavior of virions and solubilized glycoproteins. The sedimentation behavior of transmissible gastroenteritis coronavirus (TGEV) was analyzed. Upon sucrose gradient centrifugation, the major virus band was found at a density of 1.20 to 1.22 g/cm(3). This high density was observed only when TGEV with a functional sialic acid binding activity was analyzed. Mutants of TGEV that lacked sialic acid binding activity due to a point mutation in the sialic acid binding site of the S protein were mainly recovered at a lower-density position on the sucrose gradient (1.18 to 1.19 g/cm(3)). Neuraminidase treatment of purified virions resulted in a shift of the sedimentation value from the higher to the lower density. These results suggest that binding of sialoglycoproteins to the virion surface is responsible for the sedimentation behavior of TGEV. When purified virions were treated with octylglucoside to solubilize viral glycoproteins, ultracentrifugation resulted in sedimentation of the S protein of TGEV. However, when neuraminidase-treated virions or mutants with a defective sialic acid binding activity were analyzed, the S protein remained in the supernatant rather than in the pellet fraction. These results indicate that the interaction of the surface protein S with sialoglycoconjugates is maintained after solubilization of this viral glycoprotein by detergent treatment.

negative: Comparison of ATP Bioluminescence and Aerobic Bacterial Count for Evaluating Surface Cleanliness in an Italian Hospital Contaminated hospital surfaces have been demonstrated to be an important environmental reservoir of microorganisms that can increase the risk of nosocomial infection in exposed patients. As a consequence, cleaning and disinfecting hospital environments play an important role among strategies for preventing healthcare-associated colonization and infections. The aim of the present study was to evaluate whether adenosine triphosphate (ATP) presence, measured by bioluminescence methods, can predict microbiological contamination of hospital surfaces. The study was carried out between September and December 2012 at the University Hospital “P. Giaccone” of Palermo. A total of 193 randomly selected surfaces (tables, lockers, furnishings) were sampled and analyzed in order to assess ATP levels (expressed as relative light units or RLU) and aerobic colony count (ACC) or presence of S. aureus. ACC had median values of 1.85 cfu/cm(2) (interquartile range = 4.16) whereas ATP median was 44.6 RLU/cm(2) (interquartile range = 92.3). Overall, 85 (44.0%) surfaces exceeded the established microbial benchmark: 73 (37.8%) exceeded the 2.5 cfu/cm(2) ACC standard, 5 (2.6%) surfaces were positive for S. aureus and 7 (3.6%) showed both the presence of S. aureus and an ACC of more than 2.5 cfu/cm(2). ACC and bioluminescence showed significant differences in the different surface sites (p < 0.001). A significant correlation was found between ACC and RLU values (p-value < 0.001; R(2) = 0.29) and increasing RLU values were significantly associated with a higher risk of failing the benchmark (p < 0.001). Our data suggest that bioluminescence could help in measuring hygienic quality of hospital surfaces using a quick and sensitive test that can be an useful proxy of microbial contamination; however, further analysis will be necessary to assess the cost-efficacy of this methodology before requiring incorporation in hospital procedures.

negative: 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.

negative: On the stability of sequences inserted into viral genomes Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. The interplay between all factors affecting stability is complex, which makes it challenging to develop a general model to predict the stability of genomic insertions. We highlight key questions and future directions, finding that insert stability is a surprisingly complex problem and that there is need for mechanism-based, predictive models. Combining theoretical models with experimental tests for stability under varying conditions can lead to improved engineering of viral modified genomes, which is a valuable tool for understanding genome evolution as well as for biotechnological applications, such as gene therapy.

negative: Effectiveness of non-pharmaceutical measures in preventing pediatric influenza: a case–control study BACKGROUND: Hygiene behavior plays a relevant role in infectious disease transmission. The aim of this study was to evaluate non-pharmaceutical interventions (NPI) in preventing pediatric influenza infections. METHODS: Laboratory confirmed influenza cases occurred during 2009–10 and 2010–11 seasons matched by age and date of consultation. NPI (frequency of hand washing, alcohol-based hand sanitizer use and hand washing after touching contaminated surfaces) during seven days prior to onset of symptoms were obtained from parents of cases and controls. RESULTS: Cases presented higher prevalence of underlying conditions such as pneumonia [OR = 3.23; 95 % CI: 1.38 – 7.58 p = 0.007], asthma [OR = 2.45; 95 % CI: 1.17 – 5.14 p = 0.02] and having more than 1 risk factor [OR = 1.67; 95 % CI: 0.99 – 2.82 p = 0.05]. Hand washing more than 5 times per day [aOR = 0.62; 95 % CI: 0.39 – 0.99 p = 0.04] was the only statistically significant protective factor. When considering two age groups (pre-school age 0–4 yrs and school age 5–17) yrs , only the school age group showed a negative association for influenza infection for both washing more than 5 times per day [aOR = 0.47; 95 % CI: 0.22 – 0.99 p = 0.04] and hand washing after touching contaminated surfaces [aOR = 0.19; 95 % CI: 0.04 – 0.86 p = 0.03]. CONCLUSION: Frequent hand washing should be recommended to prevent influenza infection in the community setting and in special in the school age group.

negative: A novel cell-based binding assay system reconstituting interaction between SARS-CoV S protein and its cellular receptor Abstract Severe acute respiratory syndrome (SARS), a life-threatening disease, is caused by the newly identified virus SARS coronavirus (SARS-CoV). In order to study the spike (S) protein of this highly contagious virus, we established a clonal cell-line, CHO-SG, from the Chinese hamster ovary cells that stably expresses C-terminally EGFP-tagged SARS-CoV S protein (S-EGFP). The ectodomain of the S glycoprotein is localized on the surface of CHO-SG cells with N-acetyl-glucosamine-terminated carbohydrate structure. CHO-SG cells associated tightly with Vero E6 cells, a SARS-CoV receptor (ACE2) expressing cell-line, and the interaction remained stable under highly stringent condition (1M NaCl). This interaction could be blocked by either the serum from a SARS convalescent patient or a goat anti-ACE2 antibody, indicating that the interaction is specific. A binding epitope with lesser degree of glycosylation and native conformation was localized by using rabbit anti-sera raised against five denatured recombinant S protein fragments expressed in Escherichia coli. One of the sera obtained from the fragment encompassing amino acids 48-358 significantly blocked the interaction between CHO-SG and Vero E6 cells. The region is useful for studying neutralizing antibodies in future vaccine development. This paper describes an easy and safe cell-based assay suitable for studying the binding between SARS-CoV S protein and its receptor.

negative: A recombinant Lactobacillus plantarum strain expressing the spike protein of SARS-CoV-2 Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic in the past four months and causes respiratory disease in humans of almost all ages. Although several drugs have been announced to be partially effective treatments for this disease, no approved vaccine is available. Here, we described the construction of a recombinant Lactobacillus plantarum strain expressing the SARS-CoV-2 spike protein. The results showed that the spike gene with optimized codons could be efficiently expressed on the surface of recombinant L. plantarum and exhibited high antigenicity. The highest protein yield was obtained under the following conditions: cells were induced with 50 ng/mL SppIP at 37 °C for 6-10 h. The recombinant spike (S) protein was stable under normal conditions and at 50 °C, pH = 1.5, or a high salt concentration. Recombinant L. plantarum may provide a promising food-grade oral vaccine candidate against SARS-CoV-2 infection.

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: 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 subnational levels in the region.

negative: Efficacy of inactivated variant porcine epidemic diarrhea virus vaccines in growing pigs PURPOSE: The first aim of this study was to develop a novel inactivated porcine epidemic diarrhea virus (PEDV) vaccine using the recently isolated Korean PEDV QIAP1401 strain and to evaluate its protective efficacy in growing pigs. The second was to determine the optimum adjuvant formulation of the inactivated PEDV vaccine that induces protection against viral challenge. MATERIALS AND METHODS: To generate high titers of infectious PEDV, the QIAP1401 isolate was passaged in Vero cells. The experimental vaccines were prepared from a binary ethyleneimine-inactivated QIAP1401 strain passaged sequentially 70 times (QIAP1401-p70), formulated with four commercial adjuvants, and administered twice intramuscularly to growing pigs. Challenge studies using a virulent homologous strain of PEDV QIAP1401-p11, which was passaged 11 times after isolation, were performed to assess protection against disease progression and viral shedding during the 15-day observation period. The vaccine-induced antibody responses were measured in serum samples collected at predetermined time points by indirect enzyme-linked immunosorbent assay and virus neutralization test. RESULTS: The QIAP1401-p70 strain had 42 amino acid (aa) mutations, including a 25 aa deletion, and was selected as the inactivated PEDV vaccine candidate. Although none of the pigs that received the experimental vaccines were completely protected against subsequent viral challenge, they exhibited a significantly higher immune response than did non-vaccinated control pigs. Among the vaccine groups, the highest antibody responses were observed in the pigs that received an oil-based multiphasic water/oil/water (W/O/W) emulsion adjuvanted vaccine, which delayed the onset of clinical symptoms and viral shedding. CONCLUSION: A novel inactivated PEDV vaccine formulated with a W/O/W emulsion adjuvant was both immunogenic and protective against viral challenge.

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: Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.

negative: Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine Abstract Although the recent SARS coronavirus (SARS-CoV) that appeared in 2002 has now been contained, the possibility of re-emergence of SARS-CoV remains. Due to the threat of re-emergence, the overall fatality rate of ∼10%, and the rapid dispersion of the virus via international travel, viable vaccine candidates providing protection from SARS are clearly needed. We developed an attenuated VSV recombinant (VSV-S) expressing the SARS coronavirus (SARS-CoV) spike (S) protein. In cells infected with this recombinant, S protein was synthesized, glycosylated at approximately 17 Asn residues, and transported via the Golgi to the cell surface. Mice vaccinated with VSV-S developed SARS-neutralizing antibody and were able to control a challenge with SARS-CoV performed at 1 month or 4 months after a single vaccination. We also demonstrated, by passive antibody transfer, that the antibody response induced by the vaccine was sufficient for controlling SARS-CoV infection. A VSV-vectored SARS vaccine could have significant advantages over other SARS vaccine candidates described to date.

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: Pushing the Bacterial Envelope: Strategies for Re-Engineering Bacterial Surfaces with Heterologous Proteins and Sugars Over the past three decades, a powerful array of techniques has been developed for expressing heterologous proteins and saccharides on the surface of bacteria. Surface-engineered bacteria, in turn, have proven useful in a variety of settings, including high-throughput screening, biofuel production, and vaccinology. In this chapter, we provide a comprehensive review of methods for displaying polypeptides and sugars on the bacterial cell surface, and discuss the many innovative applications these methods have found to date. While already an important biotechnological tool, we believe bacterial surface display may be further improved through integration with emerging methodology in other fields, such as protein engineering and synthetic chemistry. Ultimately, we envision bacterial display becoming a multidisciplinary platform with the potential to transform basic and applied research in bacteriology, biotechnology, and biomedicine.

negative: Arenavirus Stable Signal Peptide Is the Keystone Subunit for Glycoprotein Complex Organization The rodent arenavirus glycoprotein complex encodes a stable signal peptide (SSP) that is an essential structural component of mature virions. The SSP, GP1, and GP2 subunits of the trimeric glycoprotein complex noncovalently interact to stud the surface of virions and initiate arenavirus infectivity. Nascent glycoprotein production undergoes two proteolytic cleavage events: first within the endoplasmic reticulum (ER) to cleave SSP from the remaining precursor GP1/2 (glycoprotein complex [GPC]) glycoprotein and second within the Golgi stacks by the cellular SKI-1/S1P for GP1/2 processing to yield GP1 and GP2 subunits. Cleaved SSP is not degraded but retained as an essential glycoprotein subunit. Here, we defined functions of the 58-amino-acid lymphocytic choriomeningitis virus (LCMV) SSP in regard to glycoprotein complex processing and maturation. Using molecular biology techniques, confocal microscopy, and flow cytometry, we detected SSP at the plasma membrane of transfected cells. Further, we identified a sorting signal (FLLL) near the carboxyl terminus of SSP that is required for glycoprotein maturation and trafficking. In the absence of SSP, the glycoprotein accumulated within the ER and was unable to undergo processing by SKI-1/S1P. Mutation of this highly conserved FLLL motif showed impaired glycoprotein processing and secretory pathway trafficking, as well as defective surface expression and pH-dependent membrane fusion. Immunoprecipitation of SSP confirmed an interaction between the signal peptide and the GP2 subunit; however, mutations within this FLLL motif disrupted the association of the GP1 subunit with the remaining glycoprotein complex.

negative: Coronavirus and influenza virus proteolytic priming takes place in tetraspanin-enriched membrane microdomains. UNLABELLED Coronaviruses (CoVs) and low-pathogenicity influenza A viruses (LP IAVs) depend on target cell proteases to cleave their viral glycoproteins and prime them for virus-cell membrane fusion. Several proteases cluster into tetraspanin-enriched microdomains (TEMs), suggesting that TEMs are preferred virus entry portals. Here we found that several CoV receptors and virus-priming proteases were indeed present in TEMs. Isolated TEMs, when mixed with CoV and LP IAV pseudoparticles, cleaved viral fusion proteins to fusion-primed fragments and potentiated viral transductions. That entering viruses utilize TEMs as a protease source was further confirmed using tetraspanin antibodies and tetraspanin short hairpin RNAs (shRNAs). Tetraspanin antibodies inhibited CoV and LP IAV infections, but their virus-blocking activities were overcome by expressing excess TEM-associated proteases. Similarly, cells with reduced levels of the tetraspanin CD9 resisted CoV pseudoparticle transductions but were made susceptible by overproducing TEM-associated proteases. These findings indicated that antibodies and CD9 depletions interfere with viral proteolytic priming in ways that are overcome by surplus proteases. TEMs appear to be exploited by some CoVs and LP IAVs for appropriate coengagement with cell receptors and proteases. IMPORTANCE Enveloped viruses use their surface glycoproteins to catalyze membrane fusion, an essential cell entry step. Host cell components prime these viral surface glycoproteins to catalyze membrane fusion at specific times and places during virus cell entry. Among these priming components are proteases, which cleave viral surface glycoproteins, unleashing them to refold in ways that catalyze virus-cell membrane fusions. For some enveloped viruses, these proteases are known to reside on target cell surfaces. This research focuses on coronavirus and influenza A virus cell entry and identifies TEMs as sites of viral proteolysis, thereby defining subcellular locations of virus priming with greater precision. Implications of these findings extend to the use of virus entry antagonists, such as protease inhibitors, which might be most effective when localized to these microdomains.

negative: Severe Acute Respiratory Syndrome: Pertinent Clinical Characteristics and Therapy Severe acute respiratory syndrome (SARS) is a newly emerged infection that is caused by a previously unrecognized virus–a novel coronavirus designated as SARS-associated coronavirus (SARS-CoV). From November 2002 to July 2003 the cumulative number of worldwide cases was >8000, with a mortality rate of close to 10%. The mortality has been higher in older patients and those with co-morbidities. SARS has been defined using clinical and epidemiological criteria and cases are considered laboratory-confirmed if SARS coronavirus is isolated, if antibody to SARS coronavirus is detected, or a polymerase chain reaction test by appropriate criteria is positive. At the time of writing (24 May 2004), no specific therapy has been recommended. A variety of treatments have been attempted, but there are no controlled data. Most patients have been treated throughout the illness with broad-spectrum antimicrobials, supplemental oxygen, intravenous fluids, and other supportive measures. Transmission of SARS is facilitated by close contact with patients with symptomatic infection. The majority of cases have been reported among healthcare providers and family members of SARS patients. Since SARS-CoV is contagious, measures for prevention center on avoidance of exposure, and infection control strategies for suspected cases and contacts. This includes standard precautions (hand hygiene), contact precautions (gowns, goggles, gloves) and airborne precautions (negative pressure rooms and high efficiency masks). In light of reports of new cases identified during the winter of 2003–4 in China, it seems possible that SARS will be an important cause of pneumonia in the future, and the screening of outpatients at risk for SARS may become part of the pneumonia evaluation.

negative: Manifestations of mortality based global data of COVID-19; unifying global model through single parameter Critical inspection of the world data of COVID-19 mortality rates per population number has been made and used to express extensive variations in mortality over the globe in terms of a powered parameter {lambda} varying from 0 to 1.2 expressed as a measure of strength of primary infection, originating from China source. The copying process is degenerating successively while infection is passed on to secondary subjects. We have been able to correlate global data through this parameter; any value close to or less than 1 shows significant impact of diluted multiple secondary effect. Further, the scatter diagram shows no effect of temperature of the geographical location and so is likely as the virus is only being spread from either contact or close proximity; the virus does not need to face highs and lows of temperatures of the environment. It stays only in the range of human body temperature and appears to be stable in 36 to 40C range. If it faces the environmental temperatures it is possible for its quicker deactivation but that situation never arises for this virus except when it spreads from surfaces.

negative: A process evaluation of an intervention to improve respiratory infection control practices in family physician offices. OBJECTIVE To conduct a process evaluation of a short-term intervention by public nurses for physicians to facilitate the incorporation of new respiratory infection control practices in physicians' offices. DESIGN Process evaluation. SETTING Family physician offices in Ottawa, Ontario, Canada. PARTICIPANTS Five public health nurse-facilitators and 53 primary care practices including 143 family physicians. METHOD Effectiveness of facilitator training assessed by self-administered questionnaires. Data assessing process of facilitation collected through activity logs and narrative reports. Physicians' satisfaction assessed by post-intervention questionnaire. MAIN FINDINGS Facilitators reported that training strongly contributed to their knowledge and skills and all were either satisfied or highly satisfied with their facilitation training. All practices received at least two visits by the facilitator and more than half (51%) were visited three or more times. Facilitators identified the provision of the evidence-based Tool Kit and consensus-building with office staff as key factors contributing to the intervention's success. Of the 45% of physicians who completed the questionnaire (65/143), only 5% reported being somewhat dissatisfied with the intervention, 11% reported the visits were not frequent enough, and 9% thought the visits were too close together. The majority (97%) felt the facilitation program should be available to all family physicians and 98% would continue to use the service if available. CONCLUSIONS It is feasible for public health nurses to be trained in outreach facilitation to improve respiratory infection control practices in physicians' offices and this has been widely appreciated by physicians. This model of public health/primary care collaboration deserves further exploration.

negative: Efficacy of Face Shields Against Cough Aerosol Droplets from a Cough Simulator Health care workers are exposed to potentially infectious airborne particles while providing routine care to coughing patients. However, much is not understood about the behavior of these aerosols and the risks they pose. We used a coughing patient simulator and a breathing worker simulator to investigate the exposure of health care workers to cough aerosol droplets, and to examine the efficacy of face shields in reducing this exposure. Our results showed that 0.9% of the initial burst of aerosol from a cough can be inhaled by a worker 46 cm (18 inches) from the patient. During testing of an influenza-laden cough aerosol with a volume median diameter (VMD) of 8.5 μm, wearing a face shield reduced the inhalational exposure of the worker by 96% in the period immediately after a cough. The face shield also reduced the surface contamination of a respirator by 97%. When a smaller cough aerosol was used (VMD = 3.4 μm), the face shield was less effective, blocking only 68% of the cough and 76% of the surface contamination. In the period from 1 to 30 minutes after a cough, during which the aerosol had dispersed throughout the room and larger particles had settled, the face shield reduced aerosol inhalation by only 23%. Increasing the distance between the patient and worker to 183 cm (72 inches) reduced the exposure to influenza that occurred immediately after a cough by 92%. Our results show that health care workers can inhale infectious airborne particles while treating a coughing patient. Face shields can substantially reduce the short-term exposure of health care workers to large infectious aerosol particles, but smaller particles can remain airborne longer and flow around the face shield more easily to be inhaled. Thus, face shields provide a useful adjunct to respiratory protection for workers caring for patients with respiratory infections. However, they cannot be used as a substitute for respiratory protection when it is needed.

negative: The impact of Coronavirus (COVID-19) on head and neck cancer patients’ care

negative: Persistent viral shedding of SARS-CoV-2 in faeces - a rapid review Background and aims In addition to respiratory symptoms, patients with COVID-19 can present with gastrointestinal complaints suggesting a possible faeco-oral transmission route. The primary aim of this review is to establish the incidence and timing of positive faecal samples for the SARS-CoV-2 virus in patients with COVID-19. Methods A systematic literature review was performed to identify studies describing COVID-19 patients tested for the virus in their stool. Data were extracted concerning the nature of the test, number and timing of positive samples, incidence of positive faecal tests after negative nasopharyngeal swabs and any evidence of viable faecal virus or faeco-oral transmission of the virus. Results There were 26 relevant articles identified. Combining these results demonstrated that 53.9% of those tested for faecal RNA in these studies were positive. Duration of faecal viral shedding ranged from 1 to 33 days after nasopharyngeal swab turned negative with one result remaining positive after 47 days of onset of symptoms. There was insufficient evidence to draw firm conclusions about the proportion of cases potentially transmitted through infection via faecally shed virus. Conclusions There is a relatively high rate of positive tests and persistence of the SARS-CoV-2 virus in faecal samples of selected patients with COVID-19. Further research is needed to demonstrate how much these positive tests correlate with viable virus and transmission through the faeco-oral route. This may have important implications for duration of isolation, precautions recommended in individuals undertaking a period of isolation, protective equipment for health professionals and interventional procedures involving the gastrointestinal tract.

negative: The utility of native MS for understanding the mechanism of action of repurposed therapeutics in COVID-19: heparin as a disruptor of the SARS-CoV-2 interaction with its host cell receptor The emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over six million cases and nearly four hundred thousand deaths reported world-wide by the end of May 2020. A rush to find the cures prompted re-evaluation of a range of existing therapeutics vis-à-vis their potential role in treating COVID-19, placing a premium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in supporting the mechanistic studies of drug/therapeutic target interactions, but its applications remain limited in the cases that involve systems with a high level of structural heterogeneity. Both SARS-CoV-2 spike protein (S-protein), a critical element of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, making them challenging targets for native MS. However, supplementing native MS with a gas-phase ion manipulation technique (limited charge reduction) allows meaningful information to be obtained on the non-covalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. Using this technique in combination with molecular modeling also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. Both short (pentasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with RBD, indicating the presence of a single binding site. This association alters the protein conformation (to maximize the contiguous patch of the positive charge on the RBD surface), resulting in a notable decrease of its ability to associate with ACE2. The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-pI ACE2 and the heparin segments not accommodated on the RBD surface. In addition to providing important mechanistic information on attenuation of the ACE2/RBD association by heparin, the study demonstrates the yet untapped potential of native MS coupled to gas-phase ion chemistry as a means of facilitating rational repurposing of the existing medicines for treating COVID-19.

negative: Canine Respiratory Coronavirus, Bovine Coronavirus, and Human Coronavirus OC43: Receptors and Attachment Factors Despite high similarity of canine respiratory coronavirus (CRCoV), bovine coronavirus, (BCoV) and human coronavirus OC43 (HCoV-OC43), these viruses differ in species specificity. For years it was believed that they share receptor specificity, utilizing sialic acids for cell surface attachment, internalization, and entry. Interestingly, careful literature analysis shows that viruses indeed bind to the cell surface via sialic acids, but there is no solid data that these moieties mediate virus entry. In our study, using a number of techniques, we showed that all three viruses are indeed able to bind to sialic acids to a different extent, but these molecules render the cells permissive only for the clinical strain of HCoV-OC43, while for others they serve only as attachment receptors. CRCoV and BCoV appear to employ human leukocyte antigen class I (HLA-1) as the entry receptor. Furthermore, we identified heparan sulfate as an alternative attachment factor, but this may be related to the cell culture adaptation, as in ex vivo conditions, it does not seem to play a significant role. Summarizing, we delineated early events during CRCoV, BCoV, and HCoV-OC43 entry and systematically studied the attachment and entry receptor utilized by these viruses.

negative: Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19 Abstract Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation strategies, where early diagnosis of COVID-19 is vital in controlling illness progression and limiting viral spread within the population. Thus, rapid and accurate methods of early detection are vital to contain COVID-19 and prevent further spread and predicted subsequent infectious waves of viral recurrence in future. Immediately after its initial characterization, Chinese and American Centers for Disease Control and Prevention (CDCs) rapidly employed molecular assays for detection of COVID-19, mostly employing real-time polymerase chain reaction (RT-PCR) methods. However, such methods require specific expensive items of equipment and highly trained analysts, requiring upwards of 4-8 hours to process. These requirements coupled with associated financial pressures may prevent effective deployment of such diagnostic tests. Loop mediated isothermal amplification(LAMP) is method of nucleic acid amplification which exhibits increased sensitivity and specificity are significantly rapid, and do not require expensive reagents or instruments, which aids in cost reduction for coronavirus detection. Studies have shown the successful application of LAMP assays in various forms to detect coronavirus RNA in patient samples, demonstrating that 1-10 copies of viral RNA template per reaction are sufficient for successful detection, ∼100-fold more sensitive than conventional RT-PCR methods. Importantly, studies have also now demonstrated the effectiveness of LAMP methodology in the detection of SARS-CoV-2 RNA at significantly low levels, particularly following numerous improvements to LAMP assay protocols. We hypothesise that recent advancements in enhanced LAMP protocols assay perhaps represent the best chance for a rapid and robust assay for field diagnosis of COVID-19, without the requirement of specialized equipment and highly trained professionals to interpret results. Herein, we present our arguments with a view to disseminate such findings, to assist the combat of this virus that is proving so devastating. We hope that this strategy could be applied rapidly, and confirmed for viability with clinical samples, before being rolled out for mass-diagnostic testing in these current times.

negative: 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.

negative: Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now? Abstract Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19), has posed a serious threat to global health and is currently causing a major pandemic. While patients typically present with fever and a respiratory illness, mounting evidence indicates that patients might also report extra-pulmonary manifestations, including those affecting the liver and gastrointestinal tract. This involvement may have important implications to the disease management, transmission, and prognosis, especially in patients with pre-existing hepatic or digestive co-morbidities. In this review, the characteristics and possible explanations of hepatic and gastrointestinal involvement caused by SARS-CoV-2 infection are summarized, adding to our knowledge of the spectrum of COVID-19. In addition, preventive measures implemented in endoscopy departments to prevent further dissemination of SARS-CoV-2 infection are proposed.

negative: MHV-A59 Enters Polarized Murine Epithelial Cells through the Apical Surface but Is Released Basolaterally Abstract Coronaviruses have a marked tropism for epithelial cells. Entry and release of the porcine transmissible gastroenteritis virus (TGEV) is restricted to apical surfaces of polarized epithelial cells, as we have recently shown (J. W. A. Rossen, C. P. J. Bekker, W. F. Voorhout, G. J. A. M. Strous, A. van der Ende, and P. J. M. Rottier, 1994, J. Virol. 68, 7966-7973). In this paper we analyze the interactions of mouse hepatitis coronavirus A59 (MHV-A59) with polarized murine kidney cells (mTAL) grown on permeable supports. After inoculation from the apical or basolateral side, virus entry was found to take place only through the apical membrane. The virus utilized a protein of the carcinoembryonic antigen family as its receptor. In contrast to TGEV, MHV-A59 was released preferentially from the basolateral plasma membrane domain, as evidenced by the accumulation of viral proteins and infectivity in the basolateral culture fluid as well as by electron microscopical observations in the mouse, MHV initially replicates in the nasal epithelium before being disseminated throughout the body; the basolateral release of MHV from epithelial cells into the animal's circulation may be the first step in the establishment of a systemic infection.

negative: Human–Dromedary Camel Interactions and the Risk of Acquiring Zoonotic Middle East Respiratory Syndrome Coronavirus Infection Middle East respiratory syndrome coronavirus (MERS‐CoV) cases without documented contact with another human MERS‐CoV case make up 61% (517/853) of all reported cases. These primary cases are of particular interest for understanding the source(s) and route(s) of transmission and for designing long‐term disease control measures. Dromedary camels are the only animal species for which there is convincing evidence that it is a host species for MERS‐CoV and hence a potential source of human infections. However, only a small proportion of the primary cases have reported contact with camels. Other possible sources and vehicles of infection include food‐borne transmission through consumption of unpasteurized camel milk and raw meat, medicinal use of camel urine and zoonotic transmission from other species. There are critical knowledge gaps around this new disease which can only be closed through traditional field epidemiological investigations and studies designed to test hypothesis regarding sources of infection and risk factors for disease. Since the 1960s, there has been a radical change in dromedary camel farming practices in the Arabian Peninsula with an intensification of the production and a concentration of the production around cities. It is possible that the recent intensification of camel herding in the Arabian Peninsula has increased the virus' reproductive number and attack rate in camel herds while the ‘urbanization’ of camel herding increased the frequency of zoonotic ‘spillover’ infections from camels to humans. It is reasonable to assume, although difficult to measure, that the sensitivity of public health surveillance to detect previously unknown diseases is lower in East Africa than in Saudi Arabia and that sporadic human cases may have gone undetected there.

negative: A recombinant Lactobacillus plantarum strain expressing the spike protein of SARS-CoV-2 Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic in the past four months and causes respiratory disease in humans of almost all ages. Although several drugs have been announced to be partially effective treatments for this disease, no approved vaccine is available. Here, we described the construction of a recombinant Lactobacillus plantarum strain expressing the SARS-CoV-2 spike protein. The results showed that the spike gene with optimized codons could be efficiently expressed on the surface of recombinant L. plantarum and exhibited high antigenicity. The highest protein yield was obtained under the following conditions: cells were induced with 50 ng/mL SppIP at 37 °C for 6–10 h. The recombinant spike (S) protein was stable under normal conditions and at 50 °C, pH = 1.5, or a high salt concentration. Recombinant L. plantarum may provide a promising food-grade oral vaccine candidate against SARS-CoV-2 infection.

negative: Pathogenic viruses: Molecular detection and characterization Abstract Pathogenic viruses are viruses that can infect and replicate within human cells and cause diseases. The continuous emergence and re-emergence of pathogenic viruses has become a major threat to public health. Whenever pathogenic viruses emerge, their rapid detection is critical to enable implementation of specific control measures and the limitation of virus spread. Further molecular characterization to better understand these viruses is required for the development of diagnostic tests and countermeasures. Advances in molecular biology techniques have revolutionized the procedures for detection and characterization of pathogenic viruses. The development of PCR-based techniques together with DNA sequencing technology, have provided highly sensitive and specific methods to determine virus circulation. Pathogenic viruses potentially having global catastrophic consequences may emerge in regions where capacity for their detection and characterization is limited. Development of a local capacity to rapidly identify new viruses is therefore critical. This article reviews the molecular biology of pathogenic viruses and the basic principles of molecular techniques commonly used for their detection and characterization. The principles of good laboratory practices for handling pathogenic viruses are also discussed. This review aims at providing researchers and laboratory personnel with an overview of the molecular biology of pathogenic viruses and the principles of molecular techniques and good laboratory practices commonly implemented for their detection and characterization.

negative: Chapter 15 Viral surface glycoproteins in carbohydrate recognition Structure and modelling Publisher Summary A large number of clinically important viruses utilize carbohydrate viral surface protein interactions to propagate infection and disease. The identification and structural characterization of the proteins and glycans essential in these recognition phenomena opens up new avenues for both drug discovery and vaccine development. This chapter describes some of the most significant developments in the field of structure-based investigations of viral surface-resident carbohydrate-recognizing proteins. Specifically, an overview of these carbohydrate-recognizing proteins from four important human viruses, including influenza, dengue, rotavirus, parainfluenza, and associated structural investigations will be presented. The surface of flavivirus is predominantly covered by E-glycoprotein (EGP) that forms dimers tethered to the surface by a stalk region. The EGP-associated glycan of the virus has been shown to be important for Dengue virus infection. Both human parainfluenza viruses and Newcastle disease virus have a surface-resident carbohydrate recognizing protein known as hemagglutinin-neuramindase (HN), which is involved in both cellular recognition and as a receptor-destroying enzyme. Influenza virus neuraminidase (NA) is a glycosylated homo-tetramer that is tethered to the virus surface by a long protein stalk at its C terminal.

negative: 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.

negative: Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the surface protein (spike) S1 receptor binding domain with heparin The dependence of the host on the interaction of hundreds of extracellular proteins with the cell surface glycosaminoglycan heparan sulphate (HS) for the regulation of homeostasis is exploited by many microbial pathogens as a means of adherence and invasion. The closely related polysaccharide heparin, the widely used anticoagulant drug, which is structurally similar to HS and is a common experimental proxy, can be expected to mimic the properties of HS. Heparin prevents infection by a range of viruses if added exogenously, including S-associated coronavirus strain HSR1. Heparin prevents infection by a range of viruses if added exogenously, including S-associated coronavirus strain HSR1. Here, we show that the addition of heparin to Vero cells between 6.25 - 200 μg.ml−1, which spans the concentration of heparin in therapeutic use, and inhibits invasion by SARS-CoV-2 at between 44 and 80%. We also demonstrate that heparin binds to the Spike (S1) protein receptor binding domain and induces a conformational change, illustrated by surface plasmon resonance and circular dichroism spectroscopy studies. The structural features of heparin on which this interaction depends were investigated using a library of heparin derivatives and size-defined fragments. Binding is more strongly dependent on the presence of 2-O or 6-O sulphation, and the consequent conformational consequences in the heparin structure, than on N-sulphation. A hexasaccharide is required for conformational changes to be induced in the secondary structure that are comparable to those that arise from heparin binding. Enoxaparin, a low molecular weight clinical anticoagulant, also binds the S1 RBD protein and induces conformational change. These findings have implications for the rapid development of a first-line therapeutic by repurposing heparin as well as for next-generation, tailor-made, GAG-based antiviral agents against SARS-CoV-2 and other members of the Coronaviridae.

negative: Outbreak investigation for COVID-19 in northern Vietnam

negative: SARS: responding to an unknown virus The severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus which first appeared in southern China at the end of 2002. In early 2003, through a single incident, it spread to Hong Kong, Singapore, Canada and Vietnam. For busy clinicians in large public hospitals, the response to the virus was initially based on ensuring a high level of protection for staff. However, as the epidemic progressed and more information became available about the virus, procedures were rationalized and the virus is currently under control worldwide. There are, however, numerous unanswered questions concerning super-spreading events, the modes of transmission of the virus and, perhaps most importantly, the rapid detection of the virus early in the course of disease. These issues need to be addressed in case the virus becomes more widespread in the near future.

negative: Coronavirus membrane fusion mechanism offers a potential target for antiviral development The coronavirus disease 2019 (COVID-19) pandemic has focused attention on the need to develop effective therapies against the causative agent, SARS-CoV-2, and also against other pathogenic coronaviruses (CoV) that have emerged in the past or might appear in future. Researchers are therefore focusing on steps in the CoV replication cycle that may be vulnerable to inhibition by broad-spectrum or specific antiviral agents. The conserved nature of the fusion domain and mechanism across the CoV family make it a valuable target to elucidate and develop pan-CoV therapeutics. In this article, we review the role of the CoV spike protein in mediating fusion of the viral and host cell membranes, summarizing the results of research on SARS-CoV, MERS-CoV, and recent peer-reviewed studies of SARS-CoV-2, and suggest that the fusion mechanism be investigated as a potential antiviral target. We also provide a supplemental file containing background information on the biology, epidemiology, and clinical features of all human-infecting coronaviruses, along with a phylogenetic tree of these coronaviruses.

negative: Cerebrovascular Accident in a Pediatric Patient Presenting With Influenza Abstract Background Acute ischemic stroke (AIS) in pediatric populations accounts for more than half of pediatric strokes and is associated with significant morbidity and mortality. Pediatric AIS can present with nonspecific symptoms or symptoms that mimic alternate pathology. Case Report A 4-month-old female presented to the emergency department for fever, decreased oral intake, and “limp” appearance after antibiotic administration. She was febrile, tachypneic, and hypoxic. Her skin was mottled with 3-s capillary refill, her anterior fontanelle was tense, and she had mute Babinski reflex bilaterally but was moving all extremities. The patient was hyponatremic, thrombocytopenic, and tested positive for influenza A. A computed tomography scan of the brain revealed an acute infarction involving the right frontal, parietal, temporal, and occipital lobes in addition to hyperdensities concerning for thrombosed cortical veins. The patient was transferred for specialty evaluation and was discharged 2 weeks later on levetiracetam. Why Should an Emergency Physician be Aware of This? Pediatric AIS can present with nonspecific symptoms that mimic alternate pathology. A high level of suspicion is needed so as not to miss the diagnosis of pediatric AIS in the emergency department. A thorough neurologic assessment is warranted, and subtle abnormalities should be investigated further.

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: Studies of culture conditions and environmental stability of human metapneumovirus. Human metapneumovirus (HMPV) is a paramyxovirus that is a leading cause of acute respiratory disease. HMPV is difficult to cultivate and limited published data describe the in vitro growth characteristics of the virus and its ability to replicate in different cell lines. Stability of HMPV to different temperatures or environmental conditions has not been described. Nosocomial infections due to HMPV have been reported, and thus the survival of infectious particles on environmental surfaces is important. We tested multiple cell lines for the ability to support HMPV replication both in the presence and absence of exogenous trypsin. The most permissive monkey kidney epithelial cells were LLC-MK2 and Vero, while the most permissive human airway epithelial cell line was BEAS-2B. LLC-MK2 cells were tolerant of trypsin and thus remain an ideal cell line for HMPV cultivation. Spinoculation significantly increased the infectivity of HMPV for cells in monolayer culture. Infectious virus was very stable to repeat freeze-thaw cycles, ambient room temperature, or 4 degrees C, while incubation at 37 degrees C led to degradation of virus titer. Finally, nonporous materials such as metal or plastic retained infectious virus for prolonged periods, while virus deposited on tissue and fabric rapidly lost infectivity. These findings provide guidance for laboratories attempting to culture HMPV and relevant information for infection control policies.

negative: Viral Shedding and Environmental Cleaning in Middle East Respiratory Syndrome Coronavirus Infection Viral shedding lasted 31 and 19 days from symptom onset in two patients with east respiratory syndrome coronavirus (MERS-CoV) pneumonia, respectively. Environmental real-time RT-PCR was weakly positive for bed guardrail and monitors. Even after cleaning the monitors with 70% alcohol-based disinfectant, RT-PCR was still weakly positive, and converted to negative only after wiping with diluted sodium chlorite. Further studies are required to clarify the appropriate methods to clean environments during and after treatment of patients with MERS-CoV infection.

negative: Chapter 22 Environmentally Transmitted Pathogens Publisher Summary Pathogenic microorganisms usually originate from an infected host or directly from the environment; however, only a small proportion of these microbes cause infection. This chapter discusses the pathogens that are transmitted through the environment such as bacteria, viruses, and protozoa. Many human pathogens can be transmitted only by direct or close contact with an infected person or animal such as herpesvirus. Virus transmission by the airborne route may be both direct and indirect inhalation of infectious droplets or through contact with contaminated fomites. Water-borne diseases—such as yellow fever, dengue, filariasis, malaria, onchocerciasis, and sleeping sicknessare transmitted by insects that breed in water or live near water. The common bacterial pathogens transmitted through water include Salmonella, Escherichia coli, Shigella, Campylobacter, Yersinia, Vibrio, Helicobacter, and Legionella. Opportunistic pathogens are also numerous in the environment, and the most important opportunistic pathogen is Pseudomonas aeruginosa. Viruses are a leading cause of gastroenteritis and water-borne outbreaks may be caused by norovirus, hepatitis A virus, Coxsackie virus, echovirus, and adenoviruses. Respiratory diseases are also associated with a large number of viruses such as rhinoviruses, coronaviruses, parainfluenza viruses, respiratory syncytial virus (RSV), influenza virus, and adenovirus. Generally, viral and protozoan pathogens survive longer in the environment than enteric bacterial pathogens.

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: Polyprenyl Immunostimulant Treatment of Cats with Presumptive Non-Effusive Feline Infectious Peritonitis In a Field Study Feline infectious peritonitis (FIP) is a fatal disease with no clinically effective treatment. This field study evaluated treatment with Polyprenyl Immunostimulant (PI) in cats with the non-effusive form of FIP. Because immune suppression is a major component in the pathology of FIP, we hypothesized that treatment with an immune system stimulant would increase survival times of cats with dry FIP. Sixty cats, diagnosed with dry FIP by primary care and specialist veterinarians and meeting the acceptance criteria, were treated with PI without intentional selection of less severe cases. The survival time from the start of PI treatment in cats diagnosed with dry FIP showed that of the 60 cats with dry FIP treated with PI, 8 survived over 200 days, and 4 of 60 survived over 300 days. A literature search identified 59 cats with non-effusive or dry FIP; no cat with only dry FIP lived longer than 200 days. Veterinarians of cats treated with PI that survived over 30 days reported improvements in clinical signs and behavior. The survival times in our study were significantly longer in cats who were not treated with corticosteroids concurrently with PI. While not a cure, PI shows promise in the treatment of dry form FIP, but a controlled study will be needed to verify the benefit.

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: Contamination by respiratory viruses on outer surface of medical masks used by hospital healthcare workers BACKGROUND: Medical masks are commonly used in health care settings to protect healthcare workers (HCWs) from respiratory and other infections. Airborne respiratory pathogens may settle on the surface of used masks layers, resulting in contamination. The main aim of this study was to study the presence of viruses on the surface of medical masks. METHODS: Two pilot studies in laboratory and clinical settings were carried out to determine the areas of masks likely to contain maximum viral particles. A laboratory study using a mannequin and fluorescent spray showed maximum particles concentrated on upper right, middle and left sections of the medical masks. These findings were confirmed through a small clinical study. The main study was then conducted in high-risk wards of three selected hospitals in Beijing China. Participants (n = 148) were asked to wear medical masks for a shift (6–8 h) or as long as they could tolerate. Used samples of medical masks were tested for presence of respiratory viruses in upper sections of the medical masks, in line with the pilot studies. RESULTS: Overall virus positivity rate was 10.1% (15/148). Commonly isolated viruses from masks samples were adenovirus (n = 7), bocavirus (n = 2), respiratory syncytial virus (n = 2) and influenza virus (n = 2). Virus positivity was significantly higher in masks samples worn for > 6 h (14.1%, 14/99 versus 1.2%, 1/49, OR 7.9, 95% CI 1.01–61.99) and in samples used by participants who examined > 25 patients per day (16.9%, 12/71 versus 3.9%, 3/77, OR 5.02, 95% CI 1.35–18.60). Most of the participants (83.8%, 124/148) reported at least one problem associated with mask use. Commonly reported problems were pressure on face (16.9%, 25/148), breathing difficulty (12.2%, 18/148), discomfort (9.5% 14/148), trouble communicating with the patient (7.4%, 11/148) and headache (6.1%, 9/148). CONCLUSION: Respiratory pathogens on the outer surface of the used medical masks may result in self-contamination. The risk is higher with longer duration of mask use (> 6 h) and with higher rates of clinical contact. Protocols on duration of mask use should specify a maximum time of continuous use, and should consider guidance in high contact settings. Viruses were isolated from the upper sections of around 10% samples, but other sections of masks may also be contaminated. HCWs should be aware of these risks in order to protect themselves and people around them.

negative: Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection Coronavirus disease 2019 (COVID-19) is a viral pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is predominantly defined by respiratory symptoms, but cardiac complications including arrhythmias, heart failure, and viral myocarditis are also prevalent. Although the systemic ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well-understood. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model system to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and immunofluorescence demonstrated that SARS-CoV-2 can enter and replicate within hiPSC-CMs, localizing at perinuclear locations within the cytoplasm. Viral cytopathic effect induced hiPSC-CM apoptosis and cessation of beating after 72 hours of infection. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating the mechanisms of infection and potentially a cardiac-specific antiviral drug screening platform.

negative: Cyberbiosecurity Challenges of Pathogen Genome Databases Pathogen detection, identification, and tracking is shifting from non-molecular methods, DNA fingerprinting methods, and single gene methods to methods relying on whole genomes. Viral Ebola and influenza genome data are being used for real-time tracking, while food-borne bacterial pathogen outbreaks and hospital outbreaks are investigated using whole genomes in the UK, Canada, the USA and the other countries. Also, plant pathogen genomes are starting to be used to investigate plant disease epidemics such as the wheat blast outbreak in Bangladesh. While these genome-based approaches provide never-seen advantages over all previous approaches with regard to public health and biosecurity, they also come with new vulnerabilities and risks with regard to cybersecurity. The more we rely on genome databases, the more likely these databases will become targets for cyber-attacks to interfere with public health and biosecurity systems by compromising their integrity, taking them hostage, or manipulating the data they contain. Also, while there is the potential to collect pathogen genomic data from infected individuals or agricultural and food products during disease outbreaks to improve disease modeling and forecast, how to protect the privacy of individuals, growers, and retailers is another major cyberbiosecurity challenge. As data become linkable to other data sources, individuals and groups become identifiable and potential malicious activities targeting those identified become feasible. Here, we define a number of potential cybersecurity weaknesses in today's pathogen genome databases to raise awareness, and we provide potential solutions to strengthen cyberbiosecurity during the development of the next generation of pathogen genome databases.

negative: Fast and easy disinfection of coronavirus-contaminated face masks using ozone gas produced by a dielectric barrier discharge plasma generator Face masks are one of the currently available options for preventing the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused the 2019 pandemic. However, with the increasing demand for protection, face masks are becoming limited in stock, and the concerned individuals and healthcare workers from many countries are now facing the issue of the reuse of potentially contaminated masks. Although various technologies already exist for the sterilization of medical equipment, most of them are not applicable for eliminating virus from face masks. Thus, there is an urgent need to develop a fast and easy method of disinfecting contaminated face masks. In this study, using a human coronavirus (HCoV-229E) as a surrogate for SARS-CoV-2 contamination on face masks, we show that the virus loses its infectivity to a human cell line (MRC-5) when exposed for a short period of time (1 min) to ozone gas produced by a dielectric barrier discharge plasma generator. Scanning electron microscopy and particulate filtration efficiency (PFE) tests revealed that there was no structural or functional deterioration observed in the face masks even after they underwent excessive exposure to ozone (five 1-minute exposures). Interestingly, for face masks exposed to ozone gas for 5 min, the amplification of HCoV-229E RNA by reverse transcription polymerase chain reaction suggested a loss of infectivity under the effect of ozone, primarily owing to the damage caused to viral envelopes or envelope proteins. Ozone gas is a strong oxidizing agent with the ability to kill viruses on hard-to-reach surfaces, including the fabric structure of face masks. These results suggest that it may be possible to rapidly disinfect contaminated face masks using a plasma generator in a well-ventilated place.

negative: Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission.

negative: Compounds Derived from Epigallocatechin-3-Gallate (EGCG) as a Novel Approach to the Prevention of Viral Infections. Pathogenic viral infections pose major health risks to humans and livestock due to viral infection-associated illnesses such as chronic or acute inflammation in crucial organs and systems, malignant and benign lesions. These lead to large number of illnesses and deaths worldwide each year. Outbreaks of emerging lethal viruses, such as Ebola virus, severe acute respiratory syndrome (SARS) virus and Middle East respiratory syndrome (MERS) virus, could lead to epidemics or even pandemics if they are not effectively controlled. Current strategies to prevent viral entry into the human body are focused on cleansing the surface of the skin that covers hands and fingers. Surface protection and disinfection against microorganisms, including viruses, is performed by sanitization of the skin surface through hand washing with soap and water, surface disinfectants, and hand sanitizers, particularly alcohol-based hand sanitizers. However, concerns about the overall ineffectiveness, toxicity of certain ingredients of disinfectants, pollution of the environment, and the short duration of antimicrobial activity of alcohol have not been addressed, and the epidemiology of certain major viral infections are not correlated inversely with the current measures of viral prevention. In addition to a short duration on the skin surface, alcohol is ineffective against certain viruses such as norovirus, rabies virus, and polio virus. There is a need for a novel approach to protect humans and livestock from infections of pathogenic viruses that is broadly effective, long-lasting (persistent), non-toxic, and environment-friendly. A strong candidate is a group of unique compounds found in Camellia sinensis (tea plant): the green tea polyphenols, in particular epigallocatechin-3-gallate (EGCG) and its lipophilic derivatives. This review discussed the weaknesses of current hand sanitizers, gathered published results from many studies on the antiviral activities of EGCG and its lipophilic derivatives, and the potential use of these compounds as a novel strategy for disease prevention, especially against pathogenic viruses.

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: 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: Modifiable Areal Unit Problem Abstract The modifiable areal unit problem, MAUP, is ever-present although not always appreciated. Through real examples, this article outlines the basic causes of MAUP, namely changes in the size, shape, and/or orientation of spatial categories/polygons used to map areal data. The visual effects of changes to mapped data are obvious even though the impacts on our understanding of the world are profound. The article concludes with a discussion of technical and broader strategic approaches for confronting the effects of MAUP on our treatment and interpretation of areal data.

negative: How do viruses control mitochondria-mediated apoptosis? Abstract There is no doubt that viruses require cells to successfully reproduce and effectively infect the next host. The question is what is the fate of the infected cells? All eukaryotic cells can “sense” viral infections and exhibit defence strategies to oppose viral replication and spread. This often leads to the elimination of the infected cells by programmed cell death or apoptosis. This “sacrifice” of infected cells represents the most primordial response of multicellular organisms to viruses. Subverting host cell apoptosis, at least for some time, is therefore a crucial strategy of viruses to ensure their replication, the production of essential viral proteins, virus assembly and the spreading to new hosts. For that reason many viruses harbor apoptosis inhibitory genes, which once inside infected cells are expressed to circumvent apoptosis induction during the virus reproduction phase. On the other hand, viruses can take advantage of stimulating apoptosis to (i) facilitate shedding and hence dissemination, (ii) to prevent infected cells from presenting viral antigens to the immune system or (iii) to kill non-infected bystander and immune cells which would limit viral propagation. Hence the decision whether an infected host cell undergoes apoptosis or not depends on virus type and pathogenicity, its capacity to oppose antiviral responses of the infected cells and/or to evade any attack from immune cells. Viral genomes have therefore been adapted throughout evolution to satisfy the need of a particular virus to induce or inhibit apoptosis during its life cycle. Here we review the different strategies used by viruses to interfere with the two major apoptosis as well as with the innate immune signaling pathways in mammalian cells. We will focus on the intrinsic mitochondrial pathway and discuss new ideas about how particular viruses could activately engage mitochondria to induce apoptosis of their host.

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: A One Health Approach to Tackle Cryptosporidiosis Cryptosporidiosis is a significant diarrhoeal disease in both people and animals across the world and is caused by several species of the protozoan parasite Cryptosporidium. Recent research has highlighted the longer-term consequences of the disease for malnourished children, involving growth stunting and cognitive deficits, and significant growth and production losses for livestock. There are no vaccines currently available to prevent the disease and few treatment options in either humans or animals, which has been a significant limiting factor in disease control to date. A One Health approach to tackle zoonotic cryptosporidiosis looking at new advances in veterinary, public, and environmental health research may offer several advantages and new options to help control the disease.

negative: Compassion in the Clinical Context: Constrained, Distributed, and Adaptive BACKGROUND: Compassion is intrinsically situated within particular contexts and how these contexts can shape compassion has not been well-described. OBJECTIVE: The purpose of the study was to describe how individual and contextual challenges can impact compassion within critical care and palliative care settings. DESIGN: This qualitative study adopted phenomenology and autoethnography to inform data collection, and principles of activity theory and realist inquiry for data interpretation. PARTICIPANTS: Five clinicians who work in critical care (n = 3) and palliative care (n = 3) participated in the study. APPROACH: Qualitative data were obtained from ethnographic observations, interviews, and focus groups. Participants observed and recorded field notes (n = 53) on instances of suffering and compassion in their workplace settings. At the end of the study period, they participated in a focus group or individual interview to reflect on their experiences. Data was analyzed using constructivist grounded theory techniques and iteratively synthesized through group discussion and model building. KEY RESULTS: The findings reflected four phenomena associated with compassion in context: individual gaps and lapses in compassion, relational challenges, contextual constraints on compassion, and distributed compassion. Individual gaps and lapses in compassion involved inattention, intention vs. perception, personal capacity, and personal toll. Relational challenges included receptivity, fragmentation, and lack of shared understanding. Contextual constraints consisted of situational pressures, the clinical environment, gaps in education, and organizational culture. The distribution of compassion within teams and how teams adapt their behaviors in response to perceived needs for greater compassion modulated these challenges. CONCLUSIONS: The study illustrates the many ways in which compassion can be shaped by context and highlights the role of teamwork in identifying gaps and lapses in compassion and responding in a way that supports patients, families, and colleagues. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05467-9) contains supplementary material, which is available to authorized users.

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 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.

negative: 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).

negative: Diseases of the Alimentary Tract: Nonruminant

negative: Comparing the binding interactions in the receptor binding domains of SARS-CoV-2 and SARS-CoV COVID-19, since emerged in Wuhan, China, has been a major concern due to its high infection rate, leaving more than one million infected people around the world. Huge number of studies tried to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV-1, in order to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV-1 Spike protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the spike proteins of SARS-CoV and SARS-CoV-2 to the ACE2. We found that the SARS-CoV-2 binds to ACE2 stronger than SARS-CoV by 7 kcal/mol, due to enhanced electrostatic interactions. The major contributions to the electrostatic binding energies are resulting from the salt-bridges formed between R426 and ACE2-E329 in case of SARS-CoV and K417 and ACE2-D30 for SARS-CoV2. In addition, there is no significant contribution from a single mutant to the binding energies. However, these mutations induce sophisticated structural changes that enhance the binding energies. Our results also indicate that the SARS-CoV-2 is unlikely a lab engineered virus.

negative: Efficient induction of cytotoxic T lymphocytes specific for severe acute respiratory syndrome (SARS)-associated coronavirus by immunization with surface-linked liposomal peptides derived from a non-structural polyprotein 1a Abstract Spike and nucleocapsid are structural proteins of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) and major targets for cytotoxic T lymphocytes (CTLs). In contrast, non-structural proteins encoded by two-thirds of viral genome are poorly characterized for cell-mediated immunity. We previously demonstrated that nucleocapsid-derived peptides chemically coupled to the surface of liposomes effectively elicited SARS-CoV-specific CTLs in mice. Here, we attempted to identify HLA-A*0201-restricted CTL epitopes derived from a non-structural polyprotein 1a (pp1a) of SARS-CoV, and investigated whether liposomal peptides derived from pp1a were effective for CTL induction. Out of 30 peptides predicted on computational algorithms, nine peptides could significantly induce interferon gamma (IFN-γ)-producing CD8+ T cells in mice. These peptides were coupled to the surface of liposomes, and inoculated into mice. Six liposomal peptides effectively induced IFN-γ-producing CD8+ T cells and seven liposomal peptides including the six peptides primed CTLs showing in vivo killing activities. Further, CTLs induced by the seven liposomal peptides lysed an HLA-A*0201 positive cell line expressing naturally processed, pp1a-derived peptides. Of note, one of the liposomal peptides induced high numbers of long-lasting memory CTLs. These data suggest that surface-linked liposomal peptides derived from pp1a might offer an efficient CTL-based vaccine against SARS.

negative: Methicillin-Resistant Staphylococcus aureus (MRSA) Contamination in Bedside Surfaces of a Hospital Ward and the Potential Effectiveness of Enhanced Disinfection with an Antimicrobial Polymer Surfactant The aim in this study was to assess the effectiveness of a quaternary ammonium chloride (QAC) surfactant in reducing surface staphylococcal contamination in a routinely operating medical ward occupied by patients who had tested positive for methicillin-resistant Staphylococcus aureus (MRSA). The QAC being tested is an antibacterial film that is sprayed onto a surface and can remain active for up to 8 h. A field experimental study was designed with the QAC plus daily hypochlorite cleaning as the experimental group and hypochlorite cleaning alone as the control group. The method of swabbing on moistened surfaces was used for sampling. It was found that 83% and 77% of the bedside surfaces of MRSA-positive and MRSA-negative patients respectively were contaminated with staphylococci at 08:00 hours, and that the staphylococcal concentrations increased by 80% at 1200 h over a 4-hour period with routine ward and clinical activities. Irrespective of the MRSA status of the patients, high-touch surfaces around the bed-units within the studied medical ward were heavily contaminated (ranged 1 to 276 cfu/cm(2) amongst the sites with positive culture) with staphylococcal bacteria including MRSA, despite the implementation of daily hypochlorite wiping. However, the contamination rate dropped significantly from 78% to 11% after the application of the QAC polymer. In the experimental group, the mean staphylococcal concentration of bedside surfaces was significantly (p < 0.0001) reduced from 4.4 ± 8.7 cfu/cm(2) at 08:00 hours to 0.07 ± 0.26 cfu/cm(2) at 12:00 hours by the QAC polymer. The results of this study support the view that, in addition to hypochlorite wiping, the tested QAC surfactant is a potential environmental decontamination strategy for preventing the transmission of clinically important pathogens in medical wards.

negative: 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.

negative: High transmissibility of COVID-19 near symptom onset Background The dynamics of coronavirus disease 2019 (COVID-19) transmissibility after symptom onset remains unknown. Methods We conducted a prospective case-ascertained study on laboratory-confirmed COVID-19 cases and their contacts. Secondary clinical attack rate (considering symptomatic cases only) was analyzed for different exposure windows after symptom onset of index cases and for different exposure settings. Results Thirty-two confirmed patients were enrolled and 12 paired data (index-secondary cases) were identified among the 1,043 contacts. The secondary clinical attack rate was 0.9% (95% CI 0.5-1.7%). The attack rate was higher among those whose exposure to index cases started within five days of symptom onset (2.4%, 95% CI 1.1-4.5%) than those who were exposed later (zero case from 605 close contacts, 95% CI 0-0.61%). The attack rate was also higher among household contacts (13.6%, 95% CI 4.7-29.5%) and non-household family contacts (8.5%, 95% CI 2.4-20.3%) than that in healthcare or other settings. The higher secondary clinical attack rate for contacts near symptom onset remained when the analysis was restricted to household and family contacts. There was a trend of increasing attack rate with the age of contacts (p for trend < 0.001). Conclusions High transmissibility of COVID-19 near symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized social distancing measures are required. Rapid reduction of transmissibility over time implies that prolonged hospitalization of mild cases might not be necessary in large epidemics.

negative: Glycosyltransferase complexes in eukaryotes: long-known, prevalent but still unrecognized Glycosylation is the most common and complex cellular modification of proteins and lipids. It is critical for multicellular life and its abrogation often leads to a devastating disease. Yet, the underlying mechanistic details of glycosylation in both health and disease remain unclear. Partly, this is due to the complexity and dynamicity of glycan modifications, and the fact that not all the players are taken into account. Since late 1960s, a vast number of studies have demonstrated that glycosyltransferases typically form homomeric and heteromeric complexes with each other in yeast, plant and animal cells. To propagate their acceptance, we will summarize here accumulated data for their prevalence and potential functional importance for glycosylation focusing mainly on their mutual interactions, the protein domains mediating these interactions, and enzymatic activity changes that occur upon complex formation. Finally, we will highlight the few existing 3D structures of these enzyme complexes to pinpoint their individual nature and to emphasize that their lack is the main obstacle for more detailed understanding of how these enzyme complexes interact and function in a eukaryotic cell.

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: An Introduction to the Evolutionary Ecology of Viruses

negative: TOWARD A COVID-19 SCORE-RISK ASSESSMENTS AND REGISTRY ABSTRACT Importance Critical care resources like ventilators, used to manage the current COVID-19 pandemic, are potentially inadequate. Established triage standards and guidelines may not contain the most appropriate severity assessment and outcome prediction models. Objectives Develop a draft pandemic specific triage assessment score for the current COVID-19 pandemic. Design a website where initial Toward a COVID-19 Scores (TACS) can be quickly calculated and used to compare various treatment strategies. Create a TACS Registry where data and outcomes for suspected and confirmed COVID-19 patients can be recorded. Use the TACS Registry to develop an influenza epidemic specific database and score for use in future respiratory based epidemics. Design, Setting, Participants Retrospective analysis of 3,301 ICU admissions with respiratory failure admitted to 41 U.S. Intensive Care Units from 2015-19. Independent external validation on 1,175 similar ICU Admissions using identical entry criteria from Barnes Jewish Hospital (BJH), Washington University from 2016-2019. Main Outcomes TACS was created with 16 readily available predictive variables for risk assessment of hospital mortality 24 hours after ICU Admission and the need for prolonged assisted mechanical ventilation (PAMV) ( >>96 hours) at 24- and 48-hours post ICU admission. Results TACS achieved an Area Under the Curve (AUC) for hospital mortality after 24 hours of 0.80 in the development dataset; 0.81 in the internal validation dataset. At a probability of 50% hospital mortality, positive predictive value (PPV) was 0.55, negative predictive value (NPV) 0.89; sensitivity 22%, specificity 97%. For PAMV after 24 hours, the AUC was 0.84 in the development dataset, 0.81 in the validation dataset. For PAMV after 48 hours, the AUC was 0.82 in the development dataset, 0.78 in the validation dataset. In the external validation the AUC for TACS was 0.76 +/- 0.024. We launched a website that is scaled for mobile device use ( https://covid19score.azurewebsites.net/) that provides open access to a user-friendly TACS Calculator for all predictions. We also designed a voluntary TACS Registry for collection of data and outcomes on ICU Admissions with COVID-19. Conclusions and Relevance Toward a COVID-19 score is a starting point for an epidemic specific triage assessment that could be used to evaluate various approaches to treatment. The TACS Registry provides the ability to establish a respiratory specific outcomes database that can be used to create a triage approach for future such pandemics.

negative: Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series BACKGROUND: In December, 2019, the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, causing COVID-19, a respiratory disease presenting with fever, cough, and often pneumonia. WHO has set the strategic objective to interrupt spread of SARS-CoV-2 worldwide. An outbreak in Bavaria, Germany, starting at the end of January, 2020, provided the opportunity to study transmission events, incubation period, and secondary attack rates. METHODS: A case was defined as a person with SARS-CoV-2 infection confirmed by RT-PCR. Case interviews were done to describe timing of onset and nature of symptoms and to identify and classify contacts as high risk (had cumulative face-to-face contact with a confirmed case for ≥15 min, direct contact with secretions or body fluids of a patient with confirmed COVID-19, or, in the case of health-care workers, had worked within 2 m of a patient with confirmed COVID-19 without personal protective equipment) or low risk (all other contacts). High-risk contacts were ordered to stay at home in quarantine for 14 days and were actively followed up and monitored for symptoms, and low-risk contacts were tested upon self-reporting of symptoms. We defined fever and cough as specific symptoms, and defined a prodromal phase as the presence of non-specific symptoms for at least 1 day before the onset of specific symptoms. Whole genome sequencing was used to confirm epidemiological links and clarify transmission events where contact histories were ambiguous; integration with epidemiological data enabled precise reconstruction of exposure events and incubation periods. Secondary attack rates were calculated as the number of cases divided by the number of contacts, using Fisher's exact test for the 95% CIs. FINDINGS: Patient 0 was a Chinese resident who visited Germany for professional reasons. 16 subsequent cases, often with mild and non-specific symptoms, emerged in four transmission generations. Signature mutations in the viral genome occurred upon foundation of generation 2, as well as in one case pertaining to generation 4. The median incubation period was 4·0 days (IQR 2·3–4·3) and the median serial interval was 4·0 days (3·0–5·0). Transmission events were likely to have occurred presymptomatically for one case (possibly five more), at the day of symptom onset for four cases (possibly five more), and the remainder after the day of symptom onset or unknown. One or two cases resulted from contact with a case during the prodromal phase. Secondary attack rates were 75·0% (95% CI 19·0–99·0; three of four people) among members of a household cluster in common isolation, 10·0% (1·2–32·0; two of 20) among household contacts only together until isolation of the patient, and 5·1% (2·6–8·9; 11 of 217) among non-household, high-risk contacts. INTERPRETATION: Although patients in our study presented with predominately mild, non-specific symptoms, infectiousness before or on the day of symptom onset was substantial. Additionally, the incubation period was often very short and false-negative tests occurred. These results suggest that although the outbreak was controlled, successful long-term and global containment of COVID-19 could be difficult to achieve. FUNDING: All authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.

negative: Reducing Aerosol Generation During Ventilator Weaning in a Coronavirus Disease 2019 Patient Using a Supraglottic Airway: A Case Report We report weaning from mechanical ventilation with no coughing in a patient with coronavirus disease 2019 (COVID-19). Substituting the endotracheal tube for a supraglottic airway (SGA), which is less stimulating to the trachea, can reduce coughing with weaning from mechanical ventilation and extubation. Personal protective equipment is in short supply worldwide. Reducing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is beneficial in terms of occupational health of health care workers.

negative: Long term stability and infectivity of herpesviruses in water For viruses to utilize environmental vectors (hard surfaces, soil, water) for transmission, physical and chemical stability is a prerequisite. There are many factors including pH, salinity, temperature, and turbidity that are known to contribute to the ability of viruses to persist in water. Equine herpesvirus type-1 (EHV-1) is a pathogenic alphaherpesvirus associated with domestic horses and wild equids. EHV-1 and recombinants of EHV-1 and EHV-9 are able to cause infections in non-equid animal species, particularly in captive settings. Many of the captive non-equid mammals are not naturally sympatric with equids and do not share enclosures, however, in many cases water sources may overlap. Similarly, in the wild, equids encounter many species at waterholes in times of seasonal drought. Therefore, we hypothesized that EHV-1 is stable in water and that water may act as a vector for EHV-1. In order to establish the conditions promoting or hindering EHV-1 longevity, infectivity and genomic stability in water; we exposed EHV-1 to varied water environments (pH, salinity, temperature, and turbidity) in controlled experiments over 21 days. The presence and infectivity of the virus was confirmed by both qPCR and cell culture experiments. Our results show that EHV-1 remains stable and infectious under many conditions in water for up to three weeks.

negative: Estimating Survival of Hospitalized COVID-19 Patients from Admission Information Background While clinical characteristics and a range of mortality risk factors of COVID-19 patients have been reported, a practical early clinical survival calculator specialized for the unique cohort of patients has not yet been introduced. Such a tool would provide timely and valuable guidance in clinical care decision-making during this global pandemic. Methods Demographic, laboratory, clinical, and treatment data (from 13 acute care facilities at Northwell Health) were extracted from electronic medical records and used to build and test the predictive accuracy of a survival probability calculator-the Northwell COVID-19 Survival (NOCOS) calculator-for hospitalized COVID-19 patients. The NOCOS calculator was constructed using multivariate regression with L1 regularization (LASSO). Model predictive performance was measured using Receiver Operating Characteristic (ROC) curves and the Area Under the Curve (AUC) of the calculators tested. Results A total of 5,233 inpatients were included in the study. Patient age, serum blood urea nitrogen (BUN), Emergency Severity Index (ESI), red cell distribution width (RCDW), absolute neutrophil count, serum bicarbonate, and glucose were identified as the optimal early predictors of survival by multivariate LASSO regression. The predictive performance of the Northwell COVID-19 Survival (NOCOS) calculator was assessed for 14 consecutive days. Conclusions We present a rapidly developed and deployed estimate of survival probability that outperforms other general risk models. The 7 early predictors of in-hospital survival can help clinicians identify patients with increased probabilities of survival and provide critical decision support.

negative: Growth Performance and Health of Dairy Calves Bedded with Different Types of Materials Abstract Granite fines, sand, rice hulls, long wheat straw, and wood shavings were compared as bedding for 60 female dairy calves. Growth, health, stress indices, and behavior of newly born calves, along with physical characteristics and bacterial counts of bedding, were evaluated for 42 d during August to October, 2002. Overall average daily gain and dry matter intake of calves did not differ due to bedding type, although during wk 2 calves housed on rice hulls had the greatest dry matter intake and those housed on wood shavings had the lowest. During wk 2, calves housed on granite fines and sand were treated more often for scours, and calves housed on long wheat straw received the fewest antibiotic treatments (week by bedding material interaction). Granite fines formed a harder surface than other bedding, and calves housed on granite fines scored the dirtiest. When bedding materials were evaluated, sand was scored to be the dirtiest, while pens bedded with rice hulls, long wheat straw, and wood shavings scored cleaner. Long wheat straw had the warmest surface temperature, and rice hulls and wood shavings were warmer than granite fines and sand. Serum cortisol, α 1-acid glycoprotein, immunoglobulin G concentrations, and the neutrophil:lymphocyte ratio were not affected by bedding type. On d 0, coliform counts were greatest in rice hulls. After use, coliform counts were greatest in long wheat straw (week by bedding material interaction). On d 42, the concentration of ammonia at 10cm above the bedding was lowest for long wheat straw. Growth performance of calves bedded for 42 d with 5 bedding types did not differ; however, the number of antibiotic treatments given for scours was greatest on granite fines and sand; coliform counts in the bedding were highest in rice hulls before use and in long wheat straw after 42 d of use.

negative: Hygiène des mains et masques contre COVID-19 : oser le dégradé ?

negative: Potential Treatments for COVID-19; a Narrative Literature Review SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11(th). There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.

negative: Viruses as vesicular carriers of the viral genome: A functional module perspective Abstract Enveloped viruses and cellular transport vesicles share obvious morphological and functional properties. Both are composed of a closed membrane, which is lined with coat proteins and encases cargo. Transmembrane proteins inserted into the membrane define the target membrane area with which the vesicle or virus is destined to fuse. Here we discuss recent insight into the functioning of enveloped viruses in the framework of the “functional module” concept. Vesicular transport is an exemplary case of a functional module, as defined as a part of the proteome that assembles to perform a specific autonomous function in a living cell. Cellular vesicles serve to transport cargo between membranous organelles inside the cell, while enveloped viruses can be seen as carriers of the viral genome delivering their cargo from an infected to an uninfected cell. The turnover of both vesicles and viruses involves an analogous series of submodular events. This comprises assembly of elements, budding from the donor compartment, uncoating and/or maturation, docking to and finally fusion with the target membrane to release the cargo. This modular perception enables us to define submodular building blocks so that mechanisms and elements can be directly compared. It will be analyzed where viruses have developed their own specific strategy, where they share functional schemes with vesicles, and also where they even have “hijacked” complete submodular schemes from the cell. Such a perspective may also include new and more specific approaches to pharmacological interference with virus function, which could avoid some of the most severe side effects.

negative: Forty years with coronaviruses I have been researching coronaviruses for more than forty years. This viewpoint summarizes some of the major findings in coronavirus research made before the SARS epidemic and how they inform current research on the newly emerged SARS-CoV-2.

negative: Assembly in vitro of a spanning membrane protein of the endoplasmic reticulum: the E1 glycoprotein of coronavirus mouse hepatitis virus A59. The E1 glycoprotein of coronavirus mouse hepatitis virus A59 was synthesized in vitro by translation of viral mRNA in the presence of dog pancreatic microsomes. Its disposition in the membrane was investigated by digestion with proteases and by selective NH2-terminal labeling. The protein spans the membrane, but only small portions from the NH2 and COOH terminus are exposed respectively in the lumenal and cytoplasmic domains; the bulk of the molecule is apparently buried in the membrane. The protein lacks a cleavable leader sequence and does not acquire its characteristic O-linked oligosaccharides in rough microsomes. It may enter the membrane at any stage during synthesis of the first 150 amino acid residues. These unusual features of the protein might help to explain why it is not transported to the cell surface in vivo but remains in intracellular membranes, causing the virus to bud there.

negative: COVID-19 and pediatric inflammatory bowel disease: How to manage it? Pediatric gastroenterologists, family members, and caregivers of patients with inflammatory bowel disease (IBD) are on alert; they are all focused on implementing prophylactic measures to prevent infection by severe acute respiratory syndrome coronavirus 2, evaluating the risks in each patient, guiding them in their treatment, and keeping IBD in remission. To face the current issues of the coronavirus disease pandemic, we have developed a synthesis of the main recommendations of the literature directed at pediatric gastroenterologists in control of patients with pediatric IBD and adapted to the national reality.

negative: 5.42 RNA Interference Technology This chapter replaces Z. Liang, P. Zhang, 5.15 - RNA Interference (RNAi) Technology, Editor: Murray Moo-Young, Comprehensive Biotechnology (Second Edition), Academic Press, 2011, Pages 179-187.

negative: Immunoinformatics study to search epitopes of spike glycoprotein from SARS-CoV-2 as potential vaccine The Coronavirus disease named COVID-19 is caused by the virus reported in 2019 first identified in China. The cases of this disease have increased and as of June 1st, 2020 there are more than 216 countries affected. Pharmacological treatments have been proposed based on the resemblance of the HIV virus. With regard to prevention there is no vaccine, thus, we proposed to explore the spike protein due to its presence on the viral surface, and it also contains the putative viral entry receptor as well as the fusion peptide (important in the genome release). In this work we have employed In Silico techniques such as immunoinformatics tools which permit the identification of potential immunogenic regions on the viral surface (spike glycoprotein). From these analyses, we identified four epitopes E332-370, E627-651, E440-464 and E694-715 that accomplish essential features such as promiscuity, conservation grade, exposure and universality, and they also form stable complexes with MHCII molecule. We suggest that these epitopes could generate a specific immune response, and thus, they could be used for future applications such as the design of new epitope vaccines against the SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

negative: Personal Cleanliness Activities in Preschool Classrooms One hundred and twelve preschool teachers in Indiana were asked to complete a questionnaire requesting them to indicate what personal health-related activities they were incorporating into their classroom routines, why they were incorporating them, and how often such activities were done. The results of the study indicate that the most incorporated activities were hand-washing, proper ways of coughing, and discussion on germs. The least incorporated personal health-related activities were proper use of bathroom and keeping things out of the mouth. Reasons for incorporating the activities include helping to curtail the spreading of colds and germs, helping the children to develop good life skills later in life, and helping the preschoolers know about the health hazards associated with germs, among others. The study recommends the need to make Health Education a core component of preschool teachers’ training.

negative: Reaching further by Village Health Collaborators: The informal health taskforce of Vietnam for COVID-19 responses

negative: Epithelial injury and interstitial fibrosis in the proximal alveolar regions of rats chronically exposed to a simulated pattern of urban ambient ozone Abstract Electron microcopic morphometry was used to study the development of lung injury during and after chronic (78 weeks) exposure to a pattern of ozone (O3) designed to simulate high urban ambient concentrations that occur in some environments. The daily exposure regimen consisted of a 13-hr background of 0.06 ppm, an exposure peak that rose from 0.06 to 0.25 ppm, and returned to the background level over a 9-hr period, and 2-hr downtime for maintenance. Rats were exposed for 1, 3, 13, and 78 weeks. Additional groups of rats exposed for 13 or 78 weeks were allowed to recover in filtered clean air for 6 or 17 weeks, respectively. Rats exposed to filtered air for the same lengths of time were used as controls. Samples from proximal alveolar regions and terminal bronchioles were obtained by microdissection. Analysis of the proximal alveolar region revealed a biphasic response. Acute tissue reactions after 1 week of exposure included epithelial inflammation, interstitial edema, interstitial cell hypertrophy, and influx of macrophages. These responses subsided after 3 weeks of exposure. Progressive epithelial and interstitial tissue responses developed with prolonged exposure and included epithelial hyperplasia, fibroblast proliferation, and interstitial matrix accumulation. The epithelial responses involved both type I and type II epithelial cells. Alveolar type I cells increased in number, became thicker, and covered a smaller average surface area. These changes persisted throughout the entire exposure and did not change during the recovery pefiod, indicating the sensitivity of these cells to injury. The main response of type II epithelial cells was cell proliferation. The accumulation of interstitial matrix after chronic exposure consisted of deposition of both increased amounts of basement membrane and collagen fibers. Interstitial matrix accumulation underwent partial recovery during follow-up periods in air; however, the thickening of the basement membrane did not resolve. Analysis of terminal bronchioles showed that short-term exposure to O3 caused a loss of ciliated cells and differentiation of preciliated and Clara cells. The bronchiolar cell population stabilized on continued exposure; however, chronic exposure resulted in structural changes, suggesting injury to both ciliated and Clara cells. We conclude that chronic exposure to low levels of O3 causes epithelial inflammation and interstitial fibrosis in the proximal alveolar region and bronchiolar epithelial cell injury.

negative: Airway Management in COVID-19: In the Den of the Beast

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: Summary of Infection Control in the Dental Office: A Global Prospective During the delivery of dental care, there is the potential for the dissemination and/or exposure to blood and other body fluids as well as numerous microorganisms that colonize the mouth and/or oral, nasal, and respiratory fluids/secretions. Dentists, dental staff, and patients can be exposed to a variety of pathogenic microorganisms from these sources within the dental office. Contamination from any of these organisms may result in disease transmission which may occur from direct contact with infected body fluids and tissues, or indirectly by contacting surfaces and/or devices that have been contaminated. This phenomenon can occur anywhere in the world where dental care is provided. The principles of infection control must be employed to ensure that dental care is delivered in as safe a manner as possible for both the dental providers and the patients.

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: 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: 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: Why ophthalmologists should mask: a perspective from Hong Kong

negative: Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD Coronavirus disease 19 (COVID-19) is an emerging global health crisis. With over 7 million confirmed cases to date, this pandemic continues to expand, spurring research to discover vaccines and therapies. SARS-CoV-2 is the novel coronavirus responsible for this disease. It initiates entry into human cells by binding to angiotensin-converting enzyme 2 (ACE2) via the receptor binding domain (RBD) of its spike protein (S). Disrupting the SARS-CoV-2-RBD binding to ACE2 with designer drugs has the potential to inhibit the virus from entering human cells, presenting a new modality for therapeutic intervention. Peptide-based binders are an attractive solution to inhibit the RBD-ACE2 interaction by adequately covering the extended protein contact interface. Using molecular dynamics simulations based on the recently solved cryo-EM structure of ACE2 in complex with SARS-CoV-2-RBD, we observed that the ACE2 peptidase domain (PD) α1 helix is important for binding SARS-CoV-2-RBD. Using automated fast-flow peptide synthesis, we chemically synthesized a 23-mer peptide fragment of the ACE2 PD α1 helix (SBP1) composed entirely of proteinogenic amino acids. Chemical synthesis of SBP1 was complete in 1.5 hours, and after work up and isolation >20 milligrams of pure material was obtained. Bio-layer interferometry (BLI) revealed that SBP1 associates with micromolar affinity to insect-derived SARS-CoV-2-RBD protein obtained from Sino Biological. Association of SBP1 was not observed to an appreciable extent to HEK cell-expressed SARS-CoV-2-RBD proteins and insect-derived variants acquired from other vendors. Moreover, competitive BLI assays showed SBP1 does not outcompete ACE2 binding to Sino Biological insect-derived SARS-CoV-2-RBD. Further investigations are ongoing to gain insight into the molecular and structural determinants of the variable binding behavior to different SARS-CoV-2-RBD protein variants.

negative: Rapid detection of the common avian leukosis virus subgroups by real-time loop-mediated isothermal amplification BACKGROUND: Subgroups A, B, E and J are the major subgroups of avian leukosis virus (ALV) infecting chickens. ALV infection has become endemic in China and has a significant negative effect on the poultry industry. Consequently, there is an urgent need for a specific, sensitive and rapid method for diagnosis and eradication of ALV. Therefore, we developed a simple and rapid real-time loop-mediated isothermal amplification (LAMP) reaction for the timely detection of the common ALV subgroups, whereby the amplification can be obtained in 35 min under isothermal conditions at 63 °C, ability to specific, sensitive and rapid detect all the common ALV subgroups. METHODS: A set of four specific primers was designed to target the sequences of the pol gene of ALV, and the loop-mediated isothermal amplification (LAMP) assay were developed and compared with PCR and virus isolation methods. RESULTS: The results from specificity of the LAMP assay showed that only target ALVs DNA was amplified. The LAMP assay demonstrated a sensitivity of 20 copies/reaction of ALV DNA, which was 10 times higher than the conventional PCR measurement. To further evaluate the reliability of the method, the assay was evaluated with ALV DNA from a panel of 81 clinical samples suspected of ALV infection. The results verify that the LAMP method was more sensitive than the conventional PCR and virus isolation method. CONCLUSION: In conclusion, the developed LAMP assay was a simple, inexpensive, sensitive method for the rapid detection of the most common subgroups of ALV, and it provided a useful and practical tool in the eradication program for ALV in the poultry industry.

negative: Outbreak Investigation of COVID-19 Among Residents and Staff of an Independent and Assisted Living Community for Older Adults in Seattle, Washington. Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused epidemic spread of coronavirus disease 2019 (COVID-19) in the Seattle, Washington, metropolitan area, with morbidity and mortality concentrated among residents of skilled nursing facilities. The prevalence of COVID-19 among older adults in independent/assisted living is not understood. Objectives To conduct surveillance for SARS-CoV-2 and describe symptoms of COVID-19 among residents and staff of an independent/assisted living community. Design, Setting, and Participants In March 2020, public health surveillance of staff and residents was conducted on site at an assisted and independent living residence for older adults in Seattle, Washington, after exposure to 2 residents who were hospitalized with COVID-19. Exposures Surveillance for SARS-CoV-2 infection in a congregate setting implementing social isolation and infection prevention protocols. Main Outcomes and Measures SARS-CoV-2 real-time polymerase chain reaction was performed on nasopharyngeal swabs from residents and staff; a symptom questionnaire was completed assessing fever, cough, and other symptoms for the preceding 14 days. Residents were retested for SARS-CoV-2 7 days after initial screening. Results Testing was performed on 80 residents; 62 were women (77%), with mean age of 86 (range, 69-102) years. SARS-CoV-2 was detected in 3 of 80 residents (3.8%); none felt ill, 1 male resident reported resolved cough and 1 loose stool during the preceding 14 days. Virus was also detected in 2 of 62 staff (3.2%); both were symptomatic. One week later, resident SARS-CoV-2 testing was repeated and 1 new infection detected (asymptomatic). All residents remained in isolation and were clinically stable 14 days after the second test. Conclusions and Relevance Detection of SARS-CoV-2 in asymptomatic residents highlights challenges in protecting older adults living in congregate settings. In this study, symptom screening failed to identify residents with infections and all 4 residents with SARS-CoV-2 remained asymptomatic after 14 days. Although 1 asymptomatic infection was found on retesting, a widespread facility outbreak was avoided. Compared with skilled nursing settings, in assisted/independent living communities, early surveillance to identify asymptomatic persons among residents and staff, in combination with adherence to recommended preventive strategies, may reduce viral spread.

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: Broad-spectrum antivirals against viral fusion Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This ‘one bug–one drug’ approach to antiviral drug development can be successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses, which require the fusion of viral and cell membranes for virus entry. Therefore, antivirals that target the membrane fusion process represent new paradigms for broad-spectrum antiviral discovery. In this Review, we discuss the mechanisms responsible for the fusion between virus and cell membranes and explore how broad-spectrum antivirals target this process to prevent virus entry.

negative: 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.

negative: Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the CEA family CEACAM1 is a member of the carcinoembryonic antigen (CEA) family. Isoforms of murine CEACAM1 serve as receptors for mouse hepatitis virus (MHV), a murine coronavirus. Here we report the crystal structure of soluble murine sCEACAM1a[1,4], which is composed of two Ig-like domains and has MHV neutralizing activity. Its N-terminal domain has a uniquely folded CC′ loop that encompasses key virus-binding residues. This is the first atomic structure of any member of the CEA family, and provides a prototypic architecture for functional exploration of CEA family members. We discuss the structural basis of virus receptor activities of murine CEACAM1 proteins, binding of Neisseria to human CEACAM1, and other homophilic and heterophilic interactions of CEA family members.

negative: What are the most appropriate methods of surveillance for monitoring an emerging respiratory infection such as SARS? Effective surveillance is necessary for the successful management of emerging infection. It allows public health protection measures such as contact tracing and isolation to be put in place. This study aimed to find the most appropriate surveillance method for a disease like SARS. Existing surveillance methods were evaluated against a set of new criteria in a qualitative manner. Influenza and tuberculosis (TB) surveillance were used as models. A literature search was undertaken to find relevant evidence. The results show that TB surveillance is more appropriate than influenza surveillance as a model because it is more complete in its reporting. Clinician‐based reporting is better than laboratory‐based because it is more timely. The results suggest a clinician‐based notification system would be the most appropriate form of surveillance for a disease like SARS for public health purposes.

negative: Therapeutic Efficacy and Safety of Prolonged Macrolide, Corticosteroid, Doxycycline, and Levofloxacin against Macrolide-Unresponsive Mycoplasma pneumoniae Pneumonia in Children BACKGROUND: We aimed to compare the therapeutic efficacy of prolonged macrolide (PMC), corticosteroids (CST), doxycycline (DXC), and levofloxacin (LFX) against macrolide-unresponsive Mycoplasma pneumoniae (MP) pneumonia in children and to evaluate the safety of the secondary treatment agents. METHODS: We retrospectively analyzed the data of patients with MP pneumonia hospitalized between January 2015 and April 2017. Macrolide-unresponsiveness was clinically defined with a persistent fever of ≥ 38.0°C at ≥ 72 hours after macrolide treatment. The cases were divided into four groups: PMC, CST, DXC, and LFX. We compared the time to defervescence (TTD) after secondary treatment and the TTD after initial macrolide treatment in each group with adjustment using propensity score-matching analysis. RESULTS: Among 1,165 cases of MP pneumonia, 190 (16.3%) were unresponsive to macrolides. The proportion of patients who achieved defervescence within 48 hours in CST, DXC, and LFX groups were 96.9% (31/33), 85.7% (12/14), and 83.3% (5/6), respectively. The TTD after initial macrolide treatment did not differ between PMC and CST groups (5.1 vs. 4.2 days, P = 0.085), PMC and DXC groups (4.9 vs. 5.7 days, P = 0.453), and PMC and LFX groups (4.4 vs. 5.0 days, P = 0.283). No side effects were observed in the CST, DXC, and LFX groups. CONCLUSION: The change to secondary treatment did not show better efficacy compared to PMC in children with macrolide-unresponsive MP pneumonia. Further studies are needed to guide appropriate treatment in children with MP pneumonia.

negative: The Pace and Pulse of the Fight against Coronavirus across the US, A Google Trends Approach The coronavirus pandemic is impacting our lives at unprecedented speed and scale - including how we eat and work, what we worry about, how much we move, and our ability to earn. Google Trends can be used as a proxy for what people are thinking, needing, and planning. We use it to provide both insights into, and potential indicators of, important changes in information-seeking patterns during pandemics like COVID-19. Key questions we address are: (1) What is the relationship between the coronavirus outbreak and internet searches related to healthcare seeking, government support programs, media sources of different ideologies, planning around social activities, travel, and food, and new coronavirus-specific behaviors and concerns?; (2) How does the popularity of search terms differ across states and regions and can we explain these differences?; (3) Can we find distinct, tangible search patterns across states suggestive of policy gaps to inform pandemic response? (4) Does Google Trends data correlate with and potentially precede real-life events? We suggest strategic shifts for policy makers to improve the precision and effectiveness of non-pharmaceutical interventions (NPIs) and recommend the development of a real-time dashboard as a decision-making tool. Methods used include trend analysis of US search data; geographic analyses of the differences in search popularity across US states during March 1st to April 15th, 2020; and Principal Component Analyses (PCA) to extract search patterns across states.

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: An experimental study of the survival of turkey coronavirus at room temperature and +4°C Turkey coronavirus (TCoV) is a gammacoronavirus (Coronaviridae, Nidovirales) responsible for digestive disorders in young turkeys. TCoV has been associated with poult enteritis complex, a syndrome that severely affects turkey production. No medical prophylaxis exists to control TCoV, therefore sanitary measures such as cleaning and disinfection are essential. It is thus important to evaluate temperatures that allow persistence of TCoV in the environment. Two series of aliquots of a suspension of a French isolate of TCoV (Fr TCoV) were stored at room temperature or +4°C for 0 to 40 days. As TCoV does not grow in cell culture, the presence of residual infectious TCoV in the stored samples was tested by inoculating embryonated specific pathogen free turkey eggs. As TCoV does not induce lesions in the embryo, virus replication in the jejunum and ileum of the embryos was detected 4 days post inoculation, using RNA extraction and a real-time reverse transcriptase-polymerase chain reaction based on the nucleocapsid gene. No surviving virus was detected after 10 days storage at +21.6±1.4°C or after 40 days storage at +4.1±1.6°C, these temperatures being representative of the mean summer and winter temperatures, respectively, in the major French poultry-producing region. The relatively short survival of the virus at room temperature should contribute to limited virus survival during summer months. However, infectious virus was still detected after 20 days storage at the cooler temperatures, a finding that suggests prolonged survival of Fr TCoV and easier transmission between poultry farms in a cool environment are possible.

negative: Structural Considerations in the Fitness Landscape of a Virus Viral fitness is determined by replication within hosts and transmission between them. We examine how pleiotropic mutations that have antagonistic effects (i.e., antibody evasion vs. receptor binding) on viral replication within hosts can impact viral immune escape in the host population. When the host population is vaccinated, the virus escapes from passive immunity by mutations in the antibody-binding region on the surface of the target protein. However, the reduced ability of the antibody to bind the virus is often accompanied by a reduced ability of the virus to bind the cell receptor because the antibody-binding region overlaps with the receptor-binding domain (RBD). The types of permitted mutations are limited. To investigate the causal relation between a mutation in a viral genome and adaptive evolution of a viral population, we developed a mathematical model that describes the population dynamics of viruses, antibodies, and normal/infected cells within a host. The coefficients describe the binding affinity between the virus and the induced antibody and that between the virus and its receptor. Our knowledge-based index enables us to estimate the effect of a mutation in a binding region on the binding affinity. Using population genetic theory, we evaluated the probability that a mutant is fixed in a host population. The mutations that can be fixed with high probabilities may determine how long a vaccine remains effective. We simulate the adaptive evolution of coronavirus, the etiological agent of severe acute respiratory syndrome, and show that some of mutations in the RBD may have high fixation probabilities in the vaccinated host population.

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: 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: The COVID-19 Pandemic and its Impact on Plastic Surgery in Europe - An ESPRAS Survey. The present article provides an overview of the current and expected effects of plastic surgery in Europe. It presents the experience of departments for plastic and reconstructive surgery, as evaluated by interviews with members of the Executive Committee (ExCo) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS). The objective of this overview is to summmarise current information in our area of work and to make this accessible to a broad group of readers. As our knowledge is rapidly increasing during the current pandemic, it is evident that we can only provide a snapshot and this will inevitably be incomplete.

negative: Sulforhodamine B and exogenous surfactant effects on alveolar surface tension in acute respiratory distress syndrome models BACKGROUND In the acute respiratory distress syndrome (ARDS), elevated alveolar surface tension, T, may increase ventilation-induced lung injury. Exogenous surfactant therapy has not reduced ARDS mortality. Sulforhodamine B (SRB), which acts with albumin to improve native lung surfactant efficacy, could be an alternative T-lowering therapeutic. We test whether substances suspected of elevating T in ARDS raise T in the lungs – where, unlike in most in vitro tests, the surfactant monolayer is intact – and test the abilities of exogenous surfactant and SRB to reduce T. METHODS In isolated rat lungs, we micropuncture a surface alveolus and instill a solution containing a substance purported to raise T in ARDS: control saline, cell debris, secretory phospholipase A2 (sPLA2), acid or mucins. We test each substance alone; with albumin, to model proteinaceous edema liquid; with albumin and subsequent exogenous surfactant; or with albumin and SRB. We determine T by combining servo-nulling pressure measurement with confocal microscopy, and applying the Laplace relation. RESULTS In the control group, saline, albumin and Infasurf do not alter T; SRB reduces T below normal. With albumin, the experimental substances raise T. With cell debris, surfactant does not alter T; SRB normalizes T. With sPLA2, surfactant normalizes T; SRB reduces T. With acid or mucins, neither surfactant nor SRB alters T. CONCLUSIONS The inability of surfactant to counter cell debris may contribute to the failure of surfactant therapy for ARDS. For non-aspiration ARDS, SRB, which can be delivered intravascularly to target injured lung regions, holds promise as a treatment. Summary In the acute respiratory distress syndrome (ARDS), surface tension, T, is believed to be elevated and surfactant therapy has failed to reduce mortality. Here, we test whether various substances suggested to contribute to elevated T in ARDS in fact raise T in the lungs. And we test the ability of exogenous surfactant and of a potential alternative therapeutic, sulforhodamine B (SRB), to reduce T. We find exogenous surfactant unable to lower T in the presence of cell debris but SRB, which can be administered intravascularly, a candidate for lowering T in non-aspiration ARDS.

negative: PLGA nanoparticle entrapped killed porcine reproductive and respiratory syndrome virus vaccine helps in viral clearance in pigs Abstract Porcine reproductive and respiratory syndrome (PRRS) is a chronic viral disease of pigs, has been posing a huge economic concern to pig industry worldwide. In this study, we developed biodegradable PLGA [poly(d,l-lactide-co-glycolide)] nanoparticle-entrapped killed PRRSV vaccine (Nano-KAg), and administered intranasally to pigs once and evaluated the immune correlates. In Nano-KAg vaccinated homologous virus challenged pigs, complete clearance of viremia was observed in 2 weeks, associated with a significant increase in virus neutralizing titers only in the lungs, compared to both unvaccinated and killed vaccine vaccinated pigs. The lung homogenate and sera of Nano-KAg vaccinated pigs had higher levels of IFN-γ and lower levels of TGF-β than control groups. Restimulation of mononuclear cells isolated from the lungs, blood, BAL, and TBLN of Nano-KAg vaccinated pigs’ secreted significantly increased levels of Th1 cytokines, IFN-γ and IL-12. In addition, higher frequencies of CD3+CD8+, CD4+CD8+, and γδ T cells, and reduced frequency of Foxp3+ T-regulatory cells were observed in Nano-KAg vaccinated pigs. Thus, intranasal delivery of Nano-KAg vaccine may be a suitable strategy to elicit anti-PRRSV immune response required to better clear viremia in pigs.

negative: The December 2019 New Corona Virus (SARS-CoV-2) Outbreak: A Behavioral Infectious Disease Policy Model It is critical to understand the impact of distinct policy interventions to the ongoing December 2019 coronavirus (SARS-CoV-2) pandemic. We develop a flexible behavioral, dynamic, and sectorial epidemic policy model comprising both endogenous virus transmission and public health and citizen responses. Applicable to the full epidemic cycle including resurgence, the model allows exploring the multivariate impact of distinct policy interventions, including general and targeted testing and social contact reduction efforts. Calibrating the model to the early SARS-CoV-2 outbreak at the level of continents, we demonstrate how early, rapid, and extensive buildup of testing and social contact reduction efforts interplay to suppress the outbreak. Next, applying the model within hypothetical contexts we demonstrate how: i) sociodemographic variation in vulnerability to the virus affects overall reported and actual outbreak patterns; ii) feasible timing of deconfinement depends on earlier responses to the outbreak; and, iii) targeted approaches help suppress resurgent outbreaks and their various impacts. Finally, given the importance of broad support of outbreak control efforts, across public health experts, policymakers, volunteers, media, and citizens, we make the model also accessible in the form of a free web-based management flight simulator.

negative: A Study Quantifying the Hand-to-Face Contact Rate and Its Potential Application to Predicting Respiratory Tract Infection A substantial portion of human respiratory tract infection is thought to be transmitted via contaminated hand contact with the mouth, eyes, and/or nostrils. Thus, a key risk factor for infection transmission should be the rate of hand contact with these areas termed target facial membranes. A study was conducted in which 10 subjects were each videotaped for 3 hr while performing office-type work in isolation from other persons. The number of contacts to the eyes, nostrils, and lips was scored during subsequent viewing of the tapes. The total contacts per subject had sample mean x = 47 and sample standard deviation s = 34. The average total contact rate per hour was 15.7. The authors developed a relatively simple algebraic model for estimating the dose of pathogens transferred to target facial membranes during a defined exposure period. The model considers the rate of pathogen transfer to the hands via contact with contaminated environmental surfaces, and the rate of pathogen loss from the hands due to pathogen die-off and transfer from the hands to environmental surfaces and to target facial membranes during touching. The estimation of infection risk due to this dose also is discussed. A hypothetical but plausible example involving influenza A virus transmission is presented to illustrate the model.

negative: Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins During its first month, the recently emerged 2019 Wuhan novel coronavirus (2019-nCoV) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of 2019-nCoV and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan

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: 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: Infection control and pandemic influenza. If an influenza pandemic occurs, the spread of the virus should be reduced for as long as possible while an effective vaccine is produced. Influenza spreads mainly by large respiratory droplets (> 5 microm) depositing onto the mucosal surfaces of the eye, mouth or respiratory tract. Hands are another major means for spread, and are frequently contaminated by droplets. The most effective way to reduce the spread of the virus is with good infection control practices and social distancing. Infection control practices include the use of personal protective equipment (PPE), hand hygiene, and respiratory hygiene and cough etiquette. Infected people should be isolated and spatial separation observed in common areas where infected people may be present. Any practices that create aerosols (eg, nebulisation) should be avoided, unless performed with appropriate precautions, especially with all people in the room wearing appropriate PPE. Now is the time to re-examine all our current practices so that we are better prepared, well practised and have good infection control practices in place for all transmissible respiratory infections.

negative: Reactive Polymer Targeting dsRNA as Universal Virus Detection Platform with Enhanced Sensitivity. Reactive poly(pentafluorophenyl acrylate) (PPFPA) grafted surfaces offer a versatile platform to immobilize biomolecules. Here, we utilize PPFPA grafted surface and double-stranded RNA (dsRNA) recognizing J2 antibody to construct a universal virus detection platform with enhanced sensitivity. PPFPA on silicon substrates are prepared, and surface hydrophilicity is modulated by partial substitution of the pentafluorophenyl units with poly(ethylene glycol). Following dsRNA antibody immobilization, the prepared surfaces can distinguish long dsRNAs from single-stranded RNAs of the same length and short dsRNAs. As long dsRNAs are common byproducts of viral transcription/replication, these surfaces can detect the presence of different kinds of viruses without prior knowledge of their genomic sequences. To increase dsRNA detection sensitivity, a two-step method is devised where the captured dsRNAs are visualized with multiple fluorophore-tagged J2 antibodies. We show that the developed platform can differentiate foreign long dsRNAs from cellular dsRNAs and other biomolecules present in the cell lysate. Moreover, when tested against cells infected with hepatitis A or C viruses, both viruses are successfully detected using a single platform. Our study shows that the developed PPFPA platform immobilized with J2 antibody can serve as a primary diagnostic tool to determine the infection status for a wide range of viruses.

negative: Effects of Three Needling Manipulations of Zusanli (ST 36) on Deqi Sensations and Surface Myoelectricity in Healthy Participants. OBJECTIVE To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations. METHODS Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed. RESULT Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P<0.05, OR>1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P<0.01). CONCLUSIONS The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

negative: Involvement of aminopeptidase N (CD13) in infection of human neural cells by human coronavirus 229E. Attachment to a cell surface receptor can be a major determinant of virus tropism. Previous studies have shown that human respiratory coronavirus HCV-229E uses human aminopeptidase N (hAPN [CD13]) as its cellular receptor for infection of lung fibroblasts. Although human coronaviruses are recognized respiratory pathogens, occasional reports have suggested their possible neurotropism. We have previously shown that human neural cells, including glial cells in primary cultures, are susceptible to human coronavirus infection in vitro (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800-806, 1997). However, the only reported expression of hAPN in the nervous system is at the level of nerve synapses. Therefore, we asked whether hAPN is utilized as a cellular receptor for infection of these human neural cell lines. Using flow cytometry, we were able to show the expression of hAPN on the surfaces of various human neuronal and glial cell lines that are susceptible to HCV-229E infection. An hAPN-specific monoclonal antibody (WM15), but not control antibody, inhibited the attachment of radiolabeled HCV-229E to astrocytic, neuronal, and oligodendrocytic cell lines. A correlation between the apparent amount of cell surface hAPN and the level of virus attachment was observed. Furthermore, the presence of WM15 inhibited virus infection of these cell lines, as detected by indirect immunofluorescence. These results indicate that hAPN (CD13) is expressed on neuronal and glial cell lines in vitro and serves as the receptor for infection by HCV-229E. This further strengthens the neurotropic potential of this human respiratory virus.

negative: Coronaviridae1 The family Coronavirtdae comprises a monogeneric group of 11 viruses which infect vertebrates. The main characteristics of the member viruses are: (i) Morphological: Enveloped pleomorphic particles typically 100 nm in diameter (range 60-220 nm), bearing about 20 nm long club-shaped surface projections, (ii) Structural: A single-stranded infectious molecule of genomic RNA of about (5-7) × 10(6) molecular weight. A phosphorylated nucleocapsid protein [mol.wt. (50-60) × 10(3)] complexed with the genome as a helical ribonucleoprotein; a surface (peplomer) protein, associated with one or two glycosylated polypeptides [mol.wt. (90-180) × 10(3)]; a transmembrane (matrix) protein, associated with one polypeptide which may be glycosylated to different degrees [mol.wt. (20-35) × 10(3)]. (iii) Replicative: Production in infected cells of multiple 3′ coterminal sub genomic mRNAs extending for different lengths in the 5′ direction. Virions bud intracytoplasmically. (iv) Antigenic: 3 major antigens, each corresponding to one class of virion protein, (v) Biological: Predominantly restricted to infection of natural vertebrate hosts by horizontal transmission via the fecal/oral route. Responsible mainly for respiratory and gastrointestinal disorders.

negative: Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted from person to person and, in 2 months, has caused more than 82 000 laboratory-confirmed cases of coronavirus disease 2019 (COVID-19) and 2800 deaths in 46 countries. The total number of cases and deaths has surpassed that of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV). Although both COVID-19 and severe acute respiratory syndrome (SARS) manifest as pneumonia, COVID-19 is associated with apparently more efficient transmission, fewer cases of diarrhoea, increased mental confusion, and a lower crude fatality rate. However, the underlying virus–host interactive characteristics conferring these observations on transmissibility and clinical manifestations of COVID-19 remain unknown. Methods We systematically investigated the cellular susceptibility, species tropism, replication kinetics, and cell damage of SARS-CoV-2 and compared findings with those for SARS-CoV. We compared SARS-CoV-2 and SARS-CoV replication in different cell lines with one-way ANOVA. For the area under the curve comparison between SARS-CoV-2 and SARS-CoV replication in Calu3 (pulmonary) and Caco2 (intestinal) cells, we used Student's t test. We analysed cell damage induced by SARS-CoV-2 and SARS-CoV with one-way ANOVA. Findings SARS-CoV-2 infected and replicated to comparable levels in human Caco2 cells and Calu3 cells over a period of 120 h (p=0·52). By contrast, SARS-CoV infected and replicated more efficiently in Caco2 cells than in Calu3 cells under the same multiplicity of infection (p=0·0098). SARS-CoV-2, but not SARS-CoV, replicated modestly in U251 (neuronal) cells (p=0·036). For animal species cell tropism, both SARS-CoV and SARS-CoV-2 replicated in non-human primate, cat, rabbit, and pig cells. SARS-CoV, but not SARS-CoV-2, infected and replicated in Rhinolophus sinicus bat kidney cells. SARS-CoV-2 consistently induced significantly delayed and milder levels of cell damage than did SARS-CoV in non-human primate cells (VeroE6, p=0·016; FRhK4, p=0·0004). Interpretation As far as we know, our study presents the first quantitative data for tropism, replication kinetics, and cell damage of SARS-CoV-2. These data provide novel insights into the lower incidence of diarrhoea, decreased disease severity, and reduced mortality in patients with COVID-19, with respect to the pathogenesis and high transmissibility of SARS-CoV-2 compared with SARS-CoV. Funding May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Richard Yu and Carol Yu, Michael Seak-Kan Tong, Respiratory Viral Research Foundation, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, The Hong Kong Hainan Commercial Association South China Microbiology Research Fund, The Jessie & George Ho Charitable Foundation, Perfect Shape Medical, The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government, The Theme-Based Research Scheme of the Research Grants Council, Sanming Project of Medicine in Shenzhen, and The High Level-Hospital Program, Health Commission of Guangdong Province, China.

negative: Coronavirus Disease 19 Infection Does Not Result in Acute Kidney Injury: An Analysis of 116 Hospitalized Patients from Wuhan, China BACKGROUND: Whether the patients with coronavirus disease 19 (COVID-19) infected by severe acute respiratory syndrome (SARS)-CoV-2 would commonly develop acute kidney injury (AKI) is an important issue worthy of clinical attention. This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients. METHODS: One hundred sixteen COVID-19-confirmed patients enrolled in this study were hospitalized in the Department of Infectious Diseases, Renmin Hospital of Wuhan University from January 14 to February 13, 2020. The recorded information includes demographic data, medical history, contact history, potential comorbidities, symptoms, signs, laboratory test results, chest computer tomography scans, and treatment measures. SARS-CoV-2 RNA in 53 urine sediments of enrolled patients was detected by real-time reverse transcription-polymerase chain reaction. RESULTS: Twelve (10.8%) patients showed mild increase of blood urea nitrogen or creatinine (<26 μmol/L within 48 h), and 8 (7.2%) patients showed trace or 1+ albuminuria in 111 COVID-19-confirmed patients without chronic kidney disease (CKD). All these patients did not meet the diagnostic criteria of AKI. In addition, 5 patients with CKD who were undergone regular continuous renal replacement therapy (CRRT) before admission were confirmed infection of SARS-CoV-2 and diagnosed as COVID-19. In addition to therapy for COVID-19, CRRT was also applied 3 times weekly during hospitalization for these 5 patients with CKD. In the course of treatment, the renal function indicators showed stable state in all 5 patients with CKD, without exacerbation of CKD, and pulmonary inflammation was gradually absorbed. All 5 patients with CKD were survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without CKD, and 1 patient had a positive for SARS-CoV-2 open reading frame 1ab from 5 cases with CKD. CONCLUSION: AKI was uncommon in COVID-19. SARS-CoV-2 infection does not result in AKI, or aggravate CKD in the COVID-19 patients.

negative: The Evolution and Genetics of Virus Host Shifts Emerging viral diseases are often the product of a host shift, where a pathogen jumps from its original host into a novel species. Phylogenetic studies show that host shifts are a frequent event in the evolution of most pathogens, but why pathogens successfully jump between some host species but not others is only just becoming clear. The susceptibility of potential new hosts can vary enormously, with close relatives of the natural host typically being the most susceptible. Often, pathogens must adapt to successfully infect a novel host, for example by evolving to use different cell surface receptors, to escape the immune response, or to ensure they are transmitted by the new host. In viruses there are often limited molecular solutions to achieve this, and the same sequence changes are often seen each time a virus infects a particular host. These changes may come at a cost to other aspects of the pathogen's fitness, and this may sometimes prevent host shifts from occurring. Here we examine how these evolutionary factors affect patterns of host shifts and disease emergence.

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: Does lopinavir really inhibit SARS-CoV-2?

negative: Airborne Infectious Microorganisms 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 past 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 chapter discusses human viral, bacterial, and fungal diseases transmitted via aerosols. Viral diseases presented are influenza, severe acute respiratory syndrome (SARS), Norwalk-like viruses (NLVs) and 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: Abstracts from the 5th International Conference on Prevention & Infection Control (ICPIC 2019): Geneva, Switzerland. 10-13 September 2019

negative: Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies. IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.

negative: 10th Annual European College of Equine Internal Medicine Congress: 2—4 November, 2017

negative: Outbreak Investigation of COVID-19 Among Residents and Staff of an Independent and Assisted Living Community for Older Adults in Seattle, Washington Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused epidemic spread of coronavirus disease 2019 (COVID-19) in the Seattle, Washington, metropolitan area, with morbidity and mortality concentrated among residents of skilled nursing facilities. The prevalence of COVID-19 among older adults in independent/assisted living is not understood. Objectives: To conduct surveillance for SARS-CoV-2 and describe symptoms of COVID-19 among residents and staff of an independent/assisted living community. Design, Setting, and Participants: In March 2020, public health surveillance of staff and residents was conducted on site at an assisted and independent living residence for older adults in Seattle, Washington, after exposure to 2 residents who were hospitalized with COVID-19. Exposures: Surveillance for SARS-CoV-2 infection in a congregate setting implementing social isolation and infection prevention protocols. Main Outcomes and Measures: SARS-CoV-2 real-time polymerase chain reaction was performed on nasopharyngeal swabs from residents and staff; a symptom questionnaire was completed assessing fever, cough, and other symptoms for the preceding 14 days. Residents were retested for SARS-CoV-2 7 days after initial screening. Results: Testing was performed on 80 residents; 62 were women (77%), with mean age of 86 (range, 69-102) years. SARS-CoV-2 was detected in 3 of 80 residents (3.8%); none felt ill, 1 male resident reported resolved cough and 1 loose stool during the preceding 14 days. Virus was also detected in 2 of 62 staff (3.2%); both were symptomatic. One week later, resident SARS-CoV-2 testing was repeated and 1 new infection detected (asymptomatic). All residents remained in isolation and were clinically stable 14 days after the second test. Conclusions and Relevance: Detection of SARS-CoV-2 in asymptomatic residents highlights challenges in protecting older adults living in congregate settings. In this study, symptom screening failed to identify residents with infections and all 4 residents with SARS-CoV-2 remained asymptomatic after 14 days. Although 1 asymptomatic infection was found on retesting, a widespread facility outbreak was avoided. Compared with skilled nursing settings, in assisted/independent living communities, early surveillance to identify asymptomatic persons among residents and staff, in combination with adherence to recommended preventive strategies, may reduce viral spread.

negative: Introducing special cutaneous “sign” tribute to healthcare workers managing new coronavirus disease (Covid −19)

negative: Assessing Ebola-related web search behaviour: insights and implications from an analytical study of Google Trends-based query volumes BACKGROUND: The 2014 Ebola epidemic in West Africa has attracted public interest worldwide, leading to millions of Ebola-related Internet searches being performed during the period of the epidemic. This study aimed to evaluate and interpret Google search queries for terms related to the Ebola outbreak both at the global level and in all countries where primary cases of Ebola occurred. The study also endeavoured to look at the correlation between the number of overall and weekly web searches and the number of overall and weekly new cases of Ebola. METHODS: Google Trends (GT) was used to explore Internet activity related to Ebola. The study period was from 29 December 2013 to 14 June 2015. Pearson’s correlation was performed to correlate Ebola-related relative search volumes (RSVs) with the number of weekly and overall Ebola cases. Multivariate regression was performed using Ebola-related RSV as a dependent variable, and the overall number of Ebola cases and the Human Development Index were used as predictor variables. RESULTS: The greatest RSV was registered in the three West African countries mainly affected by the Ebola epidemic. The queries varied in the different countries. Both quantitative and qualitative differences between the affected African countries and other Western countries with primary cases were noted, in relation to the different flux volumes and different time courses. In the affected African countries, web query search volumes were mostly concentrated in the capital areas. However, in Western countries, web queries were uniformly distributed over the national territory. In terms of the three countries mainly affected by the Ebola epidemic, the correlation between the number of new weekly cases of Ebola and the weekly GT index varied from weak to moderate. The correlation between the number of Ebola cases registered in all countries during the study period and the GT index was very high. CONCLUSION: Google Trends showed a coarse-grained nature, strongly correlating with global epidemiological data, but was weaker at country level, as it was prone to distortions induced by unbalanced media coverage and the digital divide. Global and local health agencies could usefully exploit GT data to identify disease-related information needs and plan proper communication strategies, particularly in the case of health-threatening events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-015-0090-9) contains supplementary material, which is available to authorized users.

negative: The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August–September 2015). To learn from our experience, we described the critical care response to the outbreak. METHODS: This observational study was conducted at the Intensive Care Department which covered 5 ICUs with 60 single-bedded rooms. We described qualitatively and, as applicable, quantitatively the response of intensive care services to the outbreak. The clinical course and outcomes of healthcare workers (HCWs) who had MERS were noted. RESULTS: Sixty-three MERS patients were admitted to 3 MERS-designated ICUs during the outbreak (peak census = 27 patients on August 25, 2015, and the last new case on September 13, 2015). Most patients had multiorgan failure. Eight HCWs had MERS requiring ICU admission (median stay = 28 days): Seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. The hospital mortality of ICU MERS patients was 63.4 % (0 % for the HCWs). In response to the outbreak, the number of negative-pressure rooms was increased from 14 to 38 rooms in 3 MERS-designated ICUs. Patients were managed with a nurse-to-patient ratio of 1:0.8. Infection prevention practices were intensified. As a surrogate, surface disinfectant and hand hygiene gel consumption increased by ~30 % and 17 N95 masks were used per patient/day on average. Family visits were restricted to 2 h/day. Although most ICU staff expressed concerns about acquiring MERS, all reported to work normally. During the outbreak, 27.0 % of nurses and 18.4 % of physicians working in the MERS-designated ICUs reported upper respiratory symptoms, and were tested for MERS-CoV. Only 2/196 (1.0 %) ICU nurses and 1/80 (1.3 %) physician tested positive, had mild disease and recovered fully. The total sick leave duration was 138 days for nurses and 30 days for physicians. CONCLUSIONS: Our hospital outbreak of MERS resulted in 63 patients requiring organ support and prolonged ICU stay with a high mortality rate. The ICU response required careful facility and staff management and proper infection control and prevention practices.

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.

negative: Susceptible supply limits the role of climate in the COVID-19 pandemic Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios of climate-dependence based on known coronavirus biology. We find that while variations in humidity may be important for endemic infections, during the pandemic stage of an emerging pathogen such as SARS-CoV-2 climate may drive only modest changes to pandemic size and duration. Our results suggest that, in the absence of effective control measures, significant cases in the coming months are likely to occur in more humid (warmer) climates, irrespective of the climate-dependence of transmission and that summer temperatures will not substantially limit pandemic growth.

negative: Immunology of Human Milk and Host Immunity

negative: "Stay Nearby or Get Checked": A Covid-19 Lockdown Exit Strategy This paper repurposes the classic insight from network theory that long-distance connections drive disease propagation into a strategy for controlling a second wave of Covid-19. We simulate a scenario in which a lockdown is first imposed on a population and then partly lifted while long-range transmission is kept at a minimum. Simulated spreading patterns resemble contemporary distributions of Covid-19 across nations, regions, and provinces, providing some model validation. Results suggest that the proposed strategy may significantly flatten a second wave. We also find that post-lockdown flare-ups remain local longer, aiding geographical containment. Public policy may target long ties by heavily focusing medical testing and mobility tracking efforts on traffic and transport. This policy can be communicated to the general public as a simple and reasonable principle: Stay nearby or get checked.