query: what evidence is there related to COVID-19 super spreaders

positive: Transmission routes of Covid-19 virus in the Diamond Princess Cruise ship Background: An outbreak of COVID-19 occurred on the Diamond Princess cruise ship in January and February 2020. We analysed information about cases to infer transmission dynamics and potential modes of transmission. Methods: We collected the daily number of 197 symptomatic cases, and that of the 146 passenger cases in two categories, i.e. those who stayed and did not stay in the same stateroom. We retrieved the quarantine details and the ship's 14-day itinerary. We searched the websites of national/local health authority along the cruise routes and local news using Google for locally confirmed cases associated with the ship. We obtained the design of air conditioning and sewage treatment of the ship from literature. We back-calculated the dates of infection from the epidemic curve and compared with the start of on-board quarantine. Results: Major infections started on Jan 28 and completed by Feb 6 for passengers except those who stayed in the same stateroom with infected individual(s). No other confirmed cases were identified among the disembarked people in Hong Kong except an 80 years old passenger. No confirmed cases were reported in three other stopovers between Jan 27-31 associated with disembarked passengers or visitors from the ship, however two Okinawa taxi drivers became confirmed cases in association with driving the ship passengers. Infection among passengers after Feb 6 was limited to those who stayed in the same stateroom with an infected passenger. Infections in crew members peaked on Feb 7, suggesting significant transmission among crew members after quarantine on Feb 5. Conclusions: We infer that the ship central air conditioning system did not play a role, i.e. the long-range airborne route was absent in the outbreak. Most transmission appears to have occurred through close contact and fomites.

positive: Modelling insights into the COVID-19 pandemic Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was declared a pandemic by the World Health Organization on 11th March, 2020. Response to this pandemic has required extensive collaboration across the scientific community in an attempt to contain the virus and limit further transmission. Mathematical modelling has been at the forefront of these response efforts by: (1) providing initial estimates of the SARS-CoV-2 reproduction rate, R(0) (of approximately 2-3); (2) updating these estimates following intervention implementation (with significantly reduced, often sub-critical, transmission rates); (3) assessing the potential for global spread through predictions of the exportation of COVID-19 before significant case numbers had been reported internationally; and (4) quantifying the severity and burden of COVID-19, indicating that the true infection rates are orders of magnitude greater than estimates based on confirmed case counts alone. In this review, we highlight the critical role played by mathematical modelling to understand COVID-19 thus far, the challenges posed by data availability and uncertainty, and the continuing utility of modelling-based approaches to inform the public health response. †Unless otherwise stated, all bracketed error margins correspond to the 95% credible interval (CrI) for reported estimates.

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

positive: Descriptive study of COVID-19 outbreak among passengers and crew on Diamond Princess cruise ship, Yokohama Port, Japan, 20 January to 9 February 2020. An outbreak of coronavirus disease (COVID-19) occurred on the Diamond Princess cruise ship making an international journey, which led to quarantine of the ship at Yokohama Port, Japan. A suspected COVID-19 case was defined as a passenger or crew member who developed a fever or respiratory symptoms, and a confirmed COVID-19 case had laboratory-confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Between 3 and 9 February 2020, 490 individuals were tested for SARS-CoV-2 and 172 were positive (152 passengers (median age: 70 years; interquartile range (IQR): 64-75; males: 45%) and 20 crew (median age: 40 years; IQR: 35-48.5; males: 80%). Other than the Hong Kong-related index case, symptom onset for the earliest confirmed case was 22 January, 2 days after the cruise ship left port. Attack rates among passengers were similar across the decks, while beverage (3.3%, 2/61) and food service staff (5.7%, 14/245) were most affected. Attack rates tended to increase with age. A comprehensive outbreak response was implemented, including surveillance, provision of essential medical care, food and medicine delivery, isolation, infection prevention and control, sampling and disembarkation.

positive: Summary of the COVID-19 outbreak in Vietnam – Lessons and suggestions

positive: Super-spreading events and contribution to transmission of MERS, SARS, and COVID-19

positive: Risk of Transmission of infection to Healthcare Workers delivering Supportive Care for Coronavirus Pneumonia;A Rapid GRADE Review Abstract Background: Avenues of treatment currently implemented for Covid-19 pandemic are largely supportive in nature. Non -availability of an effective antiviral treatment makes supportive care for acute hypoxic respiratory failure is the most crucial intervention. Highly contagious nature of Covid-19 had created stress and confusion among front line Health Care Workers (HCWs) regarding infectious risk of supportive interventions and best preventive strategies. Purpose: To analyze and summarize key evidence from published literature exploring the risk of transmission of Covid-19 related to common supportive care interventions in hospitalized patients and effectiveness of currently used preventive measures in hospital setting. Data Sources: Curated Covid-19 literature from NCBI Computational Biology Branch ,Embase and Ovid till May 20,2020.Longitudinal and reference search till June 28,2020 Study Selection: Studies pertaining to risk of infection to HCWs providing standard supportive care of hospitalized Covid-19 mainly focusing on respiratory support interventions.Indirect studies from SARS,MERS or other ARDS pathology caused by infectious agents based on reference tracking and snow ball search . Clinical, Healthy volunteer and mechanistic studies were included. Two authors independently screened studies for traditional respiratory supportive-care (Hypoxia management, ventilatory support and pulmonary toileting) related transmission of viral or bacterial pneumonia to HCWs. Data Extraction: Two authors (TK and SP) independently screened articles and verified for consensus. Quality of studies and level of evidence was assessed using Oxford Center for Evidence Based Medicine (OCEBM) , Newcastle - Ottawa quality assessment Scale for observational studies and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for grading evidence. Data Synthesis: 21 studies were eligible for inclusion. In 11 mechanistic studies, 7 were manikin based,1 was in the setting of GNB pneumonia ,2 were healthy volunteer study and 1 was heterogenous setting.Out of 10 clinical studies ,5 were case controlled and 6 were cohort studies. Risk of corona virus transmission was significantly high in HCWs performing or assisting endotracheal intubation or contact with respiratory secretion.(Moderate certainty evidence, GRADE B) Safety of nebulization treatment in corona virus pneumonia patients are questionable(Low certainty evidence, GRADE C).Very low certainty evidence exist for risk of transmission with conventional HFNC (GRADE D) and NIV (GRADE D),CPR (GRADE D),Bag and mask ventilation(GRADE D).Moderate certainty evidence exist for protective effect of wearing a multilayered mask, gown , eye protection and formal training for PPE use (GRADE B).Low certainty evidence exist for transmission risk with bag and mask ventilation, suctioning before and after intubation and prolonged exposure (GRADE C).Certainty of evidence for wearing gloves,post exposure hand washing and wearing N 95 mask is low(GRADE C). Limitations: This study was limited to articles with English abstract. Highly dynamic nature of body of literature related to Covid-19, frequent updates were necessary even during preparation of manuscript and longitudinal search was continued even after finalizing initial search. Due to the heterogeneity and broad nature of the search protocol, quantitative comparisons regarding the effectiveness of included management strategies could not be performed. Direct evidence was limited due to poor quality and non-comparative nature of available Covid-19 reporting. Conclusions: Major risk factors for transmission of corona virus infection were, performing or assisting endotracheal intubation and contact with respiratory secretion. Risk of transmission with HFNC or NIV can be significantly decreased by helmet interface, modified exhalation circuit or placing a properly fitting face mask over patient interface of HFNC. Evidence for risk of transmission with CPR, suctioning before or after intubation or bag and mask ventilation of very low certainty. Significant protective factors are Formal training for PPE use, consistently wearing mask, gown and eye protection. Primary Funding Source: None Disclosure: None of the authors have any conflict of interest to disclose.

positive: From severe acute respiratory syndrome-associated coronavirus to 2019 novel coronavirus outbreak: similarities in the early epidemics and prediction of future trends

positive: Alternating quarantine for sustainable mitigation of COVID-19 Lacking a drug or vaccine, the current strategy to contain the COVID-19 pandemic is by means of social distancing, specifically mobility restrictions and lock-downs. Such measures impose a hurtful toll on the economy, and are difficult to sustain for extended periods. The challenge is that selective isolation of the symptomatic patients is insufficient to control SARS-CoV-2, due to its relatively long incubation period, in which individuals experience no symptoms, but may already contribute to the spread. How then do we isolate these \textit{invisible} pre-symptomatic spreaders? Here we propose an alternating quarantine strategy, in which at every instance, half of the population remains under lock-down while the other half continues to be active, maintaining a routine of weekly succession between activity and quarantine. Under this regime, if an individual was exposed during their active week, by the time they complete their quarantine they will, in most cases, begin to exhibit symptoms. Hence this strategy isolates the majority of pre-symptomatic individuals during their infectious phase, leading to a rapid decline in the viral spread - all while sustaining a continuously active economy at $50\%$ capacity.

positive: Super spreader cohorts and covid-19 A simple two-cohort SIR like model can explain the qualitative behaviour of the logarithmic derivative estimations of the covid-19 epidemic evolution as observed in several countries. The model consists of a general population in which the R_0 value is slightly below 1, but in which a super-spreading small subgroup with high R_0, coupled to the general population, is contaminating a significant fraction of the population. The epidemic starts to slow down when herd immunity is reached in this subgroup. The dynamics of this system is quite robust against non-pharmaceutical measures.

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

positive: Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan and Singapore Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine if an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R0) and the dispersion factor (k) from empirical data on clusters of epidemiologically-linked COVID-19 cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.

positive: Infectious Disease in Wild Animal Populations: Examining Transmission and Control with Mathematical Models The mathematical modeling of ecological interactions is an essential tool in predicting the behavior of complex systems across landscapes. The scientific literature is growing with examples of models used to explore predator-prey interactions, resource selection, population growth, and dynamics of disease transmission. These models provide managers with an efficient alternative means of testing new management and control strategies without resorting to empirical testing that is often costly, time-consuming, and impractical. This chapter presents a review of four types of mathematical models used to understand and predict the spread of infectious diseases in wild animals: compartmental, metapopulation, spatial, and contact network models. Descriptions of each model’s uses and limitations are used to provide a look at the complexities involved in modeling the spread of diseases and the trade-offs that accompany selecting one modeling approach over another. Potential avenues for the improvement and use of these models in future studies are also discussed, as are specific examples of how each type of model has improved our understanding of infectious diseases in populations of wild animals.

positive: Minimising lockdown periods for regional elimination of covid-19 Some nations have the option of pursuing a policy of complete elimination of covid-19 instead of a policy of "flattening the curve" so that the load the dis- ease places on medical facilities is bearable. A policy of elimination requires a rather onerous "lockdown". As the goal of elimination is approached, it is therefore important that there be an informed trade-off between the risk of disease re-emergence and the duration of the "lockdown". Here it is shown that an important factor in assessing this trade-off, is the distribution of secondary cases, not just the expected value of this distribution, R0 . It is shown that a distribution in which "super-spreaders" are more prominent in the epidemiology, allows for an earlier release from "lockdown" with reasonable safety despite some probability of asymptomatic cases. There is some evidence to support such a distribution for covid-19. Analytical calculations and simulations show that once there is only one recognised case in some subregion, release from "lockdown" will be reasonably safe after just one or two further incubation periods.

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

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

positive: Searching for Superspreaders: Identifying Epidemic Patterns Associated with Superspreading Events in Stochastic Models The importance of host transmissibility in disease emergence has been demonstrated in historical and recent pandemics that involve infectious individuals, known as superspreaders, who are capable of transmitting the infection to a large number of susceptible individuals. To investigate the impact of superspreaders on epidemic dynamics, we formulate deterministic and stochastic models that incorporate differences in superspreaders versus nonsuperspreaders. In particular, continuous-time Markov chain models are used to investigate epidemic features associated with the presence of superspreaders in a population. We parameterize the models for two case studies, Middle East respiratory syndrome (MERS) and Ebola. Through mathematical analysis and numerical simulations, we find that the probability of outbreaks increases and time to outbreaks decreases as the prevalence of superspreaders increases in the population. In particular, as disease outbreaks occur more rapidly and more frequently when initiated by superspreaders, our results emphasize the need for expeditious public health interventions.

positive: 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.

positive: Characterizing super-spreading events and age-specific infectivity of COVID-19 transmission in Georgia, USA As the current COVID-19 pandemic continues to impact countries around the globe, refining our understanding of its transmission dynamics and the effectiveness of interventions is imperative. In particular, it is essential to obtain a firmer grasp on the effect of social distancing, potential individual-level heterogeneities in transmission such as age-specific infectivity, and impact of super-spreading. To this end, it is important to exploit multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatio-temporal mechanistic framework to statistically integrate case data with geo-location data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of COVID-19. We analyze reported cases from surveillance data, between March and early May 2020, in five (urban and rural) counties in the State of Georgia USA. We estimate natural history parameters of COVID-19 and infer unobserved quantities including infection times and transmission paths using Bayesian data-augmentation techniques. First, our results show that the overall median reproductive number was 2.88 (with 95% C.I. [1.85, 4.9]) before the state-wide shelter-in-place order issued in early April, and the effective reproductive number was reduced to below 1 about two weeks by the order. Super-spreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in the rural area and increasing importance towards later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases may have directly infected 20% of all infections. We estimate that the infected children and younger adults (<60 years old) may be 2.38 [1.30, 3.51] times more transmissible than infected elderly (>=60), and the former may be the main driver of super-spreading. Through the synthesis of multiple data streams using our transmission modelling framework, our results enforce and improve our understanding of the natural history and transmission dynamics of COVID-19. More importantly, we reveal the roles of age-specific infectivity and characterize systematic variations and associated risk factors of super-spreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.

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

positive: Geographical tracking and mapping of coronavirus disease COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics In December 2019, a new virus (initially called 'Novel Coronavirus 2019-nCoV' and later renamed to SARS-CoV-2) causing severe acute respiratory syndrome (coronavirus disease COVID-19) emerged in Wuhan, Hubei Province, China, and rapidly spread to other parts of China and other countries around the world, despite China's massive efforts to contain the disease within Hubei. As with the original SARS-CoV epidemic of 2002/2003 and with seasonal influenza, geographic information systems and methods, including, among other application possibilities, online real-or near-real-time mapping of disease cases and of social media reactions to disease spread, predictive risk mapping using population travel data, and tracing and mapping super-spreader trajectories and contacts across space and time, are proving indispensable for timely and effective epidemic monitoring and response. This paper offers pointers to, and describes, a range of practical online/mobile GIS and mapping dashboards and applications for tracking the 2019/2020 coronavirus epidemic and associated events as they unfold around the world. Some of these dashboards and applications are receiving data updates in near-real-time (at the time of writing), and one of them is meant for individual users (in China) to check if the app user has had any close contact with a person confirmed or suspected to have been infected with SARS-CoV-2 in the recent past. We also discuss additional ways GIS can support the fight against infectious disease outbreaks and epidemics.

positive: Agent-Based Modeling for Super-Spreading Events: A Case Study of MERS-CoV Transmission Dynamics in the Republic of Korea Super-spreading events have been observed in the transmission dynamics of many infectious diseases. The 2015 MERS-CoV outbreak in the Republic of Korea has also shown super-spreading events with a significantly high level of heterogeneity in generating secondary cases. It becomes critical to understand the mechanism for this high level of heterogeneity to develop effective intervention strategies and preventive plans for future emerging infectious diseases. In this regard, agent-based modeling is a useful tool for incorporating individual heterogeneity into the epidemic model. In the present work, a stochastic agent-based framework is developed in order to understand the underlying mechanism of heterogeneity. Clinical (i.e., an infectivity level) and social or environmental (i.e., a contact level) heterogeneity are modeled. These factors are incorporated in the transmission rate functions under assumptions that super-spreaders have stronger transmission and/or higher links. Our agent-based model has employed real MERS-CoV epidemic features based on the 2015 MERS-CoV epidemiological data. Monte Carlo simulations are carried out under various epidemic scenarios. Our findings highlight the roles of super-spreaders in a high level of heterogeneity, underscoring that the number of contacts combined with a higher level of infectivity are the most critical factors for substantial heterogeneity in generating secondary cases of the 2015 MERS-CoV transmission.

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

positive: A super-spreader of COVID-19 in Ningbo city in China An outbreak of Coronavirus Disease 2019 (COVID-19) has spread rapidly. It is imperative to control the epidemic by understanding the epidemiological feature, preventative quarantine, and effective hygiene measures. In the present study, we report a case of super-spreader who transmitted the disease to over twenty-eight persons in Ningbo, Zhejiang. Identifying and isolated super-spreaders, understanding the reasons behind the efficient transmission ability are important for the control and management of the ongoing COVID-19 pandemic.

positive: Disproportionate incidence of COVID-19 in African Americans correlates with dynamic segregation Socio-economic disparities quite often have a central role in the unfolding of large-scale catastrophic events. One of the most concerning aspects of the ongoing COVID-19 pandemics is that it disproportionately affects people from Black and African American backgrounds creating an unexpected infection gap. Interestingly, the abnormal impact on these ethnic groups seem to be almost uncorrelated with other risk factors, including co-morbidity, poverty, level of education, access to healthcare, residential segregation, and response to cures. A proposed explanation for the observed incidence gap is that people from African American backgrounds are more often employed in low-income service jobs, and are thus more exposed to infection through face-to-face contacts, but the lack of direct data has not allowed to draw strong conclusions in this sense so far. Here we introduce the concept of dynamic segregation, that is the extent to which a given group of people is internally clustered or exposed to other groups, as a result of mobility and commuting habits. By analysing census and mobility data on more than 120 major US cities, we found that the dynamic segregation of African American communities is significantly associated with the weekly excess COVID-19 incidence and mortality in those communities. The results confirm that knowing where people commute to, rather than where they live, is much more relevant for disease modelling.

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: Initial Investigation of Transmission of COVID-19 Among Crew Members During Quarantine of a Cruise Ship - Yokohama, Japan, February 2020. An outbreak of coronavirus disease 2019 (COVID-19) among passengers and crew on a cruise ship led to quarantine of approximately 3,700 passengers and crew that began on February 3, 2020, and lasted for nearly 4 weeks at the Port of Yokohama, Japan (1). By February 9, 20 cases had occurred among the ship's crew members. By the end of quarantine, approximately 700 cases of COVID-19 had been laboratory-confirmed among passengers and crew. This report describes findings from the initial phase of the cruise ship investigation into COVID-19 cases among crew members during February 4-12, 2020.

positive: Accounting for super-spreading gives the basic reproduction number R0 of COVID-19 that is higher than initially estimated Transmission of infectious diseases is characterized by the basic reproduction number R0, a metric used to assess the threat posed by an outbreak and inform proportionate preventive decision-making. Based on individual case reports from the initial stage of the coronavirus disease 2019 epidemic, R0 is often estimated to range between 2 and 4. In this report, we show that a SEIR model that properly accounts for the distribution of the incubation period suggests that R0 lie in the range 4.4 - 11.7. This estimate is based on the doubling time observed in the near-exponential phases of the epidemic spread in China, United States, and six European countries. To support our empirical estimation, we analyze stochastic trajectories of the SEIR model showing that in the presence of super-spreaders the calculations based on individual cases reported during the initial phase of the outbreak systematically overestimate the doubling time and thus underestimate the actual value of R0.

positive: Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.

positive: Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI: 0.54–0.84) and 0.25 (95% CI: 0.13–0.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.

positive: The prominence of asymptomatic superspreaders in transmission mean universal face masking should be part of COVID-19 de-escalation strategies

positive: MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease Super-spreading occurs when a single patient infects a disproportionate number of contacts. The 2015 MERS-CoV, 2003 SARS-CoV, and to a lesser extent 2014–15 Ebola virus outbreaks were driven by super-spreaders. We summarize documented super-spreading in these outbreaks, explore contributing factors, and suggest studies to better understand super-spreading.

positive: Assessment of Lockdown Effect in Some States and Overall India: A Predictive Mathematical Study on COVID-19 Outbreak In the absence of neither an effective treatment or vaccine and with an incomplete understanding of the epidemiological cycle, Govt. has implemented a nationwide lockdown to reduce COVID-19 transmission in India. To study the effect of social distancing measure, we considered a new mathematical model on COVID-19 that incorporates lockdown effect. By validating our model to the data on notified cases from five different states and overall India, we estimated several epidemiologically important parameters as well as the basic reproduction number (R(0)). Combining the mechanistic mathematical model with different statistical forecast models, we projected notified cases in the six locations for the period May 17, 2020, till May 31, 2020. A global sensitivity analysis is carried out to determine the correlation of two epidemiologically measurable parameters on the lockdown effect and also on R(0). Our result suggests that lockdown will be effective in those locations where a higher percentage of symptomatic infection exists in the population. Furthermore, a large scale COVID-19 mass testing is required to reduce community infection. Ensemble model forecast suggested a high rise in the COVID-19 notified cases in most of the locations in the coming days. Furthermore, the trend of the effective reproduction number (R(t)) during the projection period indicates if the lockdown measures are completely removed after May 17, 2020, a high spike in notified cases may be seen in those locations. Finally, combining our results, we provided an effective lockdown policy to reduce future COVID-19 transmission in India.

positive: Potential of large “first generation” human‐to‐human transmission of 2019‐nCoV To investigate the genetic diversity, time origin, and evolutionary history of the 2019‐nCoV outbreak in China and Thailand, a total of 12 genome sequences of the virus with known sampling date (24 December 2019 and 13 January 2020) and geographic location (primarily Wuhan city, Hubei Province, China, but also Bangkok, Thailand) were analyzed. Phylogenetic and likelihood‐mapping analyses of these genome sequences were performed. On the basis of our results, the star‐like signal and topology of 2019‐nCoV may be indicative of potentially large “first generation” human‐to‐human virus transmission. We estimated that 2019‐nCoV likely originated in Wuhan on 9 November 2019 (95% credible interval: 25 September 2019 and 19 December 2019), and that Wuhan is the major hub for the spread of the 2019‐nCoV outbreak in China and elsewhere. Our results could be useful for designing effective prevention strategies for 2019‐nCoV in China and beyond.

positive: Do we have enough evidence how seasonal influenza is transmitted and can be prevented in hospitals to implement a comprehensive policy? PURPOSE: To identify if there is enough evidence at low risk-of-bias to prevent influenza transmission by vaccinating health-care workers (HCWs), patients and visitors; screening for laboratory-proven influenza all entering hospitals; screening asymptomatic individuals; identifying influenza supershedders; hand-washing and mask-wearing by HCWs, patients and visitors; and cleaning hospital rooms and equipment. PRINCIPAL RESULTS: Vaccination reduces influenza episodes of vaccinated (4.81/100 HCW) compared to unvaccinated (7.54/100) HCWs/influenza season. A Cochrane review found for inactivated vaccines the Number Needed to Vaccinate (NNV) = 71 (95%CI 64%, 80%) for adults 18–60 (same age as HCWs) to prevent laboratory-proven influenza. There are no RCTs of screening HCWs, patients, visitors and influenza supershedders to prevent transmission. None of four RCTs of HCWs mask-wearing (two directly observed, two not) showed an effect because they were underpowered either due to small size or low circulation of influenza. Hospital rooms and equipment can effectively be cleaned of influenza by many chemicals and hydrogen peroxide vapor machines but the cleaning cycle needs shortening to increase the likelihood of adoption. MAJOR CONCLUSIONS: HCW vaccination is a partial solution with current vaccination levels. There are no RCTs of screening HCWs, patients and visitors demonstrating preventing influenza transmission. Only one study costed furloughing HCWs with influenza and no RCTs have identified benefits of isolating influenza supershedders. RCTs of directly- and electronically continuously-observed mask-wearing and hand-hygiene and RCTs of incentives for meticulous hygiene are required. RCTs of engineering solutions (external venting, frequent room air changes) are needed. A wide range of chemicals effectively cleans hospital rooms and equipment from influenza. Hydrogen peroxide vapor is effective against influenza and a wide range of bacterial pathogens with patient room changes, and clean areas cleaners do not clean but its cleaning cycle needs shortening to increase the likelihood of adoption of cleaning rooms vacated by influenza patients.

positive: Editorial: Herd mentality, herds of migrants/people, and COVID-19 in India

positive: Estimation of Infection Rate and Prediction of Initial Infected Individuals of COVID-19 We consider the pandemic spreading of COVID-19 for some selected countries after the outbreak of the coronavirus in Wuhan City, China. We estimated the infection rate and the initial infected individuals of COVID-19 by using the officially reported data at the early stage of the epidemic for the susceptible (S), infectable (I), quarantined (Q), and the cofirmed recovered (Rk) population model, so called SIQRk model. In the reported data we know the quarantined cases and the recovered cases. We can not know the recovered cases from the asymptomatic cases. In the SIQRk model we can estimated the model parameters and the initial infecting cases (confirmed ans asymtomatic cases) from the data fits. We obtained the infection rate in the range between 0.233 and 0.462, the basic reproduction number Ro in the range between 1.8 and 3.5, and the initial number of infected individuals in the range betwee 10 and 8409 for some selected countries. By using fitting parameters we estimated the maximum time of the infection for Germany when the government are performing the quarantine policy. The disease is undergoing to the calm state about six months after first patients were identified.

positive: Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries. A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.

positive: Reconstruction of Transmission Pairs for novel Coronavirus Disease 2019 (COVID-19) in mainland China: Estimation of Super-spreading Events, Serial Interval, and Hazard of Infection BACKGROUND: Knowledge on the epidemiological features and transmission patterns of COVID-19 is accumulating. Detailed line-list data with household settings can advance the understanding of COVID-19 transmission dynamics. METHODS: A unique database with detailed demographic characteristics, travel history, social relationships, and epidemiological timelines for 1,407 transmission pairs that formed 643 transmission clusters in mainland China was reconstructed from 9,120 COVID-19 confirmed cases reported during January 15 - February 29, 2020. Statistical model fittings were used to identify the super-spreaders and estimate serial interval distributions. Age and gender-stratified hazard of infection were estimated for household versus non-household transmissions. RESULTS: There were 34 primary cases identified as super-spreaders, with 5 super-spreading events occurred within households. Mean and standard deviation of serial intervals were estimated as 5.0 (95% CrI: 4.4, 5.5) and 5.2 (95% CrI: 4.9, 5.7) days for household transmissions and 5.2 (95% CrI: 4.6, 5.8) and 5.3 (95% CrI: 4.9, 5.7) days for non-household transmissions, respectively. Hazard of being infected outside of households is higher for age between 18 and 64 years, whereas hazard of being infected within households is higher for young and old people. CONCLUSIONS: Non-negligible frequency of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of working age indicate a significant barrier to the identification and management of COVID-19 cases, which requires enhanced non-pharmaceutical interventions to mitigate this pandemic.

positive: Identifying Influential Spreaders On a Weighted Network Using HookeRank Method Influence maximization is a significant research problem that requires the selection of influential users who are capable of spreading information in the network such that it can reach to a large number of people. Many real-world networks like Road Network, Email Networks are weighted networks. Influence maximization on weighted networks is more challenging than an unweighted network. Many methods, such as weighted-degree rank, weighted-voteRank, weighted-eigenvalue rank, and weighted-betweenness rank methods, have been used to rank the nodes in weighted networks with certain limitations. In this manuscript, we propose a Hooke’s law-based approach named HookeRank method to identify spreaders in a weighted network. We model edge weights as spring constants. The edges present in the network are modeled as springs, which are connected in series and parallel. They elongate by a distance under the effect of a given constant force following Hooke’s law of elasticity, and this is the equivalent propagation distance between nodes in the network. The proposed the model finds relevant influential nodes, that can propagate the information to other nodes. A higher HookeRank score implies the greater influential capability of the node in the network. We compared our proposed algorithm with state-of-the-art models and found that it performs reasonably well on real-life data-sets using epidemic spreading Susceptible-Infected-Recovered model.

positive: Identifying and Interrupting Superspreading Events—Implications for Control of Severe Acute Respiratory Syndrome Coronavirus 2 It appears inevitable that severe acute respiratory syndrome coronavirus 2 will continue to spread. Although we still have limited information on the epidemiology of this virus, there have been multiple reports of superspreading events (SSEs), which are associated with both explosive growth early in an outbreak and sustained transmission in later stages. Although SSEs appear to be difficult to predict and therefore difficult to prevent, core public health actions can prevent and reduce the number and impact of SSEs. To prevent and control of SSEs, speed is essential. Prevention and mitigation of SSEs depends, first and foremost, on quickly recognizing and understanding these events, particularly within healthcare settings. Better understanding transmission dynamics associated with SSEs, identifying and mitigating high-risk settings, strict adherence to healthcare infection prevention and control measures, and timely implementation of nonpharmaceutical interventions can help prevent and control severe acute respiratory syndrome coronavirus 2, as well as future infectious disease outbreaks.

positive: [Investigation of transmission chain of a cluster COVID-19 cases]. Objective: To analyze of the transmission characteristics of a cluster of COVID-19 cases in Chongqing and evaluate the infectivity of COVID-19 in the incubation period. Methods: A retrospective survey was conducted by using unified questionnaire through field and telephone interviews among 129 close contacts of COVID-19 cases. The relationship of transmission was indicated by transmission chain, and the infectivity was analyzed by the contact history. Results: This cluster of COVID-19 cases occurred after a classmate party involving members in three families and work fellows in a factory (R(0)=3.8). The infection rate during the incubation period was 17.57%. On average, it was infectious three days before onset. There was significant difference in infection rate among different contact modes (χ(2)=15.10, P<0.01),There was significant difference in infection rate among single exposureswith different time length ( χ(2)=25.08, P<0.01). Conclusions: COVID-19 is highly infectious in the incubation period. The more confined the space is, the higher the risk is,and the longer the single exposure is, the higher the risk of transmission is. Indirect contact transmission still exists.

positive: Short communication: Low risk of transmission of severe acute respiratory syndrome on airplanes: the Singapore experience The risk of transmission of severe acute respiratory syndrome (SARS) on airplanes is of major concern to the public and airline industry. We examined data from flights to Singapore with SARS patients on board in order to assess this risk. In‐flight transmission occurred only in one of the three flights with symptomatic SARS patients on board. The incidence was estimated to be 1 out of 156 passengers. The risk of in‐flight transmission of SARS appears to be far lower than that reported for influenza, but may be increased with superspreaders on board.

positive: Do superspreaders generate new superspreaders? a hypothesis to explain the propagation pattern of COVID-19 Abstract The current global propagation of COVID-19 is heterogeneous, with slow transmission continuing in many countries, and exponential propagation in others, in which the time that took to begin this explosive spread varies greatly. It is proposed that this could be explained by cascading superspreading events, in which new infections caused by a superspreader are more likely to be highly infectious. The mechanism suggested for this is related to viral loads. Exposure to high viral loads may result in infections of high intensity, which exposes new cases to high viral loads, and so on. This notion is supported by experimental veterinary research.

positive: Modeling Super-spreading Events for Infectious Diseases: Case Study SARS Super-spreading events for infectious diseases occur when some infected individuals infect more than the average number of secondary cases. Several super-spreading individuals have been identified for the 2003 outbreak of severe acute respiratory syndrome (SARS). We develop a model for super-spreading events of infectious diseases, which is based on the outbreak of SARS. Using this model we describe two methods for estimating the parameters of the model, which we demonstrate with the small-scale SARS outbreak at the Amoy Gardens, Hong Kong, and the large-scale outbreak in the entire Hong Kong Special Administrative Region. One method is based on parameters calculated for the classical susceptible - infected - removed (SIR) disease model. The second is based on parameter estimates found in the literature. Using the parameters calculated for the SIR model, our model predicts an outcome similar to that for the SIR model. On the other hand, using parameter estimates from SARS literature our model predicts a much more serious epidemic.

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

positive: Relationship between perception and anxiety about COVID-19 infection and risk behaviors for spreading infection: A national survey in Japan BACKGROUND: The novel corona virus infection (COVID-19) quickly became a pandemic state. Identifying characteristics of “possible super spreaders”, suggested as a dominant cause of rapid spreading transmission, will help us to design proper prevention strategies. METHODS: We conducted a nation-wide online survey to investigate the relationship of perception and anxiety levels about COVID-19 to the possible risk behaviors for spread of the virus in Japan. We recruited a total of 4,000 citizens, who responded to the questionnaire including several questions regarding the level of fear and anxiety about COVID-19, infection preventive behaviors and access to media with trust level about the virus as well as some demographic and socioeconomic data during March 27th and 28th, 2020. FINDINGS: Thirteen-point-three percent of the participants rated “1” on a nine-point Likert with respect to the knowledge about COVID-19. Ten-point-one percent and 11.7% presented no anxiety of being infected and transmission to others. Ten-point-eight percent showed no worry about symptomatic aggravation. Eight-point-one percent had no serious concern about expanding infection. The distribution of these items was highly correlated with each other. Participants with the low level of knowledge about COVID-19 were likely to less frequently access any information sources and neither trust them. They were less anxious about their health status, and less likely to put precautionary behaviors such as washing hands and avoiding crowded spaces, suggested by statistical analyses. INTERPRETATION: The present study suggests that it is greatly important to enlighten those have no concerns about this crisis of COVID-19 and modify their risk behavior via various ways, in order to prevent and control this viral pandemic. FUNDING: This study was funded by the management grand provided to Chiba University Graduate School of Medicine and the Japan Society for the Promotion of Science KAKENHI grants.

positive: Evolving Transmission Network Dynamics of COVID-19 Cluster Infections in South Korea: a descriptive study Background. Extensive contact tracing and testing in South Korea allows us to investigate the transmission dynamics of the COVID-19 into diverse local communities. Objective. Understand the critical aspects of transmission dynamics in a different age, sex, and clusters with various activities. Methods. We conducted a retrospective observational study with 3,127 confirmed cases' contact tracing data from the Center for Disease and Prevention (CDC) of South Korea. We investigated network property concerning infected persons' demographics and different infection clusters. Findings. Overall, women had higher centrality scores than men after week four, when the confirmed cases rapidly increased. Older adults have higher centrality than young/middle-aged adults after week 9. In the infection clusters, young/middle-aged adults' infection clusters (such as religious gatherings and gym facilities) have higher average path lengths and diameter than older adults' nursing home infection clusters. Interpretation. Some women had higher reproduction numbers and bridged successive transmission than men when the confirmed cases rapidly increased. Similarly, some older adults (who were not residents of nursing homes) had higher reproduction numbers and bridged successive transmission than young/middle-aged adults after the peak has passed. The young/middle-aged adults' religious gatherings and group workout have caused long successive transmissions. In contrast, the older adults' nursing homes were a small world where the transmissions within a few steps can reach out to many persons.

positive: Stochastic and spatio-temporal analysis of the Middle East Respiratory Syndrome outbreak in South Korea, 2015 South Korea was free of the Middle East Respiratory Syndrome (MERS) until 2015. The MERS outbreak in South Korea during 2015 was the largest outbreak of the Coronavirus outside the Middle East. The major characteristic of this outbreak is inter- or intra-hospital transmission. This recent MERS outbreak in South Korea is examined and assessed in this paper. The main objectives of the study is to characterize the pattern of the MERS outbreak in South Korea based on a basic reproductive ratio, the probability of ultimate extinction of the disease, and the spatio-temporal proximity of occurrence between patients. The survival function method and stochastic branching process model are adapted to calculate the basic reproductive ratio and the probability of ultimate extinction of the disease. We further investigate the occurrence pattern of the outbreak using a spatio-temporal autocorrelation function.

positive: Risk assessment of airborne transmission of COVID-19 by asymptomatic individuals under different practical settings The lack of quantitative risk assessment of airborne transmission of COVID-19 under practical settings leads to large uncertainties and inconsistencies in our preventive measures. Combining in situ measurements and numerical simulations, we quantify the exhaled aerosols from normal respiratory behaviors and their transport under elevator, small classroom and supermarket settings to evaluate the risk of inhaling potentially virus-containing aerosols. Our results show that the design of ventilation is critical for reducing the risk of aerosol encounters. Inappropriate design can significantly limit the efficiency of aerosol removal, create local hot spots with orders of magnitude higher risks, and enhance aerosol deposition causing surface contamination. Additionally, our measurements reveal the presence of substantial fraction of crystalline aerosols from normal breathing and its strong correlation with breathing depth.

positive: Key Questions for Modelling COVID-19 Exit Strategies Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced in countries worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement lockdown exit strategies that allow restrictions to be relaxed while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute Models for an exit strategy workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, will allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. The roadmap requires a global collaborative effort from the scientific community and policy-makers, and is made up of three parts: i. improve estimation of key epidemiological parameters; ii. understand sources of heterogeneity in populations; iii. focus on requirements for data collection, particularly in Low-to-Middle-Income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.

positive: From superspreaders to disease hotspots: linking transmission across hosts and space Since the identification and imprisonment of “Typhoid Mary,” a woman who infected at least 47 people with typhoid in the early 1900s, epidemiologists have recognized that ‘superspreading’ hosts play a key role in disease epidemics. Such variability in transmission also exists among species within a community (amplification hosts) and among habitat patches across a landscape (disease ‘hotspots’), underscoring the need for an integrative framework for studying transmission heterogeneity. Here, we synthesize literature on human, plant, and animal diseases to evaluate the relative contributions of host, pathogen, and environmental factors in driving transmission heterogeneity across hosts and space. We show that host and spatial heterogeneity are closely linked and that quantitatively assessing the contribution of infectious individuals, species, or environmental patches to overall transmission can aid management strategies. We conclude by posing hypotheses regarding how pathogen natural history influences transmission heterogeneity and highlight emerging frontiers in the study of transmission heterogeneity.

positive: Modeling COVID-19 Epidemic in Heilongjiang Province, China The Coronavirus Disease 2019 (COVID-19) surges worldwide. However, massive imported patients especially into Heilongjiang Province in China recently have been an alert for local COVID-19 outbreak. We collected data from January 23 to March 25 from Heilongjiang province and trained an ordinary differential equation model to fit the epidemic data. We extended the simulation using this trained model to characterize the effect of an imported ‘escaper’. We showed that an imported ‘escaper’ was responsible for the newly confirmed COVID-19 infections from Apr 9 to Apr 19 in Heilongjiang province. Stochastic simulations further showed that significantly increased local contacts among imported ‘escaper’, its epidemiologically associated cases and susceptible populations greatly contributed to the local outbreak of COVID-19. Meanwhile, we further found that the reported number of asymptomatic patients was markedly lower than model predictions implying a large asymptomatic pool which was not identified. We further forecasted the effect of implementing strong interventions immediately to impede COVID-19 outbreak for Heilongjiang province. Implementation of stronger interventions to lower mutual contacts could accelerate the complete recovery from coronavirus infections in Heilongjiang province. Collectively, our model has characterized the epidemic of COVID-19 in Heilongjiang province and implied that strongly controlled measured should be taken for infected and asymptomatic patients to minimize total infections.

positive: Modeling COVID-19 on a network: super-spreaders, testing and containment We use a model of covid-19 spread, an SEIR agent-based model on a graph, which takes into account several important real-life attributes of covid-19: Super-spreaders, realistic epidemiological parameters of the disease, testing and quarantine policies. We provide simulation results and mathematical arguments to argue that certain results of our simulations hold in more general settings. We find that mass-testing is much less effective than testing the symptomatic and contact tracing, and some blend of these with social distancing is required to get suppression. We also find that the fat tail of the degree distribution matters a lot for epidemic growth, and many standard models do not account for this. Additionally, the average reproduction number for individuals is not an upper bound for the effective reproduction number, R. Even with an expectation of less than one new case per person, this model shows that exponential spread is possible. The parameter which closely predicts growth rate is the ratio between 2nd to 1st moments of the degree distribution.

positive: SARS-CoV and Emergent Coronaviruses: Viral Determinants of Interspecies Transmission Most new emerging viruses are derived from strains circulating in zoonotic reservoirs. Coronaviruses, which had an established potential for cross-species transmission within domesticated animals, suddenly became relevant with the unexpected emergence of the highly pathogenic human SARS-CoV strain from zoonotic reservoirs in 2002. SARS-CoV infected approximately 8000 people worldwide before public health measures halted the epidemic. Supported by robust time-ordered sequence variation, structural biology, well-characterized patient pools, and biological data, the emergence of SARS-CoV represents one of the best studied natural models of viral disease emergence from zoonotic sources. This review article summarizes previous and more recent advances into the molecular and structural characteristics, with particular emphasis on host-receptor interactions, that drove this remarkable virus disease outbreak in human populations.

positive: Importance of Interaction Structure and Stochasticity for Epidemic Spreading: A COVID-19 Case Study In the recent COVID-19 pandemic, computer simulations are used to predict the evolution of the virus propagation and to evaluate the prospective effectiveness of non-pharmaceutical interventions. As such, the corresponding mathematical models and their simulations are central tools to guide political decision-making. Typically, ODE-based models are considered, in which fractions of infected and healthy individuals change deterministically and continuously over time. In this work, we translate an ODE-based COVID-19 spreading model from literature to a stochastic multi-agent system and use a contact network to mimic complex interaction structures. We observe a large dependency of the epidemic's dynamics on the structure of the underlying contact graph, which is not adequately captured by existing ODE-models. For instance, existence of super-spreaders leads to a higher infection peak but a lower death toll compared to interaction structures without super-spreaders. Overall, we observe that the interaction structure has a crucial impact on the spreading dynamics, which exceeds the effects of other parameters such as the basic reproduction number R0. We conclude that deterministic models fitted to COVID-19 outbreak data have limited predictive power or may even lead to wrong conclusions while stochastic models taking interaction structure into account offer different and probably more realistic epidemiological insights.

positive: Super-Spreader Businesses and Risk of COVID-19 Transmission Purpose: The United States has the highest number of confirmed COVID-19 cases in the world to date, with over 94,000 COVID-19-related deaths. The true risk of a COVID-19 resurgence as states prepare to reopen businesses is unknown. This paper aims to classify businesses by their risk of transmission and quantify the relationship between the density of super-spreader businesses and COVID-19 cases. Methods: We constructed a COVID-19 Business Transmission Risk Index based upon the frequency and duration of visits and square footage of businesses pre-pandemic in 2019 in 8 states (Massachusetts, Rhode Island, Connecticut, New Hampshire, Vermont, Maine, New York, and California). We used this index to classify businesses as super-spreaders. Then, we analyzed the association between the density of super-spreader businesses in a county and the rate of COVID-19 cases. We performed significance testing using a negative binomial regression. The main outcome of interest is the cumulative number of COVID-19 cases each week. Results: We found a positive association between the density of super-spreader businesses and COVID-19 cases. A 1 percentage point increase in the density of super-spreader businesses is associated with 5% higher COVID-19 cases, all else equal. Conclusion: Higher densities of super-spreader businesses are associated with higher rates of COVID-19 cases. This may have important implications for how states reopen super-spreader businesses.

positive: Pathogenicity and transmissibility of 2019-nCoV—A quick overview and comparison with other emerging viruses Abstract A zoonotic coronavirus, tentatively labeled as 2019-nCoV by the World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.

positive: Spatial Visualization of Cluster-Specific COVID-19 Transmission Network in South Korea During the Early Epidemic Phase Background Coronavirus disease 2019 (COVID-19) has been rapidly spreading throughout China and other countries including South Korea. As of March 12, 2020, a total number of 7,869 cases and 66 deaths had been documented in South Korea. Although the first confirmed case in South Korea was identified on January 20, 2020, the number of confirmed cases showed a rapid growth on February 19, 2020 with a total number of 1,261 cases with 12 deaths based on the Korea Centers for Disease Control and Prevention (KCDC). Method Using the data of confirmed cases of COVID-19 in South Korea that are publicly available from the KCDC, this paper aims to create spatial visualizations of COVID-19 transmission between January 20, 2020 and February 19, 2020. Results Using spatial visualization, this paper identified two early transmission clusters in South Korea (Daegu cluster and capital area cluster). Using a degree-weighted centrality measure, this paper proposes potential super-spreaders of the virus in the visualized clusters. Conclusion Compared to various epidemiological measures such as the basic reproduction number, spatial visualizations of the cluster-specific transmission networks and the proposed centrality measure may be more useful to characterize super-spreaders and the spread of the virus especially in the early epidemic phase.

positive: Significance of super spreader events in COVID-19 The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.

positive: Understanding the super-spreading events of SARS in Singapore. INTRODUCTION It has been noted that SARS transmission is characterised by a few super-spreading events (SSEs) giving rise to a disproportionate number of secondary cases. Clinical and environmental features surrounding the index cases involved were compared with cases in non- SSEs. MATERIALS AND METHODS Data on 231 cases of probable SARS admitted to Tan Tock Seng Hospital (TTSH) were used. Index cases directly causing 10 or more secondary cases were classified as having been involved in SSEs; all others were defined as non-SSEs. RESULTS Only 5 cases were involved in SSEs; all 5 were isolated on day 5 of illness or later, and spent at least a brief period in a non-isolation ward; in contrast, amongst the 226 non-SSE cases, only 40.7% and 4.0% were isolated late and admitted to non-isolation wards respectively, and only 3.1% had both these environmental features present; the differences were highly significant (P = 0.012, P <0.001 and P <0.001 by Fisher's Exact test). When compared to 7 non-SSE cases with delayed isolation and an admission to non-isolation wards, SSEs were more likely to have co-morbid disease or require ICU care at time of isolation (P = 0.045 for both factors). CONCLUSION SSEs were likely due to a conglomeration of environmental factors of delayed isolation and admission to a non-isolation ward, coupled with severe disease stage at time of isolation.

positive: Integrating behavioral surveillance into emerging infectious disease prevention

positive: The Predictive Capacity of Air Travel Patterns during the Global Spread of the COVID-19 Pandemic: Risk, Uncertainty and Randomness Air travel has a decisive role in the spread of infectious diseases at the global level. We present a methodology applied during the early stages of the COVID-19 pandemic that uses detailed aviation data at the final destination level in order to measure the risk of the disease spreading outside China. The approach proved to be successful in terms of identifying countries with a high risk of infected travellers and as a tool to monitor the evolution of the pandemic in different countries. The high number of undetected or asymptomatic cases of COVID-19, however, limits the capacity of the approach to model the full dynamics. As a result, the risk for countries with a low number of passengers from Hubei province appeared as low. Globalization and international aviation connectivity allow travel times that are much shorter than the incubation period of infectious diseases, a fact that raises the question of how to react in a potential new pandemic.

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

positive: Genomic variations of SARS-CoV-2 suggest multiple outbreak sources of transmission We examined 169 genomes of SARS-CoV-2 and found that they can be classified into two major genotypes, Type I and Type II. Type I can be further divided into Type IA and IB. Our phylogenetic analysis showed that the Type IA resembles the ancestral SARS-CoV-2 most. Type II was likely evolved from Type I and predominant in the infections. Our results suggest that Type II SARS-CoV-2 was the source of the outbreak in the Wuhan Huanan market and it was likely originated from a super-spreader. The outbreak caused by the Type I virus should have occurred somewhere else, because the patients had no direct link to the market. Furthermore, by analyzing three genomic sites that distinguish Type I and Type II strains, we found that synonymous changes at two of the three sites confer higher protein translational efficiencies in Type II strains than in Type I strains, which might explain why Type II strains are predominant, implying that Type II is more contagious (transmissible) than Type I. These findings could be valuable for the current epidemic prevention and control.

positive: Modelling the impact of Plasma Therapy and Immunotherapy for Recovery of COVID-19 Infected Individuals Since the first case of COVID-19 was detected in Wuhan, China in December 2019, COVID-19 has become a pandemic causing a global economic and public health emergency. There is no known treatment or vaccine available for COVID-19 to date. Immunotherapy and plasma therapy has been used with satisfactory efficacy over the past two decades in many viral infections like SARS (Systemic Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome), and H1N1. Limited data from China show clinical benefit, radiological resolution, reduction in viral loads, and improved survival. Our aim is to create a mathematical model for COVID-19 transmission and then apply various control parameters to see their effects on recovery from COVID-19 disease. We have formulated a system of non-linear ordinary differential equations, calculated basic reproduction R0, and applied five different controls (self-isolation, quarantine, herd immunity, immunotherapy, plasma therapy) to test the effectiveness of control strategy. Control optimality was checked by Lagrangian functions. Numerical simulations and bifurcation analyses were carried out. The study concludes that the COVID-19 outbreak can be controlled up to a significant level three weeks after applying all the control strategies together. These strategies lead to a reduction in hospitalization and a rise in recovery from infection. Immunotherapy is highly effective initially in hospitalized infected individuals however better results were seen in the long term with plasma therapy.

positive: 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.

positive: The timing of contact restrictions and pro-active testing balances the socio-economic impact of a lockdown with the control of infections During the SARS-CoV-2 pandemic, numerous mathematical models have been developed. Reporting artefacts and missing data about asymptomatic spreaders, imply considerable margins of uncertainty for model-based predictions. Epidemiological models can however also be used to investigate the consequences of measures to control the pandemic, reflected in changes to parameter values. We present a SIR-based, SUIR model in which the influence of testing and a reduction of contacts is studied by distinguishing 'Unidentified' and 'Identified' spreaders of infections. The model uses four ordinary differential equations and is kept deliberately simple to investigate general patterns occurring from testing and contact restrictions. The model goes beyond other efforts, by introducing time dependent parameter curves that represent different strategies in controlling the pandemic. Our analysis reveals the effect of 'pro-active' testing for the design of contact restriction measures. By pro-active testing we mean testing beyond those people who show symptoms. The simulations can explain why the timing of contract restrictions and pro-active testing is important. The model can also be used to study the consequence of different strategies to exit from lockdown. Our SUIR model is implemented in Python and is made available through a Juypter Notebooks. This an extensive documentation of the derivation and implementation of the model, as well as transparent and reproducible simulation studies. Our model should contribute to a better understanding of the role of testing and contact restrictions.

positive: Clustering model for transmission of the SARS virus: application to epidemic control and risk assessment Abstract We propose a new four state model for disease transmission and illustrate the model with data from the 2003 SARS epidemic in Hong Kong. The critical feature of this model is that the community is modelled as a small-world network of interconnected nodes. Each node is linked to a fixed number of immediate neighbors and a random number of geographically remote nodes. Transmission can only propagate between linked nodes. This model exhibits two features typical of SARS transmission: geographically localized outbreaks and “super-spreaders”. Neither of these features are evident in standard susceptible-infected-removed models of disease transmission. Our analysis indicates that “super-spreaders” may occur even if the infectiousness of all infected individuals is constant. Moreover, we find that nosocomial transmission in Hong Kong directly contributed to the severity of the outbreak and that by limiting individual exposure time to 3–5 days the extent of the SARS epidemic would have been minimal.

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: Assessing the Global Tendency of COVID-19 Outbreak COVID-19 is now widely spreading around the world as a global pandemic. In this report, we estimate the global tendency of COVID-19 and analyze the associated global epidemic risk, given that the status quo is continued without further measures being taken. The results show that the global R_0, excluding China, is estimated to be 2.49 (95% CI: 2.15 - 2.92). The United States, Germany, Italy and Spain have peak values over 100,000. According to dynamical model and cluster analysis, we category the globe into four type regional epicenters of the outbreak: Southeast Asia extending southward to Oceania, the Middle East, Western Europe and North America. Among them, Western Europe will become the major center of the outbreak. The peak values in Germany, Italy and Spain are estimated to be 105,903, 127,283 and 152,539, respectively. The United States is the country with the most serious outbreak trend. Based on the current control measures by Mar. 27, 2020, the peak value in the United States will reach 400,892. Above all, if the current control measures are maintained, the cumulative number of patients worldwide will be 1,442,523 (95% CI: 1,052,577 - 8,981,440). We also estimated the diagnosis rate, recovery rate and infection degree of each country or region, and use clustering algorithm to retrieve countries or regions with similar epidemic characteristics. Different suggestions are proposed for countries or regions in different clusters.

positive: Diagnosis and Management of First Case of COVID-19 in Canada: Lessons applied from SARS We report diagnosis and management of the first laboratory-confirmed case of coronavirus disease 2019 (COVID-19) hospitalized in Toronto, Canada. No healthcare-associated transmission occurred. In the face of a potential pandemic of COVID-19, we suggest sustainable and scalable control measures developed based on lessons learned from SARS.

positive: Prevalence and fatality rates of COVID-19: What are the reasons for the wide variations worldwide?

positive: Estimating finite-population reproductive numbers in heterogeneous populations Abstract The basic reproductive number, R 0 , is one of the most important epidemiological quantities. R 0 provides a threshold for elimination and determines when a disease can spread or when a disease will die out. Classically, R 0 is calculated assuming an infinite population of identical hosts. Previous work has shown that heterogeneity in the host mixing rate increases R 0 in an infinite population. However, it has been suggested that in a finite population, heterogeneity in the mixing rate may actually decrease the finite-population reproductive numbers. Here, we outline a framework for discussing different types of heterogeneity in disease parameters, and how these affect disease spread and control. We calculate “finite-population reproductive numbers” with different types of heterogeneity, and show that in a finite population, heterogeneity has complicated effects on the reproductive number. We find that simple heterogeneity decreases the finite-population reproductive number, whereas heterogeneity in the intrinsic mixing rate (which affects both infectiousness and susceptibility) increases the finite-population reproductive number when R 0 is small relative to the size of the population and decreases the finite-population reproductive number when R 0 is large relative to the size of the population. Although heterogeneity has complicated effects on the finite-population reproductive numbers, its implications for control are straightforward: when R 0 is large relative to the size of the population, heterogeneity decreases the finite-population reproductive numbers, making disease control or elimination easier than predicted by R 0 .

positive: New approaches to quantifying the spread of infection Recent major disease outbreaks, such as severe acute respiratory syndrome and foot-and-mouth disease in the UK, coupled with fears of emergence of human-to-human transmissible variants of avian influenza, have highlighted the importance of accurate quantification of disease threat when relatively few cases have occurred. Traditional approaches to mathematical modelling of infectious diseases deal most effectively with large outbreaks in large populations. The desire to elucidate the highly variable dynamics of disease spread amongst small numbers of individuals has fuelled the development of models that depend more directly on surveillance and contact-tracing data. This signals a move towards a closer interplay between epidemiological modelling, surveillance and disease-management strategies.

positive: Emergence of Novel Human Infections: New Insights and New Challenges Abstract Novel human infections have continued to emerge over the past decade. Their presentation, epidemiology, and microbiology have shifted the paradigms of traditional science. In particular insights into nongenetic or paragenetic mechanisms (plasmid mediated), modes of infection have challenged biology. In reviewing the new challenges posed by these emergent events, new technologies promise some answers; however, global health security against pandemic threats, particularly given the uneven distribution of global resources for prevention, detection, and response, remains a critical area of challenge.

positive: Predicting Super Spreading Events during the 2003 Severe Acute Respiratory Syndrome Epidemics in Hong Kong and Singapore One of the intriguing characteristics of the 2003 severe acute respiratory syndrome (SARS) epidemics was the occurrence of super spreading events (SSEs). Here, the authors report the results of identifying the occurrence of SSEs in the Hong Kong and Singapore epidemics using mathematical and statistical analysis. Their predicted occurrence of SSEs agreed well with the reported occurrence of all seven super spreaders in the two cities. Additional unidentified SSEs were also found to exist. It was found that 71.1% and 74.8% of the infections were attributable to SSEs in Hong Kong and Singapore, respectively. There also seemed to be “synchronized” occurrences of infection peaks in both the community and the hospitals in Hong Kong. The results strongly suggested that the infection did not depend on the total number of symptomatic cases, with only a very small proportion of symptomatic individuals being shown to be infectious (i.e., able to infect other individuals). The authors found that the daily infection rate did not correlate with the daily total number of symptomatic cases but with the daily number of symptomatic cases who were not admitted to a hospital within 4 days of the onset of symptoms.

positive: Forecasting Covid-19 Outbreak Progression in Italian Regions: A model based on neural network training from Chinese data Background. Epidemiological figures of Covid19 epidemic in Italy are worse than those observed in China. Methods. We modeled the Covid19 outbreak in Italian Regions vs. Lombardy to assess the epidemics progression and predict peaks of new daily infections and total cases by learning from the entire Chinese epidemiological dynamics. We trained an artificial neural network model, a modified auto-encoder with Covid19 Chinese data, to forecast epidemic curve of the different Italian regions, and use the susceptible/exposed/infected/removed (SEIR) compartment model to predict the spreading and peaks. We have estimated the basic reproduction number (R0), which represents the average number of people that can be infected by a person who has already acquired the infection - both by fitting the exponential growth rate of the infection across a one month period, and also by using a day by day assessment, based on single observations. Results. The expected peak of SEIR model for new daily cases was at the end of March at national level. The peak of overall positive cases is expected by April 11th in Southern Italian Regions, a couple of days after that of Lombardy and Northern regions. According to our model, total confirmed cases in all Italy regions could reach 160,000 cases by April 30th and stabilize at a plateau. Conclusions. Training neural networks on Chinese data and use the knowledge to forecast Italian spreading of Covid19 has resulted in a good fit, measured with the mean average precision between official Italian data and the forecast.

positive: Household transmissions of SARS-CoV-2 in the time of unprecedented travel lockdown in China IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, China, in December 2019 and then spread globally. Limited information is available for characterizing epidemiological features and transmission patterns in the regions outside of Hubei Province. Detailed data on transmission at the individual level could be an asset to understand the transmission mechanisms and respective patterns in different settings. OBJECTIVE: To reconstruct infection events and transmission clusters of SARS-CoV-2 for estimating epidemiological characteristics at household and non-household settings, including super-spreading events, serial intervals, age- and gender-stratified risks of infection in China outside of Hubei Province. DESIGN, SETTING, AND PARTICIPANTS: 9,120 confirmed cases reported online by 264 Chinese urban Health Commissions in 27 provinces from January 20 to February 19, 2020. A line-list database is established with detailed information on demographic, social and epidemiological characteristics. The infection events are categorized into the household and non-household settings. EXPOSURES: Confirmed cases of SARS-CoV-2 infections. MAIN OUTCOMES AND MEASURES: Information about demographic characteristics, social relationships, travel history, timelines of potential exposure, symptom onset, confirmation, and hospitalization were extracted from online public reports. 1,407 infection events formed 643 transmission clusters were reconstructed. RESULTS: In total 34 primary cases were identified as super spreaders, and 5 household super-spreading events were observed. The mean serial interval is estimated to be 4.95 days (standard deviation: 5.24 days) and 5.19 days (standard deviation: 5.28 days) for households and non-household transmissions, respectively. The risk of being infected outside of households is higher for age groups between 18 and 64 years, whereas the hazard of being infected within households is higher for age groups of young (<18) and elderly (>65) people. CONCLUSIONS AND RELEVANCE: The identification of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of age between 18 and 64 indicate a significant barrier to the case identification and management, which calls for intensive non-pharmaceutical interventions (e.g. cancellation of public gathering, limited access of public services) as the potential mitigation strategies.

positive: COVID-19: towards controlling of a pandemic

positive: Evidence for probable aerosol transmission of SARS-CoV-2 in a poorly ventilated restaurant Background: The role of aerosols in the transmission of SARS-CoV-2 remains debated. We analysed an outbreak involving three non-associated families in Restaurant X in Guangzhou, China, and assessed the possibility of aerosol transmission of SARS-CoV-2 and characterize the associated environmental conditions. Methods: We collected epidemiological data, obtained a video record and a patron seating-arrangement from the restaurant, and measured the dispersion of a warm tracer gas as a surrogate for exhaled droplets from the suspected index patient. Computer simulations were performed to simulate the spread of fine exhaled droplets. We compared the in-room location of subsequently infected cases and spread of the simulated virus-laden aerosol tracer. The ventilation rate was measured using the tracer decay method. Results: Three families (A, B, C), 10 members of which were subsequently found to have been infected with SARS-CoV-2 at this time, or previously, ate lunch at Restaurant X on Chinese New Year's Eve (January 24, 2020) at three neighboring tables. Subsequently, three members of family B and two members of family C became infected with SARS-CoV-2, whereas none of the waiters or 68 patrons at the remaining 15 tables became infected. During this occasion, the ventilation rate was 0.75-1.04 L/s per person. No close contact or fomite contact was observed, aside from back-to-back sitting by some patrons. Our results show that the infection distribution is consistent with a spread pattern representative of exhaled virus-laden aerosols. Conclusions: Aerosol transmission of SARS-CoV-2 due to poor ventilation may explain the community spread of COVID-19.

positive: Urgent development of effective therapeutic and prophylactic agents to control the emerging threat of Middle East respiratory syndrome (MERS)

positive: Social stigma in the time of Coronavirus The COVID-19 pandemic has dramatically changed the lives of people around the globe since it appeared in Wuhan, China, at the beginning of December 2019. The burden of disease and its death toll have had an unprecedented impact on the healthcare, economic, and financial systems of low-, middle-, and high-income countries [1–3]. Peoples’ lives have been disrupted and negatively impacted by COVID-19-related suffering and lockdowns at community and household level.

positive: Novel Coronavirus Outbreak in Wuhan, China, 2020: Intense Surveillance Is Vital for Preventing Sustained Transmission in New Locations The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has only been limited human-to-human transmission outside of China. Here, we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected early in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.41 (credible interval [0.27, 0.55]). However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.012 (credible interval [0, 0.099]). This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a global pandemic.

positive: Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak Abstract To evaluate host susceptibility factors to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we conducted a retrospective cohort study from the single largest exposure event of the 2015 Korean MERS outbreak. A total of 175 patients were closely exposed to a super-spreader, 26 of which were infected (14.9%). In a multivariate analysis, history of autologous stem cell transplantation (HR, 31.151; 95% CI, 5.447–178.145; P < 0.001) and tachypnea at ED (HR, 4.392; 95% CI, 1.402–13.761; P = 0.011) were significantly associated with MERS-CoV infection.

positive: Effects of superspreaders in spread of epidemic Abstract Within the standard SIR model with spatial structure, we propose two models for the superspreader. In one model, superspreaders have intrinsically strong infectiousness. In other model, they have many social connections. By Monte Carlo simulation, we obtain the percolation probability, the propagation speed, the epidemic curve, the distribution of secondary infected and the propagation path as functions of population and the density of superspreaders. By comparing the results with the data of SARS in Singapore 2003, we conclude that the latter model can explain the observation.

positive: Effectiveness of isolation, testing, contact tracing and physical distancing on reducing transmission of SARS-CoV-2 in different settings Isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures - including novel digital tracing approaches and less intensive physical distancing - may be required to reduce transmission. Using a model of individual-level transmission stratified by setting (household, work, school, other) based on BBC Pandemic data from 40,162 UK participants, we simulated the impact of a range of different testing, isolation, tracing and physical distancing scenarios. As well as estimating reduction in effective reproduction number, we estimated, for a given level of COVID-19 incidence, the number of contacts that would be newly quarantined each day under different strategies. Under optimistic but plausible assumptions, we estimated that combined testing and tracing strategies would reduce transmission more than mass testing or self-isolation alone (50-65% compared to 2-30%). If limits are placed on gatherings outside of home/school/work (e.g. maximum of 4 daily contacts in other settings), then manual contact tracing of acquaintances only could have a similar effect on transmission reduction as detailed contact tracing. In a scenario where there were 10,000 new symptomatic cases per day, we estimated in most contact tracing strategies, 140,000 to 390,000 contacts would be newly quarantined each day. Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimates that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number that is below one in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control.

positive: Propagation and mitigation of epidemics in a scale-free network The epidemic curve and the final extent of the COVID-19 pandemic are usually predicted from the rate of early exponential raising using the SIR model. These predictions implicitly assume a full social mixing, which is not plausible generally. Here I am showing a counterexample to the these predictions, based on random propagation of an epidemic in Barab\'asi--Albert scale-free network models. The start of the epidemic suggests $R_0=2.6$, but unlike $\Omega\approx 70\%{}$ predicted by the SIR model, they reach a final extent of only $\Omega\approx 4\%{}$ without external mitigation and $\Omega\approx 0.5$--$1.5\%{}$ with mitigation. Daily infection rate at the top is also 1--1.5 orders of magnitude less than in SIR models. Quarantining only the 1.5\%{} most active superspreaders has similar effect on extent and top infection rate as blind quarantining a random 50\%{} of the full community.

positive: Severe acute respiratory syndrome--Singapore, 2003. The Singapore Ministry of Health (MOH), with assistance from the World Health Organization (WHO), has been investigating an outbreak of severe acute respiratory syndrome (SARS). This is a novel condition caused by the SARS-associated coronavirus (SARS-CoV) and is characterized by both an atypical pneumonia and efficient nosocomial transmission. This report summarizes epidemiologic features of this outbreak in Singapore, including the influence of super spreaders and the national prevention and control strategy.

positive: SUPERSPREADING AS A REGULAR FACTOR OF THE COVID-19 PANDEMIC An impact of superspreading on the course of the COVID-19 epidemic is considered. A two-component model of the epidemic has been developed, in which all infected are divided in two groups. They are asymptomatic superspreaders spreading the infection and sensitive persons which can only get infection. Once infected the sensitive exhibit clear symptoms and become isolated. Taking into account both factors allows find the numbers of superspreaders and sensitive persons. It is shown, that the ratio of increment of the number of daily cases in the beginning of the epidemic and decrement at the end of the epidemic is equal to the ratio of numbers of the superspreaders and sensitive persons. In this way, on the base of data from 12 countries and territories, the share of asymptomatic among all infected persons is found to be (17 {+/-} 3)%. Specific measures to limit the epidemical incidence are proposed. The possibility of an allergic component in the disease is discussed.

positive: Assessing the spreading potential of an undetected case of COVID-19 in orthopaedic surgery BACKGROUND: With the novel coronavirus-induced disease (COVID-19), there is the fear of nosocomial infections and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissions to healthcare workers (HCW). We report the case of a 64-year-old male patient who underwent explantation of a shoulder prosthesis due to a periprosthetic infection. He was tested SARS-CoV-2 positive 7 days after admission to the orthopaedic department following strict infection control measures, routinely including screening all patients for multi-drug-resistant organism (MDRO) colonization upon admission. Aim of our study is to report on the spreading potential of SARS-CoV-2 in a healthcare setting if standard contact precautions and infection control measures have been established. METHODS: All HCW with exposure to the patient from day of admission until confirmed diagnosis of COVID-19 were identified and underwent oropharyngeal swab testing for SARS‐CoV‐2 by real-time RT-PCR. RESULTS: Sixty-six HCW were identified: nine orthopaedic surgeons, four anaesthesiologists, 25 orthopaedic nurses, five nurse anesthetists, eight scrub nurses, five nursing students, two medical assistants and seven service employees. Fourteen HCW (21%) showed clinical symptoms compatible with a SARS-CoV-2 infection: cough (n = 4), sore throat (n = 3), nasal congestion (n = 3), dyspnea (n = 2), fever (n = 1), headache and myalgia (n = 1). SARS-CoV-2 was not detected in any of the 66 HCW. CONCLUSION: Hygienic measures and contact precautions, aimed at preventing the spread of MRDO, may have helped to prevent a SARS-CoV-2 transmission to HCW—despite high-risk exposure during intubation, surgical treatment and general care. LEVEL OF EVIDENCE: IV, case series.

positive: Understanding and Modeling the Super-spreading Events of the Middle East Respiratory Syndrome Outbreak in Korea

positive: Impact of coronavirus (COVID‐19) on otolaryngologic surgery: Brief commentary BACKGROUND: The Coronavirus disease—2019 (COVID‐19) pandemic is a global health crisis and otolaryngologists are at increased occupational risk of contracting COVID‐19. There are currently no uniform best‐practice recommendations for otolaryngologic surgery in the setting of COVID‐19. METHODS: We reviewed relevant publications and position statements regarding the management of otolaryngology patients in the setting of COVID‐19. Recommendations regarding clinical practice during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks were also reviewed. RESULTS: Enhanced personal protective equipment (N95 respirator and face shield or powered air‐purifying respirator, disposable cap and gown, gloves) is required for any otolaryngology patient with unknown, suspected, or positive COVID‐19 status. Elective procedures should be postponed indefinitely, and clinical practice should be limited to patients with urgent or emergent needs. CONCLUSION: We summarize current best‐practice recommendations for otolaryngologists to ensure safety for themselves, their clinical staff, and their patients.

positive: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future 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.

positive: The correspondence between the structure of the terrestrial mobility network and the emergence of COVID-19 in Brazil The inter-cities mobility network is of great importance in understanding outbreaks, especially in Brazil, a continental-dimension country. Grounded on the complex networks approach, cities are here represented as nodes and the flows as weighted edges - these geographical graphs, (geo)graphs, are handled in a Geographical Information System. We adopt the IBGE database from 2016, which contains the weekly flow of people between cities in terrestrial vehicles. The present work aims to investigate the correspondences of the networks' measures, like strength, degree, and betweenness with the emergence of cities with confirmed cases of COVID-19 in Brazil, and special attention is given to the state of Sao Paulo. We show that the results are better when certain thresholds are applied to the networks' flows to neglect the lowest-frequency travels. The correspondences presented statistical significance for most measures up to a certain period. Until the end of April, the best matchings are with the strength measure (total flow related to a node/city) under a high flow threshold in the Sao Paulo state, when the most connected cities are reached. After this stage, the lower thresholds become more suitable, indicating a possible signature of the outbreak interiorization process. Surprisingly, some countryside cities such as Campina Grande (state of Paraiba), Feira de Santana (state of Bahia), and Caruaru (state of Pernambuco) have higher strengths than some states' capitals. Furthermore, some cities from the Sao Paulo state such as Presidente Prudente and Ribeirao Preto are captured in the top-rank positions of all the analyzed network measures under different flow thresholds. Their importance in mobility is crucial and they are potential super spreaders like the states' capitals. Our analysis offers additional tools for understanding and decision support to inter-cities mobility interventions regarding the SARS-CoV-2 and other epidemics.

positive: Spatial super-spreaders and super-susceptibles in human movement networks As lockdowns and stay-at-home orders start to be lifted across the globe, governments are struggling to establish effective and practical guidelines to reopen their economies. In dense urban environments with people returning to work and public transportation resuming full capacity, enforcing strict social distancing measures will be extremely challenging, if not practically impossible. Governments are thus paying close attention to particular locations that may become the next cluster of disease spreading. Indeed, certain places, like some people, can be"super-spreaders."Is a bustling train station in a central business district more or less susceptible and vulnerable as compared to teeming bus interchanges in the suburbs? Here, we propose a quantitative and systematic framework to identify spatial super-spreaders and the novel concept of super-susceptibles, i.e. respectively, places most likely to contribute to disease spread or to people contracting it. Our proposed data-analytic framework is based on the daily-aggregated ridership data of public transport in Singapore. By constructing the directed and weighted human movement networks and integrating human flow intensity with two neighborhood diversity metrics, we are able to pinpoint super-spreader and super-susceptible locations. Our results reveal that most super-spreaders are also super-susceptibles and that counterintuitively, busy peripheral bus interchanges are riskier places than crowded central train stations. Our analysis is based on data from Singapore, but can be readily adapted and extended for any other major urban center. It therefore serves as a useful framework for devising targeted and cost-effective preventive measures for urban planning and epidemiological preparedness.

positive: Connecting the Dots of COVID-19 Transmissions in India Witnessing its first case in late January 2020 India has seen a sharp rise in the number of positive cases of COVID-19. 34 States/UT (s) of the country have been found to be affected by the pandemic to date. We in this work, study the progress of COVID-19 pandemic in India. We aim to create transmission network visualization (s) of COVID-19 in India and perform analysis upon them. Using the transmission networks obtained we attempt to find the possible Super Spreader Individual (s) and Super Spreader Events (SSE) responsible for the outbreak in their respective regions. We discuss the potentials of network analysis in mitigating the further spread of the disease. This is one of the initial studies of the outbreak in India and the first attempt to study the pandemic in the country from a transmission network perspective.

positive: A Pandemic in Times of Global Tourism: Superspreading and Exportation of COVID-19 Cases from a Ski Area in Austria

positive: Super-spreaders and the rate of transmission of the SARS virus Abstract We describe a stochastic small-world network model of transmission of the SARS virus. Unlike the standard Susceptible-Infected-Removed models of disease transmission, our model exhibits both geographically localised outbreaks and “super-spreaders”. Moreover, the combination of localised and long range links allows for more accurate modelling of partial isolation and various public health policies. From this model, we derive an expression for the probability of a widespread outbreak and a condition to ensure that the epidemic is controlled. Moreover, multiple simulations are used to make predictions of the likelihood of various eventual scenarios for fixed initial conditions. The main conclusions of this study are: (i) “super-spreaders” may occur even if the infectiousness of all infected individuals is constant; (ii) consistent with previous reports, extended exposure time beyond 3–5 days (i.e. significant nosocomial transmission) was the key factor in the severity of the SARS outbreak in Hong Kong; and, (iii) the spread of SARS can be effectively controlled by either limiting long range links (imposing a partial quarantine) or enforcing rapid hospitalisation and isolation of symptomatic individuals.

positive: Roadblocks to Infection Prevention Efforts in Health Care: SARS-CoV-2/COVID-19 Response The outbreak of a novel coronavirus, SARS-CoV-2, is challenging international public health and health care efforts. As hospitals work to acquire enough personal protective equipment and brace for potential cases, the role of infection prevention efforts and programs has become increasingly important. Lessons from the 2003 SARS-CoV outbreak in Toronto and 2015 MERS-CoV outbreak in South Korea have unveiled the critical role that hospitals play in outbreaks, especially of novel coronaviruses. Their ability to amplify the spread of disease can rapidly fuel transmission of the disease, and often those failures in infection prevention and general hospital practices contribute to such events. While efforts to enhance infection prevention measures and hospital readiness are underway in the United States, it is important to understand why these programs were not able to maintain continued, sustainable levels of readiness. History has shown that infection prevention programs are primarily responsible for preparing hospitals and responding to biological events but face understaffing and focused efforts defined by administrators. The current US health care system, though, is built upon a series of priorities that often view biopreparedness as a costly endeavor. Awareness of these competing priorities and the challenges that infection prevention programs face when working to maintain biopreparedness is critical in adequately addressing this critical infrastructure in the face of an international outbreak.

positive: The role of directionality, heterogeneity and correlations in epidemic risk and spread Most models of epidemic spread, including many designed specifically for COVID-19, implicitly assume that social networks are undirected, i.e., that the infection is equally likely to spread in either direction whenever a contact occurs. In particular, this assumption implies that the individuals most likely to spread the disease are also the most likely to receive it from others. Here, we review results from the theory of random directed graphs which show that many important quantities, including the reproductive number and the epidemic size, depend sensitively on the joint distribution of in- and out-degrees ("risk"and"spread"), including their heterogeneity and the correlation between them. By considering joint distributions of various kinds we elucidate why some types of heterogeneity cause a deviation from the standard Kermack-McKendrick analysis of SIR models, i.e., so called mass-action models where contacts are homogeneous and random, and some do not. We also show that some structured SIR models informed by complex contact patterns among types of individuals (age or activity) are simply mixtures of Poisson processes and tend not to deviate significantly from the simplest mass-action model. Finally, we point out some possible policy implications of this directed structure, both for contact tracing strategy and for interventions designed to prevent superspreading events. In particular, directed networks have a forward and backward version of the classic"friendship paradox"-- forward links tend to lead to individuals with high risk, while backward links lead to individuals with high spread -- such that a combination of both forward and backward contact tracing is necessary to find superspreading events and prevent future cascades of infection.

positive: KCDC Risk Assessments on the Initial Phase of the COVID-19 Outbreak in Korea OBJECTIVES: This study aims to evaluate the risk assessments of coronavirus 2019 (COVID-19) in the Korea Centers for Disease Control and Prevention (KCDC), from the point of detection to the provision of basic information to the relevant public health authorities. METHODS: To estimate the overall risk of specific public health events, probability, and impact at the country-level were evaluated using available information. To determine the probability of particular public health events, the risk of importation and risk of transmission were taken into consideration. KCDC used 5 levels (“very low,” “low,” “moderate,” “high,” and “very high”) for each category and overall risk was eventually decided. RESULTS: A total of 8 risk assessments were performed on 8 separate occasions between January 8(th) to February 28(th), 2020, depending on the detection and report of COVID-19 cases in other countries. The overall risk of the situation in each assessment increased in severity over this period: “low” (first), “moderate” (second), “high” (third), “high” (fourth), “high” (fifth), “high” (sixth), “high” (seventh), and “very high” (eighth). CONCLUSION: The KCDC’s 8 risk assessments were utilized to activate national emergency response mechanisms and eventually prepare for the pandemic to ensure the containment and mitigation of COVID-19 with non-pharmaceutical public health measures.

positive: Impact of contact tracing on SARS-CoV-2 transmission

positive: Enhancing genetic disease control by selecting for lower host infectivity and susceptibility Infectious diseases have a huge impact on animal health, production and welfare, and human health. Understanding the role of host genetics in disease spread is important for developing disease control strategies that efficiently reduce infection incidence and risk of epidemics. While heritable variation in disease susceptibility has been targeted in livestock breeding, emerging evidence suggests that there is additional genetic variation in host infectivity, but the potential benefits of including infectivity into selection schemes are currently unknown. A Susceptible-Infected-Recovered epidemiological model incorporating polygenic genetic variation in both susceptibility and infectivity was combined with quantitative genetics selection theory to assess the non-linear impact of genetic selection on field measures of epidemic risk and severity. Response to 20 generations of selection was calculated in large simulated populations, exploring schemes differing in accuracy and intensity. Assuming moderate genetic variation in both traits, 50% selection on susceptibility required seven generations to reduce the basic reproductive number R(0) from 7.64 to the critical threshold of <1, below which epidemics die out. Adding infectivity in the selection objective accelerated the decline towards R(0) < 1, to 3 generations. Our results show that although genetic selection on susceptibility reduces disease risk and prevalence, the additional gain from selection on infectivity accelerates disease eradication and reduces more efficiently the risk of new outbreaks, while it alleviates delays generated by unfavourable correlations. In conclusion, host infectivity was found to be an important trait to target in future genetic studies and breeding schemes, to help reducing the occurrence and impact of epidemics.

positive: Stochasticity and heterogeneity in the transmission dynamics of SARS-CoV-2 SARS-CoV-2 causing COVID-19 disease has moved rapidly around the globe, infecting millions and killing hundreds of thousands. The basic reproduction number, which has been widely used and misused to characterize the transmissibility of the virus, hides the fact that transmission is stochastic, is dominated by a small number of individuals, and is driven by super-spreading events (SSEs). The distinct transmission features, such as high stochasticity under low prevalence, and the central role played by SSEs on transmission dynamics, should not be overlooked. Many explosive SSEs have occurred in indoor settings stoking the pandemic and shaping its spread, such as long-term care facilities, prisons, meat-packing plants, fish factories, cruise ships, family gatherings, parties and night clubs. These SSEs demonstrate the urgent need to understand routes of transmission, while posing an opportunity that outbreak can be effectively contained with targeted interventions to eliminate SSEs. Here, we describe the potential types of SSEs, how they influence transmission, and give recommendations for control of SARS-CoV-2.

positive: A note on community-detection (Kemeny) based testing for COVID-19 The Kemeny constant of a graph can be used to identify and analyse bridges between communities in a graph. Testing, tracking and tracing abilities have been identified as pivotal in helping countries to safely reopen activities after the first wave of the COVID-19 virus. Tracing techniques aim at reconstructing past history of contacts, but can face practical limits in an exponential growth of either testing or overly conservative quarantining. We show how this application of graph theory can be conveniently used to efficiently intercept new virus outbreaks, when they are still in their early stage. Simulations provide promising results in early identification and blocking of possible"super-spreader links that transmit disease between different communities.

positive: 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.

positive: Preliminary estimating the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea and Italy by 5 March 2020 The novel coronavirus disease 2019 (COVID-19) outbreak and Italy has caused 6088 cases and 41 deaths in Republic of Korea and 3144 cases and 107 death in Italy by 5 March 2020. We modeled the transmission process in Republic of Korea and Italy with a stochastic model and estimated the basic reproduction number R0 as 2.6 (95% CI: 2.3-2.9) or 3.2 (95% CI: 2.9-3.5) in Republic of Korea, under the assumption that the exponential growth starting on 31 January or 5 February 2020, and 2.6 (95% CI: 2.3-2.9) or 3.3 (95% CI: 3.0-3.6) in Italy, under the assumption that the exponential growth starting on 5 February or 10 February 2020. Estimates of dispersion term (k) were 10 (95% CI: 5-56) or 22 (95% CI: 8-61) in Republic of Korea, and 13 (95% CI: 5-61) or 37 (95% CI: 13-61) in Italy, and all of which imply few super-spreading events.

positive: Multi-chain Fudan-CCDC model for COVID-19 -- a revisit to Singapore's case Background: COVID-19 has been impacting on the whole world critically and constantly since late December 2019. Rapidly increasing infections has raised intense worldwide attention. How to model the evolution of COVID-19 effectively and efficiently is of great significance for prevention and control. Methods: We propose the multi-chain Fudan-CCDC model based on the original single-chain model in [8] to describe the evolution of COVID-19 in Singapore. Multi-chains can be considered as the superposition of several single chains with different characteristics. We identify parameters of models by minimizing the penalty function. Results: The numerical simulation results exhibit the multi-chain model performs well on data fitting. Though unsteady the increments are, they could still fall within the range of 25% fluctuation from simulation results. It is predicted by multi-chain models that Singapore are experiencing a nonnegligible risk of explosive outbreak, thus stronger measures are urgently needed to contain the epidemic. Conclusion: The multi-chain Fudan-CCDC model provides an effective way to early detect the appearance of imported infectors and super spreaders and forecast a second outbreak. It can also explain the data in those countries where the single-chain model shows deviation from the data.

positive: Spatial approximations of network-based individual level infectious disease models Abstract Often, when modeling infectious disease spread, the complex network through which the disease propagates is approximated by simplified spatial information. Here, we simulate epidemic spread through various contact networks and fit spatial-based models in a Bayesian framework using Markov chain Monte Carlo methods. These spatial models are individual-level models which account for the spatio-temporal dynamics of infectious disease. The focus here is on choosing a spatial model which best predicts the true probabilities of infection, as well as determining under which conditions such spatial models fail. Spatial models tend to predict infection probability reasonably well when disease spread is propagated through contact networks in which contacts are only within a certain distance of each other. If contacts exist over long distances, the spatial models tend to perform worse when compared to the network model.

positive: Molecular epidemiology of the novel coronavirus that causes severe acute respiratory syndrome Summary Background Severe acute respiratory syndrome (SARS) is a newly emerged disease caused by a novel coronavirus (SARS-CoV), which spread globally in early 2003, affecting over 30 countries. We have used molecular epidemiology to define the patterns of spread of the virus in Hong Kong and beyond. Methods The case definition of SARS was based on that recommended by WHO. We genetically sequenced the gene for the S1 unit of the viral spike protein of viruses from patients with SARS in Hong Kong (138) and Guangdong (three) in February to April, 2003. We undertook phylogenetic comparisons with 27 other sequences available from public databases (Genbank). Findings Most of the Hong Kong viruses (139/142), including those from a large outbreak in an apartment block, clustered closely together with the isolate from a single index case (HKU-33) who came from Guangdong to Hong Kong in late February. Three other isolates were genetically distinct from HKU-33 in Hong Kong during February, but none of these contributed substantially to the subsequent local outbreak. Viruses identified in Guangdong and Beijing were genetically more diverse. Interpretation The molecular epidemiological evidence suggests that most SARS-CoV from the outbreak in Hong Kong, as well as the viruses from Canada, Vietnam, and Singapore, are genetically closely linked. Three viruses found in Hong Kong in February were phylogenetically distinct from the major cluster, which suggests that several introductions of the virus had occurred, but that only one was associated with the subsequent outbreak in Hong Kong, which in turn spread globally.

positive: A stochastic, individual-based model for the evaluation of the impact of non-pharmacological interventions on COVID-19 transmission in Slovakia The COVID-19 pandemic represents one of the most significant healthcare challenges that humanity faces. We developed a stochastic, individual-based model of transmission of COVID-19 in Slovakia. The proposed model is based on current clinical knowledge of the disease and takes into account the age structure of the population, distribution of the population into the households, interactions within the municipalities, and interaction among the individuals travelling between municipalities. Furthermore, the model incorporates the effect of age-dependent severity of COVID-19 and realistic trajectories of patients through the healthcare system. We assess the impact of the governmental non-pharmacological interventions, such as population-wide social distancing, social distancing within specific subsets of population, reduction of travel between the municipalities, and self-quarantining of the infected individuals. We also evaluate the impact of relaxing of strict restrictions, efficacy of the simple state feedback-based restrictions in controlling the outbreak, and the effect of superspreaders on the disease dynamics. Our simulations show that non-pharmacological interventions reduce the number of infected individuals and the number of fatalities, especially when the social distancing of particularly susceptible subgroups of the population is employed along with case isolation.

positive: Summary of the coronavirus disease 2019 (COVID-19) update from the 2020 Conference on Retroviruses and Opportunistic Infections, 8-11 March 2020, Boston, USA

positive: Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020 Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R0 of 2019-nCoV to be around 2.2 (90% high density interval: 1.4-3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.

positive: The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID‐19): A Chinese perspective 2019 novel coronavirus (SARS‐CoV‐2), which originated in Wuhan, China, has attracted the world's attention over the last month. The Chinese government has taken emergency measures to control the outbreak and has undertaken initial steps in the diagnosis and treatment of 2019 novel coronavirus infection disease (COVID‐19). However, SARS‐CoV‐2 possesses powerful pathogenicity as well as transmissibility and still holds many mysteries that are yet to be solved, such as whether the virus can be transmitted by asymptomatic patients or by mothers to their infants. Our research presents selected available cases of COVID‐19 in China to better understand the transmission and diagnosis regarding this infectious disease.

positive: Viruses in the Intensive Care Unit (ICU) Whereas viruses are not usually considered to be important causes of ICU admission this review has demonstrated this perception to be incorrect. Viruses and their manifestations differ from continent to continent and hemisphere to hemisphere and it is essential that the intensivist be familiar with diagnosis and management of these ubiquitous organisms.

positive: Robustness analysis in an inter-cities mobility network: modeling municipal, state and federal initiatives as failures and attacks Motivated by the challenge related to the COVID-19 epidemic and the seek for optimal containment strategies, we present a robustness analysis into an inter-cities mobility complex network. We abstract municipal initiatives as nodes' failures and the federal actions as targeted attacks. The geo(graphs) approach is applied to visualize the geographical graph and produce maps of topological indexes, such as degree and vulnerability. A Brazilian data of 2016 is considered a case study, with more than five thousand cities and twenty-seven states. Based on the Network Robustness index, we show that the most efficient attack strategy shifts from a topological degree-based, for the all cities network, to a topological vulnerability-based, for a network considering the Brazilian States as nodes. Moreover, our results reveal that individual municipalities' actions do not cause a high impact on mobility restrain since they tend to be punctual and disconnected to the country scene as a whole. Oppositely, the coordinated isolation of specific cities is key to detach entire network areas and thus prevent a spreading process to prevail.

positive: Superspreaders and the spread pattern of COVID-19: Response to: “Do superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19”, International Journal of Infectious Diseases 96 (2020) 461–463

positive: Early dynamics of transmission and control of COVID-19: a mathematical modelling study Background: An outbreak of the novel coronavirus SARS-CoV-2 has led to 46,997 confirmed cases as of 13th February 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Methods: We combined a stochastic transmission model with data on cases of novel coronavirus disease (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January and February 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. Findings: We estimated that the median daily reproduction number, Rt , declined from 2.35 (95% CI: 1.15-4.77) one week before travel restrictions were introduced on 23rd January to 1.05 (95% CI: 0.413-2.39) one week after. Based on our estimates of Rt,we calculated that in locations with similar transmission potential as Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. Interpretation: Our results show that COVID-19 transmission likely declined in Wuhan during late January 2020, coinciding with the introduction of control measures. As more cases arrive in international locations with similar transmission potential to Wuhan pre-control, it is likely many chains of transmission will fail to establish initially, but may still cause new outbreaks eventually.

positive: Coronavirus Optimization Algorithm: A bioinspired metaheuristic based on the COVID-19 propagation model A novel bioinspired metaheuristic is proposed in this work, simulating how the coronavirus spreads and infects healthy people. From an initial individual (the patient zero), the coronavirus infects new patients at known rates, creating new populations of infected people. Every individual can either die or infect and, afterwards, be sent to the recovered population. Relevant terms such as re-infection probability, super-spreading rate or traveling rate are introduced in the model in order to simulate as accurately as possible the coronavirus activity. The Coronavirus Optimization Algorithm has two major advantages compared to other similar strategies. First, the input parameters are already set according to the disease statistics, preventing researchers from initializing them with arbitrary values. Second, the approach has the ability of ending after several iterations, without setting this value either. Infected population initially grows at an exponential rate but after some iterations, when considering social isolation measures and the high number recovered and dead people, the number of infected people starts decreasing in subsequent iterations. Furthermore, a parallel multi-virus version is proposed in which several coronavirus strains evolve over time and explore wider search space areas in less iterations. Finally, the metaheuristic has been combined with deep learning models, in order to find optimal hyperparameters during the training phase. As application case, the problem of electricity load time series forecasting has been addressed, showing quite remarkable performance.

positive: Why does Japan have so few cases of COVID‐19? The COVID‐19 pandemic has spread to many countries around the world, but the infection and death rates vary widely. One country that appeared to have kept the infection under control despite limited societal restrictions is Japan. This commentary explores why Japan may have, up to now, been spared an escalation of the SARS‐CoV‐2 infections.[Image: see text]

positive: Mathematical Modeling of COVID-19 Transmission Dynamics with a Case Study of Wuhan Abstract We propose a compartmental mathematical model for the spread of the COVID-19 disease with special focus on the transmissibility of super-spreaders individuals. We compute the basic reproduction number threshold, we study the local stability of the disease free equilibrium in terms of the basic reproduction number, and we investigate the sensitivity of the model with respect to the variation of each one of its parameters. Numerical simulations show the suitability of the proposed COVID-19 model for the outbreak that occurred in Wuhan, China.

positive: The role of hospital environment in transmissions of multidrug-resistant gram-negative organisms Infections by multidrug-resistant (MDR) Gram-negative organisms (GN) are associated with a high mortality rate and present an increasing challenge to the healthcare system worldwide. In recent years, increasing evidence supports the association between the healthcare environment and transmission of MDRGN to patients and healthcare workers. To better understand the role of the environment in transmission and acquisition of MDRGN, we conducted a utilitarian review based on literature published from 2014 until 2019.

positive: Early detection of superspreaders by mass group pool testing can mitigate COVID-19 pandemic Background Most of epidemiological models applied for COVID-19 do not consider heterogeneity in infectiousness and impact of superspreaders, despite the broad viral loading distributions amongst COVID-19 positive people (1-1 000 000 per mL). Also, mass group testing is not used regardless to existing shortage of tests. I propose new strategy for early detection of superspreaders with reasonable number of RT-PCR tests, which can dramatically mitigate development COVID-19 pandemic and even turn it endemic. Methods I used stochastic social-epidemiological SEIAR model, where S-suspected, E-exposed, I-infectious, A-admitted (confirmed COVID-19 positive, who are admitted to hospital or completely isolated), R-recovered. The model was applied to real COVID-19 dynamics in London, Moscow and New York City. Findings Viral loading data measured by RT-PCR were fitted by broad log-normal distribution, which governed high importance of superspreaders. The proposed full scale model of a metropolis shows that top 10% spreaders (100+ higher viral loading than median infector) transmit 45% of new cases. Rapid isolation of superspreaders leads to 4-8 fold mitigation of pandemic depending on applied quarantine strength and amount of currently infected people. High viral loading allows efficient group matrix pool testing of population focused on detection of the superspreaders requiring remarkably small amount of tests. Interpretation The model and new testing strategy may prevent thousand or millions COVID-19 deaths requiring just about 5000 daily RT-PCR test for big 12 million city such as Moscow. Though applied to COVID-19 pandemic the results are universal and can be used for other infectious heterogenous epidemics. Funding No funding

positive: Preparing for the Next Wave of COVID-19: Resilience in the Face of a Spreading Pandemic COVID-19 painfully demonstrates how little resilience our societies have to novel viruses. Societies, decision makers, and scientists lack (1) a comprehensive understanding of the complexity of viral outbreaks and their impact on society; (2) intervention portfolios; and (3) a global crisis and resilience policy, all of which are required to develop appropriate measures and to improve societal resilience. We highlight COVID-19 immunity as one key benchmark in preparation for the next wave of the pandemic. Specifically, using network scenarios, we demonstrate the substantial advantage of reintegrating health care workers with acquired COVID-19 immunity in epidemic hotspots, which would not only enable their safe contribution to the health care system but also drastically contain further spread.

positive: Susceptibility-adjusted herd immunity threshold model and potential R0 distribution fitting the observed Covid-19 data in Stockholm The reproduction number, R0, is commonly used, and sometimes misused, in conjunction with the classic Kermack and McKindrick theory based on the assumption of homogeneity, in order to estimate herd immunity threshold (HIT). This provides a crude first estimate of HIT, with more elaborate modelling required to arrive at a more realistic value. Early estimates of HIT for Covid-19 were based on this simplistic homogeneous approach, yielding high HIT values that have since been revised downwards with more sophisticated network modelling taking account of R0 heterogeneity and with reference to the low HIT found from serological sampling in Stockholm County. The aim of this paper is to describe a simple model in which host susceptibility is directly linked to the heterogeneous R0 distribution, to shed further light on the mechanisms involved and to arrive at a bimodal R0 distribution consistent with the Covid-19 HIT observed in Stockholm County.

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: Epidemiological characteristics of the first 100 cases of coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region, China, a city with a stringent containment policy BACKGROUND: Hong Kong (HK) is a densely populated city near the epicentre of the coronavirus disease 2019 (COVID-19) outbreak. Stringent border control together with aggressive case finding, contact tracing, social distancing and quarantine measures were implemented to halt the importation and spread of the virus. METHODS: We performed an epidemiological study using government information covering the first 100 confirmed cases to examine the epidemic curve, incidence, clusters, reproduction number (R(t)), incubation period and time to containment. RESULTS: A total of 93 of the 100 cases were HK residents (6 infected in Mainland China, 10 on the Diamond Princess Cruise). Seven were visitors infected in Mainland China before entering HK. The majority (76%) were aged ≥45 years, and the incidence increased with age (P < 0.001). Escalation of border control measures correlated with a decrease in the proportion (62.5% to 0%) of cases imported from Mainland China, and a reduction in R(t) (1.07 to 0.75). The median incubation period was 4.2 days [95% confidence interval (CI), 4.0–4.5; 5th and 95th percentiles: 1.3 and 14.0). Most clusters with identifiable epidemiological links were households involving 2–4 people. Three medium-spreading events were identified: two from New Year gatherings (6–11 people), and another from environmental contamination of a worship hall (12 people). Despite intensified contact tracing, containment was delayed in 78.9% of cases (mean = 5.96 days, range = 0–24 days). An unusual transmission in a multi-storey building via faulty toilet plumbing was suspected with >100 residents evacuated overnight. Our analysis indicated that faulty plumbing was unlikely to be the source of this transmission. CONCLUSIONS: Timely stringent containment policies minimized the importation and transmission of COVID-19 in HK.

positive: [Investigation of a cluster epidemic of COVID-19 in Ningbo]. Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+ generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.

positive: The Potential role of Particulate Matter in the Spreading of COVID-19 in Northern Italy: First Evidence-based Research Hypotheses Background: An epidemic model based only on respiratory droplets and close contact could not fully explain the regional differences in the spread of the recent severe acute respiratory syndrome COVID-19 in Italy, which was fast and dramatic only in Lombardy and Po Valley. On March 16th 2020, we presented a Position Paper proposing a research hypothesis concerning the association between higher mortality rates due to COVID-19 observed in Northern Italy and the peaks of particulate matter concentrations, frequently exceeding the legal limit of 50 micrograms/m3 as PM10 daily average Methods: To assess environmental factors related to the spread of the COVID-19 in Italy from February 24th to March 13th (the date when the lockdown has been imposed over Italy), official daily data relevant to ambient PM10 levels were collected from all Italian Provinces between February 9th and February 29th , taking into account the average time (estimated in 17 days) elapsed between the initial infection and the recorded COVID positivity. In addition to the number of exceedances of PM10 daily limit value, we considered also population data and daily travelling information per each Province. Results. PM10 daily limit value exceedances appear to be a significant predictor (p <0.001) of infection in univariate analyses. Less polluted Provinces had a median of 0.03 infection cases over 1000 residents, while most polluted Provinces had a median of 0.26 cases over 1000 residents. Thirty-nine out of 41 Northern Italian Provinces resulted in the category with highest PM10 levels, while 62 out of 66 Southern Provinces presented low PM10 concentrations (p<0.001). In Milan, the average growth rate before the lockdown was significantly higher than Rome (0.34 vs. 0.27 per day, with a doubling time of 2.0 days vs. 2.6), suggesting a basic reproductive number R0>6.0, comparable with the highest values estimated for China.

positive: Occupational health responses to COVID‐19: What lessons can we learn from SARS? On 31 December 2019, the World Health Organization (WHO) received reports of pneumonia cases of unknown etiology in the city of Wuhan in Hubei Province, China. The agent responsible was subsequently identified as a coronavirus—SARS‐CoV‐2. The WHO declared this disease as a Public Health Emergency of International Concern at the end of January 2020. This event evoked a sense of déjà vu, as it has many similarities to the outbreak of severe acute respiratory syndrome (SARS) of 2002‐2003. Both illnesses were caused by a zoonotic novel coronavirus, both originated during winter in China and both spread rapidly all over the world. However, the case‐fatality rate of SARS (9.6%) is higher than that of COVID‐19 (<4%). Another zoonotic novel coronavirus, MERS‐CoV, was responsible for the Middle East respiratory syndrome, which had a case‐fatality rate of 34%. Our experiences in coping with the previous coronavirus outbreaks have better equipped us to face the challenges posed by COVID‐19, especially in the health care setting. Among the insights gained from the past outbreaks were: outbreaks caused by viruses are hazardous to healthcare workers; the impact of the disease extends beyond the infection; general principles of prevention and control are effective in containing the disease; the disease poses both a public health as well as an occupational health threat; and emerging infectious diseases pose a continuing threat to the world. Given the perspectives gained and lessons learnt from these past events, we should be better prepared to face the current COVID‐19 outbreak.

positive: Assessment of Lockdown Effect in Some States and Overall India: A Predictive Mathematical Study on COVID-19 Outbreak In the absence of neither an effective treatment or vaccine and with an incomplete understanding of the epidemiological cycle, Govt. has implemented a nationwide lockdown to reduce COVID-19 transmission in India. To study the effect of social distancing measure, we considered a new mathematical model on COVID-19 that incorporates lockdown effect. By validating our model to the data on notified cases from five different states and overall India, we estimated several epidemiologically important parameters as well as the basic reproduction number ($R_{0}$). Combining the mechanistic mathematical model with different statistical forecast models, we projected notified cases in the six locations for the period May 17, 2020, till May 31, 2020. A global sensitivity analysis is carried out to determine the correlation of two epidemiologically measurable parameters on the lockdown effect and also on $R_{0}$. Our result suggests that lockdown will be effective in those locations where a higher percentage of symptomatic infection exists in the population. Furthermore, a large scale COVID-19 mass testing is required to reduce community infection. Ensemble model forecast suggested a high rise in the COVID-19 notified cases in most of the locations in the coming days. Furthermore, the trend of the effective reproduction number ($R_{t}$) during the projection period indicates if the lockdown measures are completely removed after May 17, 2020, a high spike in notified cases may be seen in those locations. Finally, combining our results, we provided an effective lockdown policy to reduce future COVID-19 transmission in India.

positive: Epidemiological and genetic analysis of severe acute respiratory syndrome Summary The severe acute respiratory syndrome (SARS) epidemics in 2002–2003 showed how quickly a novel infectious disease can spread both within communities and internationally. We have reviewed the epidemiological and genetic analyses that have been published both during and since these epidemics, and show how quickly data were collected and analyses undertaken. Key factors that determine the speed and scale of transmission of an infectious disease were estimated using statistical and mathematical modelling approaches, and phylogenetic analyses provided insights into the origin and evolution of the SARS-associated coronavirus. The SARS literature continues to grow, and it is hoped that international collaboration in the analysis of epidemiological and contact-network databases will provide further insights into the spread of this newly emergent infectious disease.

positive: Strongly heterogeneous transmission of COVID-19 in mainland China: local and regional variation Background The outbreak of novel coronavirus disease 2019 (COVID-19) started in the city of Wuhan, China, with a period of rapid initial spread. Transmission on a regional and then national scale was promoted by intense travel during the holiday period of the Chinese New Year. We studied the variation in transmission of COVID-19, locally in Wuhan, as well as on a larger spatial scale, among different cities and even among provinces in mainland China. Methods In addition to reported numbers of new cases, we have been able to assemble detailed contact data for some of the initial clusters of COVID-19. This enabled estimation of the serial interval for clinical cases, as well as reproduction numbers for small and large regions. Findings We estimated the average serial interval was 4.8 days. For early transmission in Wuhan, any infectious case produced as many as four new cases, transmission outside Wuhan was less intense, with reproduction numbers below two. During the rapid growth phase of the outbreak the region of Wuhan city acted as a hot spot, generating new cases upon contact, while locally, in other provinces, transmission was low. Interpretation COVID-19 is capable of spreading very rapidly. The sizes of outbreak in provinces of mainland China mainly depended on the numbers of cases imported from Wuhan as the local reproduction numbers were low. The COVID-19 epidemic should be controllable with appropriate interventions. Funding No specific funding.

positive: A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster BACKGROUND: An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. METHODS: In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. FINDINGS: From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6–10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. INTERPRETATION: Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. FUNDING: The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).

positive: The SARS outbreak in a general hospital in Tianjin, China -- the case of super-spreader. Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a high case-fatality rate and devastating socio-economic impact. In this report we summarized the results from an epidemiological investigation of a SARS outbreak in a hospital in Tianjin, between April and May 2003. We collected epidemiological and clinical data on 111 suspect and probable cases of SARS associated with the outbreak. Transmission chain and outbreak clusters were investigated. The outbreak was single sourced and had eight clusters. All SARS cases in the hospital were traced to a single patient who directly infected 33 people. The patients ranged from 16 to 82 years of age (mean age 38.5 years); 38.7% were men. The overall case fatality in the SARS outbreak was 11.7% (13/111). The outbreak lasted around 4 weeks after the index case was identified. SARS is a highly contagious condition associated with substantial case fatality; an outbreak can result from one patient in a relatively short period. However, stringent public health measures seemed to be effective in breaking the disease transmission chain.

positive: Chopping the tail: how preventing superspreading can help to maintain COVID-19 control Disease transmission is notoriously heterogeneous, and SARS-CoV-2 is no exception. A skewed distribution where few individuals or events are responsible for the majority of transmission can result in explosive, superspreading events, which produce rapid and volatile epidemic dynamics, especially early or late in epidemics. Anticipating and preventing superspreading events can produce large reductions in overall transmission rates. Here, we present a compartmental (SEIR) epidemiological model framework for estimating transmission parameters from multiple imperfectly observed data streams, including reported cases, deaths, and mobile phone-based mobility that incorporates individual-level heterogeneity in transmission using previous estimates for SARS-CoV-1 and SARS-CoV-2. We parameterize the model for COVID-19 epidemic dynamics by estimating a time-varying transmission rate that incorporates the impact of non-pharmaceutical intervention strategies that change over time, in five epidemiologically distinct settings—Los Angeles and Santa Clara Counties, California; Seattle (King County), Washington; Atlanta (Dekalb and Fulton Counties), Georgia; and Miami (Miami-Dade County), Florida. We find the effective reproduction number [Formula: see text] dropped below 1 rapidly following social distancing orders in mid-March, 2020 and remained there into June in Santa Clara County and Seattle, but climbed above 1 in late May in Los Angeles, Miami, and Atlanta, and has trended upward in all locations since April. With the fitted model, we ask: how does truncating the tail of the individual-level transmission rate distribution affect epidemic dynamics and control? We find interventions that truncate the transmission rate distribution while partially relaxing social distancing are broadly effective, with impacts on epidemic growth on par with the strongest population-wide social distancing observed in April, 2020. Given that social distancing interventions will be needed to maintain epidemic control until a vaccine becomes widely available, “chopping off the tail” to reduce the probability of superspreading events presents a promising option to alleviate the need for extreme general social distancing.

positive: Super-spreaders in infectious diseases Summary Early studies that explored host–pathogen interactions assumed that infected individuals within a population have equal chances of transmitting the infection to others. Subsequently, in what became known as the 20/80 rule, a small percentage of individuals within any population was observed to control most transmission events. This empirical rule was shown to govern inter-individual transmission dynamics for many pathogens in several species, and individuals who infect disproportionately more secondary contacts, as compared to most others, became known as super-spreaders. Studies conducted in the wake of the severe acute respiratory syndrome (SARS) pandemic revealed that, in the absence of super-spreading events, most individuals infect few, if any, secondary contacts. The analysis of SARS transmission, and reports from other outbreaks, unveil a complex scenario in which super-spreading events are shaped by multiple factors, including co-infection with another pathogen, immune suppression, changes in airflow dynamics, delayed hospital admission, misdiagnosis, and inter-hospital transfers. Predicting and identifying super-spreaders open significant medical and public health challenges, and represent important facets of infectious disease management and pandemic preparedness plans.

positive: Effectiveness of Vaccination Strategies for Infectious Diseases According to Human Contact Networks A ‘contact network’ modeling infection transmission comprises of nodes (or individuals) that are linked when they are in contact that possibly transmits an infection. We here studied infection transmission on contact networks of various degree distributions—scale-free, exponential and constant—under SIRV model assuming susceptible, infected, removed and vaccinated statuses of nodes. Aiming for infectious disease containment within the very early stage of spreading, we computed the minimum transmissibility at which an infectious disease epidemic begins to emerge, and its change according to mass preventive and ring post-outbreak vaccination. In the most degree-heterogeneous scale-free network, the ‘super-spreading’ by the hubs, or high-degree nodes, allowed epidemics even for low transmissibility. In compensation, vaccination was much more efficient for the scale-free network. We also found that basic reproductive number R (0) defines a measurement of epidemic emergence universally applicable to networks of various degree distributions. These results are significant for public health design.

positive: A Case Study Evaluating the Risk of Infection from Middle Eastern Respiratory Syndrome Coronavirus (MERS‐CoV) in a Hospital Setting Through Bioaerosols Middle Eastern respiratory syndrome, an emerging viral infection with a global case fatality rate of 35.5%, caused major outbreaks first in 2012 and 2015, though new cases are continuously reported around the world. Transmission is believed to mainly occur in healthcare settings through aerosolized particles. This study uses Quantitative Microbial Risk Assessment to develop a generalizable model that can assist with interpreting reported outbreak data or predict risk of infection with or without the recommended strategies. The exposure scenario includes a single index patient emitting virus‐containing aerosols into the air by coughing, leading to short‐ and long‐range airborne exposures for other patients in the same room, nurses, healthcare workers, and family visitors. Aerosol transport modeling was coupled with Monte Carlo simulation to evaluate the risk of MERS illness for the exposed population. Results from a typical scenario show the daily mean risk of infection to be the highest for the nurses and healthcare workers (8.49 × 10(−4) and 7.91 × 10(−4), respectively), and the lowest for family visitors and patients staying in the same room (3.12 × 10(−4) and 1.29 × 10(−4), respectively). Sensitivity analysis indicates that more than 90% of the uncertainty in the risk characterization is due to the viral concentration in saliva. Assessment of risk interventions showed that respiratory masks were found to have a greater effect in reducing the risks for all the groups evaluated (>90% risk reduction), while increasing the air exchange was effective for the other patients in the same room only (up to 58% risk reduction).

positive: Power Laws in Superspreading Events: Evidence from Coronavirus Outbreaks and Implications for SIR Models While they are rare, superspreading events (SSEs), wherein a few primary cases infect an extraordinarily large number of secondary cases, are recognized as a prominent determinant of aggregate infection rates (R0). Existing stochastic SIR models incorporate SSEs by fitting distributions with thin tails, or finite variance, and therefore predicting almost deterministic epidemiological outcomes in large populations. This paper documents evidence from recent coronavirus outbreaks, including SARS, MERS, and COVID-19, that SSEs follow a power law distribution with fat tails, or infinite variance. We then extend an otherwise standard SIR model with estimated power law distributions, and show that idiosyncratic uncertainties in SSEs will lead to large aggregate uncertainties in infection dynamics, even with large populations. That is, the timing and magnitude of outbreaks will be unpredictable. While such uncertainties have social costs, we also find that they on average decrease the herd immunity thresholds and the cumulative infections because per-period infection rates have decreasing marginal effects. Our findings have implications for social distancing interventions: targeting SSEs reduce not only the average rate of infection (R0) but also its uncertainty. To understand this effect, and to improve inference of the average reproduction numbers under fat tails, estimating the tail distribution of SSEs is vital.

positive: Pattern of early human-to-human transmission of Wuhan 2019-nCoV On December 31, 2019, the World Health Organization was notified about a cluster of pneumonia of unknown aetiology in the city of Wuhan, China. Chinese authorities later identified a new coronavirus (2019-nCoV) as the causative agent of the outbreak. As of January 23, 2020, 655 cases have been confirmed in China and several other countries. Understanding the transmission characteristics and the potential for sustained human-to-human transmission of 2019-nCoV is critically important for coordinating current screening and containment strategies, and determining whether the outbreak constitutes a public health emergency of international concern (PHEIC). We performed stochastic simulations of early outbreak trajectories that are consistent with the epidemiological findings to date. We found the basic reproduction number, R0, to be around 2.2 (90% high density interval 1.4—3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. These findings underline the importance of heightened screening, surveillance and control efforts, particularly at airports and other travel hubs, in order to prevent further international spread of 2019-nCoV.

positive: Accurate ranking of influential spreaders in networks based on dynamically asymmetric link weights We propose an efficient and accurate measure for ranking spreaders and identifying the influential ones in spreading processes in networks. While the edges determine the connections among the nodes, their specific role in spreading should be considered explicitly. An edge connecting nodes [Formula: see text] and [Formula: see text] may differ in its importance for spreading from [Formula: see text] to [Formula: see text] and from [Formula: see text] to [Formula: see text]. The key issue is whether node [Formula: see text] , after infected by [Formula: see text] through the edge, would reach out to other nodes that [Formula: see text] itself could not reach directly. It becomes necessary to invoke two unequal weights [Formula: see text] and [Formula: see text] characterizing the importance of an edge according to the neighborhoods of nodes [Formula: see text] and [Formula: see text]. The total asymmetric directional weights originating from a node leads to a novel measure [Formula: see text] , which quantifies the impact of the node in spreading processes. An [Formula: see text]-shell decomposition scheme further assigns an [Formula: see text]-shell index or weighted coreness to the nodes. The effectiveness and accuracy of rankings based on [Formula: see text] and the weighted coreness are demonstrated by applying them to nine real-world networks. Results show that they generally outperform rankings based on the nodes' degree and [Formula: see text]-shell index while maintaining a low computational complexity. Our work represents a crucial step towards understanding and controlling the spread of diseases, rumors, information, trends, and innovations in networks.

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

positive: Protecting healthcare personnel from 2019-nCoV infection risks: lessons and suggestions The outbreak of a novel Coronavirus disease (COVID-19, caused by the 2019-nCoV infection) in December 2019 is one of the most severe public health emergencies since the founding of People’s Republic of China in 1949. Healthcare personnel (HCP) nationwide are facing heavy workloads and high risk of infection, especially those who care for patients at the epicenter of the outbreak, Hubei Province. Sadly, as of February 20, 2020, over two thousand COVID-19 cases are confirmed among HCP from 476 hospitals nationwide, with nearly 90% of them from Hubei Province. Based on literature search and interviews with some HCP working at Wuhan, capital city of Hubei, we have summarized some of the effective measures taken to reduce infection among HCP, and also made suggestions for improving occupational safety during an infectious disease outbreak. The experience and lessons learned should be a valuable asset for international health community to contain the ongoing COVID-19 epidemic around the world.

positive: The value of early transmission dynamic studies in emerging infectious diseases

positive: The Rapid Assessment and Early Warning Models for COVID-19 Human beings have experienced a serious public health event as the new pneumonia (COVID-19), caused by the severe acute respiratory syndrome coronavirus has killed more than 3000 people in China, most of them elderly or people with underlying chronic diseases or immunosuppressed states. Rapid assessment and early warning are essential for outbreak analysis in response to serious public health events. This paper reviews the current model analysis methods and conclusions from both micro and macro perspectives. The establishment of a comprehensive assessment model, and the use of model analysis prediction, is very efficient for the early warning of infectious diseases. This would significantly improve global surveillance capacity, particularly in developing regions, and improve basic training in infectious diseases and molecular epidemiology.

positive: Epidemiologic, Clinical, and Laboratory Findings of the COVID-19 in the current pandemic BACKGROUND: The COVID-19 caused the pandemic affected the world deeply, with more than 3,000,000 people infected and nearly 200,000 deaths. This article aimed to summarize the epidemiologic traits, clinical spectrum, CT results and laboratory findings of COVID-19 pandemic. METHODS: We scoped for relevant literatures published during 1st Dec 2019 to 23rd Apr 2020 based on four databases by using English and Chinese. The evidence was synthesized narratively. RESULTS: The COVID-19 pandemic was found to have a higher transmission rate compared to SARS and MERS, and involved 4 stages of evolution. The basic reproduction number (R0) is 3.32 (95% CI:3.24–3.39) and the incubation period was 5.24 days (95% CI:3.97–6.50, 5 studies) on average, and the average time for symptoms onset varied by countries. Common clinical spectrums identified included fever (38.1–39.0°C), cough and fatigue, with Acute Respiratory Distress Syndrome (ARDS) being the most common complication reported. Body temperatures above 39.0 °C, dyspnea, and anorexia were more common symptoms in severe patients. Aged over 60 years old, having co-morbidities, and developing complications were the commonest high-risk factors associated with severe conditions. Leucopenia and lymphopenia were the most common signs of infection while liver and kidney damage were rare but may cause bad outcomes for patients. The bilateral, multifocal Ground-Glass Opacification (GGO) on peripheral, and the consolidative pulmonary opacity were the most frequent CT results and the tendency of mortality rates differed by region. CONCLUSIONS: We provided a bird’s-eye view of the COVID-19 during the current pandemic, which will help better understanding the key traits of the disease. The findings could be used for disease’s future research, control and prevention.

positive: The Effect of Social Distancing on the Reach of an Epidemic in Social Networks How does social distancing affect the reach of an epidemic in social networks? We present Monte Carlo simulation results of a Susceptible- Infected-Removed (SIR) model on a network, where individuals are limited in the number of other people they can interact with. While increased social distancing always reduces the spread of an infectious disease, the magnitude varies greatly depending on the topology of the social network. Our results also reveal the importance of coordination at the global level. In particular, the public health benefits from social distancing to a group (e.g., a country) may be completely undone if that group maintains connections with outside groups that are not social distancing.

positive: Sensitivity of commercial Anti-SARS-CoV-2 serological assays in a high-prevalence setting We analysed SARS-CoV-2 specific antibody responses in 42 social and working contacts of a super-spreader from the Heinsberg area in Germany. Consistent with a high-prevalence setting 26 individuals had SARS-CoV-2 antibodies determined by in-house neutralisation testing. These results were compared with four commercial assays, suggesting limited sensitivity of the assays in such a high-prevalence setting. Although SARS-CoV-2 nucleocapsid restricted tests showed a better sensitivity, spike based assays had a stronger correlation with neutralisation capacity.

positive: Pausing super spreader events for COVID-19 mitigation: International Hajj pilgrimage cancellation

positive: [Investigation of a cluster epidemic of COVID-19 in Ningbo] Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+ generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.

positive: Is it super-spreading? If the covid-19 virus is transmitted largely by superspreaders, it might not go pandemic, reports Debora MacKenzie

positive: Antibodies to SARS/CoV-2 in arbitrarily-selected Atlanta residents We quantitated anti-SARS/CoV-2 IgG and IgM by ELISA in self-collected blood samples (n=142) in arbitrarily-selected metro Atlanta residents, primarily acquaintances of the authors' lab members from 4/17-4/27, 2020. Archived serum (n=34), serum from nucleic acid test (NAT)-positive subjects (n=4), and samples collected from NAT-positive community members (n=4) served to validate the assay. The range of anti-SARS/CoV-2 antibodies in archived and NAT-positive sera indicated need to compromise sensitivity or specificity. Accordingly, we set a cutoff of 4 SD above the mean for IgG and 3 SD above the mean for IgM to indicate that an individual had been exposed, and developed some degree of immunity, to SARS/CoV-2. The IgG cutoff clearly compromised sensitivity but offered high specificity, both of which were harder to gauge for IgM. Based on these cutoffs, excluding subjects whose participation resulted from self-suspected SARS/CoV-2 infection, we found 7.1% positivity for anti-SARS/CoV-2 IgG (3 of 127 subjects) or IgM (6 of 127). While we do not claim this small immune survey is broadly representative of metro Atlanta, and we have greater confidence in the IgG results, which had only 2.4% positivity, it nonetheless demonstrates that persons with antibodies to SARS/CoV-2, who've not suspected they'd been exposed to this virus, can readily be found in various Atlanta area neighborhoods (9 positives were in 8 zip codes). Accordingly, these results support the notion that dissemination of the virus is more widespread than testing would indicate but also suggests that most persons in metro Atlanta remain vulnerable to this virus. More generally, these results support the general utility of sero-surveillance to guide public policy but also highlight the difficulty of discerning if individuals have immunity to SARS/CoV-2.

positive: Severe Acute Respiratory Syndrome: Developing a Research Response When severe acute respiratory syndrome (SARS) first came to world attention in March 2003, it was immediately perceived to be a global threat with a pandemic potential. To help coordinate international research efforts, the National Institute of Allergy and Infectious Diseases convened a colloquium entitled SARS: Developing a Research Response on 30 May 2003. Breakout sessions intended to identify unmet research needs in 5 areas of SARS research—clinical research, epidemiology, diagnostics, therapeutics, and vaccines—are summarized here. Since this meeting, however, the identified research needs have been only partially met. Needs that have yet to be realized include reliable methods for early identification of individuals with SARS, a full description of SARS pathogenesis and immune response, and animal models that faithfully mimic SARS respiratory symptoms. It is also of the utmost importance that the global scientific community enhance mechanisms for international cooperation and planning for SARS research, as well as for other emerging infectious disease threats that are certain to arise in the future.

positive: Commentary on the management of total laryngectomy patients during the COVID‐19 pandemic The coronavirus disease‐2019 (COVID‐19) pandemic has rapidly spread across the world, placing unprecedented strain on the health care system. Health care resources including hospital beds, ICUs, as well as personal protective equipment are becoming increasingly rationed and scare commodities. In this environment, the laryngectomee (patient having previously undergone a total laryngectomy) continues to represent a unique patient with unique needs. Given their surgically altered airway, they pose a challenge to manage for the otolaryngologist within the current COVID‐19 pandemic. In this brief report, we present special considerations and best practice recommendations in the management of total laryngectomy patients. We also discuss recommendations for laryngectomy patients and minimizing community exposures.

positive: A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment.

positive: [Epidemiological characteristics of severe acute respiratory syndrome in Tianjin and the assessment of effectiveness on measures of control]. OBJECTIVE To analyze the epidemiologic characteristics of severe acute respiratory syndrome (SARS) and to evaluate the effectiveness on its major control measures in Tianjn. METHODS Adopting two case reports 1 and 2, designed by the Tianjin Centers for Disease Control and Prevention to develop a unified case-tracing table including the map of the distribution of close contacts to SARS patients. With those methods, investigation on patients and their close contacts at hospital wards, families, communities and institutions of the patients were carried out. RESULTS From April 13 through May 8, 2003, there were 175 SARS cases including imported ones, were identified with an incidence rate of 1.9 cases per 100,000. Among them, 14 died with a fatality of 8.0%. The whole process of epidemic in Tianjin was less than one month with the following features: (1) 93.7% of the total SARS cases in Tianjin were directly or indirectly transmitted by a super-spreader. (2) 68.6% of the total SARS patients were concentrated in 3 hospitals A, B and C which was menifastated in 'clustering'. Through study on the rest of the SARS patients, results showed that 16.8% of them were transmitted through family close contact and 2.3% due to contact to colleagues. However, 12.6% of the patients were not able to show evidence that they had any contact to a diagnosed SARS patient. At the early stage of the epidemic, a number of medical practitioners were infected, taking up 38.2% of the total SARS cases. Among the total number of 1 975 medical workers who participated in the SARS medical cares and treatments, 3.4% of them got infected. During the outbreak, all index cases and chains of transmission seemed to be clear, with only 3 patients not able to be traced for the source of infection, taking up 2% of the total SARS patients in Tianjin. Among the 10 index cases, only the super spreader and another one index case transmitted the virus to their contacts but the rest of index cases did not cause any secondary infection. CONCLUSION Though SARS is clinically severe and can be spreaded quickly, the epidemic can be under control within a short period of time if chains of SARS transmission are broken down and effective measures as isolation and quarantine against patients as well as underscoring awareness among the publics in a scientific way, being carried out.

positive: Effects of density of infected population to the spreading of HIV epidemic in communities Abstract We present a dynamical model for the spread of HIV in a finite discrete population of size n represented by the set V . The model takes into account the structure of the sexual network, the density of infected population in each individual’s sexual partners, and a reasonable amount of the influence of noninfectious HIV positive individuals on HIV infectious partners which may occur in communities. In our analytic results, we give a precise epidemic threshold which, together with certain network properties, is then used to analyse and investigate the existence of epidemic and stability in the HIV spreading dynamics. Our results reproduce common observed patterns in the dynamics of HIV spreading in communities.

positive: The first case of the 2015 Korean Middle East Respiratory Syndrome outbreak This study reviewed problems in the prevention of outbreak and spread of Middle East Respiratory Syndrome (MERS) and aimed to provide assistance in establishing policies to prevent and manage future outbreaks of novel infectious diseases of foreign origin via in-depth epidemiological investigation of the patient who initiated the MERS outbreak in Korea, 2015. Personal and phone interviews were conducted with the patient and his guardians, and his activities in Saudi Arabia were investigated with the help of the Saudi Arabian Ministry of Health. Clinical courses and test results were confirmed from the medical records. The patient visited 4 medical facilities and contacted 742 people between May 11, 2015, at symptom onset, and May 20, at admission to the National Medical Center; 28 people were infected and diagnosed with MERS thereafter. Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments.

positive: Coronavirus outbreak in cheetahs: Lessons for SARS

positive: Super-spreading events of MERS-CoV infection

positive: Eat, Pray, Work: A meta-analysis of COVID-19 Transmission Risk in Common Activities of Work and Leisure ABSTRACT. BACKGROUND. When the lockdowns are relaxed, the responsibility of mitigating the COVID-19 spread shifts from the governments to the individuals. To know how to conduct one-self, it is important for everyone to know the risks of transmission during the quotidian activities - meetings, meals, etc, from individuals who are known to them and looking healthy. METHODS. The detailed case-studies corresponding to 425 infections upon point-exposures over a specified duration are curated. The data from the case studies is summarized and reorganized to reflect different situations from the daily life. A meta-analysis of the attack rates of transmission and the number of infections per infected person are performed. RESULTS. The attack rates are very high in family dinners (66.7% (48.8-80.8%)) compared to sit-down dinners with lesser mixing among people eating at different tables (15.7% (12.1-20.1%)), both lasting a couple of hours. In an open workspace office floor organized in a two-half structure with shared elevators and restrooms and the employees speaking continuously, the average attack rate over the course of a few days was much higher in one half (78.7% (70.3-85.3%)) than the one for the entire floor (43.5% (37.0-50.1%)). Inferred data suggests that the transmission in elevators and trains may be lower under the conditions of using masks. In most of the instances we studied, the infected individuals spreading (35/44) and even super-spreading (3/6) were mostly without symptoms of coughing, sneezing or a fever. CONCLUSIONS. Although the basic reproduction number R0 is around 3.0, the number of infections caused, including the super-spreading events, seem to be limited by the number of personal interactions in a group and their proximity. By acknowledging the risks in daily life, from healthy-looking persons, one may be able to organize their interactions better to reduce the chances of spreading or super-spreading infections.

positive: Transmission of SARS to healthcare workers. The experience of a Hong Kong ICU OBJECTIVE: To describe the extent and temporal pattern of transmission of severe acute respiratory syndrome (SARS) to intensive care unit staff. DESIGN: Retrospective observational cohort study. SETTING: University hospital intensive care unit, caring solely for patients with SARS or suspected to have SARS. PARTICIPANTS: Thirty-five doctors and 152 nurses and healthcare assistants who worked in the ICU during the SARS epidemic. Interventions: Infection control measures designed to prevent transmission of disease to staff were implemented. MEASUREMENTS AND RESULTS: Sixty-seven patients with SARS were admitted to the intensive care unit. Four nurses and one healthcare assistant contracted SARS, with three of these developing symptoms within 10 days of admission of the first patient with SARS. Doctors were exposed to patients with SARS for a median (IQR) of 284 (97–376) h, while nurses and healthcare assistants were exposed for a median (IQR) of 119 (57–166) h. The ICU did not meet international standards for physical space or ventilation. CONCLUSIONS: In an ICU in which infection control procedures are rigorously applied, the risk to staff of contracting SARS from patients is low, despite long staff exposure times and a sub-standard physical environment. ELECTRONIC SUPPLEMENTARY MATERIAL: The electronic reference of this article is http://dx.doi.org/10.1007/s00134-006-0081-1 The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.

positive: Impact of Superspreaders on dissemination and mitigation of COVID-19 Background: The emerging SARS-CoV-2 virus has caused a global pandemic characterized by superspreader events. Heterogeneity in transmission risk is a known phenomenon in infectious diseases and was also seen in SARS and MERS outbreaks since 2003. The pandemic has led countries to control the pandemic spread using unprecedented severe mitigation strategies that include quarantine and lock-down. This has has been highly successful in terms of halting the spread, but had enormous socioeconomic cost. We set out to theoretically explore whether a model that includes the phenomenon of superspreaders may guide us towards a cost-effective mitigation strategy. Methods: We developed an agent-based model that includes persons that spread the disease far more readily than other persons. This allow us to investigate effect of containment strategies in both a random SEIR like scenario, and in a transmission model that work with structured society. Our model considered even contact patterns in three settings: home, work and a category of "other" settings representing diffuse social contacts. We introduced superspreaders either as a fixed proportion of the population, or as a broad spectrum of infectivity. For each choice, the model was then calibrated to an overall realistic daily growth rate of 23 percentage. As sensitivity analyses we varied the fraction of superspreaders as well the distribution of their infectivity. To compare the simulation findings for each mitigation scenario we considered the maximum daily ICU utility. Results: As expected, without mitigation imposed, the inclusion of superspreaders does not meaningfully change the epidemic trajectory. However when introducing mitigation strategies imposed on each of the three settings, we find that the presence of superspreaders made a substantial difference. The simulations demonstrate that the best strategy is to focus on limiting contacts in the other category. This in particular suggests that limiting diffuse social contacts in settings such as bars, transportation, restaurants, parties, concerts and lecture halls is far more effective than limiting the same amount of contact events in the home and work setting. Conclusions: To appreciate effect of heterogeneity in various social spheres we need to rethink disease transmission models. Doing so, we found that wide distribution of infectivity favours strategies that reduces the max, while leaving the typical behaviour undisturbed. We found that most workplaces may be opened without much influence on the epidemic, while one could snuff out transmission with an effective avoidance of other contacts. Interestingly, including a consideration of superspreaders can help explain the dramatic success of even moderate lock-down strategies as that practiced in Denmark and Sweden. And it points to the need to avoid mass gatherings until either flock immunity has been achieved or an effective vaccine is available.

positive: Occupational risks for COVID-19 infection

positive: Fundamental difference between superblockers and superspreaders in networks Two important problems regarding spreading phenomena in complex topologies are the optimal selection of node sets either to minimize or maximize the extent of outbreaks. Both problems are nontrivial when a small fraction of the nodes in the network can be used to achieve the desired goal. The minimization problem is equivalent to a structural optimization. The “superblockers,” i.e., the nodes that should be removed from the network to minimize the size of outbreaks, are those nodes that make connected components as small as possible. “Superspreaders” are instead the nodes such that, if chosen as initiators, they maximize the average size of outbreaks. The identity of superspreaders is expected to depend not just on the topology, but also on the specific dynamics considered. Recently, it has been conjectured that the two optimization problems might be equivalent, in the sense that superblockers act also as superspreaders. In spite of its potential groundbreaking importance, no empirical study has been performed to validate this conjecture. In this paper, we perform an extensive analysis over a large set of real-world networks to test the similarity between sets of superblockers and of superspreaders. We show that the two optimization problems are not equivalent: superblockers do not act as optimal spreaders.

positive: Mathematical Modeling of COVID-19 Transmission Dynamics with a Case Study of Wuhan We propose a compartmental mathematical model for the spread of the COVID-19 disease with special focus on the transmissibility of super-spreaders individuals. We compute the basic reproduction number threshold, we study the local stability of the disease free equilibrium in terms of the basic reproduction number, and we investigate the sensitivity of the model with respect to the variation of each one of its parameters. Numerical simulations show the suitability of the proposed COVID-19 model for the outbreak that occurred in Wuhan, China.

positive: COVID-19: preparing for superspreader potential among Umrah pilgrims to Saudi Arabia

positive: Is the spread of COVID-19 across countries influenced by environmental, economic and social factors? The SARS-CoV-2 virus, emerged from Wuhan, China is spreading all over the world in an unprecedented manner, causing millions of infections and thousands of deaths. However, the spread of the disease across countries and regions are not even. Why some countries and regions are more affected than some other countries and regions? We employ simple statistical methods to investigate any linkage between the severity of the disease and the environmental, economic and social factors of countries. The estimation results indicate that the number of confirmed cases of Coronavirus infection is higher in countries with lower yearly average temperatures, higher economic openness, and stronger political democracy. However, findings of this analysis should be interpreted carefully keeping in mind the fact that statistical relations do not necessarily imply causation. Only clinical experiments with medical expertise can confirm how the virus behaves in the environment.

positive: Significance of super spreader events in COVID-19. The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.

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: Ultrametric model for covid-19 dynamics: an attempt to explain slow approaching herd immunity in Sweden We present a mathematical model of infection dynamics that might explain slower approaching the herd immunity during the covid-19 epidemy in Sweden than it was predicted by a variety of other models; see graphs Fig. 2. The new model takes into account the hierarchic structure of social clusters in the human society. We apply the well developed theory of random walk on the energy landscapes represented mathematically with ultrametric spaces. This theory was created for applications to spin glasses and protein dynamics. To move from one social cluster (valley) to another, the virus (its carrier) should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider linearly increasing (with respect to hierarchy's levels) barriers. This structure of barriers matches with a rather soft regulations imposed in Sweden in March 2020. In this model, the infection spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This model's feature matches with the real situation during the covid-19 epidemy, with its cluster spreading structure. Clusters need not be determined solely geographically, they are based on a number of hierarchically ordered social coordinates. The model differs crucially from the standard mathematical models of spread of disease, such as the SIR-model. In particular, our model describes such a specialty of spread of covid-19 virus as the presence of "super-spreaders" who by performing a kind of random walk on a hierarchic landscape of social clusters spreads infection. In future, this model will be completed by adding the SIR-type counterpart. But, the latter is not a specialty of covid-19 spreading.

positive: Comparison of transmissibility of coronavirus between symptomatic and asymptomatic patients: Reanalysis of the Ningbo Covid-19 data We investigate the transmissibility of coronavirus for symptomatic and asymptomatic patients using the Ningbo Covid-19 data1. Through more in-depth and comprehensive statistical analysis, we conclude that there is no difference in the transmission rates of coronavirus between the symptomatic and asymptomatic patients, which is consistent with the original findings in Chen et al.1

positive: Not all interventions are equal for the height of the second peak In this paper we conduct a simulation study of the spread of an epidemic like COVID-19 with temporary immunity on finite spatial and non-spatial network models. In particular, we assume that an epidemic spreads stochastically on a scale-free network and that each infected individual in the network gains a temporary immunity after its infectious period is over. After the temporary immunity period is over, the individual becomes susceptible to the virus again. When the underlying contact network is embedded in Euclidean geometry, we model three different intervention strategies that aim to control the spread of the epidemic: social distancing, restrictions on travel, and restrictions on maximal number of social contacts per node. Our first finding is that on a finite network, a long enough average immunity period leads to extinction of the pandemic after the first peak, analogous to the concept of"herd immunity". For each model, there is a critical average immunity length $L_c$ above which this happens. Our second finding is that all three interventions manage to flatten the first peak (the travel restrictions most efficiently), as well as decrease the critical immunity length $L_c$, but elongate the epidemic. However, when the average immunity length $L$ is shorter than $L_c$, the price for the flattened first peak is often a high second peak: for limiting the maximal number of contacts, the second peak can be as high as 1/3 of the first peak, and twice as high as it would be without intervention. Thirdly, interventions introduce oscillations into the system and the time to reach equilibrium is, for almost all scenarios, much longer. We conclude that network-based epidemic models can show a variety of behaviors that are not captured by the continuous compartmental models.

positive: COVID-19 epidemic: Power law spread and flattening of the curve In this paper, we analyze the real-time infection data of COVID-19 epidemic for nine nations. Our analysis is up to 7 April 2020. For China and South Korea, who have already flattened their infection curves, the number of infected individuals (I(t)) exhibits power-law behavior before flattening of the curve. Italy has transitioned to the power-law regime for some time. For the other six nations-USA, Spain, Germany, France, Japan, and India-a power-law regime is beginning to appear after exponential growth. We argue that the transition from an exponential regime to a power-law regime may act as an indicator for flattening of the epidemic curve. We also argue that long-term community transmission and/or the transmission by asymptomatic carriers traveling long distances may be inducing the power-law growth of the epidemic.

positive: Distribution of the 2019-nCoV Epidemic and Correlation with Population Emigration from Wuhan, China BACKGROUNDS: The ongoing new coronavirus (2019-nCoV) pneumonia outbreak is spreading in China and has not reached its peak. Five millions of people had emigrated from Wuhan before the city lockdown, which potentially represent a source of virus spreaders. Case distribution and its correlation with population emigration from Wuhan in early epidemic are of great importance for early warning and prevention of future outbreak. METHODS: The officially reported cases of 2019-nCoV pneumonia were collected as of January 30, 2020. Time and location information of these cases were extracted analyzed with ArcGIS and WinBUGS. Population migration data of Wuhan City and Hubei province were extracted from Baidu Qianxi and analyzed for their correlation with case number. FINDINGS: The 2019-nCoV pneumonia cases were predominantly distributed in Hubei and other provinces of South China. Hot spot provinces included Sichuan and Yunnan provinces that are adjacent to Hubei. While Wuhan city has the highest number of cases, the time risk is relatively stable. Numbers of cases in some cities are relatively low, but the time risks are continuously rising. The case numbers of different provinces and cities of Hubei province were highly correlated with the emigrated populations from Wuhan. Lockdown of 19 cities of Hubei province, and implementation of nationwide control measures efficiently prevented the exponential growth of case number. INTERPRETATION: Population emigrated from Wuhan was the main infection source for other cities and provinces. Some cities with low case number but were in rapid increase. Due to the upcoming Spring Festival return transport wave, understanding of the trends of risks in different regions is of great significance for preparedness for both individuals and institutions.

positive: 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.

positive: Superspreading in Early Transmissions of COVID-19 in Indonesia We estimate the basic reproduction number R0 and the overdispersion parameter K at two COVID-19 clusters in Indonesia: Jakarta-Depok and Batam. Based on the first 397 confirmed cases in both clusters, we find a high degree of individual-level variation in the transmission. The basic reproduction number R0 is estimated at 6.79 and 2.47, while the overdispersion parameter K of a negative-binomial distribution is estimated at 0.08 and 0.2 for Jakarta-Depok and Batam, respectively. This suggests that superspreading events played a key role in the early stage of the outbreak, i.e., a small number of infected individuals are responsible for large amounts of COVID-19 transmission.

positive: Progress in Global Surveillance and Response Capacity 10 Years after Severe Acute Respiratory Syndrome Ten years have elapsed since the World Health Organization issued its first global alert for an unexplained illness named severe acute respiratory syndrome (SARS). The anniversary provides an opportunity to reflect on the international response to this new global microbial threat. While global surveillance and response capacity for public health threats have been strengthened, critical gaps remain. Of 194 World Health Organization member states that signed on to the International Health Regulations (2005), <20% had achieved compliance with the core capacities required by the deadline in June 2012. Lessons learned from the global SARS outbreak highlight the need to avoid complacency, strengthen efforts to improve global capacity to address the next pandemic using all available 21st century tools, and support research to develop new treatment options, countermeasures, and insights while striving to address the global inequities that are the root cause of many of these challenges.

positive: Do superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19 The current global propagation of COVID-19 is heterogeneous, with slow transmission continuing in many countries and exponential propagation in others, where the time that it took for the explosive spread to begin varied greatly. It is proposed that this could be explained by cascading superspreading events, in which new infections caused by a superspreader are more likely to be highly infectious. The mechanism suggested for this is related to viral loads. Exposure to high viral loads may result in high-intensity infection, which exposes new cases to high viral loads. This notion is supported by experimental veterinary research.

positive: Testing for COVID-19: willful ignorance or selfless behavior? Widespread testing is key to controlling the spread of COVID-19. But should we worry about self-selection bias in the testing? The recent literature on willful ignorance says we should – people often avoid health information. In the context of COVID-19, such willful ignorance can bias testing data. Furthermore, willful ignorance often arises when selfish wants conflict with social benefits, which might be particularly likely for potential ‘super-spreaders’ – people with many social interactions – given people who test positive are urged to self-isolate for two weeks. We design a survey in which participants (n = 897) choose whether to take a costless COVID-19 test. We find that 70% would take a test. Surprisingly, the people most likely to widely spread COVID-19 – the extraverts, others who meet more people in their daily lives and younger people – are the most willing to take a test. People's ability to financially or emotionally sustain self-isolation does not matter to their decision. We conclude that people are selfless in their decision to test for COVID-19. Our results are encouraging – they imply that COVOD-19 testing may succeed in targeting those who generate the largest social benefits from self-isolation if infected, which strengthens the case for widespread testing.

positive: Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference Abstract The International Society for Influenza and other Respiratory Virus Diseases held its 5th Antiviral Group (isirv-AVG) Conference in Shanghai, China, in conjunction with the Shanghai Public Health Center and Fudan University from 14-16 June 2017. The three-day programme encompassed presentations on some of the clinical features, management, immune responses and virology of respiratory infections, including influenza A(H1N1)pdm09 and A(H7N9) viruses, MERS-CoV, SARS-CoV, adenovirus Type 80, enterovirus D68, metapneumovirus and respiratory syncytial virus (RSV). Updates were presented on several therapeutics currently in clinical trials, including influenza polymerase inhibitors pimodivir/JNJ6362387, S033188, favipiravir, monoclonal antibodies MHAA45449A and VIS410, and host directed strategies for influenza including nitazoxanide, and polymerase ALS-008112 and fusion inhibitors AK0529, GS-5806 for RSV. Updates were also given on the use of the currently licensed neuraminidase inhibitors. Given the location in China, there were also presentations on the use of Traditional Chinese Medicines. Following on from the previous conference, there were ongoing discussions on appropriate endpoints for severe influenza in clinical trials from regulators and clinicians, an issue which remains unresolved. The aim of this conference summary is to provide information for not only conference participants, but a detailed referenced review of the current status of clinical trials, and pre-clinical development of therapeutics and vaccines for influenza and other respiratory diseases for a broader audience.

positive: Closed environments facilitate secondary transmission of coronavirus disease 2019 (COVID-19) Objective: To identify common features of cases with novel coronavirus disease (COVID-19) so as to better understand what factors promote secondary transmission including superspreading events. Methods: A total of 110 cases were examined among eleven clusters and sporadic cases, and investigated who acquired infection from whom. The clusters included four in Tokyo and one each in Aichi, Fukuoka, Hokkaido, Ishikawa, Kanagawa and Wakayama prefectures. The number of secondary cases generated by each primary case was calculated using contact tracing data. Results: Of the 110 cases examined, 27 (24.6%) were primary cases who generated secondary cases. The odds that a primary case transmitted COVID-19 in a closed environment was 18.7 times greater compared to an open-air environment (95% confidence interval [CI]: 6.0, 57.9). Conclusions: It is plausible that closed environments contribute to secondary transmission of COVID-19 and promote superspreading events. Our findings are also consistent with the declining incidence of COVID-19 cases in China, as gathering in closed environments was prohibited in the wake of the rapid spread of the disease.

positive: COVID-19: Facts, Cultural Considerations, and Risk of Stigmatization Data on COVID-19 supports targeted social distancing could be an effective way to reduce morbidity and mortality, but could inadvertently increase stigma for affected populations. As health care providers we must be aware of the facts of COVID-19, cultural implications, and potential for stigmatization of populations affected by COVID-2019. It is important to consider the real economic impact related to lost workdays due to quarantine and social isolation efforts as well as travel restrictions that may negatively impact access to care and ability to pay for care. Efforts geared towards general education about the disease and the rationale for quarantine and public health information provided to the general public can reduce stigmatization. Countries who are successful at aggressive screening, early identification, patient isolation, contact tracing, quarantine, and infection control methods should also address the risk of stigmatization among populations and the negative effects which could occur. The cases of COVID-19 will continue to rise and the virus will be sustainable for future infections. Timely and appropriate public health interventions addressing cultural impact and risk for stigmatization along with proper screening, treatment, and follow up for affected individuals and close contacts can reduce the number of infections, serious illness, and deaths.

positive: Effects of operational decisions on the diffusion of epidemic disease: A system dynamics modeling of the MERS-CoV outbreak in South Korea Abstract We evaluated the nosocomial outbreak of Middle East Respiratory Syndrome (MERS) Coronavirus (CoV) in the Republic of Korea, 2015, from a healthcare operations management perspective. Establishment of healthcare policy in South Korea provides patients’ freedom to select and visit multiple hospitals. Current policy enforces hospitals preference for multi-patient rooms to single-patient rooms, to lower financial burden. Existing healthcare systems tragically contributed to 186 MERS outbreak cases, starting from single “index patient” into three generations of secondary infections. By developing a macro-level health system dynamics model, we provide empirical knowledge to examining the case from both operational and financial perspectives. In our simulation, under base infectivity scenario, high emergency room occupancy circumstance contributed to an estimated average of 101 (917%) more infected patients, compared to when in low occupancy circumstance. Economic patient room design showed an estimated 702% increase in the number of infected patients, despite the overall 98% savings in total expected costs compared to optimal room design. This study provides first time, system dynamics model, performance measurements from an operational perspective. Importantly, the intent of this study was to provide evidence to motivate public, private, and government healthcare administrators’ recognition of current shortcomings, to optimize performance as a whole system, rather than mere individual aspects.

positive: Transmission characteristics of the COVID-19 outbreak in China: a study driven by data The COVID-19 outbreak has been a serious public health threat worldwide. We use individually documented case descriptions of COVID-19 from China (excluding Hubei Province) to estimate the distributions of the generation time, incubation period, and periods from symptom onset to isolation and to diagnosis. The recommended 14-day quarantine period may lead to a 6.7% failure for quarantine. We recommend a 22-day quarantine period. The mean generation time is 3.3 days and the mean incubation period is 7.2 days. It took 3.7 days to isolate and 6.6 days to diagnose a patient after his/her symptom onset. Patients may become infectious on average 3.9 days before showing major symptoms. This makes contact tracing and quarantine ineffective. The basic reproduction number is estimated to be 1.54 with contact tracing, quarantine and isolation, mostly driven by super spreaders.

positive: Pathogenesis of COVID-19 from a cell biologic perspective COVID-19 can be understood by the region of the lung that is infected. Mild disease will be confined to the conducting airways and severe disease will involve the gas exchange portion of the lung.

positive: System Dynamics Modeling of Within-Host Viral Kinetics of Coronavirus (SARS CoV-2) Mathematical models are being used extensively in the study of SARS-CoV-2 transmission dynamics, becoming an essential tool for decision making concerning disease control. It is now required to understand the mechanisms involved in the interaction between the virus and the immune response effector cells, both innate and adaptive, in order to support lines of research related to the use of drugs, production of protective antibodies and of course, vaccines against SARS-CoV-2. The present study, using a system dynamic approach, hypothesizes over the conditions that characterize the fraction of the population which get infected by SARS-CoV-2 as the asymptomatic patients, the mild symptomatic, acute symptomatic, and also super-spreaders, in terms of innate immune response, the initial virus load, the virus burden with shedding events, and the cytokine levels.

positive: Mobility network modeling explains higher SARS-CoV-2 infection rates among disadvantaged groups and informs reopening strategies Fine-grained epidemiological modeling of the spread of SARS-CoV-2 -- capturing who is infected at which locations -- can aid the development of policy responses that account for heterogeneous risks of different locations as well as the disparities in infections among different demographic groups. Here, we develop a metapopulation SEIR disease model that uses dynamic mobility networks, derived from US cell phone data, to capture the hourly movements of millions of people from local neighborhoods (census block groups, or CBGs) to points of interest (POIs) such as restaurants, grocery stores, or religious establishments. We simulate the spread of SARS-CoV-2 from March 1-May 2, 2020 among a population of 105 million people in 10 of the largest US metropolitan statistical areas. We show that by integrating these mobility networks, which connect 60k CBGs to 565k POIs with a total of 5.4 billion hourly edges, even a relatively simple epidemiological model can accurately capture the case trajectory despite dramatic changes in population behavior due to the virus. Furthermore, by modeling detailed information about each POI, like visitor density and visit length, we can estimate the impacts of fine-grained reopening plans: we predict that a small minority of "superspreader" POIs account for a large majority of infections, that reopening some POI categories (like full-service restaurants) poses especially large risks, and that strategies restricting maximum occupancy at each POI are more effective than uniformly reducing mobility. Our models also predict higher infection rates among disadvantaged racial and socioeconomic groups solely from differences in mobility: disadvantaged groups have not been able to reduce mobility as sharply, and the POIs they visit (even within the same category) tend to be smaller, more crowded, and therefore more dangerous. By modeling who is infected at which locations, our model supports fine-grained analyses that can inform more effective and equitable policy responses to SARS-CoV-2.

positive: Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Image: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only [Image: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Image: see text], with a maximum value up to [Image: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.

positive: Behavioral changes before lockdown, and decreased retail and recreation mobility during lockdown, contributed most to the successful control of the COVID-19 epidemic in 35 Western countries The COVID-19 pandemic has prompted a lockdown in many countries to control the exponential spread of the SARS-CoV-2 virus. This resulted in curbing the epidemic by reducing the time-varying basic reproduction number (Rt) to below one. Governments are looking for evidence to balance the demand of their citizens to ease some of the restriction, against the fear of a second peak in infections. More details on the specific circumstances that promote exponential spread (i.e. Rt>1) and the measures that contributed most to a reduction in Rt are needed. Here we show that in 33 of 35 Western countries (32 European, plus Israel, USA and Canada), Rt fell to around or below one during lockdown (March - May 2020). One third of the effect happened already on average 6 days before the lockdown, with lockdown itself causing another major drop in transmission. Country-wide compulsory usage of masks was implemented only in Slovakia 10 days into lockdown, and on its own reduced transmission by half. During lockdown, decreased mobility in retail and recreation was an independent predictor of lower Rt during lockdown, while changes in other types of mobility were not. These results are consistent with anecdotal evidence that large recreational gatherings are super-spreading events, and may even suggest that infections during day-to-day contact at work are not sufficient to spark exponential growth. Our data suggest measures that will contribute to avoiding a second peak include a tight control on circumstances that facilitate massive spread such as large gatherings especially indoors, physical distancing, and mask use.

positive: Novel Percutaneous Tracheostomy for Critically Ill Patients with COVID-19 Abstract Background COVID-19 is a worldwide pandemic, with many patients requiring prolonged mechanical ventilation. Tracheostomy is not recommended by current guidelines as it is considered a super-spreading event due to aerosolization that unduly risks healthcare workers. Methods Patients with severe COVID-19 that were on mechanical ventilation ≥ 5 days were evaluated for percutaneous dilational tracheostomy. We developed a novel percutaneous tracheostomy technique that placed the bronchoscope alongside the endotracheal tube, not inside it. This improved visualization during the procedure and continued standard mechanical ventilation after positioning the inflated endotracheal tube cuff in the distal trachea. This technique offers a significant mitigation for the risk of virus aerosolization during the procedure. Results From March 10 to April 15, 2020, 270 patients with COVID-19 required invasive mechanical ventilation at New York University Langone Health Manhattan’s campus of which 98 patients underwent percutaneous dilational tracheostomy. The mean time from intubation to the procedure was 10.6 days (SD ±5 days). Currently, thirty-two (33%) patients do not require mechanical ventilatory support, 19 (19%) have their tracheostomy tube downsized and 8 (8%) were decannulated. Forty (41%) patients remain on full ventilator support, while 19 (19%) are weaning from mechanical ventilation. Seven (7%) died as result of respiratory and multiorgan failure. Tracheostomy related bleeding was the most common complication (5 patients). None of health care providers have developed symptoms or tested positive for COVID-19. Conclusions Our percutaneous tracheostomy technique appears to be safe and effective for COVID-19 patients and safe for healthcare workers.

positive: Super-spreading events of SARS in a hospital setting: who, when, and why?

positive: Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health interventions. We present an analysis of the first 10 weeks of the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. The epidemic to date has been characterized by two large clusters-initiated by two separate "super-spread" events (SSEs)-and by ongoing community transmission. By fitting a stochastic model to data on 1512 cases, including these clusters, we show that the etiological agent of SARS is moderately transmissible. Excluding SSEs, we estimate that 2.7 secondary infections were generated per case on average at the start of the epidemic, with a substantial contribution from hospital transmission. Transmission rates fell during the epidemic, primarily as a result of reductions in population contact rates and improved hospital infection control, but also because of more rapid hospital attendance by symptomatic individuals. As a result, the epidemic is now in decline, although continued vigilance is necessary for this to be maintained. Restrictions on longer range population movement are shown to be a potentially useful additional control measure in some contexts. We estimate that most currently infected persons are now hospitalized, which highlights the importance of control of nosocomial transmission.

positive: Unlinking super-linkers: the topology of epidemic response (Covid-19) A key characteristic of the spread of infectious diseases is their ability to use efficient transmission paths within contact graphs. This enables the pathogen to maximise infection rates and spread within a target population. In this work, we devise techniques to localise infections and decrease infection rates based on a principled analysis of disease transmission paths within human-contact networks (proximity graphs). Experimental results of disease spreading shows that that at low visibility rates contact tracing slows disease spreading. However to stop disease spreading, contact tracing requires both significant visibility (at least 60%) into the proximity graph and the ability to place half of the population under isolation. We find that pro-actively isolating super-links -- key proximity encounters -- has significant benefits: targeted isolation of a fourth of the population based on 35% visibility into the proximity graph prevents an epidemic outbreak. It turns out that isolating super-spreaders is more effective than contact tracing and testing but less effective than targeting super-links. We highlight the important role of topology in epidemic outbreaks. We argue that proactive innoculation of a population by disabling super-links and super-spreaders may have an important complimentary role alongside contact tracing and testing as part of a sophisticated public-health response to epidemic outbreaks.

positive: Feeder use predicts both acquisition and transmission of a contagious pathogen in a North American songbird. Individual heterogeneity can influence the dynamics of infectious diseases in wildlife and humans alike. Thus, recent work has sought to identify behavioural characteristics that contribute disproportionately to individual variation in pathogen acquisition (super-receiving) or transmission (super-spreading). However, it remains unknown whether the same behaviours enhance both acquisition and transmission, a scenario likely to result in explosive epidemics. Here, we examined this possibility in an ecologically relevant host-pathogen system: house finches and their bacterial pathogen, Mycoplasma gallisepticum, which causes severe conjunctivitis. We examined behaviours likely to influence disease acquisition (feeder use, aggression, social network affiliations) in an observational field study, finding that the time an individual spends on bird feeders best predicted the risk of conjunctivitis. To test whether this behaviour also influences the likelihood of transmitting M. gallisepticum, we experimentally inoculated individuals based on feeding behaviour and tracked epidemics within captive flocks. As predicted, transmission was fastest when birds that spent the most time on feeders initiated the epidemic. Our results suggest that the same behaviour underlies both pathogen acquisition and transmission in this system and potentially others. Identifying individuals that exhibit such behaviours is critical for disease management.

positive: The impact of super-spreaders in COVID-19: mapping genome variation worldwide The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the 21st century. We analyzed >4,700 SARS-CoV-2 genomes and associated meta-data retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and >160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a uniform mutation occurrence along branches that could complicate the design of future vaccines. The root of SARS-CoV-2 genomes locates at the Chinese haplogroup B1, with a TMRCA dating to 12 November 2019 - thus matching epidemiological records. Sub-haplogroup A2a originates in China and represents the major non-Asian outbreak. Multiple founder effect episodes, most likely associated with super-spreader hosts, explain COVID-19 pandemic to a large extent.

positive: Secondary attack rate and superspreading events for SARS-CoV-2

positive: Criminalizing Health-Related Behaviors Dangerous to Others? Disease Transmission, Transmission-Facilitation, and the Importance of Trust Statutes criminalizing behavior that risks transmission of HIV/AIDS exemplify use of the criminal law against individuals who are victims of infectious disease. These statutes, despite their frequency, are misguided in terms of the goals of the criminal law and the public health aim of reducing overall burdens of disease, for at least three important reasons. First, they identify individual offenders for punishment, a paradigm that is misplaced in the most typical contexts of transmission of infectious disease and even for HIV/AIDS, despite claims of AIDS exceptionalism. Second, although there are examples of individuals who transmit infectious disease in a manner that fits the criminal law paradigm of identification of individual offenders for deterrence or retribution, these examples are limited and can be accommodated by existing criminal laws not devoted specifically to infectious disease. Third, and most importantly, the current criminal laws regarding HIV/AIDS, like many other criminal laws applied to infectious disease transmission, have been misguided in focusing on punishment of the diseased individual as a wrongful transmitter. Instead of individual offenders, activities that enhance the scale of disease transmission—behaviors that might be characterized as ‘transmission facilitation’—are a more appropriate target for the criminal law. Examples are trafficking in human beings (including sex trafficking, organ trafficking, and labor trafficking), suppression of information about the emergence of infection in circumstances in which there is a legally established obligation to disclose, and intentional or reckless activities to discourage disease treatment or prevention. Difficulties remain with justifications for criminalizing even these behaviors, however, most importantly the need for trust in reducing overall burdens of disease, problems in identifying individual responsible offenders, and potential misalignment between static criminal law and the changing nature of infectious disease.

positive: Revised Triage and Surveillance Protocols for Temporary Emergency Department Closures in Tertiary Hospitals as a Response to COVID-19 Crisis in Daegu Metropolitan City BACKGROUND: When an emergency-care patient is diagnosed with an emerging infectious disease, hospitals in Korea may temporarily close their emergency departments (EDs) to prevent nosocomial transmission. Since February 2020, multiple, consecutive ED closures have occurred due to the coronavirus disease 2019 (COVID-19) crisis in Daegu. However, sudden ED closures are in contravention of laws for the provision of emergency medical care that enable the public to avail prompt, appropriate, and 24-hour emergency medical care. Therefore, this study ascertained the vulnerability of the ED at tertiary hospitals in Daegu with regard to the current standards. A revised triage and surveillance protocol has been proposed to tackle the current crisis. METHODS: This study was retrospectively conducted at 6 level 1 or 2 EDs in a metropolitan city where ED closure due to COVID-19 occurred from February 18 to March 26, 2020. The present status of ED closure and patient characteristics and findings from chest radiography and laboratory investigations were assessed. Based on the experience from repeated ED closures and the modified systems that are currently used in EDs, revised triage and surveillance protocols have been developed and proposed. RESULTS: During the study period, 6 level 1 or 2 emergency rooms included in the study were shut down 27 times for 769 hours. Thirty-one confirmed COVID-19 cases, of whom 7 died, were associated with the incidence of ED closure. Typical patient presentation with respiratory symptoms of COVID-19 was seen in less than 50% of patients, whereas abnormal findings on chest imaging investigations were detected in 93.5% of the study population. The chest radiography facility, resuscitation rooms, and triage area were moved to locations outside the ED, and a new surveillance protocol was applied to determine the factors warranting quarantine, including symptoms, chest radiographic findings, and exposure to a source of infection. The incidence of ED closures decreased after the implementation of the revised triage and surveillance protocols. CONCLUSION: Triage screening by emergency physicians and surveillance protocols with an externally located chest imaging facility were effective in the early isolation of COVID-19 patients. In future outbreaks of emerging infectious diseases, efforts should be focused toward the provision of continued ED treatment with the implementation of revised triage and surveillance protocols.

positive: Modelling suggests blood group incompatibility may substantially reduce SARS-CoV-2 transmission Several independent datasets suggest blood type A is over-represented and type O under-represented among COVID-19 patients. Here, I model a scenario in which ABO transfusion incompatibility reduces the chance of a patient transmitting the virus to an incompatible recipient. Comparison of model outputs to published data on COVID-19 prevalence indicates that if this scenario holds true, ABO incompatibility may reduce virus transmissibility by 60% or more. Paradoxically, however, targeted vaccination of either high-susceptibility type A or "super-spreader" type O individuals is less effective than random vaccination at blocking community spread of the virus. Instead, the key is to maintain blood type diversity amongst the remaining susceptible individuals. I stress that these results illustrate a theoretical model of ABO blood group interaction with virus transmission and require confirmation by observation.

positive: Transmission potential and severity of COVID-19 in South Korea Abstract Objectives Since the first case of 2019 novel coronavirus (COVID-19) identified on Jan 20, 2020 in South Korea, the number of cases rapidly increased, resulting in 6,284 cases including 42 deaths as of March 6, 2020. To examine the growth rate of the outbreak, we aimed to present the first study to report the reproduction number of COVID-19 in South Korea. Methods The daily confirmed cases of COVID-19 in South Korea were extracted from publicly available sources. By using the empirical reporting delay distribution and simulating the generalized growth model, we estimated the effective reproduction number based on the discretized probability distribution of the generation interval. Results We identified four major clusters and estimated the reproduction number at 1.5 (95% CI: 1.4-1.6). In addition, the intrinsic growth rate was estimated at 0.6 (95% CI: 0.6, 0.7) and the scaling of growth parameter was estimated at 0.8 (95% CI: 0.7, 0.8), indicating sub-exponential growth dynamics of COVID-19. The crude case fatality rate is higher among males (1.1%) compared to females (0.4%) and increases with older age. Conclusions Our results indicate early sustained transmission of COVID-19 in South Korea and support the implementation of social distancing measures to rapidly control the outbreak.

positive: Evidence and characteristics of human-to-human transmission of SARS-CoV-2 Background: On December 31, 2019, an outbreak of COVID-19 in humans was reported in Wuhan, and then spread fast to other provinces, China. We analyzed data from field investigations and genetic sequencing to describe the evidence and characteristics of human-to-human transmission in Guangdong Province. Methods: A confirmed COVID-19 case was defined if a suspected case was verified with positive of SARS-CoV-2 in throat swabs, nasal swabs, bronchoalveolar lavage fluid (BALF), or endotracheal aspirates by real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) or genetic sequencing. Field investigations were conducted for each confirmed case. Clinical and demographic data of confirmed cases were collected from medical records. Exposure and travel history were obtained by interview. Results: A total of 1,151 confirmed cases were identified as of February 10, 2020 in Guangdong Province, China. Of them, 697 (60.1%) cases were from 234 cluster infections. Two hundred and fourteen (18.6%) were secondary cases, in which 144 cases were from family cluster infections. With the epidemic continuing, although familial cluster events were dominated, community cluster events increased with a nosocomial event. The whole genomes within the same family cluster infections were identical, and presented a few unique single nucleotide variants (SNVs) compared with SARS-CoV-2 identified on December 2019 in Wuhan. Conclusions: We observed evident human-to-human transmissions of SARS-CoV-2 in Guangdong, China. Although most of them were from family cluster infections, community and nosocomial infections were increasing. Our findings indicate that human-to-human transmission risks are transferring from family to community in Guangdong Province.

positive: COVID-19 Super-spreaders: Definitional Quandaries and Implications Uncertainty around the role ‘super-spreaders’ play in the transmission and escalation of infectious disease is compounded by its broad and vague definition. It is a term that has been much used in relation to COVID-19, particularly in social media. On its widest definition, it refers to a propensity to infect a larger than average number of people. Given the biological, behavioural and environmental variables relevant to infectivity, this might be pertinent to almost any infected individual who is not physically isolated from others. Nor is the term confined to individuals with a propensity to spread infectious disease: it can potentially be used to describe events, policies or settings. This article explores the use of the term and considers circumstances in which the wide definition can be problematic. One problem is that it can lead to undeserved apportionment of moral blame to alleged super-spreaders. Another is that it can detract from scientific investigation of the heterogeneity of COVID-19 transmission. The author calls for a clearer epidemiological definition.

positive: The epidemiological and clinical features of COVID-19 and lessons from this global infectious public health event Abstract Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a potentially fatal disease of great global public health importance. As of March 26, 2020, the outbreak of COVID-19 has resulted in 462,801 confirmed cases and 20,839 deaths globally, which is more than those caused by SARS and Middle East respiratory syndrome (MERS) in 2003 and 2013, respectively. The epidemic has posed considerable challenges worldwide. Under a strict mechanism of massive prevention and control, China has seen a rapid decrease in new cases of coronavirus; however, the global situation remains serious. Additionally, the origin of COVID-19 has not been determined and no specific antiviral treatment or vaccine is currently available. Based on the published data, this review systematically discusses the etiology, epidemiology, clinical characteristics, and current intervention measures related to COVID-19 in the hope that it may provide a reference for future studies and aid in the prevention and control of the COVID-19 epidemic.

positive: Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respiratory syndrome coronavirus, MERS-CoV) can cause intense short-lived fatal outbreaks The current epidemic caused by the highly contagious SARS-CoV-2 and its rapid spread globally is of major concern There is scanty knowledge on the actual pandemic potential of this new SARS-like virus It might be speculated that SARS-CoV-2 epidemic is grossly underdiagnosed and that the infection is silently spreading across the globe with two consequences: (i) clusters of severe infections among frail subjects could haphazardly occur linked to unrecognized index cases;(ii) the current epidemic could naturally fall into a low-level endemic phase when a significant number of subjects will have developed immunity Understanding the role of paucisymptomatic subjects and stratifying patients according to the risk of developing severe clinical presentations is pivotal for implementing reasonable measures to contain the infection and to reduce its mortality Whilst the future evolution of this epidemic remains unpredictable, classic public health strategies must follow rational patterns The emergence of yet another global epidemic underscores the permanent challenges that infectious diseases pose and underscores the need for global cooperation and preparedness, even during inter-epidemic periods

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

positive: 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.

positive: Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1643-8 and is accessible for authorized users.

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

positive: Identification of super-transmitters of SARS-CoV-2 A newly emerged coronavirus, SARS-CoV-2, caused severe outbreaks of pneumonia in China in December 2019 and has since spread to various countries around the world. To probe the origin and transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences of viruses available in the GISAID platform as of March 05, 2020. A substantial number of earliest sequences reported in Wuhan in December 2019, including those of viruses recovered from the Huanan Seafood Market (HNSM), the site of the initial outbreak, were genetically diverse, suggesting that viruses of multiple sources were involved in the original outbreak. The viruses were subsequently disseminated to different parts of China and other countries, with diverse mutational profiles being recorded in strains recovered subsequently. Interestingly, four genetic clusters defined as Super-transmitters (STs) were found to become dominant and were responsible for the major outbreaks in various countries. Among the four clusters, ST1 is widely disseminated in Asia and the US and mainly responsible for outbreaks in the states of Washington and California in the US as well as those in South Korea at the end of February and early March, whereas ST4 contributed to the pandemic in Europe. Each ST cluster carried a signature mutation profile which allowed us to trace the origin and transmission patterns of specific viruses in different parts of the world. Using the signature mutations as markers of STs, we further analysed 1539 genome sequences reported after February 29, 2020. We found that around 90% of these genomes belonged to STs with ST4 being the dominant one and their contribution to pandemic in different continents were also depicted. The identification of these super-transmitters provides insight into the control of further transmission of SARS-CoV-2.

positive: Viral Infections, an Overview with a Focus on Prevention of Transmission Abstract Viruses are obligatory intracellular pathogens with a simple structure consisting of assembled proteins enclosing the nucleic acid genome with or without a lipid envelope. Despite increasing availability of rapid nucleic acid amplification assays for laboratory diagnosis, effective antivirals, and safe vaccines, the control of most viral infections depends on time-honored surveillance and infection control measures. Moreover most viruses can be readily destroyed by common disinfectants. This article is focused on the epidemiology, diagnosis, and control of common and emerging viral diseases.

positive: Centralized and decentralized isolation strategies and their impact on the COVID-19 pandemic dynamics The infectious diseases are spreading due to human interactions enabled by various social networks. Therefore, when a new pathogen such as SARS-CoV-2 causes an outbreak, the non-pharmaceutical isolation strategies (e.g., social distancing) are the only possible response to disrupt its spreading. To this end, we introduce the new epidemic model (SICARS) and compare the centralized (C), decentralized (D), and combined (C+D) social distancing strategies, and analyze their efficiency to control the dynamics of COVID-19 on heterogeneous complex networks. Our analysis shows that the centralized social distancing is necessary to minimize the pandemic spreading. The decentralized strategy is insufficient when used alone, but offers the best results when combined with the centralized one. Indeed, the (C+D) is the most efficient isolation strategy at mitigating the network superspreaders and reducing the highest node degrees to less than 10% of their initial values. Our results also indicate that stronger social distancing, e.g., cutting 75% of social ties, can reduce the outbreak by 75% for the C isolation, by 33% for the D isolation, and by 87% for the (C+D) isolation strategy. Finally, we study the impact of proactive versus reactive isolation strategies, as well as their delayed enforcement. We find that the reactive response to the pandemic is less efficient, and delaying the adoption of isolation measures by over one month (since the outbreak onset in a region) can have alarming effects; thus, our study contributes to an understanding of the COVID-19 pandemic both in space and time. We believe our investigations have a high social relevance as they provide insights into understanding how different degrees of social distancing can reduce the peak infection ratio substantially; this can make the COVID-19 pandemic easier to understand and control over an extended period of time.

positive: A realistic two-strain model for MERS-CoV infection uncovers the high risk for epidemic propagation Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory illness with a case fatality rate (CFR) of 35,5%. The highest number of MERS-CoV cases are from Saudi-Arabia, the major worldwide hotspot for this disease. In the absence of neither effective treatment nor a ready-to-use vaccine and with yet an incomplete understanding of its epidemiological cycle, prevention and containment measures can be derived from mathematical models of disease epidemiology. We constructed 2-strain models to predict past outbreaks in the interval 2012–2016 and derive key epidemiological information for Macca, Madina and Riyadh. We approached variability in infection through three different disease incidence functions capturing social behavior in response to an epidemic (e.g. Bilinear, BL; Non-monotone, NM; and Saturated, SAT models). The best model combination successfully anticipated the total number of MERS-CoV clinical cases for the 2015–2016 season and accurately predicted both the number of cases at the peak of seasonal incidence and the overall shape of the epidemic cycle. The evolution in the basic reproduction number (R(0)) warns that MERS-CoV may easily take an epidemic form. The best model correctly captures this feature, indicating a high epidemic risk (1≤R(0)≤2,5) in Riyadh and Macca and confirming the alleged co-circulation of more than one strain. Accurate predictions of the future MERS-CoV peak week, as well as the number of cases at the peak are now possible. These results indicate public health agencies should be aware that measures for strict containment are urgently needed before new epidemics take off in the region.

positive: 2019 novel coronavirus of pneumonia in Wuhan, China: emerging attack and management strategies An ongoing outbreak of 2019-nCoV pneumonia was first identified in Wuhan, Hubei province, China at the end of 2019. With the spread of the new coronavirus accelerating, person-to-person transmission in family homes or hospitals, and intercity spread of 2019-nCoV occurred. At least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases cured in China and worldwide 24 countries confirmed 383 cases being diagnosed, 1 case death in February 10th, 2020. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatal as many people thought. Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control. More comprehensive information is required to understand 2019-nCoV feature, the epidemiology of origin and spreading, and the clinical phenomina. According to the current status, blocking transmission, isolation, protection, and alternative medication are the urgent management strategies against 2019-nCoV.

positive: Evaluating transmission heterogeneity and super-spreading event of COVID-19 in a metropolis of China Background: COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics including heterogeneity is of vital importance for prediction and intervention of future epidemics. In addition, transmission heterogeneity usually envokes super spreading events (SSEs) where certain individuals infect large numbers of secondary cases. Till now, studies of transmission heterogeneity of COVID-19 and its underlying reason are far from reaching an agreement. MethodsWe collected information of all infected cases between January 21 and February 26, 2020 from official public sources in Tianjin, a metropolis of China. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k which characterized the transmission potential and heterogeneity, respectively. Furthermore, we studied the SSE in Tianjin outbreak and evaluated the effect of control measures undertaken by local government based on the heterogeneous model. Results: A total of 135 confirmed cases (including 34 imported cases and 101 local infections) in Tianjin by February 26th 2020 entered the study. We grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of 4 generations. The estimated reproduction number R was at 0.67 (95%CI: 0.54[~]0.84), and the dispersion parameter k was at 0.25 (95% CI: 0.13[~]0.88). A super spreader causing six infections in Tianjin, was identified. In addition, our simulation results showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since January 28th. Conclusions: Our analysis suggested that the transmission of COVID-19 was subcritical but with significant heterogeneity and may incur SSE. More efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors, which is important for developing targeted measures to curb the pandemic.

positive: Applying the unified models of ecology to forecast epidemics, with application to Covid-19 During a burgeoning outbreak of a novel disease, public attention will ordinarily expand as the severity of the outbreak expands--as infections multiply and news reports accumulate. Such public attention will in turn reinforce tactics to control the outbreak. In classical epidemiological models, effects of such tactics can be incorporated in standard parameters of transmission, recovery, and mortality. Unfortunately, early in an outbreak those individual parameters may be poorly known, hence corresponding models can get lost in uncertainty. This makes it difficult to determine whether the disease is spreading exponentially or logistically, or along another path. Examining cases over time is also problematic, as a logistically growing infection that is leveling off appears exponential in early phases. Here we report on the most basic mechanistic, ecological model we can imagine, which can help distinguish growth that is and is not under control. This approach did a satisfactory job predicting the final outcome of the Ebola outbreak of 2014-15. The model's two parameters were computable in real time, well before the outcome was actually known. The first parameter is an intrinsic rate of increase in cumulative deaths or reported cases. The second parameter is related to the human social system and represents all tactics that combine to control the outbreak. That parameter is coupled to the number of cumulative deaths or cases. We examine the basic mechanisms operating in this model and show the predictions made during the Ebola outbreak. We also consider how this basic model is performing for the Covid-19 pandemic and highlight ecological models that align with popularly discussed concepts such as flatten-the-curve, exponential growth, and inflection points of curves.

positive: Heterogeneity in SIR epidemics modeling: superspreaders Deterministic epidemic models, such as the Susceptible-Infected-Recovered (SIR) model, are immensely useful even if they lack the nuance and complexity of social contacts at the heart of network science modeling. Here we present a simple modification of the SIR equations to include the heterogeneity of social connection networks. A typical power-law model of social interactions from network science reproduces the observation that individuals with a high number of contacts, ``hubs'' or ``superspreaders'', can become the primary conduits for transmission. Conversely, once the tail of the distribution is saturated, herd immunity sets in at a smaller overall recovered fraction than in the analogous SIR model. The new dynamical equations suggest that cutting off the tail of the social connection distribution, i.e., stopping superspreaders, is an efficient non-pharmaceutical intervention to slow the spread of a pandemic, such as COVID-19.

positive: Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI: 0.54-0.84) and 0.25 (95% CI: 0.13-0.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.

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: Noninvasive ventilation in acute respiratory failure due to H1N1 influenza: A word of caution

positive: SARS, MERS and COVID-19 among Healthcare Workers: A Narrative Review Abstract In the recent two decades, three global viral infectious diseases, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and coronavirus disease (COVID-19), have occurred worldwide. SARS occurred in November 2002, causing 8,096 infected cases, as well as 774 deaths. MERS occurred in June, 2012, causing 2,519 confirmed cases, along with 866 associated deaths. COVID-19 occurred in December 2019, as of 30 April 2020, a total of 3,024,059 clinical cases have been reported, including 208,112 deaths. Healthcare workers (HCWs) need to be in close contact with these virus-infected patients and their contaminated environments at work, thus leading to be infected in some of them, even a few of them are died in line of duty. In this review, we summarized the infection status of HCWs during the outbreak of SARS, MERS and COVID-19, with in-depth discussion, hoping to provoke sufficient attention to the HCWs infection status by more people.

positive: COVID-19 Super-spreaders: Definitional Quandaries and Implications Uncertainty around the role 'super-spreaders' play in the transmission and escalation of infectious disease is compounded by its broad and vague definition. It is a term that has been much used in relation to COVID-19, particularly in social media. On its widest definition, it refers to a propensity to infect a larger than average number of people. Given the biological, behavioural and environmental variables relevant to infectivity, this might be pertinent to almost any infected individual who is not physically isolated from others. Nor is the term confined to individuals with a propensity to spread infectious disease: it can potentially be used to describe events, policies or settings. This article explores the use of the term and considers circumstances in which the wide definition can be problematic. One problem is that it can lead to undeserved apportionment of moral blame to alleged super-spreaders. Another is that it can detract from scientific investigation of the heterogeneity of COVID-19 transmission. The author calls for a clearer epidemiological definition.

positive: Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.

positive: Viral Respiratory Tract Infections in Transplant Patients: Epidemiology, Recognition and Management Viral respiratory tract infections (RTIs) are common causes of mild illness in immunocompetent children and adults, with occasional significant morbidity or mortality in the very young, very old or infirm. However, recipients of solid organ transplants (SOT) or haematopoietic stem cell transplants (HSCT) are at markedly increased risk for significant morbidity or mortality from these infections. The infections are generally acquired by transmission of large respiratory droplets and can be nosocomial in origin with many documented outbreaks on specialised transplant units. Typically, the infections begin as upper RTIs, with cough or rhinorrhoea predominating. Many will resolve at this stage, but more immunocompromised patients, typically closer in time to their SOT or HSCT, may develop progressive infection to lower RTI or pneumonia. The most common RTI pathogens are influenza viruses, parainfluenza viruses and respiratory syncytial viruses. Newer polymerase chain reaction-based diagnostic strategies are more sensitive than previous assays, and allow rapid and accurate diagnoses of these infections. These newer assays may also detect emerging pathogens of significance, one of which is human metapneumovirus. While diagnostic techniques have advanced significantly in the past decade, well established and effective specific treatments for these infections remain elusive. The epidemiology, clinical presentation, diagnosis and treatment of the common viral RTIs in SOT or HSCT recipients are reviewed, and recommendations presented based on a thorough review of recent literature.

positive: Transmission of severe acute respiratory syndrome in dynamical small-world networks The outbreak of severe acute respiratory syndrome (SARS) is still threatening the world because of a possible resurgence. In the current situation that effective medical treatments such as antiviral drugs are not discovered yet, dynamical features of the epidemics should be clarified for establishing strategies for tracing, quarantine, isolation, and regulating social behavior of the public at appropriate costs. Here we propose a network model for SARS epidemics and discuss why superspreaders emerged and why SARS spread especially in hospitals, which were key factors of the recent outbreak. We suggest that superspreaders are biologically contagious patients, and they may amplify the spreads by going to potentially contagious places such as hospitals. To avoid mass transmission in hospitals, it may be a good measure to treat suspected cases without hospitalizing them. Finally, we indicate that SARS probably propagates in small-world networks associated with human contacts and that the biological nature of individuals and social group properties are factors more important than the heterogeneous rates of social contacts among individuals. This is in marked contrast with epidemics of sexually transmitted diseases or computer viruses to which scale-free network models often apply.

positive: Spatial and temporal dynamics of superspreading events in the 2014-2015 West Africa Ebola epidemic. The unprecedented scale of the Ebola outbreak in Western Africa (2014-2015) has prompted an explosion of efforts to understand the transmission dynamics of the virus and to analyze the performance of possible containment strategies. Models have focused primarily on the reproductive numbers of the disease that represent the average number of secondary infections produced by a random infectious individual. However, these population-level estimates may conflate important systematic variation in the number of cases generated by infected individuals, particularly found in spatially localized transmission and superspreading events. Although superspreading features prominently in first-hand narratives of Ebola transmission, its dynamics have not been systematically characterized, hindering refinements of future epidemic predictions and explorations of targeted interventions. We used Bayesian model inference to integrate individual-level spatial information with other epidemiological data of community-based (undetected within clinical-care systems) cases and to explicitly infer distribution of the cases generated by each infected individual. Our results show that superspreaders play a key role in sustaining onward transmission of the epidemic, and they are responsible for a significant proportion ([Formula: see text]61%) of the infections. Our results also suggest age as a key demographic predictor for superspreading. We also show that community-based cases may have progressed more rapidly than those notified within clinical-care systems, and most transmission events occurred in a relatively short distance (with median value of 2.51 km). Our results stress the importance of characterizing superspreading of Ebola, enhance our current understanding of its spatiotemporal dynamics, and highlight the potential importance of targeted control measures.

positive: Comprehensive investigation of an in-hospital transmission cluster of a symptomatic SARS-CoV-2–positive physician among patients and healthcare workers in Germany We investigated potential transmissions of a symptomatic SARS-CoV-2–positive physician in a tertiary-care hospital who worked for 15 cumulative hours without wearing a face mask. No in-hospital transmissions occurred, despite 254 contacts among patients and healthcare workers. In conclusion, exposed hospital staff continued work, accompanied by close clinical and virologic monitoring.

positive: Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan and Singapore Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine if an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R(0)) and the dispersion factor (k) from empirical data on clusters of epidemiologically-linked COVID-19 cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.

positive: Covid-19 Outbreak Progression in Italian Regions: Approaching the Peak by the End of March in Northern Italy and First Week of April in Southern Italy Epidemiological figures of the SARS-CoV-2 epidemic in Italy are higher than those observed in China. Our objective was to model the SARS-CoV-2 outbreak progression in Italian regions vs. Lombardy to assess the epidemic’s progression. Our setting was Italy, and especially Lombardy, which is experiencing a heavy burden of SARS-CoV-2 infections. The peak of new daily cases of the epidemic has been reached on the 29th, while was delayed in Central and Southern Italian regions compared to Northern ones. In our models, we estimated the basic reproduction number (R(0)), which represents the average number of people that can be infected by a person who has already acquired the infection, both by fitting the exponential growth rate of the infection across a 1-month period and also by using day-by-day assessments based on single observations. We used the susceptible–exposed–infected–removed (SEIR) compartment model to predict the spreading of the pandemic in Italy. The two methods provide an agreement of values, although the first method based on exponential fit should provide a better estimation, being computed on the entire time series. Taking into account the growth rate of the infection across a 1-month period, each infected person in Lombardy has involved 4 other people (3.6 based on data of April 23rd) compared to a value of [Formula: see text] , as reported in the Chinese city of Wuhan. According to our model, Piedmont, Veneto, Emilia Romagna, Tuscany and Marche will reach an R(0) value of up to 3.5. The R(0) was 3.11 for Lazio and 3.14 for the Campania region, where the latter showed the highest value among the Southern Italian regions, followed by Apulia (3.11), Sicily (2.99), Abruzzo (3.0), Calabria (2.84), Basilicata (2.66), and Molise (2.6). The R(0) value is decreased in Lombardy and the Northern regions, while it is increased in Central and Southern regions. The expected peak of the SEIR model is set at the end of March, at a national level, with Southern Italian regions reaching the peak in the first days of April. Regarding the strengths and limitations of this study, our model is based on assumptions that might not exactly correspond to the evolution of the epidemic. What we know about the SARS-CoV-2 epidemic is based on Chinese data that seems to be different than those from Italy; Lombardy is experiencing an evolution of the epidemic that seems unique inside Italy and Europe, probably due to demographic and environmental factors.

positive: [Advances on presymptomatic or asymptomatic carrier transmission of COVID-19]. COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of "the degree to which presymptomatic or asymptomatic infections can transmit" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.

positive: A mathematical model of COVID-19 transmission between frontliners and the general public The number of COVID-19 cases is continuously increasing in different countries (as of March 2020) including the Philippines. It is estimated that the basic reproductive number of COVID-19 is around 1.5 to 4. The basic reproductive number characterizes the average number of persons that a primary case can directly infect in a population full of susceptible individuals. However, there can be superspreaders that can infect more than this estimated basic reproductive number. In this study, we formulate a conceptual mathematical model on the transmission dynamics of COVID-19 between the frontliners and the general public. We assume that the general public has a reproductive number between 1.5 to 4, and frontliners (e.g. healthcare workers, customer service and retail personnel, food service crews, and transport or delivery workers) have a higher reproduction number. Our simulations show that both the frontliners and the general public should be protected or resilient against the disease. Protecting only the frontliners will not result in flattening the epidemic curve. Protecting only the general public may flatten the epidemic curve but the infection risk faced by the frontliners is still high, which may eventually affect their work. Our simple model does not consider all factors involved in COVID-19 transmission in a community, but the insights from our model results remind us of the importance of community effort in controlling the transmission of the disease. All in all, the take-home message is that everyone in the community, whether a frontliner or not, should be protected or should implement preventive measures to avoid being infected.

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: Analysis of intrapatient heterogeneity uncovers the microevolution of Middle East respiratory syndrome coronavirus Genome sequence analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) variants from patient specimens has revealed the evolutionary dynamics and mechanisms of pathogenesis of the virus. However, most studies have analyzed the consensus sequences of MERS-CoVs, precluding an investigation of intrapatient heterogeneity. Here, we analyzed non–consensus sequences to characterize intrapatient heterogeneity in cases associated with the 2015 outbreak of MERS in South Korea. Deep-sequencing analysis of MERS-CoV genomes performed on specimens from eight patients revealed significant intrapatient variation; therefore, sequence heterogeneity was further analyzed using targeted deep sequencing. A total of 35 specimens from 24 patients (including a super-spreader) were sequenced to detect and analyze variants displaying intrapatient heterogeneity. Based on the analysis of non–consensus sequences, we demonstrated the intrapatient heterogeneity of MERS-CoVs, with the highest level in the super-spreader specimen. The heterogeneity could be transmitted in a close association with variation in the consensus sequences, suggesting the occurrence of multiple MERS-CoV infections. Analysis of intrapatient heterogeneity revealed a relationship between D510G and I529T mutations in the receptor-binding domain (RBD) of the viral spike glycoprotein. These two mutations have been reported to reduce the affinity of the RBD for human CD26. Notably, although the frequency of both D510G and I529T varied greatly among specimens, the combined frequency of the single mutants was consistently high (87.7% ± 1.9% on average). Concurrently, the frequency of occurrence of the wild type at the two positions was only 6.5% ± 1.7% on average, supporting the hypothesis that selection pressure exerted by the host immune response played a critical role in shaping genetic variants and their interaction in human MERS-CoVs during the outbreak.

positive: Clinical and Transmission Characteristics of Covid-19 - A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department The outbreak of corona virus disease 2019 (Covid-19) imposes a major challenge in managing patients undergoing surgical operation. In this study, we analyzed clinical and transmission features of 25 cases of Covid-19 from a single thoracic department, including 13 patients and 12 health care staff. There were 13 males and 12 females. The median age of the patients was 61 (range: 51 to 69) years. The median age of the health care staff was 35 (range: 22 to 51) years. By the end of follow-up date (Mar. 3, 2020), there were 16 non-severe cases (64%) and 9 severe cases (36%), 5 cases were dead (20%). Nineteen (76%) of the infected cases were confirmed by SARS-CoV-2 nucleic acid test, the rest were clinically diagnosed as suspected Covid-19 cases, and 19 (76%) of the infected cases had positive exposure history. We found that COPD was significantly associated with severity and death (P=0.040, and P=0.038, respectively), and chest operation was significantly associated with death for Covid-19 patients (P=0.039). A potential "super spreader" may be the source of the transmission before the implementation of quarantine and comprehensive protection. It was concluded that Covid-19 is associated with poor prognosis for patients undergoing thoracic operation, especially for those with COPD. Implementation of comprehensive protective measures is important to control nosocomial infection.

positive: Chest tube with air leaks is a potential “super spreader” of COVID-19

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: Tracking the spread of novel coronavirus (2019-nCoV) based on big data The novel coronavirus (2019-nCoV) appeared in Wuhan in late 2019 have infected 34,598 people, and killed 723 among them until 8th February 2020. The new virus has spread to at least 316 cities (until 1st February 2020) in China. We used the traffic flow data from Baidu Map, and number of air passengers who left Wuhan from 1st January to 26th January, to quantify the potential infectious people. We developed multiple linear models with local population and air passengers as predicted variables to explain the variance of confirmed cases in every city across China. We found the contribution of air passengers from Wuhan was decreasing gradually, but the effect of local population was increasing, indicating the trend of local transmission. However, the increase of local transmission is slow during the early stage of novel coronavirus, due to the super strict control measures carried out by government agents and communities.

positive: A Pandemic in Times of Global Tourism: Superspreading and Exportation of COVID-19 Cases from a Ski Area in Austria On January 7, 2020, the World Health Organization (WHO) announced a novel coronavirus to be the cause of unclear pneumonia cases in China.….

positive: Analysis of the COVID-19 pandemic by SIR model and machine learning technics for forecasting This work is a trial in which we propose SIR model and machine learning tools to analyze the coronavirus pandemic in the real world. Based on the public data from \cite{datahub}, we estimate main key pandemic parameters and make predictions on the inflection point and possible ending time for the real world and specifically for Senegal. The coronavirus disease 2019, by World Health Organization, rapidly spread out in the whole China and then in the whole world. Under optimistic estimation, the pandemic in some countries will end soon, while for most part of countries in the world (US, Italy, etc.), the hit of anti-pandemic will be no later than the end of April.

positive: Identification of a super-spreading chain of transmission associated with COVID-19 Background: Super-spreading events were associated with the outbreaks of SARS and MERS, but their association with the outbreak of COVID-19 remains unknown. Here, we report a super-spreading transmission chain of SARS-CoV-2 involving an index patient, seven cancer patients, 40 health care workers and four family members. Methods: We conducted a retrospective study to identify the index patient and the exposed individuals linked to a chain of transmission associated with COVID-19. We collected and analyzed the data on demographic features, exposure history, clinical presentation, laboratory investigation, radiological examination, and disease outcome of these patients. Results: We identified the index patient and another presumptive super-spreader, who initiated and amplified a super-spreading transmission chain associated with COVID-19, respectively. There were 31 female and 21 male patients in this cohort, and the median age was 37 years (range: 22-79 years). Each of them had an exposure history with the index patient or his close contacts. Approximately 87% (45/52) of the patients had fever or other symptoms, 96% (50/52) had abnormal chest CT-scan findings, 86% of the tested patients (39/45) were positive for SARS-CoV-2 in the nasopharyngeal or throat swab specimen, 85% of the tested patients (29/34) were positive for SARS-CoV-2-specific IgM and/or IgG, 15% of the RT-PCR positive patients were tested negative for the specific IgM and/or IgG at the convalescent phase, and 15% of the RT-PCR negative patients were tested positive for the specific IgM and/or IgG. The severe patients experienced a significant decrease in oximetry saturation, lymphocyte, and platelet counts, along with a significant increase in C-reactive protein, D-dimer, and lactate dehydrogenase. All six fatal cases had comorbidities and five of the seven cancer patients (71%) died within 2-20 days of the disease onset. Conclusions: The super-spreading events were associated with the outbreak of COVID-19 in Wuhan and its impact on disease transmission warrants further investigation. Cancer patients appeared highly vulnerable to COVID-19. The finding that a significant portion of SARS-CoV-2 infected patients were tested negative for the serum specific IgM and IgG at the convalescent phase should be addressed by additional studies.

positive: [Investigation of transmission chain of a cluster COVID-19 cases] Objective: To analyze of the transmission characteristics of a cluster of COVID-19 cases in Chongqing and evaluate the infectivity of COVID-19 in the incubation period. Methods: A retrospective survey was conducted by using unified questionnaire through field and telephone interviews among 129 close contacts of COVID-19 cases. The relationship of transmission was indicated by transmission chain, and the infectivity was analyzed by the contact history. Results: This cluster of COVID-19 cases occurred after a classmate party involving members in three families and work fellows in a factory (R(0)=3.8). The infection rate during the incubation period was 17.57%. On average, it was infectious three days before onset. There was significant difference in infection rate among different contact modes (χ(2)=15.10, P<0.01),There was significant difference in infection rate among single exposureswith different time length ( χ(2)=25.08, P<0.01). Conclusions: COVID-19 is highly infectious in the incubation period. The more confined the space is, the higher the risk is,and the longer the single exposure is, the higher the risk of transmission is. Indirect contact transmission still exists.

positive: Strategies adopted and lessons learnt during the severe acute respiratory syndrome crisis in Singapore. In Singapore, the military was actively involved in the containment of the outbreak of severe acute respiratory syndrome (SARS) last year. The outbreak started in February 2003 with three Singapore travellers to Hong Kong. At that time, nothing was known about the aetiological agent of the atypical pneumonia that was termed SARS. Unfortunately one of the travellers was a super-spreader, defined as a person with high efficiency for virus transmission, and was responsible for the expansion of the national outbreak. Not only was the Singapore military involved in contact tracing of personnel and enforcement of home quarantine, military-affiliated research institutes were also involved in providing diagnostic support. This review reconstructs the events that took place during the SARS outbreak, focusing on the special support arising from complementing the military-affiliated laboratory with the public health laboratory. A description of the diagnostic findings is provided in chronological order. The review ends with lessons Singapore learnt from the SARS crisis, stressing the importance of national preparedness for future outbreaks.

positive: Chest tube with air leaks is a potential "super spreader" of COVID-19

positive: Clinical and Transmission Characteristics of Covid-19 — A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department The outbreak of corona virus disease 2019 (Covid-19) imposes a major challenge in managing patients undergoing surgical operation. In this study, we analyzed clinical and transmission features of 25 cases of Covid-19 from a single thoracic department, including 13 patients and 12 health care staff. There were 13 males and 12 females. The median age of the patients was 61 (range: 51 to 69) years. The median age of the health care staff was 35 (range: 22 to 51) years. By the end of follow-up date (Mar. 3, 2020), there were 16 non-severe cases (64%) and 9 severe cases (36%), 5 cases were dead (20%). Nineteen (76%) of the infected cases were confirmed by SARS-CoV-2 nucleic acid test, the rest were clinically diagnosed as suspected Covid-19 cases, and 19 (76%) of the infected cases had positive exposure history. We found that COPD was significantly associated with severity and death (P=0.040, and P=0.038, respectively), and chest operation was significantly associated with death for Covid-19 patients (P=0.039). A potential “super spreader” may be the source of the transmission before the implementation of quarantine and comprehensive protection. It was concluded that Covid-19 is associated with poor prognosis for patients undergoing thoracic operation, especially for those with COPD. Implementation of comprehensive protective measures is important to control nosocomial infection.

positive: 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.

positive: Super-spreading events and contribution to transmission of MERS, SARS, and SARS-CoV-2 (COVID-19)

positive: Calculating the potential for within-flight transmission of influenza A (H1N1) BACKGROUND: Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1). However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be transmitted during commercial flights. Here we present the first quantitative risk assessment to assess the potential for within-flight transmission of H1N1. METHODS: We model airborne transmission of infectious viral particles of H1N1 within a Boeing 747 using methodology from the field of quantitative microbial risk assessment. RESULTS: The risk of catching H1N1 will essentially be confined to passengers travelling in the same cabin as the source case. Not surprisingly, we find that the longer the flight the greater the number of infections that can be expected. We calculate that H1N1, even during long flights, poses a low to moderate within-flight transmission risk if the source case travels First Class. Specifically, 0-1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and 2-5 during a 17 hour flight. However, within-flight transmission could be significant, particularly during long flights, if the source case travels in Economy Class. Specifically, two to five infections could occur during a 5 hour flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight. If the aircraft is only partially loaded, under certain conditions more infections could occur in First Class than in Economy Class. During a 17 hour flight, a greater number of infections would occur in First Class than in Economy if the First Class Cabin is fully occupied, but Economy class is less than 30% full. CONCLUSIONS: Our results provide insights into the potential utility of air travel restrictions on controlling influenza pandemics in the winter of 2009/2010. They show travel by one infectious individual, rather than causing a single outbreak of H1N1, could cause several simultaneous outbreaks. These results imply that, during a pandemic, quarantining passengers who travel in Economy on long-haul flights could potentially be an important control strategy. Notably, our results show that quarantining passengers who travel First Class would be unlikely to be an effective control strategy.

positive: Heterogenous COVID-19 transmission dynamics within Singapore: a clearer picture of future national responses

positive: Control of Severe Acute Respiratory Syndrome in Singapore A Severe Acute Respiratory Syndrome (SARS) outbreak occurred in Singapore from February to May 2003. A high vigilance for the disease, frequent and regular temperature monitoring, early case identification and isolation of patients, as well as tracing and home quarantine of contacts, played major roles in controlling the outbreak. Hospitals were dedicated to the screening and treatment of SARS patients. Within and between hospitals, movement by healthcare workers, patients and visitors were restricted, as was the number of hospital visitors. Staff education and audits of infection control practices also featured prominently. To prevent cross-border transmission, incoming travellers from SARS affected areas had to complete health declaration cards. They, as well as all outgoing travellers from Singapore, were monitored for fever. In the meantime, the public was urged to refrain from travelling to SARS affected regions. Containment elements targeting the community included school closure, public education on good hygiene and readily accessible public information. In response to a laboratory acquired SARS infection, laboratories were audited, and directives issued on the mandatory use of biosafety level 3 laboratories for SARS virus culture, and compliance of laboratory workers to biosafety guidelines.

positive: Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020 Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R(0) of 2019-nCoV to be around 2.2 (90% high density interval: 1.4–3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.

negative: Comprehensive overview of COVID-19 based on current evidence In December 2019, twenty-seven pneumonia patients with unknown causes originated in South China seafood market in Wuhan. The virus infection spread rapidly and swept through China in less than a month. Subsequently, the virus was proven a novel coronavirus and named SARS-CoV-2. The outbreak of novel coronavirus has been determined as a Public Health Emergency of International Concern (PHEIC) by WHO on January 31, 2020. Similar to other coronaviruses like the Middle East Respiratory Syndrome (MERS) CoV and Severe Acute Respiratory Syndrome (SARS) CoV, the novel coronavirus was reported to spread via respiratory droplets and close contact from human to human, which means the virus is highly infectious and dangerous. Unfortunately, till now the virus has spread to over 200 countries/territories/areas around the world and the Coronavirus Disease 2019 (COVID-19) outbreak is continuing to grow. Currently, information sharing and transparency are essential for risk assessment and epidemic control in all endemic areas. In this article, we compared SARS-CoV-2 with SARS-CoV and influenza virus, discussed current researching progress of COVID-19, including clinical characteristics, pathological changes, treatment measures, and so on.

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

negative: COVID-19 related mortality and spread of disease in long-term care: first findings from a living systematic review of emerging evidence Background: Policy responses to mitigate the impact of the COVID-19 pandemic on long-term care (LTC) require robust and timely evidence on mortality and spread of the disease in these settings. The aim of this living systematic review is to synthesise early international evidence on mortality rates and incidence of COVID-19 among people who use and provide LTC. Methods: We report the initial findings of a living systematic review (CRD42020183557), including studies identified through database searches up to 29 May 2020. We searched seven databases (MEDLINE; Embase; CINAHL Plus; Web of Science; Global Health; WHO COVID-19 Research Database; medRxiv) to identify all studies reporting primary data on COVID-19 related mortality and incidence of disease among LTC users and staff. We excluded studies not focusing on LTC. Included primary studies were critically appraised and results on number of deaths and COVID-19 related mortality rates, case fatality rates, and excess deaths (co-primary outcomes), as well as incidence of disease, hospitalisations, and ICU admissions were synthesised narratively. We further included official figures on number of deaths in LTC. Findings: A total of 30 study reports for 27 unique primary studies or outbreak reports were included. Outbreak investigations in LTC facilities found COVID-19 incidence rates of between 0.0% and 71.7% among residents and between 1.5% and 64.0% among staff. Mortality rates varied from 0.0% to 9.9% of all residents at outbreak facilities, with case fatality rates between 0.0% and 33.7%. In included studies, no LTC staff members had died. LTC residents accounted for between 0% (Hong Kong) and 82% (Canada) of COVID-related deaths, according to official figures. Interpretation: Long-term care users have been particularly vulnerable to the COVID-19 pandemic. However, we found wide variation in spread of disease and mortality rates between outbreaks at individual LTC facilities. Further research into the factors determining successful prevention and containment of COVID-19 outbreaks is needed to protect long-term care users and staff.

negative: Full spectrum of COVID-19 severity still being depicted

negative: Globe to globe: whither (local) public health?

negative: Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.

negative: Generating super-shedders: co-infection increases bacterial load and egg production of a gastrointestinal helminth Co-infection by multiple parasites is common within individuals. Interactions between co-infecting parasites include resource competition, direct competition and immune-mediated interactions and each are likely to alter the dynamics of single parasites. We posit that co-infection is a driver of variation in parasite establishment and growth, ultimately altering the production of parasite transmission stages. To test this hypothesis, three different treatment groups of laboratory mice were infected with the gastrointestinal helminth Heligmosomoides polygyrus, the respiratory bacterial pathogen Bordetella bronchiseptica lux(+) or co-infected with both parasites. To follow co-infection simultaneously, self-bioluminescent bacteria were used to quantify infection in vivo and in real-time, while helminth egg production was monitored in real-time using faecal samples. Co-infection resulted in high bacterial loads early in the infection (within the first 5 days) that could cause host mortality. Co-infection also produced helminth ‘super-shedders’; individuals that chronically shed the helminth eggs in larger than average numbers. Our study shows that co-infection may be one of the underlying mechanisms for the often-observed high variance in parasite load and shedding rates, and should thus be taken into consideration for disease management and control. Further, using self-bioluminescent bacterial reporters allowed quantification of the progression of infection within the whole animal of the same individuals at a fine temporal scale (daily) and significantly reduced the number of animals used (by 85%) compared with experiments that do not use in vivo techniques. Thus, we present bioluminescent imaging as a novel, non-invasive tool offering great potential to be taken forward into other applications of infectious disease ecology.

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

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

negative: A new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease Abstract This study aimed to find novel information concerning pathogen detection and some probable coinfection factors in hand, foot, and mouth disease (HFMD). In this study, 1104 clinically diagnosed HFMD patients were included. Enterovirus 71 (EV71), coxsackievirus A16 (CA16), and 14 different respiratory pathogens were examined from nasopharyngeal swabs using polymerase chain reaction (PCR) or reverse transcriptase PCR (RT-PCR). To evaluate the immune activation in HFMD patients, 8 cytokines and IgM antibodies to EV71 and CA16 from mild and severe patients were detected. Our results indicated that the severity of HFMD may affect the pathogen detection. The lower positive rates of enterovirus and respiratory viruses in severe HFMD cases by RT-PCR were probably related to stronger immune response. Therefore, immunological tests such as ELISA are essential supplements to PCR or RT-PCR in order to increase pathogen diagnosis in HFMD, especially in severe cases.

negative: Infectivity of Severe Acute Respiratory Syndrome during Its Incubation Period Objective To evaluate the infectivity of severe acute respiratory syndrome (SARS) during its incubation period by investigating chains of transmission and individuals isolated for medical observation with a view to providing scientific evidence for updating protocols of medical isolation. Methods Individuals related with the two SARS chains of transmission in Beijing in 2003 and a group of individuals isolated for medical observation in Haidian district of Beijing during the SARS outbreak were selected as subjects of study. Contactors with SARS patients and those with symptom development following the contacts were investigated via questionnaire. Serum samples were collected from super transmitters and tested for SARS-CoV antibody by neutralization test and enzyme linked immunosorbent assay (ELISA). Results A total of 1 112 contactors were investigated in three surveys. Of them, 669 had a history of close contact with symptomatic SARS patients, 101 developed symptoms with a rate of 15.1%, 363 had a history of close contact with patients in their incubation period, none of whom developed symptoms (0%). Serum samples were collected from 32 highly-exposed individuals, of whom 13 developing SARS symptoms after contact had serum samples positive for SARS-CoV antibody. Samples collected from the asymptomatic contactors were all negative for SARS-CoV antibody. Conclusion SARS cases are infectious only during their symptomatic period and are non-infectious during the incubation period. Isolation for medical observation should be placed for individuals who are in close contact with symptomatic SARS patients. The results of our study are of decisive significance for the Ministry of Health to the definition of SARS close contactor.

negative: MERS transmission and risk factors: a systematic review BACKGROUND: Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. However, the methodology and results of these studies have varied, and there has been no systematic review of MERS. This study reviews the characteristics and associated risk factors of MERS. METHOD: We searched international (PubMed, ScienceDirect, Cochrane) and Korean databases (DBpia, KISS) for English- or Korean-language articles using the terms “MERS” and “Middle East respiratory syndrome”. Only human studies with > 20 participants were analysed to exclude studies with low representation. Epidemiologic studies with information on transmissibility and severity of MERS as well as studies containing MERS risk factors were included. RESULT: A total of 59 studies were included. Most studies from Saudi Arabia reported higher mortality (22–69.2%) than those from South Korea (20.4%). While the R(0) value in Saudi Arabia was < 1 in all but one study, in South Korea, the R(0) value was 2.5–8.09 in the early stage and decreased to < 1 in the later stage. The incubation period was 4.5–5.2 days in Saudi Arabia and 6–7.8 days in South Korea. Duration from onset was 4–10 days to confirmation, 2.9–5.3 days to hospitalization, 11–17 days to death, and 14–20 days to discharge. Older age and concomitant disease were the most common factors related to MERS infection, severity, and mortality. CONCLUSION: The transmissibility and severity of MERS differed by outbreak region and patient characteristics. Further studies assessing the risk of MERS should consider these factors.

negative: The role of the radiologist in diagnosing the COVID-19 infection. Parma experiences. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the coronavirus disease 2019 (COVID-19), a respiratory disease that ranges from an asymptomatic or mild flu-like illness to severe pneumonia, multiorgan failure, and death. Imaging might play an important role in clinical decision making by supporting rapid triage of patients with suspected COVID-19 and assessing supervening complications, such as super-added bacterial infection and thrombosis. Further studies will clarify the real impact of imaging on COVID-19 patients' management and the potential role of radiology in future outbreaks.

negative: Protocol for a scoping review of post-trial extensions of randomised controlled trials using individually linked administrative and registry data. INTRODUCTION Well-conducted randomised controlled trials (RCTs) provide the least biased estimates of intervention effects. However, RCTs are costly and time-consuming to perform and long-term follow-up of participants may be hampered by lost contacts and financial constraints. Advances in computing and population-based registries have created new possibilities for increasing the value of RCTs by post-trial extension using linkage to routinely collected administrative/registry data in order to determine long-term interventional effects. There have been recent important examples, including 20+ years follow-up studies of trials of pravastatin and mammography. Despite the potential value of post-trial extension, there has been no systematic study of this literature. This scoping review aims to characterise published post-trial extension studies, assess their value, and identify any potential challenges associated with this approach. METHODS AND ANALYSIS This review will use the recommended methods for scoping reviews. We will search MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A draft search strategy is included in this protocol. Review of titles and abstracts, full texts of potentially eligible studies and data/information extraction will be conducted independently by pairs of investigators. Eligible studies will be RCTs that investigated healthcare interventions that were extended by individual linkage to administrative/registry/electronic medical records data after the completion of the planned follow-up period. Information concerning the original trial, characteristics of the extension study, any clinical, policy or ethical implications and methodological or practical challenges will be collected using standardised forms. ETHICS AND DISSEMINATION As this study uses secondary data, and does not include person-level data, ethics approval is not required. We aim to disseminate these findings through journals and conferences targeting triallists and researchers involved in health data linkage. We aim to produce guidance for investigators on the conduct of post-trial extensions using routinely collected data.

negative: Antiviral therapy in management of COVID-19: a systematic review on current evidence Background: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19 In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19 Method: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020 Two independent researchers performed the screening, and finally the related studies were included Results: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19 In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV Conclusion: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO) In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics

negative: Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China Abstract Background A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19. Methods We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis. Results 112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram. Conclusions The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.

negative: Interplay between collective behavior and spreading dynamics on complex networks There are certain correlations between collective behavior and spreading dynamics on some real complex networks. Based on the dynamical characteristics and traditional physical models, we construct several new bidirectional network models of spreading phenomena. By theoretical and numerical analysis of these models, we find that the collective behavior can inhibit spreading behavior, but, conversely, this spreading behavior can accelerate collective behavior. The spread threshold of spreading network is obtained by using the Lyapunov function method. The results show that an effective spreading control method is to enhance the individual awareness to collective behavior. Many real-world complex networks can be thought of in terms of both collective behavior and spreading dynamics and therefore to better understand and control such complex networks systems, our work may provide a basic framework.

negative: Targeting the catecholamine-cytokine axis to prevent SARS-CoV-2 cytokine storm syndrome The mortality of Coronavirus disease 2019 (COVID-19) appears to be driven by acute respiratory distress syndrome (ARDS) and a dysregulated immune response to SARS-CoV-2. Emerging evidence suggests that a subset of COVID-19 is characterized by the development of a cytokine storm syndrome (CSS), and interleukin (IL)-6 levels are predictors of COVID-19 severity and in-hospital mortality. Targeting hyper-inflammation in COVID-19 may be critical for reducing mortality. Catecholamines enhance inflammatory injury by augmenting the production of IL-6 and other cytokines through a self-amplifying feed-forward loop in immune cells that requires alpha-1 adrenergic receptor (α1-AR) signaling. Prophylactic inhibition of catecholamine synthesis with the α1-AR antagonist prazosin reduced catecholamines and cytokine responses in mice, and resulted in markedly increased survival following various hyper-inflammatory stimuli. These findings offer a rationale for studying α1-AR antagonists in the prophylaxis of patients with COVID-19-CSS and ARDS. As high infection rates threaten to overwhelm hospital capacity during this pandemic, preventative approaches that ameliorate COVID-19 severity and reduce excessive mortality are desperately needed. We hypothesize that treatment with prazosin of individuals who test positive for SARS-CoV-2 could reduce catecholamine surges, secondary cytokine dysregulation, and mortality. To investigate a potential role for α1-AR antagonists in preventing poor outcomes in ARDS, we conducted a retrospective analysis of hospitalized patients diagnosed with ARDS. Using data from the Truven Health MarketScan Research Database (2010-2017), we identified 13,125 men (age 45-64) with ARDS, of whom 655 patients (5.0%) were prescribed α1-AR antagonists in the previous year. Applying logistic regression models, we found that patients with prior use of α1-AR antagonists had lower odds of invasive mechanical ventilation compared to non-users (adjusted OR=0.75, 95% CI 0.59-0.95, p=0.019). Perhaps more importantly, those patients had a ~36% lower incidence of both being ventilated and dying in the hospital (adjusted OR=0.59, 95% CI 0.34-0.95, p=0.042). By contrast, prior use of beta-adrenergic receptor (β-AR) antagonists was not correlated with either outcome. We extended these analyses to patients admitted with pneumonia. Of 108,956 subjects in this cohort, 5,498 patients (5.0%) were taking α1-AR antagonist. Similar to ARDS, patients with pneumonia on α1-AR antagonists (but no β-AR antagonists) had a lower odds of mechanical ventilation (adjusted OR=0.83, 95% CI 0.75-0.92, p<0.001) and of both being ventilated and dying in the hospital (adjusted OR=0.77, 95% CI 0.62-0.94, p=0.014) compared to non-users. Mirroring findings from pre-clinical models, these data support a clinical rationale to study α1-AR antagonists in the prevention of severe complications of pneumonia, ARDS, and COVID-19. Prospective, randomized clinical trials of alpha-1 receptor antagonists (e.g. prazosin) administered prior to the onset of severe symptoms are needed to assess their efficacy in preventing CSS and reducing mortality in COVID-19.

negative: Evidence from internet search data shows information-seeking responses to news of local COVID-19 cases The COVID-19 outbreak is a global pandemic with community circulation in many countries, including the United States, with confirmed cases in all states. The course of this pandemic will be shaped by how governments enact timely policies and disseminate information and by how the public reacts to policies and information. Here, we examine information-seeking responses to the first COVID-19 case public announcement in a state. Using an event study framework for all US states, we show that such news increases collective attention to the crisis right away. However, the elevated level of attention is short-lived, even though the initial announcements are followed by increasingly strong policy measures. Specifically, searches for “coronavirus” increased by about 36% (95% CI: 27 to 44%) on the day immediately after the first case announcement but decreased back to the baseline level in less than a week or two. We find that people respond to the first report of COVID-19 in their state by immediately seeking information about COVID-19, as measured by searches for coronavirus, coronavirus symptoms, and hand sanitizer. On the other hand, searches for information regarding community-level policies (e.g., quarantine, school closures, testing) or personal health strategies (e.g., masks, grocery delivery, over-the-counter medications) do not appear to be immediately triggered by first reports. These results are representative of the study period being relatively early in the epidemic, and more-elaborate policy responses were not yet part of the public discourse. Further analysis should track evolving patterns of responses to subsequent flows of public information.

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: An agent-based model driven by tropical rainfall to understand the spatio-temporal heterogeneity of a chikungunya outbreak Abstract Vector-borne diseases, such as dengue, malaria and chikungunya, are increasing across their traditional ranges and continuing to infiltrate new, previously unaffected, regions. The spatio-temporal evolution of these diseases is determined by the interaction of the host and vector, which is strongly dependent on social structures and mobility patterns. We develop an agent-based model (ABM), in which each individual is explicitly represented and vector populations are linked to precipitation estimates in a tropical setting. The model is implemented on both scale-free and regular networks. The spatio-temporal transmission of chikungunya is analysed and the presence of asymptomatic silent spreaders within the population is investigated in the context of implementing travel restrictions during an outbreak. Preventing the movement of symptomatic individuals is found to be an insufficient mechanism to halt the spread of the disease, which can be readily carried to neighbouring nodes via sub-clinical individuals. Furthermore, the impact of topology structure vs. precipitation levels is assessed and precipitation is found to be the dominant factor driving spatio-temporal transmission.

negative: COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting? Given the current SARS-CoV-2 (COVID-19) pandemic, the availability of reliable information for clinicians and patients is paramount. There have been a number of reports stating that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. Therefore, this review aimed to collate information available in published articles to identify any evidence behind these claims with the aim of advising clinicians on how best to treat patients. This review found no published evidence for or against the use of NSAIDs in COVID-19 patients. Meanwhile, there appeared to be some evidence that corticosteroids may be beneficial if utilised in the early acute phase of infection, however, conflicting evidence from the World Health Organisation surrounding corticosteroid use in certain viral infections means this evidence is not conclusive. Given the current availability of literature, caution should be exercised until further evidence emerges surrounding the use of NSAIDs and corticosteroids in COVID-19 patients.

negative: Cerebrovascular Disease in COVID-19. Coronavirus disease 19 (COVID-19) is a pandemic originating in Wuhan, China, in December 2019. Early reports suggest that there are neurologic manifestations of COVID-19, including acute cerebrovascular disease. We report a case of COVID-19 with acute ischemic stroke. To our knowledge, this is the first reported case of COVID-19-related cerebral infarcts that includes brain imaging at multiple time points and CT angiography. There is a growing body of published evidence that complications of COVID-19 are not limited to the pulmonary system. Neuroradiologists should be aware of a wide range of neurologic manifestations, including cerebrovascular disease.

negative: Putative Receptor Binding Domain of Bat-Derived Coronavirus HKU9 Spike Protein: Evolution of Betacoronavirus Receptor Binding Motifs [Image: see text] The suggested bat origin for Middle East respiratory syndrome coronavirus (MERS-CoV) has revitalized the studies of other bat-derived coronaviruses with respect to interspecies transmission potential. Bat coronavirus (BatCoV) HKU9 is an important betacoronavirus (betaCoV) that is phylogenetically affiliated with the same genus as MERS-CoV. The bat surveillance data indicated that BatCoV HKU9 has been widely spreading and circulating in bats. This highlights the necessity of characterizing the virus for its potential to cross species barriers. The receptor binding domain (RBD) of the coronavirus spike (S) protein recognizes host receptors to mediate virus entry and is therefore a key factor determining the viral tropism and transmission capacity. In this study, the putative S RBD of BatCoV HKU9 (HKU9-RBD), which is homologous to other betaCoV RBDs that have been structurally and functionally defined, was characterized via a series of biophysical and crystallographic methods. By using surface plasmon resonance, we demonstrated that HKU9-RBD binds to neither SARS-CoV receptor ACE2 nor MERS-CoV receptor CD26. We further determined the atomic structure of HKU9-RBD, which as expected is composed of a core and an external subdomain. The core subdomain fold resembles those of other betaCoV RBDs, whereas the external subdomain is structurally unique with a single helix, explaining the inability of HKU9-RBD to react with either ACE2 or CD26. Via comparison of the available RBD structures, we further proposed a homologous intersubdomain binding mode in betaCoV RBDs that anchors the external subdomain to the core subdomain. The revealed RBD features would shed light on the evolution route of betaCoV.

negative: PACT: Privacy Sensitive Protocols and Mechanisms for Mobile Contact Tracing The global health threat from COVID-19 has been controlled in a number of instances by large-scale testing and contact tracing efforts. We created this document to suggest three functionalities on how we might best harness computing technologies to supporting the goals of public health organizations in minimizing morbidity and mortality associated with the spread of COVID-19, while protecting the civil liberties of individuals. In particular, this work advocates for a third-party free approach to assisted mobile contact tracing, because such an approach mitigates the security and privacy risks of requiring a trusted third party. We also explicitly consider the inferential risks involved in any contract tracing system, where any alert to a user could itself give rise to de-anonymizing information. More generally, we hope to participate in bringing together colleagues in industry, academia, and civil society to discuss and converge on ideas around a critical issue rising with attempts to mitigate the COVID-19 pandemic.

negative: Structural analysis of herpes simplex virus by optical super-resolution imaging Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.

negative: Read all about it: The Lancet's Paper of the Year, 2003

negative: Analysis of the scientific literature in the first 30 Days of the novel coronavirus outbreak. Introduction: Recent events highlight how emerging and re-emerging pathogens are becoming global challenges for public health. In December 2019, a novel coronavirus has emerged. This has suddenly turned out into global health concern. Objectives: Aim of this research is to focus on the bibliometric aspects in order to measure what is published in the first 30-days of a global epidemic outbreak Methods: We searched PubMed database in order to find all relevant studies in the first 30-days from the first publication. Results: From the initial 442 identified articles, 234 were read in-extenso. The majority of papers come from China, UK and USA. 63.7% of the papers were commentaries, editorials and reported data and only 17.5% of the sources used data directly collected on the field. Topics mainly addressed were epidemiology, preparedness and generic discussion. NNR showed a reduction for both the objectives assessed from January to February. Conclusions: Diagnosis and effective preventive and therapeutic measures were the fields in which more research is still needed. The vast majority of scientific literature in the first 30-days of an epidemic outbreak is based on reported data rather than primary data. Nevertheless, the scientific statements and public health decisions rely on these data.

negative: Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19) BACKGROUND: 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 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 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 recommendations in further releases of these guidelines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06022-5) contains supplementary material, which is available to authorized users.

negative: Should azithromycin be used to treat COVID-19? A rapid review BACKGROUND: There are no established effective treatments for COVID-19. While novel drugs are being developed, azithromycin has been identified as a candidate treatment in the interim. AIM: To review the evidence for the effectiveness and safety of azithromycin in treating COVID-19. DESIGN & SETTING: A rapid review of the literature was conducted. METHOD: Electronic searches were conducted on 16 April 2020 of PubMed, TRIP, EPPI COVID Living Map, MedRxiv, GoogleScholar, and Google. In vivo and in vitro studies were included assessing the safety and effectiveness of azithromycin for treatment of COVID-19, and/or the activity of azithromycin against SARS-CoV-2. In vivo studies needed to include a comparator group. RESULTS: Three studies were identified, two in vitro and one in vivo, which were suitable for inclusion. All three were published as pre-prints. The in vitro studies revealed conflicting results, with one finding anti-SARS-CoV-2 activity for azithromycin alone, while the other found activity against SARS-CoV-2 only when azithromycin was combined with hydroxychloroquine. A small trial of 36 patients, with high risk of bias, found superior viral clearance in patients with COVID-19 treated with azithromycin and hydroxychloroquine combined, compared with hydroxychloroquine alone. CONCLUSION: There is no evidence to support the use of azithromycin for the treatment of COVID-19 outside of the context of clinical trials, unless it is used to treat bacterial super-infection. There is extremely limited evidence of a possible synergy between azithromycin and hydroxychloroquine. The adverse events profile of azithromycin in the context of COVID-19 has not yet been established. Well-conducted clinical trials are urgently needed in this area.

negative: Transport impacts on atmosphere and climate: Aviation Abstract Aviation alters the composition of the atmosphere globally and can thus drive climate change and ozone depletion. The last major international assessment of these impacts was made by the Intergovernmental Panel on Climate Change (IPCC) in 1999. Here, a comprehensive updated assessment of aviation is provided. Scientific advances since the 1999 assessment have reduced key uncertainties, sharpening the quantitative evaluation, yet the basic conclusions remain the same. The climate impact of aviation is driven by long-term impacts from CO2 emissions and shorter-term impacts from non-CO2 emissions and effects, which include the emissions of water vapour, particles and nitrogen oxides (NO x ). The present-day radiative forcing from aviation (2005) is estimated to be 55 mW m−2 (excluding cirrus cloud enhancement), which represents some 3.5% (range 1.3–10%, 90% likelihood range) of current anthropogenic forcing, or 78 mW m−2 including cirrus cloud enhancement, representing 4.9% of current forcing (range 2–14%, 90% likelihood range). According to two SRES-compatible scenarios, future forcings may increase by factors of 3–4 over 2000 levels, in 2050. The effects of aviation emissions of CO2 on global mean surface temperature last for many hundreds of years (in common with other sources), whilst its non-CO2 effects on temperature last for decades. Much progress has been made in the last ten years on characterizing emissions, although major uncertainties remain over the nature of particles. Emissions of NO x result in production of ozone, a climate warming gas, and the reduction of ambient methane (a cooling effect) although the overall balance is warming, based upon current understanding. These NO x emissions from current subsonic aviation do not appear to deplete stratospheric ozone. Despite the progress made on modelling aviation's impacts on tropospheric chemistry, there remains a significant spread in model results. The knowledge of aviation's impacts on cloudiness has also improved: a limited number of studies have demonstrated an increase in cirrus cloud attributable to aviation although the magnitude varies: however, these trend analyses may be impacted by satellite artefacts. The effect of aviation particles on clouds (with and without contrails) may give rise to either a positive forcing or a negative forcing: the modelling and the underlying processes are highly uncertain, although the overall effect of contrails and enhanced cloudiness is considered to be a positive forcing and could be substantial, compared with other effects. The debate over quantification of aviation impacts has also progressed towards studying potential mitigation and the technological and atmospheric tradeoffs. Current studies are still relatively immature and more work is required to determine optimal technological development paths, which is an aspect that atmospheric science has much to contribute. In terms of alternative fuels, liquid hydrogen represents a possibility and may reduce some of aviation's impacts on climate if the fuel is produced in a carbon-neutral way: such fuel is unlikely to be utilized until a ‘hydrogen economy’ develops. The introduction of biofuels as a means of reducing CO2 impacts represents a future possibility. However, even over and above land-use concerns and greenhouse gas budget issues, aviation fuels require strict adherence to safety standards and thus require extra processing compared with biofuels destined for other sectors, where the uptake of such fuel may be more beneficial in the first instance.

negative: Hydroxychloroquine for the Prevention of Covid-19 - Searching for Evidence

negative: Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China Our manuscript was based on surveillance cases of COVID-19 identified before January 26, 2020. As of February 20, 2020, the total number of confirmed cases in mainland China has reached 18 times of the number in our manuscript. While the methods and the main conclusions in our original analyses remain solid, we decided to withdraw this preprint for the time being, and will replace it with a more up-to-date version shortly. Should you have any comments or suggestions, please feel free to contact the corresponding author.

negative: 8th Annual Toronto Critical Care Medicine Symposium, 30 October–1 November 2003, Toronto, Ontario, Canada

negative: Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China BACKGROUND: Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients remain largely unknown. PATIENTS AND METHODS: In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death. RESULTS: A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0–70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events [hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086–15.322, P = 0.037]. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498–19.748, P = 0.010). CONCLUSIONS: Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.

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: A time series method to analyze incidence pattern and estimate reproduction number of COVID-19 The ongoing pandemic of Coronavirus disease (COVID-19) emerged in Wuhan, China in the end of 2019. It has already affected more than 300,000 people, with the number of deaths nearing 13000 across the world. As it has been posing a huge threat to global public health, it is of utmost importance to identify the rate at which the disease is spreading. In this study, we propose a time series model to analyze the trend pattern of the incidence of COVID-19 outbreak. We also incorporate information on total or partial lockdown, wherever available, into the model. The model is concise in structure, and using appropriate diagnostic measures, we showed that a time-dependent quadratic trend successfully captures the incidence pattern of the disease. We also estimate the basic reproduction number across different countries, and find that it is consistent except for the United States of America. The above statistical analysis is able to shed light on understanding the trends of the outbreak, and gives insight on what epidemiological stage a region is in. This has the potential to help in prompting policies to address COVID-19 pandemic in different countries.

negative: Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study Background The ongoing epidemics of coronavirus disease 2019 (COVID-19) have caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia. Methods We conducted a case-control study to compare clinical characteristics, maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia. Results During January 24 to February 29, 2020, there were sixteen pregnant women with confirmed COVID-19 pneumonia and eighteen suspected cases who were admitted to labor in the third trimester. Two had vaginal delivery and the rest took cesarean section. Few patients presented respiratory symptoms (fever and cough) on admission, but most had typical chest CT images of COVID-19 pneumonia. Compared to the controls, COVID-19 pneumonia patients had lower counts of white blood cells (WBC), neutrophils, C-reactive protein (CRP), and alanine aminotransferase (ALT) on admission. Increased levels of WBC, neutrophils, eosinophils, and CRP were found in postpartum blood tests of pneumonia patients. There were three (18.8%) and two (10.5%) of the mothers with confirmed or suspected COVID-19 pneumonia had preterm delivery due to maternal complications, which were significantly higher than the control group. None experienced respiratory failure during hospital stay. COVID-19 infection was not found in the newborns and none developed severe neonatal complications. Conclusion Severe maternal and neonatal complications were not observed in pregnant women with COVID-19 pneumonia who had vaginal delivery or caesarean section. Mild respiratory symptoms of pregnant women with COVID-19 pneumonia highlight the need of effective screening on admission.

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

negative: Coronavirus disease (COVID‐19) and neonate: What neonatologist need to know Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS‐CoV‐2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID‐19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID‐19 infection in newborns and children.

negative: Effect of weather on COVID-19 spread in the US: A prediction model for India in 2020 Abstract The effect of weather on COVID-19 spread is poorly understood. Recently, few studies have claimed that warm weather can possibly slowdown the global pandemic, which has already affected over 1.6 million people worldwide. Clarification of such relationships in the worst affected country, the US, can be immensely beneficial to understand the role of weather in transmission of the disease in the highly populated countries, such as India. We collected the daily data of new cases in 50 US states between Jan 1–Apr 9, 2020 and also the corresponding weather information (i.e., temperature (T) and absolute humidity (AH)). Distribution modeling of new cases across AH and T, helped identify the narrow and vulnerable AH range. We validated the results for 10-day intervals against monthly observations, and also worldwide trends. The results were used to predict Indian regions which would be vulnerable to weather based spread in upcoming months of 2020. COVID-19 spread in the US is significant for states with 4 < AH < 6 g/m3 and number of new cases > 10,000, irrespective of the chosen time intervals for study parameters. These trends are consistent with worldwide observations, but do not correlate well with India so far possibly due the total cases reported per interval < 10,000. The results clarify the relationship between weather parameters and COVID-19 spread. The vulnerable weather parameters will help classify the risky geographic areas in different countries. Specifically, with further reporting of new cases in India, prediction of states with high risk of weather based spread will be apparent.

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

negative: The Effectiveness of Contact Tracing in Emerging Epidemics BACKGROUND: Contact tracing plays an important role in the control of emerging infectious diseases, but little is known yet about its effectiveness. Here we deduce from a generic mathematical model how effectiveness of tracing relates to various aspects of time, such as the course of individual infectivity, the (variability in) time between infection and symptom-based detection, and delays in the tracing process. In addition, the possibility of iteratively tracing of yet asymptomatic infecteds is considered. With these insights we explain why contact tracing was and will be effective for control of smallpox and SARS, only partially effective for foot-and-mouth disease, and likely not effective for influenza. METHODS AND FINDINGS: We investigate contact tracing in a model of an emerging epidemic that is flexible enough to use for most infections. We consider isolation of symptomatic infecteds as the basic scenario, and express effectiveness as the proportion of contacts that need to be traced for a reproduction ratio smaller than 1. We obtain general results for special cases, which are interpreted with respect to the likely success of tracing for influenza, smallpox, SARS, and foot-and-mouth disease epidemics. CONCLUSIONS: We conclude that (1) there is no general predictive formula for the proportion to be traced as there is for the proportion to be vaccinated; (2) variability in time to detection is favourable for effective tracing; (3) tracing effectiveness need not be sensitive to the duration of the latent period and tracing delays; (4) iterative tracing primarily improves effectiveness when single-step tracing is on the brink of being effective.

negative: A Systematic Review of COVID-19 Epidemiology Based on Current Evidence As the novel coronavirus (SARS-CoV-2) continues to spread rapidly across the globe, we aimed to identify and summarize the existing evidence on epidemiological characteristics of SARS-CoV-2 and the effectiveness of control measures to inform policymakers and leaders in formulating management guidelines, and to provide directions for future research. We conducted a systematic review of the published literature and preprints on the coronavirus disease (COVID-19) outbreak following predefined eligibility criteria. Of 317 research articles generated from our initial search on PubMed and preprint archives on 21 February 2020, 41 met our inclusion criteria and were included in the review. Current evidence suggests that it takes about 3-7 days for the epidemic to double in size. Of 21 estimates for the basic reproduction number ranging from 1.9 to 6.5, 13 were between 2.0 and 3.0. The incubation period was estimated to be 4-6 days, whereas the serial interval was estimated to be 4-8 days. Though the true case fatality risk is yet unknown, current model-based estimates ranged from 0.3% to 1.4% for outside China. There is an urgent need for rigorous research focusing on the mitigation efforts to minimize the impact on society.

negative: Emerging study on the transmission of the Novel Coronavirus (COVID-19) from urban perspective: Evidence from China This study presents an in-depth investigation on the transmission of the novel coronavirus (COVID-19) from the urban perspective. It focuses on the “aftermath” of the outbreak and the spread of the infection among cities. Especially, this study provides insights of the fundamentals of the factors that may affect the spread of the infection in cities, where the marginal effects of some most influential factors to the virus transmission are estimated. It reveals that the distance to epicenter is a very strong influential factor, and is negatively linked with the spread of COVID-19. In addition, subway, wastewater and residential garbage are positively connected with the virus transmission. Moreover, both urban area and population density are negatively associated with the spread of COVID-19 at the early stage of the epidemic. Furthermore, this study also provides high precision estimation of the number of COVID-19 infection in Wuhan city, which is the epicenter of the outbreak in China. Based on the real-world data of cities outside Wuhan on March 2, 2020, the estimated number is 56,944.866 (mean value), which is very close to the officially reported number. The methodology and main conclusions shown in this paper are of general interest, and they can be applied to other countries to help understand the local transmission of COVID-19 as well.

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

negative: COVID-19 transmission in Mainland China is associated with temperature and humidity: a time-series analysis COVID-19 has become a pandemic. The influence of meteorological factors on the transmission and spread of COVID-19 if of interest. This study sought to examine the associations of daily average temperature (AT) and relative humidity (ARH) with the daily count of COVID-19 cases in 30 Chinese provinces (in Hubei from December 1, 2019 to February 11, 2020 and in other provinces from January 20, 2020 to Februarys 11, 2020). A Generalized Additive Model (GAM) was fitted to quantify the province-specific associations between meteorological variables and the daily cases of COVID-19 during the study periods. In the model, the 14-day exponential moving averages (EMAs) of AT and ARH, and their interaction were included with time trend and health-seeking behavior adjusted. Their spatial distributions were visualized. AT and ARH showed significantly negative associations with COVID-19 with a significant interaction between them (0.04, 95% confidence interval: 0.004-0.07) in Hubei. Every 1°C increase in the AT led to a decrease in the daily confirmed cases by 36% to 57% when ARH was in the range from 67% to 85.5%. Every 1% increase in ARH led to a decrease in the daily confirmed cases by 11% to 22% when AT was in the range from 5.04°C to 8.2°C. However, these associations were not consistent throughout Mainland China.

negative: Recent achievements in studies on diseases of common carp (Cyprinus carpio L.) Abstract Parasitic, fungal, bacterial and viral diseases of common carp (Cyprinus carpio L.) are reviewed. Besides a general overview of parasites of carp, swimbladder inflammation, caused by Sphaerospora spp., is discussed in detail. Saprolegnia spp. is the most important fungal pathogen. Aeromonas hydrophila and the atypical Aeromonas salmonicida, as well as Flexibacter columnaris, are described as the major bacterial pathogens of carp. Spring viraemia of carp caused by Rhabdovirus carpio is presented as the main viral infection of common carp. Details on methods of treatment and prevention are presented together with a description of the given diseases. The role of environmental stress, including “normal” culture practice and pollution, in the outbreak of diseases of common carp is discussed. Prospective methods to minimize the risk of diseases as well as their limitations are presented.

negative: Comparison of transmissibility of coronavirus between symptomatic and asymptomatic patients: Reanalysis of the Ningbo COVID-19 data. BACKGROUND Since the outbreak of the novel coronavirus disease 2019 (COVID-19) in December 2019, the coronavirus has spread all over the world at an unprecedented rate. The transmissibility of coronavirus from asymptomatic patients to healthy individuals has received enormous attention. An important study using the COVID-19 data from the city Ningbo, China, was carried out to estimate and compare the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. However, in the original analysis, the usual chi-squared tests were unduly used for some contingency tables with small cell counts including zero, which may violate the assumptions for the chi-squared test. OBJECTIVE We reanalyze the data from the city Ningbo with more appropriate statistical methods to draw more reliable and sound conclusions on the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. METHODS We exclude the cases associated with the super-spreader and adopt more appropriate statistical methods, including the permutation test and Fisher's exact test, to reanalyze the COVID-19 data from the city Ningbo. RESULTS After excluding the cases related to the super-spreader, Fisher's exact test yields p-value=.84, which indicates stronger evidence of no difference in the transmission rates compared with the original analysis. The odds ratio of transmission rates of coronavirus between the symptomatic and asymptomatic patients is 1.2 with a 95% confidence interval [0.5, 2.8]. CONCLUSIONS Through a more in-depth and comprehensive statistical analysis of the Ningbo data, we conclude that there is no difference in the transmission rates of coronavirus between the symptomatic and asymptomatic patients.

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

negative: How sustainable environments have reduced the diffusion of coronavirus disease 2019: the interaction between spread of COVID-19 infection, polluting industrialization, wind (renewable) energy This study endeavors to explain the relation between air pollution and particulate compounds emissions, wind resources and energy, and the diffusion of COVID-19 infection to provide insights of sustainable policy to prevent future epidemics. The statistical analysis here focuses on case study of Italy, one of the countries to experience a rapid increase in confirmed cases and deaths. Results reveal two main findings: 1) cities in regions with high wind speed and a high wind energy production in MW have a lower number of infected individuals of COVID-19 infection and total deaths; 2) cities located in hinterland zones (mostly those bordering large urban conurbations) with high polluting industrialization, low wind speed and less cleaner production have a greater number of infected individuals and total deaths. Hence, cities with pollution industrialization and low renewable energy have also to consider low wind speed and other climatological factors that can increase stagnation of the air in the atmosphere with potential problems for public health in the presence of viral agents. Results here suggest that current pandemic of Coronavirus disease and future epidemics similar to COVID-19 infection cannot be solved only with research and practice of medicine, immunology and microbiology but also with a proactive strategy directed to interventions for a sustainable development. Overall, then, this study has to conclude that a strategy to prevent future epidemics similar to COVID-19 infection must also be based on sustainability science to support a higher level of renewable energy and cleaner production to reduce polluting industrialization and, as result, the factors determining the spread of coronavirus disease and other infections in society.

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

negative: A mathematical model to investigate the transmission of COVID-19 in the Kingdom of Saudi Arabia Since the first confirmed case of SARS-CoV-2 coronavirus (COVID-19) in the 2nd day of March, Saudi Arabia has not report a quite rapid COVD-19 spread compared to America and many European countries. Possible causes include the spread of asymptomatic cases. To characterize the transmission of COVID-19 in Saudi Arabia, this paper applies a susceptible, exposed, symptomatic, asymptomatic, hospitalized, and recovered dynamical model, along with the official COVID-19 reported data by the Ministry of Health in Saudi Arabia. The basic reproduction number R0 is estimated to range from 2.87 to 4.9.

negative: Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections. Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines. By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale. Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other. Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity. Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity. It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites. It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomatic infectious lifecycle.

negative: Focus on Middle East respiratory syndrome coronavirus (MERS-CoV) Abstract Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The vast majority of these cases (71%) were reported in Saudi Arabia but the epidemic has now spread to 27 countries and has not ceased 6 years later, unlike SARS-CoV that disappeared a little less than 2 years after emerging. Due to the high fatality rate observed in MERS-CoV infected patients (36%), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. This review focuses in particular on the origin, epidemiology and clinical manifestations of MERS-CoV, as well as the diagnosis and treatment of infected patients. The experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease.

negative: Contact Tracing: a game of big numbers in the time of COVID-19 One of the more widely advocated solutions to slowing down the spread of COVID-19 has been automated contact tracing. Since proximity data can be collected by personal mobile devices, the natural proposal has been to use this for contact tracing as this provides a major gain over a manual implementation. In this work, we study the characteristics of automated contact tracing and its effectiveness for mapping the spread of a pandemic due to the spread of SARS-CoV-2. We highlight the infrastructure and social structures required for automated contact tracing to work for the current pandemic. We display the vulnerabilities of the strategy to inadequately sample the population, which results in the inability to sufficiently determine significant contact with infected individuals. Of crucial importance will be the participation of a significant fraction of the population for which we derive a minimum threshold. We conclude that a strong reliance on contact tracing to contain the spread of the SARS-CoV-2 pandemic can lead to the potential danger of allowing the pandemic to spread unchecked. A carefully thought out strategy for controlling the spread of the pandemic along with automated contact tracing can lead to an optimal solution.

negative: Maintenance Hemodialysis and Coronavirus Disease 2019 (COVID-19): Saving Lives With Caution, Care, and Courage

negative: Underlying trend, seasonality, prediction, forecasting and the contribution of risk factors: an analysis of globally reported cases of Middle East Respiratory Syndrome Coronavirus This study set out to identify and analyse trends and seasonal variations of monthly global reported cases of the Middle East respiratory syndrome coronavirus (MERS-CoV). It also made a prediction based on the reported and extrapolated into the future by forecasting the trend. Finally, the study assessed contributions of various risk factors in the reported cases. The motivation for this study is that MERS-CoV remains among the list of blueprint priority and potential pandemic diseases globally. Yet, there is a paucity of empirical literature examining trends and seasonality as the available evidence is generally descriptive and anecdotal. The study is a time series analysis using monthly global reported cases of MERS-CoV by the World Health Organisation between January 2015 and January 2018. We decomposed the series into seasonal, irregular and trend components and identified patterns, smoothened series, generated predictions and employed forecasting techniques based on linear regression. We assessed contributions of various risk factors in MERS-CoV cases over time. Successive months of the MERS-CoV cases suggest a significant decreasing trend (P = 0.026 for monthly series and P = 0.047 for Quarterly series). The MERS-CoV cases are forecast to wane by end 2018. Seasonality component of the cases oscillated below or above the baseline (the centred moving average), but no association with the series over time was noted. The results revealed contributions of risk factors such as camel contact, male, old age and being from Saudi Arabia and Middle East regions to the overall reported cases of MERS-CoV. The trend component and several risk factors for global MERS-CoV cases, including camel contact, male, age and geography/region significantly affected the series. Our statistical models appear to suggest significant predictive capacity and the findings may well inform healthcare practitioners and policymakers about the underlying dynamics that produced the globally reported MERS-CoV cases.

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: Approximate Reaction Systems Based on Rough Set Theory In this work we investigate how Rough Set Theory could be employed to model uncertainty and information incompleteness about a Reaction System. The approach that we propose is inspired by the idea of an abstract scientific experiment: we define the notion of test, which defines an approximation space on the states of a Reaction System, and observation, to represent the interactive process of knowledge building that is typical of complex systems. We then define appropriate notions of reducts and study their characterization in terms of both computational complexity and relationships with standard definitions of reducts in terms of Information Tables.

negative: Anticipating the novel coronavirus disease (COVID-19) pandemic The infectious novel coronavirus disease COVID-19 outbreak has been declared as a public health emergency of international concern, and later as an epidemic. To date, this outbreak has infected more than one million people and killed over fifty thousand people across the world. In most countries, the COVID-19 incidence curve rises sharply in a short span of time, suggesting a transition from a disease free (or low-burden disease) equilibrium state to a sustained infected (or high-burden disease) state. Such a transition from one stable state to another state in a relatively short span of time is often termed as a critical transition. Critical transitions can be, in general, successfully forecasted using many statistical measures such as return rate, variance and lag-1 autocorrelation. Here, we report an empirical test of this forecasting on the COVID-19 data sets for nine countries including India, China and the United States. For most of the data sets, an increase in autocorrelation and a decrease in return rate predict the onset of a critical transition. Our analysis suggests two key features in predicting the COVID-19 incidence curve for a specific country: a) the timing of strict social distancing and/or lockdown interventions implemented, and b) the fraction of a nation's population being affected by COVID-19 at the time of implementation of these interventions. Further, using satellite data of nitrogen dioxide which is emitted predominantly as a result of anthropogenic activities, as an indicator of lockdown policy, we find that in countries where the lockdown was implemented early and strictly have been successful in reducing the extent of transmission of the virus. These results hold important implications for designing effective strategies to control the spread of infectious pandemics.

negative: A Lesson Learned from the Outbreak of COVID-19 in Korea Despite the fact that making all efforts to deal with COVID-19 outbreak, Korea is in urgent need of moving away from a divided community approach and adopting a total community approach. Further, the nation needs to fully establish and activate the national emergency operation framework.

negative: Super-Flexibility in Practice: Insights from a Crisis Flexibility is intuitively valued as a means of dynamically adapting to uncertainty. Historically, it has been especially prized during times of crisis. This is clearly demonstrated today as the current Coronavirus crisis is unfolding; there are many different dimensions of flexibility, ranging from versatility, agility, and resilience, to hedging, robustness and liquidity. For convenience, we fuse these terms together under the conceptual umbrella of “super-flexibility”. We define super-flexibility as a dynamic capability to simultaneously withstand turbulence AND adapt to fluid reality. Our field research has focused on how companies in Silicon Valley embrace uncertainty and drive adaptation. In this paper, we draw on the experience of a manufacturing firm facing the floods that hit Thailand in October 2011. The crisis enabled us to observe a situation in which the different nuances of flexibility collectively came into play within a compressed time-frame. In this paper, we showcase the practical application of super-flexibility in a crisis. First, we describe the conceptual foundations of flexibility and its different nuances. We then examine the chronology of the crisis as events unfolded. We conclude by distilling a number of “super-flexibility” lessons for business leaders.

negative: Complex dynamic behavior in a viral model with state feedback control strategies With the consideration of mechanism of prevention and control for the spread of viral diseases, in this paper, we propose two novel virus dynamics models where state feedback control strategies are introduced. The first model incorporates the density of infected cells (or free virus) as control threshold value; we analytically show the existence and orbit stability of positive periodic solution. Theoretical results imply that the density of infected cells (or free virus) can be controlled within an adequate level. The other model determines the control strategies by monitoring the density of uninfected cells when it reaches a risk threshold value. We analytically prove the existence and orbit stability of semi-trivial periodic solution, which show that the viral disease dies out. Numerical simulations are carried out to illustrate the main results.

negative: Dynamical asymmetry exposes 2019-nCoV prefusion spike The novel coronavirus (2019-nCoV) spike protein is a smart molecular machine that instigates the entry of coronavirus to the host cell causing the COVID-19 pandemic. In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. The study finds 2019-nCoV to adopt a unique strategy by undertaking a dynamic conformational asymmetry induced by a few unique inter-chain interactions. This results in two prevalent asymmetric structures of spike where one or two spike heads lifted up undergoing a dynamic transition likely to enhance rapid recognition of the host-cell receptor turning on its high-infectivity. The crucial interactions identified in this study are anticipated to potentially affect the efficacy of therapeutic targets. One Sentence Summary Inter-chain-interaction driven rapid symmetry breaking strategy adopted by the prefusion trimeric spike protein likely to make 2019-nCoV highly infective.

negative: Contact tracing and isolation of asymptomatic spreaders to successfully control the COVID-19 epidemic among healthcare workers in Milan (Italy) Objective To study the source, symptoms, and duration of infection, preventive measures, contact tracing and their effects on SARS-CoV-2 epidemic among healthcare workers (HCW) in 2 large hospitals and 40 external healthcare services in Milan (Italy) to propose effective measures to control the COVID-19 epidemic among healthcare workers. Design Epidemiological observational study. Setting Two large hospitals and 40 territorial healthcare units, with a total of 5700 workers. Participants 143 HCWs with a SARS-CoV-2 positive nasopharyngeal (NF) swab in a population made of 5,700 HCWs. Main outcome measures Clinical data on the history of exposure, contacts inside and outside of the hospital, NF swab dates and results. A daily online self-reported case report form consisting of the morning and evening body temperature and 11 other symptoms (cough, dyspnoea, discomfort, muscle pain, headache, sore throat, vomiting, diarrhoea, anosmia, dysgeusia, conjunctival hyperaemia). Results Most workers were tested and found positive due to a close contact with a positive colleague (49%), followed by worker-initiated testing due to symptoms (and unknown contact, 28%), and a SARS-CoV-2 positive member of the family (9.8%). 10% of NF swabs performed in the framework of contact tracing resulted positive, compared to only 2.6% through random testing. The first (index) case caused a cluster of 7 positive HCWs discovered through contact tracing and testing of 250 asymptomatic HCWs. HCWs rarely reported symptoms of a respiratory infection, and up to 90% were asymptomatic or with mild symptoms in the days surrounding the positive NF swab. During the 15-day follow-up period, up to 40% of HCWs reported anosmia and dysgeusia/ageusia as moderate or heavy, more frequently than any other symptom. The time necessary for 95% of HCWs to be considered cured (between the positive and two negative NF swabs) was 30 days. Conclusion HCWs represent the main source of infection in healthcare institutions, 90% are asymptomatic or with symptoms not common in a respiratory infection. The time needed to overcome the infection in 95% of workers was 30 days. Contact tracing allows identifying asymptomatic workers which would spread SARS-CoV-2 in the hospital and is a more successful strategy than random testing.

negative: Keeping the Wheels of the Scientific Endeavor Turning during the COVID-19 Pandemic

negative: Emergence of SARS-like coronavirus poses new challenge in China

negative: Case fatality ratio of pandemic influenza

negative: The Final Size of an Epidemic and Its Relation to the Basic Reproduction Number We study the final size equation for an epidemic in a subdivided population with general mixing patterns among subgroups. The equation is determined by a matrix with the same spectrum as the next generation matrix and it exhibits a threshold controlled by the common dominant eigenvalue, the basic reproduction number [Formula: see text]: There is a unique positive solution giving the size of the epidemic if and only if [Formula: see text] exceeds unity. When mixing heterogeneities arise only from variation in contact rates and proportionate mixing, the final size of the epidemic in a heterogeneously mixing population is always smaller than that in a homogeneously mixing population with the same basic reproduction number [Formula: see text]. For other mixing patterns, the relation may be reversed.

negative: Award Winners and Abstracts of the 31st Annual Symposium of The Protein Society, Montreal, Canada, July 24–27, 2017

negative: Designing Medical Facilities to Care for Patients with Highly Hazardous Communicable Diseases Certain highly hazardous communicable diseases (HHCD), including viral hemorrhagic fevers, the Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome virus (SARS), have caused nosocomial outbreaks in unprepared facilities. Consequently, biocontainment units have been constructed to protect caregivers, patients, and family members, in addition to providing optimal care of the infected patient. Biocontainment units have adopted many of the design features originally found in biocontainment laboratories and can serve as national referral facilities for the most severe and highly hazardous infections. Although a patient with a HHCD can show up at any healthcare facility unannounced, not every hospital can or should attempt to establish a biocontainment unit. Nevertheless, there are design features or management principles found in biocontainment units that can be adopted in most facilities. Awareness of the potential risk, in addition to adopting structural and policy control measures, can do a lot to prepare a facility for the next unexpected infectious disease outbreak.

negative: Children’s Hospital Los Angeles COVID-19 Analysis Research Database (CARD) - A Resource for Rapid SARS-CoV-2 Genome Identification Using Interactive Online Phylogenetic Tools Effective response to the Coronavirus Disease 2019 (COVID-19) pandemic requires genomic resources and bioinformatics tools for genomic epidemiology and surveillance studies that involve characterizing full-length viral genomes, identifying origins of infections, determining the relatedness of viral infections, performing phylogenetic analyses, and monitoring the continuous evolution of the SARS-CoV-2 viral genomes. The Children’s Hospital, Los Angeles (CHLA) COVID-19 Analysis Research Database (CARD) (https://covid19.cpmbiodev.net/) is a comprehensive genomic resource that provides access to full-length SARS-CoV-2 viral genomes and associated meta-data for over 30,000 (as of May 20, 2020) isolates collected from global sequencing repositories and the sequencing performed at the Center for Personalized Medicine (CPM) at CHLA. Reference phylogenetic trees of global and USA viral isolates were constructed and are periodically updated using selected high quality SARS-CoV-2 genome sequences. These provide the baseline and analytical context for identifying the origin of a viral infection, as well as the relatedness of SARS-CoV-2 genomes of interest. A web-based and interactive Phylogenetic Tree Browser supports flexible tree manipulation and advanced analysis based on keyword search while highlighting time series animation, as well as subtree export for graphical representation or offline exploration. A Virus Genome Tracker accepts complete or partial SARS-CoV-2 genome sequence, compares it against all available sequences in the database (>30,000 at time of writing), detects and annotates the variants, and places the new viral isolate within the global or USA phylogenetic contexts based upon variant profiles and haplotype comparisons, in a few seconds. The generated analysis can potentially aid in genomic surveillance to trace the transmission of any new infection. Using CHLA CARD, we demonstrate the identification of a candidate outbreak point where 13 of 31 CHLA internal isolates may have originated. We also discovered multiple indels of unknown clinical significance in the orf3a gene, and revealed a number of USA-specific variants and haplotypes.

negative: 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.

negative: Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC(50)) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC(50) concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative EC(50)s of emetine towards the coronaviruses compared with Entamoeba histolytica, emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.

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

negative: Searching for MERS and Novel Flu with Limited Resources

negative: The SARS-CoV S glycoprotein The severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein alone can mediate the membrane fusion required for virus entry and cell fusion. It is also a major immunogen and a target for entry inhibitors. Recent rapid advances in our knowledge of the structure and function of this protein have lead to the development of a number of candidate vaccine immunogens and SARS-CoV entry inhibitors.

negative: COVID-19: Recent updates on SARS-CoV-2 and Preventing its Community Transmission in India by 21 Days Lockdown The current pandemic of COVID-19 has caused havoc all over world since its emergence and rapid spread Within three months the virus SARS-CoV-2 which was isolated from pneumonia cases in Wuhan City, Hubei Province, China in late December 2019, has affected almost all countries India reported its first case of COVID-19 from state of Kerala on January 30, 2020, a student returned from city of Wuhan Till date in India the disease had affected 12759 patients with 420 deaths With every passing day the mysterious virus is been uncovered with its unique characteristics enabling the researcher to unfold the various methods including hand washing and social distancing to curtail the pandemic Measures like 21 days lockdown to certain extent are effective but considering asymptomatic spreaders, extended measured lockdowns will be useful in the long term war against COVID-19 Till the vaccine and therapeutic solutions are derived, answer to pandemic and SARS-CoV-2 lies in lockdown, social distancing, contact tracing and containment

negative: [Dynamic basic reproduction number based evaluation for current prevention and control of COVID-19 outbreak in China] Objective: To evaluate the current status of the prevention and control of coronavirus disease (COVID-19) outbreak in China, establish a predictive model to evaluate the effects of the current prevention and control strategies, and provide scientific information for decision-making departments. Methods: Based on the epidemic data of COVID-19 openly accessed from national health authorities, we estimated the dynamic basic reproduction number R(0)(t) to evaluate the effects of the current COVID-19 prevention and control strategies in all the provinces (municipalities and autonomous regions) as well as in Wuhan and the changes in infectivity of COVID-19 over time. Results: For the stability of the results, 24 provinces (municipality) with more than 100 confirmed COVID-19 cases were included in the analysis. At the beginning of the outbreak, the R(0)(t) showed unstable trend with big variances. As the strengthening of the prevention and control strategies, R(0)(t) began to show a downward trend in late January, and became stable in February. By the time of data analysis, 18 provinces (municipality) (75%) had the R(0)(t)s less than 1. The results could be used for the decision making to free population floating conditionally. Conclusions: Dynamic R(0)(t) is useful in the evaluation of the change in infectivity of COVID-19, the prevention and control strategies for the COVID-19 outbreak have shown preliminary effects, if continues, it is expected to control the COVID-19 outbreak in China in near future.

negative: Bacterial resistance: A sensitive issue Complexity of the challenge and containment strategy in Europe Abstract The development of antimicrobial agents has been a key achievement of modern medicine. However, their overuse has led to an increasing incidence of infections due to antibiotic-resistant microorganisms. Quantitative figures on the current economic and health impact of antimicrobial resistance are scant, but it is clearly a growing challenge that requires timely action. That action should be at the educational, ethical, economic and political level. An important first step would be to increase public awareness and willingness to take the necessary measures to curb resistance. Hence, studies are needed that would provide solid, quantitative data on the societal impact of antibiotic resistance. This review discusses the complexity of resistance, identifies its main drivers and proposes measures to contain it on a European scale.

negative: Some remarks on protein attribute prediction and pseudo amino acid composition Abstract With the accomplishment of human genome sequencing, the number of sequence-known proteins has increased explosively. In contrast, the pace is much slower in determining their biological attributes. As a consequence, the gap between sequence-known proteins and attribute-known proteins has become increasingly large. The unbalanced situation, which has critically limited our ability to timely utilize the newly discovered proteins for basic research and drug development, has called for developing computational methods or high-throughput automated tools for fast and reliably identifying various attributes of uncharacterized proteins based on their sequence information alone. Actually, during the last two decades or so, many methods in this regard have been established in hope to bridge such a gap. In the course of developing these methods, the following things were often needed to consider: (1) benchmark dataset construction, (2) protein sample formulation, (3) operating algorithm (or engine), (4) anticipated accuracy, and (5) web-server establishment. In this review, we are to discuss each of the five procedures, with a special focus on the introduction of pseudo amino acid composition (PseAAC), its different modes and applications as well as its recent development, particularly in how to use the general formulation of PseAAC to reflect the core and essential features that are deeply hidden in complicated protein sequences.

negative: Networks and Models with Heterogeneous Population Structure in Epidemiology Heterogeneous population structure can have a profound effect on infectious disease dynamics, and is particularly important when investigating “tactical” disease control questions. At times, the nature of the network involved in the transmission of the pathogen (bacteria, virus, macro-parasite, etc.) appears to be clear; however, the nature of the network involved is dependent on the scale (e.g. within-host, between-host, or between-population), the nature of the contact, which ranges from the highly specific (e.g. sexual acts or needle sharing at the person-to-person level) to almost completely non-specific (e.g. aerosol transmission, often over long distances as can occur with the highly infectious livestock pathogen foot-and-mouth disease virus—FMDv—at the farm-to-farm level, e.g. Schley et al. in J. R. Soc. Interface 6:455–462, 2008), and the timescale of interest (e.g. at the scale of the individual, the typical infectious period of the host). Theoretical approaches to examining the implications of particular network structures on disease transmission have provided critical insight; however, a greater challenge is the integration of network approaches with data on real population structures. In this chapter, some concepts in disease modelling will be introduced, the relevance of selected network phenomena discussed, and then results from real data and their relationship to network analyses summarised. These include examinations of the patterns of air traffic and its relation to the spread of SARS in 2003 (Colizza et al. in BMC Med., 2007; Hufnagel et al. in Proc. Natl. Acad. Sci. USA 101:15124–15129, 2004), the use of the extensively documented Great Britain livestock movements network (Green et al. in J. Theor. Biol. 239:289–297, 2008; Robinson et al. in J. R. Soc. Interface 4:669–674, 2007; Vernon and Keeling in Proc. R. Soc. Lond. B, Biol. Sci. 276:469–476, 2009) and the growing interest in combining contact structure data with phylogenetics to identify real contact patterns as they directly relate to diseases of interest (Cottam et al. in PLoS Pathogens 4:1000050, 2007; Hughes et al. in PLoS Pathogens 5:1000590, 2009).

negative: The sociopolitical context of the COVID-19 response in South Korea

negative: Sustaining Bioethical Contributions in Times of Crisis and Change

negative: Insights from early mathematical models of 2019-nCoV acute respiratory disease (COVID-19) dynamics In December 2019, a novel coronavirus (SARS-CoV-2) has been identified to cause acute respiratory disease in humans. An outbreak of this disease has been reported in mainland China with the city of Wuhan as the recognized epicenter. The disease has also been exported to other countries, including the Philippines, but the level of spread is still under control (as of 08 February 2020). To describe and predict the dynamics of the disease, several preliminary mathematical models are formulated by various international study groups. Here, the insights that can be drawn from these models are discussed, especially as inputs for designing strategies to control the epidemics. Proposed model-based strategies on how to prevent the spread of the disease in local setting, such as during large social gatherings, are also presented. The model shows that the exposure time is a significant factor in spreading the disease. With a basic reproduction number equal to 2, and 14-day infectious period, an infected person staying more than 9 hours in the event could infect other people. Assuming the exposure time is 18 hours, the model recommends that attendees of the social gathering should have a protection with more than 70 percent effectiveness.

negative: Human Saliva: Non-Invasive Fluid for Detecting Novel Coronavirus (2019-nCoV) The breakthrough of novel coronavirus (2019-nCoV) in Wuhan, a city of China, has damaged the status of health and quality of life In the sequel of this epidemic or contagious disease, the patient experiences fever, chest paint, chills, a rapid heartbeat, breathing difficulties, pneumonia, and kidney failure It has been suggested that this disease can spread through human-to-human transmission or by super spreading By the help of the non-invasive fluid “saliva”, it is easy to detect the virus This can help with the comfort of the patient as well as healthcare personnel Under this perspective, we discuss the epidemic situation of 2019-nCOV and its relationship with human saliva

negative: Emergency cesarean section in an epidemic of the middle east respiratory syndrome: a case report Only a few reports have been published on women with an infectious respiratory viral pathogen, such as Middle East Respiratory Syndrome (MERS) Coronavirus delivering a baby. A laboratory confirmed case of MERS was reported during a MERS outbreak in the Republic of Korea in a woman at gestational week 35 + 4. She recovered, and delivered a healthy baby by emergency cesarean section (C-sec). We present the clinical course and the emergency C-sec in a pregnant woman with MERS.

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

negative: Aspects médico-psychologiques relatifs à l’épidémie de coronavirus (Covid-19) : l’apport de la théorie de la détection du signal et du concept de lieu de contrôle

negative: Coronavirus-19 Disease (COVID-19): A case series of early suspects reported and the implications towards the response to the pandemic in Zimbabwe Abstract Zimbabwe is among the countries that have been identified to be at risk of the COVID-19 pandemic. As of the 15th of March 2020, there has been no confirmed case of the virus. Official reports of suspect cases were used to appraise the general screening, case management, and preparedness of the country towards the COVID-19 pandemic. In terms of the surveillance and capacity to screen at ports of entry, the country seems to be faring well. The country might not be screening optimally, considering the number of COVID-19 tests conducted to date and suspected cases who missed testing. Three of the suspected cases faced mental, social, and psychological consequences due to them being suspects of COVID-19. There is a need to enhance the screening process and infrastructure at all ports of entry. More COVID-19 diagnostic tests should be procured to increase the testing capacity. Training and awareness of mental, social, and psychological consequences of COVID-19 should be offered to health care workers and the public. More financial resources should be sourced to enable the country to control the pandemic.

negative: CONTAIN: Privacy-oriented Contact Tracing Protocols for Epidemics Pandemic and epidemic diseases such as CoVID-19, SARS-CoV2, and Ebola have spread to multiple countries and infected thousands of people. Such diseases spread mainly through person-to-person contacts. Health care authorities recommend contact tracing procedures to prevent the spread to a vast population. Although several mobile applications have been developed to trace contacts, they typically require collection of privacy-intrusive information such as GPS locations, and the logging of privacy-sensitive data on a third party server, or require additional infrastructure such as WiFi APs with known locations. In this paper, we introduce CONTAIN, a privacy-oriented mobile contact tracing application that does not rely on GPS or any other form of infrastructure-based location sensing, nor the continuous logging of any other personally identifiable information on a server. The goal of CONTAIN is to allow users to determine with complete privacy if they have been within a short distance, specifically, Bluetooth wireless range, of someone that is infected, and potentially also when. We identify and prove the privacy guarantees provided by our approach. Our simulation study utilizing an empirical trace dataset (Asturies) involving 100 mobile devices and around 60000 records shows that users can maximize their possibility of identifying if they were near an infected user by turning on the app during active times.

negative: Large Arabic Twitter Dataset on COVID-19 The 2019 coronavirus disease (COVID-19), emerged late December 2019 in China, is now rapidly spreading across the globe. At the time of writing this paper, the number of global confirmed cases has passed two millions and half with over 180,000 fatalities. Many countries have enforced strict social distancing policies to contain the spread of the virus. This have changed the daily life of tens of millions of people, and urged people to turn their discussions online, e.g., via online social media sites like Twitter. In this work, we describe the first Arabic tweets dataset on COVID-19 that we have been collecting since January 1st, 2020. The dataset would help researchers and policy makers in studying different societal issues related to the pandemic. Many other tasks related to behavioral change, information sharing, misinformation and rumors spreading can also be analyzed.

negative: Spread and dynamics of the COVID-19 epidemic in Italy: Effects of emergency containment measures The spread of coronavirus disease 2019 (COVID-19) in Italy prompted drastic measures for transmission containment. We examine the effects of these interventions, based on modeling of the unfolding epidemic. We test modeling options of the spatially explicit type, suggested by the wave of infections spreading from the initial foci to the rest of Italy. We estimate parameters of a metacommunity Susceptible-Exposed-Infected-Recovered (SEIR)-like transmission model that includes a network of 107 provinces connected by mobility at high resolution, and the critical contribution of presymptomatic and asymptomatic transmission. We estimate a generalized reproduction number ([Formula: see text] = 3.60 [3.49 to 3.84]), the spectral radius of a suitable next-generation matrix that measures the potential spread in the absence of containment interventions. The model includes the implementation of progressive restrictions after the first case confirmed in Italy (February 21, 2020) and runs until March 25, 2020. We account for uncertainty in epidemiological reporting, and time dependence of human mobility matrices and awareness-dependent exposure probabilities. We draw scenarios of different containment measures and their impact. Results suggest that the sequence of restrictions posed to mobility and human-to-human interactions have reduced transmission by 45% (42 to 49%). Averted hospitalizations are measured by running scenarios obtained by selectively relaxing the imposed restrictions and total about 200,000 individuals (as of March 25, 2020). Although a number of assumptions need to be reexamined, like age structure in social mixing patterns and in the distribution of mobility, hospitalization, and fatality, we conclude that verifiable evidence exists to support the planning of emergency measures.

negative: The basic reproduction number and prediction of the epidemic size of the novel coronavirus (COVID-19) in Shahroud, Iran Objectives: To estimate the basic reproduction number (R0) of COVID-19 in the early stage of the epidemic and predict the expected number of new cases in Shahroud, Northeast of Iran. Methods: The R0 of COVID-19 was estimated using the serial interval distribution and the number of incidence cases. The serial interval was fit with a gamma distribution. The probable incidence and cumulative incidence in the next 30 days were predicted using the assumption that daily incidence follows a Poisson distribution determined by daily infectiousness. Data analysis was done using earlyR and projections packages in R software. Results: The maximum-likelihood value of R0 was 2.7 (95% confidence interval (CI): 2.1 to 3.4) for the COVID-19 epidemic in the early 14 days and decreased to 1.13 (95% CI: 1.03 to 1.25) by the end of the day 41. The expected average number of new cases in Shahroud is 9.0 case/day with a standard deviation of 3.8, which means an estimated total of 271 (95% CI: 178-383) new cases in the next 30 days. Conclusions: It is essential to reduce the R0 to values below one. Therefore, we strongly recommend enforcing and continuing the current preventive measures, restricting travel, and providing screening tests for a larger proportion of the population.

negative: CD4 rat × rat and mouse × rat T cell hybridomas produced by fusion of established T cell lines and clones to W/Fu (C58NT)D Previously, fusion of established T cell lines or clones has been claimed to be difficult. We now report our experiences in the fusion of both long term cultures of rat T cell clones and mouse T cell lines to rat W/Fu (C58NT)D. Upon fusion of rat T cell clones the hybrids obtained expressed antigen specificities identical to those of the parent clones. In addition, C58 was used for interspecies hybridisation of murine T cell lines. The specificity of intra- and inter-species hybrids was maintained by subcloning. We conclude that the C58 cell line can be used to generate continuously growing monoclonal T-cell reagents of sufficient stability using both intra- and inter-species hybri disation.

negative: Evaluation of the potential incidence of COVID-19 and effectiveness of contention measures in Spain: a data-driven approach Our society is currently experiencing an unprecedented challenge, managing and containing an outbreak of a new coronavirus disease known as COVID-19. While China - were the outbreak started - seems to have been able to contain the growth of the epidemic, different outbreaks are nowadays being detected in multiple countries. Much is currently unknown about the natural history of the disease, such as a possible asymptomatic spreading or the role of age in both the susceptibility and mortality of the disease. Nonetheless, authorities have to take action and implement contention measures, even if not everything is known. To facilitate this task, we have studied the effect of different containment strategies that can be put into effect. Our work specifically refers to the situation in Spain as of February 28th, 2020, where a few dozens of cases have been detected. We implemented an SEIR-metapopulation model that allows tracing explicitly the spatial spread of the disease through data-driven stochastic simulations. Our results are in line with the most recent recommendations from the World Health Organization, namely, that the best strategy is the early detection and isolation of individuals with symptoms, followed by interventions and public recommendations aimed at reducing the transmissibility of the disease, which although not efficacious for disease eradication, would produce as a second-order effect a delay of several days in the raise of the number of infected cases

negative: Predictions, role of interventions and effects of a historic national lockdown in India's response to the COVID-19 pandemic: data science call to arms Importance: India has taken strong and early public health measures for arresting the spread of the COVID-19 epidemic. With only 536 COVID-19 cases and 11 fatalities, India - a democracy of 1.34 billion people - took the historic decision of a 21-day national lockdown on March 25. The lockdown was further extended to May 3, soon after the analysis of this paper was completed. Objective: To study the short- and long-term impact of an initial 21-day lockdown on the total number of COVID-19 cases in India compared to other less severe non-pharmaceutical interventions using epidemiological forecasting models and Bayesian estimation algorithms; to compare effects of hypothetical durations of lockdown from an epidemiological perspective; to study alternative explanations for slower growth rate of the virus outbreak in India, including exploring the association of the number of cases and average monthly temperature; and finally, to outline the pivotal role of reliable and transparent data, reproducible data science methods, tools and products as we reopen the country and prepare for a post lock-down phase of the pandemic. Design, Setting, and Participants: We use the daily data on the number of COVID-19 cases, of recovered and of deaths from March 1 until April 7, 2020 from the 2019 Novel Coronavirus Visual Dashboard operated by the Johns Hopkins University Center for Systems Science and Engineering (JHU CSSE). Additionally, we use COVID-19 incidence counts data from Kaggle and the monthly average temperature of major cities across the world from Wikipedia. Main Outcome and Measures: The current time-series data on daily proportions of cases and removed (recovered and death combined) from India are analyzed using an extended version of the standard SIR (susceptible, infected, and removed) model. The eSIR model incorporates time-varying transmission rates that help us predict the effect of lockdown compared to other hypothetical interventions on the number of cases at future time points. A Markov Chain Monte Carlo implementation of this model provided predicted proportions of the cases at future time points along with credible intervals (CI). Results: Our predicted cumulative number of COVID-19 cases in India on April 30 assuming a 1-week delay in people's adherence to a 21-day lockdown (March 25 - April 14) and a gradual, moderate resumption of daily activities after April 14 is 9,181 with upper 95% CI of 72,245. In comparison, the predicted cumulative number of cases under "no intervention" and "social distancing and travel bans without lockdown" are 358 thousand and 46 thousand (upper 95% CI of nearly 2.3 million and 0.3 million) respectively. An effective lockdown can prevent roughly 343 thousand (upper 95% CI 1.8 million) and 2.4 million (upper 95% CI 38.4 million) COVID-19 cases nationwide compared to social distancing alone by May 15 and June 15, respectively. When comparing a 21-day lockdown with a hypothetical lockdown of longer duration, we find that 28-, 42-, and 56-day lockdowns can approximately prevent 238 thousand (upper 95% CI 2.3 million), 622 thousand (upper 95% CI 4.3 million), 781 thousand (upper 95% CI 4.6 million) cases by June 15, respectively. We find some suggestive evidence that the COVID-19 incidence rates worldwide are negatively associated with temperature in a crude unadjusted analysis with Pearson correlation estimates [95% confidence interval] between average monthly temperature and total monthly incidence around the world being -0.185 [-0.548, 0.236] for January, -0.110 [-0.362, 0.157] for February, and -0.173 [-0.314, -0.026] for March. Conclusions and Relevance: The lockdown, if implemented correctly in the end, has a high chance of reducing the total number of COVID-19 cases in the short term, and buy India invaluable time to prepare its healthcare and disease monitoring system. Our analysis shows we need to have some measures of suppression in place after the lockdown for the best outcome. We cannot heavily rely on the hypothetical prevention governed by meteorological factors such as temperature based on current evidence. From an epidemiological perspective, a longer lockdown between 42-56 days is preferable. However, the lockdown comes at a tremendous price to social and economic health through a contagion process not dissimilar to that of the coronavirus itself. Data can play a defining role as we design post-lockdown testing, reopening and resource allocation strategies. Software: Our contribution to data science includes an interactive and dynamic app (covind19.org) with short- and long-term projections updated daily that can help inform policy and practice related to COVID-19 in India. Anyone can visualize the observed data for India and create predictions under hypothetical scenarios with quantification of uncertainties. We make our prediction codes freely available (https://github.com/umich-cphds/cov-ind-19) for reproducible science and for other COVID-19 affected countries to use them for their prediction and data visualization work.

negative: Experience with intravenous ribavirin in the treatment of hemorrhagic fever with renal syndrome in Korea Abstract Results of a clinical study using intravenous (IV) ribavirin for treating Department of Defense personnel with hemorrhagic fever with renal syndrome (HFRS) acquired in Korea from 1987 to 2005 were reviewed to determine the clinical course of HFRS treated with IV ribavirin. A total of 38 individuals enrolled in the study had subsequent serological confirmation of HFRS. Four of the 38 individuals received three or fewer doses of ribavirin and were excluded from treatment analysis. Of the remaining 34 individuals, oliguria was present in one individual at treatment initiation; none of the remaining 33 subjects developed oliguria or required dialysis. The mean peak serum creatinine was 3.46mg/dl and occurred on day 2 of ribavirin therapy. Both the peak serum creatinine and the onset of polyuria occurred on mean day 6.8 of illness. Reversible hemolytic anemia was the main adverse event of ribavirin, with a ≥25% decrease in hematocrit observed in 26/34 (76.5%) individuals. While inability to adjust for all baseline variables prevents comparison to historical cohorts in Korea where oliguria has been reported in 39–69% cases and dialysis required in approximately 40% HFRS cases caused by Hantaan virus, the occurrence of 3% oliguria and 0% dialysis requirement in the treatment cohort is supportive of a previous placebo-controlled HFRS trial in China where IV ribavirin given early resulted in decreased occurrence of oliguria and decreased severity of renal insufficiency.

negative: An Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in South Korea, 2015

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

negative: Contentious issues and evolving concepts in the clinical presentation and management of patients with COVID-19 infectionwith reference to use of therapeutic and other drugs used in Co-morbid diseases (Hypertension, diabetes etc) Abstract Background and aims Multiple issues in management of COVID have emerged, but confusion persists regarding rational interpretation. Aim of this brief review is to review these issues based on current literature. Methods This is a narrative review with Pubmed and Google Scholar search till 23 March 2020. Search terms were, COVID-19, treatment of coronavirus, COVID 19 and following terms; chloroquine, hydroxychloroquine, ibuprofen, ACE-inhibitors or angiotensin receptor blockers, cardiovascular disease, diarrhoea, liver, testis and gastrointestinal disease. Results We discuss evidence regarding role of chloroquine and hydroxychloroquine in treatment and prophylaxis, use of inhibitors of the renin angiotensin system, safety of ibuprofen, unusual clinical features like gastrointestinal symptoms and interpretation of tests for cardiac enzymes and biomarkers. Conclusions While our conclusions on management of COVID-19 patients with co-morbidities are based on current evidence, however, data is limited and there is immediate need for fast track research.

negative: Building resilience against biological hazards and pandemics: COVID-19 and its implications for the Sendai Framework Abstract 2020 has become the year of coping with COVID-19. This year was to be the “super year” for sustainability, a year of strengthening global actions to accelerate the transformations required for achieving the 2030 agenda. We argue that 2020 can and must be a year of both. Thus we call for more utilisation of the health-emergency disaster risk management (Health-EDRM) framework to complement current responses to COVID-19 and the patent risk of similar phenomena in the future. To make our case, we examine current responses to COVID-19 and their implications for the SFDRR. We argue that current mechanisms and strategies for disaster resilience, as outlined in the SFDRR, can enhance responses to epidemics or global pandemics such as COVID-19. In this regard, we make several general and DRR-specific recommendations. These recommendations concern knowledge and science provision in understanding disaster and health-related emergency risks, the extension of disaster risk governance to manage both disaster risks and potential health-emergencies, particularly for humanitarian coordination aspects; and the strengthening of community-level preparedness and response.

negative: Stopping the SuperSpreader Epidemic, Part II: MERS Goes Pandemic In a paper of August 2013, I discussed the so-called SuperSpreader (SS) epidemic model and emphasized that it has dynamics differing greatly from the more-familiar uniform (or Poisson) textbook model. In that paper, SARS in 2003 was the representative instance and it was suggested that MERS may be another. In April 2014, MERS incident cases showed a spectacular spike (going from a handful in the previous April to more than 260 in that month of 2014) reminiscent of a figure I published nine months earlier. Here I refit the two-level and several variant SS models to incident data from January 1, 2013--April 30, 2014 and conclude that MERS will go pandemic (all other factors remaining the same). In addition, I discuss a number of model-realism and fitting methodology issues relevant to analysing SS epidemics.

negative: Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic virus considered as one of the major public threat with a total number of 2 298 laboratory-confirmed cases and 811 associated deaths reported by World Health Organization as of January 2019. The transmission of the virus was expected to be from the camels found in Middle Eastern countries via the animal and human interaction. The genome structure provided information about the pathogenicity and associated virulent factors present in the virus. Recent studies suggested that there were limited insight available on the development of novel therapeutic strategies to induce immunity against the virus. The severities of MERS-CoV infection highlight the necessity of effective approaches for the development of various therapeutic remedies. Thus, the present review comprehensively and critically illustrates the recent aspects on the epidemiology of the virus, the structural and functional features of the viral genome, viral entry and transmission, major mechanisms of pathogenesis and associated virulent factors, current animal models, detection methods and novel strategies for the development of vaccines against MERS-CoV. The review further illustrates the molecular and computational virtual screening platforms which provide insights for the identification of putative drug targets and novel lead molecules toward the development of therapeutic remedies.

negative: Middle East respiratory syndrome (MERS) in Asia: lessons gleaned from the South Korean outbreak

negative: No indications for overt innate immune suppression in critically ill COVID-19 patients At the end of March 2020, there were in excess of 800.000 confirmed cases of coronavirus disease 2019 (COVID-19) worldwide. Several reports suggest that, in severe cases, COVID-19 may cause a hyperinflammatory 'cytokine storm'. However, unlike SARS-CoV infection, high levels of anti-inflammatory mediators have also been reported in COVID-19 patients. One study reported that 16% of COVID-19 patients who died developed secondary infection, which might indicate an immune-suppressed state. We explored kinetics of mHLA-DR expression, the most widely used marker of innate immune suppression in critically ill patients, in COVID-19 patients admitted to the ICU. Twenty-four confirmed COVID-19 patients were included, of which 75% was male and 79% had comorbidities. All patients were mechanically ventilated and exhibited large high levels of inflammatory parameters such as CRP and PCT. mHLA-DR expression levels were mostly within the normal range of 15000 - 45000 mAb/cell and showed no change over time. COVID-19 patients displayed notably higher mHLA-DR expression levels compared with bacterial septic shock patients. None of the COVID-19 patients developed a secondary infection. In conclusion, despite a pronounced inflammatory response, mHLA-DR expression kinetics indicate no overt innate immune suppression in COVID-19 patients. These data signify that innate immune suppression as a negative feedback mechanism following PAMP-induced inflammation appears not to be present in COVID-19.

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

negative: Transplant programmes during COVID-19: Unintended consequences for health inequality. Transplant programmes are being scaled back as healthcare systems worldwide respond to COVID-19. Most centres are now taking only super urgent and urgent cases, if at all. Management of donor organs is also impacted. Contingency protocols may prioritise distance over equitable sharing principles. Live and deceased donation is either being selectively paused or operating under stringent criteria based on local capacity. This will inevitably lead to variable patient experience.

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

negative: Data analysis on Coronavirus spreading by macroscopic growth laws To evaluate the effectiveness of the containment on the epidemic spreading of the new Coronavirus disease 2019, we carry on an analysis of the time evolution of the infection in a selected number of different Countries, by considering well-known macroscopic growth laws, the Gompertz law, and the logistic law. We also propose here a generalization of Gompertz law. Our data analysis permits an evaluation of the maximum number of infected individuals. The daily data must be compared with the obtained fits, to verify if the spreading is under control. From our analysis it appears that the spreading reached saturation in China, due to the strong containment policy of the national government. In Singapore a large growth rate, recently observed, suggests the start of a new strong spreading. For South Korea and Italy, instead, the next data on new infections will be crucial to understand if the saturation will be reached for lower or higher numbers of infected individuals.

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

negative: Predictions for COVID-19 outbreak in India using Epidemiological models COVID-19 data from India is compared against several countries as well as key states in the US with a major outbreak, and it is found that the basic reproduction number R_0 for India is in the expected range of 1.4-3.9. Further, the rate of growth of infections in India is very close to that in Washington and California. Exponential and classic susceptible-infected-recovered (SIR) models based on available data are used to make short and long-term predictions on a daily basis. Based on the SIR model, it is estimated that India will enter equilibrium by the end of May 2020 with the final epidemic size of approximately 13,000. However, this estimation will be invalid if India enters the stage of community transmission. The impact of social distancing, again with the assumption of no community transmission, is also assessed by comparing data from different geographical locations.

negative: Research on the Influence of Information Diffusion on the Transmission of the Novel Coronavirus (COVID-19) With the rapid development of mobile Internet in China, the information of the epidemic is full-time and holographic, and the role of information diffusion in epidemic control is increasingly prominent. At the same time, the publicity of all kinds of big data also provides the possibility to explore the impact of media information diffusion on disease transmission. This paper explores the mechanism of the influence of information diffusion on the spread of the novel coronavirus, develops a model of the interaction between information diffusion and disease transmission based on the SIR model, and empirically tests the role and mechanism of information diffusion in the spread of COCID-19 by using econometric method. The result shows that there was a significant negative correlation between the information diffusion and the spread of the novel coronavirus; The result of robust test shows that the spread of both epidemic information and protection information hindered the further spread of the epidemic.

negative: Understand Research Hotspots Surrounding COVID-19 and Other Coronavirus Infections Using Topic Modeling Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that causes severe respiratory illness in humans, which eventually results in the current outbreak of novel coronavirus disease (COVID-19) around the world. The research community is interested to know what are the hotspots in coronavirus (CoV) research and how much is known about COVID-19. This study aimed to evaluate the characteristics of publications involving coronaviruses as well as COVID-19 by using a topic modeling analysis. Methods: We extracted all abstracts and retained the most informative words from the COVID-19 Open Research Dataset, which contains all the 35,092 pieces of coronavirus related literature published up to March 20, 2020. Using Latent Dirichlet Allocation modeling, we trained an eight-topic model from the corpus. We then analyzed the semantic relationships between topics and compared the topic distribution between COVID-19 and other CoV infections. Results: Eight topics emerged overall: clinical characterization, pathogenesis research, therapeutics research, epidemiological study, virus transmission, vaccines research, virus diagnostics, and viral genomics. It was observed that COVID-19 research puts more emphasis on clinical characterization, epidemiological study, and virus transmission at present. In contrast, topics about diagnostics, therapeutics, vaccines, genomics and pathogenesis only accounted for less than 10% or even 4% of all the COVID-19 publications, much lower than those of other CoV infections. Conclusions: These results identified knowledge gaps in the area of COVID-19 and offered directions for future research. Keywords: COVID-19, coronavirus, topic modeling, hotspots, text mining

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

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

negative: COVID-19 social distancing in the Kingdom of Saudi Arabia: Bold measures in the face of political, economic, social and religious challenges Abstract Social distancing at its various levels has been a key measure to mitigate the transmission of COVID-19. The implementation of strict measures for social distancing is challenging, including in the Kingdom of Saudi Arabia (KSA) due to its level of urbanizations, its social and religious norms and its annual hosting of high visibility international religious mass gatherings. KSA started introducing decisive social distancing measures early before the first case of COVID-19 was confirmed in the Kingdom. These ranged from suspension or cancelations of religious, entertainment and sporting mass gatherings and events such as the Umrah, shutting of educational establishments and mosques and postponing all non-essential gatherings, to imposing a partial curfew. These measures were taken in spite of their socio-economic, political and religious challenges in the interest of public and global health. The effect of these actions on the epidemic curve of the Kingdom and on the global fight against COVID-19 remains to be seen. However, given the current COVID-19 situation, further bold and probably unpopular measures are likely to be introduced in the future.

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

negative: Contact tracing and disease control. Contact tracing, followed by treatment or isolation, is a key control measure in the battle against infectious diseases. It is an extreme form of locally targeted control, and as such has the potential to be highly efficient when dealing with low numbers of cases. For this reason it is frequently used to combat sexually transmitted diseases and new invading pathogens. Accurate modelling of contact tracing requires explicit information about the disease-transmission pathways from each individual, and hence the network of contacts. Here, pairwise-approximation methods and full stochastic simulations are used to investigate the utility of contact tracing. A simple relationship is found between the efficiency of contact tracing necessary for eradication and the basic reproductive ratio of the disease. This holds for a wide variety of realistic situations including heterogeneous networks containing core-groups or super-spreaders, and asymptomatic individuals. Clustering (transitivity) within the transmission network is found to destroy the relationship, requiring lower efficiency than predicted.

negative: MERS-CoV: transmisión y el papel de nuevas especies hospederas

negative: Grandpa, grandpa, tell me the one about Bitcoin being a safe haven: Evidence from the COVID-19 pandemics Bitcoin being a safe haven asset is one of the traditional stories in the cryptocurrency community. However, during its existence and relevant presence, i.e. approximately since 2013, there has been no severe situation on the financial markets globally to prove or disprove this story until the COVID-19 pandemics. We study the quantile correlations of Bitcoin and two benchmarks -- S\&P500 and VIX -- and we make comparison with gold as the traditional safe haven asset. The Bitcoin safe haven story is shown and discussed to be unsubstantiated and far-fetched, while gold comes out as a clear winner in this contest.

negative: Commentary: COVID-19 in patients with diabetes

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

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: 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.

negative: Coronavirus disease (COVID-19) Community Testing Team in Scotland: A 14-day review, 6 to 20 February 2020 In response to the outbreak of COVID-19, we set up a team to carry out sampling in the community. This enabled individuals to remain in self-isolation in their own homes and to prevent healthcare settings and services from being overwhelmed by admissions for sampling of suspected cases. There is evidence that this is a cost effective, safe and necessary service to complement COVID-19 testing in hospitals.

negative: Rethinking the financial network On 16 November 2002, the first official case of Severe Acute Respiratory Syndrome (SARS) was recorded in Guangdong Province, China. Panic ensued. Uncertainty about its causes and contagious consequences brought many neighbouring economies across Asia to a standstill. Hotel occupancy rates in Hong Kong fell from over 80 % to less than 15 %, while among Beijing’s 5-star hotels occupancy rates fell below 2 %.

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

negative: Coronaviruses — drug discovery and therapeutic options In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd.2015.37) contains supplementary material, which is available to authorized users.

negative: Adoption of COVID-19 triage strategies for low-income settings

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

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

negative: Infectious bronchitis corona virus establishes productive infection in avian macrophages interfering with selected antimicrobial functions Infectious bronchitis virus (IBV) causes respiratory disease leading to loss of egg and meat production in chickens. Although it is known that macrophage numbers are elevated in the respiratory tract of IBV infected chickens, the role played by macrophages in IBV infection, particularly as a target cell for viral replication, is unknown. In this study, first, we investigated the ability of IBV to establish productive replication in macrophages in lungs and trachea in vivo and in macrophage cell cultures in vitro using two pathogenic IBV strains. Using a double immunofluorescent technique, we observed that both IBV Massachusetts-type 41 (M41) and Connecticut A5968 (Conn A5968) strains replicate in avian macrophages at a low level in vivo. This in vivo observation was substantiated by demonstrating IBV antigens in macrophages following in vitro IBV infection. Further, IBV productive infection in macrophages was confirmed by demonstrating corona viral particles in macrophages and IBV ribonucleic acid (RNA) in culture supernatants. Evaluation of the functions of macrophages following infection of macrophages with IBV M41 and Conn A5968 strains revealed that the production of antimicrobial molecule, nitric oxide (NO) is inhibited. It was also noted that replication of IBV M41 and Conn A5968 strains in macrophages does not interfere with the induction of type 1 IFN activity by macrophages. In conclusion, both M41 and Con A5968 IBV strains infect macrophages in vivo and in vitro resulting productive replications. During the replication of IBV in macrophages, their ability to produce NO can be affected without affecting the ability to induce type 1 IFN activity. Further studies are warranted to uncover the significance of macrophage infection of IBV in the pathogenesis of IBV infection in chickens.

negative: Management of gastrointestinal leaks after surgery for clinically severe obesity. BACKGROUND Gastrointestinal leaks after bariatric surgery are the primary cause of serious morbidity and mortality nationwide. Enteric leaks can differ in severity, presentation, and management, depending on the type of bariatric surgery performed. Our objective was to describe the clinical presentation and treatment outcomes in patients who developed postoperative leaks at a university hospital bariatric referral center. METHODS A retrospective observational study using descriptive statistics was conducted on data from 1499 bariatric operations performed at our institution from 1994 to 2010. The procedures included a variant of biliopancreatic diversion with long limb reconstruction (BPD-LL) in 820 patients (791 open and 29 laparoscopic), Roux-en-Y gastric bypass (RYGB) in 301 patients (105 open and 196 laparoscopic), and sleeve gastrectomy (SG) in 208 patients (5 open and 203 laparoscopic). RESULTS Of these patients, 30 (2%) developed a postoperative leak at a median of 18 days (range 2-32) postoperatively. The primary procedure was laparoscopic SG in 12 patients (5.8%), laparoscopic RYGB in 5 patients (1.6%), and BPD-LL (12 open and 1 laparoscopic) in 13 patients (1.6%). In all patients who underwent laparoscopic SG, the leak site was along the staple line. The gastrojejunal anastomosis was leaking in 4 (80%) and 12 (92.3%) patients in the RYGB and BPD-LL group, respectively. The enteroenteral anastomosis was leaking in 1 patient each in the RYGB and BPD-LL groups (20% and 7.7%, respectively). Three patients (10%; 2 from the BPD-LL group and 1 from the RYGB group) presented with generalized peritonitis and underwent emergency re-exploration; nonoperative treatment was successful in the remaining 27 patients (90%). Stent placement for persistent gastrocutaneous fistula was used in 9 patients (30%; 8 from the SG cohort and 1 from the BPD-LL group). The overall mortality rate was 3.3%. CONCLUSION In our experience, most leaks resulting from antiobesity surgery were successfully managed using nonoperative methods. Rapid management of gastrointestinal leaks using computed tomography-guided drainage and/or intraluminal stent placement could be the treatment of choice in selected patients.

negative: On the global trends and spread of the COVID-19 outbreak: preliminary assessment of the potential relation between location-specific temperature and UV index The novel coronavirus, since its first outbreak in December, has, up till now, affected approximately 114,542 people across 115 countries. Many international agencies are devoting efforts to enhance the understanding of the evolving COVID-19 outbreak on an international level, its influences, and preparedness. At present, COVID-19 appears to affect individuals through person-to-person means, like other commonly found cold or influenza viruses. It is widely known and acknowledged that viruses causing influenza peak during cold temperatures and gradually subside in the warmer temperature, owing to their seasonality. Thus, COVID-19, due to its regular flu-like symptoms, is also expected to show similar seasonality and subside as the global temperatures rise in the northern hemisphere with the onset of spring. Despite these speculations, however, the systematic analysis in the global perspective of the relation between COVID-19 spread and meteorological parameters is unavailable. Here, by analyzing the region- and city-specific affected global data and corresponding meteorological parameters, we show that there is an optimum range of temperature and UV index strongly affecting the spread and survival of the virus, whereas precipitation, relative humidity, cloud cover, etc. have no effect on the virus. Unavailability of pharmaceutical interventions would require greater preparedness and alert for the effective control of COVID-19. Under these conditions, the information provided here could be very helpful for the global community struggling to fight this global crisis. It is, however, important to note that the information presented here clearly lacks any physiological evidences, which may merit further investigation. Thus, any attempt for management, implementation, and evaluation strategies responding to the crisis arising due to the COVID-19 outbreak must not consider the evaluation presented here as the foremost factor.

negative: Fuzzy Clustering Stability Evaluation of Time Series The discovery of knowledge by analyzing time series is an important field of research. In this paper we investigate multiple multivariate time series, because we assume a higher information value than regarding only one time series at a time. There are several approaches which make use of the granger causality or the cross correlation in order to analyze the influence of time series on each other. In this paper we extend the idea of mutual influence and present FCSETS (Fuzzy Clustering Stability Evaluation of Time Series), a new approach which makes use of the membership degree produced by the fuzzy c-means (FCM) algorithm. We first cluster time series per timestamp and then compare the relative assignment agreement (introduced by Eyke Hüllermeier and Maria Rifqi) of all subsequences. This leads us to a stability score for every time series which itself can be used to evaluate single time series in the data set. It is then used to rate the stability of the entire clustering. The stability score of a time series is higher the more the time series sticks to its peers over time. This not only reveals a new idea of mutual time series impact but also enables the identification of an optimal amount of clusters per timestamp. We applied our model on different data, such as financial, country related economy and generated data, and present the results.

negative: Characterizing transcriptional regulatory sequences in coronaviruses and their role in recombination Novel coronaviruses, including SARS-CoV-2, SARS, and MERS, often originate from recombination events. The mechanism of recombination in RNA viruses is template switching. Coronavirus transcription also involves template switching at specific regions, called transcriptional regulatory sequences (TRS). It is hypothesized but not yet verified that TRS sites are prone to recombination events. Here, we developed a tool called SuPER to systematically identify TRS in coronavirus genomes and then investigated whether recombination is more common at TRS. We ran SuPER on 506 coronavirus genomes and identified 465 TRS-L and 3509 TRS-B. We found that the TRS-L core sequence (CS) and the secondary structure of the leader sequence are generally conserved within coronavirus genera but different between genera. By examining the location of recombination breakpoints with respect to TRS-B CS, we observed that recombination hotspots are more frequently co-located with TRS-B sites than expected.

negative: The role of particle size in aerosolised pathogen transmission: A review Summary Understanding respiratory pathogen transmission is essential for public health measures aimed at reducing pathogen spread. Particle generation and size are key determinant for pathogen carriage, aerosolisation, and transmission. Production of infectious respiratory particles is dependent on the type and frequency of respiratory activity, type and site of infection and pathogen load. Further, relative humidity, particle aggregation and mucus properties influence expelled particle size and subsequent transmission. Review of 26 studies reporting particle sizes generated from breathing, coughing, sneezing and talking showed healthy individuals generate particles between 0.01 and 500 μm, and individuals with infections produce particles between 0.05 and 500 μm. This indicates that expelled particles carrying pathogens do not exclusively disperse by airborne or droplet transmission but avail of both methods simultaneously and current dichotomous infection control precautions should be updated to include measures to contain both modes of aerosolised transmission.

negative: Diabetes and COVID-19: evidence, current status and unanswered research questions. Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.

negative: Epidemics on networks: Reducing disease transmission using health emergency declarations and peer communication Understanding individual decisions in a world where communications and information move instantly via cell phones and the internet, contributes to the development and implementation of policies aimed at stopping or ameliorating the spread of diseases. In this manuscript, the role of official social network perturbations generated by public health officials to slow down or stop a disease outbreak are studied over distinct classes of static social networks. The dynamics are stochastic in nature with individuals (nodes) being assigned fixed levels of education or wealth. Nodes may change their epidemiological status from susceptible, to infected and to recovered. Most importantly, it is assumed that when the prevalence reaches a pre-determined threshold level, [Formula: see text] , information, called awareness in our framework, starts to spread, a process triggered by public health authorities. Information is assumed to spread over the same static network and whether or not one becomes a temporary informer, is a function of his/her level of education or wealth and epidemiological status. Stochastic simulations show that threshold selection [Formula: see text] and the value of the average basic reproduction number impact the final epidemic size differentially. For the Erdős-Rényi and Small-world networks, an optimal choice for [Formula: see text] that minimize the final epidemic size can be identified under some conditions while for Scale-free networks this is not case.

negative: COVID-19-Related Web Search Behaviors and Infodemic Attitudes in Italy: Infodemiological Study BACKGROUND: Since the beginning of the novel coronavirus disease (COVID-19) outbreak, fake news and misleading information have circulated worldwide, which can profoundly affect public health communication. OBJECTIVE: We investigated online search behavior related to the COVID-19 outbreak and the attitudes of “infodemic monikers” (ie, erroneous information that gives rise to interpretative mistakes, fake news, episodes of racism, etc) circulating in Italy. METHODS: By using Google Trends to explore the internet search activity related to COVID-19 from January to March 2020, article titles from the most read newspapers and government websites were mined to investigate the attitudes of infodemic monikers circulating across various regions and cities in Italy. Search volume values and average peak comparison (APC) values were used to analyze the results. RESULTS: Keywords such as “novel coronavirus,” “China coronavirus,” “COVID-19,” “2019-nCOV,” and “SARS-COV-2” were the top infodemic and scientific COVID-19 terms trending in Italy. The top five searches related to health were “face masks,” “amuchina” (disinfectant), “symptoms of the novel coronavirus,” “health bulletin,” and “vaccines for coronavirus.” The regions of Umbria and Basilicata recorded a high number of infodemic monikers (APC weighted total >140). Misinformation was widely circulated in the Campania region, and racism-related information was widespread in Umbria and Basilicata. These monikers were frequently searched (APC weighted total >100) in more than 10 major cities in Italy, including Rome. CONCLUSIONS: We identified a growing regional and population-level interest in COVID-19 in Italy. The majority of searches were related to amuchina, face masks, health bulletins, and COVID-19 symptoms. Since a large number of infodemic monikers were observed across Italy, we recommend that health agencies use Google Trends to predict human behavior as well as to manage misinformation circulation in Italy.

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

negative: Preventing COVID-19 from the perspective of industrial information integration: Evaluation and continuous improvement of information networks for sustainable epidemic prevention COVID-19 is accelerating industrial information integration (III) for sustainable epidemic prevention and innovation design. It is important to emphasize that this interaction makes it reciprocal. To prevent COVID-19, the III of industrial sectors should be strengthened to encourage innovation for sustainable epidemic prevention. Accordingly, we studied the overall dynamic change trend of industrial sectors’ information integration networks (IIN), the characteristics of individual IIN, and their influence on IIN performance. In the study, the gravity model and social network analysis were used to determine the variables of industrial sectors’ information distance and quality, and to construct the IIN of industrial sectors. The results show that the overall relevance of the IIN of industrial sectors is low, and the network density fluctuates, with high network efficiency and poor stability. Two-way, strong correlation between industrial sectors is relatively low. The spillover effect of industrial sectors in the upstream of the industrial chain is poor, and it is difficult to have a strong information integration driving effect on the downstream industrial sectors. The interplate linkage of the IIN of industrial sectors is insufficient. Compared with point centrality and closeness, improvement of the betweenness centrality of industrial sectors can significantly improve IIN performance.

negative: Respiratory Viruses and Atypical Bacteria

negative: Superspreading and the effect of individual variation on disease emergence Population-level analyses often use average quantities to describe heterogeneous systems, particularly when variation does not arise from identifiable groups(1,2). A prominent example, central to our current understanding of epidemic spread, is the basic reproductive number, R(0), which is defined as the mean number of infections caused by an infected individual in a susceptible population(3,4). Population estimates of R(0) can obscure considerable individual variation in infectiousness, as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous ‘superspreading events’ in which certain individuals infected unusually large numbers of secondary cases(5,6,7,8,9,10). For diseases transmitted by non-sexual direct contacts, such as SARS or smallpox, individual variation is difficult to measure empirically, and thus its importance for outbreak dynamics has been unclear(2,10,11). Here we present an integrated theoretical and statistical analysis of the influence of individual variation in infectiousness on disease emergence. Using contact tracing data from eight directly transmitted diseases, we show that the distribution of individual infectiousness around R(0) is often highly skewed. Model predictions accounting for this variation differ sharply from average-based approaches, with disease extinction more likely and outbreaks rarer but more explosive. Using these models, we explore implications for outbreak control, showing that individual-specific control measures outperform population-wide measures. Moreover, the dramatic improvements achieved through targeted control policies emphasize the need to identify predictive correlates of higher infectiousness. Our findings indicate that superspreading is a normal feature of disease spread, and to frame ongoing discussion we propose a rigorous definition for superspreading events and a method to predict their frequency. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature04153) contains supplementary material, which is available to authorized users.

negative: Molecular, serological, and biochemical diagnosis and monitoring of COVID-19: IFCC taskforce evaluation of the latest evidence. The global coronavirus disease 2019 (COVID-19) has presented major challenges for clinical laboratories, from initial diagnosis to patient monitoring and treatment. Initial response to this pandemic involved the development, production, and distribution of diagnostic molecular assays at an unprecedented rate, leading to minimal validation requirements and concerns regarding their diagnostic accuracy in clinical settings. In addition to molecular testing, serological assays to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now becoming available from numerous diagnostic manufacturers. In both cases, the lack of peer-reviewed data and regulatory oversight, combined with general misconceptions regarding their appropriate use, have highlighted the importance of laboratory professionals in robustly validating and evaluating these assays for appropriate clinical use. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 has been established to synthesize up-to-date information on the epidemiology, pathogenesis, and laboratory diagnosis and monitoring of COVID-19, as well as to develop practical recommendations on the use of molecular, serological, and biochemical tests in disease diagnosis and management. This review summarizes the latest evidence and status of molecular, serological, and biochemical testing in COVID-19 and highlights some key considerations for clinical laboratories operating to support the global fight against this ongoing pandemic. Confidently this consolidated information provides a useful resource to laboratories and a reminder of the laboratory's critical role as the world battles this unprecedented crisis.

negative: International Course on Emerging Viruses in the Amazon Region

negative: The time scale of asymptomatic transmission affects estimates of epidemic potential in the COVID-19 outbreak The role of asymptomatic carriers in transmission poses challenges for control of the COVID-19 pandemic. Study of asymptomatic transmission and implications for surveillance and disease burden are ongoing, but there has been little study of the implications of asymptomatic transmission on dynamics of disease. We use a mathematical framework to evaluate expected effects of asymptomatic transmission on the basic reproduction number [Formula: see text] (i.e., the expected number of secondary cases generated by an average primary case in a fully susceptible population) and the fraction of new secondary cases attributable to asymptomatic individuals. If the generation-interval distribution of asymptomatic transmission differs from that of symptomatic transmission, then estimates of the basic reproduction number which do not explicitly account for asymptomatic cases may be systematically biased. Specifically, if asymptomatic cases have a shorter generation interval than symptomatic cases, [Formula: see text] will be over-estimated, and if they have a longer generation interval, [Formula: see text] will be under-estimated. Estimates of the realized proportion of asymptomatic transmission during the exponential phase also depend on asymptomatic generation intervals. Our analysis shows that understanding the temporal course of asymptomatic transmission can be important for assessing the importance of this route of transmission, and for disease dynamics. This provides an additional motivation for investigating both the importance and relative duration of asymptomatic transmission.

negative: An Epidemiological Study on COVID-19: A Rapidly Spreading Disease Background The outbreak of the novel coronavirus disease in 2019 (COVID-19) caused a major public health crisis worldwide and challenged healthcare systems across the six continents. The high infectivity of the disease led many governments to adopt strict regulations and measures with the aim of containing its spread. The purpose of this study is to assess the incidence, severity, and territorial expansion of COVID-19. Methods Data from the World Health Organization was screened, and COVID-19 situation reports were extracted from January 21 up till March 14 (inclusive). Our data included the total number of cases, total number of new cases, total number of cured cases, and total number of related deaths. Percentage change of cases over the days of our study were calculated using the Joinpoint regression, with a significance level set at greater than 0.05. Results The total number of COVID-19 cases reached 156,622, with 5,845 subsequent deaths. China, Italy, and Iran have the highest number of cases worldwide. During the first 22 days, the incidence rate of COVID-19 increased significantly to reach 1.81 cases per million persons (p<0.001). That was followed by a significant decrease over the next 11 days (p<0.001) to reach 0.071 cases per million persons. A steady rise then followed, which saw a significant increase in incidence rate to 1.429 cases per million persons (p<0.001). Percentages of death and cured cases varied across the different countries; nevertheless, death percentages have generally been decreasing since the start of the crisis. Conclusion Adopting precautionary regulations such as social isolation, increasing sanitation, and employing strict quarantine measures have proved to be beneficial in containing the virus. Further research needs to be conducted to help discover therapeutic modalities and improve outcomes.

negative: Griffithsin protects mice from genital herpes by preventing cell-to-cell spread. Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpes simplex virus 2 (HSV-2), a cofactor for HIV acquisition, in vitro and in a murine model. Safety was evaluated by examining its impact on epithelial barrier integrity in polarized cultures and testing whether repeated intravaginal dosing potentiates the susceptibility of mice to genital herpes. Griffithsin displayed modest inhibitory activity against HSV-2 if present during viral entry but completely blocked plaque formation if present postentry, reduced plaque size, and prevented cell-to-cell spread. These in vitro findings translated to significant protection against genital herpes in mice treated with 0.1% griffithsin gel. Griffithsin, but not placebo gel, prevented viral spread (visualized with a luciferase-expressing virus), significantly reduced disease scores, and resulted in greater survival (P < 0.05, log rank test). Protection persisted when HSV-2 was introduced in seminal plasma. Although griffithsin triggered a small decline in transepithelial electrical resistance in polarized cultures, this did not translate to any significant increase in the ability of HIV to migrate from the apical to the basolateral chamber nor to an increase in susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days. These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread and support its further development for HIV and HSV-2 prevention.

negative: Role of China in the Quest to Define and Control Severe Acute Respiratory Syndrome China holds the key to solving many questions crucial to global control of severe acute respiratory syndrome (SARS). The disease appears to have originated in Guangdong Province, and the causative agent, SARS coronavirus, is likely to have originated from an animal host, perhaps sold in public markets. Epidemiologic findings, integral to defining an animal-human linkage, may then be confirmed by laboratory studies; once animal host(s) are confirmed, interventions may be needed to prevent further animal-to-human transmission. Community seroprevalence studies may help determine the basis for the decline in disease incidence in Guangdong Province after February 2002. China will also be able to contribute key data about how the causative agent is transmitted and how it is evolving, as well as identifying pivotal factors influencing disease outcome. There must be support for systematically addressing these fundamental questions in China and rapidly disseminating results.

negative: Emerging horizon for bat borne viral zoonoses Bats are the only flying placental mammals that constitute the second largest order of mammals and present all around the world except in Arctic, Antarctica and a few oceanic islands. Sixty percent of emerging infectious diseases originating from animals are zoonotic and more than two-thirds of them originate in wildlife. Bats were evolved as a super-mammal for harboring many of the newly identified deadly diseases without any signs and lesions. Their unique ability to fly, particular diet, roosting behavior, long life span, ability to echolocate and critical susceptibility to pathogens make them suitable host to harbor numerous zoonotic pathogens like virus, bacteria and parasite. Many factors are responsible for the emergence of bat borne zoonoses but the most precipitating factor is human intrusions. Deforestation declined the natural habitat and forced the bats and other wild life to move out of their niche. These stressed bats, having lost foraging and behavioral pattern invade in proximity of human habitation. Either directly or indirectly they transmit the viruses to humans and animals. Development of fast detection modern techniques for viruses from the diseased and environmental samples and the lessons learned in the past helped in preventing the severity during the latest outbreaks.

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: Development of a rapid test kit for SARS-CoV-2: an example of product design We present an example of applying ‘need-driven’ product design principle to the development of a rapid test kit to detect SARS-COV-2 (COVID-19). The tests are intended for use in the field and, longer term, for home use. They detect whether a subject is currently infected with the virus and is infectious. The urgent need for large numbers of tests in field setting imposes constraints such as short test time and lack of access to specialist equipment, laboratories and skilled technicians to perform the test and interpret results. To meet these needs, an antigen test based on RT-LAMP with colorimetric readout was chosen. Direct use of swab sample with no RNA extraction was explored. After extensive experimental study (reported elsewhere), a rapid test kit has been fabricated to satisfy all design criteria.

negative: The Coronavirus Pandemic: "The Show Must Not Go On"

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

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

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: Detection of spreader nodes and ranking of interacting edges in Human-SARS-CoV protein interaction network The entire world has recently witnessed the commencement of coronavirus disease 19 (COVID-19) pandemic. It is caused by a novel coronavirus (n-CoV) generally distinguished as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It has exploited human vulnerabilities to coronavirus outbreak. SARS-CoV-2 promotes fatal chronic respiratory disease followed by multiple organ failure which ultimately puts an end to human life. No proven vaccine for n-CoV is available till date in spite of significant research efforts worldwide. International Committee on Taxonomy of Viruses (ICTV) has reached to a consensus that the virus SARS-CoV-2 is highly genetically similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) outbreak of 2003. It has been reported that SARS-CoV has ∼89% genetic similarities with n-CoV. With this hypothesis, the current work focuses on the identification of spreader nodes in SARS-CoV protein interaction network. Various network characteristics like edge ratio, neighborhood density and node weight have been explored for defining a new feature spreadability index by virtue of which spreader nodes and edges are identified. The selected top spreader nodes having high spreadability index have been also validated by Susceptible-Infected-Susceptible (SIS) disease model. Initially, the proposed method is applied on a synthetic protein interaction network followed by SARS-CoV-human protein interaction network. Hence, key spreader nodes and edges (ranked edges) are unmasked in SARS-CoV proteins and its connected level 1 and level 2 human proteins. The new network attribute spreadability index along with generated SIS values of selected top spreader nodes when compared with the other network centrality based methodologies like Degree centrality (DC), Closeness centrality (CC), Local average centrality (LAC) and Betweeness centrality (BC) is found to perform relatively better than the existing-state-of-art.

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

negative: Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China BACKGROUND: A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19. METHODS: We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis. RESULTS: 112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram. CONCLUSIONS: The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.

negative: Preliminary estimating the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea and Italy by 5 March 2020 Abstract The novel coronavirus disease 2019 (COVID-19) outbreak and Italy has caused 6088 cases and 41 deaths in Republic of Korea and 3144 cases and 107 death in Italy by 5 March 2020. We modeled the transmission process in Republic of Korea and Italy with a stochastic model and estimated the basic reproduction number R 0 as 2.6 (95% CI: 2.3-2.9) or 3.2 (95% CI: 2.9-3.5) in Republic of Korea, under the assumption that the exponential growth starting on 31 January or 5 February 2020, and 2.6 (95% CI: 2.3-2.9) or 3.3 (95% CI: 3.0-3.6) in Italy, under the assumption that the exponential growth starting on 5 February or 10 February 2020.

negative: Relationship between the ABO Blood Group and the COVID-19 Susceptibility The novel coronavirus disease-2019 (COVID-19) has been spreading around the world rapidly and declared as a pandemic by WHO. Here, we compared the ABO blood group distribution in 2,173 patients with COVID-19 confirmed by SARS-CoV-2 test from three hospitals in Wuhan and Shenzhen, China with that in normal people from the corresponding regions. The results showed that blood group A was associated with a higher risk for acquiring COVID-19 compared with non-A blood groups, whereas blood group O was associated with a lower risk for the infection compared with non-O blood groups. This is the first observation of an association between the ABO blood type and COVID-19. It should be emphasized, however, that this is an early study with limitations. It would be premature to use this study to guide clinical practice at this time, but it should encourage further investigation of the relationship between the ABO blood group and the COVID-19 susceptibility.

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: Initial Investigation of Transmission of COVID-19 Among Crew Members During Quarantine of a Cruise Ship - Yokohama, Japan, February 2020 An outbreak of coronavirus disease 2019 (COVID-19) among passengers and crew on a cruise ship led to quarantine of approximately 3,700 passengers and crew that began on February 3, 2020, and lasted for nearly 4 weeks at the Port of Yokohama, Japan (1). By February 9, 20 cases had occurred among the ship's crew members. By the end of quarantine, approximately 700 cases of COVID-19 had been laboratory-confirmed among passengers and crew. This report describes findings from the initial phase of the cruise ship investigation into COVID-19 cases among crew members during February 4-12, 2020.

negative: Adaptive cyclic exit strategies from lockdown to suppress COVID-19 and allow economic activity Many countries have applied lockdown that helped suppress COVID-19, but with devastating economic consequences. Here we propose exit strategies from lockdown that provide sustainable, albeit reduced, economic activity. We use mathematical models to show that a cyclic schedule of 4-day work and 10-day lockdown, or similar variants, can prevent resurgence of the epidemic while providing part-time employment. The cycle pushes the reproduction number R below one by reduced exposure time and by exploiting the virus latent period: those infected during work days reach peak infectiousness during lockdown days. The number of work days can be adapted in response to observations. Throughout, full epidemiological measures need to continue including hygiene, physical distancing, compartmentalization, testing and contact tracing. This conceptual framework, when combined with other interventions to control the epidemic, can offer the beginnings of predictability to many economic sectors.

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: 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.

negative: Hate multiverse spreads malicious COVID-19 content online beyond individual platform control We show that malicious COVID-19 content, including hate speech, disinformation, and misinformation, exploits the multiverse of online hate to spread quickly beyond the control of any individual social media platform. Machine learning topic analysis shows quantitatively how online hate communities are weaponizing COVID-19, with topics evolving rapidly and content becoming increasingly coherent. Our mathematical analysis provides a generalized form of the public health R0 predicting the tipping point for multiverse-wide viral spreading, which suggests new policy options to mitigate the global spread of malicious COVID-19 content without relying on future coordination between all online platforms.

negative: Quantify the role of superspreaders -opinion leaders- on COVID-19 information propagation in the Chinese Sina-microblog BACKGROUD: Effective communication of accurate information through social media constitutes an important component of public health interventions in modern time, when traditional public health approaches such as contact tracing, quarantine and isolation are among the few options for the containing the disease spread in the population. The success of control of COVID-19 outbreak started from Wuhan, the capital city of Hubei Province of China relies heavily on the resilience of residents to follow public health interventions which induce substantial interruption of social-economic activities, and evidence shows that opinion leaders have been playing significant roles in the propagation of epidemic information and public health policy and implementations. METHODS: We design a mathematical model to quantify the roles of information superspreaders in single specific information which outbreaks rapidly and usually has a short duration period, and to examine the information propagation dynamics in the Chinese Sina-microblog. Our opinion-leader susceptible-forwarding-immune (OL-SFI) model is formulated to track the temporal evolution of forwarding quantities generated by opinion leaders and normal users. RESULTS: Data fitting from the real data of COVID-19 obtained from Chinese Sina-microblog can identify the different contact rates and forwarding probabilities (and hence calculate the basic information forwarding reproduction number of superspreaders), and can be used to evaluate the roles of opinion leaders in different stages of the information propagation and the outbreak unfolding. CONCLUSIONS: The parameterized model can be used to nearcast the information propagation trend, and the model-based sensitivity analysis can help to explore important factors for the roles of opinion leaders.

negative: Six weeks into the 2019 coronavirus disease outbreak: it is time to consider strategies to impede the emergence of new zoonotic infections

negative: SARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps, and Opportunities Approximately 3 billion people around the world have gone into some form of social separation to mitigate the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The uncontrolled influx of patients in need of emergency care has rapidly brought several national health systems to near-collapse with deadly consequences to those afflicted by Coronavirus Disease 2019 (COVID-19) and other critical diseases associated with COVID-19. Solid scientific evidence regarding SARS-CoV-2/COVID-19 remains scarce; there is an urgent need to expand our understanding of the SARS-CoV-2 pathophysiology to facilitate precise and targeted treatments. The capacity for rapid information dissemination has emerged as a double-edged sword; the existing gap of high-quality data is frequently filled by anecdotal reports, contradictory statements, and misinformation. This review addresses several important aspects unique to the SARS-CoV-2/COVID-19 pandemic highlighting the most relevant knowledge gaps and existing windows-of-opportunity. Specifically, focus is given on SARS-CoV-2 immunopathogenesis in the context of experimental therapies and preclinical evidence and their applicability in supporting efficacious clinical trial planning. The review discusses the existing challenges of SARS-CoV-2 diagnostics and the potential application of translational technology for epidemiological predictions, patient monitoring, and treatment decision-making in COVID-19. Furthermore, solutions for enhancing international strategies in translational research, cooperative networks, and regulatory partnerships are contemplated.

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

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

negative: Transmission interval estimates suggest pre-symptomatic spread of COVID-19 Background: As the COVID-19 epidemic is spreading, incoming data allows us to quantify values of key variables that determine the transmission and the effort required to control the epidemic. We determine the incubation period and serial interval distribution for transmission clusters in Singapore and in Tianjin. We infer the basic reproduction number and identify the extent of pre-symptomatic transmission. Methods: We collected outbreak information from Singapore and Tianjin, China, reported from Jan.19-Feb.26 and Jan.21-Feb.27, respectively. We estimated incubation periods and serial intervals in both populations. Results: The mean incubation period was 7.1 (6.13, 8.25) days for Singapore and 9 (7.92, 10.2)days for Tianjin. Both datasets had shorter incubation periods for earlier-occurring cases. The mean serial interval was 4.56 (2.69, 6.42) days for Singapore and 4.22 (3.43, 5.01) for Tianjin. We inferred that early in the outbreaks, infection was transmitted on average 2.55 and 2.89days before symptom onset (Singapore, Tianjin). The estimated basic reproduction number for Singapore was 1.97 (1.45, 2.48) secondary cases per infective; for Tianjin it was 1.87 (1.65,2.09) secondary cases per infective. Conclusions: Estimated serial intervals are shorter than incubation periods in both Singapore and Tianjin, suggesting that pre-symptomatic transmission is occurring. Shorter serial intervals lead to lower estimates of R0, which suggest that half of all secondary infections should be prevented to control spread.

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: Network Analysis of MERS Coronavirus within Households, Communities, and Hospitals to Identify Most Centralized and Super-Spreading in the Arabian Peninsula, 2012 to 2016 Contact history is crucial during an infectious disease outbreak and vital when seeking to understand and predict the spread of infectious diseases in human populations. The transmission connectivity networks of people infected with highly contagious Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia were assessed to identify super-spreading events among the infected patients between 2012 and 2016. Of the 1379 MERS cases recorded during the study period, 321 (23.3%) cases were linked to hospital infection, out of which 203 (14.7%) cases occurred among healthcare workers. There were 1113 isolated cases while the number of recorded contacts per MERS patient is between 1 (n=210) and 17 (n=1), with a mean of 0.27 (SD = 0.76). Five super-important nodes were identified based on their high number of connected contacts worthy of prioritization (at least degree of 5). The number of secondary cases in each SSE varies (range, 5–17). The eigenvector centrality was significantly (p < 0.05) associated with place of exposure, with hospitals having on average significantly higher eigenvector centrality than other places of exposure. Results suggested that being a healthcare worker has a higher eigenvector centrality score on average than being nonhealthcare workers. Pathogenic droplets are easily transmitted within a confined area of hospitals; therefore, control measures should be put in place to curtail the number of hospital visitors and movements of nonessential staff within the healthcare facility with MERS cases.

negative: Isolation and contact tracing can tip the scale to containment of COVID-19 in populations with social distancing Background: Novel coronavirus (SARS-CoV-2) has extended its range of transmission in all parts of the world, with substantial variation in rates of transmission and severity of associated disease. Many countries have implemented social distancing as a measure to control further spread. Methods: We evaluate whether and under which conditions containment or slowing down COVID-19 epidemics are possible by isolation and contact tracing in settings with various levels of social distancing. We use a stochastic transmission model in which every person generates novel infections according to a probability distribution that is affected by the incubation period distribution (time from infection to symptoms), distribution of the latent period (time from infection to onset of infectiousness), and overall transmissibility. The model distinguishes between close contacts (e.g., within a household) and other contacts in the population. Social distancing affects the number of contacts outside but not within the household. Findings: The proportion of asymptomatic or unascertained cases has a strong impact on the controllability of the disease. If the proportion of asymptomatic infections is larger than 30%, contact tracing and isolation cannot achieve containment for an R0 of 2.5. Achieving containment by social distancing requires a reduction of numbers of non-household contacts by around 90%. Depending on the realized level of contact reduction, tracing and isolation of only household contacts, or of household and non-household contacts are necessary to reduce the effective reproduction number to below 1. A combination of social distancing with isolation and contact tracing leads to synergistic effects that increase the prospect of containment. Interpretation: Isolation and contact tracing can be an effective means to slow down epidemics, but only if the majority of cases are ascertained. In a situation with social distancing, contact tracing can act synergistically and tip the scale towards containment, and can therefore be a tool for controlling COVID-19 epidemics as part of an exit strategy from current lockdown measures.

negative: Food Delivery Service During Social Distancing: Proactively Preventing or Potentially Spreading Coronavirus Disease–2019?

negative: Cytokine Storm in COVID-19 patients transforms to a Cytokine Super Cyclone in patients with risk factors The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses like SARS-CoV and MERS-CoV, which are established to cause lower respiratory tract infection. The viral infection can be fatal as the disease advances to pneumonia followed by acute respiratory distress syndrome (ARDS). Increasingly higher cytokine concentration on account of over-stimulated immune response against the virus, or the ‘cytokine storm’, is the reason behind the manifestation of lethal clinical symptoms. In this article, we discuss the immune pathogenesis of cytokine storm and its relation with SARS-CoV2/COVID-19 risk factors. People with underlying risk factors are more susceptible to fatal complications of COVID-19 infection leading to poor clinical outcome. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 to a Cytokine Super Cyclone. We also overviewed antiviral immune response provided by BCG vaccine involving the IL-1β, IL-6 and TNF-α secretion via ‘trained monocytes’, which confers early protection against SARS-CoV2.

negative: Taste Changes (Dysgeusia) in COVID-19: A systematic review and metaanalysis

negative: Estimating the Efficacy of Traffic Blockage and Quarantine for the Epidemic Caused by 2019-nCoV (COVID-19) Background: Since the 2019-nCoV (COVID-19) outbreaks in Wuhan, China, the cumulative number of confirmed cases is increasing every day, and a large number of populations all over the world are at risk. The quarantine and traffic blockage can alleviate the risk of the epidemic and the infections, henceforth evaluating the efficacy of such actions is essential to inform policy makers and raise the public awareness of the importance of self-isolation and quarantine. Method: We collected confirmed case data and the migration data, and introduced the quarantine factor and traffic blockage factor to the Flow-SEIR model. By varying the quarantine factor and traffic blockage factor, we simulated the change of the peak number and arrival time of infections, then the efficacy of these two intervation measures can be analyzed in our simulation. In our study, the self-protection at home is also included in quarantine. Results: In the simulated results, the quarantine and traffic blockage are effective for epidemic control. For Hubei province, the current quarantine factor is estimaed to be 0.405, which means around 40.5% of suceptibles who are close contacting with are in quarantine, and the current traffic blockage factor is estimaed to be 0.66, which indicates around 34% of suceptibles who had flowed out from Hubei. For the other provinces outside Hubei, the current quarantine factor is estimated to be 0.285, and the current traffic blockage factor is estimated to be 0.26. With the quarantine and traffic blockage factor increasing, the number of infections decrease dramatically. We also simulated the start dates of quarantine and traffic blockage at four time points, the simulated results show that the early of warning is also effective for epidemic containing. However, provincial level traffic blockage can only alleviate 21.06% - 22.38% of the peak number of infections. In general, the quarantine is much more effective than the traffic blockage control. Conclusion: Both of quarantine and traffic blockage are effective ways to control the spread of COVID-19. However, the eff icacy of quarantine is found to be much stronger than that of traffic blockage. Considering traffic blockage may also cause huge losses of economy, we propose to gradually deregulate the traffic blockage, and improve quarantine instead. Also, there might be a large number of asymptomatic carriers of COVID-19, the quarantine should be continued for a long time until the epidemic is totally under control.

negative: Escherichia coli, cattle and the propagation of disease Several early models describing host–pathogen interaction have assumed that each individual host has approximately the same likelihood of becoming infected or of infecting others. More recently, a concept that has been increasingly emphasized in many studies is that for many infectious diseases, transmission is not homogeneous but highly skewed at the level of populations. In what became known as the ‘20/80 rule’, about 20% of the hosts in a population were found to contribute to about 80% of the transmission potential. These heterogeneities have been described for the interaction between many microorganisms and their human or animal hosts. Several epidemiological studies have reported transmission heterogeneities for Escherichia coli by cattle, a phenomenon with far-reaching agricultural, medical and public health implications. Focusing on E. coli as a case study, this paper will describe super-spreading and super-shedding by cattle, review the main factors that shape these transmission heterogeneities and examine the interface with human health. Escherichia coli super-shedding and super-spreading by cattle are shaped by microorganism-specific, cattle-specific and environmental factors. Understanding the factors that shape heterogeneities in E. coli dispersion by cattle and the implications for human health represent key components that are critical for targeted infection control initiatives.

negative: Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding:National Science and Technology Major Project.

negative: Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients Effective strategy to mitigate the ongoing pandemic of 2019 novel coronavirus (COVID-19) require a comprehensive understanding of humoral responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the emerging virus causing COVID-19. The dynamic profile of viral replication and shedding along with viral antigen specific antibody responses among COVID-19 patients started to be reported but there is no consensus on their patterns. Here, we conducted a serial investigation on 21 individuals infected with SARS-CoV-2 in two medical centres from Jiangsu Province, including 11 non-severe COVID-19 patients, and 5 severe COVID-19 patients and 5 asymptomatic carriers based on nucleic acid test and clinical symptoms. The longitudinal swab samples and sera were collected from these people for viral RNA testing and antibody responses, respectively. Our data revealed different pattern of seroconversion among these groups. All 11 non-severe COVID-19 patients and 5 severe COVID-19 patients were seroconverted during hospitalization or follow-up period, suggesting that serological testing is a complementary assay to nucleic acid test for those symptomatic COVID-19 patients. Of note, immediate antibody responses were identified among severe cases, compared to non-severe cases. On the other hand, only one were seroconverted for asymptomatic carriers. The SARS-CoV-2 specific antibody responses were well-maintained during the observation period. Such information is of immediate relevance and would assist COVID-19 clinical diagnosis, prognosis and vaccine design.

negative: The outbreak of coronavirus disease in China: Risk perceptions, knowledge, and information sources among prenatal and postnatal women BACKGROUND: The COVID-19 pandemic has created anxiety among members of the public, including all women over the childbirth continuum, who are considered to be at a greater risk of contracting most infectious diseases. Understanding the perspectives of health care consumers on COVID-19 will play a crucial role in the development of effective risk communication strategies. This study aimed to examine COVID-19-related risk perceptions, knowledge, and information sources among prenatal and postnatal Chinese women during the initial phase of the COVID-19 pandemic. METHODS: A cross-sectional survey design was adopted, and a four-section online questionnaire was used to collect data. Using a social media platform, the online survey was administered to 161 participants during the outbreak of COVID-19 in Nanjing, China, in February 2020. RESULTS: The participants perceived their risk of contracting and dying from COVID-19 to be lower than their risk of contracting influenza, however many of them were worried that they might contract COVID-19. The participants demonstrated adequate knowledge about COVID-19. The three major sources from which they obtained information about COVID-19 were doctors, nurses/midwives, and the television, and they placed a high level of confidence in these sources. There was no significant relationship between the perceived risk of contracting COVID-19 and knowledge about this disease. CONCLUSION: The present findings offer valuable insights to healthcare professionals, including midwives, who serve on the frontline and provide care to pregnant women. Although the participants were adequately knowledgeable about COVID-19, they had misunderstood some of the recommendations of the World Health Organization.

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

negative: Objective Determination of End of MERS Outbreak, South Korea, 2015

negative: Understanding the fate of corona virus transmission using a simple model We propose a simple model for understanding the kinetics of corona virus transmission. Our model assume spreading of corona virus can happen from one to another only, if someone without enough protection comes close contact to a person carrying the corona virus. Therefore this virus spreads on a large scale within a short time through chains of such events. Using our model we provide an estimation of the number of people affected by this virus within reasonable duration of time. We choose values of different parameters of our model by non-linear least square fit of the real time data and we predict fate of this corona virus transmission using our model.

negative: 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.

negative: La comunicación científica y el acceso abierto en la contención de enfermedades: El caso del Coronavirus novel 2019 (2019-nCoV)

negative: A note on blind contact tracing at scale with applications to the COVID-19 pandemic The current COVID-19 pandemic highlights the utility of contact tracing, when combined with case isolation and social distancing, as an important tool for mitigating the spread of a disease [1]. Contact tracing provides a mechanism of identifying individuals with a high likelihood of previous exposure to a contagious disease, allowing additional precautions to be put in place to prevent continued transmission. Here we consider a cryptographic approach to contact tracing based on secure two-party computation (2PC). We begin by considering the problem of comparing a set of location histories held by two parties to determine whether they have come within some threshold distance while at the same time maintaining the privacy of the location histories. We propose a solution to this problem using pre-shared keys, adapted from an equality testing protocol due to Ishai et al [2]. We discuss how this protocol can be used to maintain privacy within practical contact tracing scenarios, including both app-based approaches and approaches which leverage location history held by telecoms and internet service providers. We examine the efficiency of this approach and show that existing infrastructure is sufficient to support anonymised contact tracing at a national level.

negative: Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

negative: Interventions to Decrease Use in Prehospital and Emergency Care Settings Among Super-Utilizers in the United States: A Systematic Review. Interest in high users of acute care continues to grow as health care organizations look to deliver cost-effective and high-quality care to patients. Since "super-utilizers" of acute care are responsible for disproportionately high health care spending, many programs and interventions have been implemented to reduce medical care use and costs in this population. This article presents a systematic review of the peer-reviewed and grey literature on evaluations of interventions to decrease prehospital and emergency care use among U.S. super-utilizers. Forty-six distinct evaluations were included in the review. The most commonly evaluated intervention was case management. Although a number of interventions reported reductions in prehospital and emergency care utilization and costs, methodological and study design weaknesses-especially regression to the mean-were widespread and call into question reported positive findings. More high-quality research is needed to accurately assess the impact of interventions to reduce prehospital and emergency care use in the super-utilizer population.

negative: Medically unexplained symptoms in the times of Covid-19 pandemic: a case-report Abstract In early 2020, a novel coronavirus (SARS-CoV-2) leading to a potentially fatal condition was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread worldwide becoming a pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the psychological impact that COVID-19 may have, especially on vulnerable individuals with pre-existing mental health conditions. Somatic symptom disorder (SSD) is characterized by a dysfunctional preoccupation with physical symptoms leading to excessive and unnecessary healthcare utilization. Despite being quite common, such condition remains underrecognized. We report a detailed clinical case of a 16 years old adolescent, who presented with a history suggestive of COVID-19 infection and associated psychological distress. Despite testing negative for the presence of SARS-CoV-2, his extreme and persisting health preoccupations required an inpatient admission to the Child and Adolescent Neuropsychiatric Unit. He responded rapidly to a low dose of antipsychotic and an antidepressant. Based on his medical history and current presentation, he received a diagnosis of SSD. When COVID-19-like symptoms occur, we highlight the importance of differentially diagnosing a possible exacerbation of a pre-existing SSD, triggered by fear of being infected. This may help preventing further burden to the healthcare system.

negative: Clinical use of Convalescent Plasma in the COVID-19 pandemic; a transfusion-focussed gap analysis with recommendations for future research priorities. BACKGROUND AND OBJECTIVES Use of convalescent plasma for Coronavirus disease 2019 (COVID-19) treatment has gained interest worldwide. However, there is lack of evidence on its dosing, safety and effectiveness. Until data from clinical studies are available to provide solid evidence for worldwide applicable guidelines, there is a need to provide guidance to the transfusion community and researchers on this emergent therapeutic option. This paper aims to identify existing key gaps in current knowledge in the clinical application of COVID-19 convalescent plasma (CCP). MATERIALS AND METHODS The International Society of Blood Transfusion (ISBT) initiated a multidisciplinary working group with worldwide representation from all six continents with the aim of reviewing existing practices on CCP use from donor, product and patient perspectives. A subgroup of clinical transfusion professionals was formed to draft a document for CCP clinical application to identify the gaps in knowledge in existing literature. RESULTS Gaps in knowledge were identified in the following main domains: study design, patient eligibility, CCP dose, frequency and timing of CCP administration, parameters to assess response to CCP treatment and long-term outcome, adverse events, and CCP application in less resourced countries as well as in paediatrics and neonates. CONCLUSION This paper outlines a framework of gaps in the knowledge of clinical deployment of CPP that were identified as being most relevant. Studies to address the identified gaps are required to provide better evidence on the effectiveness and safety of CCP use.

negative: Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study BACKGROUND: The Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015. METHODS: To assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks. RESULTS: A significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal–Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %. CONCLUSIONS: Our study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since 2003 or differences in transmission mechanisms of these coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0450-0) contains supplementary material, which is available to authorized users.

negative: 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).

negative: Risk factors related to hepatic injury in patients with corona virus disease 2019 Aims: Corona virus disease 2019 (COVID-19) has rapidly become the most severe public health issue all over the world. Despite respiratory symptoms, hepatic injury has also been observed in clinical settings. This study aimed to investigate the risk factors involved with hepatic injury in the patients with COVID-19. Methods: A total of 85 hospitalized patients who were diagnosed with COVID-19 in Beijing Youan Hospital were retrospectively analyzed. According to liver function, they were divided into ALT normal group (n=52) and ALT elevation group (n=33). Clinical features and laboratory data were compared between the two groups. The independent risk factors for liver injury were analyzed. Results: There were 33 patients with hepatic injury in our study, accounting for 38.8% (33/85). The patients in ALT elevation group were older than those in ALT normal group. The levels of lactic acid, CRP, myoglobin, and neutrophils were significantly higher in ALT elevation group. The lymphocytes and albumin were significantly lower in ALT elevation group. The proportion of severe and critical patients in ALT elevation group was significantly higher. Multivariate logistic regression analysis showed CRP ≥20 mg/L and lymphocyte count< 1.1*10^9/L were independently related to hepatic injury. Conclusions: Lymphopenia and CRP may serve as the risk factors related to hepatic injury in patients with COVID-19, which might be related to inflammatory cytokine storm in liver injury. Early detection and timely treatment of hepatic injury in patients with COVID-19 are necessary.

negative: Precision public health to inhibit the contagion of disease and move toward a future in which microbes spread health Antimicrobial resistance continues to outpace the development of new chemotherapeutics. Novel pathogens continue to evolve and emerge. Public health innovation has the potential to open a new front in the war of “our wits against their genes” (Joshua Lederberg). Dense sampling coupled to next generation sequencing can increase the spatial and temporal resolution of microbial characterization while sensor technologies precisely map physical parameters relevant to microbial survival and spread. Microbial, physical, and epidemiological big data could be combined to improve prospective risk identification. However, applied in the wrong way, these approaches may not realize their maximum potential benefits and could even do harm. Minimizing microbial-human interactions would be a mistake. There is evidence that microbes previously thought of at best “benign” may actually enhance human health. Benign and health-promoting microbiomes may, or may not, spread via mechanisms similar to pathogens. Infectious vaccines are approaching readiness to make enhanced contributions to herd immunity. The rigorously defined nature of infectious vaccines contrasts with indigenous “benign or health-promoting microbiomes” but they may converge. A “microbial Neolithic revolution” is a possible future in which human microbial-associations are understood and managed analogously to the macro-agriculture of plants and animals. Tradeoffs need to be framed in order to understand health-promoting potentials of benign, and/or health-promoting microbiomes and infectious vaccines while also discouraging pathogens. Super-spreaders are currently defined as individuals who play an outsized role in the contagion of infectious disease. A key unanswered question is whether the super-spreader concept may apply similarly to health-promoting microbes. The complex interactions of individual rights, community health, pathogen contagion, the spread of benign, and of health-promoting microbiomes including infectious vaccines require study. Advancing the detailed understanding of heterogeneity in microbial spread is very likely to yield important insights relevant to public health.

negative: Can we perform like SUPER-CRIPPLES during these crazy times of coronavirus pandemic?

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

negative: Asymptomatic Middle East Respiratory Syndrome coronavirus infection using a serologic survey in Korea OBJECTIVES: The rates of asymptomatic infection with Middle East Respiratory Syndrome (MERS) coronavirus vary. A serologic study was conducted to determine the asymptomatic MERS infection rate in healthcare workers and non-healthcare workers by exposure status. METHODS: Study participants were selected from contacts of MERS patients based on a priority system in 4 regions strongly affected by the 2015 MERS outbreak. A sero-epidemiological survey was performed in 1,610 contacts (average duration from exposure to test, 4.8 months), and the collected sera were tested using an enzyme-linked immunespecific assay (ELISA), immunofluorescence assay (IFA), and plaque reduction neutralization antibody test (PRNT). Among the 1,610 contacts, there were 7 ELISA-positive cases, of which 1 exhibited positive IFA and PRNT results. RESULTS: The asymptomatic infection rate was 0.060% (95% confidence interval, 0.002 to 0.346). The asymptomatic MERS case was a patient who had been hospitalized with patient zero on the same floor of the hospital at the same time. The case was quarantined at home for 2 weeks after discharge, and had underlying diseases, including hypertension, angina, and degenerative arthritis. CONCLUSIONS: The asymptomatic infection was acquired via healthcare-associated transmission. Thus, it is necessary to extend serologic studies to include inpatient contacts who have no symptoms.

negative: Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or 'virus spreaders'. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID-19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.

negative: Initial evidence of higher morbidity and mortality due to SARS-CoV-2 in regions with lower air quality COVID-19 has spread in all continents in a span of just over three months, escalating into a pandemic that poses several humanitarian as well as scientific challenges. We here investigated the geographical expansion of the infection and correlate it with the annual indexes of air quality observed from the Sentinel-5 satellite orbiting around China, Italy and the U.S.A. Controlling for population size, we find more viral infections in those areas afflicted by Carbon Monoxide (CO) and Nitrogen Dioxide (NO2). Higher mortality was also correlated with poor air quality, namely with high PM2.5, CO and NO2 values. In Italy, the correspondence between poor air quality and SARS-CoV-2 appearance and induced mortality was the starkest. Similar to smoking, people living in polluted areas are more vulnerable to SARS-CoV-2 infections and induced mortality. This further suggests the detrimental impact climate change will have on the trajectory of future epidemics.

negative: Generality of the Final Size Formula for an Epidemic of a Newly Invading Infectious Disease The well-known formula for the final size of an epidemic was published by Kermack and McKendrick in 1927. Their analysis was based on a simple susceptible-infected-recovered (SIR) model that assumes exponentially distributed infectious periods. More recent analyses have established that the standard final size formula is valid regardless of the distribution of infectious periods, but that it fails to be correct in the presence of certain kinds of heterogeneous mixing (e.g., if there is a core group, as for sexually transmitted diseases). We review previous work and establish more general conditions under which Kermack and McKendrick's formula is valid. We show that the final size formula is unchanged if there is a latent stage, any number of distinct infectious stages and/or a stage during which infectives are isolated (the durations of each stage can be drawn from any integrable distribution). We also consider the possibility that the transmission rates of infectious individuals are arbitrarily distributed—allowing, in particular, for the existence of super-spreaders—and prove that this potential complexity has no impact on the final size formula. Finally, we show that the final size formula is unchanged even for a general class of spatial contact structures. We conclude that whenever a new respiratory pathogen emerges, an estimate of the expected magnitude of the epidemic can be made as soon the basic reproduction number ℝ(0) can be approximated, and this estimate is likely to be improved only by more accurate estimates of ℝ(0), not by knowledge of any other epidemiological details.

negative: COVID-19: Importance of the Awareness of the Clinical Syndrome by Urologists

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

negative: Update on Ebola Treatment Center Costs and Sustainability, United States, 2019 We surveyed 56 Ebola treatment centers (ETCs) in the United States and identified costs incurred since 2014 ($1.76 million/ETC) and sustainability strategies. ETCs reported heavy reliance on federal funding. It is uncertain if, or for how long, ETCs can maintain capabilities should federal funding expire in 2020.

negative: A reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the rapid detection of SARS-CoV-2 within nasopharyngeal and oropharyngeal swabs at Hampshire Hospitals NHS Foundation Trust The COVID-19 pandemic has illustrated the importance of rapid, accurate diagnostic testing for the effective triaging and cohorting of patients and timely tracking and tracing of cases. However, a surge in diagnostic testing quickly resulted in worldwide competition for the same sample preparation and real-time RT-PCR diagnostic reagents (rRT-PCR). Consequently, Hampshire Hospitals NHS Foundation Trust, UK sought to diversify their diagnostic portfolio by exploring alternative amplification chemistries including those that permit direct testing without RNA extraction. This study describes the validation of a SARS-CoV-2 RT-LAMP assay, which is an isothermal, autocycling, strand displacement nucleic acid amplification technique which can be performed on extracted RNA, (RNA RT-LAMP) or directly from swab (Direct RT-LAMP). Analytical specificity (ASp) of this new RT-LAMP assay was 100% and analytical sensitivity (ASe) was between 1x101 and 1x102 copies when using a synthetic DNA target. The overall diagnostic sensitivity (DSe) and specificity (DSp) of RNA RT LAMP was 97% and 99% respectively, relative to the standard of care (SoC) rRT-PCR. When a CT cut-off of 33 was employed, above which increasingly, evidence suggests there is a very low risk of patients shedding infectious virus, the diagnostic sensitivity was 100%. The DSe and DSp of Direct-RT LAMP was 67% and 97%, respectively. When setting CT cut-offs of <33 and <25, the DSe increased to 75% and 100%, respectively. Time from swab-to-result for a strong positive sample (CT < 25) was < 15 minutes. We propose that RNA RT-LAMP could replace rRT-PCR where there is a need for increase in throughput, whereas Direct RT-LAMP could be used as a screening tool for triaging patients into appropriate hospitals wards, at GP surgeries and in care homes, or for population screening to identify highly contagious individuals (super shedders). Direct RT-LAMP could also be used during times of high prevalence to save critical extraction and rRT-PCR reagents by screening out those strong positives from diagnostic pipelines.

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

negative: Coevolution spreading in complex networks The propagations of diseases, behaviors and information in real systems are rarely independent of each other, but they are coevolving with strong interactions. To uncover the dynamical mechanisms, the evolving spatiotemporal patterns and critical phenomena of networked coevolution spreading are extremely important, which provide theoretical foundations for us to control epidemic spreading, predict collective behaviors in social systems, and so on. The coevolution spreading dynamics in complex networks has thus attracted much attention in many disciplines. In this review, we introduce recent progress in the study of coevolution spreading dynamics, emphasizing the contributions from the perspectives of statistical mechanics and network science. The theoretical methods, critical phenomena, phase transitions, interacting mechanisms, and effects of network topology for four representative types of coevolution spreading mechanisms, including the coevolution of biological contagions, social contagions, epidemic–awareness, and epidemic–resources, are presented in detail, and the challenges in this field as well as open issues for future studies are also discussed.

negative: Optimal control application to an Ebola model Abstract Ebola virus is a severe, frequently fatal illness, with a case fatality rate up to 90%. The outbreak of the disease has been acknowledged by World Health Organization as Public Health Emergency of International Concern. The threat of Ebola in West Africa is still a major setback to the socioeconomic development. Optimal control theory is applied to a system of ordinary differential equations which is modeling Ebola infection through three different routes including contact between humans and a dead body. In an attempt to reduce infection in susceptible population, a preventive control is put in the form of education and campaign and two treatment controls are applied to infected and late-stage infected (super) human population. The Pontryagins maximum principle is employed to characterize optimality control, which is then solved numerically. It is observed that time optimal control is existed in the model. The activation of each control showed a positive reduction of infection. The overall effect of activation of all the controls simultaneously reduced the effort required for the reduction of the infection quickly. The obtained results present a good framework for planning and designing cost-effective strategies for good interventions in dealing with Ebola disease. It is established that in order to reduce Ebola threat all the three controls must be taken into consideration concurrently.

negative: The clinical and virological features of the first imported case causing MERS-CoV outbreak in South Korea, 2015 BACKGROUND: In 2015, the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside the Middle East occurred in South Korea. We summarized the epidemiological, clinical, and laboratory findings of the first Korean case of MERS-CoV and analyzed whole-genome sequences of MERS-CoV derived from the patient. CASE PRESENTATION: A 68-year-old man developed fever and myalgia 7 days after returning to Korea, following a 10-day trip to the Middle East. Before diagnosis, he visited 4 hospitals, potentially resulting in secondary transmission to 28 patients. On admission to the National Medical Center (day 9, post-onset of clinical illness), he presented with drowsiness, hypoxia, and multiple patchy infiltrations on the chest radiograph. He was intubated (day 12) because of progressive acute respiratory distress syndrome (ARDS) and INF-α2a and ribavirin treatment was commenced. The treatment course was prolonged by superimposed ventilator associated pneumonia. MERS-CoV PCR results converted to negative from day 47 and the patient was discharged (day 137), following rehabilitation therapy. The complete genome sequence obtained from a sputum sample (taken on day 11) showed the highest sequence similarity (99.59%) with the virus from an outbreak in Riyadh, Saudi Arabia, in February 2015. CONCLUSIONS: The first case of MERS-CoV infection had high transmissibility and was associated with a severe clinical course. The patient made a successful recovery after early treatment with antiviral agents and adequate supportive care. This first case in South Korea became a super-spreader because of improper infection control measures, rather than variations of the virus.

negative: Metabolism of Bradykinin by Peptidases in Health and Disease This chapter provides an overview of the metabolism of bradykinin (BK) by peptidases in health and disease. The enzymatic breakdown of kinins affects the duration of their biological actions as the plasma half-life of intravenously injected BK is in the range of seconds. Kinins are cleaved in vitro and in vivo by enzymes that belong to families, such as zinc-metallopeptidases, astacin-like metallopeptidases, and catheptic enzymes. Vane noted the importance of the pulmonary circulation in the metabolism of vasoactive substances, such as BK as well as angiotensin 1 and 5- hydroxytryptamine. It is clear after decades of research that angiotensin 1-converting enzyme (ACE) on the vascular endothelial cell surface is the most important inactivator of blood-borne BK. BK may act primarily in an autocrine and paracrine fashion, establishing the importance of local regulation of its activity by enzymes on cell surfaces. Thus, the assortment of other enzymes that can inactivate BK is important in a variety of physiological and pathological situations. Most physiological systems have redundant pathways of metabolism so that the abolishment of one pathway is compensated for by the presence of others. This is demonstrated by the pharmacological inhibition of ACE in hypertension.

negative: Viral Diversity of Microbats within the South West Botanical Province of Western Australia Bats are known reservoirs of a wide variety of viruses that rarely result in overt clinical disease in the bat host. However, anthropogenic influences on the landscape and climate can change species assemblages and interactions, as well as undermine host-resilience. The cumulative result is a disturbance of bat–pathogen dynamics, which facilitate spillover events to sympatric species, and may threaten bat communities already facing synergistic stressors through ecological change. Therefore, characterisation of viral pathogens in bat communities provides important basal information to monitor and predict the emergence of diseases relevant to conservation and public health. This study used targeted molecular techniques, serological assays and next generation sequencing to characterise adenoviruses, coronaviruses and paramyxoviruses from 11 species of insectivorous bats within the South West Botanical Province of Western Australia. Phylogenetic analysis indicated complex ecological interactions including virus–host associations, cross-species infections, and multiple viral strains circulating concurrently within selected bat populations. Additionally, we describe the entire coding sequences for five alphacoronaviruses (representing four putative new species), and one novel adenovirus. Results indicate that viral burden (both prevalence and richness) is not homogeneous among species, with Chalinolobus gouldii identified as a key epidemiological element within the studied communities.

negative: Rapid typing of influenza viruses using super high-speed quantitative real-time PCR Abstract The development of a rapid and sensitive system for detecting influenza viruses is a high priority for controlling future epidemics and pandemics. Quantitative real-time PCR is often used for detecting various kinds of viruses; however, it requires more than 2h per run. Detection assays were performed with super high-speed RT-PCR (SHRT-PCR) developed according to a newly designed heating system. The new method uses a high-speed reaction (18s/cycle; 40 cycles in less than 20min) for typing influenza viruses. The detection limit of SHRT-PCR was 1 copy/reaction and 10−1 plaque-forming unit/reaction for viruses in culture supernatants during 20min. Using SHRT-PCR, 86 strains of influenza viruses isolated by the Tokyo Metropolitan Institute of Public Health were tested; the results showed 100% sensitivity and specificity for each influenza A and B virus, and swine-origin influenza virus. Twenty-seven swabs collected from the pharyngeal mucosa of outpatients were also tested, showing positive signs for influenza virus on an immunochromatographic assay; the results between SHRT-PCR and immunochromatography exhibited 100% agreement for both positive and negative results. The rapid reaction time and high sensitivity of SHRT-PCR makes this technique well suited for monitoring epidemics and pre-pandemic influenza outbreaks.

negative: EARLY DETECTION OF COVID-19 Since SARS-Cov-2 epidemic appeared in Wuhan China, it became challenge for health authorities to counter Covid-19 epidemic. Early evaluation of suspects, screening for Covid-19 and management posed challenge to health authorities especially in developing countries which were not ready to cope with it. Early mild symptoms appeared during course of disease provide a chance to early detect Covid-19. We use retrospective methodology to collect available data on early sign and symptoms of Covid-19 through accessing World Health Organization (WHO) webpages, New England Journal of Medicine (NEJM), Nature Journal, Journal of American Medical Association (JAMA) network, British Medical Journal (BJM), Lancet and other world renowned journal publications to establish a relationship of early symptoms for detection of Covid-19. Data of 2707 Covid-19 laboratory confirmed cases was collected and analyzed for early signs. Available data was categorized into physical and blood biomarkers. This categorized data was assessed for scoring early detection of Covid-19 by scoring Hashmi-Asif Covid-19 formula. Each characteristic was given a score in Hashmi-Asif Covid-19 chart with maximum score of 28. Scoring 16 on chart means Covid-19 will fully develop in near future. Correlation of each sign and symptoms with development of Covid-19 in formula showed significant correlation assessed by Pearson correlation and Spearman Correlation coefficient (rho) showed significant correlation of development of Covid-19 with fever 64.11% (P=0.001), cough 65% and dry mucus 19.67% equally sensitive (P=0.000), leukopenia 19.06% (P=0.006), lymphopenia 52.93% (P=0.005), thrombopenia 19.1% (P=0.013), elevated Aspartate aminotransferase 12.79% (P=0.007) and elevated Alanine aminotransferase 11.34% (P=0.006). Chart can sense Covid-19 progression 72-96 hours earlier compared to usual course of disease and detection by standard method. Chart for early detection provides early quarantine decision to reduce disease spread and give ample time for intervening disease progression to reduce morbidity time due to Covid-19

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: 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.

negative: MERS: emergence of a novel human coronavirus A novel coronavirus (CoV) that causes a severe lower respiratory tract infection in humans, emerged in the Middle East region in 2012. This virus, named Middle East respiratory syndrome (MERS)-CoV, is phylogenetically related to bat CoVs, but other animal species like dromedary camels may potentially act as intermediate hosts by spreading the virus to humans. Although human to human transmission has been demonstrated, analysis of human MERS clusters indicated that chains of transmission were not self-sustaining, especially when infection control was implemented. Thus, timely identification of new MERS cases followed by their quarantine, combined with measures to limit spread of the virus from the (intermediate) host to humans, may be crucial in controlling the outbreak of this emerging CoV.

negative: Prediction of COVID-19 Disease Progression in India : Under the Effect of National Lockdown In this policy paper, we implement the epidemiological SIR to estimate the basic reproduction number $\mathcal{R}_0$ at national and state level. We also developed the statistical machine learning model to predict the cases ahead of time. Our analysis indicates that the situation of Punjab ($\mathcal{R}_0\approx 16$) is not good. It requires immediate aggressive attention. We see the $\mathcal{R}_0$ for Madhya Pradesh (3.37) , Maharastra (3.25) and Tamil Nadu (3.09) are more than 3. The $\mathcal{R}_0$ of Andhra Pradesh (2.96), Delhi (2.82) and West Bengal (2.77) is more than the India's $\mathcal{R}_0=2.75$, as of 04 March, 2020. India's $\mathcal{R}_0=2.75$ (as of 04 March, 2020) is very much comparable to Hubei/China at the early disease progression stage. Our analysis indicates that the early disease progression of India is that of similar to China. Therefore, with lockdown in place, India should expect as many as cases if not more like China. If lockdown works, we should expect less than 66,224 cases by May 01,2020. All data and \texttt{R} code for this paper is available from \url{https://github.com/sourish-cmi/Covid19}

negative: Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study Abstract An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its caused coronavirus disease 2019 (COVID-19) has been reported in China since December 2019. More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was about 1%–2%. No specific treatment has been reported. Herein, we examine the effects of Favipiravir (FPV) versus Lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million U twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million U twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance time was found for the FPV arm versus the control arm (median (interquartile range, IQR), 4 (2.5–9) d versus 11 (8–13) d, P < 0.001). The FPV arm also showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest imaging. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse reactions were found in the FPV arm than in the control arm. In this open-label nonrandomized control study, FPV showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance; if causal, these results should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection.

negative: Expert committee reviews SARS outbreak in Hong Kong

negative: COVID-19 and smoking: A systematic review of the evidence COVID-19 is a coronavirus outbreak that initially appeared in Wuhan, Hubei Province, China, in December 2019, but it has already evolved into a pandemic spreading rapidly worldwide(1,2). As of 18 March 2020, a total number of 194909 cases of COVID-19 have been reported, including 7876 deaths, the majority of which have been reported in China (3242) and Italy (2505)(3). However, as the pandemic is still unfortunately under progression, there are limited data with regard to the clinical characteristics of the patients as well as to their prognostic factors(4). Smoking, to date, has been assumed to be possibly associated with adverse disease prognosis, as extensive evidence has highlighted the negative impact of tobacco use on lung health and its causal association with a plethora of respiratory diseases(5). Smoking is also detrimental to the immune system and its responsiveness to infections, making smokers more vulnerable to infectious diseases(6). Previous studies have shown that smokers are twice more likely than non-smokers to contract influenza and have more severe symptoms, while smokers were also noted to have higher mortality in the previous MERS-CoV outbreak(7,8). Given the gap in the evidence, we conducted a systematic review of studies on COVID-19 that included information on patients’ smoking status to evaluate the association between smoking and COVID-19 outcomes including the severity of the disease, the need for mechanical ventilation, the need for intensive care unit (ICU) hospitalization and death. The literature search was conducted on 17 March 2020, using two databases (PubMed, ScienceDirect), with the search terms: [‘smoking’ OR ‘tobacco’ OR ‘risk factors’ OR ‘smoker*’] AND [‘COVID-19’ OR ‘COVID 19’ OR ‘novel coronavirus’ OR ‘sars cov-2’ OR ‘sars cov 2’] and included studies published in 2019 and 2020. Further inclusion criteria were that the studies were in English and referred to humans. We also searched the reference lists of the studies included. A total of 71 studies were retrieved through the search, of which 66 were excluded after full-text screening, leaving five studies that were included. All of the studies were conducted in China, four in Wuhan and one across provinces in mainland China. The populations in all studies were patients with COVID-19, and the sample size ranged from 41 to 1099 patients. With regard to the study design, retrospective and prospective methods were used, and the timeframe of all five studies covered the first two months of the COVID-19 pandemic (December 2019, January 2020). Specifically, Zhou et al.(9) studied the epidemiological characteristics of 191 individuals infected with COVID-19, without, however, reporting in more detail the mortality risk factors and the clinical outcomes of the disease. Among the 191 patients, there were 54 deaths, while 137 survived. Among those that died, 9% were current smokers compared to 4% among those that survived, with no statistically significant difference between the smoking rates of survivors and non-survivors (p=0.21) with regard to mortality from COVID-19. Similarly, Zhang et al.(10) presented clinical characteristics of 140 patients with COVID-19. The results showed that among severe patients (n=58), 3.4% were current smokers and 6.9% were former smokers, in contrast to non-severe patients (n=82) among which 0% were current smokers and 3.7% were former smokers , leading to an OR of 2.23; (95% CI: 0.65–7.63; p=0.2). Huang et al.(11) studied the epidemiological characteristics of COVID-19 among 41 patients. In this study, none of those who needed to be admitted to an ICU (n=13) was a current smoker. In contrast, three patients from the non-ICU group were current smokers, with no statistically significant difference between the two groups of patients (p=0.31), albeit the small sample size of the study. The largest study population of 1099 patients with COVID-19 was provided by Guan et al.(12) from multiple regions of mainland China. Descriptive results on the smoking status of patients were provided for the 1099 patients, of which 173 had severe symptoms, and 926 had non-severe symptoms. Among the patients with severe symptoms, 16.9% were current smokers and 5.2% were former smokers, in contrast to patients with non-severe symptoms where 11.8% were current smokers and 1.3% were former smokers. Additionally, in the group of patients that either needed mechanical ventilation, admission to an ICU or died, 25.5% were current smokers and 7.6% were former smokers. In contrast, in the group of patients that did not have these adverse outcomes, only 11.8% were current smokers and 1.6% were former smokers. No statistical analysis for evaluating the association between the severity of the disease outcome and smoking status was conducted in that study. Finally, Liu et al.(13) found among their population of 78 patients with COVID-19 that the adverse outcome group had a significantly higher proportion of patients with a history of smoking (27.3%) than the group that showed improvement or stabilization (3.0%), with this difference statistically significant at the p=0.018 level. In their multivariate logistic regression analysis, the history of smoking was a risk factor of disease progression (OR=14.28; 95% CI: 1.58–25.00; p= 0.018). We identified five studies that reported data on the smoking status of patients infected with COVID-19. Notably, in the largest study that assessed severity, there were higher percentages of current and former smokers among patients that needed ICU support, mechanical ventilation or who had died, and a higher percentage of smokers among the severe cases(12). However, from their published data we can calculate that the smokers were 1.4 times more likely (RR=1.4, 95% CI: 0.98–2.00) to have severe symptoms of COVID-19 and approximately 2.4 times more likely to be admitted to an ICU, need mechanical ventilation or die compared to non-smokers (RR=2.4, 95% CI: 1.43–4.04). In conclusion, although further research is warranted as the weight of the evidence increases, with the limited available data, and although the above results are unadjusted for other factors that may impact disease progression, smoking is most likely associated with the negative progression and adverse outcomes of COVID-19.

negative: How to Return to Normalcy: Fast and Comprehensive Contact Tracing of COVID-19 through Proximity Sensing Using Mobile Devices We outline a contact-tracing strategy based on proximity sensing using mobile devices. We discuss what an ideal system should look like and what it can do. We show that, when adopted sufficiently broadly, such a contact-tracing strategy can bring COVID-19 under complete control, end the need of social distancing, and return the society to full normalcy. We also review some of the challenges faced by the current generation of proximity-sensing technologies, including Bluetooth Low Energy used by phones, and consider both interim and longer-term solutions. Our main contribution is that we reason through why such a contact-tracing strategy is likely to achieve the stated goal of returning to full normalcy. Using probabilistic models, we show that universal adoption is not necessary to achieve the stated goal, thus there is some room for exceptions; however, the adoption rate needs to be very high, e.g., above $95\%$ depending on the disease parameters. With more vigilance in disease surveillance to detect mild cases earlier, the number may be brought down to about $90\%$. The results call for deployment effort to be led by public authorities at the state or federal level so that the required adoption rate can be reached and the tracing coverage is wide enough to be relevant for disease control.

negative: Examining Lead-Lag Relationships In-Depth, With Focus On FX Market As Covid-19 Crises Unfolds The lead-lag relationship plays a vital role in financial markets. It is the phenomenon where a certain price-series lags behind and partially replicates the movement of leading time-series. The present research proposes a new technique which helps better identify the lead-lag relationship empirically. Apart from better identifying the lead-lag path, the technique also gives a measure for adjudging closeness between financial time-series. Also, the proposed measure is closely related to correlation, and it uses Dynamic Programming technique for finding the optimal lead-lag path. Further, it retains most of the properties of a metric, so much so, it is termed as loose metric. Tests are performed on Synthetic Time Series (STS) with known lead-lag relationship and comparisons are done with other state-of-the-art models on the basis of significance and forecastability. The proposed technique gives the best results in both the tests. It finds paths which are all statistically significant, and its forecasts are closest to the target values. Then, we use the measure to study the topology evolution of the Foreign Exchange market, as the COVID-19 pandemic unfolds. Here, we study the FX currency prices of 29 prominent countries of the world. It is observed that as the crises unfold, all the currencies become strongly interlinked to each other. Also, USA Dollar starts playing even more central role in the FX market. Finally, we mention several other application areas of the proposed technique for designing intelligent systems.

negative: An Introduction to COVID-19 A novel coronavirus (CoV) named ‘2019-nCoV’ or ‘2019 novel coronavirus’ or ‘COVID-19’ by the World Health Organization (WHO) is in charge of the current outbreak of pneumonia that began at the beginning of December 2019 near in Wuhan City, Hubei Province, China [1–4]. COVID-19 is a pathogenic virus. From the phylogenetic analysis carried out with obtainable full genome sequences, bats occur to be the COVID-19 virus reservoir, but the intermediate host(s) has not been detected till now.

negative: The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing The novel coronavirus SARS-CoV-2, etiological agent of recently named Coronavirus infected disease (COVID-19) by WHO, has caused more than 2, 000 deaths worldwide since its emergency in Wuhan City, Hubei province, China, in December, 2019. The symptoms of COVID-19 varied from modest, mild to acute respiratory distress syndrome (ARDS), and the latter of which is generally associated with deregulated immune cytokine production; however, we currently know little as to the interplay between the extent of clinical symptoms and the compositions of lung immune microenvironment. Here, we comprehensively characterized the lung immune microenvironment with the bronchoalveolar lavage fluid (BALF) from 3 severe and 3 mild COVID-19 patients and 8 previously reported healthy lung controls through single-cell RNA sequence (scRNA-seq) combined with TCR-seq. Our data shows that monocyte-derived FCN1+ macrophages, whereas notFABP4+ alveolar macrophages that represent a predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Furthermore, the formation of tissue resident, highly expanded clonal CD8+ T cells in the lung microenvironment of mild symptom patients suggests a robust adaptive immune response connected to a better control of COVID-19. This study first reported the cellular atlas of lung bronchoalveolar immune microenvironment in COVID-19 patients at the single-cell resolution, and unveiled the potential immune mechanisms underlying disease progression and protection in COVID-19.

negative: Identifying determinants of heterogeneous transmission dynamics of the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, 2015: a retrospective epidemiological analysis OBJECTIVES: To investigate the heterogeneous transmission patterns of Middle East respiratory syndrome (MERS) in the Republic of Korea, with a particular focus on epidemiological characteristics of superspreaders. DESIGN: Retrospective epidemiological analysis. SETTING: Multiple healthcare facilities of secondary and tertiary care centres in an urban setting. PARTICIPANTS: A total of 185 laboratory-confirmed cases with partially known dates of illness onset and most likely sources of infection. PRIMARY AND SECONDARY OUTCOME MEASURES: Superspreaders were identified using the transmission tree. The reproduction number, that is, the average number of secondary cases produced by a single primary case, was estimated as a function of time and according to different types of hosts. RESULTS: A total of five superspreaders were identified. The reproduction number throughout the course of the outbreak was estimated at 1.0 due to reconstruction of the transmission tree, while the variance of secondary cases generated by a primary case was 52.1. All of the superspreaders involved in this outbreak appeared to have generated a substantial number of contacts in multiple healthcare facilities (association: p<0.01), generating on average 4.0 (0.0–8.6) and 28.6 (0.0–63.9) secondary cases among patients who visited multiple healthcare facilities and others. The time-dependent reproduction numbers declined substantially below the value of 1 on and after 13 June 2015. CONCLUSIONS: Superspreaders who visited multiple facilities drove the epidemic by generating a disproportionate number of secondary cases. Our findings underscore the need to limit the contacts in healthcare settings. Contact tracing efforts could assist early laboratory testing and diagnosis of suspected cases.

negative: Editorial Concern-Possible Reporting of the Same Patients With COVID-19 in Different Reports.

negative: Effectiveness of control strategies for Coronavirus Disease 2019: a SEIR dynamic modeling study Background: Since its first cases occurrence in Wuhan, China, the Coronavirus Disease 2019 (COVID-19) has been spreading rapidly to other provinces and neighboring countries. A series of intervention strategies have been implemented, but didn't stop its spread. Methods: Two mathematical models have been developed to simulate the current epidemic situation in the city of Wuhan and in other parts of China. Special considerations were given to the mobility of people for the estimation and forecast the number of asymptomatic infections, symptomatic infections, and the infections of super-spreading events (Isse). Findings: The basic reproductive number (R0) was calculated for the period between 18 January 2020 and 16 February 2020: R0 declined from 5.75 to 1.69 in Wuhan and from 6.22 to 1.67 in the entire country (not including the Wuhan area). At the same time, Wuhan is estimated to observe a peak in the number of confirmed cases around 6 February 2020. The number of infected individuals in the entire country (not including the Wuhan area) peaked around February 3. The results also show that the peak of new asymptomatic cases per day in Wuhan occurred on February 6, and the peak of new symptomatic infections have occurred on February 3. Concurrently, while the number of confirmed cases nationwide would continue to decline, the number of real-time COVID-19 inpatients in Wuhan has reached a peak of 13,030 on February 14 before it decreases. The model further shows that the COVID-19 cases will gradually wane by the end of April 2020, both in Wuhan and the other parts of China. The number of confirmed cases would reach the single digit on March 27 in Wuhan and March 19 in the entire country. The five cities with top risk index in China with the exclusion of Wuhan are: Huanggang, Xiaogan, Jingzhou, Chongqing, and Xiangyang city. Interpretations: Although the national peak time has been reached, a significant proportion of asymptomatic patients and the infections of super-spreading events (Isse) still exist in the population, indicating the potential difficulty for the prevention and control of the disease. As the Return-to-Work tide is approaching and upgrading, further measures (e.g., escalatory quarantine, mask wearing when going out, and sit apart when taking vehicles) will be particularly crucial to stop the COVID-19 in other cities outside of Wuhan.

negative: Further evidence that chilblains are a cutaneous manifestation of COVID-19 infection

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: Impact of Local Congruences in Attribute Reduction Local congruences are equivalence relations whose equivalence classes are convex sublattices of the original lattice. In this paper, we present a study that relates local congruences to attribute reduction in FCA. Specifically, we will analyze the impact in the context of the use of local congruences, when they are used for complementing an attribute reduction.

negative: A Multicentre Study of 2019 Novel Coronavirus Disease Outcomes of Cancer Patients in Wuhan, China Background: At present, there is a global pandemic of coronavirus disease 2019 (COVID-19) pneumonia. Two previous case series from China have suggested that cancer patients are at a higher risk of COVID-19 pneumonia, but the reports were limited by small numbers and few clinical information. Objective: To study clinical characteristics and outcomes of cancer patients infected with COVID-19. Design: Retrospective study. Setting: Four designated COVID-16 hospitals in Wuhan, Hubei province, China. Participants: Medical records of 67 cancer patients admitted to hospitals between Jan 5, 2020 to Feb 18, 2020 were included. Measurements: Demographic, clinical, laboratory, radiological and treatment data were collected. Survival data of the cohort was cut-off on Mar 10, 2020. Results: Of the 67 patients (median age: 66 years), the median age of patients who had severe illness was older than that of patients who had mild symptoms (P<0.001). Forty-three (64.2%) patients had other concurrent chronic diseases, and the proportion of severe patients had co-morbidities was higher than patients with mild disease (P=0.004). Twenty-three (34.3%) patients were still at the anticancer treatment phase, but no tumour progression and recurrence was observed for all the patients during the treatment of COVID-19 pneumonia. About 70% of these patients had fever (n=53, 79.1%) and/or cough (n=50, 74.6%). Lymphocytopenia was the main laboratory finding accompanying increased C-reactive protein and procalcitonin in cancer patients, especially in severe cases. By Mar 10, 2020, 18 (26.9%) patients died from COVID-19, and 39 (58.2%) patients have been discharged. The median age of survivors was younger than that of deaths (P=0.014). Lung cancer (n=15, 22.4%) with COVID-19 was the most common cancer type and accounted for the highest proportion COVID-19 resulted deaths (33.3%, 5/15). We observed a tendency that patients at the follow-up phase had a better prognosis than that at anticancer treatment phase (P=0.095). Limitation: This is a retrospective study with only 67 cases from four hospitals. And some specific clinical information was insufficient. Conclusion: This study showed COVID-19 patients with cancer seem to have a higher proportion of severe cases and poorer prognosis. The tendency of poor prognosis was more obvious in patients at anticancer treatment phase. We should pay more intensive attentions to cancer patients infected with COVID-19.

negative: Using the LIST model to Estimate the Effects of Contact Tracing on COVID-19 Endemic Equilibria in England and its Regions Governments across Europe are preparing for the emergence from lockdown, in phases, to prevent a resurgence in cases of COVID-19. Along with social distancing (SD) measures, contact tracing comprising find, track, trace and isolate (FTTI) policies are also being implemented. Here, we investigate FTTI policies in terms of their impact on the endemic equilibrium. We used a generative model, the dynamic causal 'Location', 'Infection', 'Symptom' and 'Testing' (LIST) model to identify testing, tracing, and quarantine requirements. We optimised LIST model parameters based on time series of daily reported cases and deaths of COVID-19 in England and based upon reported cases in the nine regions of England and in all 150 upper tier local authorities. Using these optimised parameters, we forecasted infection rates and the impact of FTTI for each area; national, regional, and local. Predicting data from early June 2020, we find that under conditions of medium-term immunity, a '40%' FTTI policy (or greater), could reach a distinct endemic equilibrium that produces a significantly lower death rate and a decrease in ICU occupancy. Considering regions of England in isolation, some regions could substantially reduce death rates with 20% efficacy. We characterise the accompanying endemic equilibria in terms of dynamical stability, observing bifurcation patterns whereby relatively small increases in FTTI efficacy result in stable states with reduced overall morbidity and mortality. These analyses suggest that FTTI will not only save lives, even if only partially effective, and could underwrite the stability of any endemic steady-state we manage to attain.

negative: Reaction‐Superdiffusion Systems in Epidemiology, an Application of Fractional Calculus Spatially extended stochastic processes in epidemiology lead to classical reaction‐diffusion process, when infection spreads only locally. This notion can be generalized using fractional derivatives, especially fractional Laplacian operators, leading to Lévy flights and sub‐ or super‐diffusion. Especially super‐diffusion is a more realistic mechanism of spreading epidemics than ordinary diffusion.

negative: The Imperfect Cytokine Storm: Severe COVID-19 with ARDS in Patient on Durable LVAD Support Abstract As health systems worldwide grapple with the COVID-19 pandemic, patients on durable LVAD support represent a unique population at risk for the disease. We outline such a patient who developed COVID-19 complicated by “cytokine storm” with severe ARDS and myocardial injury; and describe the challenges that arose during management.

negative: Association of BCG vaccination policy with prevalence and mortality of COVID-19 There is some evidence that tuberculosis vaccine bacillus Calmette-Guérin (BCG) has non-specific beneficial effects against non-related infections. Here, we examined the possible association between BCG vaccination with prevalence and mortality by COVID-19 by using publicly available data of COVID-19 in 199 countries/regions and the BCG World Atlas. By using linear regression modeling, we found that the number of total cases and deaths per one million population were significantly associated with the country's policy concerning BCG vaccine administration. The amount of variance in cases and deaths explained by BCG vaccination policy ranged between 12.5% and 38%. Importantly, this effect remained significant after controlling for the country's life expectancy and the average temperature in February and March 2020, which themselves are significantly correlated with the cases and deaths indices, respectively. By contrast, the ratio between deaths and cases was weakly affected. This latter outcome suggested that BCG vaccination may have hindered the overall spread of the virus or progression of the disease rather than reducing mortality rates (i.e., deaths/cases ratio). Finally, by roughly dividing countries into three categories showing high, middle, or low growth rate of the cases, we found a highly significant difference between the slope categories among the BCG groups, suggesting that the time since the onset of the spread of the virus was not a major confounding factor. While this study potentially suffers from a number of unknown confounding factors, these associations support the idea that BCG vaccination may provide protection against SARS-CoV-2, which, together with its proven safety, encourages consideration of further detailed epidemiological studies, large-scale clinical trials on the efficacy of this vaccine on COVID-19, and/or re-introduction of BCG vaccination practice in the countries which are currently devoid of the practice.

negative: Mohs surgery: proclamation, proof, principles, and promise

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: Similarities and Differences in COVID-19 Awareness, Concern, and Symptoms by Race and Ethnicity in the United States: Cross-Sectional Survey BACKGROUND: Existing health disparities based on race and ethnicity in the United States are contributing to disparities in morbidity and mortality during the coronavirus disease (COVID-19) pandemic. We conducted an online survey of American adults to assess similarities and differences by race and ethnicity with respect to COVID-19 symptoms, estimates of the extent of the pandemic, knowledge of control measures, and stigma. OBJECTIVE: The aim of this study was to describe similarities and differences in COVID-19 symptoms, knowledge, and beliefs by race and ethnicity among adults in the United States. METHODS: We conducted a cross-sectional survey from March 27, 2020 through April 1, 2020. Participants were recruited on social media platforms and completed the survey on a secure web-based survey platform. We used chi-square tests to compare characteristics related to COVID-19 by race and ethnicity. Statistical tests were corrected using the Holm Bonferroni correction to account for multiple comparisons. RESULTS: A total of 1435 participants completed the survey; 52 (3.6%) were Asian, 158 (11.0%) were non-Hispanic Black, 548 (38.2%) were Hispanic, 587 (40.9%) were non-Hispanic White, and 90 (6.3%) identified as other or multiple races. Only one symptom (sore throat) was found to be different based on race and ethnicity (P=.003); this symptom was less frequently reported by Asian (3/52, 5.8%), non-Hispanic Black (9/158, 5.7%), and other/multiple race (8/90, 8.9%) participants compared to those who were Hispanic (99/548, 18.1%) or non-Hispanic White (95/587, 16.2%). Non-Hispanic White and Asian participants were more likely to estimate that the number of current cases was at least 100,000 (P=.004) and were more likely to answer all 14 COVID-19 knowledge scale questions correctly (Asian participants, 13/52, 25.0%; non-Hispanic White participants, 180/587, 30.7%) compared to Hispanic (108/548, 19.7%) and non-Hispanic Black (25/158, 15.8%) participants. CONCLUSIONS: We observed differences with respect to knowledge of appropriate methods to prevent infection by the novel coronavirus that causes COVID-19. Deficits in knowledge of proper control methods may further exacerbate existing race/ethnicity disparities. Additional research is needed to identify trusted sources of information in Hispanic and non-Hispanic Black communities and create effective messaging to disseminate correct COVID-19 prevention and treatment information.

negative: Estimation of country-level basic reproductive ratios for novel Coronavirus (COVID-19) using synthetic contact matrices The outbreak of novel coronavirus (COVID-19) has the potential for global spread, infecting large numbers in all countries. In this case, estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of contacts through which the disease can spread - with this network determined by socio-demographics including age-structure and household composition. Here we focus on the age-structured transmission within the population, using data from China to inform age-dependent susceptibility and synthetic age-mixing matrices to inform the contact network. This allows us to determine the country-specific basic reproductive ratio as a multiplicative scaling of the value from China. We predict that R0 will be highest across Eastern Europe and Japan, and lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly.

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: Comprehensive Identification and Isolation Policies Have Effectively Suppressed the Spread of COVID-19 The outbreak of COVID-19 has caused severe life and economic damage worldwide. Since the absence of medical resources or targeted therapeutics, systemic containment policies have been prioritized but some critics query what extent can they mitigate this pandemic. We construct a fine-grained transmission dynamics model to forecast the crucial information of public concern, therein using dynamical coefficients to quantify the impact of the implement schedule and intensity of the containment policies on the spread of epidemic. Statistical evidences show the comprehensive identification and quarantine policies eminently contributed to reduce casualties during the phase of a dramatic increase in diagnosed cases in Wuhan and postponing or weakening such policies would undoubtedly exacerbate the epidemic. Hence we suggest that governments should swiftly execute the forceful public health interventions in the initial stage until the pandemic is blocked.

negative: Thiopurine Derivative-Induced Fpg/Nei DNA Glycosylase Inhibition: Structural, Dynamic and Functional Insights DNA glycosylases are emerging as relevant pharmacological targets in inflammation, cancer and neurodegenerative diseases. Consequently, the search for inhibitors of these enzymes has become a very active research field. As a continuation of previous work that showed that 2-thioxanthine (2TX) is an irreversible inhibitor of zinc finger (ZnF)-containing Fpg/Nei DNA glycosylases, we designed and synthesized a mini-library of 2TX-derivatives (TXn) and evaluated their ability to inhibit Fpg/Nei enzymes. Among forty compounds, four TXn were better inhibitors than 2TX for Fpg. Unexpectedly, but very interestingly, two dithiolated derivatives more selectively and efficiently inhibit the zincless finger (ZnLF)-containing enzymes (human and mimivirus Neil1 DNA glycosylases hNeil1 and MvNei1, respectively). By combining chemistry, biochemistry, mass spectrometry, blind and flexible docking and X-ray structure analysis, we localized new TXn binding sites on Fpg/Nei enzymes. This endeavor allowed us to decipher at the atomic level the mode of action for the best TXn inhibitors on the ZnF-containing enzymes. We discovered an original inhibition mechanism for the ZnLF-containing Fpg/Nei DNA glycosylases by disulfide cyclic trimeric forms of dithiopurines. This work paves the way for the design and synthesis of a new structural class of inhibitors for selective pharmacological targeting of hNeil1 in cancer and neurodegenerative diseases.

negative: Spread and dynamics of the COVID-19 epidemic in Italy: Effects of emergency containment measures The spread of coronavirus disease 2019 (COVID-19) in Italy prompted drastic measures for transmission containment. We examine the effects of these interventions, based on modeling of the unfolding epidemic. We test modeling options of the spatially explicit type, suggested by the wave of infections spreading from the initial foci to the rest of Italy. We estimate parameters of a metacommunity Susceptible–Exposed–Infected–Recovered (SEIR)-like transmission model that includes a network of 107 provinces connected by mobility at high resolution, and the critical contribution of presymptomatic and asymptomatic transmission. We estimate a generalized reproduction number ([Formula: see text] = 3.60 [3.49 to 3.84]), the spectral radius of a suitable next-generation matrix that measures the potential spread in the absence of containment interventions. The model includes the implementation of progressive restrictions after the first case confirmed in Italy (February 21, 2020) and runs until March 25, 2020. We account for uncertainty in epidemiological reporting, and time dependence of human mobility matrices and awareness-dependent exposure probabilities. We draw scenarios of different containment measures and their impact. Results suggest that the sequence of restrictions posed to mobility and human-to-human interactions have reduced transmission by 45% (42 to 49%). Averted hospitalizations are measured by running scenarios obtained by selectively relaxing the imposed restrictions and total about [Formula: see text] individuals (as of March 25, 2020). Although a number of assumptions need to be reexamined, like age structure in social mixing patterns and in the distribution of mobility, hospitalization, and fatality, we conclude that verifiable evidence exists to support the planning of emergency measures.

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

negative: Livestock infectious diseases and zoonoses. Infectious diseases of livestock are a major threat to global animal health and welfare and their effective control is crucial for agronomic health, for safeguarding and securing national and international food supplies and for alleviating rural poverty in developing countries. Some devastating livestock diseases are endemic in many parts of the world and threats from old and new pathogens continue to emerge, with changes to global climate, agricultural practices and demography presenting conditions that are especially favourable for the spread of arthropod-borne diseases into new geographical areas. Zoonotic infections that are transmissible either directly or indirectly between animals and humans are on the increase and pose significant additional threats to human health and the current pandemic status of new influenza A (H1N1) is a topical example of the challenge presented by zoonotic viruses. In this article, we provide a brief overview of some of the issues relating to infectious diseases of livestock, which will be discussed in more detail in the papers that follow.

negative: The TVBG-SEIR spline model for analysis of COVID-19 spread, and a Tool for prediction scenarios Mathematical models are traditionally used to analyze the long-term global evolution of epidemics, to determine the potential and severity of an outbreak, and to provide critical information for identifying the type of disease interventions and intensity. One of the widely used mathematical models of long-term spreading of epidemics are the so-called deterministic compartmental models (SIR/SEIR type models). One of the main purposes of applying such models is to assess how the expensive restriction measures imposed by the authorities (home and social isolation/quarantine, travel restrictions, etc.) can effectively reduce the control reproduction number of the disease and its transmission risk. However the classical SIR/SEIR models have been primarily studied in what may be called stationary case, where the main parameters, the Transmission rate Beta (reflecting the virus spread by infected individuals) and the Removed rate Gamma (reflecting the hospitalization/isolation measures) remain constant during the whole period of interest. Hence, it is important to extend the classical SIR/SEIR models by creating new ansatzes for the dynamics of the transmission rates Beta(t) (which we will call further just Beta) and removed rates Gamma(t) (which we will call further just Gamma). The main purpose of the present research is to introduce a spline-based SEIR model with Time-varying Beta and Gamma parameters, or abbreviated TVBG-SEIR model, which is used to estimate the practical implications of the public health interventions and measures. We have designed a Tool based on the TVBG-SEIR model, which may be used as a Decision Support Tool to assist the health decision- and policy-makers in creating predictive scenarios.

negative: Institutional Preparedness to Prevent Future Middle East Respiratory Syndrome Coronavirus-Like Outbreaks in Republic of Korea A year has passed since the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea. This 2015 outbreak led to a better understanding of healthcare infection control. The first Korean patient infected by Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was diagnosed on May 20, 2015, after he returned from Qatar and Bahrain. Thereafter, 186 Korean people were infected with the MERS-CoV in a short time through human-to-human transmission. All these cases were linked to healthcare settings, and 25 (13.5 %) infected patients were healthcare workers. Phylogenetic analysis suggested that the MERS-CoV isolate found in the Korean patient was closely related to the Qatar strain, and did not harbor transmission efficiency-improving mutations. Nevertheless, with the same infecting virus strain, Korea experienced the largest MERS-CoV outbreak outside the Arabian Peninsula, primarily due to the different characteristics of population density and the healthcare system. We aimed to review the epidemiological features and existing knowledge on the Korean MERS outbreak, and suggest methods to prevent future epidemics.

negative: Deep Impact of COVID-19 in the HealthCare of Latin America: the case of Brazil

negative: Using predicted imports of 2019-nCoV cases to determine locations that may not be identifying all imported cases Cases from the ongoing outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV) exported from mainland China can lead to self-sustained outbreaks in other populations. Internationally imported cases are currently being reported in several different locations. Early detection of imported cases is critical for containment of the virus. Based on air travel volume estimates from Wuhan to international destinations and using a generalized linear regression model we identify locations which may potentially have undetected internationally imported cases.

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: Minimizing the risk of international spread of coronavirus disease 2019 (COVID-19) outbreak by targeting travelers The Coronavirus Disease-2019 (COVID-19) outbreak has become a global health emergency owing to its magnitude, attributed deaths, and its propensity to spread across the world. In-fact, owing to its quick spread across international boundaries and the resulting caseload, the disease has been declared as a Public Health Emergency of International Concern on 30 January 2020. It is worth noting that out of the 395 cases detected in other nations, 165 (41.8%) have a positive history of travel to China. As of now, the World Health Organization has not recommended for any restrictions on the travel or trade aspects, but has clearly specified that implementation of International Health Regulations should be strictly done at the airports and seaports. In conclusion, the COVID- 19 outbreak has created an alarm across the globe as the causative virus is novel in nature. However, strengthening of standard infection control practices and adoption of preventive measures for travelers can significantly minimize the threat of further transmission of the disease.

negative: 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 virus-laden droplet and aerosol transmission by such practices is poorly understood. This review paper intends to outline the literature concerning the transmission of virus-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. The infection propensities in confined spaces (airplane, passenger car, and healthcare center) by the transmission of droplets and aerosols under varying ventilation conditions were discussed. Interestingly, the nosocomial transmission by airborne SARS-CoV-2 virus-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.

negative: 33 Viral Respiratory Infections Abstract Acute respiratory illnesses are the most frequently occurring illness in all age groups globally. Disease is mostly limited to the upper airways and is self-limiting, but a small percentage can progress to lower respiratory tract infections as bronchiolitis and pneumonia. Children and elderly people are at increased risk, especially in developing countries. The most important etiologic agents of severe lower respiratory illness are bacteria such as Streptococcus pneumoniae and Haemophilus influenzae and viruses such as respiratory syncytial virus (RSV) and influenza virus. Efficacious vaccines are available against the two bacteria and the influenza virus. Viruses are much more important in mild upper and middle respiratory tract infections and in bronchiolitis in children, whereas bacteria are the main cause of pneumonia, especially in adults. Clinical syndromes overlap considerably, and there is increasing evidence of bacterial-viral co-infections and of bacterial pneumonia being secondary to viral respiratory tract infection.

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: Using models to identify routes of nosocomial infection: a large hospital outbreak of SARS in Hong Kong. Two factors dominated the epidemiology of severe acute respiratory syndrome (SARS) during the 2002-2003 global outbreak, namely super-spreading events (SSE) and hospital infections. Although both factors were important during the first and the largest hospital outbreak in Hong Kong, the relative importance of different routes of infection has not yet been quantified. We estimated the parameters of a novel mathematical model of hospital infection using SARS episode data. These estimates described levels of transmission between the index super-spreader, staff and patients, and were used to compare three plausible hypotheses. The broadest of the supported hypotheses ascribes the initial surge in cases to a single super-spreading individual and suggests that the per capita risk of infection to patients increased approximately one month after the start of the outbreak. Our estimate for the number of cases caused by the SSE is substantially lower than the previously reported values, which were mostly based on self-reported exposure information. This discrepancy suggests that the early identification of the index case as a super-spreader might have led to biased contact tracing, resulting in too few cases being attributed to staff-to-staff transmission. We propose that in future outbreaks of SARS or other directly transmissible respiratory pathogens, simple mathematical models could be used to validate preliminary conclusions concerning the relative importance of different routes of transmission with important implications for infection control.

negative: Outbreak of COVID-19 - an urgent need for good science to silence our fears?

negative: The Longevity-Frailty Hypothesis: Evidence from COVID-19 Death Rates in Europe COVID-19 death rates vary strikingly across Europe. The death rate in Spain, for example, is greater than the death rate in Germany by more than a factor of ten. Few if any epidemiological indicators distinguish the countries of Europe by such a vast margin. Evidence on age-specific case-fatality rates (deaths over observed infections) and age-specific death rates (deaths over population) indicate that COVID-19 disproportionately afflicts the elderly and frail, suggesting that the share of elderly population (≥ 65 years of age) in a country ought to be a strong predictor of the COVID-19 death rate. However, the COVID-19 death rate and the share of elderly population are statistically uncorrelated (r = 0.163, p = 0.399). Share of population ≥ 65 years of age is confounded by mortality selection, as well as other demographic dynamics. By contrast, elderly longevity or life expectancy at 65 more effectively captures population survival and the accumulation of age-related frailty in society. We find a strong statistical relationship between the COVID-19 death rate (r = 0.839, p < .001) and elderly longevity, and a moderately strong relationship between the date of epidemic timing and elderly longevity (r = −0.634, p < .001). These relationships are robust to the inclusion of statistical controls for international tourism inflow and hospital bed capacity. While the countries of Europe vary meaningfully in healthcare system capacity and in the timing and intensity of non-pharmaceutical interventions, the striking variation in COVID-19 death rates across these countries is statistically and intuitively associated with elderly survival and consequent frailty.

negative: COVID-19 pandemic: Emerging perspectives and future trends World is living on the edge. The human cost of COVID pandemic could be extraordinary. We find ourselves in a time of great economic, social, and medical uncertainty. The pandemic demands action on many fronts, from prevention to testing to treatment. We need to create simple, cheap, more accessible testing for SARS-CoV-2. A faster way has to be developed to identify antibodies that neutralize the virus. More than 100 vaccines for the SARS-CoV-2 are at various stages of development. Some six groups have already begun injecting formulations into volunteers in safety trials; others have started testing in animals. The biggest challenge is to determine which vaccine is ideal. Reason and science have to guide us. There is urgent need to critically appraise evidence in deciding how to treat patients. We need a drug or combination of drugs that work. Remdesivir has generated hope. It may prove to be a magic bullet. Countries like Taiwan, Vietnam, Singapore, Hong Kong, South Korea, New Zealand have done exceptionally well to contain the spread of COVID-19. It is widely believed that during the pandemic treatment suffers. Patients with diseases like cancer, diabetes, renal failure, CAD and pregnant women need special attention. As the pandemic pushes up levels of hunger among the global poor, governments must prevent devastating nutrition and health consequences for children missing out on school meals amid school closures. Nations will have endemic SARS-CoV-2 infection for the foreseeable future. A structured and well-coordinated approach is critical for tackling this global crisis.

negative: Emergence of a novel coronavirus causing respiratory illness from Wuhan, China

negative: A prospect on the use of antiviral drugs to control local outbreaks of COVID-19 Background: Current outbreaks of COVID-19 are threatening the health care systems of several countries around the world. Control measures, based on isolation and quarantine, have been shown to decrease and delay the burden of the ongoing epidemic. With respect to the ongoing COVID-19 epidemic, recent modelling work shows that this intervention technique may be inadequate to control local outbreaks, even when perfect isolation is assumed. Furthermore, the effect of infectiousness prior to symptom onset combined with a significant proportion of asymptomatic infectees further complicates the use of contact tracing. Antivirals, which decrease the viral load and reduce the infectiousness, could be integrated in the control measures in order to augment the feasibility of controlling the epidemic. Methods: Using a simulation-based model of viral transmission we tested the efficacy of different intervention measures for the control of COVID-19. For individuals that were identified through contact tracing, we evaluate two procedures: monitoring individuals for symptoms onset and testing of individuals. Moreover, we investigate the effect of a potent antiviral compound on the contact tracing process. Findings: The use of an antiviral drug, in combination with contact tracing, quarantine and isolation, results in a significant decrease of the final size, the peak incidence, and increases the probability that the outbreak will fade out. Interpretation: For an infectious disease in which presymptomatic infections are plausible, an intervention measure based on contact tracing performs better when realized together with testing instead of monitoring, provided that the test is able to detect infections during the incubation period. In addition, in all tested scenarios, the model highlights the benefits of the administration of an antiviral drug in addition to quarantine, isolation and contact tracing. The resulting control measure, could be an effective strategy to control local and re-emerging outbreaks of COVID-19.

negative: Addressing COVID‐19 Drug Development with Artificial Intelligence The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus that led to the COVID‐19 (Coronavirus Disease 2019) pandemic, has resulted in substantial overburdening of healthcare systems as well as an economic crisis on a global scale. This has in turn resulted in widespread efforts to identify suitable therapies to address this aggressive pathogen. Therapeutic antibody and vaccine development are being actively explored, and a phase I clinical trial of mRNA‐1273 which is developed in collaboration between the National Institute of Allergy and Infectious Diseases and Moderna, Inc. is currently underway. Timelines for the broad deployment of a vaccine and antibody therapies have been estimated to be 12–18 months or longer. These are promising approaches that may lead to sustained efficacy in treating COVID‐19. However, its emergence has also led to a large number of clinical trials evaluating drug combinations composed of repurposed therapies. As study results of these combinations continue to be evaluated, there is a need to move beyond traditional drug screening and repurposing by harnessing artificial intelligence (AI) to optimize combination therapy design. This may lead to the rapid identification of regimens that mediate unexpected and markedly enhanced treatment outcomes.

negative: The interconnected and cross-border nature of risks posed by infectious diseases Infectious diseases can constitute public health emergencies of international concern when a pathogen arises, acquires new characteristics, or is deliberately released, leading to the potential for loss of human lives as well as societal disruption. A wide range of risk drivers are now known to lead to and/or exacerbate the emergence and spread of infectious disease, including global trade and travel, the overuse of antibiotics, intensive agriculture, climate change, high population densities, and inadequate infrastructures, such as water treatment facilities. Where multiple risk drivers interact, the potential impact of a disease outbreak is amplified. The varying temporal and geographic frequency with which infectious disease events occur adds yet another layer of complexity to the issue. Mitigating the emergence and spread of infectious disease necessitates mapping and prioritising the interdependencies between public health and other sectors. Conversely, during an international public health emergency, significant disruption occurs not only to healthcare systems but also to a potentially wide range of sectors, including trade, tourism, energy, civil protection, transport, agriculture, and so on. At the same time, dealing with a disease outbreak may require a range of critical sectors for support. There is a need to move beyond narrow models of risk to better account for the interdependencies between health and other sectors so as to be able to better mitigate and respond to the risks posed by emerging infectious disease.

negative: Coupling infectious diseases, human preventive behavior, and networks – A conceptual framework for epidemic modeling Human-disease interactions involve the transmission of infectious diseases among individuals and the practice of preventive behavior by individuals. Both infectious diseases and preventive behavior diffuse simultaneously through human networks and interact with one another, but few existing models have coupled them together. This article proposes a conceptual framework to fill this knowledge gap and illustrates the model establishment. The conceptual model consists of two networks and two diffusion processes. The two networks include: an infection network that transmits diseases and a communication network that channels inter-personal influence regarding preventive behavior. Both networks are composed of same individuals but different types of interactions. This article further introduces modeling approaches to formulize such a framework, including the individual-based modeling approach, network theory, disease transmission models and behavioral models. An illustrative model was implemented to simulate a coupled-diffusion process during an influenza epidemic. The simulation outcomes suggest that the transmission probability of a disease and the structure of infection network have profound effects on the dynamics of coupled-diffusion. The results imply that current models may underestimate disease transmissibility parameters, because human preventive behavior has not been considered. This issue calls for a new interdisciplinary study that incorporates theories from epidemiology, social science, behavioral science, and health psychology.

negative: An Information-Theoretic and Dissipative Systems Approach to the Study of Knowledge Diffusion and Emerging Complexity in Innovation Systems The paper applies information theory and the theory of dissipative systems to discuss the emergence of complexity in an innovation system, as a result of its adaptation to an uneven distribution of the cognitive distance between its members. By modelling, on one hand, cognitive distance as noise, and, on the other hand, the inefficiencies linked to a bad flow of information as costs, we propose a model of the dynamics by which a horizontal network evolves into a hierarchical network, with some members emerging as intermediaries in the transfer of knowledge between seekers and problem-solvers. Our theoretical model contributes to the understanding of the evolution of an innovation system by explaining how the increased complexity of the system can be thermodynamically justified by purely internal factors. Complementing previous studies, we demonstrate mathematically that the complexity of an innovation system can increase not only to address the complexity of the problems that the system has to solve, but also to improve the performance of the system in transferring the knowledge needed to find a solution.

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: 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.

negative: PCR sequencing of the spike genes of geographically and chronologically distinct human coronaviruses 229E Abstract A reverse transcription nested PCR (RT-PCR) sequencing methodology was developed and used to generate sequence data from the spike genes of three geographically and chronologically distinct human coronaviruses 229E. These three coronaviruses were isolated originally from the USA in the 1960s (human coronavirus 229E strain ATCC VR-74), the UK in the 1990s (human coronavirus 229E LRI 281) and Ghana (human coronavirus 229E A162). Upon translation and alignment with the published spike protein sequence of human coronavirus 229E ‘LP’ (isolated in the UK in the 1970s), it was found that variation within the translated protein sequences was rather limited. In particular, minimal variation was observed between the translated spike protein sequence of human coronaviruses 229E LP and ATCC VR-74 (1/1012 amino acid differences), whilst most variation was observed between the translated spike protein sequence of human coronaviruses 229E LP and A162 (47/1012 amino acid changes). Further, the translated spike protein sequence of human coronavirus 229E A162 showed three clusters of amino acid changes, situated within the 5′ half of the translated spike protein sequence.

negative: Mental health during the COVID-19 pandemic in two longitudinal UK population cohorts Background: The impact of COVID-19 on mental health is unclear. Evidence from longitudinal studies with pre pandemic data are needed to address (1) how mental health has changed from pre-pandemic levels to during the COVID-19 pandemic and (2), whether there are groups at greater risk of poorer mental health during the pandemic? Methods: We used data from COVID-19 surveys (completed through April/May 2020), nested within two large longitudinal population cohorts with harmonised measures of mental health: two generations of the Avon Longitudinal Study of Parents and Children (ALPSAC): the index generation ALSPAC-G1 (n= 2850, mean age 28) and the parents generation ALSPAC-G0 (n= 3720, mean age = 59) and Generation Scotland: Scottish Family Health Study (GS, (n= 4233, mean age = 59), both with validated pre-pandemic measures of mental health and baseline factors. To answer question 1, we used ALSPAC-G1, which has identical mental health measures before and during the pandemic. Question 2 was addressed using both studies, using pre-pandemic and COVID-19 specific factors to explore associations with depression and anxiety in COVID-19. Findings: In ALSPAC-G1 there was evidence that anxiety and lower wellbeing, but not depression, had increased in COVID-19 from pre-pandemic assessments. The percentage of individuals with probable anxiety disorder was almost double during COVID-19: 24% (95% CI 23%, 26%) compared to pre-pandemic levels (13%, 95% CI 12%, 14%), with clinically relevant effect sizes. In both ALSPAC and GS, depression and anxiety were greater in younger populations, women, those with pre-existing mental and physical health conditions, those living alone and in socio-economic adversity. We did not detect evidence for elevated risk in key workers or health care workers. Interpretation: These results suggest increases in anxiety and lower wellbeing that may be related to the COVID-19 pandemic and/or its management, particularly in young people. This research highlights that specific groups may be disproportionally at risk of elevated levels of depression and anxiety during COVID-19 and supports recent calls for increasing funds for mental health services. Funding: The UK Medical Research Council (MRC), the Wellcome Trust and University of Bristol.

negative: Healthcare-associated infections: the hallmark of Middle East respiratory syndrome coronavirus with review of the literature Summary Middle East respiratory syndrome coronavirus (MERS-CoV) is capable of causing acute respiratory illness. Laboratory-confirmed MERS-CoV cases may be asymptomatic, have mild disease, or have a life-threatening infection with a high case fatality rate. There are three patterns of transmission: sporadic community cases from presumed non-human exposure, family clusters arising from contact with an infected family index case, and healthcare-acquired infections among patients and from patients to healthcare workers. Healthcare-acquired MERS infection has become a well-known characteristic of the disease and a leading means of spread. The main factors contributing to healthcare-associated outbreaks include delayed recognition, inadequate infection control measures, inadequate triaging and isolation of suspected MERS or other respiratory illness patients, crowding, and patients remaining in the emergency department for many days. A review of the literature suggests that effective control of hospital outbreaks was accomplished in most instances by the application of proper infection control procedures. Prompt recognition, isolation and management of suspected cases are key factors for prevention of the spread of MERS. Repeated assessments of infection control and monitoring of corrective measures contribute to changing the course of an outbreak. Limiting the number of contacts and hospital visits are also important factors to decrease the spread of infection.

negative: Topological dynamics of the 2015 South Korea MERS-CoV spread-on-contact networks Network analysis to examine infectious contact relations provides an important means to uncover the topologies of individual infectious contact networks. This study aims to investigate the spread of diseases among individuals over contact networks by exploring the 2015 Middle East Respiratory Syndrome (MERS) outbreak in Korea. We present several distinct features of MERS transmission by employing a comprehensive approach in network research to examine both the traced relationship matrix of infected individuals and their bipartite transmission routes among healthcare facilities visited for treatment. The results indicate that a few super-spreaders were more likely to hold certain structural advantages by linking to an exceptional number of other individuals, causing several ongoing transmission events in neighbourhoods without the aid of any intermediary. Thus, the infectious contact network exhibited small-world dynamics characterised by locally clustered contacts exposed to transmission paths via short path lengths. In addition, nosocomial infection analysis shows the pattern of a common-source outbreak followed by secondary person-to-person transmission of the disease. Based on the results, we suggest policy implications related to the redesign of prevention and control strategies against the spread of epidemics.

negative: The COVID-19 pandemic: is our medicine still evidence-based? There is no randomized controlled trial that demonstrated the efficacy of antiviral therapy against COVID-19 yet. However, physicians are prescribing different drugs to a large part of COVID-19 population in the hope they will cure them. This does not reflect the evidence-based medicine approach. What we need is more evidence-based knowledge about what routine care practices we should to apply to ameliorate symptoms of patients and fight COVID-19 pathology.

negative: Potential applications of plant biotechnology against SARS-CoV-2 Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for an ongoing human pandemic (COVID-19). There is a massive international effort underway to develop diagnostic reagents, vaccines and antiviral drugs in a bid to slow down the spread of the disease and save lives. One part of that international effort involves the research community working with plants, bringing researchers from all over the world together with commercial enterprises in order to achieve the rapid supply of protein antigens and antibodies for diagnostic kits, and scalable production systems for the emergency manufacturing of vaccines and antiviral drugs. Here we look at some of the ways in which plants can and are being used in the fight against COVID-19.

negative: Molecular epidemiology of SARS-CoV-2 in Faisalabad, Pakistan: A real-world clinical experience Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-2019 is a new global health challenge which causes severe respiratory complications. As of May 17th, 2020, SARS-CoV-2 has infected 4.6 million people and caused 310,000 deaths, worldwide. In order to study potential impact of infection, complete epidemiological information should be reported on regular basis however, data from Pakistan has not yet been published. This retrospective study is the first report of epidemiological trends of COVID-19 in Faisalabad, Pakistan. On April 4th, 2020, 128 nasopharyngeal swabs collected from city Faisalabad were transported to Postgraduate Research Institute, Lahore for further processing. RNA was extracted using QIAsymphony DSP Virus/Pathogen Midi Kit and real-time PCR was performed to quantify COVID-19. Our finding showed that overall prevalence of COVID-19 in Faisalabad on April 4th was 17.18% (22 of 128). Prevalence was higher in males (n = 17; 77.2%) as compared to females (n = 5; 22.8%) but this gender-wise difference was not statistically significant. Patients belonging to age group 37–47 years were found to be most (45.5%) infected with COVID-19.

negative: 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.

negative: BAR scaffolds drive membrane fission by crowding disordered domains Cellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysin-rvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain–containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules. But in nature, proteins that contain BAR domains often also contain large intrinsically disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain–containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fission. Specifically, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. These data suggest that the ability to concentrate disordered domains is a key driver of membrane remodeling and fission by BAR domain–containing proteins.

negative: A Hybrid Model for Disease Spread and an Application to the SARS Pandemic Pandemics can cause immense disruption and damage to communities and societies. Thus far, modeling of pandemics has focused on either large-scale difference equation models like the SIR and the SEIR models, or detailed micro-level simulations, which are harder to apply at a global scale. This paper introduces a hybrid model for pandemics considering both global and local spread of infections. We hypothesize that the spread of an infectious disease between regions is significantly influenced by global traffic patterns and the spread within a region is influenced by local conditions. Thus we model the spread of pandemics considering the connections between regions for the global spread of infection and population density based on the SEIR model for the local spread of infection. We validate our hybrid model by carrying out a simulation study for the spread of SARS pandemic of 2002-2003 using available data on population, population density, and traffic networks between different regions. While it is well-known that international relationships and global traffic patterns significantly influence the spread of pandemics, our results show that integrating these factors into relatively simple models can greatly improve the results of modeling disease spread.

negative: Pangolin homology associated with 2019-nCoV To explore potential intermediate host of a novel coronavirus is vital to rapidly control continuous COVID-19 spread. We found genomic and evolutionary evidences of the occurrence of 2019-nCoV-like coronavirus (named as Pangolin-CoV) from dead Malayan Pangolins. Pangolin-CoV is 91.02% and 90.55% identical at the whole genome level to 2019-nCoV and BatCoV RaTG13, respectively. Pangolin-CoV is the lowest common ancestor of 2019-nCoV and RaTG13. The S1 protein of Pangolin-CoV is much more closely related to 2019-nCoV than RaTG13. Five key amino-acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and 2019-nCoV but four amino-acid mutations occur in RaTG13. It indicates Pangolin-CoV has similar pathogenic potential to 2019-nCoV, and would be helpful to trace the origin and probable intermediate host of 2019-nCoV.

negative: Coronavirus (COVID-19): A Review of Clinical Features, Diagnosis, and Treatment Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. A total of six species have been identified to cause disease in humans. They are known to infect the neurological, respiratory, enteric, and hepatic systems. The past few decades have seen endemic outbreaks in the form of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome related coronavirus (SARS-CoV). Yet again, we see the emergence of another outbreak due to a new strain called the SARS-CoV-2 virus. The most recent outbreak initially presented as pneumonia of unknown etiology in a cluster of patients in Wuhan, China. The epicenter of infection was linked to seafood and exotic animal wholesale markets in the city. SARS-CoV-2 is highly contagious and has resulted in a rapid pandemic of COVID-19. As the number of cases continues to rise, it is clear that these viruses pose a threat to public health. This review will introduce a general overview of coronavirus and describe the clinical features, evaluation, and treatment of COVID-19 patients. It will also provide a means to raise awareness among primary and secondary healthcare providers during the current pandemic. Furthermore, our review focuses on the most up-to-date clinical information for the effective management, prevention, and counseling of patients worldwide.

negative: Severe Acute Respiratory Syndrome (SARS)

negative: Strong effect of socioeconomic levels on the spread and treatment of the 2019 novel coronavirus (COVID-19) in China Background: Global response to the COVID-19 epidemic presents strengths and weaknesses in national and regional social governance capacities to address public health challenges. The emergence, detection, spread, treatment and containment of infectious diseases shows the considerable political and economic impacts in a highly interconnected world. We aimed to estimate the effects of socioeconomic levels on the spread and treatment of COVID-19 in China. Methods: We obtained daily COVID-19 cases at a city level in China. We used migration data from the major cities in Hubei Province, and macroeconomic data at city and province levels. We obtained social management measures in response to COVID-19 outbreak. We assessed the association between measures, migration and COVID-19 spread, and the association between socioeconomic levels and COVID-19 treatment capacity. Findings: On January 1, 2020, COVID-19 spread that affected by management measures and migration started across China. After Wuhan lockdown, the case number reached peak in 12 days, and COVID-19 outbreak was basically contained in China in four weeks due to intensive measures. Guangdong, Jiangsu and Zhejiang Provinces showed the most excellent COVID-19 treatment capacities. Socioeconomic levels in these provinces ranked top in China. Guangdong achieved the largest decline in severe case rate by 22.1%. Jiangsu had the lowest average rate of severe cases (1.7%) and zero death. Among the regions with top case number, Zhejiang showed the highest rate of cured cases on confirmed cases (96.3%), the lowest average rate of severe cases (7.7%), and one death. The COVID-19 treatment capacities were strongly affected by regional economics and measures on control, detection and treatment. Interpretation: Socioeconomic levels had strong effect on the spread and treatment of COVID-19 in China. Further investigations are needed on the effectiveness of Chinese measures and the effects of socioeconomic levels on COVID-19 treatment outside China. Fund Guangdong Natural Science Foundation

negative: How related is SARS-CoV-2 to other coronaviruses?

negative: Epidemiology of Coronavirus COVID-19: Forecasting the Future Incidence in Different Countries This paper forecasts the future spread of COVID-19 by exploiting the identified lead-lag effects between different countries. Specifically, we first determine the past relation among nations with the aid of dynamic time warping. This procedure allows an elastic adjustment of the time axis to find similar but phase-shifted sequences. Afterwards, the established framework utilizes information about the leading country to predict the Coronavirus spread of the following nation. The presented methodology is applied to confirmed Coronavirus cases from 1 January 2020 to 28 March 2020. Our results show that China leads all other countries in the range of 29 days for South Korea and 44 days for the United States. Finally, we predict a future collapse of the healthcare systems of the United Kingdom and Switzerland in case of our explosion scenario.

negative: Estimating the size of COVID-19 epidemic outbreak In this work, we analyze the epidemic data of cumulative infected cases collected from many countries as reported by WHO starting from January 21st,2020 and up till March 21st,2020. Our inspection is motivated by the renormalization group (RG) framework. Here we propose the RG-inspired logistic function of the form αE(t) = a(1 + ec(t-t0))-n as an epidemic strength function with n being asymmetry in the modified logistic function. We perform the non-linear least-squares analysis with data from various countries. The uncertainty for model parameters is computed using the squared root of the corresponding diagonal components of the covariance matrix. We carefully divide countries under consideration into 2 categories based on the estimation of the inflection point: the maturing phase and the growth-dominated phase. We observe that long-term estimations of cumulative infected cases of countries in the maturing phase for both n=1 and n≠ 1 are close to each other. We find from the value of root mean squared error (RMSE) that the RG-inspired logistic model with n≠ 1 is slightly preferable in this category. We also argue that n determines the characteristic of the epidemic at an early stage. However, in the second category, the estimated asymptotic number of cumulative infected cases contain rather large uncertainty. Therefore, in the growth-dominated phase, we focus on using n≠ 1 for countries in this phase. Some of them are in an early stage of an epidemic with an insufficient amount of data leading to a large uncertainty on parameter fits. In terms of the accuracy of the size estimation, the results do strongly depend on limitations on data collection and the epidemic phase for each country.

negative: Characterizing super-spreading in microblog: An epidemic-based information propagation model Abstract As the microblogging services are becoming more prosperous in everyday life for users on Online Social Networks (OSNs), it is more favorable for hot topics and breaking news to gain more attraction very soon than ever before, which are so-called “super-spreading events”. In the information diffusion process of these super-spreading events, messages are passed on from one user to another and numerous individuals are influenced by a relatively small portion of users, a.k.a. super-spreaders. Acquiring an awareness of super-spreading phenomena and an understanding of patterns of wide-ranged information propagations benefits several social media data mining tasks, such as hot topic detection, predictions of information propagation, harmful information monitoring and intervention. Taking into account that super-spreading in both information diffusion and spread of a contagious disease are analogous, in this study, we build a parameterized model, the SAIR model, based on well-known epidemic models to characterize super-spreading phenomenon in tweet information propagation accompanied with super-spreaders. For the purpose of modeling information diffusion, empirical observations on a real-world Weibo dataset are statistically carried out. Both the steady-state analysis on the equilibrium and the validation on real-world Weibo dataset of the proposed model are conducted. The case study that validates the proposed model shows that the SAIR model is much more promising than the conventional SIR model in characterizing a super-spreading event of information propagation. In addition, numerical simulations are carried out and discussed to discover how sensitively the parameters affect the information propagation process.

negative: GeoWeb and crisis management: issues and perspectives of volunteered geographic information Mapping, and more generally geopositioning, has become ubiquitous on the Internet. This democratization of geomatics through the GeoWeb results in the emergence of a new form of mapping based on Web 2.0 technologies. Described as Web-mapping 2.0, it is especially characterized by high interactivity and geolocation-based contents generated by users. A series of recent events (hurricanes, earthquakes, pandemics) have urged the development of numerous mapping Web applications intended to provide information to the public, and encourage their contribution to support crisis management. This new way to produce and spread geographic information in times of crisis brings up many questions and new potentials with regard to urgency services, Non Governmental Organisations (NGO), as well as individuals. This paper aims at putting into perspective the development of GeoWeb, both in terms of technologies and applications, against crisis management processes.

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: Uncertainties about the transmission routes of 2019 novel coronavirus

negative: Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number [Formula: see text]). We found that in countries with low connectivity to China but with relatively high [Formula: see text] , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low [Formula: see text] benefit the most from policies that further reduce [Formula: see text]. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.

negative: Association between short-term exposure to air pollution and COVID-19 infection: Evidence from China Abstract The novel coronavirus pneumonia, namely COVID-19, has become a global public health problem. Previous studies have found that air pollution is a risk factor for respiratory infection by carrying microorganisms and affecting body's immunity. This study aimed to explore the relationship between ambient air pollutants and the infection caused by the novel coronavirus. Daily confirmed cases, air pollution concentration and meteorological variables in 120 cities were obtained from January 23, 2020 to February 29, 2020 in China. We applied a generalized additive model to investigate the associations of six air pollutants (PM2.5, PM10, SO2, CO, NO2 and O3) with COVID-19 confirmed cases. We observed significantly positive associations of PM2.5, PM10, NO2 and O3 in the last two weeks with newly COVID-19 confirmed cases. A 10-μg/m3 increase (lag0–14) in PM2.5, PM10, NO2, and O3 was associated with a 2.24% (95% CI: 1.02 to 3.46), 1.76% (95% CI: 0.89 to 2.63), 6.94% (95% CI: 2.38 to 11.51), and 4.76% (95% CI: 1.99 to 7.52) increase in the daily counts of confirmed cases, respectively. However, a 10-μg/m3 increase (lag0–14) in SO2 was associated with a 7.79% decrease (95% CI: −14.57 to −1.01) in COVID-19 confirmed cases. Our results indicate that there is a significant relationship between air pollution and COVID-19 infection, which could partially explain the effect of national lockdown and provide implications for the control and prevention of this novel disease.

negative: [Analysis of application of herd immunity as a control strategy for COVID-19]. Novel coronavirus spreads very fast and is not easy to control. It has spread over 200 countries or territories. China has taken action to implement containment strategies, including active COVID-19 case finding, tracing, and 14-day quarantine of close contacts, and home isolation of 1.39 billion of people countywide for at least 2 weeks, etc. The combination of these strategies has brought the epidemic under control in China. The United Kingdom had deliberately not implemented containment measures for a while, instead opting to allow herd immunity strategy to develop over time. This is a "do-nothing" strategy whereby the virus is allowed to move through communities naturally until certain proportion of people has been infected, and the epidemic ends without intervention. The author assesses containment strategies versus this herd immunity strategy in real-world application to the COVID-19 epidemic. The author suggests an innovative strategy to balance controlling the epidemic and preventing impediment to economic and social development.

negative: The Role of Personality and Linguistic Patterns in Discriminating Between Fake News Spreaders and Fact Checkers Users play a critical role in the creation and propagation of fake news online by consuming and sharing articles with inaccurate information either intentionally or unintentionally. Fake news are written in a way to confuse readers and therefore understanding which articles contain fabricated information is very challenging for non-experts. Given the difficulty of the task, several fact checking websites have been developed to raise awareness about which articles contain fabricated information. As a result of those platforms, several users are interested to share posts that cite evidence with the aim to refute fake news and warn other users. These users are known as fact checkers. However, there are users who tend to share false information, who can be characterised as potential fake news spreaders. In this paper, we propose the CheckerOrSpreader model that can classify a user as a potential fact checker or a potential fake news spreader. Our model is based on a Convolutional Neural Network (CNN) and combines word embeddings with features that represent users’ personality traits and linguistic patterns used in their tweets. Experimental results show that leveraging linguistic patterns and personality traits can improve the performance in differentiating between checkers and spreaders.

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: Phase- and epidemic region-adjusted estimation of the number of coronavirus disease 2019 cases in China The outbreak of the coronavirus disease 2019 was first reported in Wuhan in December 2019 and gradually spread to other areas in China. After implementation of prevention and control measures, the estimation of the epidemic trend is needed. A phase- and region-adjusted SEIR model was applied for modeling and predicting the number of cases in Wuhan, Hubei Province and regions outside Hubei Province in China. The estimated number of infections could reach its peak in late February 2020 in Wuhan and Hubei Province, which is 55 303–84 520 and 83 944–129 312, respectively, while the epidemic peaks in regions outside Hubei Province in China could appear on February 13, 2020 with the estimated 13 035–19 108 cases. According to the estimation, the outbreak would abate in March and April all over China. Current estimation provided evidence for planned work resumption under stringent prevention and control in China to further support the fight against the epidemic. Nevertheless, there is still possibility of the second outbreak brought by the work resumption and population migration, especially from Hubei Province and high intensity cities outside Hubei Province. Strict prevention and control measures still need to be considered in the regions with high intensity of epidemic and densely-populated cities.

negative: COVID-19: Melatonin as a potential adjuvant treatment Abstract This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis. The recent outbreak of COVID-19 has become a pandemic with tens of thousands of infected patients. Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology. This leads to a cytokine storm and subsequent progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and often death. Melatonin, a well-known anti-inflammatory and anti-oxidative molecule, is protective against ALI/ARDS caused by viral and other pathogens. Melatonin is effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes for COVID-19 patients. Notably, melatonin has a high safety profile. There is significant data showing that melatonin limits virus-related diseases and would also likely be beneficial in COVID-19 patients. Additional experiments and clinical studies are required to confirm this speculation.

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: Estimating cost-benefit of quarantine length for COVID-19 mitigation Background: The international community has been put in an unprecedented situation by the COVID-19 pandemic. Creating models to describe and quantify alternative mitigation strategies becomes increasingly urgent. Methods: In this study, we propose an agent-based model of disease transmission in a society divided into closely connected families, workplaces, and social groups. This allows us to discuss mitigation strategies, including targeted quarantine measures. Results: We find that workplace and more diffuse social contacts are roughly equally important to disease spread, and that an effective lockdown must target both. We examine the cost-benefit of replacing a lockdown with tracing and quarantining contacts of the infected. Quarantine can contribute substantially to mitigation, even if it has short duration and is done within households. When reopening society, testing and quarantining is a strategy that is much cheaper in terms of lost workdays than a long lockdown of workplaces. Conclusions: A targeted quarantine strategy is quite efficient with only 5 days of quarantine, and its relative effect increases when supplemented with other measures that reduce disease transmission.

negative: Investigating duration and intensity of Covid-19 social-distancing strategies The exponential character of the recent Covid-19 outbreak requires a change in strategy from containment to mitigation. Meanwhile, most countries apply social distancing with the objective to keep the number of critical cases below the capabilities of the health care system. Due to the novelty and rapid spread of the virus, an a priori assessment of this strategy was not possible. In this study, we present a model-based systems analysis to assess the effectiveness of social distancing measures in terms of intensity and duration of application. Results show a super-linear scaling between intensity (percent contact reduction) and required duration of application to have an added value (lower fatality rate). This holds true for an effective reproduction of R > 1 and is reverted for R < 1. If R is not reduced below 1, secondary effects of required long-term isolation are likely to unravel the added value of disease mitigation. We recommend an extinction strategy implemented by intense countermeasures.

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: 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: Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV/SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R(0) of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious, and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of R(t). In the first assumption, R(t) was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with R(t) = 1.9, 2.6, or 3.1. The number of infections would reach 11,044, 70,258, and 227,989, respectively, by 29 February 2020. In the second assumption, R(t) was assumed to gradually decrease at different phases from high level of transmission (R(t) = 3.1, 2.6, and 1.9) to below 1 (R(t) = 0.9 or 0.5) owing to increasingly implemented public health intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077–84,520 or 55,869–81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce R(t) to an ideal level and control the infection.

negative: Covert coronavirus infections could be seeding new outbreaks.

negative: Social determinants of health inequalities: towards a theoretical perspective using systems science A systems approach offers a novel conceptualization to natural and social systems. In recent years, this has led to perceiving population health outcomes as an emergent property of a dynamic and open, complex adaptive system. The current paper explores these themes further and applies the principles of systems approach and complexity science (i.e. systems science) to conceptualize social determinants of health inequalities. The conceptualization can be done in two steps: viewing health inequalities from a systems approach and extending it to include complexity science. Systems approach views health inequalities as patterns within the larger rubric of other facets of the human condition, such as educational outcomes and economic development. This anlysis requires more sophisticated models such as systems dynamic models. An extension of the approach is to view systems as complex adaptive systems, i.e. systems that are 'open' and adapt to the environment. They consist of dynamic adapting subsystems that exhibit non-linear interactions, while being 'open' to a similarly dynamic environment of interconnected systems. They exhibit emergent properties that cannot be estimated with precision by using the known interactions among its components (such as economic development, political freedom, health system, culture etc.). Different combinations of the same bundle of factors or determinants give rise to similar patterns or outcomes (i.e. property of convergence), and minor variations in the initial condition could give rise to widely divergent outcomes. Novel approaches using computer simulation models (e.g. agent-based models) would shed light on possible mechanisms as to how factors or determinants interact and lead to emergent patterns of health inequalities of populations.

negative: The global battle against SARS-CoV-2 and COVID-19

negative: Effects of media reporting on mitigating spread of COVID-19 in the early phase of the outbreak. The 2019 novel coronavirus disease (COVID-19) is running rampantly in China and is swiftly spreading to other countries in the world, which causes a great concern on the global public health. The absence of specific therapeutic treatment or effective vaccine against COVID-19 call for other avenues of the prevention and control measures. Media reporting is thought to be effective to curb the spreading of an emergency disease in the early stage. Cross-correlation analysis based on our collected data demonstrated a strong correlation between media data and the infection case data. Thus we proposed a deterministic dynamical model to examine the interaction of the disease progression and the media reports and to investigate the effectiveness of media reporting on mitigating the spread of COVID-19. The basic reproduction number was estimated as 5.3167 through parameterization of the model with the number of cumulative confirmed cases, the number of cumulative deaths and the daily number of media items. Sensitivity analysis suggested that, during the early phase of the COVID-19 outbreak, enhancing the response rate of the media reporting to the severity of COVID-19, and enhancing the response rate of the public awareness to the media reports, both can bring forward the peak time and reduce the peak size of the infection significantly. These findings suggested that besides improving the medical levels, media coverage can be considered as an effective way to mitigate the disease spreading during the initial stage of an outbreak.

negative: Estimating Potential Infection Transmission Routes in Hospital Wards Using Wearable Proximity Sensors BACKGROUND: Contacts between patients, patients and health care workers (HCWs) and among HCWs represent one of the important routes of transmission of hospital-acquired infections (HAI). A detailed description and quantification of contacts in hospitals provides key information for HAIs epidemiology and for the design and validation of control measures. METHODS AND FINDINGS: We used wearable sensors to detect close-range interactions (“contacts”) between individuals in the geriatric unit of a university hospital. Contact events were measured with a spatial resolution of about 1.5 meters and a temporal resolution of 20 seconds. The study included 46 HCWs and 29 patients and lasted for 4 days and 4 nights. 14,037 contacts were recorded overall, 94.1% of which during daytime. The number and duration of contacts varied between mornings, afternoons and nights, and contact matrices describing the mixing patterns between HCW and patients were built for each time period. Contact patterns were qualitatively similar from one day to the next. 38% of the contacts occurred between pairs of HCWs and 6 HCWs accounted for 42% of all the contacts including at least one patient, suggesting a population of individuals who could potentially act as super-spreaders. CONCLUSIONS: Wearable sensors represent a novel tool for the measurement of contact patterns in hospitals. The collected data can provide information on important aspects that impact the spreading patterns of infectious diseases, such as the strong heterogeneity of contact numbers and durations across individuals, the variability in the number of contacts during a day, and the fraction of repeated contacts across days. This variability is however associated with a marked statistical stability of contact and mixing patterns across days. Our results highlight the need for such measurement efforts in order to correctly inform mathematical models of HAIs and use them to inform the design and evaluation of prevention strategies.

negative: More effective strategies are required to strengthen public awareness of COVID-19: Evidence from Google Trends BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has posed stress on the health and well-being of both Chinese people and the public worldwide. Global public interest in this new issue largely reflects people’s attention to COVID-19 and their willingness to take precautionary actions. This study aimed to examine global public awareness of COVID-19 using Google Trends. METHODS: Using Google Trends, we retrieved public query data for terms of “2019-nCoV + SARS-CoV-2 + novel coronavirus + new coronavirus + COVID-19 + Corona Virus Disease 2019” between the 31(st) December 2019 and the 24(th) February 2020 in six major English-speaking countries, including the USA, the UK, Canada, Ireland, Australia, and New Zealand. Dynamic series analysis demonstrates the overall change trend of relative search volume (RSV) for the topic on COVID-19. We compared the top-ranking related queries and sub-regions distribution of RSV about COVID-19 across different countries. The correlation between daily search volumes on the topic related to COVID-19 and the daily number of people infected with SARS-CoV-2 was analyzed. RESULTS: The overall search trend of RSV regarding COVID-19 increased during the early period of observing time and reached the first apex on 31(st) January 2020. A shorter response time and a longer duration of public attention to COVID-19 was observed in public from the USA, the UK, Australia, and Canada, than that in Ireland and New Zealand. A slightly positive correlation between daily RSV about COVID-19 and the daily number of confirmed cases was observed (P < 0.05). People across countries presented a various interest to the RSV on COVID-19, and public awareness of COVID-19 was different in various sub-regions within countries. CONCLUSIONS: The results suggest that public response time to COVID-19 was different across countries, and the overall duration of public attention was short. The current study reminds us that governments should strengthen the publicity of COVID-19 nationally, strengthen the public's vigilance and sensitivity to COVID-19, inform public the importance of protecting themselves with enough precautionary measures, and finally control the spread of COVID-19 globally.

negative: Neonatal Resuscitation Where the Mother Has a Suspected or Confirmed Novel Coronavirus (SARS-CoV-2) Infection: Suggestion for a Pragmatic Action Plan Coronavirus disease 2019 (COVID-19), caused by the novel SARS-CoV-2 virus, is rapidly spreading across the world. As the number of infections increases, those of infected pregnant women and children will rise as well. Controversy exists whether COVID-19 can be transmitted in utero and lead to disease in the newborn. As this chance cannot be ruled out, strict instructions for the management of mothers and newborn infants are mandatory. This perspective aims to be a practical support tool for the planning of delivery and neonatal resuscitation of infants born by mothers with suspected or confirmed COVID-19 infection.

negative: Diarrhea may be underestimated: a missing link in 2019 novel coronavirus The outbreak of pneumonia caused by the 2019 Novel Coronavirus (2019-nCoV) was reported in Wuhan City, China. However, the clinical symptoms varied in different reports. Based on the results of inter-group difference test, we found that the incidence of diarrhea differed in three recent reports. As 2019-nCoV utilizes the same cell entry receptor ACE2 as severe acute respiratory syndrome coronavirus (SARS-CoV) and ACE2 tightly controls intestinal inflammation, to trace the route of infection mediated by 2019-nCoV, we used the single-cell RNA sequencing data for analysis. We found that the ACE2 mRNA was highly expressed in the healthy human small intestine rather than the lung. Besides, single-cell RNA sequencing data showed that ACE2 was significantly elevated in the proximal and distal enterocytes, where the small intestinal epithelium is exposed to the foreign pathogen. Thus, we suspect that ACE2-expressing small intestinal epithelium cells might be vulnerable to 2019-nCoV infection when people eat infected wild animals and diarrhea may serve as an indicator for infection, suggesting that clinicians should pay more attention to patients with diarrhea during the outbreak of pneumonia.

negative: Severe Acute Respiratory Syndrome (SARS) in a Liver Transplant Recipient and Guidelines for Donor SARS Screening Severe acute respiratory syndrome (SARS) is a recently described infectious entity with salient features of fever, headache and malaise, with rapid progression to pneumonitis. The etiology of SARS is likely a novel coronavirus. During the winter of 2003, an outbreak of SARS involving several hospitals occurred in Toronto, Canada. We describe a patient post liver transplant who contracted SARS and died during the outbreak, with subsequent infection of family and several health‐care workers. A novel coronavirus was detected in respiratory specimens by PCR. Due to the potential severity of SARS in transplant recipients and the large number of cases of SARS in the community, in order to avoid transmission of SARS from a donor, we developed guidelines for SARS screening of organ donors. A screening tool based on potential hospital SARS exposure, clinical symptoms, and epidemiological exposure was used to stratify donors as high, intermediate or low risk for SARS. As SARS spreads throughout the world, it may become an increasingly significant problem for transplant patients and programs.

negative: Novel Coronavirus 2019 (Covid-19) epidemic scale estimation: topological network-based infection dynamic model Backgrounds: An ongoing outbreak of novel coronavirus pneumonia (Covid-19) hit Wuhan and hundreds of cities, 29 territories globally. We present a method for scale estimation in dynamic while most of the researchers used static parameters. Methods: We use historical data and the SEIR model for important parameters assumption. And according to the timeline, we use dynamic parameters for infection topology network building. Also, the migration data is used for the Non-Wuhan area estimation which can be cross-validated for the Wuhan model. All data are from the public. Results: The estimated number of infections is 61,596 (95%CI: 58,344.02-64,847.98) by 25 Jan in Wuhan. And the estimation number of the imported cases from Wuhan of Guangzhou was 170 (95%CI: 161.27-179.26), infection scale in Guangzhou is 315 (95%CI: 109.20-520.79), while the imported cases are 168 and the scale of the infection is 339 published by the authority. Conclusions: Using dynamic network models and dynamic parameters for different time periods is an effective way of infection scale modeling.

negative: Air transportation, population density and temperature predict the spread of COVID-19 in Brazil There is evidence that COVID-19, the disease caused by the betacoronavirus SARS-CoV-2, is sensitive to environmental conditions. However, such conditions often correlate with demographic and socioeconomic factors at larger spatial extents, which could confound this inference. We evaluated the effect of meteorological conditions (temperature, solar radiation, air humidity and precipitation) on 292 daily records of cumulative number of confirmed COVID-19 cases across the 27 Brazilian capital cities during the 1st month of the outbreak, while controlling for an indicator of the number of tests, the number of arriving flights, population density, proportion of elderly people and average income. Apart from increasing with time, the number of confirmed cases was mainly related to the number of arriving flights and population density, increasing with both factors. However, after accounting for these effects, the disease was shown to be temperature sensitive: there were more cases in colder cities and days, and cases accumulated faster at lower temperatures. Our best estimate indicates that a 1 °C increase in temperature has been associated with a decrease in confirmed cases of 8%. The quality of the data and unknowns limit the analysis, but the study reveals an urgent need to understand more about the environmental sensitivity of the disease to predict demands on health services in different regions and seasons.

negative: COVID-19 and Iranian Medical Students; A Survey on Their Related-Knowledge, Preventive Behaviors and Risk Perception. BACKGROUND Since December 2019, a novel coronavirus disease (COVID-19) began its journey around the world. Medical students, as frontline healthcare workers, are more susceptible to be infected by the virus. The aim of this study was to assess COVID-19 related knowledge, self-reported preventive behaviors and risk perception among Iranian medical students within the first week after the onset of the outbreak in Iran. METHODS This cross-sectional study was conducted from 26th to 28th of February, 2020. Participants were Iranian medical students (5th-7th year) whose knowledge, preventive behaviors and risk perceptions of COVID-19 were assessed using an online questionnaire. The questionnaire consisted of 26 questions including 15 items about COVID-19 related knowledge, 9 items regarding preventive measures and 2 items about COVID-19 risk perception. The validity and reliability of the questionnaire were shown to be satisfactory. RESULTS A total of 240 medical students completed the questionnaire. The mean age of participants was 23.67 years. The average of correct answers of knowledge was 86.96%; and 79.60% had high level of related knowledge. The average rate of practicing preventive behaviors was 94.47%; and 94.2% had high level of performance in preventive behaviors. The cumulative score of risk perception was 4.08 out of 8 which was in moderate range. Risk perception was significantly different between stagers and interns and between those being trained in emergency room (ER) and non-ER wards. There was a significant negative correlation between preventive behaviors and risk perception. CONCLUSION We found a high level of COVID-19 related knowledge and self-reported preventive behaviors and moderate risk perception among Iranian medical students.

negative: 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.

negative: Synergistic Inhibitor Binding to the Papain-Like Protease of Human SARS Coronavirus – Mechanistic and Inhibitor Design Implications We have previously developed two potent chemical classes that inhibit the essential papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, we applied a novel approach to identify small fragments that act synergistically with these inhibitors. A fragment library was screened in combination with four previously developed lead inhibitors by fluorescence-based enzymatic assays. Several fragment compounds synergistically enhanced the inhibitory activity of the lead inhibitors by approximately an order of magnitude. Surface plasmon resonance (SPR) measurements showed that three fragments bind specifically to the PLpro enzyme. Mode of inhibition, computational solvent mapping, and molecular docking studies suggest that these fragments bind adjacent to the binding site of the lead inhibitors and further stabilize the inhibitor-bound state. We propose potential next generation compounds based upon a computational, fragment-merging approach. This approach provides an alternative strategy for lead optimization in cases where direct co-crystallization is difficult.

negative: Early and late HHV-6 gene transcripts in multiple sclerosis lesions and normal appearing white matter Multiple sclerosis is an inflammatory demyelinating disease of the CNS, the aetiology of which is believed to have both genetic and environmental components. We have investigated one of the candidate viruses for the environmental component of multiple sclerosis, the neurotropic human herpesvirus 6 (HHV-6). Utilizing fluorescent in situ hybridization (FISH) techniques, we have examined human post-mortem tissues for the presence of immediate early and late viral gene expression in multiple sclerosis patient normal appearing white matter (NAWM), lesional tissue and normal control brain samples. HHV-6 gene transcription was detected in all tissue samples and was restricted to oligodendrocytes, as determined by double mRNA FISH analysis. Quantitative analysis of viral mRNA expression indicated that both NAWM and lesional multiple sclerosis samples exhibited significantly higher levels of HHV-6 expression compared with the normal control samples. Lesional samples exhibited the highest levels of viral gene expression, with NAWM exhibiting an intermediate level between lesional and control tissues. Immunofluorescence against early and late HHV-6 proteins verified active translation of HHV-6 viral mRNA in oligodendrocytes. Southern blot analysis of nested polymerase chain reactions using extracted genomic DNA and cDNA confirmed the presence of the HHV-6 genome in all individuals, with the active expression profile mirroring the FISH results. The frequent high level of HHV-6 infection in multiple sclerosis samples suggests a possible role in pathogenesis.

negative: 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.

negative: Emerging Infections: What Have We Learned from SARS?

negative: Connecting BCG Vaccination and COVID-19: Additional Data The reasons for a wide variation in severity of coronavirus disease 2019 (COVID-19) across the affected countries of the world are not known. Two recent studies have suggested a link between the BCG vaccination policy and the morbidity and mortality due to COVID-19. In the present study we compared the impact of COVID-19 in terms of case fatality rates (CFR) between countries with high disease burden and those with BCG revaccination policies presuming that revaccination practices would have provided added protection to the population against severe COVID-19. We found a significant difference in the CFR between the two groups of countries. Our data further supports the view that universal BCG vaccination has a protective effect on the course of COVID-19 probably preventing progression to severe disease and death. Clinical trials of BCG vaccine are urgently needed to establish its beneficial role in COVID-19 as suggested by the epidemiological data, especially in countries without a universal BCG vaccination policy. Keywords: COVID-19, BCG vaccination, case fatality ratio, mortality, low resource countries

negative: The Indian perspective of COVID-19 outbreak The emerging infection of COVID-19 was initiated from Wuhan, China, have been spread to more than 210 countries around the globe including India. The clinical symptoms of COVID-19 are very similar to other respiratory viruses. The number of laboratory-confirmed cases and associated deaths are increasing regularly in various parts of the World. Seven coronaviruses (229E, NL63, OC43, HKU1, SARS, MERS and, COVID-19) can naturally infect human beings. Out of these four (229E-CoV, NL63-CoV, OC43-CoV, HKU1-CoV) are responsible for mild upper respiratory infections, while SARS-CoV, MERS-CoV, and COVID-19 are well known for their high mortality. Few mild strains of coronaviruses are circulating in India but there is no evidence of SARS and MERS outbreaks. The COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality of COVID-19 is low as compared with SARS and MERS, the majority of its cases are recovered. The death toll of COVID-19 is high even after its low mortality because COVID-19 causes a pandemic while SARS-CoV and MERS-CoV cause epidemics only. COVID-19 influenced the large segments of the world population, which led to a public health emergency of international concern, putting all health organizations on high alert. COVID-19 is the first coronavirus after Spanish Flu 1918–1919, who has extremely influenced the health system, economy, and psychology of India. The present study review is on the general continent, virology, pathogenesis, global epidemiology, clinical presentation, diagnosis, treatment and control of COVID-19 with the reference to India.

negative: Bayesian Reconstruction of Disease Outbreaks by Combining Epidemiologic and Genomic Data Recent years have seen progress in the development of statistically rigorous frameworks to infer outbreak transmission trees (“who infected whom”) from epidemiological and genetic data. Making use of pathogen genome sequences in such analyses remains a challenge, however, with a variety of heuristic approaches having been explored to date. We introduce a statistical method exploiting both pathogen sequences and collection dates to unravel the dynamics of densely sampled outbreaks. Our approach identifies likely transmission events and infers dates of infections, unobserved cases and separate introductions of the disease. It also proves useful for inferring numbers of secondary infections and identifying heterogeneous infectivity and super-spreaders. After testing our approach using simulations, we illustrate the method with the analysis of the beginning of the 2003 Singaporean outbreak of Severe Acute Respiratory Syndrome (SARS), providing new insights into the early stage of this epidemic. Our approach is the first tool for disease outbreak reconstruction from genetic data widely available as free software, the R package outbreaker. It is applicable to various densely sampled epidemics, and improves previous approaches by detecting unobserved and imported cases, as well as allowing multiple introductions of the pathogen. Because of its generality, we believe this method will become a tool of choice for the analysis of densely sampled disease outbreaks, and will form a rigorous framework for subsequent methodological developments.

negative: About the Cover Vincent van Gogh (1853–1890). The Prison Courtyard (1890)

negative: A review of initial data on pregnancy during the COVID-19 outbreak: implications for assisted reproductive treatments The current outbreak of the novel 2019 coronavirus disease (COVID-19) started in China in December 2019 and has since spread to several other countries. On March 25, 2020, a total of 375,498 cases had been confirmed globally with 2,201 cases in Brazil, showing the urgency of reacting to this international public health emergency. While in most cases, mild symptoms are observed, in some cases the infection leads to serious pulmonary disease. As a result, the possible consequences of the COVID-19 outbreak for pregnant women and its potential effects on the management of assisted reproductive treatments, demand attention. In this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women, and discuss the current evidence of COVID-19 infections during pregnancy and its potential consequences for assisted reproductive treatments. Reported data suggest that symptoms in pregnant women are similar to those in other people, and that there is no evidence for higher maternal or fetal risks. However, considering the initial data and lack of comprehensive knowledge on the pathogenesis of SARS-CoV-2 during pregnancy, human reproduction societies have recommended postponing the embryo transfers and do not initiate new treatment cycles. New evidence must be considered carefully in order to adjust these recommendations accordingly at any time and to guide assisted reproductive treatments.

negative: Novel coronavirus infection and children. BACKGROUND AND AIM Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its outbreak in many states of the world, forced the World Health Organization (WHO) to declare a pandemic. Currently, COVID-19 has infected 1 991 562 patients causing 130 885 deaths globally as of 16 April 2020. The aim of this review is to underline the epidemiological, clinical and management characteristics in children affected by COVID-19. METHODS We searched Pubmed, from January to April 2020, for the following search terms: "COVID-19", "children", "SARS-COV2", "complications", "epidemiology", "clinical features", focusing our attention mostly on epidemiology and symptoms of COVID-19 in children. RESULTS Usually, infants and children present milder symptoms of the disease with a better outcome than adults. Consequently, children may be considered an infection reservoir that may play a role as spreader of the infection in community.

negative: Pathogenicity-associated protein domains: The fiercely-conserved evolutionary signatures Abstract Proteins have highly conserved domains that determine their functionality. Out of the thousands of domains discovered so far across all living forms, some of the predominant clinically-relevant domains include IENR1, HNHc, HELICc, Pro-kuma_activ, Tryp_SPc, Lactamase_B, PbH1, ChtBD3, CBM49, acidPPc, G3P_acyltransf, RPOL8c, KbaA, HAMP, HisKA, Hr1, Dak2, APC2, Citrate_ly_lig, DALR, VKc, YARHG, WR1, PWI, ZnF_BED, TUDOR, MHC_II_beta, Integrin_B_tail, Excalibur, DISIN, Cadherin, ACTIN, PROF, Robl_LC7, MIT, Kelch, GAS2, B41, Cyclin_C, Connexin_CCC, OmpH, Bac_rhodopsin, AAA, Knot1, NH, Galanin, IB, Elicitin, ACTH, Cache_2, CHASE, AgrB, PRP, IGR, and Antimicrobial21. These domains are distributed in nucleases/helicases, proteases, esterases, lipases, glycosylase, GTPases, phosphatases, methyltransferases, acyltransferase, acetyltransferase, polymerase, kinase, ligase, synthetase, oxidoreductase, protease inhibitors, nucleic acid binding proteins, adhesion and immunity-related proteins, cytoskeletal component-manipulating proteins, lipid biosynthesis and metabolism proteins, membrane-associated proteins, hormone-like and signaling proteins, etc. These domains are ubiquitous stretches or folds of the proteins in pathogens and allergens. Pathogenesis alleviation efforts can benefit enormously if the characteristics of these domains are known. Hence, this review catalogs and discusses the role of such pivotal domains, suggesting hypotheses for better understanding of pathogenesis at molecular level.

negative: An Evaluation of the Vulnerable Physician Workforce in the United States During the Coronavirus Disease-19 Pandemic Background: The coronavirus disease-19 (COVID-19) pandemic threatens to overwhelm the healthcare resources of the country, but also poses a personal hazard to healthcare workers, including physicians. To address the potential impact of excluding physicians with a high risk of adverse outcomes based on age, we evaluated the current patterns of age of licensed physicians across the United States. Methods: We compiled information from the 2018 database of actively licensed physicians in the Federation of State Medical Boards (FSMB) across the US. Both at a national- and the state-level, we assessed the number and proportion of physicians who would be at an elevated risk due to age over 60 years. Results: Of the 985,026 licensed physicians in the US, 235857 or 23.9% were aged 25-40 years, 447052 or 45.4% are 40-60 years, 191794 or 19.5% were 60-70 years, and 106121 or 10.8% were 70 years or older. Age was not reported in 4202 or 0.4% of physicians. Overall, 297915 or 30.2% of physicians were 60 years of age or older, 246167 (25.0%) 65 years and older, and 106121 (10.8%) 70 years or older. States in the US reported that a median 5470 licensed physicians (interquartile range [IQR], 2394 to 10108) were 60 years of age or older. Notably, states of North Dakota (n=1180) and Vermont (n = 1215) had the lowest and California (n=50786) and New York (n=31582) the highest number of physicians over the age of 60 years (Figure 1). Across states, the median proportion of physicians aged 60 years and older was 28.9% (IQR, 27.2%, 31.4%), and ranged between 25.9% for Nebraska to 32.6% for New Mexico (Figure 2). Discussion: Older physicians represent a large proportion of the US physician workforce, particularly in states with the worst COVID-19 outbreak. Therefore, their exclusion from patient care will be impractical. Optimizing care practices by limiting direct patient contact of physicians vulnerable to adverse outcomes from COVID-19, potentially by expanding their participation in telehealth may be a strategy to protect them.

negative: Better preventing and mitigating the effects of Covid-19 Currently, there are no proven medical treatments against SARS-CoV-2, the virus responsible for Covid-19. In addition to the all important public health measures needed to prevent the spread of this disease, a number of strategies related to our exposome are recommended herein, to better prevent and mitigate the effects of a SARS-CoV-2 infection through enhancement of our immune system and reduction of inflammation.

negative: Predicting the receptor-binding domain usage of the coronavirus based on kmer frequency on spike protein

negative: Inferring COVID-19 spreading rates and potential change points for case number forecasts As COVID-19 is rapidly spreading across the globe, short-term modeling forecasts provide time-critical information for decisions on containment and mitigation strategies. A main challenge for short-term forecasts is the assessment of key epidemiological parameters and how they change as first governmental intervention measures are showing an effect. By combining an established epidemiological model with Bayesian inference, we analyze the time dependence of the effective growth rate of new infections. For the case of COVID-19 spreading in Germany, we detect change points in the effective growth rate which correlate well with the times of publicly announced interventions.Thereby, we can (a) quantify the effects of recent governmental measures to mitigating the disease spread, and (b) incorporate analogue change points to forecast future scenarios and case numbers.Our code is freely available and can be readily adapted to any country or region.

negative: Coronaphobia: Fear and the 2019-nCoV outbreak

negative: Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV) that vary fundamentally in their virulence, but are indistinguishable by a number of diagnostic methods. This review focuses on all important steps every veterinary practitioner has to deal with and new diagnostic tests that can be considered when encountering a cat with suspected FIP with the aim to establish a definitive diagnosis. It gives an overview on all available direct and indirect diagnostic tests and their sensitivity and specificity reported in the literature in different sample material. By providing summarized data for sensitivity and specificity of each diagnostic test and each sample material, which can easily be accessed in tables, this review can help to facilitate the interpretation of different diagnostic tests and raise awareness of their advantages and limitations. Additionally, diagnostic trees depict recommended diagnostic steps that should be performed in cats suspected of having FIP based on their clinical signs or clinicopathologic abnormalities. These steps can easily be followed in clinical practice.

negative: An Evaluation of Publicly Available Deep Learning Based Commercial Information Retrieval Systems to search Biomedical Articles related to COVID-19 The COVID-19 pandemic has resulted in a tremendous need for access to the latest scientific information, primarily through the use of text mining and search tools. This has led to both corpora for biomedical articles related to COVID-19 (such as the CORD-19 corpus (Wang et al., 2020)) as well as search engines to query such data. While most research in search engines is performed in the academic field of information retrieval (IR), most academic search engines--though rigorously evaluated--are sparsely utilized, while major commercial web search engines (e.g., Google, Bing) dominate. This relates to COVID-19 because it can be expected that commercial search engines deployed for the pandemic will gain much higher traction than those produced in academic labs, and thus leads to questions about the empirical performance of these search tools. This paper seeks to empirically evaluate two such commercial search engines for COVID-19, produced by Google and Amazon, in comparison to the more academic prototypes evaluated in the context of the TREC-COVID track (Roberts et al., 2020). To ensure a fair comparison, we limit the number of documents in the retrieved runs and also annotate additional documents. We find that the top-performing system from TREC-COVID on bpref metric performed the best among the different systems evaluated in this study on all the metrics.

negative: Bat super immunity to lethal disease could help protect people

negative: The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020 A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred.

negative: COVID-19, superinfections and antimicrobial development: What can we expect? Coronavirus disease 2019 (COVID-19) arose at a time of great concern about antimicrobial resistance (AMR). No studies have specifically assessed COVID-19-associated superinfections or AMR. Based on limited data from case series, it is reasonable to anticipate that an appreciable minority of patients with severe COVID-19 will develop superinfections, most commonly pneumonia due to nosocomial bacteria and Aspergillus. Microbiology and AMR patterns are likely to reflect institutional ecology. Broad-spectrum antimicrobial use is likely to be widespread among hospitalized patients, both as directed and empiric therapy. Stewardship will have a crucial role in limiting unnecessary antimicrobial use and AMR. Congressional COVID-19 relief bills are considering antimicrobial reimbursement reforms and antimicrobial subscription models, but it is unclear if these will be included in final legislation. Prospective studies on COVID-19 superinfections are needed, data from which can inform rational antimicrobial treatment and stewardship strategies, and models for market reform and sustainable drug development.

negative: Cybercare 2.0: meeting the challenge of the global burden of disease in 2030 In this paper, we propose to advance and transform today’s healthcare system using a model of networked health care called Cybercare. Cybercare means “health care in cyberspace” — for example, doctors consulting with patients via videoconferencing across a distributed network; or patients receiving care locally — in neighborhoods, “minute clinics,” and homes — using information technologies such as telemedicine, smartphones, and wearable sensors to link to tertiary medical specialists. This model contrasts with traditional health care, in which patients travel (often a great distance) to receive care from providers in a central hospital. The Cybercare model shifts health care provision from hospital to home; from specialist to generalist; and from treatment to prevention. Cybercare employs advanced technology to deliver services efficiently across the distributed network — for example, using telemedicine, wearable sensors and cell phones to link patients to specialists and upload their medical data in near-real time; using information technology (IT) to rapidly detect, track, and contain the spread of a global pandemic; or using cell phones to manage medical care in a disaster situation. Cybercare uses seven “pillars” of technology to provide medical care: genomics; telemedicine; robotics; simulation, including virtual and augmented reality; artificial intelligence (AI), including intelligent agents; the electronic medical record (EMR); and smartphones. All these technologies are evolving and blending. The technologies are integrated functionally because they underlie the Cybercare network, and/or form part of the care for patients using that distributed network. Moving health care provision to a networked, distributed model will save money, improve outcomes, facilitate access, improve security, increase patient and provider satisfaction, and may mitigate the international global burden of disease. In this paper we discuss how Cybercare is being implemented now, and envision its growth by 2030.

negative: Emergence of SARS-like coronavirus in China: An update

negative: Passive immunotherapy of viral infections: ‘super-antibodies’ enter the fray Antibodies have been used for more than 100 years in the therapy of infectious diseases but a new generation of highly potent and/or broadly cross-reactive human monoclonal antibodies (sometimes referred to as ‘super-antibodies’) offers new opportunities for intervention. The isolation of these antibodies, which are often rarely induced in human infections, has primarily been achieved by large-scale screening for suitable donors and new single B cell approaches to human monoclonal antibody generation. Engineering the antibodies to improve half-life and effector functions has further augmented their in vivo activity in some cases. Super-antibodies offer promise for the prophylaxis and therapy of infections with a range of viruses, including those that are highly antigenically variable and those that are newly emerging or have pandemic potential. The next few years will be decisive in the realization of the promise of super-antibodies.

negative: Practical insights for paediatric otolaryngology surgical cases and performing microlaryngobronchoscopy during the COVID-19 pandemic Abstract Paediatric otolaryngology practice involves examining and operating in anatomical locations with high levels of aerosol generation and transmission of COVID-19 to treating clinicians, especially from the asymptomatic patient populations including children. During the COVID-19 pandemic all emergent otolaryngological conditions affecting the airway, oral, and nasal cavities should be managed medically where possible and any operating deferred. We present guidelines for operating on paediatric otolaryngological patients when necessary during the COVID-19 pandemic, and incorporate experience gathered during microlaryngobronchoscopy on a COVID-19 positive infant at our institution.

negative: Healthcare worker exposure to Middle East respiratory syndrome coronavirus (MERS-CoV): Revision of screening strategies urgently needed Abstract Objectives Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause frequent hospital outbreaks in Saudi Arabia, with emergency departments as the initial site of the spread of this virus. Methods The risk of transmission of MERS-CoV infection to healthcare workers (HCWs) was assessed in an outbreak in Riyadh. All HCWs with unprotected exposure to confirmed cases were tested after 24h of exposure. Two negative results for MERS-CoV obtained 3days apart and being free of any suggestive signs and symptoms were used to end the isolation of the HCWs and allow their return to duty. Results Overall 17 out of 879 HCWS with different levels of exposure tested positive for MERS-CoV. Of the 15 positive HCWS with adequate follow-up, 40% (6/15 HCWs) tested positive on the first sampling and 53% (8/15) tested positive on the second sampling. The time to negative results among the 15 positive HCWs ranged between 4 and 47days (average 14.5 days) and the infected HCWs needed on average two samples for clearance. All positive HCWs were either asymptomatic or had mild disease. Conclusions The data obtained in this study support the widespread testing of all close contacts of MERS-CoV cases, regardless of the significance of the contact or presence or absence of symptoms. In addition, urgent careful review of guidance regarding the return of asymptomatic MERS-CoV-positive HCWs under investigation to active duty is needed.

negative: Comparison of risk factors for viral and nonviral asthma exacerbations

negative: Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 Severe coronavirus disease 2019 (COVID-19) is commonly complicated with coagulopathy, the difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 has not been analyzed. Coagulation results and clinical features of consecutive patients with severe pneumonia induced by SARS-CoV2 (COVID group) and non-SARS-CoV2 (non-COVID group) in Tongji hospital were retrospectively analyzed and compared. Whether patients with elevated D-dimer could benefit from anticoagulant treatment was evaluated. There were 449 COVID patients and 104 non-COVID patients enrolled into the study. The 28-day mortality in COVID group was approximately twofold of mortality in non-COVID group (29.8% vs. 15.4%, P = 0.003), COVID group were older (65.1 ± 12.0 vs. 58.4 ± 18.0, years, P < 0.001) and with higher platelet count (215 ± 100 vs. 188 ± 98, ×10(9)/L, P = 0.015), comparing to non-COVID group. The 28-day mortality of heparin users were lower than nonusers In COVID group with D-dimer > 3.0 μg/mL (32.8% vs. 52.4%, P = 0.017). Patients with severe pneumonia induced by SARS-CoV2 had higher platelet count than those induced by non-SARS-CoV2, and only the former with markedly elevated D-dimer may benefit from anticoagulant treatment.

negative: Biological and Epidemiological Trends in the Prevalence and Mortality due to Outbreaks of Novel Coronavirus COVID-19 Abstract The novel coronavirus (Covid-19) infection outbreak has posed a major threat to international health system and economy. This study is aimed at investigating the biological and epidemiological trends in the prevalence and mortality due to outbreaks of novel coronavirus (COVID-19) infections. The data on the global outbreak of COVID-19, were obtained from World Health Organization (WHO), Worldometer, Centers for Disease Control and Prevention (CDC), and research institutes. The information was also recorded from research documents published in global scientific journals indexed in Pub Med and Institute of Scientific Information (ISI) Web of Science on the trends in the prevalence and mortality due to COVID-19 infection outbreaks. The results show rising trends in the transmission, prevalence and mortality rate due to coronavirus COVID-19. During the period of December 29, 2019 through March 31, 2020, it has infected 750890 people worldwide, resulting in 36405 deaths with a mortality rate of 4.84%. The infections were more frequent among male gender with above 60 years of age. The mean growth rate index for total number of cases from January 23 to March 31, 2020 was 1.20 and growth rate index for mortality rate was 1.12. There was a positive association between the prevalence and mortality rate (R2=0.996). The novel coronavirus COVID-19 is highly contagious and has affected a large number of people worldwide. It is still spreading with mutable prevalence and mortality outbreak trends. The global health officials have taken priority measures to prevent the further outbreaks of this emerging pathogen across the globe. However, the rising number of cases and mortality risk estimates are demonstrating that enhanced public health mediations, good hygienic conditions, social distancing and movement limitations may control the COVID-19 epidemics.

negative: Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM Since December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.

negative: COVID-19 Transmission in Dental Practice: Brief Review of Preventive Measures in Italy The outbreak and diffusion of SARS-CoV-2, responsible for the coronavirus disease (COVID-19), has caused an emergency in the health system worldwide. After a first development in Wuhan, China, the virus spread in other countries, with Italy registering the second highest number of cases in Europe on the 7th of April 2020 (135,586 in total). The World Health Organization declared the pandemic diffusion of COVID-19, and restrictive measures to limit contagion have been taken in several countries. The virus has a predominantly respiratory transmission through aerosol and droplets. The importance of infection control is therefore crucial in limiting the effects of virus diffusion. We aim to discuss the risks related to dental practice and current recommendations for dental practitioners. A literature search was performed to retrieve articles on the management of COVID-19 diffusion in dental practice. The documented clinical experience, the measures of professional prevention, and the actual Italian situation were reported and described. Four articles were retrieved from the literature search. Among the eligible articles, 3 reported measures to contrast COVID-19 diffusion. The infection management protocols suggested were reviewed. Finally, recommendations based on the Italian experience in terms of patient triage, patients' entrance into the practice, dental treatment, and after-treatment management are reported and discussed. COVID-19 is a major emergency worldwide, which should not be underestimated. Due to the rapidly evolving situation, further assessment of the implications of COVID-19 outbreak in dental practice is needed.

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

negative: No evidence of viral polymorphisms associated with Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS). Generally, children and teenagers do not become seriously ill with COVID-19. However, in countries with high rates of coronavirus disease, children with the syndrome COVID-19 associated inflammation syndrome referred to as PIMS-TS have been reported. Similarities noted between SARS-CoV-2 Spike protein sequences and those of other super antigens has prompted the suggestion that this might be the mechanism by SARS-CoV-ST triggers PIMS-TS. It has also been suggested that the D614G variant found more commonly in the US and across European countries may explain why PIMS-TS appears to be common in these countries. Here we analysed viral sequences from 13 paediatric COVID-19 patients of whom five were diagnosed with PIMS-TS. This is the first characterisation of viruses from PIMS-TS patients. In contrast to what has been hypothesised, we found no evidence of unique sequences associated with the viruses from PIMS-TS patients.

negative: Maximal Clique Based Influence Maximization in Networks Influence maximization is a fundamental problem in several real life applications such as viral marketing, recommendation system, collaboration and social networks. Maximizing influence spreading in a given network aims to find the initially active vertex set of size k called seed nodes (or initial spreaders (In this paper, we use seed set and initial spreaders interchangeably.)) which maximizes the expected number of the infected vertices. The state-of-the-art local-based techniques developed to solve this problem are based on local structure information such as degree centrality, nodes clustering coefficient, and others utilize the whole network structure, such as k-core decomposition, and node betweenness. In this paper, we aim at solving the problem of influence maximization using maximal clique problem. Our intuition is based on the fact that the presence of a dense neighborhood around a node is fundamental to the maximization of influence. Our approach follows the following three steps: (1) discovering all the maximal cliques from the complex network; (2) filtering the set of maximal cliques; we then denote the vertices belonging to the rest of maximal cliques as superordinate vertices, and (3) ranking the superordinate nodes according to some indicators. We evaluate the proposed framework empirically against several high-performing methods on a number of real-life datasets. The experimental results show that our algorithms outperform existing state-of-the-art methods in finding the best initial spreaders in networks.

negative: First month of the epidemic caused by COVID-19 in Italy: current status and real-time outbreak development forecast Background: The first outbreaks of COVID-19 in Italy occurred during the second half of February 2020 in some areas in the North of the country. Due to the high contagiousness of the infection, further spread by asymptomatic people, Italy has become in a few weeks the country with the greatest number of infected people after China. The large number of severe cases among infected people in Italy led to the hospitalization of thousands of patients, with a heavy burden on the National Health Service. Methods: We analyzed data provided daily by Italian Authorities for the period from 24 February 2020 to 26 March 2020. Considering such information, we developed a forecast model in real-time, based on the cumulative logistic distribution. We then produced an estimate of the overall number of potentially infected individuals and epidemic duration at a national and Regional level, for the most affected Regions. Results: We reported the daily distribution of performed swabs and confirmed cases, and the cumulative distribution of confirmed cases, of patients quarantined at home (42%), hospitalized in non-intensive care (31%), recovered or discharged (13%), deceased (10%), and hospitalized in intensive care (4%). The forecast model estimated a number of infected persons for Italy of 115,000 about, and a duration of the epidemic not less than 2 months. Conclusions: Once month after the first outbreaks there seems to be the first signs of a decrease in the number of infections, showing that we could be now facing the descending phase of the epidemic. The forecast obtained thanks to our model could be used by decision-makers to implement coordinative and collaborative efforts in order to control the epidemic.

negative: SARS Coronavirus Detection We developed a set of three real-time reverse transcription–polymerase chain reaction (PCR) assays that amplify three different regions of the SARS-associated coronavirus (SARS-CoV), can be run in parallel or in a single tube, and can detect <10 genome equivalents of SARS-CoV. The assays consider all currently available SARS-CoV sequences and are optimized for two prominent real-time PCR platforms.

negative: Climatic influences on the worldwide spread of SARS-CoV-2 The rapid global spread of the novel, pathogenic, SARS-CoV-2 causing the severe acute respiratory disease COVID-19, becomes a major health problem worldwide and pose the need for international predictive programs. Given the lack of both specific drugs and an efficient preventive vaccine, the expectation that SARS-CoV-2 transmission rate might decrease in temperate regions during summer, dominated the social scene. Here, we attempted a prediction of the worldwide spread of the infections based on climatic data, expressed by 19 bioclimatic variables. The calculated probability maps shown that potential areas of infection follow a shift from the Tropical to Temperate and Mediterranean Bioclimatic regions, and back to the Tropics again. Maps show an increased probability of infections in Europe, followed by an expansion covering areas of the Middle East and Northern Africa, as well as Eastern coastal areas of North America, South-Eastern coastal areas of Latin America and two areas of Southern Australia, and later return to areas of Southeastern Asia, in a manner similar to that of influenza strains (H3N2). Our approach may therefore be of value for the worldwide spread of SARS-CoV-2, suggesting an optimistic scenario of asynchronous seasonal global outbreaks, like other viral respiratory diseases. Consequently, we suggest the incorporation of a climatic impact in the design and implementation of public health policies. Maps of our model are available (constantly updated up to the saturation of the model) at: https://navaak.shinyapps.io/CVRisk/.

negative: How many are at increased risk of severe COVID-19 disease? Rapid global, regional and national estimates for 2020 Background The risk of severe COVID-19 disease is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 illness, and how this varies between countries may inform the design of possible strategies to shield those at highest risk. Methods We estimated the number of individuals at increased risk of severe COVID-19 disease by age (5-year age groups), sex and country (n=188) based on prevalence data from the Global Burden of Disease (GBD) study for 2017 and United Nations population estimates for 2020. We also calculated the number of individuals without an underlying condition that could be considered at-risk because of their age, using thresholds from 50-70 years. The list of underlying conditions relevant to COVID-19 disease was determined by mapping conditions listed in GBD to the guidelines published by WHO and public health agencies in the UK and US. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. Results We estimate that 1.7 (1.0 - 2.4) billion individuals (22% [15-28%] of the global population) are at increased risk of severe COVID-19 disease. The share of the population at increased risk ranges from 16% in Africa to 31% in Europe. Chronic kidney disease (CKD), cardiovascular disease (CVD), diabetes and chronic respiratory disease (CRD) were the most prevalent conditions in males and females aged 50+ years. African countries with a high prevalence of HIV/AIDS and Island countries with a high prevalence of diabetes, also had a high share of the population at increased risk. The prevalence of multimorbidity (>1 underlying conditions) was three times higher in Europe than in Africa (10% vs 3%). Conclusion Based on current guidelines and prevalence data from GBD, we estimate that one in five individuals worldwide has a condition that is on the list of those at increased risk of severe COVID-19 disease. However, for many of these individuals the underlying condition will be undiagnosed or not severe enough to be captured in health systems, and in some cases the increase in risk may be quite modest. There is an urgent need for robust analyses of the risks associated with different underlying conditions so that countries can identify the highest risk groups and develop targeted shielding policies to mitigate the effects of the COVID-19 pandemic.

negative: Infection control practices for SARS in Lao People's Democratic Republic, Taiwan, and Thailand: Experience from mobile SARS containment teams, 2003 BACKGROUND: Despite available recommendations on infection control for severe acute respiratory syndrome (SARS), information is limited on actual practices in Asian hospitals during the epidemic. We describe practices observed by mobile SARS containment teams (mobile teams) during outbreak investigations. METHODS: We retrospectively summarized infection control practices observed in hospitals visited by mobile teams in the Lao People's Democratic Republic (PDR), Taiwan, and Thailand, during March and April 2003. RESULTS: Mobile teams investigated 22 reports of SARS in 20 hospitals (1, 5, and 14 hospitals in Lao PDR, Taiwan, and Thailand, respectively). Facilities ranged from urban hospitals with negative-pressure isolation rooms and high-efficiency particulate air filtration to rural hospitals with patient rooms open to outside air circulation and intermittent running water. At the time of mobile team visits, 5 (25%) hospitals implemented infection control practices consistent with World Health Organization recommendations on visitor policies, private negative-pressure rooms, and personal protective equipment. CONCLUSIONS: Early in the SARS epidemic, mobile teams found wide variations in infection control practices and resources among Asian hospitals evaluating patients for SARS, indicating the importance of ongoing assessment during SARS preparedness. Mobile teams are one mechanism to assess practices and promote implementation of recommended infection control measures.

negative: SARS‐CoV‐2 and human milk: What is the evidence? The novel coronavirus SARS‐CoV‐2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS‐CoV‐2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS‐CoV‐2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS‐CoV in human milk (it was negative); and no published data on MERS‐CoV and human milk. We identified 13 studies reporting human milk tested for SARS‐CoV‐2; one study (a non‐peer‐reviewed preprint) detected the virus in one milk sample, and another study detected SARS‐CoV‐2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS‐CoV‐2) during breastfeeding are discussed.

negative: Symptom-Based Isolation Policies: Evidence from a Mathematical Model of Outbreaks of Influenza and COVID-19 BACKGROUND: Controlling the transmission of respiratory infections such as influenza and COVID-19 is a critical public health priority. Non-pharmaceutical intervention policies such as community quarantines, closures and travel bans are often implemented in emergencies but many of them are disruptive and difficult to maintain for extended periods of time. A promising alternative recommended by the CDC for influenza is requiring individuals showing fever symptoms to remain isolated at home until they are fever-free for at least one day, but there is limited evidence to support the effectiveness of such symptom-based isolation policies. METHODS: Here we introduce a computational model of symptom-based isolation that accounts for the timing of symptoms, viral shedding and the population structure. It was validated on outbreaks of influenza in schools and modified to account for COVID-19. It was then used to estimate the outbreak curves and the attack rates (the proportion of the population infected) under one or more days of fever-based isolation. RESULTS: Using the model we find evidence that symptom-based isolation policies could reduce the attack rates of both influenza and COVID-19 outbreaks, and flatten the outbreak curves. Specifically, we found that across a range of influenza scenarios, a CDC-recommended policy of one day isolation following fever can reduce the attack rate from 27% of the population to 12%, and to 3% if the isolation is extended to two days. In COVID-19 transmission, we estimate that implementing one day post-fever isolation would reduce the attack rate from 79% to 71%, and there is possible benefit from isolation for six days. In both influenza and COVID-19, the policies are predicted to reduce the peak number of infected but not shorten the outbreak duration. CONCLUSIONS: Symptom-based isolation could be an important tool to control influenza and COVID-19 outbreaks in schools, and potentially other settings. We recommend that schools implement a post-fever isolation policy of two days for influenza and six days for COVID-19.

negative: Microecology of Infections Associated with Surgery and Trauma Trauma is one of the leading worldwide causes of death at present and fatal trauma cases are the fourth highest cause of death in youths. As a consequence of improved emergency medical treatment, early death rates (48 h post injury) have been significantly reduced. However, death rates resulting from trauma-related complications have not diminished. The most common and dangerous complication that can develop post surgery/trauma is infection caused by opportunistic pathogens, which pose a significant challenge to the healing process ([1]). In addition to interference with the healing process and direct damage to infected tissues caused by the infecting organism, systemic complications, including acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), systemic inflammatory response syndrome (SIRS) and acute renal failure (ARF) can develop. These complications significantly exacerbate a patient’s already deteriorating health and increase recovery times that correlate directly with increased mortality. Therefore, these infections are a major threat to trauma patients, early detection and control of respective infectious agents is essential in decreasing the rates of post trauma-associated morbidity and mortality.

negative: Antibody-Validated Proteins in Inflamed Islets of Fulminant Type 1 Diabetes Profiled by Laser-Capture Microdissection Followed by Mass Spectrometry BACKGROUND: There are no reports of proteomic analyses of inflamed islets in type 1 diabetes. PROCEDURES: Proteins expressed in the islets of enterovirus-associated fulminant type 1 diabetes (FT1DM) with extensive insulitis were identified by laser-capture microdissection mass spectrometry using formalin-fixed paraffin-embedded pancreatic tissues. RESULTS: Thirty-eight proteins were identified solely in FT1DM islets, most of which have not been previously linked to type 1 diabetes. Five protein-protein interacting clusters were identified, and the cellular localization of selected proteins was validated immunohistochemically. Migratory activity-related proteins, including plastin-2 (LCP1), moesin (MSN), lamin-B1 (LMNB1), Ras GTPase-activating-like protein (IQGAP1) and others, were identified in CD8(+) T cells and CD68(+) macrophages infiltrated to inflamed FT1DM islets. Proteins involved in successive signaling in innate/adaptive immunity were identified, including SAM domain and HD domain-containing protein 1 (SAMHD1), Ras GTPase-activating-like protein (IQGAP1), proteasome activator complex subunit 1 (PSME1), HLA class I histocompatibility antigen (HLA-C), and signal transducer and activator of transcription 1-alpha/beta (STAT1). Angiogenic (thymidine phosphorylase (TYMP)) and anti-angiogenic (tryptophan-tRNA ligase (WARS)) factors were identified in migrating CD8(+) T cells and CD68(+) macrophages. Proteins related to virus replication and cell proliferation, including probable ATP-dependent RNA helicase DEAD box helicase 5 (DDX5) and heterogeneous nuclear ribonucleoprotein H (HNRNPH1), were identified. The anti-apoptotic protein T-complex protein 1 subunit epsilon (CCT5), the anti-oxidative enzyme 6-phosphogluconate dehydrogenase (PDG), and the anti-viral and anti-apoptotic proteins serpin B6 (SERPINB6) and heat shock 70 kDa protein1-like (HSPA1L), were identified in FT1DM-affected islet cells. CONCLUSION: The identified FT1DM-characterizing proteins include those involved in aggressive beta cell destruction through massive immune cell migration and proteins involved in angiogenesis and islet vasculature bleeding, cell repair, and anti-inflammatory processes. Several target proteins for future type 1 diabetes interventions were identified.

negative: Spread of the Novel Coronavirus (SARS-CoV-2): Modeling and Simulation of Control Strategies The coronavirus disease 2019 (COVID-19) is spreading throughout the world and all healthcare systems are loaded beyond its capacity. The virus is named as SARS-CoV-2. In this situation, rational decisions need to be made on how the care is provided for patients with COVID-19. The Incidence report, general symptoms and readily available testing kits, different control strategies, the basic compartmental model, and some of the current research on the epidemiology of the disease are discussed and previously published models are reviewed. Modeling this disease helps in understanding the spread, and predict its future to evaluate different control strategies (Social Distancing, Contact Tracing and Hospitalization). Compartmental modeling framework is used in this work. The non-linear equations are formulated and fitted to the cumulative case and mortality data. Analytical analysis along with uncertainty analysis and sensitivity analysis is performed, and the conditions to achieve disease free equilibrium is evaluated. Finally, Different control strategies are simulated to show their importance. This paper aims to shows the advantage of mathematical modeling and their simulations in times like now, during which the COVID-19 spreading like wildfire. It also includes Pre-symptomatic and asymptomatic individuals in the modeling. The simulations are performed for the model fit to Cumulative Case and Mortality data in the United States of America. The Reproduction number is found to be 2.71914.

negative: Epidemic Models of Contact Tracing: Systematic Review of Transmission Studies of Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome The emergence and reemergence of coronavirus epidemics sparked renewed concerns from global epidemiology researchers and public health administrators. Mathematical models that represented how contact tracing and follow-up may control Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) transmissions were developed for evaluating different infection control interventions, estimating likely number of infections as well as facilitating understanding of their likely epidemiology. We reviewed mathematical models for contact tracing and follow-up control measures of SARS and MERS transmission. Model characteristics, epidemiological parameters and intervention parameters used in the mathematical models from seven studies were summarized. A major concern identified in future epidemics is whether public health administrators can collect all the required data for building epidemiological models in a short period of time during the early phase of an outbreak. Also, currently available models do not explicitly model constrained resources. We urge for closed-loop communication between public health administrators and modelling researchers to come up with guidelines to delineate the collection of the required data in the midst of an outbreak and the inclusion of additional logistical details in future similar models.

negative: Identification of mesenchymal stromal cells in human lung parenchyma capable of differentiating into aquaporin 5-expressing cells. The lack of effective therapies for end-stage lung disease validates the need for stem cell-based therapeutic approaches as alternative treatment options. In contrast with exogenous stem cell sources, the use of resident progenitor cells is advantageous considering the fact that the lung milieu is an ideal and familiar environment, thereby promoting the engraftment and differentiation of transplanted cells. Recent studies have shown the presence of multipotent 'mesenchymal stem cells' in the adult lung. The majority of these reports are, however, limited to animal models, and to date, there has been no report of a similar cell population in adult human lung parenchyma. Here, we show the identification of a population of primary human lung parenchyma (pHLP) mesenchymal stromal cells (MSCs) derived from intraoperative normal lung parenchyma biopsies. Surface and intracellular immunophenotyping by flow cytometry revealed that cultures do not contain alveolar type I epithelial cells or Clara cells, and are devoid of the following hematopoietic markers: CD34, CD45 and CXCR4. Cells show an expression pattern of surface antigens characteristic of MSCs, including CD73, CD166, CD105, CD90 and STRO-1. As per bone marrow MSCs, our pHLP cells have the ability to differentiate along the adipogenic, osteogenic and chondrogenic mesodermal lineages when cultured in the appropriate conditions. In addition, when placed in small airway growth media, pHLP cell cultures depict the expression of aquaporin 5 and Clara cell secretory protein, which is identified with that of alveolar type I epithelial cells and Clara cells, respectively, thereby exhibiting the capacity to potentially differentiate into airway epithelial cells. Further investigation of these resident cells may elucidate a therapeutic cell population capable of lung repair and/or regeneration.

negative: Multiple drivers of the COVID-19 spread: role of climate, international mobility, and region-specific conditions The novel Coronavirus Disease 2019 (COVID-19) has spread quickly across the globe. Here, we evaluated the role of climate (temperature and precipitation), region-specific susceptibility (BCG vaccination, malaria infection, and elderly population) and international traveller population (human mobility) in shaping the geographical patterns of COVID-19 cases across 1,055 countries/regions, and examined the sequential shift of multiple drivers of the accumulated cases from December, 2019 to April 12, 2020. The accumulated numbers of COVID-19 cases (per 1 million population) were well explained by a simple regression model. The explanatory power (R2) of the model increased up to > 70% in April 2020 as the COVID-19 spread progressed. Climate, host mobility, and host susceptibility largely explained the variance of the COVID-19 cases (per 1 million population), and their explanatory power improved as the pandemic progressed; the relative importance of host mobility and host susceptibility have been greater than that of climate. The number of days from outbreak onset showed greater explanatory power in the earlier stages of COVID-19 spread but rapidly lost its influence. Our findings demonstrate that the COVID-19 pandemic is deterministically driven by climate suitability, cross-border human mobility, and region-specific susceptibility. The present distribution of COVID-19 cases has not reached an equilibrium and is changing daily, especially in the Southern Hemisphere. Nevertheless, the present results, based on mapping the spread of COVID-19 and identifying multiple drivers of this outbreak trajectory, may contribute to a better understanding of the COVID-19 disease transmission risk and the measures against long-term epidemic.

negative: Epidemiological and clinical characteristics of 136 cases of COVID-19 in main district of Chongqing Background We did a comprehensive exploration of the epidemiological and clinical characteristics of 136 patients with confirmed COVID-19 in main district of Chongqing which was adjacent to the west of Hubei province. Methods This study was conducted on 136 patients with COVID-19 in main district of Chongqing from Jan 25 to Feb 20, 2020. Data of patients included demographic, epidemiological, clinical features, chest radiographs of imported cases, local cases, second-generation cases and third-generation cases. Student's t-test was adopted for quantitative variables while Pearson Chi-squared test or Fisher's exact test for categorical variables. Results The median age was 47 years and common symptoms of illness were cough (50.7%), fever (47.1%) and fatigue (14.0%). The time from contact symptomatic case to illness was 7.7 days, and 88 patients (64.7%) were cluster cases, radiological evidence found bilateral lung involvement was common (57.4%).Compared with the imported cases, the local cases were significantly older, the proportion of men is lower. There was higher proportion of cluster cases in local cases. Unlike imported cases, which fever was the dominant symptom, the local cases have more cough patients, with a significant higher proportion of asymptomatic patients. The third-generation cases have a significant higher proportion of asymptomatic patients. Conclusions We concluded the epidemiological and clinical characteristics of the cases andsuggested to take more comprehensive measures for screening patients, especially for elderly person, avoid family gatherings, and implement more closely surveillance of suspect patients and their close contacts.

negative: GIS-based spatial modeling of COVID-19 incidence rate in the continental United States Abstract During the first 90 days of the COVID-19 outbreak in the United States, over 675,000 confirmed cases of the disease have been announced, posing unprecedented socioeconomic burden to the country. Due to inadequate research on geographic modeling of COVID-19, we investigated county-level variations of disease incidence across the continental United States. We compiled a geodatabase of 35 environmental, socioeconomic, topographic, and demographic variables that could explain the spatial variability of disease incidence. Further, we employed spatial lag and spatial error models to investigate spatial dependence and geographically weighted regression (GWR) and multiscale GWR (MGWR) models to locally examine spatial non-stationarity. The results suggested that even though incorporating spatial autocorrelation could significantly improve the performance of the global ordinary least square model; these models still represent a significantly poor performance compared to the local models. Moreover, MGWR could explain the highest variations (adj. R2: 68.1%) with the lowest AICc compared to the others. Mapping the effects of significant explanatory variables (i.e., income inequality, median household income, the proportion of black females, and the proportion of nurse practitioners) on spatial variability of COVID-19 incidence rates using MGWR could provide useful insights to policymakers for targeted interventions.

negative: Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling Positive-sense RNA viruses hijack intracellular membranes that provide niches for viral RNA synthesis and a platform for interactions with host proteins. However, little is known about host factors at the interface between replicase complexes and the host cytoplasm. We engineered a biotin ligase into a coronaviral replication/transcription complex (RTC) and identified >500 host proteins constituting the RTC microenvironment. siRNA-silencing of each RTC-proximal host factor demonstrated importance of vesicular trafficking pathways, ubiquitin-dependent and autophagy-related processes, and translation initiation factors. Notably, detection of translation initiation factors at the RTC was instrumental to visualize and demonstrate active translation proximal to replication complexes of several coronaviruses. Collectively, we establish a spatial link between viral RNA synthesis and diverse host factors of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA viruses and provide a starting point for a comprehensive analysis of critical virus-host interactions that represent targets for therapeutic intervention.

negative: Response to the COVID-19 Epidemic: The Chinese Experience and Implications for Other Countries The ongoing outbreak of the novel coronavirus disease (COVID-19) that occurred in China is rapidly spreading globally. China’s bond and strict containment measures have been proved (in practice) to significantly reduce the spread of the epidemic. This was obtained through the use of emergency control measures in the epidemic areas and the integration of resources from multiple systems, including business, community, technology, education, and transportation, across the country. In order to better understand how China has managed to reduce the public health and economic impacts of the COVID-19 epidemic, this editorial systematically reviews the specific measures for infection prevention and control of the disease. The best practices for COVID-19 eradication in China provide evidence-based strategies that could be replicated in other countries.

negative: NSAIDs in patients with viral infections, including Covid-19: victims or perpetrators? Abstract Taking anti-inflammatory drugs, including non-steroidal (NSAIDs), during Covid-19 infection, how much is risky? The French Minister of Health, who has raised an alarm on a possible risk deriving from the use of ibuprofen for the control of fever and other symptoms during the disease, opened the debate a few days ago. In this paper we examine available evidence from preclinical and clinical studies that had analysed the role of COX in the inflammatory process and the effects of NSAIDs in patients with infections. Most of the published studies that suggested not protective effects of NSAIDs were mainly performed in vitro or on animals. Therefore, their meaning in humans is to be considered with great caution. Based also on data suggesting protective effects of NSAIDs, we concluded that currently there is no evidence suggesting a correlation between NSAIDs and a worsening of infections. Further studies will be certainly needed to better define the role of NSAIDs and particularly COX2 inhibitors in patients with infections. In the meantime, we must wait for results of the revision started by the PRAC on May 2019 on the association ibuprofen/ketoprofen and worsening of infections. Since nowadays no scientific evidence establishes a correlation between NSAIDS and worsening of COVID-19, patients should be advice against any NSAIDs self-medication when COVID-19 like symptoms are present.

negative: Clinical features and sexual transmission potential of SARS-CoV-2 infected female patients: a descriptive study in Wuhan, China Background: As of March 2, 2020, SARS-CoV-2 has infected more than 80174 people and caused 2915 deaths in China. This virus rapidly spreads to 56 countries worldwide. Thus, in order to effectively block its transmission, it is urgent to uncover all the possible transmission routes of SARS-CoV-2. Methods: From January 28 to February 18, 2020, 35 female patients diagnosed with COVID-19 in Tongji Hospital were included in this descriptive study. The gynecologic history, clinical characteristics, laboratory findings and chest computed tomography (CT) of all patients were recorded in detail. To examine whether there is sexual transmission through vaginal from female to her partner, we employed real-time polymerase chain reaction testing (RT-PCR) to detect SARS-CoV-2 in vaginal environment (including vaginal discharge, cervical or vaginal residual exfoliated cells) and anal swab samples, and inquired recent sexual behaviors from the patients. Findings: The age range of the 35 patients with COVID-19 was 37-88 years. Over 50% patients infected with SARS-CoV-2 had chronic diseases. We tested the vaginal environment and anal swabs from the 35 female patients with COVID-19 and found that only an anal swab sample from one patient was positive for SARS-CoV-2. All the samples from vaginal environment were negative for SARS-CoV-2. The infection rate of the patients' sexual partner was 42.9%. Additionally, two female patients admitted having sex with their partners during a possible infection incubation period, while one patient's partner was uninfected and the other patient's partner was diagnosed with COVID-19 (after the diagnosis of the female patient). Conclusion: No positive RT-PCR result was found in the vaginal environment perhaps due to the lack of ACE2 expression, which is the receptor of SARS-CoV-2, in the vagina and cervix tissues (human protein atlas). The results from this study show no evidence of transmission of SARS-CoV-2 through vaginal sex from female to her partner. However, the risk of infection of non vaginal sex and other intimate contacts during vaginal sex should not be ignored.

negative: Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China Background: Since mid-December 2019, a cluster of pneumonia-like diseases caused by a novel coronavirus, now designated COVID-19 by the WHO, emerged in Wuhan city and rapidly spread throughout China. Here we identify the clinical characteristics of COVID-19 in a cohort of patients in Shanghai. Methods: Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, laboratory and radiological features. Results: Of 198 patients, the median duration from disease onset to hospital admission was 4 days. The mean age of the patients was 50.1 years, and 51.0% patients were male. The most common symptom was fever. Less than half of the patients presented with respiratory systems including cough, sputum production, itchy or sore throat, shortness of breath, and chest congestion. 5.6% patients had diarrhoea. On admission, T lymphocytes were decreased in 45.8% patients. Ground glass opacity was the most common radiological finding on chest computed tomography. 9.6% were admitted to the ICU because of the development of organ dysfunction. Compared with patients not treated in ICU, patients treated in the ICU were older, had longer waiting time to admission, fever over 38.5o C, dyspnoea, reduced T lymphocytes, elevated neutrophils and organ failure. Conclusions: In this single centre cohort of COVID-19 patients, the most common symptom was fever, and the most common laboratory abnormality was decreased blood T cell counts. Older age, male, fever over 38.5oC, symptoms of dyspnoea, and underlying comorbidity, were the risk factors most associated with severity of disease. Key words: 2019 novel coronavirus; acute respiratory infection; risk factors for disease severity

negative: Automatic Textual Evidence Mining in COVID-19 Literature We created this EVIDENCEMINER system for automatic textual evidence mining in COVID-19 literature. EVIDENCEMINER is a web-based system that lets users query a natural language statement and automatically retrieves textual evidence from a background corpora for life sciences. It is constructed in a completely automated way without any human effort for training data annotation. EVIDENCEMINER is supported by novel data-driven methods for distantly supervised named entity recognition and open information extraction. The named entities and meta-patterns are pre-computed and indexed offline to support fast online evidence retrieval. The annotation results are also highlighted in the original document for better visualization. EVIDENCEMINER also includes analytic functionalities such as the most frequent entity and relation summarization.

negative: ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics BACKGROUND: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. METHODS: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. RESULTS: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as "bridge regions" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. CONCLUSIONS: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.

negative: Severe acute respiratory syndrome from the trenches, at a Singapore university hospital Summary The epidemiology and virology of severe acute respiratory syndrome (SARS) have been written about many times and several guidelines on the infection control and public health measures believed necessary to control the spread of the virus have been published. However, there have been few reports of the problems that infectious disease clinicians encounter when dealing with the protean manifestations of this pathogen. This is a qualitative account of some of the issues faced by an infectious disease physician when identifying and treating patients with SARS as well as protecting other healthcare workers and patients, including: identification of the chain of contagion, early recognition of the disease in the absence of a reliable and rapid diagnostic test, appropriate use of personal protective equipment, and the use of isolation to prevent super-spreading events. Many issues need to be addressed if clinicians are to be able to manage the virus should it reappear.

negative: 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.

negative: Comparative Epidemiology of Human Infections with Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome Coronaviruses among Healthcare Personnel The largest nosocomial outbreak of Middle East respiratory syndrome (MERS) occurred in South Korea in 2015. Health Care Personnel (HCP) are at high risk of acquiring MERS-Coronavirus (MERS-CoV) infections, similar to the severe acute respiratory syndrome (SARS)-Coronavirus (SARS-CoV) infections first identified in 2003. This study described the similarities and differences in epidemiological and clinical characteristics of 183 confirmed global MERS cases and 98 SARS cases in Taiwan associated with HCP. The epidemiological findings showed that the mean age of MERS-HCP and total MERS cases were 40 (24~74) and 49 (2~90) years, respectively, much older than those in SARS [SARS-HCP: 35 (21~68) years, p = 0.006; total SARS: 42 (0~94) years, p = 0.0002]. The case fatality rates (CFR) was much lower in MERS-HCP [7.03% (9/128)] or SARS-HCP [12.24% (12/98)] than the MERS-non-HCP [36.96% (34/92), p<0.001] or SARS-non-HCP [24.50% (61/249), p<0.001], however, no difference was found between MERS-HCP and SARS-HCP [p = 0.181]. In terms of clinical period, the days from onset to death [13 (4~17) vs 14.5 (0~52), p = 0.045] and to discharge [11 (5~24) vs 24 (0~74), p = 0.010] and be hospitalized days [9.5 (3~22) vs 22 (0~69), p = 0.040] were much shorter in MERS-HCP than SARS-HCP. Similarly, days from onset to confirmation were shorter in MERS-HCP than MERS-non-HCP [6 (1~14) vs 10 (1~21), p = 0.044]. In conclusion, the severity of MERS-HCP and SARS-HCP was lower than that of MERS-non-HCP and SARS-non-HCP due to younger age and early confirmation in HCP groups. However, no statistical difference was found in MERS-HCP and SARS-HCP. Thus, prevention of nosocomial infections involving both novel Coronavirus is crucially important to protect HCP.

negative: Mathematical Modeling of Coronavirus Reproduction Rate with Policy and Behavioral Effects In this paper a modified mathematical model based on the SIR model used which can predict the spreading of the corona virus disease (COVID-19) and its effects on people in the days ahead. This model takes into account all the death, infected and recovered characteristics of this disease. To determine the extent of the risk posed by this novel coronavirus; the transmission rate (R0) is utilized for a time period from the beginning of spreading virus. In particular, it includes a novel policy to capture the R0 response in the virus spreading over time. The model estimates the vulnerability of the pandemic with a prediction of new cases by estimating a time-varying R0 to capture changes in the behavior of SIR model implies to new policy taken at different times and different locations of the world. This modified SIR model with the different values of R0 can be applied to different country scenario using the real time data report provided by the authorities during this pandemic. The effective evaluation of R0 can forecast the necessity of lockdown as well as reopening the economy.

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: COVID-19, Patents and the Never-Ending Tension between Proprietary Rights and the Protection of Public Health

negative: An Epidemic Model SIPHERD and its application for prediction of the spread of COVID-19 infection for India and USA We propose an epidemic model SIPHERD in which three categories of infection carriers Symptomatic, Purely Asymptomatic, and Exposed are considered with different rates of transmission of infection that are taken dependent on the lockdown and social distancing. The rate of detection of the infected carriers is taken dependent on the tests done per day. The model is applied for the COVID outbreak in Germany and South Korea to validate its predictive capabilities and then applied to India and the United States for the prediction of its spread with different lockdown situations and testing in the coming months.

negative: Características de las infecciones respiratorias agudas causadas por los coronavirus OC43, NL63 y 229E Resumen Antecedentes y objetivos Las infecciones respiratorias agudas son una entidad muy frecuente en la población general. La mayoría de ellas son debidas a infecciones víricas. Este estudio pretende precisar las características clínicas y epidemiológicas de los pacientes adultos con infección respiratoria por los coronavirus OC43, NL63 y 229E. Pacientes y métodos Entre enero del 2013 y febrero del 2014 se estudió prospectivamente a todos los pacientes con sospecha clínica de infección respiratoria mediante la toma de un frotis faríngeo y la realización de una reacción en cadena de la polimerasa en transcripción reversa en tiempo real en búsqueda de coronavirus. Resultados En 48 casos (7,0% de los 686 pacientes incluidos; 12,6% de los 381 en los que se detectó algún virus) se pudo demostrar la presencia de algún coronavirus. En 24 casos se trataba del OC43 (50%), en 14 del NL63 (29%) y en 10 del 229E (21%). La edad media fue de 54,5 años, con un ligero predominio de varones. Las presentaciones clínicas más frecuentes fueron el cuadro gripal inespecífico (43,7%), la neumonía (29,2%) y la agudización de enfermedad pulmonar obstructiva crónica (8,3%). El 52% de los pacientes precisaron ingreso hospitalario, en 2 ocasiones en cuidados intensivos. No se produjo ningún fallecimiento. Conclusión Las infecciones respiratorias agudas causadas por coronavirus inciden preferentemente en varones fumadores en la edad media de la vida, frecuentemente afectados de enfermedades previas. La sintomatología clínica mas frecuente ha sido el cuadro gripal inespecífico. Abstract Background and objectives Acute respiratory infection is a very common condition in the general population. The majority of these infections are due to viruses. This study attempted to determine the clinical and epidemiological characteristics of adult patients with respiratory infection by the coronavirus OC43, NL63 and 229E. Patients and methods Between January 2013 and February 2014, we prospectively studied all patients with suspected clinical respiratory infection by taking throat swabs and performing a reverse transcription polymerase chain reaction in search of coronavirus. Results In 48 cases (7.0% of the 686 enrolled patients; 12.6% of the 381 in whom a virus was detected) the presence of a coronavirus demonstrated. In 24 cases, the virus was OC43 (50%); in 14 cases, the virus was NL63 (29%); and in 10 cases, the virus was 229E (21%). The mean age was 54.5 years, with a slight predominance of men. The most common clinical presentations were nonspecific influenza symptoms (43.7%), pneumonia (29.2%) and chronic obstructive pulmonary disease exacerbation (8.3%). Fifty-two percent of the patients required hospitalization, and 2 patients required intensive care. There were no deaths. Conclusion Acute respiratory infections caused by coronavirus mainly affect middle-aged male smokers, who are often affected by previous diseases. The most common clinical picture has been nonspecific influenza symptoms.

negative: Taking Account of Asymptomatic Infections in Modeling the Transmission Potential of the COVID-19 Outbreak on the Diamond Princess Cruise Ship We take the case of the Diamond Princess (DP) cruise ship as an experimental model for studying the transmission potential of COVID-19 in a closed environment. We investigate the changes in R0 for COVID-19 on the DP from January 21 to February 19, 2020 with a chain-binomial model at different times under two scenarios: no quarantine assuming a random mixing condition, and quarantine of passengers in cabins -- passengers may get infected either by an infectious case in a shared cabin or by asymptomatic crew who continued to work. Our modeling approach takes account of the asymptomatic ratio of crew members during the quarantine of passengers, which has not been explored in the literature. Assuming an asymptomatic ratio 0.505 and the proportion of infections in cabins 0.2, R0 at the beginning of the epidemic was 3.27 (95% CI (3.02, 3.54)) and 3.78 (95% CI (3.49, 4.09)) respectively for serial intervals of 5 and 6 days, and increased for passengers in contact with asymptomatic crew during quarantine. We find evidence to support a CDC report that "a high proportion of asymptomatic infections could partially explain the high attack rate among cruise ship passengers and crew." This emphasizes the importance of improved reporting and quarantine of asymptomatic cases, and raises questions on quarantine procedures in closed environments such as military vessels, cruise ships, dormitories, prisons, and other enclosed living complexes with high population densities.

negative: Reproductive number of COVID-19: A systematic review and meta-analysis based on global level evidence Background The coronavirus (COVID-19) is now a global concern because of its higher transmission capacity and associated adverse consequences including death. The reproductive number of COVID-19 provides an estimate on the possible extent of the transmission. This study aims to provide the average reproductive number of COVID-19 based on available global level evidence. Methods We searched three databases (PubMed, Web of Science, and Science Direct) to find studies reported the reproductive number of COVID-19. The searches were conducted using a pre-specified search strategy that includes keywords of COVID-19 and its reproductive number related terms, which were combined using the Boolean operators. Narrative synthesis was used to explain the studies included and the meta-analysis was used to estimate the average reproduction number of COVID-19. Results Total of 30 studies included in this review whereas 24 of them were included in the meta-analysis. The average estimated reproductive number was 2.70 (95% CI, 2.21-3.30). We found evidence of very high heterogeneity (99.5%) of the reproductive numbers reported in the included studies. The highest reproductive number was reported for Diamond Princes Cruise Ship, Japan (14.8). In the country-level, the higher reproductive number was reported for France (R, 6.32, 95% CI, 5.72-6.98) following Germany (R, 6.07, 95% CI, 5.51-6.69) and Spain (R, 5.08, 95% CI, 4.50-5.73). We also found estimation models, methods, and the number of cases considered to estimate reproductive number were played a role in arising the heterogeneity of the estimated reproductive number. Conclusion The estimated reproductive number indicates an exponential increase of COVID-19 infection in the coming days. Comprehensive policies and programs are important to reduce new infections as well as the associated adverse consequences including death.

negative: À propos de chirurgie et COVID-19 : quelques précautions complémentaires. Réponse à : « Stratégie pour la pratique de la chirurgie digestive et oncologique en situation d’épidémie de COVID-19 »()

negative: Towards Characterizing COVID-19 Awareness on Twitter The coronavirus (COVID-19) pandemic has significantly altered our lifestyles as we resort to minimize the spread through preventive measures such as social distancing and quarantine. An increasingly worrying aspect is the gap between the exponential disease spread and the delay in adopting preventive measures. This gap is attributed to the lack of awareness about the disease and its preventive measures. Nowadays, social media platforms (ie., Twitter) are frequently used to create awareness about major events, including COVID-19. In this paper, we use Twitter to characterize public awareness regarding COVID-19 by analyzing the information flow in the most affected countries. Towards that, we collect more than 46K trends and 622 Million tweets from the top twenty most affected countries to examine 1) the temporal evolution of COVID-19 related trends, 2) the volume of tweets and recurring topics in those trends, and 3) the user sentiment towards preventive measures. Our results show that countries with a lower pandemic spread generated a higher volume of trends and tweets to expedite the information flow and contribute to public awareness. We also observed that in those countries, the COVID-19 related trends were generated before the sharp increase in the number of cases, indicating a preemptive attempt to notify users about the potential threat. Finally, we noticed that in countries with a lower spread, users had a positive sentiment towards COVID-19 preventive measures. Our measurements and analysis show that effective social media usage can influence public behavior, which can be leveraged to better combat future pandemics.

negative: COVID‐2019: The role of the nsp2 and nsp3 in its pathogenesis Last December 2019, a new virus, named novel Coronavirus (COVID‐2019) causing many cases of severe pneumonia was reported in Wuhan, China. The virus knowledge is limited and especially about COVID‐2019 pathogenesis. The Open Reading Frame 1ab (ORF1ab) of COVID‐2019 has been analyzed to evidence the presence of mutation caused by selective pressure on the virus. For selective pressure analysis fast‐unconstrained Bayesian approximation (FUBAR) was used. Homology modelling has been performed by SwissModel and HHPred servers. The presence of transmembrane helical segments in Coronavirus ORF1ab non structural protein 2 (nsp2) and nsp3 was tested by TMHMM, MEMSAT, and MEMPACK tools. Three‐dimensional structures have been analyzed and displayed using PyMOL. FUBAR analysis revealed the presence of potential sites under positive selective pressure (P < .05). Position 723 in the COVID‐2019 has a serine instead a glycine residue, while at aminoacidic position 1010 a proline instead an isoleucine. Significant (P < .05) pervasive negative selection in 2416 sites (55%) was found. The positive selective pressure could account for some clinical features of this virus compared with severe acute respiratory syndrome (SARS) and Bat SARS‐like CoV. The stabilizing mutation falling in the endosome‐associated‐protein‐like domain of the nsp2 protein could account for COVID‐2019 high ability of contagious, while the destabilizing mutation in nsp3 proteins could suggest a potential mechanism differentiating COVID‐2019 from SARS. These data could be helpful for further investigation aimed to identify potential therapeutic targets or vaccine strategy, especially in the actual moment when the epidemic is ongoing and the scientific community is trying to enrich knowledge about this new viral pathogen.

negative: Structural disorder in the proteome and interactome of Alkhurma virus (ALKV) Infection by the Alkhurma virus (ALKV) leading to the Alkhurma hemorrhagic fever is a common thread in Saudi Arabia, with no efficient treatment or prevention available as of yet. Although the rational drug design traditionally uses information on known 3D structures of viral proteins, intrinsically disordered proteins (i.e., functional proteins that do not possess unique 3D structures), with their multitude of disorder-dependent functions, are crucial for the biology of viruses. Here, viruses utilize disordered regions in their invasion of the host organisms and in hijacking and repurposing of different host systems. Furthermore, the ability of viruses to efficiently adjust and accommodate to their hostile habitats is also intrinsic disorder-dependent. However, little is currently known on the level of penetrance and functional utilization of intrinsic disorder in the ALKV proteome. To fill this gap, we used here multiple computational tools to evaluate the abundance of intrinsic disorder in the ALKV genome polyprotein. We also analyzed the peculiarities of intrinsic disorder predisposition of the individual viral proteins, as well as human proteins known to be engaged in interaction with the ALKV proteins. Special attention was paid to finding a correlation between protein functionality and structural disorder. To the best of our knowledge, this work represents the first systematic study of the intrinsic disorder status of ALKV proteome and interactome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-018-2968-8) contains supplementary material, which is available to authorized users.

negative: Public perceptions of non-pharmaceutical interventions for reducing transmission of respiratory infection: systematic review and synthesis of qualitative studies BACKGROUND: Non-pharmaceutical public health interventions may provide simple, low-cost, effective ways of minimising the transmission and impact of acute respiratory infections in pandemic and non-pandemic contexts. Understanding what influences the uptake of non-pharmaceutical interventions such as hand and respiratory hygiene, mask wearing and social distancing could help to inform the development of effective public health advice messages. The aim of this synthesis was to explore public perceptions of non-pharmaceutical interventions that aim to reduce the transmission of acute respiratory infections. METHODS: Five online databases (MEDLINE, PsycINFO, CINAHL, EMBASE and Web of Science) were systematically searched. Reference lists of articles were also examined. We selected papers that used a qualitative research design to explore perceptions and beliefs about non-pharmaceutical interventions to reduce transmission of acute respiratory infections. We excluded papers that only explored how health professionals or children viewed non-pharmaceutical respiratory infection control. Three authors performed data extraction and assessment of study quality. Thematic analysis and components of meta-ethnography were adopted to synthesise findings. RESULTS: Seventeen articles from 16 studies in 9 countries were identified and reviewed. Seven key themes were identified: perceived benefits of non-pharmaceutical interventions, perceived disadvantages of non-pharmaceutical interventions, personal and cultural beliefs about infection transmission, diagnostic uncertainty in emerging respiratory infections, perceived vulnerability to infection, anxiety about emerging respiratory infections and communications about emerging respiratory infections. The synthesis showed that some aspects of non-pharmaceutical respiratory infection control (particularly hand and respiratory hygiene) were viewed as familiar and socially responsible actions to take. There was ambivalence about adopting isolation and personal distancing behaviours in some contexts due to their perceived adverse impact and potential to attract social stigma. Common perceived barriers included beliefs about infection transmission, personal vulnerability to respiratory infection and concerns about self-diagnosis in emerging respiratory infections. CONCLUSIONS: People actively evaluate non-pharmaceutical interventions in terms of their perceived necessity, efficacy, acceptability, and feasibility. To enhance uptake, it will be necessary to address key barriers, such as beliefs about infection transmission, rejection of personal risk of infection and concern about the potential costs and stigma associated with some interventions.

negative: SARS-CoV-2 and gastrointestinal tract: the dark side of the pandemic

negative: Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia BACKGROUND: The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. METHODS: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. RESULTS: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). CONCLUSIONS: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)

negative: The Powerful Immune System Against Powerful COVID-19: A Hypothesis Abstract On March 11, 2020, the World Health Organization declared the coronavirus outbreak a pandemic. Since December 2019, the world has experienced an outbreak of coronavirus disease 2019 (COVID-19). Epidemiology, risk factors, and clinical characteristics of patients with COVID-19 have been reported but the factors affecting the immune system against COVID-19 have not been well described. In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19.

negative: Nursing care of patients with severe acute respiratory syndrome in the intensive care unit: case reports in Hong Kong Abstract Severe acute respiratory syndrome (SARS) was diagnosed in more than 8437 patients in 25 countries between February and July 2003. During this period the World Health Organisation issued a global alert about SARS and together with the Centre for Disease Control have coordinated their efforts to investigate its pathogenesis and treatment. The outbreak in Hong Kong has been dramatic due to its geographical proximity with Guangdong province, China where the first case of SARS was reported. SARS has been described as a rapidly progressive, sometimes fatal pneumonia with a case fatality rate of 7.6% requiring intensive care. The four case reports illustrate a number of important points concerning the recognition, treatment, management and prevention of SARS, and highlights the importance of considering vigilant assessment and monitoring of patients with SARS. The purpose of this paper is to share our experiences in caring for critically ill patients with SARS in the intensive care unit to nurses globally in order to reduce SARS’ morbidity and mortality as well as to protect nurses and other healthcare workers from this disease that is so far threatening the community at large.

negative: Clinical course and mortality risk of severe COVID-19

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: Hong Kong under WHO spotlight after flu outbreak.

negative: The spread of the COVID‐19 coronavirus: Health agencies worldwide prepare for the seemingly inevitability of the COVID‐19 coronavirus becoming endemic While it is too late to confine the COVID‐19 coronovirus outbreak to China, a wealth of data spurs epidemiological and vaccine research. [Image: see text]

negative: Successful containment of COVID-19: the WHO-Report on the COVID-19 outbreak in China

negative: Evaluating new evidence in the early dynamics of the novel coronavirus COVID-19 outbreak in Wuhan, China with real time domestic traffic and potential asymptomatic transmissions The novel coronavirus (COVID-19), first detected in Wuhan, China in December 2019, has spread to 28 countries/regions with over 43,000 confirmed cases. Much about this outbreak is still unknown. At this early stage of the epidemic, it is important to investigate alternative sources of information to understand its dynamics and spread. With updated real time domestic traffic, this study aims to integrate recent evidence of international evacuees extracted from Wuhan between Jan. 29 and Feb. 2, 2020 to infer the dynamics of the COVD-19 outbreak in Wuhan. In addition, a modified SEIR model was used to evaluate the empirical support for the presence of asymptomatic transmissions. Based on the data examined, this study found little evidence for the presence of asymptomatic transmissions. However, it is still too early to rule out its presence conclusively due to sample size and other limitations. The updated basic reproductive number was found to be 2.12 on average with a 95% credible interval of [2.04, 2.18]. It is smaller than previous estimates probably because the new estimate factors in the social and non-pharmaceutical mitigation implemented in Wuhan through the evacuee dataset. Detailed predictions of infected individuals exported both domestically and internationally were produced. The estimated case confirmation rate has been low but has increased steadily to 23.37% on average. The findings of this study depend on the validity of the underlying assumptions, and continuing work is needed, especially in monitoring the current infection status of Wuhan residents.

negative: Clinical characteristics of novel coronavirus pneumonia in organ transplant recipients and management strategy during the epidemic (1st edition)/ 器官移植 In December 2019, a number of cases of pneumonia with unknown causes were successively reported in multiple hospitals in Wuhan City, Hubei Province, China. The pathogen is a novel coronavirus, which can lead to novel coronavirus pneumonia (COVID-19) and even threaten the patients' lives. In the following, the COVID-19 epidemic is spreading rapidly in many provinces and cities. It is particularly important to summarize and analyze the clinical characteristics of COVID-19 in solid organ transplantation (SOT) recipients and to optimize the prevention, early diagnosis and treatment strategies. Therefore, we organized Chinese experts in the field of organ transplantation to draft this article according to the characteristics of lung infection of SOT recipients and the characteristics of current COVID-19 by referring to relevant guidelines and specifications at home and abroad, aiming to provide reference for transplant physicians in China. This management strategy will be revised at any time with the deepening understanding of the COVID-19 infection.

negative: Comparison of clinical course of patients with severe acute respiratory syndrome among the multiple generations of nosocomial transmission. BACKGROUND Severe acute respiratory syndrome (SARS) is characterized by both an atypical pneumonia and efficient nosocomial transmission. However, it remains unknown whether the infectivity and the virulence of the pathogen will change throughout the successive transmission. This study was conducted to compare the clinical features and management regimens of patients with SARS among the multiple generations from nosocomial transmission initiated by a super-spreader. METHODS The clinical data of 84 epidemiologically-linked SARS patients from a hospital outbreak were retrospectively studied. All patients, in whom a clear-cut transmission generation could be noted, had a direct or indirect exposure to the index patient and the epidemic successively propagated through the multiple generations of cases within a short period of time. RESULTS There were 66 women and 18 men with mean age of (29.2 +/- 10.3) years in this cluster; and 96.4% of whom were health care workers. Detailed contact tracing identified 35 (41.7%) first-generation cases, 34 (40.5%) second-generation cases, and 15 (17.8%) third-generation cases. No statistical differences among the multiple generations of transmission were found in terms of age, gender, incubation period and length of hospital stay. With the advanced transmission generations, the initial temperature lowered, the number of cases with dry cough decreased. There were no statistical differences in the peak temperature and duration of fever, other accompanying symptoms, leucopenia; however, the time from initial pulmonary infiltrates to radiographic recovery shortened (P < 0.05). No differences were found in maximum number of lung fields involved, duration from the onset of fever to the occurrence of pulmonary infiltrates and time from the initial pulmonary infiltrate to its peak among the multiple transmission generations (P > 0.05). No statistical differences were found in modes of oxygen therapy and sorts of antibiotics prescribed among the various transmission generations (P > 0.05); however, as with the advanced transmission generations, the number of cases prescribed with methylprednisolone, human gamma-globulin, interferon-alpha, antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and time from admission to starting these medication shortened (P < 0.05). CONCLUSIONS There is no evidence that SARS infection will evolve or transmit within a fashion that permits it to become less powerful throughout the successive transmission within a short time.

negative: Evaluating the potential impact of targeted vaccination strategies against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks in the healthcare setting BACKGROUND: Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are two coronaviruses with demonstrated potential to generate significant nosocomial outbreaks. In particular, MERS continues to pose a significant threat in the Middle East since 2012. Currently, no licensed vaccine or drug treatment is available to treat patients infected with either coronavirus. However, there are some MERS vaccines in the preclinical stage of development. We sought to evaluate the potential impact of targeted vaccination strategies for mitigating SARS and MERS outbreaks in healthcare settings using simple mathematical models and detailed historic transmission trees describing the progression of past nosocomial outbreaks of SARS and MERS. RESULTS: Our findings suggest that vaccination strategies targeting patients and healthcare workers, which have been disproportionately affected during past outbreaks, and assuming two vaccination coverage levels at 50 and 75% have the potential to avert nearly 50% or more of MERS or SARS cases. CONCLUSION: Our modeling results informed by historic outbreak data for SARS and MERS suggest that vaccination strategies targeting patients could be an effective measure to mitigate and prevent outbreaks in the healthcare setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12976-019-0112-6) contains supplementary material, which is available to authorized users.

negative: Use Stones from Another Mountain to Polish One’s Jade: Learn from MERS Studies toexplore potential mechanisms underlying the effect of diabetes mellitus on COVID-19/ 中华内分泌代谢杂志 Epidemiology studies suggest that comorbid diabetes may have negative impact on the progression and severity of the coronavirus disease 2019 (COVID-19), which first occurred in Wuhan. However, the exact mechanism remains unclear. A recent study on another type of coronavirus infection, Middle East Respiratory Syndrome (MERS), investigated its relationship with diabetes. This essay aims to give a brief introduction to this report and related studies, and to propose suggestions on what we can learn from these investigations to conduct further studies on the potential mechanisms underlying the effect of diabetes mellitus on COVID-19.

negative: Design of Peptide-Based Nanovaccines Targeting Leading Antigens From Gynecological Cancers to Induce HLA-A2.1 Restricted CD8(+) T Cell Responses Gynecological cancers are a leading cause of mortality in women. CD8(+) T cell immunity largely correlates with enhanced survival, whereas inflammation is associated with poor prognosis. Previous studies have shown polystyrene nanoparticles (PSNPs) are biocompatible, do not induce inflammation and when used as vaccine carriers for model peptides induce CD8(+) T cell responses. Herein we test the immunogenicity of 24 different peptides, from three leading vaccine target proteins in gynecological cancers: the E7 protein of human papilloma virus (HPV); Wilms Tumor antigen 1 (WT1) and survivin (SV), in PSNP conjugate vaccines. Of relevance to vaccine development was the finding that a minimal CD8(+) T cell peptide epitope from HPV was not able to induce HLA-A2.1 specific CD8(+) T cell responses in transgenic humanized mice using conventional adjuvants such as CpG, but was nevertheless able to generate strong immunity when delivered as part of a specific longer peptide conjugated to PSNPs vaccines. Conversely, in most cases, when the minimal CD8(+) T cell epitopes were able to induce immune responses (with WT1 or SV super agonists) in CpG, they also induced responses when conjugated to PSNPs. In this case, extending the sequence around the CD8(+) T cell epitope, using the natural protein context, or engineering linker sequences proposed to enhance antigen processing, had minimal effects in enhancing or changing the cross-reactivity pattern induced by the super agonists. Nanoparticle approaches, such as PSNPs, therefore may offer an alternative vaccination strategy when conventional adjuvants are unable to elicit the desired CD8(+) T cell specificity. The findings herein also offer sequence specific insights into peptide vaccine design for nanoparticle-based vaccine carriers.

negative: Modified delta-shaped gastroduodenostomy consisting of linear stapling and single-layer suturing with the operator positioned between the patient's legs: A technique preventing intraoperative duodenal injury and postoperative anastomotic stenosis. BACKGROUND The drawback of the delta-shaped gastroduodenostomy (DSG) in totally laparoscopic distal gastrectomy (TLDG) is the presence of intraoperative duodenal injury and postoperative anastomotic stenosis, which can occur due to a relatively short duodenal bulb diameter. MATERIALS AND METHODS From June 2013 to June 2019, 35 patients with gastric cancer underwent TLDG with a modified DSG consisting of linear stapling and single-layer hand suturing in our institution. All anastomotic procedures were performed by the right hand of the operator positioned between the patient's legs. Linear stapling of the posterior walls of the remnant stomach and duodenum without creating a gap was performed using a 45-mm linear stapler, considering the prevention of intraoperative duodenal injury. The stapler entry hole was closed using a single-layer full-thickness hand suturing technique with knotted sutures and a knotless barbed suture. We described the clinical data and outcomes in the present retrospective patient series. RESULTS No intraoperative duodenal injury occurred in any of the 35 patients. The median staple length at linear stapling of the posterior walls of the remnant stomach and duodenum was 41.7 ± 4.2 (30-45) mm, and 2 patients (5.7%) had a staple length of 30 mm. There were no incidences of postoperative anastomotic stenosis. CONCLUSIONS We suggest that a modified DSG consisting of linear stapling and single-layer hand suturing performed by an operator positioned between the patient's legs can be one option for B-Ⅰ reconstruction following TLDG because it can aid in preventing both intraoperative duodenal injury and postoperative anastomotic stenosis.

negative: Infección por coronavirus (COVID-19) en Anales de Pediatría

negative: Risk Factors for Transmission of Middle East Respiratory Syndrome Coronavirus Infection During the 2015 Outbreak in South Korea BACKGROUND. Transmission heterogeneity was observed during the 2015 Korean outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Only 22 of 186 cases transmitted the infection, and 5 super-spreading events caused 150 transmissions. We investigated the risk factors for MERS-CoV transmission. METHODS. Epidemiological reports were used to classify patients as nonspreaders, spreaders, or those associated with a super-spreading event (5 or more transmissions). Logistic regression analyses were used to evaluate the factors for MERS-CoV transmission. RESULTS. Compared to nonspreaders, spreaders exhibited a longer interval from symptom onset to isolation (7 days vs 3 days) and more frequent pre-isolation pneumonia diagnoses (68.2% vs 17.1%). Spreaders also exhibited higher values for pre-isolation contacts (149 vs 17.5), pre-isolation hospitalization (68.2% vs 16.5%), and emergency room (ER) visits (50% vs 7.3%). Spreaders exhibited lower cycle thresholds for the upE and ORF1a genes (22.7 vs 27.2 and 23.7 vs 27.9, respectively). In multivariate analysis, transmission was independently associated with the cycle threshold (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75–0.96) and pre-isolation hospitalization or ER visits (OR, 6.82; 95% CI, 2.06–22.84). The super-spreading events exhibited higher values for pre-isolation contacts (777 vs 78), pre-isolation ER visits (100% vs 35.3%), and doctor shopping (100% vs 47.1%) compared to non-super-spreading events. CONCLUSIONS. These findings indicate that transmission is determined by host infectivity and the number of contacts, whereas super-spreading events were determined by the number of contacts and hospital visits. These relationships highlight the importance of rapidly enforcing infection control measures to prevent outbreaks.

negative: Current evidence for directed and supportive investigational therapies against COVID-19 Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.

negative: 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.

negative: Reopening schools after the COVID-19 lockdown

negative: Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. BACKGROUND Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

negative: [Strategy of dental clinics to cope with the epidemic period of infectious diseases based on the experience of corona virus disease outbreak]. The outbreak of corona virus disease (COVID-19) has raised concerns among dentists to develop strategies to prevent infection of dental equipment, materials, and patients during an epidemic period. Strategies following the National Laws and Standards of China and local standards of several provinces for controlling cross-infection and instituting protective measures for medical staff in dental clinics during an epidemic period are discussed. A proposal is put forth for dental clinics that will face similar situations in the future. Further research is warranted to address potential problems that will be encountered under such dire circumstances.

negative: Chloroquine and hydroxychloroquine for the treatment of COVID-19: A living systematic review protocol OBJECTIVE: To determine the relative impact of the use of chloroquine and hydroxychloroquine on outcomes important to patients with COVID 19. DESIGN: This is the protocol of a living systematic review. DATA SOURCES: We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries, grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We will follow a common protocol for multiple parallel systematic reviews, already published and submitted to PROSPERO (awaiting ID allocation). We will include randomised controlled trials evaluating the effect of chloroquine and hydroxychloroquine - as monotherapy or in combination with other drugs - versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating chloroquine and hydroxychloroquine in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. ETHICS AND DISSEMINATION: No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.

negative: Viral interference between low pathogenic avian influenza H9N2 and avian infectious bronchitis viruses in vitro and in ovo Abstract Background Low pathogenic avian influenza (LPAI) H9N2 and infectious bronchitis virus (IBV) are important pathogens of poultry, causing important economic losses for the sector. Replication interference between these two viruses was described using cell cultures (CC) and embryonated chicken eggs (ECE). Chicken embryo lung (CEL) and ECE were simultaneously or sequentially infected with IBV vaccine strain (H120) and LPAIV-H9N2 (A/Ck/TUN/145/2012) to evaluate viral interactionsin vitro and in ovo, respectively. Real-time RT-PCR was developed to specifically quantify both AIV and IBV genomes as well as viral gene copy numbers during mixed infections. The amount of IL-1 beta, in supernatants of co-infected cell cultures, was determined using an ELISA assay. Results Quantitative results of AIV and IBV co-infection showed that interferences between the two viruses yielded decreased viral growth. However, in the case of super-infection, the second virus, either AIV or IBV, induced a decrease in the growth of the first inoculated virus. Conclusion It appears that either AIV or IBV has a negative impact on the other virus growth when they are inoculated simultaneously or sequentially. The ELISA results showed that higher level of secreted IL-1beta varies, depending on the viral interference conditions between both viruses, during mixed infections.

negative: Acute Portal Vein Thrombosis in SARS-CoV-2 Infection: A Case Report

negative: Impact of city and residential unit lockdowns on prevention and control of COVID-19 With respect to the asymptomatic transmission characteristics of the novel coronavirus that appeared in 2019 (COVID-19), a susceptible-asymptomatic-infected-recovered-death (SAIRD) model that considered human mobility was constructed in this study. The dissemination of COVID-19 was simulated using computational experiments to identify the mechanisms underlying the impact of city and residential lockdowns on controlling the spread of the epidemic. Results: The implementation of measures to lock down cities led to higher mortality rates in these cities, due to reduced mobility. Moreover, implementing city lockdown along with addition of hospital beds led to improved cure and reduced mortality rates. Stringent implementation and early lockdown of residential units effectively controlled the spread of the epidemic, and reduced the number of hospital bed requirements. Collectively, measures to lock down cities and residential units should be taken to prevent the spread of COVID-19. In addition, medical resources should be increased in cities under lockdown. Implementation of these measures would reduce the spread of the virus to other cities and allow appropriate treatment of patients in cities under lockdown.

negative: Achieving a Popliteal Venous Access for RRT in Critically Ill COVID-19 Patient in Prone position This patient is a 67-year-old male who initially presented to our facility with acute respiratory failure secondary to COVID-19. Soon after arrival at our facility, the patient decompensated, developing severe ARDS requiring intubation and prone positioning to maintain adequate oxygenation. Over the next few days, the patient developed acute kidney injury with oliguria and severe volume overload. The vascular surgery service was consulted to obtain central venous access for emergent CRRT. Upon our exam, the patient was sedated and paralyzed in a rotating prone-positioning bed. He could not be positioned supine without immediately becoming hypoxic and decompensating. A 50-cm Permcath was inserted via left popliteal vein. This case report outlines a possible challenging scenario that may encounter vascular interventionist when dealing with COVID-19 patients with respiratory compromise in prone position.

negative: Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review BACKGROUND: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION: Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION: There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

negative: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management and Infection Control in a Radiology Department Abstract Objective To describe the strategy and the emergency management and infection control procedure of our radiology department during the coronavirus disease 2019 (COVID-19) outbreak. Methods We set up emergency management and sensing control teams. The team formulated various measures: reconfiguration of the radiology department, personal protection and training of staff, examination procedures for patients suspected of or confirmed with COVID-19 as well as patients without an exposure history or symptoms. Those with suspected or confirmed COVID-19 infection were scanned in the designated fever-CT unit. Results From January 21, 2020, to March 9, 2020, 3,083 people suspected or confirmed to be infected with COVID-19 underwent fever-CT examinations. Including initial examinations and re-examinations, the total number of fever-CT examinations numbered 3,340. As a result of our precautions, none of the staff of the radiology department were infected with COVID-19. Conclusion Strategic planning and adequate protections can help protect patients and staff against a highly infectious disease while maintaining function at a high-volume capacity.

negative: Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) The recent global outbreak of viral pneumonia designated as Coronavirus Disease 2019 (COVID-19) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability.

negative: Aerosol generating procedures and infective risk to healthcare workers: SARS-CoV-2 - the limits of the evidence The transmission behaviour of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being defined. It is likely that it is transmitted predominantly by droplets and direct contact and it is possible that there is at least opportunistic airborne transmission. In order to protect healthcare staff adequately is necessary that we establish whether aerosol generating procedures (AGPs) increase the risk of transmission of SARS-CoV-2. Where we do not have evidence relating to SARS-CoV-2, guidelines for safely conducting these procedures should consider what risk procedures would have of transmitting related pathogens. Currently there is very little evidence detailing the transmission of SARS-CoV-2 associated with any specific procedures. Regarding aerosol generating procedures and respiratory pathogens in general, there is still a large knowledge gap that will leave clinicians unsure what risk they are putting themselves in when offering these procedures. This review aimed to summarise the evidence (and gaps in evidence) around AGPs and SARS-CoV-2.

negative: Role of hubs in the synergistic spread of behavior The spread of behavior in a society has two major features: the synergy of multiple spreaders and the dominance of hubs. While strong synergy is known to induce mixed-order transitions (MOTs) at percolation, the effects of hubs on the phenomena are yet to be clarified. By analytically solving the generalized epidemic process on random scale-free networks with the power-law degree distribution [Formula: see text] , we clarify how the dominance of hubs in social networks affects the conditions for MOTs. Our results show that, for [Formula: see text] , an abundance of hubs drive MOTs, even if a synergistic spreading event requires an arbitrarily large number of adjacent spreaders. In particular, for [Formula: see text] , we find that a global cascade is possible even when only synergistic spreading events are allowed. These transition properties are substantially different from those of cooperative contagions, which are another class of synergistic cascading processes exhibiting MOTs.

negative: Platelet functions and activities as potential hematologic parameters related to Coronavirus Disease 2019 (Covid-19). Coronavirus disease 2019 (COVID-19) is a new infectious disease that currently lacks standardized and established laboratory markers to evaluate its severity. In COVID-19 patients, the number of platelets (PLTs) and dynamic changes of PLT-related parameters are currently a concern. The present paper discusses the potential link between PLT parameters and COVID-19. Several studies have identified a link between severe COVID-19 patients and specific coagulation index, in particular, high D-dimer level, prolonged prothrombin time, and low PLT count. These alterations reflect the hypercoagulable state present in severe COVID-19 patients, which could promote microthrombosis in the lungs, as well as in other organs. Further information and more advanced hematological parameters related to PLTs are needed to better estimate this link, also considering COVID-19 patients at different disease stages and stratified in different cohorts based on preexisting co-morbidity, age, and gender. Increasing the understanding of PLT functions in COVID-19 will undoubtedly improve our knowledge on disease pathogenesis, clinical management, and therapeutic options, but could also lead to the development of more precise therapeutic strategies for COVID-19 patients.

negative: Jordan Field Epidemiology Training Program: Critical Role in National and Regional Capacity Building Field Epidemiology Training Programs (FETPs) are 2-year training programs in applied epidemiology, established with the purpose of increasing a country’s capacity within the public health workforce to detect and respond to health threats and develop internal expertise in field epidemiology. The Jordan Ministry of Health, in partnership with the US Centers for Disease Control and Prevention, started the Jordan FETP (J-FETP) in 1998. Since then, it has achieved a high standard of success and has been established as a model for FETPs in the Eastern Mediterranean Region. Here we describe the J-FETP, its role in building the epidemiologic capacity of Jordan’s public health workforce, and its activities and achievements, which have grown the program to be self-sustaining within the Jordan Ministry of Health. Since its inception, the program’s residents and graduates have assisted the country to improve its surveillance systems, including revising the mortality surveillance policy, implementing the use of electronic data reporting, investigating outbreaks at national and regional levels, contributing to noncommunicable disease research and surveillance, and responding to regional emergencies and disasters. J-FETP’s structure and systems of support from the Jordan Ministry of Health and local, regional, and international partners have contributed to the success and sustainability of the J-FETP. The J-FETP has contributed significantly to improvements in surveillance systems, control of infectious diseases, outbreak investigations, and availability of reliable morbidity and mortality data in Jordan. Moreover, the program has supported public health and epidemiology in the Eastern Mediterranean Region. Best practices of the J-FETP can be applied to FETPs throughout the world.

negative: Utility of Substandard Face Mask Options for Health Care Workers During the COVID-19 Pandemic

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

negative: Analyzing barriers for implementation of public health and social measures to prevent the transmission of COVID-19 disease using DEMATEL method BACKGROUND AND AIMS: COVID-19 is a contagious disease caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Till now there are no vaccines and explicit medicines available for the treatment of COVID-19 disease, therefore the initiatives like public health and social measures are helpful in limiting the quantity of contaminations and saving lives. Keeping this in view, an attempt has been made in the present work to identify the barriers which hinder the implementation of these public health and social measures METHODS: The barriers to implement public health and social measures for preventing transmission of COVID-19 are identified using systematic literature review and these barriers are then categorized using Decision-making trial and evaluation laboratory (DEMATEL) method. RESULTS: Results reveal that among ten identified barriers, Lack of resources for implementing public health and social measures is found to be the most influential barrier to implement public health and social measures for preventing transmission of COVID-19. CONCLUSIONS: The successful implementation of public health and social measures depends on the adequate availability of resources which include medical equipment, personnel and financial dealings. The outcome of this research work will benefit and motivate the higher authorities to consider and overcome various challenges to prevent the transmission of COVID-19.

negative: Effects of media reporting on mitigating spread of COVID-19 in the early phase of the outbreak The 2019 novel coronavirus disease (COVID-19) is running rampantly in China and is swiftly spreading to other countries in the world, which causes a great concern on the global public health. The absence of specific therapeutic treatment or effective vaccine against COVID-19 call for other avenues of the prevention and control measures. Media reporting is thought to be effective to curb the spreading of an emergency disease in the early stage. Cross-correlation analysis based on our collected data demonstrated a strong correlation between media data and the infection case data. Thus we proposed a deterministic dynamical model to examine the interaction of the disease progression and the media reports and to investigate the effectiveness of media reporting on mitigating the spread of COVID-19. The basic reproduction number was estimated as 5.3167 through parameterization of the model with the number of cumulative confirmed cases, the number of cumulative deaths and the daily number of media items. Sensitivity analysis suggested that, during the early phase of the COVID-19 outbreak, enhancing the response rate of the media reporting to the severity of COVID-19, and enhancing the response rate of the public awareness to the media reports, both can bring forward the peak time and reduce the peak size of the infection significantly. These findings suggested that besides improving the medical levels, media coverage can be considered as an effective way to mitigate the disease spreading during the initial stage of an outbreak.

negative: Introducing the Outbreak Threshold in Epidemiology When a pathogen is rare in a host population, there is a chance that it will die out because of stochastic effects instead of causing a major epidemic. Yet no criteria exist to determine when the pathogen increases to a risky level, from which it has a large chance of dying out, to when a major outbreak is almost certain. We introduce such an outbreak threshold (T(0)), and find that for large and homogeneous host populations, in which the pathogen has a reproductive ratio R(0), on the order of 1/Log(R(0)) infected individuals are needed to prevent stochastic fade-out during the early stages of an epidemic. We also show how this threshold scales with higher heterogeneity and R(0) in the host population. These results have implications for controlling emerging and re-emerging pathogens.

negative: Evolving consensus on managing vitreo-retina and uvea practice in post-COVID-19 pandemic era. The COVID-19 pandemic has brought new challenges to the health care community. Many of the super-speciality practices are planning to re-open after the lockdown is lifted. However there is lot of apprehension in everyone's mind about conforming practices that would safeguard the patients, ophthalmologists, healthcare workers as well as taking adequate care of the equipment to minimize the damage. The aim of this article is to develop preferred practice patterns, by developing a consensus amongst the lead experts, that would help the institutes as well as individual vitreo-retina and uveitis experts to restart their practices with confidence. As the situation remains volatile, we would like to mention that these suggestions are evolving and likely to change as our understanding and experience gets better. Further, the suggestions are for routine patients as COVID-19 positive patients may be managed in designated hospitals as per local protocols. Also these suggestions have to be implemented keeping in compliance with local rules and regulations.

negative: The 2014–2015 Ebola outbreak in West Africa: Hands On The International Consortium for Prevention and Infection Control (ICPIC) organises a biannual conference (ICPIC) on various subjects related to infection prevention, treatment and control. During ICPIC 2015, held in Geneva in June 2015, a full one-day session focused on the 2014–2015 Ebola virus disease (EVD) outbreak in West Africa. This article is a non-exhaustive compilation of these discussions. It concentrates on lessons learned and imagining a way forward for the communities most affected by the epidemic. The reader can access video recordings of all lectures delivered during this one-day session, as referenced. Topics include the timeline of the international response, linkages between the dynamics of the epidemic and infection prevention and control, the importance of community engagement, and updates on virology, diagnosis, treatment and vaccination issues. The paper also includes discussions from public health, infectious diseases, critical care and infection control experts who cared for patients with EVD in Africa, in Europe, and in the United Sates and were involved in Ebola preparedness in both high- and low-resource settings and countries. This review concludes that too little is known about the pathogenesis and treatment of EVD, therefore basic and applied research in this area are urgently required. Furthermore, it is clear that epidemic preparedness needs to improve globally, in particular through the strengthening of health systems at local and national levels. There is a strong need for culturally sensitive approaches to public health which could be designed and delivered by social scientists and medical professionals working together. As of December 2015, this epidemic killed more than 11,000 people and infected more than 28,000; it has also generated more than 17,000 survivors and orphans, many of whom face somatic and psychological complications. The continued treatment and rehabilitation of these people is a public health priority, which also requires an integration of specific medical and social science approaches, not always available in West Africa.

negative: Comparative Global Epidemiological Investigation of SARS-CoV-2 and SARS-CoV Diseases Using Meta-MUMS Tool Through Incidence, Mortality, and Recovery Rates COVID-19 is a novel coronavirus that was reported by the world health organization in late December 2019. As an unexplained respiratory disease epidemic, which is similar to respiratory syndrome coronavirus SARS-CoV, it rapidly spread all over the world. The study aims to compare several parameters of COVID-19 and SARS-CoV infectious diseases in terms of incidence, mortality, and recovery rates. The publicly available dataset Worldometer (extracted on April 5, 2020) confirmed by WHO report was available for meta-analysis purposes using the Meta-MUMS tool. And, the reported outcomes of the analysis used a random-effects model to evaluate the event rate, and risk ratios thorough subgroup analysis forest plots. Seventeen countries for COVID-19 and eight countries of SARS infections, including COVID-19 group n = 1124243, and SARS-CoV group n = 8346, were analyzed. In this meta-analysis, a random effect model of relations of incidence, mortality, and recovery rates of COVID-19 and SARS world infections were determined. The meta-analysis and forest plots of two viral world infections showed that the incidence rate of COVID-19 infection is more than SARS infections, while recovery and mortality event rates of SARS-CoV are more than COVID-19 infection. And subgroup analysis showed that the mortality and recovery rates were higher in both SARS-CoV wand COVID-19 in comparison to incidence and mortality rates, respectively. In conclusion, the meta-analysis approach on the abovementioned dataset revealed the epidemiological and statistical analyses for comparing COVID-19 and SARS-CoV outbreaks.

negative: One month of the novel coronavirus 2019 outbreak: Is it still a threat? The novel coronavirus 2019 disease (COVID-19) is now in an outbreak not only in China but also around the world, suspected to be originated from a wet market in Wuhan, Hubei province, China. The flare-up of COVID-19, it has already been infected 78,811 people with 2462 fatalities in 1 month window. The most alarming issue is the virus can transmit from host to host and still asymptomatic. Currently, 24 counties with 505 confirmed cases have been reported. Presently, there is no specific treatment or vaccine but physicians are battling with the use of antibiotics, steroid, anti-viral and anti-HIV drugs and some of the infected cases are testified improved. WHO and China National health Commission are cooperatively striving to come up with elucidation but it will take a minimum of 3 to 4 months at least to undergo a phase-1 trial. However, the soaring rates of spreading each day has become much stable which might even improve within the next few weeks in China but not for some other countries. Healthy peoples are instructed to avoid public gathering, always wearing the mask and frequently wash hands. Currently, China has able to hold up more than 97.7% infection within China but a scientific breakthrough is crucial before it’s too late.

negative: Global implications of bio-aerosol in pandemic

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: COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease. As of 22 February 2020, more than 77662 cases of confirmed COVID-19 have been documented globally with over 2360 deaths. Common presentations of confirmed cases include fever, fatigue, dry cough, upper airway congestion, sputum production, shortness of breath, myalgia/arthralgia with lymphopenia, prolonged prothrombin time, elevated C-reactive protein, and elevated lactate dehydrogenase. The reported severe/critical case ratio is approximately 7-10% and median time to intensive care admission is 9.5-10.5 days with mortality of around 1-2% varied geographically. Similar to outbreaks of other newly identified virus, there is no proven regimen from conventional medicine and most reports managed the patients with lopinavir/ritonavir, ribavirin, beta-interferon, glucocorticoid and supportive treatment with remdesivir undergoing clinical trial. In China, Chinese medicine is proposed as a treatment option by national and provincial guidelines with substantial utilization. We reviewed the latest national and provincial clinical guidelines, retrospective cohort studies, and case series regarding the treatment of COVID-19 by add-on Chinese medicine. We have also reviewed the clinical evidence generated from SARS and H1N1 management with hypothesized mechanisms and latest in silico findings to identify candidate Chinese medicines for the consideration of possible trials and management. Given the paucity of strongly evidence-based regimens, the available data suggest that Chinese medicine could be considered as an adjunctive therapeutic option in the management of COVID-19.

negative: Analysing the combined health, social and economic impacts of the corovanvirus pandemic using agent-based social simulation During the COVID-19 crisis there have been many difficult decisions governments and other decision makers had to make. E.g. do we go for a total lock down or keep schools open? How many people and which people should be tested? Although there are many good models from e.g. epidemiologists on the spread of the virus under certain conditions, these models do not directly translate into the interventions that can be taken by government. Neither can these models contribute to understand the economic and/or social consequences of the interventions. However, effective and sustainable solutions need to take into account this combination of factors. In this paper, we propose an agent-based social simulation tool, ASSOCC, that supports decision makers understand possible consequences of policy interventions, bu exploring the combined social, health and economic consequences of these interventions.

negative: Day Level Forecasting for Coronavirus Disease (COVID-19) Spread: Analysis, Modeling and Recommendations In mid of March 2020, Coronaviruses such as COVID-19 is declared as an international epidemic. More than 125000 confirmed cases and 4,607 death cases have been recorded around more than 118 countries. Unfortunately, a coronavirus vaccine is expected to take at least 18 months if it works at all. Moreover, COVID -19 epidemics can mutate into a more aggressive form. Day level information about the COVID -19 spread is crucial to measure the behavior of this new virus globally. Therefore, this study presents a comparison of day level forecasting models on COVID-19 affected cases using time series models and mathematical formulation. The forecasting models and data strongly suggest that the number of coronavirus cases grows exponentially in countries that do not mandate quarantines, restrictions on travel and public gatherings, and closing of schools, universities, and workplaces (Social Distancing).

negative: Generality of endemic prevalence formulae Abstract In simple infection models, the susceptible proportion s * in endemic equilibrium is related to the basic reproduction number R 0 by s * = 1 / R 0 . We investigate the extent to which this relationship remains valid under more realistic modelling assumptions. In particular, we relax the biologically implausible assumptions that individuals’ lifetimes and infectious periods follow exponential distributions; allow a general recruitment process; allow for multiple stages of infection; and consider extension to a multigroup model in which the groups may represent, for instance, spatial heterogeneity, or the existence of super-spreaders. For a homogeneous population, we find that: (i) the susceptible proportion is s * = 1 / R 0 e , where R 0 e is a modified reproduction number, equal to R 0 only in certain circumstances; (ii) the proportions of the population in each stage of infection are proportional to the expected time spent by an infected individual in that stage before recovery or death. We demonstrate robustness of the formula s * = 1 / R 0 for many human infections by noting conditions under which R 0 e is approximately equal to R 0, while pointing out other circumstances under which this approximation fails. For heterogeneous populations, the formula s * = 1 / R 0 does not hold in general, but we are able to exhibit symmetry conditions under which it is valid.

negative: Is the epidemic spread related to GDP? Visualizing the distribution of COVID-19 in Chinese Mainland In December 2019, COVID-19 were detected in Wuhan City, Hubei Province of China. SARS-CoV-2 rapidly spread to the whole Chinese mainland with the people during the Chinese Spring Festival Travel Rush. As of 19 February 2020, 74576 confirmed cases of COVID-19 had been reported in Chinese Mainland. What kind of cities have more confirmed cases, and is there any relationship between GDP and confirmed cases? In this study, we explored the relationship between the confirmed cases of COVID-19 and GDP at the prefectural-level, found a positive correlation between them. This finding warns high GDP areas should pay more prevention and control efforts when an epidemic outbreak, as they have greater risks than other areas nearby.

negative: Preliminary estimates of the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea and Italy by 5 March 2020 The novel coronavirus disease 2019 (COVID-19) outbreak has caused 6088 cases and 41 deaths in Republic of Korea, and 3144 cases and 107 death in Italy by 5 March 2020, respectively. We modelled the transmission process in the Republic of Korea and Italy with a stochastic model, and estimated the basic reproduction number R0 as 2.6 (95% CI: 2.3-2.9) or 3.2 (95% CI: 2.9-3.5) in the Republic of Korea, under the assumption that the exponential growth starting on 31 January or 5 February 2020, and 2.6 (95% CI: 2.3-2.9) or 3.3 (95% CI: 3.0-3.6) in Italy, under the assumption that the exponential growth starting on 5 February or 10 February 2020, respectively.

negative: Management strategies in a SEIR model of COVID 19 community spread The 2019 Novel Corona virus infection (COVID-19) is an ongoing public health emergency of international focus. Significant gaps persist in our knowledge of COVID-19 epidemiology, transmission dynamics, investigation tools and management, despite (or possibly because of) the fact that the outbreak is an unprecedented global threat. On the positive side, enough is currently known about the epidemic process to permit the construction of mathematical predictive models. We construct and analyze here one first step: that of adapting a traditional SEIR epidemic model to the specific dynamic compartments and epidemic parameters of COVID-19, as it spreads in an age-heterogeneous community. We analyze the current management strategy of the epidemic course (travel bans, service closures and interruptions, social distancing). We generate predictions, and assess the efficiency of these control measures, in the context in which their sustainability is currently being questioned.

negative: Counting the cost of COVID-19 Coronavirus disease 2019 (COVID-19) is the name given by the World Health Organization (WHO) to the highly contagious and infectious disease caused by the Novel Corona Virus or SARS-CoV-2, which was first reported on 31 December 2019 in Wuhan city of the capital of China's Hubei province. Due to the rapid increase in the number of infections worldwide, the WHO in March 2020, declared COVID-19 as a pandemic. Historically, first coronavirus had surfaced in 1965 with symptoms of common cold. Since then five different strands of this virus have emerged, most lethal of them was the Severe Acute Respiratory Syndrome (SARS), which infected about eight thousand people, killing ten percent of them. The COVID-19 is not the most deadly pandemic world has ever witnessed as the Spanish influenza pandemic, during 1918–19, killed more than fifty million people. Indeed COVID-19 has turned out to be the most lethal of all coronaviruses as it has infected at least three million people killing more than two hundred thousands of them in the first 4 months of its spread. Many politicians and social scientists have dubbed the depression, being caused by COVID-19, worse than that caused by the Second World War. In this article, we shall analyze economic, social, cultural, educational and political impact of the COVID-19.

negative: User Concerns&Tradeoffs in Technology-Facilitated Contact Tracing Contact tracing apps are one of the primary technology-facilitated Coronavirus (COVID) responses currently proposed. In the majority of Western nations there is the expectation that citizens will have the autonomy to decide whether or not to install a COVID-related app. Yet, the more users who install a COVID app, the greater the impact on public health. As explained by Chan et al. the value of users installing a contact-tracing app grows quadratically with the number of users who install. How can we get users to install COVID apps? By understanding and mitigating user concerns and tradeoffs. This document provides a framework for considering the user-relevant components of COVID apps and corresponding user tradeoffs related to these apps. Specifically, we enumerate user tradeoffs related to data collection, data quality, identifier/data encryption, privacy invasion, mobile costs, user agency, benefits from app use, and app transparency. We break down which tradeoffs are relevant for which contact tracing implementations (centralized vs. decentralized, location- vs. proximity-based). Additionally, we compare contact tracing to an alternative technology-facilitated COVID solution: narrowcasts. Narrowcasts are location-personalized broadcasts about COVID hotspots in your vicinity.

negative: The Effect of Large-Scale Anti-Contagion Policies on the Coronavirus (COVID-19) Pandemic Governments around the world are responding to the novel coronavirus (COVID-19) pandemic with unprecedented policies designed to slow the growth rate of infections. Many actions, such as closing schools and restricting populations to their homes, impose large and visible costs on society. In contrast, the benefits of these policies, in the form of infections that did not occur, cannot be directly observed and are currently understood through process-based simulations. Here, we compile new data on 1,659 local, regional, and national anti-contagion policies recently deployed in the ongoing pandemic across localities in China, South Korea, Iran, Italy, France, and the United States (US). We then apply reduced-form econometric methods, commonly used to measure the effect of policies on economic growth, to empirically evaluate the effect that these anti-contagion policies have had on the growth rate of infections. In the absence of any policy actions, we estimate that early infections of COVID-19 exhibit exponential growth rates of roughly 42% per day. We find that anti-contagion policies collectively have had significant effects slowing this growth. Our results suggest that similar policies may have different impacts on different populations, but we obtain consistent evidence that the policy packages now deployed are achieving large, beneficial, and measurable health outcomes. We estimate that, to date, current policies have already prevented or delayed on the order of 62 million infections across these six countries. These findings may help inform whether or when these ongoing policies should be lifted or intensified, and they can support decision-making in the other 180+ countries where COVID-19 has been reported.

negative: Information Seeking Responses to News of Local COVID-19 Cases: Evidence from Internet Search Data The novel coronavirus (COVID-19) outbreak is a global pandemic with community circulation in many countries, including the U.S. where every state is reporting confirmed cases. The course of this pandemic will be largely shaped by how governments enact timely policies, disseminate the information, and most importantly, how the public reacts to them. Here, we examine informationseeking responses to the first COVID-19 case public announcement in a state. By using an eventstudy framework, we show that such news increases collective attention to the crisis right away, but the elevated level of attention is short-lived, even though the initial announcements were followed by increasingly strong measures. We find that people respond to the first report of COVID-19 in their state by immediately seeking information about COVID-19, as measured by searches for coronavirus, coronavirus symptoms and hand sanitizer. On the other hand, searches for information regarding community level policies (e.g., quarantine, school closures, testing), or personal health strategies (e.g., masks, grocery delivery, over-the-counter medications) do not appear to be immediately triggered by first reports. These results are encouraging given our study period is relatively early in the epidemic and more elaborate policy responses were not yet part of the public discourse. Further analysis will track evolving patterns of responses to subsequent flows of public information.

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 a 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 T(C) = 86.1 ± 4.3 F(0).

negative: Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19

negative: Laser Spectroscopic Technique for Direct Identification of a Single Virus I: FASTER CARS From the famous 1918 H1N1 influenza to the present COVID-19 pandemic, the need for improved virial detection techniques is all too apparent. The aim of the present paper is to show that identification of individual virus particles in clinical sample materials quickly and reliably is near at hand. First of all, our team has developed techniques for identification of virions based on a modular atomic force microscopy (AFM). Furthermore, Femtosecond Adaptive Spectroscopic Techniques with Enhanced Resolution via Coherent Anti-Stokes Raman Scattering (FASTER CARS) [1] using tip-enhanced techniques markedly improves the sensitivity.

negative: Community pharmacist in public health emergencies: Quick to action against the coronavirus 2019-nCoV outbreak The 2019-nCoV infection that is caused by a novel strain of coronavirus was first detected in China in the end of December 2019 and declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Community pharmacists in one of the first areas that had confirmed cases of the viral infection, Macau, joined the collaborative force in supporting the local health emergency preparedness and response arrangements. This paper aimed to improve the understanding of community pharmacists’ role in case of 2019-CoV outbreak based on the practical experiences in consultation with the recommendations made by the International Pharmaceutical Federation on the Coronavirus 2019-nCoV outbreak.

negative: Moving interdisciplinary science forward: integrating participatory modelling with mathematical modelling of zoonotic disease in Africa This review outlines the benefits of using multiple approaches to improve model design and facilitate multidisciplinary research into infectious diseases, as well as showing and proposing practical examples of effective integration. It looks particularly at the benefits of using participatory research in conjunction with traditional modelling methods to potentially improve disease research, control and management. Integrated approaches can lead to more realistic mathematical models which in turn can assist with making policy decisions that reduce disease and benefit local people. The emergence, risk, spread and control of diseases are affected by many complex bio-physical, environmental and socio-economic factors. These include climate and environmental change, land-use variation, changes in population and people’s behaviour. The evidence base for this scoping review comes from the work of a consortium, with the aim of integrating modelling approaches traditionally used in epidemiological, ecological and development research. A total of five examples of the impacts of participatory research on the choice of model structure are presented. Example 1 focused on using participatory research as a tool to structure a model. Example 2 looks at identifying the most relevant parameters of the system. Example 3 concentrates on identifying the most relevant regime of the system (e.g., temporal stability or otherwise), Example 4 examines the feedbacks from mathematical models to guide participatory research and Example 5 goes beyond the so-far described two-way interplay between participatory and mathematical approaches to look at the integration of multiple methods and frameworks. This scoping review describes examples of best practice in the use of participatory methods, illustrating their potential to overcome disciplinary hurdles and promote multidisciplinary collaboration, with the aim of making models and their predictions more useful for decision-making and policy formulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0110-4) contains supplementary material, which is available to authorized users.

negative: Modeling and analysis of epidemic spreading on community networks with heterogeneity Abstract A large number of real world networks exhibit community structure, and different communities may often possess heterogeneity. In this paper, considering the heterogeneity among communities, we construct a new community network model in which the communities show significant differences in average degree. Based on this heterogeneous community network, we propose a novel mathematical epidemic model for each community and study the epidemic dynamics in this network model. We find that the location of the initial infection node only affects the spreading velocity and barely influences the epidemic prevalence. And the epidemic threshold of entire network decreases with the increase of heterogeneity among communities. Moreover, the epidemic prevalence increases with the increase of heterogeneity around the epidemic threshold, while the converse situation holds when the infection rate is much greater than the epidemic threshold.

negative: Epidemiology and Clinical Features of Coronavirus disease 2019 in Children Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and has been declared a worldwide pandemic in March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients with outbreaks and is often milder than adults, but can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may play a role as a spreader in the community. In this review, we summarize what is known about COVID-19 in children and adolescents until now.

negative: A phenomenological approach to COVID-19 spread in a population A phenomenological model to describe the Corona Virus(covid-19) Pandemic spread in a given population is developed. It enables the identification of the key quantities required to form adequate policies for control and mitigation in terms of observable parameters using the Landau-Stuart equation. It is intended to be complementary to detailed simulations and methods published recently by Ferguson and collaborators, March 16, (2020). The results suggest that the initial growth/spreading rate gamma-c of the disease, and the fraction of infected persons in the population p-i can be used to define a `retardation/inhibition coefficient' k-star , which is a measure of the effectiveness of the control policies adopted. The results are obtained analytically and numerically using a simple Python code. The solutions provide both qualitative and quantitative information. They substantiate and justify two basic control policies enunciated by WHO and adopted in many countries: a) Systematic and early intensive testing individuals for covid-19 and b) Sequestration policies such as `social/physical distancing' and population density reduction by strict quarantining are essential for making k-star greater than 1, necessary for suppressing the pandemic. The model indicates that relaxing such measures when the infection rate starts to decrease as a result of earlier policies could simply restart the infection rate in the non-infected population. Presently available available statistical data in WHO and other reports can be readily used to determine the the key parameters of the model. Possible extensions to the basic model to make it more realistic are indicated.

negative: A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19 PURPOSE: COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19. METHODS: PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19. RESULTS: We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro. CONCLUSIONS: There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed.

negative: Clinical Decision Support Tool and Rapid Point-of-Care Platform for Determining Disease Severity in Patients with COVID-19 SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40–83) and 9 (6–17), respectively, and area under the curve of 0.94 (95% CI 0.89–0.99). These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.

negative: Rapid response in the COVID-19 pandemic: a Delphi study from the European Pediatric Dialysis Working Group BACKGROUND: COVID-19 was declared a global health emergency. Since children are less than 1% of reported cases, there is limited information to develop evidence-based practice recommendations. The objective of this study was to rapidly gather expert knowledge and experience to guide the care of children with chronic kidney disease during the COVID-19 pandemic. METHODS: A four-round multi-center Delphi exercise was conducted among 13 centers in 11 European countries of the European Pediatric Dialysis Working Group (EPDWG) between March, 16th and 20th 2020. Results were analyzed using a mixed methods qualitative approach and descriptive statistics. RESULTS: Thirteen COVID-19 specific topics of particular need for guidance were identified. Main themes encompassed testing strategies and results (n = 4), changes in use of current therapeutics (n = 3), preventive measurements of transmission and management of COVID-19 (n = 3), and changes in standard clinical care (n = 3). Patterns of center-specific responses varied according to regulations and to availability of guidelines. CONCLUSIONS: As limited quantitative evidence is available in real time during the rapid spread of the COVID-19 pandemic, qualitative expert knowledge and experience represent the best evidence available. This Delphi exercise demonstrates that use of mixed methodologies embedded in an established network of experts allowed prompt analysis of pediatric nephrologists’ response to COVID-19 during this fast-emerging public health crisis. Such rapid sharing of knowledge and local practices is essential to timely and optimal guidance for medical management of specific patient groups in multi-country health care systems such as those of Europe and the US. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00467-020-04584-6) contains supplementary material, which is available to authorized users.

negative: Epidemiological and Clinical Aspects of COVID-19;a Narrative Review There are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of COVID-19 as a new emerging epidemic In addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable However, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic Accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities

negative: Global Spread of Hemorrhagic Fever Viruses: Predicting Pandemics As successive epidemics have swept the world, the scientific community has quickly learned from them about the emergence and transmission of communicable diseases. Epidemics usually occur when health systems are unprepared. During an unexpected epidemic, health authorities engage in damage control, fear drives action, and the desire to understand the threat is greatest. As humanity recovers, policy-makers seek scientific expertise to improve their “preparedness” to face future events. Global spread of disease is exemplified by the spread of yellow fever from Africa to the Americas, by the spread of dengue fever through transcontinental migration of mosquitos, by the relentless influenza virus pandemics, and, most recently, by the unexpected emergence of Ebola virus, spread by motorbike and long haul carriers. Other pathogens that are remarkable for their epidemic expansions include the arenavirus hemorrhagic fevers and hantavirus diseases carried by rodents over great geographic distances and the arthropod-borne viruses (West Nile, chikungunya and Zika) enabled by ecology and vector adaptations. Did we learn from the past epidemics? Are we prepared for the worst? The ultimate goal is to develop a resilient global health infrastructure. Besides acquiring treatments, vaccines, and other preventive medicine, bio-surveillance is critical to preventing disease emergence and to counteracting its spread. So far, only the western hemisphere has a large and established monitoring system; however, diseases continue to emerge sporadically, in particular in Southeast Asia and South America, illuminating the imperfections of our surveillance. Epidemics destabilize fragile governments, ravage the most vulnerable populations, and threaten the global community. Pandemic risk calculations employ new technologies like computerized maintenance of geographical and historical datasets, Geographic Information Systems (GIS), Next Generation sequencing, and Metagenomics to trace the molecular changes in pathogens during their emergence, and mathematical models to assess risk. Predictions help to pinpoint the hot spots of emergence, the populations at risk, and the pathogens under genetic evolution. Preparedness anticipates the risks, the needs of the population, the capacities of infrastructure, the sources of emergency funding, and finally, the international partnerships needed to manage a disaster before it occurs. At present, the world is in an intermediate phase of trying to reduce health disparities despite exponential population growth, political conflicts, migration, global trade, urbanization, and major environmental changes due to global warming. For the sake of humanity, we must focus on developing the necessary capacities for health surveillance, epidemic preparedness, and pandemic response.

negative: COVID-19 and animals: What do we know? Coronaviruses, which were generally considered harmless to humans before 2003, have appeared again with a pandemic threatening the world since December 2019 after the epidemics of SARS and MERS. It is known that transmission from person to person is the most important way to spread. However, due to the widespread host diversity, a detailed examination of the role of animals in this pandemic is essential to effectively fight against the outbreak. Although coronavirus infections in pets are known to be predominantly related to the gastrointestinal tract, it has been observed that there are human-to-animal transmissions in this outbreak and some animals have similar symptoms to humans. Although animal-to-animal transmission has been shown to be possible, there is no evidence of animal-to-human transmission.

negative: Bayesian modelling of an epidemic of severe acute respiratory syndrome This paper analyses data arising from a SARS epidemic in Shanxi province of China involving a total of 354 people infected with SARS-CoV between late February and late May 2003. Using Bayesian inference, we have estimated critical epidemiological determinants. The estimated mean incubation period was 5.3 days (95% CI 4.2–6.8 days), mean time to hospitalisation was 3.5 days (95% CI 2.8–3.6 days), mean time from symptom onset to recovery was 26 days (95% CI 25–27 days) and mean time from symptom onset to death was 21 days (95% CI 16–26 days). The reproduction ratio was estimated to be 4.8 (95% CI 2.2–8.8) in the early part of the epidemic (February and March 2003) reducing to 0.75 (95% CI 0.65–0.85) in the later part of the epidemic (April and May 2003). The infectivity of symptomatic SARS cases in hospital and in the community was estimated. Community SARS cases caused transmission to others at an estimated rate of 0.4 per infective per day during the early part of the epidemic, reducing to 0.2 in the later part of the epidemic. For hospitalised patients, the daily infectivity was approximately 0.15 early in the epidemic, but fell to 0.0006 in the later part of the epidemic. Despite the lower daily infectivity level for hospitalised patients, the long duration of the hospitalisation led to a greater number of transmissions within hospitals compared with the community in the early part of the epidemic, as estimated by this study. This study investigated the individual infectivity profile during the symptomatic period, with an estimated peak infectivity on the ninth symptomatic day.

negative: First respiratory transmitted food borne outbreak? Abstract The world is faced with a remarkable coronavirus outbreak with epicentre in Wuhan, China. Altogether 40554 cases have been confirmed globally with novel coronavirus (SARS-CoV-2) until February 10, 2020. Rigorous surveillance in other countries is required to prevent further global expansion of the outbreak, but resolving the exact mechanism of the initial transmission events is crucial. Most initial cases had visited Huanan South Seafood Market in Wuhan selling also various exotic live animals. Based on the limited initial human-to-human transmission and timely clustering of cases in Huanan market among elderly men, coupled with knowledge that coronaviruses are derived from animals and relationship of SARS-CoV-2 to bat coronavirus, zoonotic transmission in the first instance is probable. To target the actions, similar epidemiological actions to human cases are needed with animal or food exposures. According to current information, an exceptionally wide contamination of seafood market might explain the initiation of the SARS-CoV-2 outbreak. Seafood tanks, air contamination by live animals or rodents are possibilities, but sold animals normally come from various sources. The mode of transmission may become clearer in future: usually in outbreak investigations, hindsight is easy, but for now information about the initial source of this outbreak is limited.

negative: Severe Middle East Respiratory Syndrome (MERS) Pneumonia Abstract Middle East Respiratory Syndrome (MERS) is a viral respiratory infection, which ranges from asymptomatic infection to severe pneumonia and multiorgan failure, caused by a novel coronavirus named Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Majority of cases have been reported from Saudi Arabia. MERS cases occur as sporadic cases or as clusters or hospital outbreaks. Dromedary camels are thought to be a host for MERS-CoV. Direct contact with dromedary camels within 14days prior to infection was identified as an independent risk factor for MERS. Diagnosis of MERS is based on a positive real-time reverse transcriptase polymerase chain reaction (rRT-PCR), obtained from a respiratory specimen. The mainstay of management of MERS-CoV infection is supportive care. There is no specific antiviral therapy for MERS-CoV infection at present, although several modalities of treatment options have been examined or are under investigation.

negative: Comment to Döhla et al., Rapid point-of-care testing for SARS-CoV- 2 in a community screening setting shows low sensitivity

negative: Prediction of COVID-19 transmission dynamics using a mathematical model considering behavior changes in Korea OBJECTIVES: Since the report of the first confirmed case in Daegu on February 18, 2020, local transmission of coronavirus disease 2019 (COVID-19) in Korea has continued. In this study, we aimed to identify the pattern of local transmission of COVID-19 using mathematical modeling and predict the epidemic size and the timing of the end of the spread. METHODS: We modeled the COVID-19 outbreak in Korea by applying a mathematical model of transmission that factors in behavioral changes. We used the Korea Centers for Disease Control and Prevention data of daily confirmed cases in the country to estimate the nationwide and Daegu/Gyeongbuk area-specific transmission rates as well as behavioral change parameters using a least-squares method. RESULTS: The number of transmissions per infected patient was estimated to be about 10 times higher in the Daegu/Gyeongbuk area than the average of nationwide. Using these estimated parameters, our models predicts that about 13,800 cases will occur nationwide and 11,400 cases in the Daegu/Gyeongbuk area until mid-June. CONCLUSIONS: We mathematically demonstrate that the relatively high per-capita rate of transmission and the low rate of changes in behavior have caused a large-scale transmission of COVID-19 in the Daegu/Gyeongbuk area in Korea. Since the outbreak is expected to continue until May, non-pharmaceutical interventions that can be sustained over the long term are required.

negative: Global Infodemiology of COVID-19: Focus on Google web searches and Instagram hashtags Background: Several studies have been conducted using 'infodemiological' methods in COVID-19 research, but studies focusing to examine the extent of infodemic monikers (misinformation) on the internet is very limited. Aim: We aimed to investigate the internet search behavior related to COVID-19 and the extent of infodemic monikers circulating in Google and Instagram during the pandemic period in the world. Methods: Using Google Trends and Instagram hashtags (#), we explored the internet search activities and behaviors related to COVID-19 pandemic all over the world from February 20, 2020, to May 06, 2020. Briefly, we investigated the names used to identify the virus, health and risk perception, life during the lockdown, and also information related to the adoption of infodemic monikers related to COVID-19. We computed the average peak volume (APC) with a 95% confidence interval (CI) during the study period. Results: The top five COVID-19 related terms used in Google searches were "coronavirus", "corona", "COVID", "virus", "corona virus", and "COVID-19". Countries with a higher number of COVID-19 cases have greater Google searches queries related to COVID-19. "coronavirus ozone", "coronavirus laboratory", "coronavirus 5G", "coronavirus conspiracy" and "coronavirus bill gates" are widely circulated infodemic monikers on the internet. Searches related to 'tips and cures' to COVID-19 spiked when the US president suggested an unproven drug as a 'miracle cure' and suggested injecting disinfectant to treat COVID-19. Around two-thirds (66.1%) of the Instagram users use "COVID-19", and "coronavirus" hashtags to disperse the information related to COVID-19. Conclusion: Globally, there is a growing interest in COVID-19 and a large number of infodemic monikers are circulating on the internet. Therefore, mass media regulators and health organizers should be vigilant to diminish the infodemic monikers dispersing on the internet and also should take serious actions against those spreading misinformation in social media.

negative: Hipsters on networks: How a minority group of individuals can lead to an antiestablishment majority The spread of opinions, memes, diseases, and “alternative facts” in a population depends both on the details of the spreading process and on the structure of the social and communication networks on which they spread. One feature that can change spreading dynamics substantially is heterogeneous behavior among different types of individuals in a social network. In this paper, we explore how antiestablishment nodes (e.g., hipsters) influence the spreading dynamics of two competing products. We consider a model in which spreading follows a deterministic rule for updating node states (which indicate which product has been adopted) in which an adjustable probability [Formula: see text] of the nodes in a network are hipsters, who choose to adopt the product that they believe is the less popular of the two. The remaining nodes are conformists, who choose which product to adopt by considering which products their immediate neighbors have adopted. We simulate our model on both synthetic and real networks, and we show that the hipsters have a major effect on the final fraction of people who adopt each product: even when only one of the two products exists at the beginning of the simulations, a small fraction of hipsters in a network can still cause the other product to eventually become the more popular one. To account for this behavior, we construct an approximation for the steady-state adoption fractions of the products on [Formula: see text]-regular trees in the limit of few hipsters. Additionally, our simulations demonstrate that a time delay [Formula: see text] in the knowledge of the product distribution in a population, as compared to immediate knowledge of product adoption among nearest neighbors, can have a large effect on the final distribution of product adoptions. Using a local-tree approximation, we derive an analytical estimate of the spreading of products and obtain good agreement if a sufficiently small fraction of the population consists of hipsters. In all networks, we find that either of the two products can become the more popular one at steady state, depending on the fraction of hipsters in the network and on the amount of delay in the knowledge of the product distribution. Our simple model and analysis may help shed light on the road to success for antiestablishment choices in elections, as such success—and qualitative differences in final outcomes between competing products, political candidates, and so on—can arise rather generically in our model from a small number of antiestablishment individuals and ordinary processes of social influence on normal individuals.

negative: Mechanisms of recoverable prevalence and extinction of viruses on linearly growing scale-free networks We investigate mechanisms of the typically observed recoverable prevalence in epidemic spreading. Assuming the time-independent connectivity correlations, we analyze the dynamics of spreading on linearly growing scale-free (SF) networks, and derive the extinction condition related to the rates of network growth, infection, and immunization of viruses. The behavior is consistent with the previous results for SF networks by a mean-field approximation without connectivity correlations. In particular, it is suggested that the growing must be stopped to prevent the spreading of infection. This insight helps to understand the spreading phenomena on communication or social networks.

negative: Social Media as a Sensor of Air Quality and Public Response in China BACKGROUND: Recent studies have demonstrated the utility of social media data sources for a wide range of public health goals, including disease surveillance, mental health trends, and health perceptions and sentiment. Most such research has focused on English-language social media for the task of disease surveillance. OBJECTIVE: We investigated the value of Chinese social media for monitoring air quality trends and related public perceptions and response. The goal was to determine if this data is suitable for learning actionable information about pollution levels and public response. METHODS: We mined a collection of 93 million messages from Sina Weibo, China’s largest microblogging service. We experimented with different filters to identify messages relevant to air quality, based on keyword matching and topic modeling. We evaluated the reliability of the data filters by comparing message volume per city to air particle pollution rates obtained from the Chinese government for 74 cities. Additionally, we performed a qualitative study of the content of pollution-related messages by coding a sample of 170 messages for relevance to air quality, and whether the message included details such as a reactive behavior or a health concern. RESULTS: The volume of pollution-related messages is highly correlated with particle pollution levels, with Pearson correlation values up to .718 (n=74, P<.001). Our qualitative results found that 67.1% (114/170) of messages were relevant to air quality and of those, 78.9% (90/114) were a firsthand report. Of firsthand reports, 28% (32/90) indicated a reactive behavior and 19% (17/90) expressed a health concern. Additionally, 3 messages of 170 requested that action be taken to improve quality. CONCLUSIONS: We have found quantitatively that message volume in Sina Weibo is indicative of true particle pollution levels, and we have found qualitatively that messages contain rich details including perceptions, behaviors, and self-reported health effects. Social media data can augment existing air pollution surveillance data, especially perception and health-related data that traditionally requires expensive surveys or interviews.

negative: What are the Underlying Transmission Patterns of COVID-19 Outbreak? – An Age-specific Social Contact Characterization Abstract Background COVID-19 has spread to 6 continents. Now is opportune to gain a deeper understanding of what may have happened. The findings can help inform mitigation strategies in the disease-affected countries. Methods In this work, we examine an essential factor that characterizes the disease transmission patterns: the interactions among people. We develop a computational model to reveal the interactions in terms of the social contact patterns among the population of different age-groups. We divide a city's population into seven age-groups: 0-6 years old (children); 7-14 (primary and junior high school students); 15-17 (high school students); 18-22 (university students); 23-44 (young/middle-aged people); 45-64 years old (middle-aged/elderly people); and 65 or above (elderly people). We consider four representative settings of social contacts that may cause the disease spread: (1) individual households; (2) schools, including primary/high schools as well as colleges and universities; (3) various physical workplaces; and (4) public places and communities where people can gather, such as stadiums, markets, squares, and organized tours. A contact matrix is computed to describe the contact intensity between different age-groups for each of the four settings. By integrating the four contact matrices with the next-generation matrix, we quantitatively characterize the underlying transmission patterns of COVID-19 among different populations. Findings We focus our study on 6 representative cities in China: Wuhan, the epicenter of COVID-19, together with Beijing, Tianjin, Hangzhou, Suzhou, and Shenzhen, which are five major cities from three key economic zones. The results show that the social contact-based analysis can readily explain the underlying disease transmission patterns as well as the associated risks (including both confirmed and unconfirmed cases). In Wuhan, the age-groups involving relatively intensive contacts in households and public/communities are dispersedly distributed. This can explain why the transmission of COVID-19 in the early stage mainly took place in public places and families in Wuhan. We estimate that Feb. 11, 2020 was the date with the highest transmission risk in Wuhan, which is consistent with the actual peak period of the reported case number (Feb. 4-14). Moreover, the surge in the number of new cases reported on Feb. 12-13 in Wuhan can readily be captured using our model, showing its ability in forecasting the potential/unconfirmed cases. We further estimate the disease transmission risks associated with different work resumption plans in these cities after the outbreak. The estimation results are consistent with the actual situations in the cities with relatively lenient control policies, such as Beijing, and those with strict control policies, such as Shenzhen. Interpretation With an in-depth characterization of age-specific social contact-based transmission, the retrospective and prospective situations of the disease outbreak, including the past and future transmission risks, the effectiveness of different interventions, and the disease transmission risks of restoring normal social activities, are computationally analyzed and reasonably explained. The conclusions drawn from the study not only provide a comprehensive explanation of the underlying COVID-19 transmission patterns in China, but more importantly, offer the social contact-based risk analysis methods that can readily be applied to guide intervention planning and operational responses in other countries, so that the impact of COVID-19 pandemic can be strategically mitigated. Funding General Research Fund of the Hong Kong Research Grants Council; Key Project Grants of the National Science Foundation of China.

negative: Acyclonucleosides: Part 2. diseco-Nucleosides* * Part 1 is in Volume 67 and Part 3 is in Volume 69. This chapter is the second of a sequence of three chapters that appears in successive volumes of this series dealing with the chemistry of acyclonucleosides. The first chapter appeared in the previous volume [97AHC391] and dealt with seco-nucleosides (one bond disconnection). This chapter deals with diseco-nucleosides (two bond disconnections). The final chapter of this series will deal with tri-, tetra-, and pentaseco-nucleosides, as well as contain an appendix of the literature that appeared after the three chapters were prepared.

negative: Chapter 6 Public Health, Communicable Diseases and Global Health Public health professionals are considering how molecular medicine applications can impact on preventive medicine and health provision enabling interventions to start earlier. There is the potential for molecular medicine to improve the workplace although inappropriate use will lead to discrimination. The public health issue of communicable diseases is being addressed through molecular medicine in more effective and early detection and a better understanding of pathogenesis. A threat from emerging and re-emerging infections requires multiple approaches but early and definitive detection will need nucleic acid based approaches. The non-communicable diseases are now a global world problem, particularly obesity. While molecular medicine is still to make a significant impact on this disorder some interesting findings are emerging about the role of genes in obesity. Ultimately, global health issues must include more efficient and environmentally sustainable strategies. Molecular technologies provide a promising approach for the way forward. Keywords Epidemiology, workplace, diagnostics, resistance, virulence, emerging and re-emerging infections, obesity, bioeconomy

negative: Privacy-Preserving Contact Tracing: current solutions and open questions The COVID-19 pandemic has posed a unique challenge for the world to find solutions, ranging from vaccines to ICT solutions to slow down the virus spreading. Due to the highly contagious nature of the virus, social distancing is one fundamental measure which has already adopted by many countries. At the technical level, this prioritises contact tracing solutions, which can alert the users who have been in close contact with the infected persons and meanwhile allow heath authorities to take proper actions. In this paper, we examine several existing privacy-aware contact tracing solutions and analyse their (dis)advantages. At the end, we describe several major observations and outline an interdisciplinary research agenda towards more comprehensive and effective privacy-aware contact tracing solutions.

negative: Contesting the (Super)Natural Origins of Ebola in Macenta, Guinea: Biomedical and Popular Approaches In December 2013, a two-year-old child died from viral haemorrhagic fever in Méliandou village in the South-East of Guinea, and constituted the likely index case of a major epidemic. When the virus was formally identified as Ebola, epidemiologists started to investigate the chains of transmission, while local people were trying to make sense out of these deaths. The epidemic control measures taken by national and international health agencies were soon faced by strong reluctance and a sometimes aggressive attitude of the affected communities. Based on ethnographic work in Macenta (Forest region) in the autumn of 2014 for the Global Outbreak and Alert Response Network (GOARN) of the World Health Organization, this chapter shows that while epidemiologists involved in the outbreak response attributed the first Ebola deaths in the Forest region to the transmission of a virus from an unknown animal reservoir, local citizens believed these deaths were caused by the breach of a taboo. Epidemiological and popular explanations, mainly evolving in parallel, but sometimes overlapping, were driven by different explanatory models: a biomedical model embodying nature in the guise of an animal disease reservoir, which in turn poses as threat to humanity, and a traditional-religious model wherein nature and culture are not dichotomized. The chapter will argue that epidemic responses must be flexible and need to systematically document popular discourse(s), rumours, codes, practices, knowledge and opinions related to the outbreak event. This precious information must be used not only to shape and adapt control interventions and health promotion messages, but also to trace the complex biosocial dynamics of such zoonotic disease beyond the usual narrow focus on wild animals as the sources of infection.

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: Infection control and MERS-CoV in health-care workers

negative: Kinetics of Serologic Responses to MERS Coronavirus Infection in Humans, South Korea We investigated the kinetics of serologic responses to Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using virus neutralization and MERS-CoV S1 IgG ELISA tests. In most patients, robust antibody responses developed by the third week of illness. Delayed antibody responses with the neutralization test were associated with more severe disease.

negative: Racial/ethnic and socioeconomic disparities of Covid-19 attacks rates in Suffolk County communities We investigated the dependence of Covid-19 attack rates on demographic and socioeconomic factors for the communities in Suffolk County (Long Island, New York State), presently the 5th most-affected county in the United States. Confirming the previous observations that minorities are disproportionately impacted by the Covid-19 disease, we found that the attack rate is strongly correlated with the minority population proportion, with an alarmingly high $\sim4$-fold attack rate increase for Black and Hispanic populations.

negative: Original research: How accurate are digital symptom assessment apps for suggesting conditions and urgency advice?: a clinical vignettes comparison to GPs Objectives To compare breadth of condition coverage, accuracy of suggested conditions and appropriateness of urgency advice of 8 popular symptom assessment apps with each other and with 7 General Practitioners. Design Clinical vignettes study. Setting 200 clinical vignettes representing real-world scenarios in primary care. Intervention/comparator Condition coverage, suggested condition accuracy, and urgency advice performance was measured against the vignettes' gold-standard diagnoses and triage level. Primary outcome measures Outcomes included (i) proportion of conditions 'covered' by an app, i.e. not excluded because the patient was too young/old, pregnant, or comorbid, (ii) proportion of vignettes in which the correct primary diagnosis was amongst the top 3 conditions suggested, and, (iii) proportion of 'safe' urgency level advice (i.e. at gold standard level, more conservative, or no more than one level less conservative). Results Condition-suggestion coverage was highly variable, with some apps not offering a suggestion for many users: in alphabetical order, Ada: 99.0%; Babylon: 51.5%; Buoy: 88.5%; K Health: 74.5%; Mediktor: 80.5%; Symptomate: 61.5%; Your.MD: 64.5%. The top-3 suggestion accuracy (M3) of GPs was on average 82.1{+/-}5.2%. For the apps it was - Ada: 70.5%; Babylon: 32.0%; Buoy: 43.0%; K Health: 36.0%; Mediktor: 36.0%; Symptomate: 27.5%; WebMD: 35.5%; Your.MD: 23.5%. Some apps exclude certain user groups (e.g. younger users) or certain conditions - for these apps condition-suggestion performance is generally greater with exclusion of these vignettes. For safe urgency advice, tested GPs had an average of 97.0{+/-}2.5%. For the vignettes with advice provided, only three apps had safety performance within 1 S.D. of the GPs (mean) - Ada: 97.0%; Babylon: 95.1%; Symptomate: 97.8%. One app had a safety performance within 2 S.D.s of GPs - Your.MD: 92.6%. Three apps had a safety performance outside 2 S.D.s of GPs - Buoy: 80.0% (p< 0.001); K Health: 81.3% (p< 0.001); Mediktor: 87.3% (p=1.3x10-3). Conclusions The utility of digital symptom assessment apps relies upon coverage, accuracy, and safety. While no digital tool outperformed GPs, some came close, and the nature of iterative improvements to software offers scalable improvements to care.

negative: Middle East Respiratory Syndrome Coronavirus Superspreading Event Involving 81 Persons, Korea 2015 Since the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported on May 20, 2015 in Korea, there have been 186 laboratory-confirmed cases of MERS-CoV infection with 36 fatalities. Ninety-seven percent (181/186) of the cases had exposure to the health care facilities. We are reporting a superspreading event that transmitted MERS-CoV to 81 persons at a hospital emergency room (ER) during the Korean outbreak in 2015. The index case was a 35-yr-old man who had vigorous coughing while staying at the ER for 58 hr. As in severe acute respiratory syndrome outbreaks, superspreading events can cause a large outbreak of MERS in healthcare facilities with severe consequences. All healthcare facilities should establish and implement infection prevention and control measure as well as triage policies and procedures for early detection and isolation of suspected MERS-CoV cases.

negative: Quarantine for pandemic influenza control at the borders of small island nations BACKGROUND: Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure. METHODS: Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered. RESULTS: We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals). CONCLUSION: Quarantine at the borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available).

negative: Coupled disease–behavior dynamics on complex networks: A review Abstract It is increasingly recognized that a key component of successful infection control efforts is understanding the complex, two-way interaction between disease dynamics and human behavioral and social dynamics. Human behavior such as contact precautions and social distancing clearly influence disease prevalence, but disease prevalence can in turn alter human behavior, forming a coupled, nonlinear system. Moreover, in many cases, the spatial structure of the population cannot be ignored, such that social and behavioral processes and/or transmission of infection must be represented with complex networks. Research on studying coupled disease–behavior dynamics in complex networks in particular is growing rapidly, and frequently makes use of analysis methods and concepts from statistical physics. Here, we review some of the growing literature in this area. We contrast network-based approaches to homogeneous-mixing approaches, point out how their predictions differ, and describe the rich and often surprising behavior of disease–behavior dynamics on complex networks, and compare them to processes in statistical physics. We discuss how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies. We also describe the growing sources of digital data that are facilitating research in this area. Finally, we suggest pitfalls which might be faced by researchers in the field, and we suggest several ways in which the field could move forward in the coming years.

negative: An evidence-based framework for priority clinical research questions for COVID-19 BACKGROUND: On 31 December, 2019, the World Health Organization China Country Office was informed of cases of pneumonia of unknown aetiology. Since then, there have been over 75 000 cases globally of the 2019 novel coronavirus (COVID-19), 2000 deaths, and over 14 000 cases recovered. Outbreaks of novel agents represent opportunities for clinical research to inform real-time public health action. In 2018, we conducted a systematic review to identify priority research questions for Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related coronavirus (MERS-CoV). Here, we review information available on COVID-19 and provide an evidenced-based framework for priority clinical research in the current outbreak. METHODS: Three bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to clinical research questions addressed. In February 2020, available information on COVID19 was reviewed and compared to the results of the SARS-CoV and MERS-CoV systematic review. RESULTS: From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. For COVID19, some information on clinical presentation, diagnostic testing, and aetiology is available but many clinical research gaps have yet to be filled. CONCLUSIONS: Based on a systematic review of other severe coronaviruses, we summarise the state of clinical research for COVID-19, highlight the research gaps, and provide recommendations for the implementation of standardised protocols. Data based on internationally standardised protocols will inform clinical practice real-time.

negative: Does COVID-19 Spread Through Droplets Alone?

negative: Epidemiological study of novel coronavirus (COVID-19) We report a statistical analysis of some highly infected countries by the novel coronavirus (COVID-19). The cumulative infected data were fitted with various growth models (e.g. Logistic equation, Weibull equation and Hill equation) and obtained the power index of top ten highly infected countries. The newly infected data were fitted with Gaussian distribution with the peak at ~40 days for the countries whose infection curves are seem to be saturated. The similarity in growth kinetics of infected people of different countries provides first-hand guidelines to take proper precautions to minimize human damage.

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

negative: Covid-19 Outbreak Progression in Italian Regions: Approaching the Peak by March 29th Setting: Italy and especially Lombardy is experiencing a heavy burden of Covid-19 infection. The peak of the epidemics has not yet been reached and it is expected to be delayed in Central and Southern Italian regions compared to Northern ones. Objective: We have modeled the Covid-19 outbreak progression in Italian Regions vs. Lombardy to assess the epidemics. Primary and Secondary Measures: In our models, we have estimated the basic reproduction number (R0) which represents the average number of people that can be infected by a person who has already acquired the infection both by fitting the exponential growth rate of the infection across a 1month period and also by using day by day assessment, based on single observations. We used the susceptible exposed infected removed (SEIR) compartment model to predict the spreading of the pandemic in Italy. Results. The two methods provide agreements of values, although the first method based on exponential fit should provide a better estimation, being computed on the entire time series. Taking into account the growth rate of the infection across a 1-month period, in Lombardy each infected person has involved other 5 people (4.94 based on data of March 22nd) compared to a value of R0=2.68 reported in the Chinese city of Whuan. According to our model and Piedmont, Veneto, Emilia Romagna, Tuscany and Marche reach an R0 value up to 4. The R0 is 3.7 for Lazio and 3.6 for Campania region, where this latter shows the highest value among the Southern Italian regions, followed by Apulia (3.5), Sicily (3.4), Abruzzo (3.4), Calabria (3.1), Basilicata (2.5) and Molise (2.4). The value of R0 is decreasing in Lombardy and Northern Regions, while it is increasing in Central and Southern Regions. Conclusion. The peak is expected by March 29th at national level.

negative: New Technologies for the Diagnosis of Infection

negative: COVID-19, City Lockdown, and Air Pollution: Evidence from China The rapid spread of COVID-19 is a global public health challenge. To prevent the escalation of its transmission, China locked down one-third of its cities and strictly restricted human mobility and economic activities. Using timely and comprehensive air quality data in China, we show that these counter-COVID-19 measures led to remarkable improvement in air quality. Within weeks, the Air Quality Index and PM2.5 concentrations were brought down by 25%. The effects are larger in colder, richer, and more industrialized cities. We estimate that such improvement would avert 24,000 to 36,000 premature deaths from air pollution on a monthly basis.

negative: Loop-anchor purse-string closure of gastrotomy in NOTES(R) procedures: survival studies in a porcine model. INTRODUCTION Transgastric NOTES(®) procedures remain without a simple method to close the gastrotomy. In four survival swine studies, we have tested a novel gastric closure device: the loop-anchor purse-string (LAPS) closure system. METHODS In four anesthetized pigs, an endoscopic gastrotomy was performed. Four loop anchors were arrayed in a 2-cm square pattern around the gastrotomy. The endoscope was passed into the abdominal cavity, and the gastrotomy was cinched closed. RESULTS Procedure times ranged from 50-180 minutes. Three pigs survived 14 days. One animal was sacrificed early due to signs of sepsis. Another animal developed fevers and was treated with antibiotics. At necropsy, there were no abscesses, including in the septic animal. Histologic examination revealed evidence of healing in all animals. DISCUSSION The LAPS system holds promise with early success in an animal model. Future human studies are needed to determine viability as a human visceral closure device.

negative: On the evolutionary epidemiology of SARS-CoV-2 There is no doubt that the novel coronavirus SARS-CoV-2 that causes COVID-19 is mutating and thus has the potential to adapt during the current pandemic. Whether this evolution will lead to changes in the transmission, the duration, or the severity of the disease is not clear. This has led to considerable scientific and media debate, from raising alarms about evolutionary change to dismissing it. Here we review what little is currently known about the evolution of SARS-CoV-2 and extend existing evolutionary theory to consider how selection might be acting upon the virus during the COVID-19 pandemic. While there is currently no definitive evidence that SARS-CoV-2 is undergoing further adaptation, continued, evidence-based, analysis of evolutionary change is important so that public health measures can be adjusted in response to substantive changes in the infectivity or severity of COVID-19.

negative: Coronavirus envelope protein: current knowledge BACKGROUND: Coronaviruses (CoVs) primarily cause enzootic infections in birds and mammals but, in the last few decades, have shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. A renewed interest in coronaviral research has led to the discovery of several novel human CoVs and since then much progress has been made in understanding the CoV life cycle. The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis. Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins. MAIN BODY: This review aims to establish the current knowledge on CoV E by highlighting the recent progress that has been made and comparing it to previous knowledge. It also compares E to other viral proteins of a similar nature to speculate the relevance of these new findings. Good progress has been made but much still remains unknown and this review has identified some gaps in the current knowledge and made suggestions for consideration in future research. CONCLUSIONS: The most progress has been made on SARS-CoV E, highlighting specific structural requirements for its functions in the CoV life cycle as well as mechanisms behind its pathogenesis. Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates. The high mortality rate of certain CoVs, along with their ease of transmission, underpins the need for more research into CoV molecular biology which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.

negative: Systematic Literature Review on the Spread of Health-related Misinformation on Social Media Contemporary commentators describe the current period as “an era of fake news” in which misinformation, generated intentionally or unintentionally, spreads rapidly. Although affecting all areas of life, it poses particular problems in the health arena, where it can delay or prevent effective care, in some cases threatening the lives of individuals. While examples of the rapid spread of misinformation date back to the earliest days of scientific medicine, the internet, by allowing instantaneous communication and powerful amplification has brought about a quantum change. In democracies where ideas compete in the marketplace for attention, accurate scientific information, which may be difficult to comprehend and even dull, is easily crowded out by sensationalized news. In order to uncover the current evidence and better understand the mechanism of misinformation spread, we report a systematic review of the nature and potential drivers of health-related misinformation. We searched PubMed, Cochrane, Web of Science, Scopus and Google databases to identify relevant methodological and empirical articles published between 2012 and 2018. A total of 57 articles were included for full-text analysis. Overall, we observe an increasing trend in published articles on health-related misinformation and the role of social media in its propagation. The most extensively studied topics involving misinformation relate to vaccination, Ebola and Zika Virus, although others, such as nutrition, cancer, fluoridation of water and smoking also featured. Studies adopted theoretical frameworks from psychology and network science, while co-citation analysis revealed potential for greater collaboration across fields. Most studies employed content analysis, social network analysis or experiments, drawing on disparate disciplinary paradigms. Future research should examine susceptibility of different sociodemographic groups to misinformation and understand the role of belief systems on the intention to spread misinformation. Further interdisciplinary research is also warranted to identify effective and tailored interventions to counter the spread of health-related misinformation online.

negative: Chapter 2 Expanding the Concept of Public Health Abstract Ancient societies recognized the needs of sanitation, food safety, workers’ health, and medical care to protect against disease and to promote well-being and civic prosperity. New energies and knowledge since the eighteenth century produced landmark discoveries such as prevention of scurvy and vaccination against smallpox. The biological germ theory and competing miasma theory each proved effective in sanitation, and immunization in control of infectious diseases. Non-communicable diseases as the leading causes of mortality have responded to innovative preventive care of health risk factors, smoking, hypertension, obesity, physical inactivity, unhealthful diets, and diabetes mellitus. Health promotion proved effective to modern public health in tackling disease origins, individual behavior, and social and economic conditions. The global burden of infectious and non-communicable diseases, aging and chronic illness faces rising costs and still inadequate prevention. The evolution of concepts of public health will have to address these new challenges of population health.

negative: Laparoscopic ovariectomy in dogs: comparison between single portal and two-portal access. OBJECTIVE To compare surgical times and perioperative complication rates of single portal access and 2-portal laparoscopic ovariectomy (LapOVE) in dogs using a bipolar vessel sealer/divider device, and to evaluate the performance of novice laparoscopists for right ovariectomy. STUDY DESIGN Controlled clinical trial. ANIMALS Female dogs (n=42). METHODS Dogs were divided into groups: 1=single portal and 2=2 portal. LapOVE was performed using a 5 mm vessel sealer/divider device and a 10 mm operating laparoscope (Group 1) or a 5 mm laparoscope (Group 2). Dog characteristics (weight, body condition score, ovarian ligament fat score), operative time, and perioperative complication rate were compared between groups. Right ovariectomy duration was evaluated for 2 novice laparoscopists. RESULTS No significant difference was found in mean total surgical time between group 1 (21.07 min/s) and group 2 (19.06 min/s). Factors significantly affecting times included body condition scores, ovarian ligament fat score, ovarian bleeding, and surgeon expertise. Minor complications (bleeding from ovaries or after splenic trauma) occurred and were similar in both groups. Bleeding was correlated to body condition score and ovarian ligament fat score. Interindividual differences were found among surgeons for right ovariectomy time. CONCLUSIONS Single portal access LapOVE using vessel sealer/divider device is feasible, safe, and does not significantly increase total surgical time in comparison with 2-portal approach. Laparoscopic skills may play a role in ability to perform single portal LapOVE. CLINICAL RELEVANCE LapOVE can be performed using single portal access.

negative: Estimating the transmission potential of supercritical processes based on the final size distribution of minor outbreaks Use of the final size distribution of minor outbreaks for the estimation of the reproduction numbers of supercritical epidemic processes has yet to be considered. We used a branching process model to derive the final size distribution of minor outbreaks, assuming a reproduction number above unity, and applying the method to final size data for pneumonic plague. Pneumonic plague is a rare disease with only one documented major epidemic in a spatially limited setting. Because the final size distribution of a minor outbreak needs to be normalized by the probability of extinction, we assume that the dispersion parameter (k) of the negative-binomial offspring distribution is known, and examine the sensitivity of the reproduction number to variation in dispersion. Assuming a geometric offspring distribution with k = 1, the reproduction number was estimated at 1.16 (95% confidence interval: 0.97–1.38). When less dispersed with k = 2, the maximum likelihood estimate of the reproduction number was 1.14. These estimates agreed with those published from transmission network analysis, indicating that the human-to-human transmission potential of the pneumonic plague is not very high. Given only minor outbreaks, transmission potential is not sufficiently assessed by directly counting the number of offspring. Since the absence of a major epidemic does not guarantee a subcritical process, the proposed method allows us to conservatively regard epidemic data from minor outbreaks as supercritical, and yield estimates of threshold values above unity.

negative: The 2019 Novel Coronavirus Outbreak - A Global Threat The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international significance. There are significant knowledge gaps in the epidemiology, transmission dynamics, investigation tools and management. In this article, we review the available evidence about this disease. Every decade has witnessed the evolution of a new coronavirus epidemic since the last three decades. The varying transmission patterns, namely, nosocomial transmission and spread through mildly symptomatic cases is an area of concern. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, ARDS, acute cardiac injury and septic shock. Presence of bilateral ground glass opacity and consolidation on imaging in appropriate clinical background should raise a suspicion about COVID 19. Poor prognostic factors include Multilobular infiltration on chest imaging, Lymphopenia, Bacterial co-infection, Smoking history, Chronic medical conditions like Hypertension and age >60 years (MuLBSTA score). Diagnosis is confirmed with PCR based testing of appropriate respiratory samples. Management is primarily supportive, with newer antivirals (lopinavir ritonavir and Remdesivir) under investigation. Role of steroids is still inconclusive. Standard infection control and prevention techniques should be followed. Vigilant screening of suspected cases and their contacts is important. Isolation of symptomatic cases and home quarantine of asymptomatic contacts is recommended. To conclude, controlling this highly transmissible disease requires international co-ordination.

negative: Plausibility of therapeutic effects of Rho kinase inhibitors against Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19)

negative: Genetic drift and environmental spreading dynamics of COVID-19 Objective To delineate the genetic and environmental determinants of COVID-19 spreading. Design Retrospective case series. Setting Spain, Italy, Sweden, Finland, Norway. Participants All laboratory-confirmed infection cases (n=168,089) collected from February 21st to April 14th 2020. Main outcome measures Infection spreading velocity according to viral mutation load and to climate region. Results The mean doubling time of COVID-19 was 6.63 days in northern Italy, 5.87 days in central areas, and 5.38 days in southern Italy, with shorter COVID-19 doubling time in warmer regions. Spain extended this trend, with a mean COVID-19 doubling time of 4.2 days. At the other end of the spectrum, slower diffusion across progressively colder regions was observed in Scandinavia, with 9.4 days COVID-19 doubling time in Sweden, 10.8 days in Finland and 12.95 days in Norway. Mutations and mutation rates of SARS-CoV-2 versus COVID-19 spreading were analyzed worldwide. Models of increased aggressiveness of SARS-CoV-2 upon progressive acquisition of genetic changes were not supported by regional mutation data. Conclusion Current propagation models suggest dependence of COVID-19 pandemic spreading on wintertime conditions, with expected waning over the summer. Our findings indicate association of COVID-19 to a sharp North/South climate gradient, with faster spreading in southern regions. Thus, warmer climate conditions may not limit SARS-CoV-2 diffusion. Very cold regions may be better spared by recurrent courses of infection.

negative: Shared Tasks on Authorship Analysis at PAN 2020 The paper gives a brief overview of the four shared tasks that are to be organized at the PAN 2020 lab on digital text forensics and stylometry, hosted at CLEF conference. The tasks include author profiling, celebrity profiling, cross-domain author verification, and style change detection, seeking to advance the state of the art and to evaluate it on new benchmark datasets.

negative: [Impact of complicated myocardial injury on the clinical outcome of severe or critically ill COVID-19 patients]. Objective: To analyze the clinical characteristics of the severe or critically ill patients with novel coronavirus pneumonia (COVID-19), and evaluate the impact of complicated myocardial injury on the prognosis of these patients. Methods: A retrospective study was conducted in 54 patients who admitted to Tongji hospital from February 3, 2020 to February 24, 2020 and met the criteria of severe or critical conditions of COVID-19. The clinical characteristics and hospital mortality rate were analyzed and compared between the patients with or without myocardial injury, which was defined with 3 times higher serum cardiac troponin value. Results: The median age of the 54 patients was 68 (59.8, 74.3) years. Among all the patients, 24 (44.4%) patients were complicated with hypertension, 13 (24.1%) with diabetes, 8 (14.8%) with coronary heart disease, and 3 (5.6%) with previous cerebral infarction. During hospitalization, 24 (44.4%) of the patients were complicated with myocardial injury and 26 (48.1%) patients died in hospital. In-hospital mortality was significantly higher in patients with myocardial injury than in patients without myocardial injury (14 (60.9%) vs. 8 (25.8%), P=0.013). Moreover, the levels of C-reactive protein (153.6 (80.3, 240.7) ng/L vs. 49.8 (15.9, 101.9) ng/L) and N-terminal pro-B-type natriuretic peptide (852.0 (400.0, 2 315.3) ng/L vs. 197.0 (115.3, 631.0) ng/L) were significantly higher than patients without myocardial injury (all P<0.01). Conclusions: Prevalence of myocardial injury is high among severe or critically ill COVID-19 patients. Severe or critically ill COVID-19 patients with myocardial injury face a significantly higher risk of in-hospital mortality. The study suggests that it is important to monitor and manage the myocardial injury during hospitalization for severe or critically ill COVID-19 patients.

negative: Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID-19 Abstract Case details: A case of a 50-year old HIV-positive man is presented, with focus on visualization of post-mortem computed tomography (PMCT) of the lungs, in comparison to a forensic control case. He had been found dead at home, a day after his nasopharyngeal swab had returned positive for SARS-COV-2, three days after the sample had been taken as an outpatient, over five weeks after first exhibiting possible symptoms. 3D-visualization was performed by visually discriminating correlates for aerated, poorly aerated and non-aerated lung regions. The visual side-by-side comparison with a control case shows the deterioration beyond any ”normal” post-mortem finding, however. The PMCT findings in the lungs resemble those of patients with acute respiratory distress syndrome (ARDS), while histologically identified inflammation also shows, in part binuclear, lymphocytes. In addition, acute liver dystrophy and acute tubular necrosis in the kidneys were found. Except coronary artery atherosclerosis, there appeared to be no remarkable pathology of the heart. Comment: With the pandemic impact of SARS-COV-2, a range of issues unfolds, also for medicolegal investigations into deaths, as we report the first Swiss case with post-mortem CT where death had occurred due to a SARS-COV-2 infection, with features of a severe acute respiratory distress syndrome, as an outpatient. As this pandemic from the view of risk assessment does constitute a black swan, underestimated fat tails as technical reason should be addressed by also analyzing apparent extreme single observations. This case of an outpatient (without hospital or intensive-care treatment) shows a pulmonary progression beyond the typical findings of COVID-19, to a non-specific picture of ARDS, where histologically, in part binuclear lymphocytes were remarked. What appeared to be an initially slow progression with final rapid escalation raises the question whether nasopharyngeal swabs alone or added pulmonary CT might be better for screening high-risk patients. The reported symptoms and relatively late medical consultation in this case appeared to contrast with the extensive pathology, raising the question whether any search for super-spreaders should not just focus on asymptomatic but under-reported symptomatic patients, and whether their prolonged circulation in everyday life would justify measures such as for example more extensive face mask policies. As post-mortem testing for SARS-COV-2 may not be available for every case, PMCT may provide sensitive testing for lung changes related to COVID-19. In order to allow for more precise medicolegal investigations in the context of COVID-19, however, any more specific extra tests may have to be financed by stakeholders in epidemiology, infectious disease or policy.

negative: Human Saliva: Non-Invasive Fluid for Detecting Novel Coronavirus (2019-nCoV) The breakthrough of novel coronavirus (2019-nCoV) in Wuhan, a city of China, has damaged the status of health and quality of life. In the sequel of this epidemic or contagious disease, the patient experiences fever, chest paint, chills, a rapid heartbeat, breathing difficulties, pneumonia, and kidney failure. It has been suggested that this disease can spread through human-to-human transmission or by super spreading. By the help of the non-invasive fluid “saliva”, it is easy to detect the virus. This can help with the comfort of the patient as well as healthcare personnel. Under this perspective, we discuss the epidemic situation of 2019-nCOV and its relationship with human saliva.

negative: The effect of network mixing patterns on epidemic dynamics and the efficacy of disease contact tracing In networks, nodes may preferentially contact other nodes with similar (assortatively mixed) or dissimilar (disassortatively mixed) numbers of contacts. Different patterns of contact support different epidemic dynamics, potentially affecting the efficacy of control measures such as contact tracing, which aims to identify and isolate nodes with infectious contacts. We used stochastic simulations to investigate the effects of mixing patterns on epidemic dynamics and contact-tracing efficacy. For uncontrolled epidemics, outbreaks occur at lower infection rates for more assortatively mixed networks, with faster initial epidemic growth rate and shorter epidemic duration than for disassortatively mixed networks. Contact tracing performs better for assortative mixing where epidemic size is large and tracing rate low, but it performs better for disassortative mixing at higher contact rates. For assortatively mixed networks, disease spreads first to highly connected nodes, but this is balanced by contact tracing quickly identifying these same nodes. The converse is true for disassortative mixing, where both disease and tracing are less likely to target highly connected nodes. For small epidemics, contact tracing is more effective on disassortative networks due to the greater resilience of assortative networks to link removal. Multi-step contact tracing is more effective than single-step tracing for assortative mixing, but this effect is smaller for disassortatively mixed networks.

negative: Response to “The imaginary ‘Asian Super Consumer’: A critique of demand reduction campaigns for the illegal wildlife trade” Abstract In a recent paper in Geoforum, Margulies et al. (2019) outline what they perceive as a bias toward an “Asian super consumer”. They argue that wildlife trade demand reduction campaigns are unfocused, untargeted, and therefore have a tendency to place blame on people of colour and communities in the Global South as key actors in driving illegal wildlife trade. As researchers and practitioners, we have been studying the demand for wildlife and wildlife products for many years. While we agree that it is vitally important to consider the cultural nuances of illegal and unsustainable wildlife trade and to operate in a manner that is respectful toward different cultures, we believe that the authors have overlooked the fact that modern wildlife trade demand reduction campaigns are already conducting this research and using it to target their campaigns to specific groups.

negative: Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof) Abstract The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease-19 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically-available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically-available and investigational immunomodulators, such as the IL-6 inhibitors tocilizumab and sarilumab and the anti-GMCSF lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.

negative: And now for something completely different: from 2019-nCoV and COVID-19 to 2020-nMan

negative: SARS and MERS: recent insights into emerging coronaviruses The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.81) contains supplementary material, which is available to authorized users.

negative: Actitud diagnóstica y terapéutica ante la sospecha de infección broncopulmonar aguda en pacientes inmunocompetentes Resumen Las infecciones respiratorias agrupan tres entidades con indicaciones terapéuticas diferentes: la bronquitis aguda, la neumonía aguda y las exacerbaciones de la bronquitis crónica. Por consiguiente, es importante diferenciarlas. La bronquitis aguda es muy frecuente, de fácil diagnóstico y de evolución benigna. Por regla general, es de origen viral, y la antibioticoterapia no está justificada. Por el contrario, las neumonías agudas son poco frecuentes pero tienen un riesgo evolutivo de potencial gravedad y representan la sexta causa de mortalidad. Su etiología suele ser bacteriana en el adulto y siempre requieren antibioticoterapia. Su diagnóstico clínico es de presunción, basado en los siguientes signos: fiebre, taquicardia, taquipnea, dolor torácico, estertores crepitantes en el foco de infección e impresión de gravedad. Estos signos justifican la realización de una radiografía de tórax. Las exacerbaciones de la bronquitis crónica pueden ser de origen bacteriano, viral o no infeccioso. Las indicaciones de la antibioticoterapia dependerán de la probabilidad de su etiología bacteriana (aumento de volumen y aspecto purulento de la expectoración, aparición o empeoramiento de la disnea) y del estadio evolutivo de la bronquitis crónica (simple, obstructiva sin insuficiencia respiratoria crónica, insuficiencia respiratoria crónica).

negative: Anesthetic Management of Patients with COVID 19 Infections during Emergency Procedures Objectives The aim of the present study was to prevent cross-infection in the operating room during emergency procedures for patients with confirmed or suspected 2019 novel coronavirus (2019-nCoV) by following anesthesia management protocols, and to document clinical- and anesthesia-related characteristics of these patients. Design This was a retrospective, multicenter clinical study. Setting This study used a multicenter dataset from 4 hospitals in Wuhan, China. Participants Patients and health care providers with confirmed or suspected 2019-nCoV from January 23 to 31, 2020, at the Wuhan Union Hospital, the Wuhan Children's Hospital, The Central Hospital of Wuhan, and the Wuhan Fourth Hospital in Wuhan, China. Interventions Anesthetic management and infection control guidelines for emergency procedures for patients with suspected 2019-nCoV were drafted and applied in 4 hospitals in Wuhan. Measurements and Main Results Cross-infection in the operating rooms of the 4 hospitals was effectively reduced by implementing the new measures and procedures. The majority of patients with laboratory-confirmed 2019-nCoV infection or suspected infection were female (23 [62%] of 37), and the mean age was 41.0 years old (standard deviation 19.6; range 4-78). 10 (27%) patients had chronic medical illnesses, including 4 (11%) with diabetes, 8 (22%) with hypertension, and 8 (22%) with digestive system disease. Twenty-five (68%) patients presented with lymphopenia, and 23 (62%) patients exhibited multiple mottling and ground-glass opacity on computed tomography scanning. Conclusions The present study indicates that COVID 19–specific guidelines for emergency procedures for patients with confirmed or suspected 2019-nCoV may effectively prevent cross-infection in the operating room. Most patients with confirmed or suspected COVID 19 presented with fever and dry cough and demonstrated bilateral multiple mottling and ground-glass opacity on chest computed tomography scans.

negative: Cats, coronaviruses and coronavirus antibody tests Feline infectious peritonitis and other coronavirus infections of cats are briefly reviewed. Interpretation and applications of feline coronavirus antibody tests are described, and general recommendations are provided for practitioners. Some of the major unresolved questions regarding coronavirus infections of cats are delineated.

negative: Asymptomatic carriers of COVID-19 as a concern for disease prevention and control: more testing, more follow-up Following a containment phase of two months, China has transitioned to the mitigation phase. However, China still faces the risk of COVID-19 spreading due to not only to sporadic new cases and imported cases but also asymptomatic carriers. According to daily reports from the National Health Commission of the People's Republic of China from March 31, 2020 to April 7, 2020, the number of new asymptomatic cases reported daily greatly exceeded that of new imported cases. As of 24:00 on April 7, there were a total of 1,095 asymptomatic cases with COVID-19 under medical observation on the Chinese mainland, including 358 imported cases. A growing number of studies have indicated that asymptomatic carriers are infectious to an extent and can potentially transmit COVID-19. At present, China's measures for managing asymptomatic carriers are 14 days of centralized quarantine and observation; in principle, people with two consecutive negative nucleic acid tests (at an interval of at least 24 hours) can be released from quarantine. However, asymptomatic carriers will not be included in confirmed cases unless they develop clinical manifestations while in quarantine. As "silent spreaders", asymptomatic carriers warrant attention as part of disease prevention and control. The testing and follow-up of asymptomatic carriers should be expanded to include people in close contact with patients with confirmed COVID-19 and asymptomatic cases, clusters of outbreaks, and key areas and populations with a high risk of infection.

negative: Effective containment explains sub-exponential growth in confirmed cases of recent COVID-19 outbreak in Mainland China The recent outbreak of COVID-19 in Mainland China is characterized by a distinctive algebraic, sub-exponential increase of confirmed cases with time during the early phase of the epidemic, contrasting an initial exponential growth expected for an unconstrained outbreak with sufficiently large reproduction rate. Although case counts vary significantly between affected provinces in Mainland China, the scaling law t^μ is surprisingly universal, with a range of exponents μ = 2.1 ± 0.3. The universality of this behavior indicates that, in spite of social, regional, demographical, geographical, and socio-economical heterogeneities of affected Chinese provinces, this outbreak is dominated by fundamental mechanisms that are not captured by standard epidemiological models. We show that the observed scaling law is a direct consequence of containment policies that effectively deplete the susceptible population. To this end we introduce a parsimonious model that captures both, quarantine of symptomatic infected individuals as well as population wide isolation in response to mitigation policies or behavioral changes. For a wide range of parameters, the model reproduces the observed scaling law in confirmed cases and explains the observed exponents. Quantitative fits to empirical data permit the identification of peak times in the number of asymptomatic or oligo-symptomatic, unidentified infected individuals, as well as estimates of local variations in the basic reproduction number. The model implies that the observed scaling law in confirmed cases is a direct signature of effective contaiment strategies and/or systematic behavioral changes that affect a substantial fraction of the susceptible population. These insights may aid the implementation of containment strategies in potential export induced COVID-19 secondary outbreaks elsewhere or similar future outbreaks of other emergent infectious diseases.

negative: Modeling the heterogeneous disease-behavior-information dynamics during epidemics The transmission of infectious diseases depends on the social networks among people and the protections that people have taken before being exposed to the disease. Mass media is playing a key role in making the public aware of the disease and its transmissibility and severity. Motivated by the importance of heterogeneous risk perception in the population to response to infectious disease outbreaks, we propose a heterogeneous three-layer network model, namely the Susceptible-Exposed-Infectious-Recovered Unaware-Aware-Protected (SEIR-UAP) model, where people's vulnerability to the disease is influenced by the processes of awareness information diffusion, preventive behavior change and infectious disease transmission. We found that (a) the awareness of the disease plays the central role in preventing disease outbreak; (b) we need a reasonable ratio of"over-reacting"nodes to effectively control the disease outbreak; (c) diseases with a longer incubation period and a higher recovery rate are easier to control because the processes of information diffusion and behavior change can help people prepare for the upcoming exposure to the disease; (d) it is more difficult to control the disease with asymptomatic cases. The results provide evidence that mass media should not play down the transmissibility and severity of diseases, so that the public can become aware of the disease as soon as possible.

negative: Outbreak of novel coronavirus (COVID-19): What is the role of radiologists? • Novel coronavirus (COVID-19)-infected pneumonia usually manifests as bilateral ground-glass opacities in the lung periphery on chest CT scans. • Role of radiologists includes not only early detection of lung abnormality, but also suggestion of disease severity, potential progression to acute respiratory distress syndrome, and possible bacterial co-infection in hospitalized patients.

negative: The 2019 novel coronavirus disease (COVID-19) pandemic: A review of the current evidence A novel coronavirus (nCoV) spillover event, with its epicenter in Wuhan, People's Republic of China, has emerged as a public health emergency of international concern. This began as an outbreak in December 2019, and till February 28, 2020, there have been 83,704 confirmed cases of novel coronavirus disease 2019 (COVID-19) globally, with 2,859 deaths, resulting in an overall case fatality rate of 3.41 per cent (95% confidence interval 3.29-3.54%). By this time (February 28, 2020) 58 countries or territories and one international conveyance (Diamond Princess Cruise Ship) were affected. As a part of the global response to manage and contain the pandemic, major emphasis was placed on generating research intelligence to guide evidence-based responses to contain the virus, which was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), owing to its genetic similarities with the SARS virus. This review summarizes the emerging evidence which can help guide the public health response, particularly in India. Key areas have been identified in which research needs to be conducted to generate critical intelligence for advising prevention and control efforts. The emergence of SARS-CoV-2 has once again exposed the weaknesses of global health systems preparedness, ability to respond to an infectious threat, the rapidity of transmission of infections across international borders and the ineffectiveness of knee-jerk policy responses to emerging/re-emerging infectious disease threats. The review concludes with the key learning points from the ongoing efforts to prevent and contain COVID-19 and identifies the need to invest in health systems, community-led response mechanisms and the need for preparedness and global health security.

negative: Ethical, legal and societal considerations on Zika virus epidemics complications in scaling-up prevention and control strategies Much of the fear and uncertainty around Zika epidemics stem from potential association between Zika virus (ZIKV) complications on infected pregnant women and risk of their babies being born with microcephaly and other neurological abnormalities. However, much remains unknown about its mode of transmission, diagnosis and long-term pathogenesis. Worries of these unknowns necessitate the need for effective and efficient psychosocial programs and medical-legal strategies to alleviate and mitigate ZIKV related burdens. In this light, local and global efforts in maintaining fundamental health principles of moral, medical and legal decision-making policies, and interventions to preserve and promote individual and collectiveHuman Rights, autonomy, protection of the most vulnerable, equity, dignity, integrity and beneficence that should not be confused and relegated by compassionate humanitarian assistance and support. This paper explores the potential medical and ethical-legal implications of ZIKV epidemics emergency response packages and strategies alongside optimizing reproductive and mental health policies, programs and best practice measures. Further long-term cross-borders operational research is required in elucidating Zika-related population-based epidemiology, ethical-medical and societal implications in guiding evidence-based local and global ZIKV maternal-child health complications related approaches and interventions. Core programs and interventions including future Zika safe and effective vaccines for global Zika immunization program in most vulnerable and affected countries and worldwide should be prioritized.

negative: Genetic diversity and potential recombination between ferret coronaviruses from European and American lineages

negative: Coupling dynamics of epidemic spreading and information diffusion on complex networks Abstract The interaction between disease and disease information on complex networks has facilitated an interdisciplinary research area. When a disease begins to spread in the population, the corresponding information would also be transmitted among individuals, which in turn influence the spreading pattern of the disease. In this paper, firstly, we analyze the propagation of two representative diseases (H7N9 and Dengue fever) in the real-world population and their corresponding information on Internet, suggesting the high correlation of the two-type dynamical processes. Secondly, inspired by empirical analyses, we propose a nonlinear model to further interpret the coupling effect based on the SIS (Susceptible-Infected-Susceptible) model. Both simulation results and theoretical analysis show that a high prevalence of epidemic will lead to a slow information decay, consequently resulting in a high infected level, which shall in turn prevent the epidemic spreading. Finally, further theoretical analysis demonstrates that a multi-outbreak phenomenon emerges via the effect of coupling dynamics, which finds good agreement with empirical results. This work may shed light on the in-depth understanding of the interplay between the dynamics of epidemic spreading and information diffusion.

negative: Connecting clusters of COVID-19: an epidemiological and serological investigation Summary Background Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19. Methods In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection. Findings Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320. Interpretation Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods. Funding National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).

negative: Wuhan and Hubei COVID-19 mortality analysis reveals the critical role of timely supply of medical resources • COVID-19 mortality rates in Wuhan and Hubei decay exponentially. • COVID-19 mortality rates outside Hubei and Wuhan are nearly constant. • COVID-19 recovery rates in Wuhan and Hubei grow exponentially. • Over 40,000 aided health workers help Hubei to effectively treat patients. • Newly supplied beds allow over 38,000 patients in Wuhan to be treated in hospitals.

negative: A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.

negative: China's fight against COVID-19: What we have done and what we should do next? Background: On 12 March, the World Health Organization Director-General declared that "the threat of a global pandemic has become a reality", and the disease caused by the novel coronavirus, known as COVID-19, has become a global concern. Chinese efforts in curbing the virus have widely been recognized. Even the WHO has lauded the efforts of the Chinese government and advised the world to learn from China in fighting the disease. Since the outbreak of COVID-19, to curb the spread of the epidemic, the Chinese government has implemented unprecedented prevention interventions at the nationwide level. Currently, the outbreak in Wuhan is changing in a positive direction and has been effectively controlled. However, it is not clear what these measures were and how these measures changed to curb the outbreak of COVID-19 quickly. This study explored the characteristics and identified that China's control strategies have changed the epidemiological curve of rapidly rising new confirmed cases of COVID-19. This study also seeks to expand the experiences and lessons from this outbreak. Methods: We collected public health interventions measures from Jan 20, 2020, to 5 March 2020, and data from COVID-19 daily newly confirmed cases and daily cumulates cases to compare the control effects and changing trends. We performed a retrospective description of these intervention strategies from three stages. Besides, from the perspective of public health, the experiences and lessons exposed by this outbreak were roughly summarized. Results: These non-pharmacology interventions measures adopted by the Chinese government by the instruction and spirit of President Xi Jinping were timely and efficient. Conclusions: The present study was conducted to comprehensively analyze from a social epidemiology context. The results confirmed that these radical interventions taken by the Chinese government were effective, ambitious, and agile. However, we must be aware that the epidemic situation in Wuhan is still challenging. Keywords: China; COVID-19; intervention measures; change features, lessons

negative: [An increased neutrophil/lymphocyte ratio is an early warning signal of severe COVID-19]. OBJECTIVE To identify the biomarkers as early warning signals for severe COVID-19. METHODS We retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19. RESULTS The patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels (P < 0.05). The co- morbidity of diabetes, NLR, SSA and CRP were found to positively correlate and ALB to inversely correlate with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for severe COVID-19 (OR=1.264, 95% CI: 1.046-1.526, P=0.015) with an AUC of 0.831 (95% CI: 0.730-0.932), an optimal diagnostic threshold of 4.795, a sensitivity of 0.839, and a specificity of 0.750. CONCLUSIONS An increased NLR can serve as an early warning signal of severe COVID-19.

negative: COVID-19 and Lessons to Be Learned from Prior Coronavirus Outbreaks

negative: Coronavirus disease 2019 (COVID-19): current status and future perspectives ABSTRACT Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.

negative: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain Coronaviruses have developed various measures to evade innate immunity. We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. M protein from human coronavirus HKU1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response.

negative: 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 outbreak of COVID-19 coronavirus and its impact on global mental health BACKGROUND: The current outbreak of COVID-19 coronavirus infection among humans in Wuhan (China) and its spreading around the globe is heavily impacting on the global health and mental health. Despite all resources employed to counteract the spreading of the virus, additional global strategies are needed to handle the related mental health issues. METHODS: Published articles concerning mental health related to the COVID-19 outbreak and other previous global infections have been considered and reviewed. COMMENTS: This outbreak is leading to additional health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear globally. Collective concerns influence daily behaviors, economy, prevention strategies and decision-making from policy makers, health organizations and medical centers, which can weaken strategies of COVID-19 control and lead to more morbidity and mental health needs at global level.

negative: Association between mobility patterns and COVID-19 transmission in the USA: a mathematical modelling study BACKGROUND: Within 4 months of COVID-19 first being reported in the USA, it spread to every state and to more than 90% of all counties. During this period, the US COVID-19 response was highly decentralised, with stay-at-home directives issued by state and local officials, subject to varying levels of enforcement. The absence of a centralised policy and timeline combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the USA a challenge. METHODS: We used daily mobility data derived from aggregated and anonymised cell (mobile) phone data, provided by Teralytics (Zürich, Switzerland) from Jan 1 to April 20, 2020, to capture real-time trends in movement patterns for each US county, and used these data to generate a social distancing metric. We used epidemiological data to compute the COVID-19 growth rate ratio for a given county on a given day. Using these metrics, we evaluated how social distancing, measured by the relative change in mobility, affected the rate of new infections in the 25 counties in the USA with the highest number of confirmed cases on April 16, 2020, by fitting a statistical model for each county. FINDINGS: Our analysis revealed that mobility patterns are strongly correlated with decreased COVID-19 case growth rates for the most affected counties in the USA, with Pearson correlation coefficients above 0·7 for 20 of the 25 counties evaluated. Additionally, the effect of changes in mobility patterns, which dropped by 35-63% relative to the normal conditions, on COVID-19 transmission are not likely to be perceptible for 9-12 days, and potentially up to 3 weeks, which is consistent with the incubation time of severe acute respiratory syndrome coronavirus 2 plus additional time for reporting. We also show evidence that behavioural changes were already underway in many US counties days to weeks before state-level or local-level stay-at-home policies were implemented, implying that individuals anticipated public health directives where social distancing was adopted, despite a mixed political message. INTERPRETATION: This study strongly supports a role of social distancing as an effective way to mitigate COVID-19 transmission in the USA. Until a COVID-19 vaccine is widely available, social distancing will remain one of the primary measures to combat disease spread, and these findings should serve to support more timely policy making around social distancing in the USA in the future. FUNDING: None.

negative: Stability of the spreading in small-world network with predictive controller Abstract In this Letter, we apply the predictive control strategy to suppress the propagation of diseases or viruses in small-world network. The stability of small-world spreading model with predictive controller is investigated. The sufficient and necessary stability condition is given, which is closely related to the controller parameters and small-world rewiring probability p. Our simulations discover a phenomenon that, with the fixed predictive controller parameters, the spreading dynamics become more and more stable when p decreases from a larger value to a smaller one, and the suitable controller parameters can effectively suppress the spreading behaviors even when p varies within the whole spectrum, and the unsuitable controller parameters can lead to oscillation when p lies within a certain range.

negative: Citrus tristeza virus: Evolution of Complex and Varied Genotypic Groups Amongst the Closteroviridae, Citrus tristeza virus (CTV) is almost unique in possessing a number of distinct and characterized strains, isolates of which produce a wide range of phenotype combinations among its different hosts. There is little understanding to connect genotypes to phenotypes, and to complicate matters more, these genotypes are found throughout the world as members of mixed populations within a single host plant. There is essentially no understanding of how combinations of genotypes affect symptom expression and disease severity. We know little about the evolution of the genotypes that have been characterized to date, little about the biological role of their diversity and particularly, about the effects of recombination. Additionally, genotype grouping has not been standardized. In this study we utilized an extensive array of CTV genomic information to classify the major genotypes, and to determine the major evolutionary processes that led to their formation and subsequent retention. Our analyses suggest that three major processes act on these genotypes: (1) ancestral diversification of the major CTV lineages, followed by (2) conservation and co-evolution of the major functional domains within, though not between CTV genotypes, and (3) extensive recombination between lineages that have given rise to new genotypes that have subsequently been retained within the global population. The effects of genotype diversity and host-interaction are discussed, as is a proposal for standardizing the classification of existing and novel CTV genotypes.

negative: Antiviral therapy in management of COVID-19: a systematic review on current evidence BACKGROUND: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19. METHOD: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included. RESULTS: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV. CONCLUSION: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.

negative: Study of Epidemiological Characteristics and In-silico Analysis of the Effect of Interventions in the SARS-CoV-2 Epidemic in India After SARS-CoV-2 set foot in India, the Government took a number of steps to limit the spread of the disease in the country. This study involves assessing how the disease affected the population in the initial days of the epidemic. Data was collected from government-controlled and crowdsourced websites and analysed. Studying age and sex parameters of 413 Indian COVID-19 patients, the median age of the affected individuals was found to be 36 years (IQR, 25-54) with 20-39 years males being the most affected group. The number of affected males (66.34%) was more than that of the females (33.66%). Using Susceptible-Infected- Removed (SIR) model, the range of contact rate (β) of India was calculated and the role of public health interventions was assessed. If current contact rate continues, India may have 5583 to 13785 active cases at the end of 21 days lockdown.

negative: SARS and West Nile Virus Clinical presentation of SARS is nonspecific; the important clinical findings in West Nile virus infection are those associated with neurological complications. Rapid and accurate diagnosis of SARS and West Nile virus infection remains an important clinical challenge. Older adults are at higher risk of complications, including death from SARS and West Nile virus. At present, there is no effective therapy for these infections. Although efforts are under way, there are presently no effective vaccines for SARS or West Nile virus.

negative: Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals(1). However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread(2). Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection(3,4). Viral genome analysis revealed close relatedness to coronaviruses found in bats(5). Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature12005) contains supplementary material, which is available to authorized users.

negative: Transplant programs during COVID-19: Unintended consequences for health inequality

negative: MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. METHODS: We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. FINDINGS: 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% [23/117] vs 5% [3/58] in group B vs 1% [4/500] in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2–17, IQR 5–10). The median incubation period was significantly shorter in group A than in group C (5 days [IQR 4–8] vs 11 days [6–12]; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure. INTERPRETATION: Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. FUNDING: None.

negative: Early detection of SARS-CoV-2 antibodies in COVID-19 patients as a serologic marker of infection BACKGROUND: Thousands of medical staff had been infected with SARS-CoV-2 virus with hundreds of deaths reported. Such loss could be prevented if there is a serologic assay for SARS-CoV-2-specific antibodies for serological surveillance of its infection at the early stage of disease. METHODS: Using CHO cell expressed full length SARS-CoV-2 S1 protein as capturing antigen, a COVID-19/SARS-CoV-2 S1 serology ELISA kit was developed and validated with negative samples collected prior to the outbreaks or during the outbreak, and positive samples from patients confirmed with COVID-19. RESULTS: The specificity of the ELISA kit was 97.5%, as examined against total 412 normal human samples. The sensitivity was 97.1% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. The assay was able to detect SARS-CoV-2 antibody on day one after the onset of COVID-19 disease. The average antibody levels increased during the hospitalization and after been discharged for two weeks. SARS-CoV-2 antibodies were detected in 28 out of 276 asymptomatic medical staff and one out of five nucleic acid test-negative “Close contacts” of COVID-19 patient. CONCLUSION: With the assays developed here, we can screen medical staff, in-coming patients, passengers and people who are in close contact with the confirmed patients to identify the “innocent viral spreaders”, protect the medical staff and stop the further spreading of the virus.

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: A case of 2019 Novel Coronavirus in a pregnant woman with preterm delivery We presented a case of a 30-week pregnant woman with COVID-19 delivering a healthy baby with no evidence of COVID-19.

negative: 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.

negative: Mouse Hepatitis Virus This chapter attempts to provide an overview of the important aspects of mouse hepatitis virus (MHV) experimental biology while emphasizing the virus as a naturally occurring mouse pathogen. Even this is complicated, as it is impossible to generalize with this virus, due to marked differences in the biologic behavior of the myriad virus strains, plus the marked effects of a large number of host factors. It is now known that the MHV group is represented by numerous variants that are constantly mutating, and that these viruses can be biologically separated into respiratory (polytropic) MHVs and enterotropic MHVs, with distinctly different patterns of tissue tropism. This dichotomy is emphasized for discussion, but biology is never absolute. Many of the early MHV isolations are made as a result of contamination of biological materials that correlated with their polytropic biologic behavior. Their stated tropisms frequently were the result of the investigators' research interests and many have therefore been subjected to selective passage that favors a particular tissue tropism. All MHV isolates are related genetically and antigenically, but isolates can be differentiated by genetic sequencing, cross-serum neutralization, or with monoclonal antibodies. Genetic and antigenic relationships are not predictive of biologic behavior.

negative: 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: Computational modeling of Human-nCoV protein-protein interaction network COVID-19 has created a global pandemic with high morbidity and mortality in 2020. Novel coronavirus (nCoV), also known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), is responsible for this deadly disease. International Committee on Taxonomy of Viruses (ICTV) has declared that nCoV is highly genetically similar to SARS-CoV epidemic in 2003 (89% similarity). Limited number of clinically validated Human-nCoV protein interaction data is available in the literature. With this hypothesis, the present work focuses on developing a computational model for nCoV-Human protein interaction network, using the experimentally validated SARS-CoV-Human protein interactions. Initially, level-1 and level-2 human spreader proteins are identified in SARS-CoV-Human interaction network, using Susceptible-Infected-Susceptible (SIS) model. These proteins are considered as potential human targets for nCoV bait proteins. A gene-ontology based fuzzy affinity function has been used to construct the nCoV-Human protein interaction network at 99.98% specificity threshold. This also identifies the level-1 human spreaders for COVID-19 in human protein-interaction network. Level-2 human spreaders are subsequently identified using the SIS model. The derived host-pathogen interaction network is finally validated using 7 potential FDA listed drugs for COVID-19 with significant overlap between the known drug target proteins and the identified spreader proteins.

negative: Mechanisms of viral emergence A number of virologic and environmental factors are involved in the emergence and re-emergence of viral disease. Viruses do not conservatively occupy a single and permanent ecological niche. Rather, due to their intrinsic capacity for genetic change, and to the evolvability of fitness levels, viruses display a potential to parasitize alternative host species. Mutation, recombination and genome segment reassortment, and combination of these molecular events, produce complex and phenotypically diverse populations of viruses, which constitute the raw material on which selection acts. The majority of emerging viral diseases of humans have a zoonotic origin. Sociologic and ecologic factors produce diverse and changing environments in which viral subpopulations have ample opportunities to be selected from intrinsically heterogeneous viral populations, particularly in the case of RNA viruses. In this manner, new human, animal and plant viruses have emerged periodically and, from all evidence, will continue to emerge. This article reviews some of the mechanisms that have been identified in viral emergence, with a focus on the importance of genetic variation of viruses, and on the general concept of biological complexity.

negative: Impact of the Perceived Threat of COVID-19 on Variety-seeking Abstract The COVID-19 pandemic has significantly influenced our daily and social lives as well as our consumption patterns. This paper focuses on the relationship between the COVID-19 threat and variety-seeking. Based on several theories, including reactance theory and terror management theory, we predict that the perceived threat of COVID-19 will increase the tendency to choose more and different options in multiple choice settings. Firstly, two empirical studies demonstrate that variety-seeking in food and stationery choices is enhanced as people's perceived threat from the disease increases. Study 3 further suggests the boundary conditions of the above pattern in that the type of decision (i.e., multiple option selections across different brands vs. within the same brand) will moderate the impact of the perceived threat on varietyseeking. Specifically, when the decision involved choice across different brands, participants showed higher variety-seeking under high (vs. low) perceived threat. However, the opposite pattern was true when the decision involved choice within the same brand. This research offers a deeper understanding of how variety-seeking can be changed by the perceived threat of COVID-19.

negative: Fatalism in the context of COVID-19: Perceiving coronavirus as a death sentence predicts reluctance to perform recommended preventative behaviors() To manage the spread of coronavirus, health entities have urged the public to take preventative measures such as social distancing and handwashing. Yet, many appear reluctant to take these measures. Research is needed to understand factors underlying such reluctance, with the aim of developing targeted health interventions. We identify associating coronavirus with death as one such factor. 590 participants completed surveys in mid-March 2020, which included attitudes toward coronavirus, preventative behavioral intentions, and sociodemographic factors. Associating coronavirus with death negatively predicted intentions to perform preventative behaviors. Further, associating coronavirus with death was not evenly distributed throughout the sample and was related with a number of sociodemographic factors including age, race, and availability of sick leave. Following recommended preventative measures to slow the spread of coronavirus appears to relate to the degree to which people associate coronavirus with death. These findings can be used by public health researchers and practitioners to identify those for whom targeted health communication and interventions would be most beneficial, as well as to frame health messaging in ways that combat fatalism.

negative: Pangolins Harbor SARS-CoV-2-Related Coronaviruses The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed a severe threat to global public health. Yet, the origin of SARS-CoV-2 remains mysterious. Several recent studies (e.g., Lam et al ., Xiao et al .) identified SARS-CoV-2-related viruses in pangolins, providing novel insights into the evolution and diversity of SARS-CoV-2-related viruses.

negative: The biggest mystery: what it will take to trace the coronavirus source

negative: Early epidemiological assessment of the transmission potential and virulence of coronavirus disease 2019 (COVID-19) in Wuhan City: China, January-February, 2020 Background: Since the first cluster of cases was identified in Wuhan City, China, in December, 2019, coronavirus disease 2019 (COVID-19) has rapidly spread across China, causing multiple introductions in 109 countries/territories/areas as of March 10th. Despite the scarcity of publicly available data, scientists around the world have made strides in estimating the magnitude of the epidemic, the basic reproduction number, and transmission patterns. Recently more evidence suggests that a substantial fraction of the infected individuals with the novel coronavirus show little if any symptoms, which suggest the need to reassess the transmission potential of this emerging disease. In this study, we derive estimates of the transmissibility and virulence of COVID-19 in Wuhan City, China, by reconstructing the underlying transmission dynamics using multiple data sources. Methods: We employ statistical methods and publicly available epidemiological datasets to jointly derive estimates of transmissibility and severity associated with the novel coronavirus. For this purpose, the daily series of laboratory-confirmed COVID-19 cases and deaths in Wuhan City and epidemiological data of Japanese evacuees from Wuhan City on board government-chartered flights were integrated into our analysis. Results: Our posterior estimates of basic reproduction number (R) in Wuhan City, China in 2019-2020 reached values as high as 5.20 (95%CrI: 5.04-5.47) and the enhanced public health intervention after January 23rd in 2020 was associated with a declined R at 0.58 (95%CrI: 0.51-0.64), with the total number of infections (i.e. cumulative infections) estimated at 1905526 (95%CrI: 1350283-2655936) in Wuhan City, raising the proportion of infected individuals to 19.1% (95%CrI: 13.5-26.6%). We also found that most recent crude infection fatality ratio (IFR) and time-delay adjusted IFR is estimated to be 0.04% (95% CrI: 0.03-0.06%) and 0.12% (95%CrI: 0.08-0.17%), which is several orders of magnitude smaller than the crude CFR estimated at 4.19% Conclusions: We have estimated key epidemiological parameters of the transmissibility and virulence of COVID-19 in Wuhan, China during January-February, 2020 using an ecological modelling approach. The power of our approach lies in the ability to infer epidemiological parameters with quantified uncertainty from partial observations collected by surveillance systems.

negative: Effect of Alert Level 4 on effective reproduction number: review of international COVID-19 cases The effective reproduction number, Reff, is an important measure of transmission potential in the modelling of epidemics. It measures the average number of people that will be infected by a single contagious individual. A value of Reff > 1 suggests that an outbreak will occur, while Reff< 1 suggests the virus will die out. In response to the COVID-19 pandemic, countries worldwide are implementing a range of intervention measures, such as population-wide social distancing and case isolation, with the goal of reducing Reff to values below one, to slow or eliminate transmission. We analyse case data from 25 international locations to estimate their Reff values over time and to assess the effectiveness of interventions, equivalent to New Zealand's Alert Levels 1-4, for reducing transmission. Our results show that strong interventions, equivalent to NZ's Alert Level 3 or 4, have been successful at reducing Reff below the threshold for outbreak. In general, countries that implemented strong interventions earlier in their outbreak have managed to maintain case numbers at lower levels. These estimates provide indicative ranges of Reff for each Alert Level, to inform parameters in models of COVID-19 spread under different intervention scenarios in New Zealand and worldwide. Predictions from such models are important for informing policy and decisions on intervention timing and stringency during the pandemic.

negative: Dynamic models for Coronavirus Disease 2019 and data analysis In this letter, two time delay dynamic models, a Time Delay Dynamical–Novel Coronavirus Pneumonia (TDD‐NCP) model and Fudan‐Chinese Center for Disease Control and Prevention (CCDC) model, are introduced to track the data of Coronavirus Disease 2019 (COVID‐19). The TDD‐NCP model was developed recently by Chengąŕs group in Fudan and Shanghai University of Finance and Economics (SUFE). The TDD‐NCP model introduced the time delay process into the differential equations to describe the latent period of the epidemic. The Fudan‐CDCC model was established when Wenbin Chen suggested to determine the kernel functions in the TDD‐NCP model by the public data from CDCC. By the public data of the cumulative confirmed cases in different regions in China and different countries, these models can clearly illustrate that the containment of the epidemic highly depends on early and effective isolations.

negative: SIR HELMET (Safety In Radiology HEalthcare Localised Metrological EnviromenT): a low-cost negative-pressure isolation barrier for shielding MRI frontline workers from COVID-19 exposure • Low cost reusable acrylic and silicone rubber barrier shield design. • Localised negative pressure environment simulating isolation rooms. • Does not affect MRI image quality even on the most sensitive sequences. • Additional personal protective equipment for frontline healthcare professionals.

negative: Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein A novel coronavirus (the SARS-CoV-2) has been identified in January 2020 as the causal pathogen for COVID-19 pneumonia, an outbreak started near the end of 2019 in Wuhan, China. The SARS-CoV-2 was found to be closely related to the SARS-CoV, based on the genomic analysis. The Angiotensin converting enzyme 2 protein (ACE2) utilized by the SARS-CoV as a receptor was found to facilitate the infection of SARS-CoV-2 as well, initiated by the binding of the spike protein to the human ACE2. Using homology modeling and molecular dynamics (MD) simulation methods, we report here the detailed structure of the ACE2 in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The predicted model is highly consistent with the experimentally determined complex structures. Plausible binding modes between human ACE2 and the RBD were revealed from all-atom MD simulations. The simulation data further revealed critical residues at the complex interface and provided more details about the interactions between the SARS-CoV-2 RBD and human ACE2. Two mutants mimicking rat ACE2 were modeled to study the mutation effects on RBD binding to ACE2. The simulations showed that the N-terminal helix and the K353 of the human ACE2 alter the binding modes of the CoV2-RBD to the ACE2.

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: Impact of RNA Virus Evolution on Quasispecies Formation and Virulence RNA viruses are known to replicate by low fidelity polymerases and have high mutation rates whereby the resulting virus population tends to exist as a distribution of mutants. In this review, we aim to explore how genetic events such as spontaneous mutations could alter the genomic organization of RNA viruses in such a way that they impact virus replications and plaque morphology. The phenomenon of quasispecies within a viral population is also discussed to reflect virulence and its implications for RNA viruses. An understanding of how such events occur will provide further evidence about whether there are molecular determinants for plaque morphology of RNA viruses or whether different plaque phenotypes arise due to the presence of quasispecies within a population. Ultimately this review gives an insight into whether the intrinsically high error rates due to the low fidelity of RNA polymerases is responsible for the variation in plaque morphology and diversity in virulence. This can be a useful tool in characterizing mechanisms that facilitate virus adaptation and evolution.

negative: Computed tomography manifestations in super early stage 2019 novel coronavirus pneumonia BACKGROUND: The recent outbreak of pneumonia cases in Wuhan, PR China, was caused by a novel beta coronavirus, the 2019 novel coronavirus (COVID-19). PURPOSE: To summarize chest computed tomography (CT) manifestations of the early stage of COVID-19 infection and provide a piece of reliable imaging evidence for initial screening and diagnosis. MATERIAL AND METHODS: From 10 January 2020 to 10 February 2020, we continuously observed chest CT imaging of 14 patients with clinically suspected new coronavirus infection in the two weeks after onset of symptoms. Ground-glass opacity (GGO), consolidation, reticular pattern, and ground-glass mimic nodules in each patient's chest CT image were recorded. RESULTS: We enrolled 14 patients, of which nine patients had the infection confirmed by reverse transcription polymerase chain reaction (RT-PCR). Five patients were highly suspected of infection. All cases had epidemiological evidence. GGO was a dominant imaging manifestation in the initial days of infection. GGO performance accounts for 40% in 1- 2 days, 90% in 3- 6 days, and 85% in 7- 10 days. With disease progression, consolidation appeared on follow-up CT. Consolidation performance accounts for 0% in 1- 2 days, 40% in 3- 6 days, and 71% in 7- 10 days. The lesions are mostly near the pleura. The number of lesions and the extent of the lesions increased as the disease progressed. CONCLUSION: Patients with novel coronavirus pneumonia have characteristic CT features in the initial stage of infection, which can be used as an essential supplement for nucleic acid examination.

negative: ACE2 variants underlie interindividual variability and susceptibility to COVID-19 in Italian population In December 2019, an initial cluster of unexpected interstitial bilateral pneumonia emerged in Wuhan, Hubei province. A human-to-human transmission was immediately assumed and a previously unrecognized entity, termed coronavirus disease 19 (COVID-19) due to a novel coronavirus (2019-nCov) was suddenly described. The infection has rapidly spread out all over the world and Italy has been the first European Country experiencing the endemic wave with unexpected clinical severity in comparison with Asian countries. It has recently been shown that 2019-nCov utilizes host receptors namely angiotensin converting enzyme 2 (ACE2) as host receptor and host proteases for cell surface binding and internalization. Thus, a predisposing genetic background can give reason for interindividual disease susceptibility and/or severity. Taking advantage of the Network of Italian Genomes (NIG), here we mined around 7000 exomes from 5 different Centers looking for ACE2 variants. A number of variants with a potential impact on protein stability were identified. Among these, three missense changes, p.Asn720Asp, p.Lys26Arg, p.Gly211Arg (MAF 0.002 to 0.015), which have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants likely interfering with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed. These findings suggest that a predisposing genetic background may contribute to the observed inter-individual clinical variability associated with COVID-19. They allow an evidence-based risk assessment opening up the way to personalized preventive measures and therapeutic options.

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: The economic impact of quarantine: SARS in Toronto as a case study Abstract Objectives Over time, quarantine has become a classic public health intervention and has been used repeatedly when newly emerging infectious diseases have threatened to spread throughout a population. Here, we weigh the economic costs and benefits associated with implementing widespread quarantine in Toronto during the SARS outbreaks of 2003. Methods We compared the costs of two outbreak scenarios: in Scenario A, SARS is able to transmit itself throughout a population without any significant public health interventions. In Scenario B, quarantine is implemented early on in an attempt to contain the virus. By evaluating these situations, we can investigate whether or not the use of quarantine is justified by being either cost-saving, life saving, or both. Results Our results indicate that quarantine is effective in containing newly emerging infectious diseases, and also cost saving when compared to not implementing a widespread containment mechanism. Conclusions This paper illustrates that it is not only in our humanitarian interest for public health and healthcare officials to remain aggressive in their response to newly emerging infections, but also in our collective economic interest. Despite somewhat daunting initial costs, quarantine saves both lives and money.

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: SARS Severe acute respiratory syndrome (SARS) emerged in southern China in late 2002. It first spread within Guangdong Province and then to other parts of China. Via air travelers, it quickly reached various countries around the globe, causing several major hospital outbreaks. Within weeks, the causative agent, a previously unknown coronavirus (SARS-CoV), was identified, thanks to an unprecedented international effort led by the World Health Organization (WHO). Its origin was quickly traced to wild animals traded locally for culinary purposes. Masked palm civet and some other species seem to have acted as intermediate hosts. Since then, SARS-like coronaviruses were found in different bat species in China and elsewhere, and bats are now regarded as the wildlife reservoir for SARS-CoV. Fortunately, the SARS outbreak could be contained within months. Until July 2003, it had caused 8096 cases, with 774 deaths. Once adequate measures such as isolating patients and quarantining their contacts were strictly adhered to, further transmission between human beings could be interrupted. SARS is an example of how rapidly an infectious agent can spread in the modern world. At the same time, it should serve as a showcase of how international cooperation and modern science can help to combat the spread of infectious diseases.

negative: Serological diagnostic kit of SARS-CoV-2 antibodies using CHO-expressed full-length SARS-CoV-2 S1 proteins WHO has declared COVID-19 a pandemic with more than 300,000 confirmed cases and more than 14,000 deaths. There is urgent need for accurate and rapid diagnostic kits. Here we report the development and validation of a COVID-19/SARS-CoV-2 S1 serology ELISA kit for the detection of total anti-virus antibody (IgG+IgM) titers in sera from either the general population or patients suspected to be infected. For indirect ELISA, CHO-expressed recombinant full length SARS-CoV-2-S1 protein with 6*His tag was used as the coating antigen to capture the SARS-CoV-2-S1 antibodies specifically. The specificity of the ELISA kit was determined to be 97.5%, as examined against total 412 normal human sera including 257 samples collected prior to the outbreak and 155 collected during the outbreak. The sensitivity of the ELISA kit was determined to be 97.5% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. Most importantly, in one case study, the ELISA test kit was able to identify an infected person who had previously been quarantined for 14 days after coming into contact with a confirmed COVID-19 patient, and discharged after testing negative twice by nucleic acid test. With the assays developed here, we can screen millions of medical staffs in the hospitals and people in residential complex, schools, public transportations, and business parks in the epidemic centers of the outbreaks to fish out the "innocent viral spreaders", and help to stop the further spreading of the virus.

negative: Outbreaks of Pandemic (H1N1) 2009 and Seasonal Influenza A (H3N2) on Cruise Ship To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship’s childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.

negative: Pregnancy and breastfeeding during COVID-19 pandemic: A systematic review of published pregnancy cases Background: The COVID-19 pandemic is an emerging concern regarding the potential adverse effects during pregnancy. This study reviews knowledge on the impact of COVID-19 on pregnancy and describes the outcome of published cases of pregnant women diagnosed with COVID-19, as well as the characteristics of COVID-19 positive women who delivered in Portugal by 31 of March 2020. Methods: Searches were conducted in PubMed up to 8 April 2020, using PRISMA standards, to identify original published studies describing pregnant women at any gestational age diagnosed COVID-19. There were no date or language restrictions on the search. All identified studies were included irrespective of assumptions on study quality. Portuguese cases were ascertained by contact with all Portuguese maternities and based on the information provided by their health professionals. Results: We identified 30 original studies reporting 212 cases of pregnant women with COVID-19 (30 discharged while pregnant), 200 from China and 12 from other countries. The 182 published deliveries resulted in one stillbirth and 185 live births. Four women with severe COVID-19 required admission to an intensive care unit but no cases of maternal death were reported. There was one neonatal death. Preterm births occurred in 28.7% of cases, but it is unclear whether this was iatrogenic. All cases with amniotic fluid, placenta, and/or cord blood analyzed for the SARS-CoV-2 virus were negative. Four newborns were positive for SARS-CoV-2 and three newborns had high levels of IgM antibodies. None of the first eight infants born in Portugal tested positive. Breast milk samples from 13 mothers and described in seven studies showed no evidence of SARS-CoV-2. Conclusion: The evidence related to the effect of COVID-19 on pregnant women is still limited. Pregnant women and newborns should be considered particularly vulnerable populations regarding COVID-19 prevention and management strategies.

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: Changing transmission dynamics of COVID-19 in China: a nationwide population-based piecewise mathematical modelling study Background: The first case of COVID-19 atypical pneumonia was reported in Wuhan, China on December 1, 2019. Since then, at least 33 other countries have been affected and there is a possibility of a global outbreak. A tremendous amount of effort has been made to understand its transmission dynamics; however, the temporal and spatial transmission heterogeneity and changing epidemiology have been mostly ignored. The epidemic mechanism of COVID-19 remains largely unclear. Methods: Epidemiological data on COVID-19 in China and daily population movement data from Wuhan to other cities were obtained and analyzed. To describe the transmission dynamics of COVID-19 at different spatio-temporal scales, we used a three-stage continuous-time Susceptible-Exposed-Infectious-Recovered (SEIR) meta-population model based on the characteristics and transmission dynamics of each stage: 1) local epidemic from December 1, 2019 to January 9, 2020; 2) long-distance spread due to the Spring Festival travel rush from January 10 to 22, 2020; and 3) intra-provincial transmission from January 23, 2020 when travel restrictions were imposed. Together with the basic reproduction number (R_0) for mathematical modelling, we also considered the variation in infectivity and introduced the controlled reproduction number (R_c) by assuming that exposed individuals to be infectious; we then simulated the future spread of COVID across Wuhan and all the provinces in mainland China. In addition, we built a novel source tracing algorithm to infer the initial exposed number of individuals in Wuhan on January 10, 2020, to estimate the number of infections early during this epidemic. Findings: The spatial patterns of disease spread were heterogeneous. The estimated controlled reproduction number (R_c) in the neighboring provinces of Hubei province were relatively large, and the nationwide reproduction number (except for Hubei) ranged from 0.98 to 2.74 with an average of 1.79 (95% CI 1.77-1.80). Infectivity was significantly greater for exposed than infectious individuals, and exposed individuals were predicted to have become the major source of infection after January 23. For the epidemic process, most provinces reached their epidemic peak before February 10, 2020. It is expected that the maximum number of infections will be approached by the end of March. The final infectious size is estimated to be about 58,000 for Wuhan, 20,800 for the rest of Hubei province, and 17,000 for the other provinces in mainland China. Moreover, the estimated number of the exposed individuals is much greater than the officially reported number of infectious individuals in Wuhan on January 10, 2020. Interpretation: The transmission dynamics of COVID-19 have been changing over time and were heterogeneous across regions. There was a substantial underestimation of the number of exposed individuals in Wuhan early in the epidemic, and the Spring Festival travel rush played an important role in enhancing and accelerating the spread of COVID-19. However, China's unprecedented large-scale travel restrictions quickly reduced R_c. The next challenge for the control of COVID-19 will be the second great population movement brought by removing these travel restrictions.

negative: Expected impact of COVID-19 outbreak in a major metropolitan area in Brazil In January 2020 China reported to the World Health Organization an outbreak of pneumonia of undetermined origin in the city of Wuhan, Hubei. In January 30, 2020, the World Health Organization declared the outbreak of COVID-19 as a Public Health Emergency of International Interest (PHEI). Objectives: The aim of this study is to assess the impact of a COVID-19 epidemic in the metropolitan region of Sao Paulo, Brazil. Methods: We used a generalized SEIR (Susceptibles, Exposed, Infectious, Recovered) model, with additional Hospitalized variables (SEIHR model) and age-stratified structure to analyze the expected time evolution during the onset of the epidemic in the metropolitan area of Sao Paulo. The model allows to determine the evolution of the number of cases, the number of patients admitted to hospitals and deaths caused by COVID-19. In order to investigate the sensibility of our results with respect to parameter estimation errors we performed Monte Carlo analysis with 100 000 simulations by sampling parameter values from an uniform distribution in the confidence interval. Results: We estimate 1 368 (IQR: 880, 2 407) cases, 301 (22%) in older people (more than 60 years), 81 (50, 143) hospitalizations, and 14 (9, 26) deaths in the first 30 days, and 38 583 (IQR: 16 698, 113, 163) cases, 8 427 (21.8%) in older people (more than 60 years), 2181 (914, 6392) hospitalizations, and 397(166, 1205) deaths in the first 60 days. Limitations: We supposed a constant transmission probability Pc among different age-groups, and that every severe and critic case will be hospitalized, as well as that the detection capacity in all the primary healthcare services does not change during the outbreak. Conclusion: Supposing the reported parameters in the literature apply in the city of Sao Paulo, our study shows that it is expected that the impact of a COVID-19 outbreak will be important, requiring special planning from the authorities. This is the first study for a major metropolitan center in the south hemisphere, and we believe it can provide policymakers with a prognosis of the burden of the pandemic not only in Brazil, but also in other tropical zones, allowing to estimate total cases, hospitalization, and deaths, in support to the management of the public health emergence caused by COVID-19.

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: Hand-hygiene mitigation strategies against global disease spreading through the air transportation network Hand hygiene is considered as an efficient and cost-effective way to limit the spread of diseases and, as such, it is recommended by both the World Health Organization (WHO) and the Centres for Disease Control and Prevention (CDC). While the effect of hand washing on individual transmissibility of a disease has been studied through medical and public-health research, its potential as a mitigation strategy against a global pandemic has not been fully explored yet. In this study, we investigate contagion dynamics through the world air transportation network and analyze the impact of hand-hygiene behavioural changes of airport population against the spread of infectious diseases worldwide. Using a granular dataset of the world air transportation traffic, we build a detailed individual mobility model that controls for the correlated and recurrent nature of human travel and the waiting-time distributions of individuals at different locations. We perform a Monte-Carlo simulation study to assess the impact of different hand-washing mitigation strategies at the early stages of a global epidemic. From the simulation results we find that increasing the hand cleanliness homogeneously at all airports in the world can inhibit the impact of a potential pandemic by 24 to 69%. By quantifying and ranking the contribution of the different airports to the mitigation of an epidemic outbreak, we identify ten key airports at the core of a cost-optimal deployment of the hand-washing strategy: increasing the engagement rate at those locations alone could potentially reduce a world pandemic by 8 to 37%. This research provides evidence of the effectiveness of hand hygiene in airports on the global spread of infectious diseases, and has important implications for the way public-health policymakers may design new effective strategies to enhance hand hygiene in airports through behavioral changes.

negative: [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Objective: An outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. Here, we report results of a descriptive, exploratory analysis of all cases diagnosed as of February 11, 2020. Methods: All COVID-19 cases reported through February 11, 2020 were extracted from China's Infectious Disease Information System. Analyses included: 1) summary of patient characteristics; 2) examination of age distributions and sex ratios; 3) calculation of case fatality and mortality rates; 4) geo-temporal analysis of viral spread; 5) epidemiological curve construction; and 6) subgroup analysis. Results: A total of 72 314 patient records-44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, 10567 (14.6%) clinical diagnosed cases (Hubei only), and 889 asymptomatic cases (1.2%)-contributed data for the analysis. Among confirmed cases, most were aged 30-79 years (86.6%), diagnosed in Hubei (74.7%), and considered mild (80.9%). A total of 1 023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%. The COVID-19 spread outward from Hubei sometime after December 2019 and by February 11, 2020, 1 386 counties across all 31 provinces were affected. The epidemic curve of onset of symptoms peaked in January 23-26, then began to decline leading up to February 11. A total of 1 716 health workers have become infected and 5 have died (0.3%). Conclusions: The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest of Mainland China. With many people returning from a long holiday, China needs to prepare for the possible rebound of the epidemic.

negative: 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: [COVID-19: what does epidemiology tell to decisionmakers?]

negative: COVID-19 and type 1 diabetes: dealing with the difficult duo BACKGROUND: Coronavirus disease 2019 (COVID-19) has aroused global health concerns, particularly in relation to diabetes where it has been associated with poorer outcomes. The bulk of the evolving evidence in diabetes and COVID-19 relates to type 2 diabetes (T2D). Since there are a significant number of patients with type 1 diabetes (T1D) with unique concerns and challenges during the ongoing COVID-19 pandemic, we reviewed existing literature, relevant websites, and related guidelines to form this narrative review to help address key questions in this area. METHODS: We systematically searched the PubMed database up to May 31, 2020, and retrieved all the articles published on T1D and COVID-19. RESULTS: We found 18 relevant articles, each of which carried a part of the evidence regarding the risk of contracting COVID-19 in patients with T1D, effect of COVID-19 on development of T1D, outcomes in T1D with COVID-19, and special management issues in T1D in the light of COVID-19. These have been documented in the present review. CONCLUSION: COVID-19 with T1D presents special challenges. While the available evidence does shed some light, we need more evidence to deal with this difficult duo.

negative: 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.

negative: Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists Coronavirus disease 2019 (COVID‐19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or ‘virus spreaders’. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID‐19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.

negative: Work-related COVID-19 transmission in six Asian countries/areas: A follow-up study OBJECTIVE: There is limited evidence of work-related transmission in the emerging coronaviral pandemic. We aimed to identify high-risk occupations for early coronavirus disease 2019 (COVID-19) local transmission. METHODS: In this observational study, we extracted confirmed COVID-19 cases from governmental investigation reports in Hong Kong, Japan, Singapore, Taiwan, Thailand, and Vietnam. We followed each country/area for 40 days after its first locally transmitted case, and excluded all imported cases. We defined a possible work-related case as a worker with evidence of close contact with another confirmed case due to work, or an unknown contact history but likely to be infected in the working environment (e.g. an airport taxi driver). We calculated the case number for each occupation, and illustrated the temporal distribution of all possible work-related cases and healthcare worker (HCW) cases. The temporal distribution was further defined as early outbreak (the earliest 10 days of the following period) and late outbreak (11(th) to 40(th) days of the following period). RESULTS: We identified 103 possible work-related cases (14.9%) among a total of 690 local transmissions. The five occupation groups with the most cases were healthcare workers (HCWs) (22%), drivers and transport workers (18%), services and sales workers (18%), cleaning and domestic workers (9%) and public safety workers (7%). Possible work-related transmission played a substantial role in early outbreak (47.7% of early cases). Occupations at risk varied from early outbreak (predominantly services and sales workers, drivers, construction laborers, and religious professionals) to late outbreak (predominantly HCWs, drivers, cleaning and domestic workers, police officers, and religious professionals). CONCLUSIONS: Work-related transmission is considerable in early COVID-19 outbreaks, and the elevated risk of infection was not limited to HCW. Implementing preventive/surveillance strategies for high-risk working populations is warranted.

negative: Coronavirus Disease 2019 (COVID-19): An Evidence Map of Medical Literature Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of May 2020, gaps in the existing literature remain unidentified and, hence, unaddressed. In this paper, we summarise the medical literature on COVID-19 between 1 January and 24 March 2020 using evidence maps and bibliometric analysis in order to systematically identify gaps and propose areas for valuable future research. The examined COVID-19 medical literature originated primarily from Asia and focussed mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health research, the use of novel technologies and artificial intelligence, research on the pathophysiology of COVID-19 within different body systems, and research on indirect effects of COVID-19 on the care of non-COVID-19 patients. Research collaboration at the international level was limited although improvements may aid global containment efforts.

negative: Transmission dynamics of the COVID‐19 outbreak and effectiveness of government interventions: A data‐driven analysis Using the parameterized susceptible‐exposed‐infectious‐recovered model, we simulated the spread dynamics of coronavirus disease 2019 (COVID‐19) outbreak and impact of different control measures, conducted the sensitivity analysis to identify the key factor, plotted the trend curve of effective reproductive number (R), and performed data fitting after the simulation. By simulation and data fitting, the model showed the peak existing confirmed cases of 59 769 arriving on 15 February 2020, with the coefficient of determination close to 1 and the fitting bias 3.02%, suggesting high precision of the data‐fitting results. More rigorous government control policies were associated with a slower increase in the infected population. Isolation and protective procedures would be less effective as more cases accrue, so the optimization of the treatment plan and the development of specific drugs would be of more importance. There was an upward trend of R in the beginning, followed by a downward trend, a temporary rebound, and another continuous decline. The feature of high infectiousness for severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2) led to an upward trend, and government measures contributed to the temporary rebound and declines. The declines of R could be exploited as strong evidence for the effectiveness of the interventions. Evidence from the four‐phase stringent measures showed that it was significant to ensure early detection, early isolation, early treatment, adequate medical supplies, patients’ being admitted to designated hospitals, and comprehensive therapeutic strategy. Collaborative efforts are required to combat the novel coronavirus, focusing on both persistent strict domestic interventions and vigilance against exogenous imported cases.

negative: Prevención del riesgo infeccioso en el consultorio de pediatría y en el hospital En Francia, el Ministerio de Sanidad establece en su programa nacional de prevención de infecciones asociadas a la asistencia sanitaria o infecciones nosocomiales de 2015 que los centros sanitarios, así como los establecimientos médico-sociales y los médicos locales deben prevenir este tipo de infecciones. Este artículo describe la prevención de la transmisión de microorganismos procedentes de pacientes o ambientales. Dicha prevención incluye siempre la aplicación de una serie de precauciones estándar (lavado y/o desinfección de manos, uso de guantes ante el menor riesgo de contacto con líquidos biológicos, uso de batas, gafas y mascarillas si existe un riesgo de proyección o de aerosolización de sangre o de cualquier otro producto de origen humano), así como la desinfección del material y de las superficies contaminadas. En algunos casos, es preciso adoptar precauciones específicas complementarias, como las basadas en la transmisión por contacto, por ejemplo en caso de gastroenteritis, las basadas en la transmisión por gotas, en caso de infecciones pulmonares u otorrinolaringológicas, y las específicas de la transmisión aérea, en caso de tuberculosis, sarampión o varicela. El artículo describe la prevención de infecciones asociadas a intervenciones invasivas (colocación de dispositivos urinarios, dispositivos intravasculares, actos quirúrgicos) y de infecciones en piel lesionada o en orificios de ostomía. También contempla la prevención de accidentes por exposición a la sangre (AES): uso de materiales de seguridad, definición clara y escrita de la conducta necesaria ante un AES, vacunación del personal. La emergencia de la resistencia a los antibióticos es un desafío para la salud pública. El control de la difusión de bacterias multirresistentes a los antibióticos y de bacterias altamente resistentes está basado a su vez en el control de la prescripción de antibióticos y de la prevención de la difusión de infecciones a partir de pacientes portadores (transmisión cruzada).

negative: Zoonotic origins of human coronaviruses Mutation and adaptation have driven the co-evolution of coronaviruses (CoVs) and their hosts, including human beings, for thousands of years. Before 2003, two human CoVs (HCoVs) were known to cause mild illness, such as common cold. The outbreaks of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) have flipped the coin to reveal how devastating and life-threatening an HCoV infection could be. The emergence of SARS-CoV-2 in central China at the end of 2019 has thrusted CoVs into the spotlight again and surprised us with its high transmissibility but reduced pathogenicity compared to its sister SARS-CoV. HCoV infection is a zoonosis and understanding the zoonotic origins of HCoVs would serve us well. Most HCoVs originated from bats where they are non-pathogenic. The intermediate reservoir hosts of some HCoVs are also known. Identifying the animal hosts has direct implications in the prevention of human diseases. Investigating CoV-host interactions in animals might also derive important insight on CoV pathogenesis in humans. In this review, we present an overview of the existing knowledge about the seven HCoVs, with a focus on the history of their discovery as well as their zoonotic origins and interspecies transmission. Importantly, we compare and contrast the different HCoVs from a perspective of virus evolution and genome recombination. The current CoV disease 2019 (COVID-19) epidemic is discussed in this context. In addition, the requirements for successful host switches and the implications of virus evolution on disease severity are also highlighted.

negative: Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients BACKGROUND: The novel coronavirus pneumonia COVID-19 caused by SARS-CoV-2 infection could lead to a serious of clinical symptoms and severe illness, including acute respiratory distress syndrome (ARDS) and fatal organ failure. We report the fundamental pathological investigation in the lungs and other organs of fatal cases for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. METHODS: The autopsy and pathological investigations of specimens were performed on bodies of two deceased cases with COVID-19. Gross anatomy and histological investigation by Hematoxylin and eosin (HE) stained were reviewed on each patient. Alcian blue/periodic acid-Schiff (AB-PAS) staining and Masson staining were performed for the examinations of mucus, fibrin and collagen fiber in lung tissues. Immunohistochemical staining were performed on the slides of lung tissues from two patients. Real-time PCR was performed to detect the infection of SARS-CoV-2. Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages. FINDINGS: The main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction. INTERPRETATION: Infection of Alveolar macrophage by SARS-CoV-2 might be drivers of the “cytokine storm”, which might result in damages in pulmonary tissues, heart and lung, and leading to the failure of multiple organs . FUNDING: Shanghai Guangci Translational Medical Research Development Foundation, Shanghai, China

negative: A survey of UK acute clinicians' knowledge of personal protective requirements for infectious diseases and chemical, biological, and radiological warfare agents

negative: 04 – Apport des explorations microbiologiques au diagnostic des infections des voies respiratoires basses The diagnosis of community-acquired pneumonia is usually based on clinical and radiological criteria. The identification of a causative organism is not required for the diagnosis. Although numerous microbiological techniques are available, their sensitivity and specificity are not high enough to guide first-line antimicrobial therapy. Consequently, this treatment remains most often empiric. If the causative organism is identified, the antimicrobial treatment is adapted. Sputum analysis may be proposed as a diagnostic tool for patients with an acute exacerbation of chronic obstructive pulmonary disease, in specific cases (prior antibiotherapy, hospitalization, failure of the empiric antimicrobial treatment).

negative: Health-seeking behavior and transmission dynamics in the control of influenza infection among different age groups BACKGROUND: It has been found that health-seeking behavior has a certain impact on influenza infection. However, behaviors with/without risk perception on the control of influenza transmission among age groups have not been well quantified. OBJECTIVES: The purpose of this study was to assess to what extent, under scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection. MATERIALS AND METHODS: A behavior-influenza model was used to estimate the spread rate of age-specific risk perception in response to an influenza outbreak. A network-based information model was used to assess the effect of network-driven risk perception information transmission on influenza infection. A probabilistic risk model was used to assess the infection risk effect of risk perception with a health behavior change. RESULTS: The age-specific overlapping percentage was estimated to be 40%–43%, 55%–60%, and 19%–35% for child, teenage and adult, and elderly age groups, respectively. Individuals perceive the preventive behavior to improve risk perception information transmission among teenage and adult and elderly age groups, but not in the child age group. The population with perceived health behaviors could not effectively decrease the percentage of infection risk in the child age group, whereas for the elderly age group, the percentage of decrease in infection risk was more significant, with a 97.5th percentile estimate of 97%. CONCLUSION: The present integrated behavior-infection model can help health authorities in communicating health messages for an intertwined belief network in which health-seeking behavior plays a key role in controlling influenza infection.

negative: Epidemiological and Clinical Aspects of COVID-19; a Narrative Review. There are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of COVID-19 as a new emerging epidemic. In addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable. However, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic. Accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities.

negative: COVID-19 outbreak: less stethoscope, more ultrasound

negative: Super-factors associated with transmission of occupational COVID-2019 infection among healthcare staff in Wuhan , China. BACKGROUND Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3·23). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0·37). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5·64). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working.

negative: Critical care lessons from severe acute respiratory syndrome. PURPOSE OF REVIEW Severe acute respiratory syndrome (SARS) is a new disease that caused large outbreaks in several countries in the first half of 2003, resulting in infection in more than 8000 people and more than 900 deaths. During that time, a large body of literature rapidly emerged describing the clinical disease, the etiologic viral agent, and management options. This paper reviews the current status of this knowledge base, with particular reference to the critically ill patient. RECENT FINDINGS Case series of patients from Hong Kong, China, Singapore, and Toronto have characterized the disease with remarkable uniformity. A similarly consistent picture of the SARS patient with respiratory failure has emerged from studies from Toronto and Singapore. Worldwide collaboration led to the rapid identification and gene sequencing of the etiologic virus, SARS-CoV. SUMMARY SARS is a predominantly respiratory illness, spread through droplets from respiratory secretions and possibly via a fecal-oral route. A small number of "super-spreaders" appear to have contributed to the rapid proliferation of the disease. Infection control precautions are an essential component of management. Approximately 20% of patients develop progressive pulmonary infiltrates and respiratory failure, and the mortality rate is as high as 10%. Treatment strategies with antiviral agents such as ribavirin have not clearly demonstrated a benefit, but high-dose corticosteroids appear to be beneficial in patients with progressive disease. The recent outbreaks highlighted the potential for this disease to overwhelm critical care resources, by the volume of patients and loss of healthcare workers to illness and quarantine.

negative: Presymptomatic Transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020 Presymptomatic transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), might pose challenges for disease control. The first case of COVID-19 in Singapore was detected on January 23, 2020, and by March 16, a total of 243 cases had been confirmed, including 157 locally acquired cases. Clinical and epidemiologic findings of all COVID-19 cases in Singapore through March 16 were reviewed to determine whether presymptomatic transmission might have occurred. Presymptomatic transmission was defined as the transmission of SARS-CoV-2 from an infected person (source patient) to a secondary patient before the source patient developed symptoms, as ascertained by exposure and symptom onset dates, with no evidence that the secondary patient had been exposed to anyone else with COVID-19. Seven COVID-19 epidemiologic clusters in which presymptomatic transmission likely occurred were identified, and 10 such cases within these clusters accounted for 6.4% of the 157 locally acquired cases. In the four clusters for which the date of exposure could be determined, presymptomatic transmission occurred 1-3 days before symptom onset in the presymptomatic source patient. To account for the possibility of presymptomatic transmission, officials developing contact tracing protocols should strongly consider including a period before symptom onset. Evidence of presymptomatic transmission of SARS-CoV-2 underscores the critical role social distancing, including avoidance of congregate settings, plays in controlling the COVID-19 pandemic.

negative: Peripheral nerve lesion produces increased levels of major histocompatibility complex antigens in the central nervous system Proliferation of central nervous system (CNS) glia in response to peripheral nerve injury occurs without apparent participation of cells of the immune system. It is shown here that following transection of the rat facial nerve there is strongly elevated expression of class I, and to a lesser extent, class II antigens of the major histocompatibility complex (MHC) in the facial nucleus. It is demonstrated by double-immunofluorescence studies that the cells responsible for increased levels of MHC class I antigens are endogenous brain microglia. These findings emphasize the thought that microglia are immunocompetent cells, but, at the same time, raise the possibility for a non-immubological function of MHC antigens under conditions of neural regeneration.

negative: Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health 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 countries affected. 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.

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

negative: Strategies for Controlling the Spread of COVID-19 We consider a deterministic epidemiological compartmental model that includes age and social contact structure for the COVID-19 crisis and explore the consequences of different strategies for easing current lockdown measures that are in place in many countries. We apply the model to the specific circumstances in the state of New Jersey, in the United States of America. As expected, only a rigorous program of testing, tracing and isolation of cases will allow the state to ease its lockdown with a reduced number of deaths. We also find that a slightly earlier date of lockdown, while reducing the number of deaths in the short term, will only reduce the total number of deaths in the long run if the ensuing strategies in easing the lockdown are carried out with the aforementioned test, trace and isolation program. Otherwise, a slightly earlier lockdown will result in increased deaths as the expected second wave of infection sweeps through the state in the coming months.

negative: Children are not COVID-19 super spreaders: time to go back to school.

negative: Health system capacity in Sydney, Australia in the event of a biological attack with smallpox Planning for a re-emergent epidemic of smallpox requires surge capacity of space, resources and personnel within health systems. There are many uncertainties in such a scenario, including likelihood and size of an attack, speed of response and health system capacity. We used a model for smallpox transmission to determine requirements for hospital beds, contact tracing and health workers (HCWs) in Sydney, Australia, during a modelled epidemic of smallpox. Sensitivity analysis was done on attack size, speed of response and proportion of case isolation and contact tracing. We estimated 100638 clinical HCWs and 14595 public hospital beds in Sydney. Rapid response, case isolation and contact tracing are influential on epidemic size, with case isolation more influential than contact tracing. With 95% of cases isolated, outbreak control can be achieved within 100 days even with only 50% of contacts traced. However, if case isolation and contact tracing both fall to 50%, epidemic control is lost. With a smaller initial attack and a response commencing 20 days after the attack, health system impacts are modest. The requirement for hospital beds will vary from up to 4% to 100% of all available beds in best and worst case scenarios. If the response is delayed, or if the attack infects 10000 people, all available beds will be exceeded within 40 days, with corresponding surge requirements for clinical health care workers (HCWs). We estimated there are 330 public health workers in Sydney with up to 940,350 contacts to be traced. At least 3 million respirators will be needed for the first 100 days. To ensure adequate health system capacity, rapid response, high rates of case isolation, excellent contact tracing and vaccination, and protection of HCWs should be a priority. Surge capacity must be planned. Failures in any of these could cause health system failure, with inadequate beds, quarantine spaces, personnel, PPE and inability to manage other acute health conditions.

negative: Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review BACKGROUND: The coronavirus disease (COVID-19) has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. As of 31 January 2020, this epidemic had spread to 19 countries with 11 791 confirmed cases, including 213 deaths. The World Health Organization has declared it a Public Health Emergency of International Concern. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O’Malley. In this scoping review, 65 research articles published before 31 January 2020 were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors’ affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. RESULTS: Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus’ origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as ways to reduce transmission. To date, no specific antiviral treatment has proven effective; hence, infected people primarily rely on symptomatic treatment and supportive care. CONCLUSIONS: There has been a rapid surge in research in response to the outbreak of COVID-19. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies are relevant to control the current public emergency, more high-quality research is needed to provide valid and reliable ways to manage this kind of public health emergency in both the short- and long-term.

negative: Updating the diagnostic criteria of COVID-19 “suspected case” and “confirmed case” is necessary On 6 February 2020, our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infection, and this guideline provided our experience and make well reference for fighting against this pandemic worldwide. However, the coronavirus disease 2019 (COVID-19) is a new disease, our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience; hence, the strategies of diagnosis and treatment are also continually updated. In this letter, we answered one comment on our guideline and provided the newest diagnostic criteria of “suspected case” and “confirmed case” according to the latest Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People’s Republic of China.

negative: No evidence for distinct types in the evolution of SARS-CoV-2 A recent study by Tang et al. (2020) claimed that two major types of SARS-CoV-2 had evolved in the ongoing COVID-19 pandemic and that one of these types was more “aggressive” than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al, and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.

negative: Dynamical Theory and Cellular Automata Simulations of Pandemic Spread: Understanding Different Temporal Patterns of Infections Here we propose and implement a generalized mathematical model to find the time evolution of population in infectious diseases and apply the model to study the recent COVID-19 pandemic. Our model at the core is a non-local generalization of the widely used Kermack-McKendrick(KM) model where the susceptible(S) population evolves into two other categories, namely infectives(I) and removed(R). This is the well-known SIR model in which we further divide both S and I into high and low risk categories. We first formulate a set of non-local dynamical equations for the time evolution of distinct population distributions under this categorization in an attempt to describe the general scenario of infectious disease progression. We then solve the non-linear coupled differential equations-(i) numerically by the method of propagation, and (ii) a more flexible and versatile cellular automata (CA) simulation which provides a coarse-grained description of the generalized non-local model. In order to account for multiple factors such as role of spreaders before containment, we introduce a time dependent rate which appears to be essential to explain the sudden spikes before the plateau observed in many cases (for example like China). We demonstrate how this generalized approach allows us to handle the effects of (i) time-dependence of the rate-constants of spread, (ii) different population density, (iii) the age ratio, (iv) quarantine, (v) lockdown, and (vi) social distancing. Our study allows us to make certain predictions regarding the nature of spread with respect to several external parameters, treated as control variables. Analysis of the model clearly shows that due to the strong heterogeneity in the epidemic process originating from the distribution of initial infectives, the theory must be local in character but at the same time connect to a global perspective.

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: Tracing Contacts to Control the COVID-19 Pandemic The control of the COVID-19 pandemic requires a considerable reduction of contacts mostly achieved by imposing movement control up to the level of enforced quarantine. This has lead to a collapse of substantial parts of the economy. Carriers of the disease are infectious roughly 3 days after exposure to the virus. First symptoms occur later or not at all. As a consequence tracing the contacts of people identified as carriers is essential for controlling the pandemic. This tracing must work everywhere, in particular indoors, where people are closest to each other. Furthermore, it should respect people's privacy. The present paper presents a method to enable a thorough traceability with very little risk on privacy. In our opinion, the latter capabilities are necessary to control the pandemic during a future relaunch of our economy.

negative: Risk for Transportation of 2019 Novel Coronavirus (COVID-19) from Wuhan to Cities in China On January 23, 2020, China quarantined Wuhan to contain an emerging coronavirus (COVID-19). We estimated the probability of transportation of COVID-19 from Wuhan to 369 cities in China before the quarantine. The expected risk is >50% in 130 (95% CI 89–190) cities and >99% in the 4 largest metropolitan areas of China.

negative: Mathematical and computational approaches to epidemic modeling: a comprehensive review Mathematical and computational approaches are important tools for understanding epidemic spread patterns and evaluating policies of disease control. In recent years, epidemiology has become increasingly integrated with mathematics, sociology, management science, complexity science, and computer science. The cross of multiple disciplines has caused rapid development of mathematical and computational approaches to epidemic modeling. In this article, we carry out a comprehensive review of epidemic models to provide an insight into the literature of epidemic modeling and simulation. We introduce major epidemic models in three directions, including mathematical models, complex network models, and agent-based models. We discuss the principles, applications, advantages, and limitations of these models. Meanwhile, we also propose some future research directions in epidemic modeling.

negative: Lopinavir/ritonavir for the treatment of COVID-19: A living systematic review protocol Objective To assess the efficacy and safety of lopinavir/ritonavir for the treatment of patients with COVID-19. Design This is the protocol of a living systematic review. Data sources We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. Eligibility criteria for selecting studies and methods We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomised trials evaluating the effect of lopinavir/ritonavir - as monotherapy or in combination with other drugs - versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating lopinavir/ritonavir in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. Ethics and dissemination No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.

negative: Vaccine against Middle East respiratory syndrome coronavirus

negative: Evaluation of the Secondary Transmission Pattern and Epidemic Prediction of COVID-19 in the Four Metropolitan Areas of China Understanding the transmission dynamics of COVID-19 is crucial for evaluating its spread pattern, especially in metropolitan areas of China, as its spread could lead to secondary outbreaks. In addition, the experiences gained and lessons learned from China have the potential to provide evidence to support other metropolitan areas and large cities outside China with their emerging cases. We used data reported from January 24, 2020, to February 23, 2020, to fit a model of infection, estimate the likely number of infections in four high-risk metropolitan areas based on the number of cases reported, and increase the understanding of the COVID-19 spread pattern. Considering the effect of the official quarantine regulations and travel restrictions for China, which began January 23~24, 2020, we used the daily travel intensity index from the Baidu Maps app to roughly simulate the level of restrictions and estimate the proportion of the quarantined population. A group of SEIR model statistical parameters were estimated using Markov chain Monte Carlo (MCMC) methods and fitting on the basis of reported data. As a result, we estimated that the basic reproductive number, R(0), was 2.91 in Beijing, 2.78 in Shanghai, 2.02 in Guangzhou, and 1.75 in Shenzhen based on the data from January 24, 2020, to February 23, 2020. In addition, we inferred the prediction results and compared the results of different levels of parameters. For example, in Beijing, the predicted peak number of cases was 467 with a peak time of March 01, 2020; however, if the city were to implement different levels (strict, moderate, or weak) of travel restrictions or regulation measures, the estimation results showed that the transmission dynamics would change and that the peak number of cases would differ by between 54% and 209%. We concluded that public health interventions would reduce the risk of the spread of COVID-19 and that more rigorous control and prevention measures would effectively contain its further spread, and awareness of prevention should be enhanced when businesses and social activities return to normal before the end of the epidemic. Further, the experiences gained and lessons learned from China offer the potential to provide evidence supporting other metropolitan areas and big cities with their emerging cases outside China.

negative: Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.

negative: Epidemic Landscape and Forecasting of SARS-CoV-2 in India BACKGROUND India was one of the countries to institute strict measures for SARS-CoV-2 control in early phase. Since, then, the epidemic growth trajectory was slow before registering an explosion of cases due to local cluster transmissions. METHODS We estimated growth rate and doubling time of SARS-CoV-2 for India and high burden states using crowd sourced time series data. Further, we also estimated Basic Reproductive Number (R0) and time dependent reproductive number (Rt) using serial intervals from the data. We compared the R0 estimated from five different methods and R0 from SB was further used in analysis. We modified standard SIR models to SIRD model to accommodate deaths using R0 with the Sequential Bayesian method (SBM) for simulation in SIRD models. RESULTS On an average, 2.8 individuals were infected by an index case. The mean serial interval was 3.9 days. The R0 estimated from different methods ranged from 1.43 to 1.85. The mean time to recovery was 14, SD 5.3 days. Daily epidemic growth rate of India was 0.16 [95%CI; 0.14, 0.17] with a doubling time of 4.30 days [95%CI; 3.96, 4.70]. From the SIRD model, it can be deduced that the peak of SARS-CoV-2 in India will be around mid-July to early August 2020 with around 12.5% likely to be infected at peak time of incidence. CONCLUSIONS The pattern of spread of SARS-CoV-2 in India is suggestive of community transmission. There is a need to increase fund for infectious disease research and epidemiologic studies. All the current gains may be reversed rapidly if air travel and social mixing resumes rapidly. For the time being, these must be resumed only in a phased manner, and should be back to normal levels only after we are prepared to deal with the disease with efficient tools like vaccine or a medicine.

negative: Virus respiratorios: viejos y nuevos virus. Revisión de métodos diagnósticos Las infecciones respiratorias agudas de etiología viral se encuentran entre las principales causas de morbimortalidad infecciosa en el mundo. Junto a los virus tradicionalmente reconocidos, como los de la gripe, virus respiratorio sincitial, rinovirus, parainfluenza 1 a 4 y adenovirus, se han incorporado otros virus, como metaneumovirus, nuevos coronavirus (coronavirus humanos NL63 y HKU1 y coronavirus causante del síndrome respiratorio agudo grave [SRAG]) y, recientemente, los bocavirus. Aunque la mayoría de estas viriasis son clínicamente benignas y autolimitadas cuando afectan a adultos sanos, sus repercusiones sanitarias se incrementan cuando afectan a niños, ancianos o personas inmunodeprimidas o con enfermedades crónicas de base. Son una importante causa de hospitalización y defunción, fundamentalmente en los meses fríos y, desde el punto de vista sociosanitario, suponen un gran consumo de recursos económicos y una frecuente causa de absentismo laboral. Ocasionalmente, algunos de estos virus dan lugar a problemas sanitarios emergentes en todo el mundo, como sucede con las cepas pandémicas de gripe o el coronavirus asociado al SRAG. Si bien para los virus respiratorios tradicionales los métodos de diagnóstico clásicos, basados en el cultivo y la detección de antígenos, siguen siendo útiles, para los virus recientemente descritos el diagnóstico se realiza fundamentalmente por técnicas de amplificación genómica. Acute respiratory infections (ARI) of viral origin are one of the main causes of morbidity and mortality worldwide. In addition to traditional viruses, such as the influenza virus, respiratory syncytial virus, rhinovirus, parainfluenza viruses 1 to 4, and adenovirus, other viruses such as metapneumovirus, new coronaviruses (human coronavirus NL63 and HKU1 and severe acute respiratory syndrome [SARS]-coronavirus), and recently bocaviruses, have been identified as causal agents of ARI. Although most of these viral infections follow a benign and selflimiting course in healthy adults, the consequences for the health care systems increase when they involve children, the elderly, immunosuppressed individuals, or those with chronic underlying diseases. These viral infections are an important cause of hospitalization and death, mainly during the cold months of the year, and, from a social-health perspective, ARI are a drain on economic resources and a frequent cause of work absenteeism. Occasionally, some of these viruses may cause emergent world health problems, as has occurred with the influenza virus pandemic strain and SARScoronavirus. While classical diagnostic methods based on culture and antigen detection remain useful for traditional respiratory viruses, recently described viruses are diagnosed mainly by molecular amplification techniques.

negative: Adaptive memory and evolution of the human naturalistic mind: Insights from the use of medicinal plants Throughout evolutionary history, humans have been exposed to a wide variety of diseases, some of which have serious and even lethal consequences. Memorizing medicinal plants for the treatment of serious diseases likely maximized the chances of survival and reproduction and was instrumental in the evolutionary success of our species. In the present study, we used the idea of adaptive memory to understand whether human memory evolved to recall information about medicinal plants for the treatment of serious diseases. We considered plant-disease pairs of words as units of information available in a medical system based on the use of medicinal plants. The pairs included in the categories of chronic infectious diseases and transmissible infectious diseases were considered to be of higher adaptive value, whereas those included in the category of common conditions were considered to be of lower adaptive value. Pairs grouped into the category of emerging and reemerging diseases were employed to investigate conformity bias; pairs belonging to the category esthetic uses were considered to be of little adaptive relevance and utilized as an experimental control. Our results revealed that plant-disease pairs associated with the category of common conditions, considered by us to be of lower severity and less adaptive relevance for humans, were better remembered and retained in the participants' memory. We believe that prior experience with common conditions and the frequency of these conditions in the population may have intensified the ability to remember the plant-disease pairs associated with this group of diseases.

negative: Single-cell Analysis of ACE2 Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection Since December 2019, a novel coronavirus named 2019 coronavirus (2019-nCoV) has emerged in Wuhan of China and spread to several countries worldwide within just one month. Apart from fever and respiratory complications, acute kidney injury has been observed in some patients with 2019-nCoV. In a short period of time, angiotensin converting enzyme II (ACE2), have been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same for severe acute respiratory syndrome coronavirus (SARS). To investigate the possible cause of kidney damage in 2019-nCoV patients, we used both published kidney and bladder cell atlas data and an independent unpublished kidney single cell RNA-Seq data generated in-house to evaluate ACE2 gene expressions in all cell types in healthy kidneys and bladders. Our results showed the enriched expression of all subtypes of proximal tubule cells of kidney and low but detectable levels of expression in bladder epithelial cells. These results indicated the urinary system is a potential route for 2019-nCoV infection, along with the respiratory system and digestion system. Our findings suggested the kidney abnormalities of SARS and 2019-nCoV patients may be due to proximal tubule cells damage and subsequent systematic inflammatory response induced kidney injury. Beyond that, laboratory tests of viruses and related indicators in urine may be needed in some special patients of 2019-nCoV.

negative: Transmission and epidemiological characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19): preliminary evidence obtained in comparison with 2003-SARS Objectives: Latest epidemic data of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19) was collected and a detailed statistical analysis was carried out to make comparison with 2003-SARS in order to provide scientific reference for the prevention and control of COVID-19. Methods: The information of COVID-19 and 2003-SARS from websites of NHCPRC and the World Health Organization was collected, and then the transmission dynamics of the two kinds of infectious diseases were analyzed. The information of 853 confirmed COVID-19 patients obtained from the website of health committees of 18 provinces. A descriptive epidemiological analysis method was employed to carefully analyze the epidemic characteristics. Subsequently, the COVID-19 epidemic data in Wuhan and other inland regions of China was analyzed separately and compared. A multivariate function model was constructed based on the confirmed COVID-19 case data. Results: The growth rate of new cases and deaths of COVID-19 were significantly faster than those of 2003-SARS. The number of confirmed cases in Wuhan and other inland areas both showed increasing trends. 853 confirmed COVID-19 cases aged 1 months to 94 years and the average age was (45.05 ± 17.22) years. The gender ratio (M: F) was 1.12: 1. Conclusions: The fatality rate of COVID-19 is lower than that of 2003-SARS and the cure rate is higher. The age of COVID-19 patients is mainly concentrated in the 30-50 years old (60.61%). The harm of the first-generation COVID-19 patients is higher than that of secondary cases.

negative: All together to Fight COVID-19 Novel coronavirus disease (COVID-19), named a pandemic by the WHO, is the current global health crisis. National and international collaboration are indispensable for combating COVID-19 and other similar potential outbreaks. International efforts to tackle this complex problem have led to remarkable scientific advances. Yet, as a global society, we can and must take additional measures to fight this pandemic. Undoubtedly, our approach toward COVID-19 was not perfect, and testing has not been deployed fast enough to arrest the epidemic early on. It is critical that we revise our approaches to be more prepared for pandemics as a united body by promoting global cooperation and commitment.

negative: Emerging Infectious Diseases: Trends and Issues, 2nd Edition

negative: Spread and control of COVID-19 in China and their associations with population movement, public health emergency measures, and medical resources ABSTRACT BACKGROUND The COVID-19 epidemic, first emerged in Wuhan during December 2019, has spread globally. While the mass population movement for Chinese New Year has significantly influenced spreading the disease, little direct evidence exists about the relevance to epidemic and its control of population movement from Wuhan, local emergency response, and medical resources in China. METHODS Spearman's correlation analysis was performed between official data of confirmed COVID-19 cases from Jan 20th to Feb 19th, 2020 and real-time travel data and health resources data. RESULTS There were 74,675 confirmed COVID-19 cases in China by Feb 19th, 2020. The overall fatality rate was 2.84%, much higher in Hubei than in other regions (3.27% vs 0.73%). The index of population inflow from Hubei was positively correlated with total (Provincial r=0.9159, p<0.001; City r=0.6311, p<0.001) and primary cases (Provincial r=0.8702, p<0.001; City r=0.6358, p<0.001). The local health emergency measures (eg, city lockdown and traffic control) were associated with reduced infections nationwide. Moreover, the number of public health employees per capita was inversely correlated with total cases (r=-0.6295, p<0.001) and infection rates (r=-0.4912, p<0.01). Similarly, cities with less medical resources had higher fatality (r=-0.4791, p<0.01) and lower cure rates (r=0.5286, p<0.01) among the confirmed cases. CONCLUSIONS The spread of the COVID-19 in China in its early phase was attributed primarily to population movement from Hubei, and effective governmental health emergency measures and adequate medical resources played important roles in subsequent control of epidemic and improved prognosis of affected individuals.

negative: Group Testing for COVID-19: How to Stop Worrying and Test More The corona virus disease 2019 (COVID-19) caused by the novel corona virus has an exponential rate of infection. COVID-19 is particularly notorious as the onset of symptoms in infected patients are usually delayed and there exists a large number of asymptomatic carriers. In order to prevent overwhelming of medical facilities and large fatality rate, early stage testing and diagnosis are key requirements. In this article, we discuss the methodologies from the group testing literature and its relevance to COVID-19 diagnosis. Specifically, we investigate the efficiency of group testing using polymerase chain reaction (PCR) for COVID-19. Group testing is a method in which multiple samples are pooled together in groups and fewer tests are performed on these groups to discern all the infected samples. We study the effect of dilution due to pooling in group testing and show that group tests can perform well even in the presence of dilution effects. We present multiple group testing algorithms that could reduce the number of tests performed for COVID-19 diagnosis. We analyze the efficiency of these tests and provide insights on their practical relevance. With the use of algorithms described here, test plans can be developed that can enable testing centers to increase the number of diagnosis performed without increasing the number of PCR tests. The codes for generating test plans are available online at [1].

negative: Middle East respiratory syndrome: what we learned from the 2015 outbreak in the Republic of Korea Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. The 2015 Korea outbreak of MERSCoV involved 186 cases, including 38 fatalities. A total of 83% of transmission events were due to five superspreaders, and 44% of the 186 MERS cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. The epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbreak. This outbreak provides a unique opportunity to fill the gap in our knowledge of MERS-CoV infection. Therefore, in this paper, we review the literature on epidemiology, virology, clinical features, and prevention of MERS-CoV, which were acquired from the 2015 Korea outbreak of MERSCoV.

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: Estimation of Time-Dependent Reproduction Numbers for Porcine Reproductive and Respiratory Syndrome across Different Regions and Production Systems of the US Porcine reproductive and respiratory syndrome (PRRS) is, arguably, the most impactful disease for the North American swine industry, due to its known considerable economic losses. The Swine Health Monitoring Project (SHMP) monitors and reports weekly new PRRS cases in 766 sow herds across the US. The time-dependent reproduction number (TD-R) is a measure of a pathogen’s transmissibility. It may serve to capture and report PRRS virus (PRRSV) spread at the regional and system levels. The primary objective of the study here was to estimate the TD-R values for PRRSV using regional and system-level PRRS data, and to contrast it with commonly used metrics of disease, such as incidence estimates and space–time clusters. The second objective was to test whether the estimated TD-Rs were homogenous across four US regions. Retrospective monthly incidence data (2009–2016) were available from the SHMP. The dataset was divided into four regions based on location of participants, and demographic and environmental features, namely, South East (North Carolina), Upper Midwest East (UME, Minnesota/Iowa), Upper Midwest West (Nebraska/South Dakota), and South (Oklahoma panhandle). Generation time distributions were fit to incidence data for each region, and used to calculate the TD-Rs. The Kruskal–Wallis test was used to determine whether the median TD-Rs differed across the four areas. Furthermore, we used a space–time permutation model to assess spatial–temporal patterns for the four regions. Results showed TD-Rs were right skewed with median values close to “1” across all regions, confirming that PRRS has an overall endemic nature. Variation in the TD-R patterns was noted across regions and production systems. Statistically significant periods of PRRSV spread (TD-R > 1) were identified for all regions except UME. A minimum of three space–time clusters were detected for all regions considering the time period examined herein; and their overlap with “spreader events” identified by the TD-R method varied according to region. TD-Rs may help to measure PRRS spread to understand, in quantitative terms, disease spread, and, ultimately, support the design, implementation, and monitoring of interventions aimed at mitigating the impact of PRRSV spread in the US.

negative: Discovery of a missing disease spreader This study presents a method to discover an outbreak of an infectious disease in a region for which data are missing, but which is at work as a disease spreader. Node discovery for the spread of an infectious disease is defined as discriminating between the nodes which are neighboring to a missing disease spreader node, and the rest, given a dataset on the number of cases. The spread is described by stochastic differential equations. A perturbation theory quantifies the impact of the missing spreader on the moments of the number of cases. Statistical discriminators examine the mid-body or tail-ends of the probability density function, and search for the disturbance from the missing spreader. They are tested with computationally synthesized datasets, and applied to the SARS outbreak and flu pandemic.

negative: The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

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

negative: Using Insights from Behavioral Economics to Mitigate the Spread of COVID-19 The outbreak of 2019 coronavirus disease (COVID-19) has become a public health emergency of international concern. The number of COVID-infected individuals and related deaths continues to rise rapidly. Encouraging people to adopt and sustain preventive behaviors is a central focus of public health policies that seek to mitigate the spread of COVID-19. Public health policy needs improved methods to encourage people to adhere to COVID-19-preventive behaviors. In this paper, we introduce a number of insights from behavioral economics that help explain why people may behave irrationally during the COVID-19 pandemic. In particular, present bias, status quo bias, framing effect, optimism bias, affect heuristic, and herding behavior are discussed. We hope this paper will shed light on how insights from behavioral economics can enrich public health policies and interventions in the fight against COVID-19.

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: Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis The novel coronavirus 2019-nCoV has caused major outbreaks in many parts of the world. A better understanding of the pathophysiology of COVID-19 is urgently needed. Clinically, it is important to identify who may be susceptible to infection and identify treatments for the disease. There is good evidence that ACE2 is a receptor for 2019-nCoV, and studies also suggested that high expression of ACE2 may increase susceptibility to infection. Here we conducted a phenome-wide Mendelian randomization (MR) study to prioritize diseases/traits and blood proteins that may be causally linked to ACE2 expression in the lung. Expression data was based on GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR analysis, as these drugs could potentially alter ACE2 expression and may be clinically relevant. Notably, MR is much less vulnerable to confounding and reverse causality compared to observational studies. The most consistent finding was a tentative causal association between diabetes-related traits and increased ACE2 expression. Based on one of the largest GWAS on type II diabetes (T2DM) to date (N=898,130), we found that T2DM is causally linked to raised ACE2 expression (beta=0.1835, 95% CI 0.0853-0.2817; p=2.49E-4; GSMR method). Significant associations (at nominal level; p<0.05) was also observed across multiple datasets, with different analytic methods, and for both type I and II diabetes. Other diseases/traits having nominal significant associations with increased ACE2 included inflammatory bowel disease, (ER+) breast and lung cancers, asthma, smoking and elevated ALT, among others. We also uncovered a number of plasma/serum proteins potentially linked to altered ACE2 expression, and the top enriched pathways included cytokine-cytokine-receptor interaction, VEGF signaling, JAK-STAT signaling etc. We also explored drugs that target some of the top-ranked proteins in the MR analysis. In conclusion, the current MR analysis reveals diseases/traits and blood proteins that may causally affect ACE2 expression, which in turn may influence susceptibility to the infection. The proteome-wide MR analysis may shed light on the molecular mechanisms underlying ACE2 expression, and may help guide drug repositioning in the future. Nevertheless, we stress that further studies are required to verify our findings due to various limitations and the exploratory nature of some analyses.

negative: Airflow as a Possible Transmission Route of Middle East Respiratory Syndrome at an Initial Outbreak Hospital in Korea In this study, the results of an airflow investigation conducted on 7 June 2015 as part of a series of epidemiologic investigations at Pyeongtaek St. Mary’s Hospital, South Korea, were investigated. The study involved 38 individuals who were infected directly and indirectly with Middle East Respiratory Syndrome (MERS), by a super-spreader patient. Tracer gas experiments conducted on the eighth floor, where the initial patient was hospitalized, confirmed that the tracer gas spread to adjacent patient rooms and rooms across corridors. In particular, the experiment with an external wind direction and speed similar to those during the hospitalization of the initial patient revealed that the air change rate was 17–20 air changes per hour (ACH), with air introduced through the window in the room of the infected patient (room 8104). The tracer gas concentration of room 8110, which was the farthest room, was 7.56% of room 8104, indicating that a high concentration of gas has spread from room 8104 to rooms across the corridor. In contrast, the tracer gas was barely detected in a maternity ward to the south of room 8104, where there was no secondary infected patient. Moreover, MERS is known to spread mainly by droplets through close contact, but long-distance dispersion is probable in certain environments, such as that of a super-spreader patient hospitalized in a room without ventilation, hospitals with a central corridor type, and indoor airflow dispersion due to external wind.

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: Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk BACKGROUND: The new Middle East respiratory syndrome coronavirus (MERS-CoV) infection shares many clinical, epidemiological, and virological similarities with that of severe acute respiratory syndrome (SARS)-CoV. We aimed to estimate virus transmissibility and the epidemic potential of MERS-CoV, and to compare the results with similar findings obtained for prepandemic SARS. METHODS: We retrieved data for MERS-CoV clusters from the WHO summary and subsequent reports, and published descriptions of cases, and took into account 55 of the 64 laboratory-confirmed cases of MERS-CoV reported as of June 21, 2013, excluding cases notified in the previous 2 weeks. To assess the interhuman transmissibility of MERS-CoV, we used Bayesian analysis to estimate the basic reproduction number (R(0)) and compared it to that of prepandemic SARS. We considered two scenarios, depending on the interpretation of the MERS-CoV cluster-size data. RESULTS: With our most pessimistic scenario (scenario 2), we estimated MERS-CoV R(0) to be 0·69 (95% CI 0·50–0·92); by contrast, the R(0) for prepandemic SARS-CoV was 0·80 (0·54–1·13). Our optimistic scenario (scenario 1) yielded a MERS-CoV R(0) of 0·60 (0·42–0·80). Because of recent implementation of effective contact tracing and isolation procedures, further MERS-CoV transmission data might no longer describe an entire cluster, but only secondary infections directly caused by the index patient. Hence, we calculated that, under scenario 2, eight or more secondary infections caused by the next index patient would translate into a 5% or higher chance that the revised MERS-CoV R(0) would exceed 1—ie, that MERS-CoV might have pandemic potential. INTERPRETATION: Our analysis suggests that MERS-CoV does not yet have pandemic potential. We recommend enhanced surveillance, active contact tracing, and vigorous searches for the MERS-CoV animal hosts and transmission routes to human beings. FUNDING: Agence Nationale de la Recherche (Labex Integrative Biology of Emerging Infectious Diseases), and the European Community's Seventh Framework Programme project PREDEMICS.

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: Impact of edge-removal on the centrality betweenness of the best spreaders The control of epidemic spreading is essential to avoid potential fatal consequences and also, to lessen unforeseen socio-economic impact. The need for effective control is exemplified during the severe acute respiratory syndrome (SARS) in 2003, which has inflicted near to a thousand deaths as well as bankruptcies of airlines and related businesses. In this article, we examine the efficacy of control strategies on the propagation of infectious diseases based on removing connections within real world airline network with the associated economic and social costs taken into account through defining appropriate quantitative measures. We uncover the surprising results that removing less busy connections can be far more effective in hindering the spread of the disease than removing the more popular connections. Since disconnecting the less popular routes tend to incur less socio-economic cost, our finding suggests the possibility of trading minimal reduction in connectivity of an important hub with efficiencies in epidemic control. In particular, we demonstrate the performance of various local epidemic control strategies, and show how our approach can predict their cost effectiveness through the spreading control characteristics.

negative: IFITM3 and Susceptibility to Respiratory Viral Infections in the Community Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM 1,2, and 3) are viral restriction factors that mediate cellular resistance to several viruses. We have genotyped a possible splice-site altering single-nucleotide polymorphism (rs12252) in the IFITM3 gene in 34 patients with H1N1 influenza and severe pneumonia, and >5000 individuals comprising patients with community-acquired mild lower respiratory tract infection and matched controls of Caucasian ancestry. We found evidence of an association between rs12252 rare allele homozygotes and susceptibility to mild influenza (in patients attending primary care) but could not confirm a previously reported association between this single-nucleotide polymorphism and susceptibility to severe H1N1 infection.

negative: Prevention is Better than Cure: An Application of Big Data and Geospatial Technology in Mitigating Pandemic COVID-19 has been a severe threat to city’s dense ecosystem and has collapsed the urban life. These spread has raised question on urban health infrastructure and coping capacity. To maintain social distance and providing community with essentials is a challenging task for government and city planners in dense urban area. Spatial mapping of resources, patients, medical infrastructure, potential open space, places which can be turned to quarantine centers, etc. has been done using GIS for city of Surat. Larger open spaces within the urban fabric are identified to implement emergency services and evacuation protocols. This tool will defiantly be helpful to the city administration in maintaining the cluster, quarantine tracking of the infected community and flow of daily essential, supply chain in cities with restriction in the infected cluster. Even having better technology to fight against any pandemic, geospatial technology will help to prevent the pandemic to spread further and hence, it is known as prevention is better then cure.

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: Modeling Approaches Toward Understanding Infectious Disease Transmission Long-standing neglected diseases continue to challenge our global health infrastructure, and emerging pathogens pose new threats worldwide. To inform prevention and response efforts, mathematical models of infectious disease dynamics are being increasingly applied. Here we explain how models can be developed to enhance our understanding and predictive power over population-level disease trends, by capturing both fundamental aspects of transmission and also the effects of medical and behavioral interventions. We review advances in transdisciplinary approaches of disease modeling and illustrate these advances with applications including community-based initiatives undertaken during the Ebola epidemic in West Africa and age-targeting of influenza vaccination in the USA. We further discuss how modern statistical inference facilitates the incorporation of data from behavioral sciences and epidemiology into models, highlighting how data-driven models can constitute powerful tools to inform and improve public health strategies.

negative: There are asymptomatic and pre-symptomatic patients infected with COVID-19. So what? Pandemic response implications Abstract Asymptomatic but infectious people have been reported in many infectious diseases. Asymptomatic and pre-symptomatic carriers would be a hidden reservoir of COVID-19. Aim This review identifies primary empirical evidence about the ability of asymptomatic carriers to infect others with COVID-19 pandemic and reflects on the implications for control measures. Methods A systematic review is followed by a narrative report and commentary inclusion criteria were: studies reporting primary data on asymptomatic or pre-symptomatic patients, who were considered to have passed on COVID-19 infection; and published in indexed journals or in peer review between January 1 and March 31, 2020. Results Nine articles reported on 83 asymptomatic or pre-symptomatic persons. Conclusions The evidence confirms COVID-19 transmission from people who were asymptomatic at the time. A series of implications for health service response are laid out. Keywords: Covid-19, Asymptomatic, Pre-symptomatic, Public Health

negative: Protease inhibitors broadly effective against feline, ferret and mink coronaviruses Abstract Ferret and mink coronaviruses typically cause catarrhal diarrhea in ferrets and minks, respectively. In recent years, however, systemic fatal coronavirus infection has emerged in ferrets, which resembles feline infectious peritonitis (FIP) in cats. FIP is a highly fatal systemic disease caused by a virulent feline coronavirus infection in cats. Despite the importance of coronavirus infections in these animals, there are no effective commercial vaccines or antiviral drugs available for these infections. We have previously reported the efficacy of a protease inhibitor in cats with FIP, demonstrating that a virally encoded 3C-like protease (3CLpro) is a valid target for antiviral drug development for coronavirus infections. In this study, we extended our previous work on coronavirus inhibitors and investigated the structure-activity relationships of a focused library of protease inhibitors for ferret and mink 3CLpro. Using the fluorescence resonance energy transfer assay, we identified potent inhibitors broadly effective against feline, ferret and mink coronavirus 3CLpro. Multiple amino acid sequence analysis and modelling of 3CLpro of ferret and mink coronaviruses were conducted to probe the structural basis for these findings. The results of this study provide support for further research to develop broad-spectrum antiviral agents for multiple coronavirus infections. To the best of our knowledge, this is the first report on small molecule inhibitors of ferret and mink coronaviruses.

negative: Evidence-Based Medicine in the Intensive Care Unit

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: 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: The Effects of a Novel Global Pandemic (COVID-19) on a Plastic Surgery Department

negative: Estimation of transmission parameters of a fluoroquinolone-resistant Escherichia coli strain between pigs in experimental conditions Antimicrobial resistance is of primary importance regarding public and animal health issues. Persistence and spread of resistant strains within a population contribute to the maintenance of a reservoir and lead to treatment failure. An experimental trial was carried out to study the horizontal transmission of a fluoroquinolone-resistant Escherichia coli strain from inoculated to naïve pigs. All naïve contact pigs had positive counts of fluoroquinolone-resistant E. coli after only two days of contact. Moreover, re-infections of inoculated pigs caused by newly contaminated animals were suspected. A maximum likelihood method, based on a susceptible-infectious-susceptible (SIS) model, was used to determine the transmission parameters. Two transmission levels were identified depending on the quantity of bacteria shed by infected individuals: (i) low-shedders with bacterial counts of resistant E. coli in the faeces between 5*10(3 )and 10(6 )CFU/g (β(L )= 0.41 [0.27; 0.62]), (ii) high shedders with bacterial counts above 10(6 )CFU/g (β(H )= 0.98 [0.59; 1.62]). Hence, transmission between animals could be pivotal in explaining the persistence of resistant bacteria within pig herds.

negative: Airflow analysis of Pyeongtaek St Mary's Hospital during hospitalization of the first Middle East respiratory syndrome patient in Korea Middle East respiratory syndrome (MERS) is known to be transmitted through close contact. However, epidemiological surveys of MERS in Korea indicated that some secondary patients were infected without close contact. Therefore, the possibility of other transmission routes must be identified. In this study, the possibility of MERS spreading through airflow was investigated on the eighth floor of Pyeongtaek St Mary's Hospital. Computational fluid dynamics was used to analyse the indoor airflow and passive tracer diffusion during the index patient's stay. Six cases were simulated for different outdoor wind directions and indoor mechanical ventilation operations. When a passive tracer was released in ward 8104, where the index patient was hospitalized, the passive tracer spread through the indoor airflow, which was created by the outdoor airflow. Ward 8109, which had the largest number of infected cases and was far distant from ward 8104, showed passive tracer concentration in all cases. This result indicates that MERS may have spread through airflow. The study results do not imply that the infection pathway of MERS is airborne. However, the results show the possibility of MERS spreading through airflow in specific environments such as poor ventilation environments.

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

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

negative: Health screening strategies for international air travelers during an epidemic or pandemic Abstract Air travelers can carry an infectious disease's pathogenic microorganism in their bodies and spread the disease from one country to another in a few days. To delay the spread, health screening stations may be set up at airport terminals to screen travelers. This research tested three different health screening strategies, each with a different combination of screening stations at trip origins, destinations and connecting airports. Discrete event simulations were performed, based on the 2014 to 2016 Ebola virus epidemic, with special focus on travelers from the West African countries traveling to the United States, including travelers who transferred flights at airports in European Union member states. The effectiveness of the screening strategies was analyzed in terms of correct detection, missed detection and false alarm rate. The results showed that exit screening at trip origins brought big improvements in the performance measurements compared to no screening. However, additional screening at the destinations and connecting airports contributed marginal benefits.

negative: COVID-19 virus outbreak lockdown: What impacts on household food wastage? The 2019–2020 coronavirus disease (COVID-19) is a public health issue. Lockdown is among options suggested to reduce spread of the virus. This study aimed to determining the impact of COVID-19 lockdown on Tunisian consumer awareness, attitudes and behaviors related to food wastage. An online survey was conducted during the first 2 weeks of COVID-19 lockdown. The survey collected information on demographic data, awareness and attitudes toward food waste, food purchase behavior and household food expenditure estimation; extent of household food waste; willingness and information needs to reduce food waste. This study included 284 respondents. About 89% of respondents claimed to be aware of food waste, and the COVID-19 lockdown would impact for 93% of respondents, their waste levels, and for 80%, their grocery shopping habits. Interestingly, the COVID-19 lockdown improved food shopping performances and pushed toward a positive behavioral change regarding food wastage: 85% respondents declared nothing of what they bought would be discarded, and most of the respondents have set up a strategy of saving, storing and eating leftovers. The most cited reasons given for discarding food were overcooking, inappropriate storage and overbuying. Consumers’ changes in food waste prevention might be probably driven more by the socioeconomical context of the COVID-19 lockdown (i.e. food availability, restricted movements, loss of income), than by a pro-environmental concern. Finally, our study pointed out the consumers’ needs of information for taking further action. In conclusion, our study can constitute a basis to further promote household food waste prevention behavior, outlasting the COVID-19 crisis.

negative: History of coronary heart disease increases the mortality rate of COVID-19 patients: a nested case-control study Background: China has experienced an outbreak of a novel human coronavirus (SARS-CoV-2) since December 2019, which quickly became a worldwide pandemic in early 2020. There is limited evidence on the mortality risk effect of pre-existing comorbidities for coronavirus disease 2019 (COVID-19), which has important implications for early treatment. Objective: Evaluate the risk of pre-existing comorbidities on COVID-19 mortality, and provide clinical suggestions accordingly. Method: This study used a nested case-control design. A total of 94 publicly reported deaths in locations outside of Hubei Province, China, between December 18th, 2019 and March 8th, 2020 were included as cases. Each case was matched with up to three controls, based on gender and age (94 cases and 181 controls). The inverse-probability-weighted Cox proportional hazard model was performed. Results: History of comorbidities significantly increased the death risk of COVID-19: one additional pre-existing comorbidity led to an estimated 40% higher risk of death (p<0.001). The estimated mortality risk in patients with CHD was three times of those without CHD (p<0.001). The estimated 30-day survival probability for a profile patient with pre-existing CHD (65-year-old female with no other comorbidities) was 0.53 (95% CI [0.34-0.82]), while it was 0.85 (95% CI [0.79-0.91]) for those without CHD. Older age was also associated with increased death risk: every 5-year increase in age was associated with a 20% increased risk of mortality (p<0.001). Conclusion: Extra care and early medical intervention are needed for patients with pre-existing comorbidities, especially CHD.

negative: COVID-19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures BACKGROUND: Cruise ships carry a large number of people in confined spaces with relative homogeneous mixing. On 3 February, 2020, an outbreak of COVID-19 on cruise ship Diamond Princess was reported with 10 initial cases, following an index case on board around 21-25th January. By 4th February, public health measures such as removal and isolation of ill passengers and quarantine of non-ill passengers were implemented. By 20th February, 619 of 3700 passengers and crew (17%) were tested positive. METHODS: We estimated the basic reproduction number from the initial period of the outbreak using SEIR models. We calibrated the models with transient functions of countermeasures to incidence data. We additionally estimated a counterfactual scenario in absence of countermeasures, and established a model stratified by crew and guests to study the impact of differential contact rates among the groups. We also compared scenarios of an earlier versus later evacuation of the ship. RESULTS: The basic reproduction rate was initially 4 times higher on-board compared to the ${R}_0$ in the epicentre in Wuhan, but the countermeasures lowered it substantially. Based on the modeled initial ${R}_0$ of 14.8, we estimated that without any interventions within the time period of 21 January to 19 February, 2920 out of the 3700 (79%) would have been infected. Isolation and quarantine therefore prevented 2307 cases, and lowered the ${R}_0$ to 1.78. We showed that an early evacuation of all passengers on 3 February would have been associated with 76 infected persons in their incubation time. CONCLUSIONS: The cruise ship conditions clearly amplified an already highly transmissible disease. The public health measures prevented more than 2000 additional cases compared to no interventions. However, evacuating all passengers and crew early on in the outbreak would have prevented many more passengers and crew from infection.

negative: $\alpha$-Satellite: An AI-driven System and Benchmark Datasets for Hierarchical Community-level Risk Assessment to Help Combat COVID-19 The novel coronavirus and its deadly outbreak have posed grand challenges to human society: as of March 26, 2020, there have been 85,377 confirmed cases and 1,293 reported deaths in the United States; and the World Health Organization (WHO) characterized coronavirus disease (COVID-19) - which has infected more than 531,000 people with more than 24,000 deaths in at least 171 countries - a global pandemic. A growing number of areas reporting local sub-national community transmission would represent a significant turn for the worse in the battle against the novel coronavirus, which points to an urgent need for expanded surveillance so we can better understand the spread of COVID-19 and thus better respond with actionable strategies for community mitigation. By advancing capabilities of artificial intelligence (AI) and leveraging the large-scale and real-time data generated from heterogeneous sources (e.g., disease related data from official public health organizations, demographic data, mobility data, and user geneated data from social media), in this work, we propose and develop an AI-driven system (named $\alpha$-Satellite}, as an initial offering, to provide hierarchical community-level risk assessment to assist with the development of strategies for combating the fast evolving COVID-19 pandemic. More specifically, given a specific location (either user input or automatic positioning), the developed system will automatically provide risk indexes associated with it in a hierarchical manner (e.g., state, county, city, specific location) to enable individuals to select appropriate actions for protection while minimizing disruptions to daily life to the extent possible. The developed system and the generated benchmark datasets have been made publicly accessible through our website. The system description and disclaimer are also available in our website.

negative: SARS Revisited: The Challenge of Controlling Emerging Infectious Diseases at the Local, Regional, Federal, and Global Levels

negative: 10. The Political Ecology of Plague in the Global Network of Cities: The Sars Epidemic of 2002–2003 In the late autumn of 2002 Severe Acute Respiratory Syndrome (SARS) broke out in Foshan city in the People's Republic of China, and over the next few months it rapidly spread to every continent and 29 countries. Although plagues may be global events, they are ultimately fought at the local level. In discussing the SARS epidemic, I present two theses. (1) In the wake of a plague, politics tends to shape a community's response in protecting the system, evaluating performances and allocating blame, punishments, and rewards, and restructuring organizations. (2) Because of their potential for demographic and institutional destruction, systemic responses to plague tend to become entwined in politics at all levels – the local, national, and international.

negative: Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications Summary Background Since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea was reported on 20th May 2015, there have been 186 confirmed cases, 38 deaths and 16,752 suspected cases. Previously published research on South Korea's MERS outbreak was limited to the early stages, when few data were available. Now that the outbreak has ended, albeit unofficially, a more comprehensive review is appropriate. Methods Data were obtained through the MERS portal by the Ministry for Health and Welfare (MOHW) and Korea Centres for Disease Control and Prevention, press releases by MOHW, and reports by the MERS Policy Committee of the Korean Medical Association. Cases were analysed for general characteristics, exposure source, timeline and infection generation. Sex, age and underlying diseases were analysed for the 38 deaths. Findings Beginning with the index case that infected 28 others, an in-depth analysis was conducted. The average age was 55 years, which was a little higher than the global average of 50 years. As in most other countries, more men than women were affected. The case fatality rate was 19.9%, which was lower than the global rate of 38.7% and the rate in Saudi Arabia (36.5%). In total, 184 patients were infected nosocomially and there were no community-acquired infections. The main underlying diseases were respiratory diseases, cancer and hypertension. The main contributors to the outbreak were late diagnosis, quarantine failure of ‘super spreaders’, familial care-giving and visiting, non-disclosure by patients, poor communication by the South Korean Government, inadequate hospital infection management, and ‘doctor shopping’. The outbreak was entirely nosocomial, and was largely attributable to infection management and policy failures, rather than biomedical factors.

negative: Outcome of Coronavirus spectrum infections (SARS, MERS, COVID 1 -19) during pregnancy: a systematic review and meta-analysis ABSTRACT Objective The aim of this systematic review was to report pregnancy and perinatal outcomes of Coronavirus (CoV) spectrum infections, and particularly COVID-19 disease due to SARS-COV-2 infection during pregnancy. Data sources Medline, Embase, Cinahl and Clinicaltrials.gov databases were searched electronically utilizing combinations of word variants for “coronavirus” or “severe acute respiratory syndrome” or “SARS” or “Middle East respiratory syndrome” or “MERS” or “COVID-19” and “pregnancy”. The search and selection criteria were restricted to English language. Study eligibility criteria Inclusion criteria were pregnant women with a confirmed Coronavirus related illness, defined as either SARS, MERS or COVID-19. Study appraisal and synthesis methods We used meta-analyses of proportions to combine data and reported pooled proportions. The pregnancy outcomes observed included miscarriage, preterm birth, pre-eclampsia, preterm prelabor rupture of membranes, fetal growth restriction, and mode of delivery. The perinatal outcomes observed were fetal distress, Apgar score < 7 at five minutes, neonatal asphyxia, admission to neonatal intensive care unit, perinatal death, and evidence of vertical transmission. Results 19 studies including 79 women were eligible for this systematic review: 41 pregnancies (51.9%) affected by COVID-19, 12 (15.2%) by MERS, and 26 (32.9%) by SARS. An overt diagnosis of pneumonia was made in 91.8% and the most common symptoms were fever (82.6%), cough (57.1%) and dyspnea (27.0%). For all CoV infections, the rate of miscarriage was 39.1% (95% CI 20.2-59.8); the rate of preterm birth < 37 weeks was 24.3% (95% CI 12.5-38.6); premature prelabor rupture of membranes occurred in 20.7% (95% CI 9.5-34.9), preeclampsia in 16.2% (95% CI 4.2-34.1), and fetal growth restriction in 11.7% (95% CI 3.2-24.4); 84% were delivered by cesarean; the rate of perinatal death was 11.1% (95% CI 84.8-19.6) and 57.2% (95% CI 3.6-99.8) of newborns were admitted to the neonatal intensive care unit. When focusing on COVID-19, the most common adverse pregnancy outcome was preterm birth < 37 weeks, occurring in 41.1% (95% CI 25.6-57.6) of cases, while the rate of perinatal death was 7.0% (95% CI 1.4-16.3). None of the 41 newborns assessed showed clinical signs of vertical transmission. Conclusion In mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, PTB is the most common adverse pregnancy outcome. Miscarriage, preeclampsia, cesarean, and perinatal death (7-11%) were also more common than in the general population. There have been no published cases of clinical evidence of vertical transmission. Evidence is accumulating rapidly, so these data may need to be updated soon. The findings from this study can guide and enhance prenatal counseling of women with COVID-19 infection occurring during pregnancy.

negative: Preventive Behavioral Responses to the 2015 Middle East Respiratory Syndrome Coronavirus Outbreak in Korea This study examined the public’s preventive behavioral responses during the 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in Korea and the influencing factors. Two cross-sectional telephone surveys were conducted by Gallup Korea using random digit dialing in June 2015 (n = 2004). The main outcome variables were nonpharmaceutical preventive measures (survey (1): Measures for reducing transmission (handwashing, face masks); and survey (2): Measures for avoiding contact with others). Multiple logistic regression was used to identify the factors influencing preventive behaviors. In survey (1), 60.3% of respondents reported more frequent handwashing and 15.5% reported wearing face masks at least once due to the MERS-CoV epidemic. In survey (2), 41–56% of respondents reported practicing avoidance measures. The concerned group was more likely to practice reducing transmission measures (odds ratio (OR) 4.5; 95% confidence interval (CI) 3.3–6.1) and avoidance measures (OR = 9.6; 95% CI, 6.4–14.4). The respondents who had low trust in president or ruling party had a higher practice rate of reducing transmission measures (OR = 1.7; 95% CI, 1.2–2.6) and avoidance measures (OR = 2.1; 95% CI, 1.2–3.5). Cooperative prevention measures need appropriated public concern based on effective risk communication.

negative: SARS: clinical virology and pathogenesis Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus, called the SARS coronavirus (SARS‐CoV). Over 95% of well characterized cohorts of SARS have evidence of recent SARS‐CoV infection. The genome of SARS‐CoV has been sequenced and it is not related to any of the previously known human or animal coronaviruses. It is probable that SARS‐CoV was an animal virus that adapted to human‐human transmission in the recent past. The virus can be found in nasopharyngeal aspirate, urine and stools of SARS patients. Second generation reverse transcriptase polymerase chain reaction assays are able to detect SARS‐CoV in nasopharyngeal aspirates of approximately 80% of patients with SARS within the first 3 days of illness. Seroconversion for SARS‐CoV using immunofluorescence on infected cells is an excellent method of confirming the diagnosis, but antibody responses only appear around day 10 of the illness. Within the first 10 days the histological picture is that of acute phase diffuse alveolar damage (DAD) with a mixture of inflammatory infiltrate, oedema and hyaline membrane formation. Desquamation of pneumocytes is prominent and consistent. After 10 days of illness the picture changes to one of organizing DAD with increased fibrosis, squamous metaplasia and multinucleated giant cells. The role of cytokines in the pathogenesis of SARS is still unclear.

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: The international response to the outbreak of SARS in 2003. The sudden arrival of an internationally spreading outbreak of a newly identified infectious disease in early 2003, severe acute respiratory syndrome (SARS), provided an opportunity for a coordinated international response based on information and evidence obtained in real time through standard and electronic communications. Its containment represents a new way of working internationally, and demonstrates how intense collaboration in virology, clinical medicine and epidemiology can rapidly provide the information necessary to create and implement evidence-based control measures. The SARS outbreak serves as a reminder of the need for a strong national surveillance and response to infectious diseases, evidence-based international travel recommendations, and a global alert and response network to serve as a safety net when national surveillance fails.

negative: Pneumonia in the Pregnant Patient Community acquired pneumonia is a common illness, and pneumonia and influenza serve as the seventh leading cause of death in the United States. In the pregnant patient, pneumonia is the most common cause of fatal non-obstetric infection (1–3). Pneumonia can have adverse consequences for both the mother and her fetus, with certain infections (particularly viral and fungal) assuming greater virulence and mortality than in non-pregnant women of similar age (2, 3). Pneumonia is a relatively common cause of respiratory failure in pregnant patients, but in contrast to older studies, newer data suggest that not all pneumonias are more common or more serious in pregnant women than in other populations. However, because pneumonia can impact both the mother and fetus, it may lead to an increased likelihood of complicated preterm delivery, compared to pregnancies in which infection is absent. The pathogens responsible for community-acquired pneumonia (CAP) are similar in pregnant and non-pregnant patients, with Streptococcus pneumoniae, Hemophilus influenzae, Mycoplasma pneumoniae, Legionella spp., Chlamydophila pneumoniae, and influenza A accounting for the majority of cases (2–4). However, reduction in cell-mediated immunity associated with pregnancy (especially during the third trimester) places women at an increased risk of more severe forms of pneumonia and disseminated diseases from pathogens normally contained by this type of immune response, including herpes virus, influenza, varicella, and coccidioidomycosis (3, 5–7).

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: Communicable Disease Surveillance Ethics in the Age of Big Data and New Technology Surveillance is essential for communicable disease prevention and control. Traditional notification of demographic and clinical information, about individuals with selected (notifiable) infectious diseases, allows appropriate public health action and is protected by public health and privacy legislation, but is slow and insensitive. Big data–based electronic surveillance, by commercial bodies and government agencies (for profit or population control), which draws on a plethora of internet- and mobile device–based sources, has been widely accepted, if not universally welcomed. Similar anonymous digital sources also contain syndromic information, which can be analysed, using customised algorithms, to rapidly predict infectious disease outbreaks, but the data are nonspecific and predictions sometimes misleading. However, public health authorities could use these online sources, in combination with de-identified personal health data, to provide more accurate and earlier warning of infectious disease events—including exotic or emerging infections—even before the cause is confirmed, and allow more timely public health intervention. Achieving optimal benefits would require access to selected data from personal electronic health and laboratory (including pathogen genomic) records and the potential to (confidentially) re-identify individuals found to be involved in outbreaks, to ensure appropriate care and infection control. Despite existing widespread digital surveillance and major potential community benefits of extending its use to communicable disease control, there is considerable public disquiet about allowing public health authorities access to personal health data. Informed public discussion, greater transparency and an ethical framework will be essential to build public trust in the use of new technology for communicable disease control.

negative: China coronavirus: partial border closures into Hong Kong are not enough, say doctors.

negative: Early detection of SARS-CoV-2 antibodies in COVID-19 patients as a serologic marker of infection BACKGROUND: Thousands of medical staff had been infected with SARS-CoV-2 virus with hundreds of deaths reported. Such loss could be prevented if there is a serologic assay for SARS-CoV-2-specific antibodies for serological surveillance of its infection at the early stage of disease. METHODS: Using CHO cell expressed full length SARS-CoV-2 S1 protein as capturing antigen, a COVID-19/SARS-CoV-2 S1 serology ELISA kit was developed and validated with negative samples collected prior to the outbreaks or during the outbreak, and positive samples from patients confirmed with COVID-19. RESULTS: The specificity of the ELISA kit was 97.5%, as examined against total 412 normal human samples. The sensitivity was 97.1% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. The assay was able to detect SARS-CoV-2 antibody on day one after the onset of COVID-19 disease. The average antibody levels increased during the hospitalization and after been discharged for two weeks. SARS-CoV-2 antibodies were detected in 28 out of 276 asymptomatic medical staff and one out of five nucleic acid test-negative "Close contacts" of COVID-19 patient. CONCLUSION: With the assays developed here, we can screen medical staff, in-coming patients, passengers and people who are in close contact with the confirmed patients to identify the "innocent viral spreaders", protect the medical staff and stop the further spreading of the virus.

negative: Co-circulation of human metapneumovirus and SARS-associated coronavirus during a major nosocomial SARS outbreak in Hong Kong Abstract Background The clinico-epidemiological significance of human metapneumovirus (hMPV) detected during the SARS outbreak is unknown. Objectives To characterize a nosocomial hMPV outbreak during the 2003 SARS epidemic. Study design and methods All available nasopharyngeal aspirate (NPA) collected from confirmed patients during the first 8 weeks of the SARS outbreak in 2003 were tested for hMPV by a nested RT-PCR assay targeting the F-gene. Clinico-epidemiological information was used to analyze the relationship of hMPV co-infection to specific risk factors (demographics/symptoms/outcomes; status as health-care workers (HCWs)/patients; history of exposure/contact; ward location). Multivariate logistic regression analysis was performed to determine independent risk factors. Results An hMPV outbreak occurred during 6–16 March 2003 (first week of the Hong Kong SARS epidemic). hMPV RNA was detected in 31 of 155 (20%) NPAs from SARS patients. HCW status (OR 2.72, 95% CI 1.11–6.68; p =0.029) or epidemiological linkage to the SARS outbreak ward (OR 3.59, 95% CI 1.42–9.05; p =0.007) were independent factors associated with hMPV infection. Symptoms of cough and coryza were more common in co-infected individuals (22.6% vs. 15.9%) but this was not statistically significant. Other clinical manifestations and outcomes were not different in co-infected patients. Conclusions A major nosocomial hMPV outbreak involving HCWs occurred during the early SARS epidemic. Patients with dual hMPV and SARS infection were not sicker than those with SARS infection only.

negative: Comparison of Transmissibility of Coronavirus Between Symptomatic and Asymptomatic Patients: Reanalysis of the Ningbo COVID-19 Data BACKGROUND: Since the outbreak of the novel coronavirus disease (COVID-19) in December 2019, the coronavirus has spread all over the world at an unprecedented rate. The transmissibility of the coronavirus from asymptomatic patients to healthy individuals has received enormous attention. An important study using COVID-19 data from the city of Ningbo, China, was carried out to estimate and compare the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. However, in the original analysis, the usual chi-square tests were unduly used for some contingency tables with small cell counts including zero, which may violate the assumptions for the chi-square test. OBJECTIVE: We reanalyze the data from the city of Ningbo with more appropriate statistical methods to draw more reliable and sound conclusions on the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. METHODS: We excluded the cases associated with the super-spreader and adopted a more appropriate statistical method, including the permutation test and the Fisher exact test, to reanalyze the COVID-19 data from the city of Ningbo. RESULTS: After excluding the cases related to the super-spreader, the Fisher exact test yields a P value of .84, which indicates stronger evidence of no difference in the transmission rates compared with the original analysis. The odds ratio of the coronavirus transmission rates between the symptomatic and asymptomatic patients is 1.2 with a 95% confidence interval 0.5-2.8. CONCLUSIONS: Through a more in-depth and comprehensive statistical analysis of the Ningbo data, we concluded that there is no difference in the transmission rates of coronavirus between symptomatic and asymptomatic patients.

negative: Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study BACKGROUND: Since the coronavirus disease 2019 outbreak began in the Chinese city of Wuhan on Dec 31, 2019, 68 imported cases and 175 locally acquired infections have been reported in Singapore. We aimed to investigate options for early intervention in Singapore should local containment (eg, preventing disease spread through contact tracing efforts) be unsuccessful. METHODS: We adapted an influenza epidemic simulation model to estimate the likelihood of human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a simulated Singaporean population. Using this model, we estimated the cumulative number of SARS-CoV-2 infections at 80 days, after detection of 100 cases of community transmission, under three infectivity scenarios (basic reproduction number [R(0)] of 1·5, 2·0, or 2·5) and assuming 7·5% of infections are asymptomatic. We first ran the model assuming no intervention was in place (baseline scenario), and then assessed the effect of four intervention scenarios compared with a baseline scenario on the size and progression of the outbreak for each R(0) value. These scenarios included isolation measures for infected individuals and quarantining of family members (hereafter referred to as quarantine); quarantine plus school closure; quarantine plus workplace distancing; and quarantine, school closure, and workplace distancing (hereafter referred to as the combined intervention). We also did sensitivity analyses by altering the asymptomatic fraction of infections (22·7%, 30·0%, 40·0%, and 50·0%) to compare outbreak sizes under the same control measures. FINDINGS: For the baseline scenario, when R(0) was 1·5, the median cumulative number of infections at day 80 was 279 000 (IQR 245 000–320 000), corresponding to 7·4% (IQR 6·5–8·5) of the resident population of Singapore. The median number of infections increased with higher infectivity: 727 000 cases (670 000–776 000) when R(0) was 2·0, corresponding to 19·3% (17·8–20·6) of the Singaporean population, and 1 207 000 cases (1 164 000–1 249 000) when R(0) was 2·5, corresponding to 32% (30·9–33·1) of the Singaporean population. Compared with the baseline scenario, the combined intervention was the most effective, reducing the estimated median number of infections by 99·3% (IQR 92·6–99·9) when R(0) was 1·5, by 93·0% (81·5–99·7) when R(0) was 2·0, and by 78·2% (59·0 −94·4) when R(0) was 2·5. Assuming increasing asymptomatic fractions up to 50·0%, up to 277 000 infections were estimated to occur at day 80 with the combined intervention relative to 1800 for the baseline at R(0) of 1·5. INTERPRETATION: Implementing the combined intervention of quarantining infected individuals and their family members, workplace distancing, and school closure once community transmission has been detected could substantially reduce the number of SARS-CoV-2 infections. We therefore recommend immediate deployment of this strategy if local secondary transmission is confirmed within Singapore. However, quarantine and workplace distancing should be prioritised over school closure because at this early stage, symptomatic children have higher withdrawal rates from school than do symptomatic adults from work. At higher asymptomatic proportions, intervention effectiveness might be substantially reduced requiring the need for effective case management and treatments, and preventive measures such as vaccines. FUNDING: Singapore Ministry of Health, Singapore Population Health Improvement Centre.

negative: Electroconvulsive Therapy During COVID-19: An Essential Medical Procedure-Maintaining Service Viability and Accessibility

negative: Public Health Communication in Time of Crisis: Readability of On-Line COVID-19 Information OBJECTIVE: The purpose of this study was to assess the readability of information on the Internet posted about coronavirus disease 2019 (COVID-19) to determine how closely these materials are written to the recommended reading levels. METHODS: Using the search term “coronavirus,” information posted on the first 100 English language websites was identified. Using an online readability calculator, multiple readability tests were conducted to ensure a comprehensive representation would result. RESULTS: The mean readability scores ranged between grade levels 6.2 and 17.8 (graduate school level). Four of the 5 measures (GFI, CLI, SMOG, FRE) found that readability exceeded the 10th grade reading level indicating that the text of these websites would be difficult for the average American to read. The mean reading level for nearly all noncommercial and commercial websites was at or above the 10th grade reading level. CONCLUSIONS: Messages about COVID-19 must be readable at an “easy” level, and must contain clear guidelines for behavior. The degree to which individuals seek information in response to risk messages is positively related to the expectation that the information will resolve uncertainty. However, if the information is too complex to interpret and it fails to lead to disambiguation, this can contribute to feelings of panic.

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

negative: Clinical features, pathogenesis and immunobiology of severe acute respiratory syndrome. PURPOSE OF REVIEW Severe acute respiratory syndrome coronavirus is a novel virus responsible for the major pandemic in 2003, and it re-emerged in China in late 2003 and 2004 following resumption of wild animal trading activities. Over the past few years, research work has looked into factors that may lead to super-spreading events, clinical/laboratory parameters that may differentiate severe acute respiratory syndrome from other causes of community-acquired pneumonia, the origin of severe acute respiratory syndrome, reservoir host distribution and transmission routes. A better understanding of these issues may help prevent and control future outbreaks of severe acute respiratory syndrome. RECENT FINDINGS Bats are natural reservoirs of severe acute respiratory syndrome like coronaviruses. The human and civet isolates of severe acute respiratory syndrome coronavirus nestle phylogenetically within the spectrum of severe acute respiratory syndrome like coronaviruses. Severe acute respiratory syndrome has the potential of being converted from droplet to airborne transmission. When evaluating epidemiologically high-risk patients with community-acquired pneumonia and no immediate alternative diagnosis, a low absolute neutrophil count on presentation, along with poor responses after 72 h of antibiotic treatment, may raise the index of suspicion for severe acute respiratory syndrome. SUMMARY The presence of severe acute respiratory syndrome like coronaviruses in horseshoe bats raises the possible role of bats in previous and potentially future severe acute respiratory syndrome outbreaks in human. Healthcare workers should take adequate respiratory protection in addition to strict contact and droplet precautions when managing patients with severe acute respiratory syndrome.

negative: The 2019 Novel Coronavirus: A Crown Jewel of Pandemics?

negative: Risk Attitudes Affect Livestock Biosecurity Decisions With Ramifications for Disease Control in a Simulated Production System Hog producers' operational decisions can be informed by an awareness of risks associated with emergent and endemic diseases. Outbreaks of porcine epidemic diarrhea virus (PEDv) have been re-occurring every year since the first onset in 2013 with substantial losses across the hog production supply chain. Interestingly, a decreasing trend in PEDv incidence is visible. We assert that changes in human behaviors may underlie this trend. Disease prevention using biosecurity practices is used to minimize risk of infection but its efficacy is conditional on human behavior and risk attitude. Standard epidemiological models bring important insights into disease dynamics but have limited predictive ability. Since research shows that human behavior plays a driving role in the disease spread process, the explicit inclusion of human behavior into models adds an important dimension to understanding disease spread. Here we analyze PEDv incidence emerging from an agent-based model (ABM) that uses both epidemiological dynamics and algorithms that incorporate heterogeneous human decisions. We investigate the effects of shifting fractions of hog producers between risk tolerant and risk averse positions. These shifts affect the dynamics describing willingness to increase biosecurity as a response to disease threats and, indirectly, change infection probabilities and the resultant intensity and impact of the disease outbreak. Our ABM generates empirically verifiable patterns of PEDv transmission. Scenario results show that relatively small shifts (10% of the producer agents) toward a risk averse position can lead to a significant decrease in total incidence. For significantly steeper decreases in disease incidence, the model's hog producer population needed at least 37.5% of risk averse. Our study provides insight into the link between risk attitude, decisions related to biosecurity, and consequent spread of disease within a livestock production system. We suggest that it is possible to create positive, lasting changes in animal health by nudging the population of livestock producers toward more risk averse behaviors. We make a case for integrating social and epidemiological aspects in disease spread models to test intervention strategies intended to improve biosecurity and animal health at the system scale.

negative: Molecular pathology of emerging coronavirus infections Respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life-threatening lower respiratory tract infections, including the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Viral clearance and subsequent recovery from infection require activation of an effective host immune response; however, many immune effector cells may also cause injury to host tissues. Severe acute respiratory syndrome (SARS) coronavirus and Middle East respiratory syndrome (MERS) coronavirus cause severe infection of the lower respiratory tract, with 10% and 35% overall mortality rates, respectively; however, >50% mortality rates are seen in the aged and immunosuppressed populations. While these viruses are susceptible to interferon treatment in vitro, they both encode numerous genes that allow for successful evasion of the host immune system until after high virus titres have been achieved. In this review, we discuss the importance of the innate immune response and the development of lung pathology following human coronavirus infection.

negative: Spatially Adjusted Time-varying Reproductive Numbers: Understanding the Geographical Expansion of Urban Dengue Outbreaks The basic reproductive number (R(0)) is a fundamental measure used to quantify the transmission potential of an epidemic in public health practice. However, R(0) cannot reflect the time-varying nature of an epidemic. A time-varying effective reproductive number R(t) can provide more information because it tracks the subsequent evolution of transmission. However, since it neglects individual-level geographical variations in exposure risk, R(t) may smooth out interpersonal heterogeneous transmission potential, obscure high-risk spreaders, and hence hamper the effectiveness of control measures in spatial dimension. Therefore, this study proposes a new method for quantifying spatially adjusted (time-varying) reproductive numbers that reflects spatial heterogeneity in transmission potential among individuals. This new method estimates individual-level effective reproductive numbers (R(j)) and a summarized indicator for population-level time-varying reproductive number (R(t)). Data from the five most severe dengue outbreaks in southern Taiwan from 1998–2015 were used to demonstrate the ability of the method to highlight early spreaders contributing to the geographic expansion of dengue transmission. Our results show spatial heterogeneity in the transmission potential of dengue among individuals and identify the spreaders with the highest R(j) during the epidemic period. The results also reveal that super-spreaders are usually early spreaders that locate at the edges of the epidemic foci, which means that these cases could be the drivers of the expansion of the outbreak. Therefore, our proposed method depicts a more detailed spatial-temporal dengue transmission process and identifies the significant role of the edges of the epidemic foci, which could be weak spots in disease control and prevention.

negative: Utilize State Transition Matrix Model to Predict the Novel Corona Virus Infection Peak and Patient Distribution Background: Since December 2019, a pneumonia caused by the 2019 novel coronavirus (2019-nCoV) has broken out in Wuhan, Hubei province, China. The continuous rising of infected cases has imposed overwhelming pressure on public health decision and medical resource allocation in China. We managed to forecast the infection peak time in Hubei province and the severe and critical case distribution. Methods: We used data resource according to cases reported by the National Health Commission of the People's Republic of China (Jan 25, 2019, to Feb 28, 2020) as the training set to deduce the arrival of the peak infection time and the number of severe and critical cases in Wuhan on subsequent days. Medical observation, discharge, infected, non-Severe, infected and severe, cure and death data were collected and analyzed. Using this state transition matrix model, we will be able predict when the inflection peak time (the maximum open infection cases) in Hubei Province will occur. Also, we can use this model to predict the patient distribution (severe, non-severe) to better allocate medical resource. Under relative pessimistic scenario, the inflection peak time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively. Results: In very optimistic scenarios (daily NCC decay rate of -10%), the peak time of open inflection cases will arrive around February 23-February 26. At the same time, there will be a peak in the numbers of severely ill and critically ill patients, between 6800-7200 and 1800-2000, respectively. In a relative optimistic scenario (daily NCC decay rate of -5%), the inflection case peak time will arrive around February 28-March 2. The numbers of critically ill and critically ill patients will lie between 7100-7800 and 1900-2200, respectively. In a relatively pessimistic scenario (daily NCC decay rate of -1%), the inflection peak time does not arrive around the end of March. Estimated time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively. We are using the diagnosis rate, mortality rate, cure rate as the 2/8 data. There should be room for improvement, if these metrics continue to improve. In that case, the peak time will arrive earlier than our estimation. Also, the severe and critical case ratios are likely to decline as the virus becomes less toxic and medical conditions improve. If that happens, the peak numbers will be lower than predicted above. Conclusion: We can infer that we are still not close to the end of this outbreak and the number of critically ill patients is still climbing. Assisting critical care resources in Hubei province requires the government to consider further tilt, and it is vital to make reasonable management of doctors and medical assistance systems to curb the transmission trend.

negative: Effectiveness of Testing, Tracing, Social Distancing and Hygiene in Tackling Covid-19 in India: A System Dynamics Model We present a System Dynamics (SD) model of the Covid-19 pandemic spread in India. The detailed age-structured compartment-based model endogenously captures various disease transmission pathways, expanding significantly from the standard SEIR model. The model is customized for India by using the appropriate population pyramid, contact rate matrices, external arrivals (as per actual data), and a few other calibrated fractions based on the reported cases of Covid-19 in India. Also, we have explicitly modeled, using independent time-variant levers, the effects of testing, contact tracing, isolating Covid-positive patients, quarantining, use of mask/better hygiene practices, social distancing through contact rate reductions at distinct zones of home(H), work(W), school(S) and other(O) locations. Simulation results show that, even after an extended lock-down, some non-trivial number of infections (even asymptomatic) will be left and the pandemic will resurface. Only tools that work against the pandemic is high rate of testing of those who show Covid-19 like symptoms, isolating them if they are positive and contact tracing all contacts of positive patients and quarantining them, in combination with use of face masks and personal hygiene. A wide range of combination of effectiveness of contact tracing, isolation, quarantining and personal hygiene measures help minimize the pandemic impact and some imperfections in implementation of one measure can be compensated by better implementation of other measures.

negative: The risk of SARS-CoV-2 transmission in the healthcare setting and potential impact of cohorting strategies The threat of the COVID-19 pandemic of SARS-CoV-2 virus has grown since its start late last year. A customary response to a surge of a communicable disease is to separate healthcare systems into cohorts, such that patients with other conditions can be treated safely without risk of infection. A challenge with COVID-19 is the existence of currently asymptomatic infections, which without aggressive testing and isolation might enter the non-COVID-19 cohort either through unknowingly infected patients or health care workers. Using stochastic simulations we study the impacts of testing and personal protective equipment (PPE) use. In the base case without testing or PPE, healthcare is rapidly overwhelmed, and becomes a net contributor to the force of infection. We find that effective use of PPE by both HCW and patients can prevent this situation, while testing alone is less effective. We also find that even imperfectly effective use of PPE can provide substantial protection and decrease the force of infection. This illustrates the importance of maintaining supplies of PPE throughout healthcare systems

negative: 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.

negative: Evidence for Limited Early Spread of COVID-19 Within the United States, January–February 2020 From January 21 through February 23, 2020, public health agencies detected 14 U.S. cases of coronavirus disease 2019 (COVID-19), all related to travel from China (1,2). The first nontravel-related U.S. case was confirmed on February 26 in a California resident who had become ill on February 13 (3). Two days later, on February 28, a second nontravel-related case was confirmed in the state of Washington (4,5). Examination of four lines of evidence provides insight into the timing of introduction and early transmission of SARS-CoV-2, the virus that causes COVID-19, into the United States before the detection of these two cases. First, syndromic surveillance based on emergency department records from counties affected early by the pandemic did not show an increase in visits for COVID-19-like illness before February 28. Second, retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20. Third, analysis of viral RNA sequences from early cases suggested that a single lineage of virus imported directly or indirectly from China began circulating in the United States between January 18 and February 9, followed by several SARS-CoV-2 importations from Europe. Finally, the occurrence of three cases, one in a California resident who died on February 6, a second in another resident of the same county who died February 17, and a third in an unidentified passenger or crew member aboard a Pacific cruise ship that left San Francisco on February 11, confirms cryptic circulation of the virus by early February. These data indicate that sustained, community transmission had begun before detection of the first two nontravel-related U.S. cases, likely resulting from the importation of a single lineage of virus from China in late January or early February, followed by several importations from Europe. The widespread emergence of COVID-19 throughout the United States after February highlights the importance of robust public health systems to respond rapidly to emerging infectious threats.

negative: Coronavirus disease 2019 (COVID-19): current status and future perspectives 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: Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer Abstract There is currently a lack of pathologic data on the novel coronavirus (severe acute respiratory syndrome coronavirus 2) pneumonia, or coronavirus disease 2019 (COVID-19), from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of the operation. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Because both patients did not exhibit symptoms of pneumonia at the time of operation, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.

negative: The outbreak of COVID-19 coronavirus and its impact on global mental health. BACKGROUND The current outbreak of COVID-19 coronavirus infection among humans in Wuhan (China) and its spreading around the globe is heavily impacting on the global health and mental health. Despite all resources employed to counteract the spreading of the virus, additional global strategies are needed to handle the related mental health issues. METHODS Published articles concerning mental health related to the COVID-19 outbreak and other previous global infections have been considered and reviewed. COMMENTS This outbreak is leading to additional health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear globally. Collective concerns influence daily behaviors, economy, prevention strategies and decision-making from policy makers, health organizations and medical centers, which can weaken strategies of COVID-19 control and lead to more morbidity and mental health needs at global level.

negative: Viral Infections, an Overview with a Focus on Prevention of Transmission

negative: Interdisciplinarity and Infectious Diseases: An Ebola Case Study

negative: Rising evidence of COVID-19 transmission potential to and between animals: do we need to be concerned? Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--the virus that causes coronavirus disease (COVID-19)--has been detected in domestic dogs and cats, raising concerns of transmission from, to, or between these animals. There is currently no indication that feline- or canine-to-human transmission can occur, though there is rising evidence of the reverse. To explore the extent of animal-related transmission, we aggregated 17 case reports on confirmed SARS-CoV-2 infections in animals as of 15 May 2020. All but two animals fully recovered and had only mild respiratory or digestive symptoms. Using data from probable cat-to-cat transmission in Wuhan, China, we estimated the basic reproduction number R0 under this scenario at 1.09 (95% confidence interval: 1.05, 1.13). This value is much lower than the R0 reported for humans and close to one, indicating that the sustained transmission between cats is unlikely to occur. Our results support the view that the pet owners and other persons with COVID-19 in close contact with animals should be cautious of the way they interact with them.

negative: The effect of human mobility and control measures on the COVID-19 epidemic in China The ongoing coronavirus disease 2019 (COVID-19) outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions were undertaken to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We used real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation in transmission in cities across China and to ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was explained well by human mobility data. After the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside of Wuhan. This study shows that the drastic control measures implemented in China substantially mitigated the spread of COVID-19.

negative: Compensating for the ‘Authoritarian Advantage’ in Crisis Response: A Comparative Case Study of SARS Pandemic Responses in China and Taiwan Why do some countries more effectively respond to crises than others? This paper compares China’s relatively effective response to the 2002–3 SARS outbreak with Taiwan’s relatively ineffective response, focusing on three variables that constitute China’s ‘authoritarian advantage’ - centralized decision making powers; public support; and, relations with the mass media. The paper rejects a fourth explanatory variable specific to the Taiwan case – membership in international organizations. Drawing heavily on the Taiwan example, the paper concludes by suggesting options for overcoming the authoritarian advantage in pandemic response.

negative: Emerging and Reemerging Infectious Disease Threats

negative: Invasive Aspergillosis as an Underrecognized Superinfection in COVID-19

negative: Awareness, knowledge, attitude and practice towards measures for prevention of the spread of COVID-19 in the Ugandans: A nationwide online cross-sectional Survey Background The world is facing the Coronavirus pandemic which is highly infectious. A number of measures have been put in place to prevent its spread among the population. However, for these preventive measures to be effective, the population requires an appropriate and sufficient knowledge. Thus, a survey was conducted with the aim of assessing the awareness, knowledge, attitude and practices towards measures for prevention of the spread of Covid-19 amongst Ugandans. Methods This was a cross-sectional study conducted during the lockdown in Uganda. An online questionnaire and a snowballing approach was used for participant recruitment of 18 years above literate Ugandans. Data collection was done from 6th to 15th April 2020 during which 1763 people participated. We analyzed all data using STATA 14.2, applying appropriate statistical tests. Results Out of 1763 participants, 97.6% were aware of the current pandemic. 83.9% of participants had a good knowledge score (21.8/27), 72.4% had a good attitude and 85.3% were practicing measures to prevent the spread of the Coronavirus disease. The ordered logistic regression showed that being a Health worker was significantly associated with a high knowledge (aOR:6 (3.32-10.93); a good attitude (aOR:2.5(1.68-3.8)]) and good practice (aOR:2.9 (1.95-4.2). On contrary, being a driver, business entrepreneur and a security personnel were found to have less rate in awareness, knowledge, attitude and practice. Conclusions Ugandans had a good overall awareness, knowledge, attitude and practice. However, there is still a gap of knowledge, attitude and practice among drivers, business entrepreneur and security personnel. There is a need to mobilize the population in the country to have the same degree of awareness and knowledge which will have an impact on attitude and practice to prevent spread of COVID-19.

negative: Skepticism and rumor spreading: the role of spatial correlations Critical thinking and skepticism are fundamental mechanisms that one may use to prevent the spreading of rumors, fake-news and misinformation. We consider a simple model in which agents without previous contact with the rumor, being skeptically oriented, may convince spreaders to stop their activity or, once exposed to the rumor, decide not to propagate it as a consequence, for example, of fact-checking. We extend a previous, mean-field analysis of the combined effect of these two mechanisms, active and passive skepticism, to include spatial correlations. This can be done either analytically, through the pair approximation, or simulating an agent-based version on diverse networks. Our results show that while in mean-field there is no coexistence between spreaders and susceptibles (although, depending on the parameters, there may be bistability depending on the initial conditions), when spatial correlations are included, because of the protective effect of the isolation provided by removed agents, coexistence is possible.

negative: Simulation Based Exploration of Bacterial Cross Talk Between Spatially Separated Colonies in a Multispecies Biofilm Community We present a simple mesoscopic model for bacterial cross-talk between growing biofilm colonies. The simulation setup mimics a novel microfludic biofilm growth reactor which allows a 2D description. The model is a stiff quasilinear system of diffusion-reaction equations with simultaneously a super-diffusion singularity and a degeneracy (as in the porous medium equation) that leads to the formation of sharp interfaces with finite speed of propagation and gradient blow up. We use a finite volume method with arithmetic flux averaging, and a time adaptive stiff time integrator. We find that signal and nutrient transport between colonies can greatly control and limit biofilm response to induction signals, leading to spatially heterogeneous biofilm behavior.

negative: Getting Back to Work: Risk Assessing Personal Vulnerabilities to COVID-19

negative: Isolation of Middle East Respiratory Syndrome Coronavirus from a Patient of the 2015 Korean Outbreak During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV.

negative: Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster Abstract Objectives With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. Methods A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also affirmed them with the patients and their families. Results Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not travelled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days 2 through 3 of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhoea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical or radiographic abnormalities. All the cases had an increasing level of C-reactive protein. Conclusions Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period.

negative: Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe. Considering the potential threat of a pandemic, scientists and physicians have been racing to understand this new virus and the pathophysiology of this disease to uncover possible treatment regimens and discover effective therapeutic agents and vaccines. To support the current research and development, CAS has produced a special report to provide an overview of published scientific information with an emphasis on patents in the CAS content collection. It highlights antiviral strategies involving small molecules and biologics targeting complex molecular interactions involved in coronavirus infection and replication. The drug-repurposing effort documented herein focuses primarily on agents known to be effective against other RNA viruses including SARS-CoV and MERS-CoV. The patent analysis of coronavirusrelated biologics includes therapeutic antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression as well as various types of vaccines. More than 500 patents disclose methodologies of these four biologics with the potential for treating and preventing coronavirus infections, which may be applicable to COVID-19. The information included in this report provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines.

negative: Discovery and Genomic Characterization of a Novel Ovine Partetravirus and a New Genotype of Bovine Partetravirus Partetravirus is a recently described group of animal parvoviruses which include the human partetravirus, bovine partetravirus and porcine partetravirus (previously known as human parvovirus 4, bovine hokovirus and porcine hokovirus respectively). In this report, we describe the discovery and genomic characterization of partetraviruses in bovine and ovine samples from China. These partetraviruses were detected by PCR in 1.8% of bovine liver samples, 66.7% of ovine liver samples and 71.4% of ovine spleen samples. One of the bovine partetraviruses detected in the present samples is phylogenetically distinct from previously reported bovine partetraviruses and likely represents a novel genotype. The ovine partetravirus is a novel partetravirus and phylogenetically most related to the bovine partetraviruses. The genome organization is conserved amongst these viruses, including the presence of a putative transmembrane protein encoded by an overlapping reading frame in ORF2. Results from the present study provide further support to the classification of partetraviruses as a separate genus in Parvovirinae.

negative: Politics, media and microbiologists Severe acute respiratory syndrome (SARS) took everybody by surprise. Its emergence was one of the most significant microbiological events of 2003. It challenged microbiologists to identify the aetiological agent and satisfy Koch's postulates — in so far as they ever can be met for a virus — in real time. Not only were the patients' respiratory secretions and the agents grown in cultured cells put under the microscope, but so were the actions of politicians. What lessons can we learn from SARS?

negative: How Risk Perceptions, Not Evidence, Have Driven Harmful Policies on COVID-19 COVID-19 hits all of the cognitive triggers for how the lay public misjudges risk. Robust findings from the field of risk perception have identified unique characteristics of a risk that allow for greater attribution of frequency and probability than is likely to be aligned with the base-rate statistics of the risk. COVID-19 embodies these features. It is unfamiliar, invisible, dreaded, potentially endemic, involuntary, disproportionately impacts vulnerable populations such as the elderly and has the potential for widespread catastrophe. When risks with such characteristics emerge, it is imperative for there to be trust between those in governance and communication and the lay public in order to quell public fears. This is not the environment in which COVID-19 has emerged, potentially resulting in even greater perceptions of risk.

negative: The emergence of the Middle East Respiratory Syndrome coronavirus (MERS-CoV) On September 20, 2012, a Saudi Arabian physician reported the isolation of a novel coronavirus from a patient with pneumonia on ProMED-mail. Within a few days the same virus was detected in a Qatari patient receiving intensive care in a London hospital, a situation reminiscent of the role air travel played in the spread of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2002. SARS-CoV originated in China’s Guangdong Province and affected more than 8000 patients in 26 countries before it was contained six months later. Over a year after the emergence of this novel coronavirus—Middle East Respiratory Syndrome coronavirus (MERS-CoV)—it has caused 178 laboratory confirmed cases and 76 deaths The emergence of a second highly pathogenic coronavirus within a decade highlights the importance of a coordinated global response incorporating reservoir surveillance, high-containment capacity with fundamental and applied research programs, and dependable communication pathways to ensure outbreak containment. Here we review the current state of knowledge on the epidemiology, ecology, molecular biology, clinical features and intervention strategies of the novel coronavirus, MERS-CoV.

negative: Data-driven modeling reveals a universal dynamic underlying the COVID-19 pandemic under social distancing We show that the COVID-19 pandemic under social distancing exhibits universal dynamics. The cumulative numbers of both infections and deaths quickly cross over from exponential growth at early times to a longer period of power law growth, before eventually slowing. In agreement with a recent statistical forecasting model by the IHME, we show that this dynamics is well described by the erf function. Using this functional form, we perform a data collapse across countries and US states with very different population characteristics and social distancing policies, confirming the universal behavior of the COVID-19 outbreak. We show that the predictive power of statistical models is limited until a few days before curves flatten, forecast deaths and infections assuming current policies continue and compare our predictions to the IHME models. We present simulations showing this universal dynamics is consistent with disease transmission on scale-free networks and random networks with non-Markovian transmission dynamics.

negative: What needs to be done to control the spread of Middle East respiratory syndrome coronavirus? Up to November 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) has infected 935 individuals and killed 371, all originating in or with links to the Middle East. The mechanisms of transmission of the disease are not fully understood, but MERS-CoV seems to sustain itself in the human population through repeated re-introduction from a camel reservoir and is able to cause nosocomial outbreaks. The risk of a global spread of MERS-CoV is low. Epidemiological, serological and phylogenetic research, combined with one health surveillance, dynamic case definitions, active case finding, rigorous infection control, culturally sensitive risk communication and a continuous re-evaluation of new evidence will enable to better understand the disease, limit its spread and quantify its risk in order to better prepare for a hypothetical spread.

negative: KNOWLEDGE AND BEHAVIORS RELATED TO THE COVID-19 PANDEMIC IN MALAWI Background: There are limited data on knowledge and behaviors related to COVID-19, and on the adoption of preventive behaviors, in sub-Saharan countries. Methods: Between April 25th and May 23rd, we contacted 793 individuals aged 18 and older, who previously participated in studies conducted in the Karonga Health and Demographic Surveillance Site in Karonga District, Malawi. During an interview by mobile phone, we ascertained sources of information about COVID-19 and we evaluated knowledge of respondents about the transmission and course of SARS-CoV-2/COVID-19. We also asked them to evaluate their own risk of infection and severe illness. Finally, we inquired about the preventive measures they had adopted in response to the pandemic. We describe patterns of knowledge and behaviors among survey respondents, by area of residence (rural vs. urban). Results: We interviewed 630 respondents (79.5% response rate) which included 260 men and 370 women. Four hundred and eighty-nine respondents resided in rural areas (77.6%) and 141 resided in urban areas (22.4%). Only one respondent had never heard of COVID-19. Respondents reported on average 4 distinct sources of information about COVID-19. Misconceptions about the modes of transmission of SARS-CoV-2, and about the course and severity of COVID-19, were common. For example, two thirds of respondents believed that everyone with COVID-19 would eventually become severely ill. Increased hand washing and avoiding crowds were the most reported strategies to prevent the spread of SARS-CoV-2. Use of face masks was more common among urban residents (22.5%) than among rural residents (5.0%). Conclusion: Despite widespread access to information about the COVID-19 pandemic, gaps in knowledge about COVID-19 persist in this population. The adoption of preventive strategies remains limited, possibly due to limited perceived risk of infection among a large fraction of the population.

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: Management of Aerosol during Noninvasive Ventilation for Patients with Sleep-Disordered Breathing: Important Messages during the COVID-19 Pandemic With the advent of COVID-19 infection and its rapid spread, preventive strategies are being developed worldwide, besides following the universal infection control guidelines. Prevention of spread through aerosol generation is one of the essential strategies in this regard, particularly for patients with sleep-disordered breathing at home and during hospital admission. Aerosols are produced, at home and in health care facilities, by natural processes and aerosol-generating procedures. To address this impinging problem, aerosol-generating procedures, like non-invasive ventilation (NIV), are to be handled meticulously, which might warrant isolation and sometimes device/interface modifications.

negative: Comparative Effectiveness of Laparoscopic Sleeve Gastrectomy on Morbidly Obese, Super-Obese, and Super-Super Obese Patients for the Treatment of Morbid Obesity. BACKGROUNDS The management of super-super obese patients is challenging for bariatric surgeons. Laparoscopic sleeve gastrectomy (LSG) is feasible as two-stage treatment for high-risk patients. However, its efficacy as a stand-alone procedure in super-super obese (SSO) patients is controversial. The study objective was to demonstrate the safety and efficacy of LSG in super-obese (SO) and SSO patients. METHODS A retrospective analysis was performed of consecutive patients undergoing LSG. The patients were classified into three groups: morbidly obese (MO), SO, and SSO. The patients' data, including each patient's characteristics, body mass index (BMI), preoperative comorbidities, postoperative complications, the resolution of comorbidities, percentage of excess weight loss (%EWL), and total weight loss (%TWL) were compared between groups. RESULTS Of the 186 patients, 163 (87.6%) were followed up for 41.2 ± 7.3 months (range 33-54 months). The mean BMI was 52.6 kg/m2. Eighty-three patients (50.9%) were MO, 52 (31.9%) were SO, and 28 (17.2%) were SSO. The groups were similar in terms of preoperative characteristics and postoperative complications. The mean %TWL were lower for the SSO group with no significant difference. The mean %TWL at 12, 24, 36, and 41.2 months postoperatively was 34.7, 34.4, 31.4, and 29.6% in SSO group, respectively. Also, the %EWL for the SSO group was significantly lower (48.3%) at the end of the follow-up period. However, the rate of significant improvement or complete resolution of comorbidities was similar in all groups. CONCLUSION Although %EWL was lower in the SSO group, LSG was a feasible and safe stand-alone bariatric surgical procedure for the resolution of comorbidities in MO, SO, and SSO patients.

negative: Global profiling of SARS-CoV-2 specific IgG/ IgM responses of convalescents using a proteome microarray COVID-19 is caused by SARS-CoV-2, and has become a global pandemic. There is no highly effective medicine or vaccine, most of the patients were recovered by their own immune response, especially the virus specific IgG and IgM responses. However, the IgG/ IgM responses is barely known. To enable the global understanding of SARS-CoV-2 specific IgG/ IgM responses, a SARS-CoV-2 proteome microarray with 18 out of the 28 predicted proteins was constructed. The microarray was applied to profile the IgG/ IgM responses with 29 convalescent sera. The results suggest that at the convalescent phase 100% of patients had IgG/ IgM responses to SARS-CoV-2, especially to protein N, S1 but not S2. S1 purified from mammalian cell demonstrated the highest performance to differentiate COVID-19 patients from controls. Besides protein N and S1, significant antibody responses to ORF9b and NSP5 were also identified. In-depth analysis showed that the level of S1 IgG positively correlate to age and the level of LDH (lactate dehydrogenase), especially for women, while the level of S1 IgG negatively correlate to Ly% (Lymphocyte percentage). This study presents the first whole picture of the SARS-CoV-2 specific IgG/ IgM responses, and provides insights to develop precise immuno-diagnostics, effective treatment and vaccine.

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

negative: Teicoplanin potently blocks the cell entry of 2019-nCoV Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection.

negative: Q&A: The novel coronavirus outbreak causing COVID-19

negative: What Dentists Need to Know about COVID-19 Abstract This article aims at collecting all information needed for dentists regarding the COVID-19 pandemic throughout the world by reviewing articles published by now. In late 2019, a pneumonia outbreak of uncertain etiology happened in Wuhan, China. There were many reports related to a live-animal and seafood market, supporting that the pathogens were transferred from animals to humans, rapidly evolving into transmission from human to human. The pathogen was classified as 2019 Novel Corona Virus (2019-nCoV), and the disease was named COrona VIrus Disease 2019 (COVID-19). Given that COVID-19 has lately been detected in infected patients’ saliva, the COVID-19 outbreak is an alert that all dental and other health professionals must be vigilant in defending against the infectious disease spread, and it may enable to assess whether non-invasive saliva diagnostic for COVID-19. There has so far been no evidence from randomized controlled trials to prescribe any particular anti-nCoV treatment or vaccine, and COVID-19 management has been widely supportive. Since the ACE-2 was expressing on oral cavity mucosa, there is a potentially huge COVID-19 infectious vulnerability risk for oral cavity and brought up a proof for the future prevention procedure in dental practice and daily life. As a result, the whole dental teams should be vigilant and keep patients and themselves in a safe environment by following the guideline in this study.

negative: Infektiologie Die Infektiologie ist ein Gebiet, das zahlreiche Schwerpunkte der Inneren Medizin, wie z. B. die Pulmologie oder Gastroenterologie, streift. Entsprechend behandelt das Kapitel alle wichtigen und häufigen Infektionen, mit denen ein Internist in der Praxis konfrontiert sein kann: von den unterschiedlichen Pneumonieformen, der Tuberkulose und Influenza über Noro-Virus-Erkrankungen, Cholera und EHEC-Infektionen bis hin zu sexuell übertragbaren Erkrankungen (HIV, Lues, Gonorrhö), die unterschiedlichen Herpes-Virus-Infektionen (Varizella-Zoster-, Herpes-simplex-, Eppstein-Barr- und Zytomegalie-Virus-Infektionen), Mykosen (Candidiasis, Aspergillose etc.) und andere häufig vorkommende Infektionskrankheiten.

negative: 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.

negative: Gryphon: A Hybrid Agent-Based Modeling and Simulation Platform for Infectious Diseases In this paper we present Gryphon, a hybrid agent-based stochastic modeling and simulation platform developed for characterizing the geographic spread of infectious diseases and the effects of interventions. We study both local and non-local transmission dynamics of stochastic simulations based on the published parameters and data for SARS. The results suggest that the expected numbers of infections and the timeline of control strategies predicted by our stochastic model are in reasonably good agreement with previous studies. These preliminary results indicate that Gryphon is able to characterize other future infectious diseases and identify endangered regions in advance.

negative: Chinese Public Attention to COVID-19 Epidemic: Based on Social Media Background: Since the new coronavirus epidemic in China in December 2019, information and discussions about COVID-19 have spread rapidly on the Internet and have quickly become the focus of worldwide attention, especially on social media. Objective: This study aims to investigate and analyze the public's attention to COVID-19-related events in China at the beginning of the COVID-19 epidemic in China (December 31, 2019, to February 20, 2020) through the Sina Microblog hot search list. Methods: We collected topics related to the COVID-19 epidemic on the Sina Microblog hot search list from December 31, 2019, to February 20, 2020 and described the trend of public attention on COVID-19 epidemic-related topics. ROST CM6.0 (ROST Content Mining System Version 6.0) was used to analyze the collected text for word segmentation, word frequency, and sentiment analysis. We further described the hot topic keywords and sentiment trends of public attention. We used VOSviewer to implement a visual cluster analysis of hot keywords and build a social network of public opinion content. Results: The study has four main findings. First, we analyzed the changing trend of the public's attention to the COVID-19 epidemic, which can be divided into three stages. Second, the hot topic keywords of public attention at each stage are slightly different. In addition, the emotional tendency of the public toward the COVID-19 epidemic-related hot topics has changed from negative to neutral, with negative emotions weakening and positive emotions increasing as a whole. Finally, we divided the COVID-19 topics with the most public concern into five categories: (1) new COVID-19 epidemics and their impact; (2) frontline reporting of the epidemic and prevention and control measures; (3) expert interpretation and discussion on the source of infection; (4) medical services on the frontline of the epidemic; and (5) focus on the global epidemic and the search for suspected cases. Conclusions: This is the first study of public attention on the COVID-19 epidemic using a Chinese social media platform (i.e., Sina Microblog). Our study found that social media (e.g., Sina Microblog) can be used to measure public attention to public health emergencies. During the epidemic of the novel coronavirus, a large amount of information about the COVID-19 epidemic was disseminated on Sina Microblog and received widespread public attention. We have learned about the hotspots of public concern regarding the COVID-19 epidemic. These findings can help the government and health departments better communicate with the public on health and translate public health needs into practice to create targeted measures to prevent and control the spread of COVID-19. Keywords: COVID-19; Sina Microblog; Public attention; Social media; China; Public health emergency

negative: Temperature significant change COVID-19 Transmission in 429 cities Background There is no evidence supporting that temperature changes COVID-19 transmission. Methods We collected the cumulative number of confirmed cases of all cities and regions affected by COVID-19 in the world from January 20 to February 4, 2020, and calculated the daily means of the average, minimum and maximum temperatures in January. Then, restricted cubic spline function and generalized linear mixture model were used to analyze the relationships. Results There were in total 24,232 confirmed cases in China and 26 overseas countries. In total, 16,480 cases (68.01%) were from Hubei Province. The lgN rose as the average temperature went up to a peak of 8.72℃ and then slowly declined. The apexes of the minimum temperature and the maximum temperature were 6.70℃ and 12.42℃ respectively. The curves shared similar shapes. Under the circumstance of lower temperature, every 1℃ increase in average, minimum and maximum temperatures led to an increase of the cumulative number of cases by 0.83, 0.82 and 0.83 respectively. In the single-factor model of the higher-temperature group, every 1℃ increase in the minimum temperature led to a decrease of the cumulative number of cases by 0.86. Conclusion The study found that, to certain extent, temperature could significant change COVID-19 transmission, and there might be a best temperature for the viral transmission, which may partly explain why it first broke out in Wuhan. It is suggested that countries and regions with a lower temperature in the world adopt the strictest control measures to prevent future reversal.

negative: Three months of informational trends in COVID-19 across New York City In the midst of widespread community transmission of coronavirus disease 2019 (COVID-19) in New York, residents have sought information about COVID-19. We analyzed trends in New York State (NYS) and New York City (NYC) data to quantify the extent of COVID-19-related queries. Data on the number of 311 calls in NYC, Google Trend data on the search term ‘Coronavirus’ and information about trends in COVID-19 cases in NYS and the USA were compiled from multiple sources. There were 1228 994 total calls to 311 between 22 January 2020 and 22 April 2020, with 50 845 calls specific to COVID-19 in the study period. The proportion of 311 calls related to COVID-19 increased over time, while the ‘interest over time’ of the search term ‘Coronavirus’ has exponentially increased since the end of February 2020. It is vital that public health officials provide clear and up-to-date information about protective measures and crucial communications to respond to information-seeking behavior across NYC.

negative: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well.

negative: Inferring Contagion Patterns in Social Contact Networks with Limited Infection Data The spread of infectious disease is an inherently stochastic process. As such, real time control and prediction methods present a significant challenge. For diseases which spread through direct human interaction, (e.g., transferred from infected to susceptible individuals) the contagion process can be modeled on a social-contact network where individuals are represented as nodes, and contacts between individuals are represented as links. The model presented in this paper seeks to identify the infection pattern which depicts the current state of an ongoing outbreak. This is accomplished by inferring the most likely paths of infection through a contact network under the assumption of partially available infection data. The problem is formulated as a bi-linear integer program, and heuristic solution methods are developed based on sub-problems which can be solved much more efficiently. The heuristic performance is presented for a range of randomly generated networks and different levels of information. The model results, which include the most likely set of infection spreading contacts, can be used to provide insight into future epidemic outbreak patterns, and aid in the development of intervention strategies.

negative: Mathematical model of infection kinetics and its analysis for COVID-19, SARS and MERS The purpose of this paper is to reveal the spread rules of the three pneumonia: COVID-19, SARS and MERS. We compare the new spread characteristics of COVID-19 with those of SARS and MERS. By considering the growth rate and inhibition constant of infectious diseases, their propagation growth model is established. The parameters of the three coronavirus transmission growth models are obtained by nonlinear fitting. Parametric analysis shows that the growth rate of COVID-19 is about twice that of the SARS and MERS, and the COVID-19 doubling cycle is two to three days, suggesting that the number of COVID-19 patients would double in two to three days without human intervention. The infection inhibition constant in Hubei is two orders of magnitude lower than in other regions, which reasonably explains the situation of the COVID-19 outbreak in Hubei.

negative: The spread and control of rumors in a multilingual environment This paper studies the rumor propagation model with heterogeneous networks in a multilingual environment. Firstly, a rumor propagation model with two language spreaders, in which the immunologic mechanism is considered in the ignorant, is proposed on heterogeneous networks. Secondly, the basic reproduction number and the dynamic behaviors are analyzed by using the next-generation matrix method and Lyapunov stability theory, respectively. Moreover, two control strategies are designed to effectively suppress the spread of the rumor. The one is continuous control strategy. By applying real-time control to the spreaders, the rumor spreading time can be greatly reduced and the rumor can die out in a short time. The other is event-triggered impulsive control strategy, which can effectively reduce the consumption of resources and ensure the extinction of the rumor. Finally, the correctness of theoretical analysis and the feasibility of control methods are verified by numerical simulations.

negative: Active surveillance for suspected COVID-19 cases in inpatients with information technology

negative: COVID-19 and maternal mental health: Are we getting the balance right? This paper presents a rapid evidence review into the clinical and psychological impacts of COVID-19 on perinatal women and their infants. Literature search revealed that there is very little formal evidence on the impact of COVID-19 on pregnant, labouring and postnatal women or their babies. The clinical evidence to date suggests that pregnant and childbearing women, and their babies are not at increased risk of either getting infected, or of having severe symptoms or consequences than the population as a whole. There is no evidence on the short- and longer-term psychological impacts of restrictive practices or social and personal constraints for childbearing women during COVID-19 in particular, or infection pandemics in general. The potential for adverse mental health consequences of the pandemic should be recognised as a critical public health concern, together with appropriate care and support to prevent and ameliorate any negative impacts.

negative: Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function (“dysbiosis”) in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.

negative: Part of the Cure or Spreader of the Disease?

negative: Identifying Influential Spreaders of Epidemics on Community Networks An efficient strategy for the identification of influential spreaders that could be used to control epidemics within populations would be of considerable importance. Generally, populations are characterized by its community structures and by the heterogeneous distributions of weak ties among nodes bridging over communities. A strategy for community networks capable of identifying influential spreaders that accelerate the spread of disease is here proposed. In this strategy, influential spreaders serve as target nodes. This is based on the idea that, in k-shell decomposition, weak ties and strong ties are processed separately. The strategy was used on empirical networks constructed from online social networks, and results indicated that this strategy is more accurate than other strategies. Its effectiveness stems from the patterns of connectivity among neighbors, and it successfully identified the important nodes. In addition, the performance of the strategy remained robust even when there were errors in the structure of the network.

negative: The 2019 coronavirus: Learning curves, lessons, and the weakest link In the space of just six weeks, a new coronavirus, from a family that historically was not viewed as a global health concern, has become daily headline news around the globe. The 21st century marked its arrival with the emergence of three previously unknown coronaviruses. SARS-CoV (severe acute respiratory syndrome coronavirus) was recognized in November 2002 [1, 2], MERS-CoV (Middle East respiratory syndrome coronavirus) in June 2012 [3, 4], and 2019-nCoV in December 2019 [5]. Previously, human coronaviruses, known since the 1960s, were viewed as being only marginally relevant to the clinic, except for infants, the elderly, and immunocompromised individuals [1, 6, 7].

negative: 2019-20 Wuhan coronavirus outbreak: Intense surveillance is vital for preventing sustained transmission in new locations The outbreak of pneumonia originating in Wuhan, China, has generated 830 confirmed cases, including 26 deaths, as of 24 January 2020. The virus (2019-nCoV) has spread elsewhere in China and to other countries, including South Korea, Thailand, Japan and USA. Fortunately, there has not yet been evidence of sustained human-to-human transmission outside of China. Here we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.37. However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.005. This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a large global epidemic.

negative: Coronavirus disease 2019: What we know? In late December 2019, a cluster of unexplained pneumonia cases has been reported in Wuhan, China. A few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 and the relevant infected disease has been named as coronavirus disease 2019 (COVID‐19) by the World Health Organization, respectively. The COVID‐19 epidemic is spreading in China and all over the world now. The purpose of this review is primarily to review the pathogen, clinical features, diagnosis, and treatment of COVID‐19, but also to comment briefly on the epidemiology and pathology based on the current evidence.

negative: A review of modern technologies for tackling COVID-19 pandemic Abstract Objective Science and technology sector constituting of data science, machine learning and artificial intelligence are contributing towards COVID-19. The aim of the present study is to discuss the various aspects of modern technology used to fight against COVID-19 crisis at different scales, including medical image processing, disease tracking, prediction outcomes, computational biology and medicines. Methods A progressive search of the database related to modern technology towards COVID-19 is made. Further, a brief review is done on the extracted information by assessing the various aspects of modern technologies for tackling COVID-19 pandemic. Results We provide a window of thoughts on review of the technology advances used to decrease and smother the substantial impact of the outburst. Though different studies relating to modern technology towards COVID-19 have come up, yet there are still constrained applications and contributions of technology in this fight. Conclusions On-going progress in the modern technology has contributed in improving people's lives and hence there is a solid conviction that validated research plans including artificial intelligence will be of significant advantage in helping people to fight this infection.

negative: A structured model for COVID-19 spread: modelling age and healthcare inequities We use stochastic branching process model, structured by age and level of healthcare access, to look at the heterogeneous spread of COVID-19 within a population. We examine the effect of control scenarios targeted at particular groups, such as school closures or social distancing by older people. Although we currently lack detailed empirical data about contact and infection rates between different age groups and groups with different levels of healthcare access within New Zealand, these scenarios illustrate how such evidence could be used to inform specific interventions. We find that an increase in the transmission rates amongst children as a result of reopening schools is, on its own, unlikely to significantly increase the number of cases. However, if this is accompanied by a change in adult behaviour, for example increased contact rates among parents, it could have a much bigger effect. We also find that there is a risk of undetected outbreaks occurring in communities that have low access to healthcare and that are socially isolated from more privileged communities. The greater the inequity and the greater the degree of social segregation, the longer it will take before any outbreaks are detected. Well-established evidence for health inequities, particularly in accessing primary healthcare and testing, indicates that M[a]ori and Pacific peoples are at higher risk of undetected outbreaks in Aotearoa New Zealand. This highlights the importance of ensuring that community needs for access to healthcare, including early proactive testing, rapid contact tracing, and the ability to isolate, are being met equitably. Finally, these scenarios illustrate how information concerning contact and infection rates across different demographic groups may be useful in informing specific policy interventions.

negative: Travellers give wings to novel coronavirus (2019-nCoV) A novel coronavirus, probably of bat origin, has caused an outbreak of severe respiratory infection in humans in Wuhan, China and has been dispersed globally by travelers. The WHO has declared the spread of the infection a Public Health Emergency of International Concern.

negative: Eco-epidemiological assessment of the COVID-19 epidemic in China, January-February 2020 Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance elsewhere. Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation. Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25° latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5-7 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios. Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 cases. Weekly means of maximum daily temperature varied from -28.0 to 30.1 °C, minimum daily temperature from -42.4 to 23.0 °C, maximum solar radiation from 0.04 to 2.74 MJm-2 and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence. Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.

negative: Investigation of Nosocomial SARS-CoV-2 Transmission from Two Patients to Health Care Workers Identifies Close Contact but not Airborne Transmission Events. OBJECTIVE To describe the pattern of transmission of SARS-CoV-2 during 2 nosocomial outbreaks of COVID-19 with regard to the possibility of airborne transmission. DESIGN Contact investigations with active case finding were used to assess the pattern of spread from 2 COVID-19 index patients. SETTING A community hospital and university medical center in the United States, in February and March, 2020, early in the COVID-19 pandemic. PATIENTS Two index patients and 421 exposed health care workers. METHODS Exposed staff were identified by analyzing the EMR and conducting active case finding in combination with structured interviews. Staff were tested for COVID-19 by obtaining oropharyngeal/nasopharyngeal specimens, with RT-PCR testing to detect SARS-CoV-2. RESULTS Two separate index patients were admitted in February and March 2020, without initial suspicion for COVID-19 and without contact or droplet precautions in place; both patients underwent several aerosol generating procedures in this context. A total of 421 health care workers were exposed in total, and the results of the case contact investigations identified 8 secondary infections in health care workers. In all 8 cases, the staff had close contact with the index patients without sufficient personal protective equipment. Importantly, despite multiple aerosol generating procedures, there was no evidence of airborne transmission. CONCLUSION These observations suggest that, at least in a healthcare setting, a majority of SARS-CoV-2 transmission is likely to take place during close contact with infected patients through respiratory droplets, rather than by long-distance airborne transmission.

negative: Contact tracing to control infectious disease: when enough is enough Contact tracing (also known as partner notification) is a primary means of controlling infectious diseases such as tuberculosis (TB), human immunodeficiency virus (HIV), and sexually transmitted diseases (STDs). However, little work has been done to determine the optimal level of investment in contact tracing. In this paper, we present a methodology for evaluating the appropriate level of investment in contact tracing. We develop and apply a simulation model of contact tracing and the spread of an infectious disease among a network of individuals in order to evaluate the cost and effectiveness of different levels of contact tracing. We show that contact tracing is likely to have diminishing returns to scale in investment: incremental investments in contact tracing yield diminishing reductions in disease prevalence. In conjunction with a cost-effectiveness threshold, we then determine the optimal amount that should be invested in contact tracing. We first assume that the only incremental disease control is contact tracing. We then extend the analysis to consider the optimal allocation of a budget between contact tracing and screening for exogenous infection, and between contact tracing and screening for endogenous infection. We discuss how a simulation model of this type, appropriately tailored, could be used as a policy tool for determining the appropriate level of investment in contact tracing for a specific disease in a specific population. We present an example application to contact tracing for chlamydia control.

negative: From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic Hospitals worldwide are facing an increasing incidence of hard-to-treat infections. Limiting infections and providing patients with optimal drug regimens require timely strain identification as well as virulence and drug-resistance profiling. Additionally, prophylactic interventions based on the identification of environmental sources of recurrent infections (e.g., contaminated sinks) and reconstruction of transmission chains (i.e., who infected whom) could help to reduce the incidence of nosocomial infections. WGS could hold the key to solving these issues. However, uptake in the clinic has been slow. Some major scientific and logistical challenges need to be solved before WGS fulfils its potential in clinical microbial diagnostics. In this review we identify major bottlenecks that need to be resolved for WGS to routinely inform clinical intervention and discuss possible solutions.

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: CO.ME.T.A. -- covid-19 media textual analysis. A dashboard for media monitoring The focus of this paper is to trace how mass media, particularly newspapers, have addressed the issues about the containment of contagion or the explanation of epidemiological evolution. We propose an interactive dashboard: CO.ME.T.A.. During crises it is important to shape the best communication strategies in order to respond to critical situations. In this regard, it is important to monitor the information that mass media and social platforms convey. The dashboard allows to explore the mining of contents extracted and study the lexical structure that links the main discussion topics. The dashboard merges together four methods: text mining, sentiment analysis, textual network analysis and latent topic models. Results obtained on a subset of documents show not only a health-related semantic dimension, but it also extends to social-economic dimensions.

negative: Epidemiology and etiology of community-acquired pneumonia The seriousness of community-acquired pneumonia (CAP), despite being a reasonably common and potentially lethal disease, often is under estimated by physicians and patients alike. CAP results in more than 10 million visits to physicians, 64 million days of restricted activity, and 600,000 hospitalizations. This article discusses the epidemiology and bacterial causes of CAP in immunocompetent adults and the severe acute respiratory syndrome coronavirus.

negative: COVID-19: Immunology and treatment options Abstract The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.

negative: Heparin enhances the furin cleavage of HIV-1 gp160 peptides Abstract Infectious HIV-1 requires gp160 cleavage by furin at the REKR511↓ motif (site1) into the gp120/gp41 complex, whereas the KAKR503 (site2) sequence remains uncleaved. We synthesized 41mer and 51mer peptides, comprising site1 and site2, to study their conformation and in vitro furin processing. We found that, while the previously reported 19mer and 13mer analogues represent excellent in vitro furin substrates, the present extended sequences require heparin for optimal processing. Our data support the hypothesis of a direct binding of heparin with site1 and site2, allowing selective exposure/accessibility of the REKR sequence, which is only then optimally cleaved by furin.

negative: Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2 The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.

negative: Network theory and SARS: predicting outbreak diversity Abstract Many infectious diseases spread through populations via the networks formed by physical contacts among individuals. The patterns of these contacts tend to be highly heterogeneous. Traditional “compartmental” modeling in epidemiology, however, assumes that population groups are fully mixed, that is, every individual has an equal chance of spreading the disease to every other. Applications of compartmental models to Severe Acute Respiratory Syndrome (SARS) resulted in estimates of the fundamental quantity called the basic reproductive number R 0 —the number of new cases of SARS resulting from a single initial case—above one, implying that, without public health intervention, most outbreaks should spark large-scale epidemics. Here we compare these predictions to the early epidemiology of SARS. We apply the methods of contact network epidemiology to illustrate that for a single value of R 0 , any two outbreaks, even in the same setting, may have very different epidemiological outcomes. We offer quantitative insight into the heterogeneity of SARS outbreaks worldwide, and illustrate the utility of this approach for assessing public health strategies.

negative: Evaluation of the secondary transmission pattern and epidemic prediction of COVID-19 in the four metropolitan areas of China Understanding the transmission dynamics of COVID-19 is crucial for evaluating its spread pattern, especially in metropolitan areas of China, as its spread can lead to secondary outbreaks outside Wuhan, the center of the new coronavirus disease outbreak. In addition, the experiences gained and lessons learned from China have the potential to provide evidence to support other metropolitan areas and large cities outside China with emerging cases. We used data reported from January 24, 2020, to February 23, 2020, to fit a model of infection, estimate the likely number of infections in four high-risk metropolitan areas based on the number of cases reported, and increase the understanding of the COVID-19 spread pattern. Considering the effect of the official quarantine regulations and travel restrictions for China, which began January 23~24, 2020, we used the daily travel intensity index from the Baidu Maps app to roughly simulate the level of restrictions and estimate the proportion of the quarantined population. A group of SEIR model statistical parameters were estimated using Markov chain Monte Carlo (MCMC) methods and fitting on the basis of reported data. As a result, we estimated that the basic reproductive number, R0, was 2.91 in Beijing, 2.78 in Shanghai, 2.02 in Guangzhou, and 1.75 in Shenzhen based on the data from January 24, 2020, to February 23, 2020. In addition, we inferred the prediction results and compared the results of different levels of parameters. For example, in Beijing, the predicted peak number of cases was approximately 466 with a peak time of February 29, 2020; however, if the city were to implement different levels (strict, mild, or weak) of travel restrictions or regulation measures, the estimation results showed that the transmission dynamics would change and that the peak number of cases would differ by between 56% and ~159%. We concluded that public health interventions would reduce the risk of the spread of COVID-19 and that more rigorous control and prevention measures would effectively contain its further spread but that the risk will increase when businesses and social activities return to normal before the end of the epidemic. Besides, the experiences gained and lessons learned from China are potential to provide evidences supporting for other metropolitan areas and big cities with emerging cases outside China.

negative: The potential of targeted antibody prophylaxis in SARS outbreak control: A mathematic analysis Summary Background Severe acute respiratory syndrome (SARS) coronavirus-like viruses continue to circulate in animal reservoirs. If new mutants of SARS coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that contained the first SARS outbreak. Method We developed a mathematical model to investigate the effects of hospital admission and targeted antibody prophylaxis on the reproduction number R, defined as the number of secondary cases generated by an index case, during different SARS outbreak scenarios. Results Assuming a basic reproduction number R 0=3, admission of patients to hospital within 4.3 days of symptom onset is necessary to achieve outbreak control without the need to further reduce community-based transmission. Control may be enhanced by providing pre-exposure prophylaxis to contacts of hospitalized patients, and through contact tracing and provision of post-exposure prophylaxis. Antibody prophylaxis may also be employed to reduce R below one and thereby restrict outbreak size and duration. Conclusions Patient isolation alone can be sufficient to control SARS outbreaks provided that the time from onset to admission is short. Antibody prophylaxis as supplemental measure generally allows for containment of higher R 0 values and restricts both the size and duration of an outbreak.

negative: A Model for Coupled Outbreaks Contained by Behavior Change Large epidemics such as the recent Ebola crisis in West Africa occur when local efforts to contain outbreaks fail to overcome the probabilistic onward transmission to new locations. As a result, there may be large differences in total epidemic size from similar initial conditions. This work seeks to determine the extent to which the effects of behavior changes and metapopulation coupling on epidemic size can be characterized. While mathematical models have been developed to study local containment by social distancing, intervention and other behavior changes, their connection to larger-scale transmission is relatively underdeveloped. We make use of the assumption that behavior changes limit local transmission before susceptible depletion to develop a time-varying birth-death process capturing the dynamic decrease of the transmission rate associated with behavior changes. We derive an expression for the mean outbreak size of this model and show that the distribution of outbreak sizes is approximately geometric. This allows a probabilistic extension whereby infected individuals may initiate new outbreaks. From this model we characterize the overall epidemic size as a function of the behavior change rate and the probability that an infected individual starts a new outbreak. We find good agreement between the analytical results and stochastic simulations leading to novel findings including critical learning rates that demarcate large and small epidemic sizes.

negative: The Efficacy of Contact Tracing for the Containment of the 2019 Novel Coronavirus (COVID-19). Contact tracing is a central public health response to infectious disease outbreaks, especially in the early stages of an outbreak when specific treatments are limited. Importation of novel Coronavirus (COVID-19) from China and elsewhere into the United Kingdom highlights the need to understand the impact of contact tracing as a control measure. Using detailed survey information on social encounters coupled to predictive models, we investigate the likely efficacy of the current UK definition of a close contact (within 2 meters for 15 minutes or more) and the distribution of secondary cases that may go untraced. Taking recent estimates for COVID-19 transmission, we show that less than 1 in 5 cases will generate any subsequent untraced cases, although this comes at a high logistical burden with an average of 36.1 individuals (95th percentiles 0-182) traced per case. Changes to the definition of a close contact can reduce this burden, but with increased risk of untraced cases; we estimate that any definition where close contact requires more than 4 hours of contact is likely to lead to uncontrolled spread.

negative: Arbitrary Scale Super-Resolution for Brain MRI Images Recent attempts at Super-Resolution for medical images used deep learning techniques such as Generative Adversarial Networks (GANs) to achieve perceptually realistic single image Super-Resolution. Yet, they are constrained by their inability to generalise to different scale factors. This involves high storage and energy costs as every integer scale factor involves a separate neural network. A recent paper has proposed a novel meta-learning technique that uses a Weight Prediction Network to enable Super-Resolution on arbitrary scale factors using only a single neural network. In this paper, we propose a new network that combines that technique with SRGAN, a state-of-the-art GAN-based architecture, to achieve arbitrary scale, high fidelity Super-Resolution for medical images. By using this network to perform arbitrary scale magnifications on images from the Multimodal Brain Tumor Segmentation Challenge (BraTS) dataset, we demonstrate that it is able to outperform traditional interpolation methods by up to 20[Formula: see text] on SSIM scores whilst retaining generalisability on brain MRI images. We show that performance across scales is not compromised, and that it is able to achieve competitive results with other state-of-the-art methods such as EDSR whilst being fifty times smaller than them. Combining efficiency, performance, and generalisability, this can hopefully become a new foundation for tackling Super-Resolution on medical images.

negative: Analysis of Spatial-temporal Behavior Pattern of the Share Bike Usage during COVID-19 Pandemic in Beijing During the epidemics of COVID-19, the whole world is experiencing a serious crisis on public health and economy. Detailed information in the behavior of residents during epidemic benefits emergency management when one tries to design intervention strategies and resilience measures. From the perspective of movements, the widely used Bike Sharing System (BSS) in China is capable of characterizing the behavior patterns over time&space within big cities. Although share bikes are playing an important role as data sources in data mining, they could be of help but are rarely reported in pandemic-related researches. Based on the share bike records in Beijing, we constructed a behavior pattern analysis framework, then analyzed the spatiotemporal behavior patterns of residents, figured out the key time nodes of different pandemic periods, and demonstrated the variations in mobility due to the onset of the COVID-19 threat and administrative restrictions. The impact of the pandemic was assessed by performing co-location analysis between share bike usage and POIs (Point Of Interest). Classification of POIs is helpful to distinguish the behavior patterns generated by various the productive and social activities. Discussions with evolving confirmed COVID-19 cases suggest the effectiveness and necessity of the public interventions in the COVID-19 containment during the resilience period. These findings provide critical information on how to respond to the current COVID-19 outbreak and other epidemic events.

negative: 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.

negative: Different Epidemic Curves for Severe Acute Respiratory Syndrome Reveal Similar Impacts of Control Measures Severe acute respiratory syndrome (SARS) has been the first severe contagious disease to emerge in the 21st century. The available epidemic curves for SARS show marked differences between the affected regions with respect to the total number of cases and epidemic duration, even for those regions in which outbreaks started almost simultaneously and similar control measures were implemented at the same time. The authors developed a likelihood-based estimation procedure that infers the temporal pattern of effective reproduction numbers from an observed epidemic curve. Precise estimates for the effective reproduction numbers were obtained by applying this estimation procedure to available data for SARS outbreaks that occurred in Hong Kong, Vietnam, Singapore, and Canada in 2003. The effective reproduction numbers revealed that epidemics in the various affected regions were characterized by markedly similar disease transmission potentials and similar levels of effectiveness of control measures. In controlling SARS outbreaks, timely alerts have been essential: Delaying the institution of control measures by 1 week would have nearly tripled the epidemic size and would have increased the expected epidemic duration by 4 weeks.

negative: Estimating and modelling the transmissibility of Middle East Respiratory Syndrome CoronaVirus during the 2015 outbreak in the Republic of Korea BACKGROUND: Emerging respiratory infections represent a significant public health threat. Because of their novelty, there are limited measures available to control their early spread. Learning from past outbreaks is important for future preparation. The Middle Eastern Respiratory Syndrome CoronaVirus (MERS‐CoV ) 2015 outbreak in the Republic of Korea (ROK) provides one such opportunity. OBJECTIVES: We demonstrated through quantitative methodologies how to estimate MERS‐CoV's transmissibility and identified the effective countermeasures that stopped its spread. METHODS: Using the outbreak data, statistical methods were employed to estimate the basic reproductive number R (0), the average number of secondary cases produced by a typical primary case during its entire infectious period in a fully susceptible population. A transmission dynamics model was also proposed to estimate R (0) and to identify the most effective countermeasures. The consistency between results will provide cross‐validation of the approaches. RESULTS: R (0) ranged from 2.5 with 95% confidence interval (CI): [1.7, 3.1] (using the sequential Bayesian method) to 7.2 with 95% CI: [5.3, 9.4] (using the Nowcasting method). Estimates from transmission model were higher but overlapped with these. Personal protection and rapid confirmation of cases were identified as the most important countermeasures. CONCLUSIONS: Our estimates were in agreement with others from the ROK outbreak, albeit significantly higher than estimates based on other small outbreaks and sporadic cases of MERS‐CoV. The large‐scale outbreak in the ROK was jointly due to the high transmissibility in the healthcare‐associated setting and the Korean culture‐associated contact behaviour. Limiting such behaviour by rapidly identifying and isolating cases and avoiding high‐risk contacts effectively stopped further transmission.

negative: Co-infection with SARS-CoV-2 and influenza A virus Coronavirus Disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is spreading globally and poses a major public health threat. We reported a case of influenza A virus and SARS-CoV-2 co-infection. As the number of COVID-19 cases increase, it will be necessary to comprehensively evaluate imaging and other clinical findings as well as consider co-infection with other respiratory viruses.

negative: Clinical and pathological characteristics of 2019 novel coronavirus disease (COVID-19): a systematic review Importance: In 2002-2003, a severe pulmonary infectious disease occurred in Guangdong, China. The disease was caused by SARS-CoV, 17 years apart, also happen in China, and SARS-CoV-2, this epidemic has posed a significant hazard to people health both China and the whole world. Objective: Summarized the latest epidemiological changes, clinical manifestations, auxiliary examination and pathological characteristics of COVID-19. Evidence Review: PubMed database were searched from 2019 to 2020 using the index terms novel coronavirus or COVID-19 or 2019-nCoV or SARS-CoV-2 and synonyms. Articles that reported clinical characteristics, laboratory results, imageological diagnosis and pathologic condition were included and were retrospectively reviewed for these cases. This paper adopts the method of descriptive statistics. Results: 34 COVID-19-related articles were eligible for this systematic review;Four of the articles were related to pathology. We found that Fever (86.0%), cough (63.9%) and Malaise/Fatigue (34.7%) were the most common symptoms in COVID-19. But in general, the clinical symptoms and signs of COVID-19 were not obvious. Compared with SARS, COVID-19 was transmitted in a more diverse way. The mortality rates of COVID-19 were 2.5%, and the overall infection rate of healthcare worker of COVID-19 was 3.9%. We also found that the pathological features of COVID-19 have greatly similar with SARS, which manifested as ARDS. But the latest pathological examination of COVID-19 revealed the obvious mucinous secretions in the lungs. Interpretation: The clinical and pathological characteristics of SARS and COVID-19 in China are very similar, but also difference. The latest finds of pathological examination on COVID-19 may upend existing treatment schemes, so the early recognition of disease by healthcare worker is very important.

negative: The far side of the COVID-19 epidemic curve: local re-openings based on globally coordinated triggers may work best In the late stages of an epidemic, infections are often sporadic and geographically distributed. Spatially structured stochastic models can capture these important features of disease dynamics, thereby allowing a broader exploration of interventions. Here we develop a stochastic model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission amongst an interconnected group of population centres representing counties, municipalities and districts (collectively, ``counties''). The model is parameterized with demographic, epidemiological, testing, and travel data from the province of Ontario, Canada. We explore the effects of different control strategies after the epidemic curve has been flattened. We compare a local strategy of re-opening (and re-closing, as needed) schools and workplaces county-by-county according to triggers for county-specific infection prevalence, to a global strategy of province-wide re-opening and re-closing according to triggers for province-wide infection prevalence. We find that the local strategy results in far fewer person-days of closure but only slightly more coronavirus disease (COVID-19) cases, even under assumptions of high inter-county travel. However, both cases and person-days lost to closure rise significantly when county triggers are not coordinated by the province and when testing rates vary among counties. Finally, we show that local strategies can also do better in the early epidemic stage but only if testing rates are high and the trigger prevalence is low. Our results suggest that phased plans for re-opening economies on the far side of the COVID-19 epidemic curve should consider preceding larger-scale re-openings with coordinated local re-openings.

negative: 2019_nCoV/SARS‐CoV‐2: rapid classification of betacoronaviruses and identification of Traditional Chinese Medicine as potential origin of zoonotic coronaviruses The current outbreak of a novel severe acute respiratory syndrome‐like coronavirus, 2019_nCoV (now named SARS‐CoV‐2), illustrated difficulties in identifying a novel coronavirus and its natural host, as the coding sequences of various Betacoronavirus species can be highly diverse. By means of whole‐genome sequence comparisons, we demonstrate that the noncoding flanks of the viral genome can be used to correctly separate the recognized four betacoronavirus subspecies. The conservation would be sufficient to define target sequences that could, in theory, classify novel virus species into their subspecies. Only 253 upstream noncoding sequences of Sarbecovirus are sufficient to identify genetic similarities between species of this subgenus. Furthermore, it was investigated which bat species have commercial value in China, and would thus likely be handled for trading purposes. A number of coronavirus genomes have been published that were obtained from such bat species. These bats are used in Traditional Chinese Medicine, and their handling poses a potential risk to cause zoonotic coronavirus epidemics. SIGNIFICANCE AND IMPACT OF THE STUDY: The noncoding upstream and downstream flanks of coronavirus genomes allow for rapid classification of novel Betacoronavirus species and correct identification of genetic relationships. Although bats are the likely natural host of 2019_nCoV, the exact bat species that serves as the natural host of the virus remains as yet unknown. Chinese bat species with commercial value were identified as natural reservoirs of coronaviruses and are used in Traditional Chinese Medicine. Since their trading provides a potential risk for spreading zoonoses, a change in these practices is highly recommended.

negative: Novel coronavirus infection and children BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its outbreak in many states of the world, forced the World Health Organization (WHO) to declare a pandemic. Currently, COVID-19 has infected 1 991 562 patients causing 130 885 deaths globally as of 16 April 2020. The aim of this review is to underline the epidemiological, clinical and management characteristics in children affected by COVID-19. METHODS: We searched Pubmed, from January to April 2020, for the following search terms: "COVID-19", "children", "SARS-COV2", "complications", "epidemiology", "clinical features", focusing our attention mostly on epidemiology and symptoms of COVID-19 in children. RESULTS: Usually, infants and children present milder symptoms of the disease with a better outcome than adults. Consequently, children may be considered an infection reservoir that may play a role as spreader of the infection in community.

negative: Analysis of the Summer Season Home Range of Domestic Feral Cats ( Felis catus ) - Focused on the Surroundings of Rural and Suburban Areas Abstract In order to analyze the home range of feral cats residing in the surroundings of rural and suburban areas, we collected coordination information data from five feral cats. As a result of such research, 100% MCP was defined as minimum 31,500 and maximum 351,900, and 95% KR was defined as minimum 9,400 and maximum 502,800, 75% KR was defined as minimum 3,600 and maximum 126,900, and 50% MCP was defined as minimum 1,800 and maximum 51,700. The home range of feral cats was also analyzed during daytime and nighttime, and all five individuals showed a wider home range during the nighttime than daytime. The analysis of gender shows that the average home range of female feral cats is larger than the average of males. Meanwhile, the results of information data with wide-open areas such as farm land and terrace land on the river showed that the analyzed value was increased generally, and showed variable values depending on the gender and size of each individual feral cat.

negative: Coronavirus Goes Viral: Quantifying the COVID-19 Misinformation Epidemic on Twitter Background Since the beginning of the coronavirus disease 2019 (COVID-19) epidemic, misinformation has been spreading uninhibited over traditional and social media at a rapid pace. We sought to analyze the magnitude of misinformation that is being spread on Twitter (Twitter, Inc., San Francisco, CA) regarding the coronavirus epidemic. Materials and methods We conducted a search on Twitter using 14 different trending hashtags and keywords related to the COVID-19 epidemic. We then summarized and assessed individual tweets for misinformation in comparison to verified and peer-reviewed resources. Descriptive statistics were used to compare terms and hashtags, and to identify individual tweets and account characteristics. Results The study included 673 tweets. Most tweets were posted by informal individuals/groups (66%), and 129 (19.2%) belonged to verified Twitter accounts. The majority of included tweets contained serious content (91.2%); 548 tweets (81.4%) included genuine information pertaining to the COVID-19 epidemic. Around 70% of the tweets tackled medical/public health information, while the others were pertaining to sociopolitical and financial factors. In total, 153 tweets (24.8%) included misinformation, and 107 (17.4%) included unverifiable information regarding the COVID-19 epidemic. The rate of misinformation was higher among informal individual/group accounts (33.8%, p: <0.001). Tweets from unverified Twitter accounts contained more misinformation (31.0% vs 12.6% for verified accounts, p: <0.001). Tweets from healthcare/public health accounts had the lowest rate of unverifiable information (12.3%, p: 0.04). The number of likes and retweets per tweet was not associated with a difference in either false or unverifiable content. The keyword “COVID-19” had the lowest rate of misinformation and unverifiable information, while the keywords “#2019_ncov” and “Corona” were associated with the highest amount of misinformation and unverifiable content respectively. Conclusions Medical misinformation and unverifiable content pertaining to the global COVID-19 epidemic are being propagated at an alarming rate on social media. We provide an early quantification of the magnitude of misinformation spread and highlight the importance of early interventions in order to curb this phenomenon that endangers public safety at a time when awareness and appropriate preventive actions are paramount.

negative: Social distancing prevents infections, but it can have unintended consequences In response to the coronavirus pandemic, public health officials are asking us to do something that does not come naturally to our very social species: Stay away from each other Such social distancing—avoiding large gatherings and close contact with others—is crucial for slowing the spread of the virus and preventing our health care system from getting overwhelmed But it won’t be easy

negative: 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.

negative: Work-related COVID-19 transmission in six Asian countries/areas: A follow-up study OBJECTIVE: There is limited evidence of work-related transmission in the emerging coronaviral pandemic. We aimed to identify high-risk occupations for early coronavirus disease 2019 (COVID-19) local transmission. METHODS: In this observational study, we extracted confirmed COVID-19 cases from governmental investigation reports in Hong Kong, Japan, Singapore, Taiwan, Thailand, and Vietnam. We followed each country/area for 40 days after its first locally transmitted case, and excluded all imported cases. We defined a possible work-related case as a worker with evidence of close contact with another confirmed case due to work, or an unknown contact history but likely to be infected in the working environment (e.g. an airport taxi driver). We calculated the case number for each occupation, and illustrated the temporal distribution of all possible work-related cases and healthcare worker (HCW) cases. The temporal distribution was further defined as early outbreak (the earliest 10 days of the following period) and late outbreak (11th to 40th days of the following period). RESULTS: We identified 103 possible work-related cases (14.9%) among a total of 690 local transmissions. The five occupation groups with the most cases were healthcare workers (HCWs) (22%), drivers and transport workers (18%), services and sales workers (18%), cleaning and domestic workers (9%) and public safety workers (7%). Possible work-related transmission played a substantial role in early outbreak (47.7% of early cases). Occupations at risk varied from early outbreak (predominantly services and sales workers, drivers, construction laborers, and religious professionals) to late outbreak (predominantly HCWs, drivers, cleaning and domestic workers, police officers, and religious professionals). CONCLUSIONS: Work-related transmission is considerable in early COVID-19 outbreaks, and the elevated risk of infection was not limited to HCW. Implementing preventive/surveillance strategies for high-risk working populations is warranted.

negative: Traffic-derived particulate matter and angiotensin-converting enzyme 2 expression in human airway epithelial cells Background The mechanism for the association between traffic-derived particulate matter less than 10 microns (PM10) and cases of COVID-19 disease reported in epidemiological studies is unknown. To infect cells, the spike protein of SARS-CoV-2 interacts with angiotensin-converting enzyme 2 (ACE2) on host airway cells. Increased ACE2 expression in lower airway cells in active smokers, suggests a potential mechanism whereby PM10 increases vulnerability to COVID-19 disease. Objective To assess the effect of traffic-derived PM10 on human airway epithelial cell ACE2 expression in vitro. Methods PM10 was collected from Marylebone Road (London) using a kerbside impactor. A549 and human primary nasal epithelial cells were cultured with PM10 for 2 h, and ACE2 expression (median fluorescent intensity; MFI) assessed by flow cytometry. We included cigarette smoke extract as a putative positive control. Data were analysed by either Mann-Whitney test, or Kruskal-Wallis with Dunn’s multiple comparisons test. Results PM10 at 10 μg/mL, and 20 μg/mL increased ACE2 expression in A549 cells (P<0.05, 0.01 vs. medium control, respectively). Experiments using a single PM10 concentration (10 μg/mL), found increased ACE2 expression in both A549 cells (control vs. PM10, median (IQR) MFI; 470 (0.1 to 1114) vs 6217 (5071 to 8506), P<0.01), and in human primary epithelial cells (0 (0 to 591) vs. 4000 (2610 to 7853), P<0.05). Culture of A549 cells with 5% cigarette smoke extract increased ACE2 expression (n=4, 0 (0 to 28) vs. 9088 (7557 to 15831, P<0.05). Conclusion Traffic-related PM10 increases the expression of the receptor for SARS-CoV-2 in human respiratory epithelial cells.

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

negative: Global transmission network of SARS-CoV-2: from outbreak to pandemic BACKGROUND. The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is straining health systems around the world. Although the Chinese government implemented a number of severe restrictions on people’s movement in an attempt to contain its local and international spread, the virus had already reached many areas of the world in part due to its potent transmissibility and the fact that a substantial fraction of infected individuals develop little or no symptoms at all. Following its emergence, the virus started to generate sustained transmission in neighboring countries in Asia, Western Europe, Australia, Canada and the United States, and finally in South America and Africa. As the virus continues its global spread, a clear and evidence-based understanding of properties and dynamics of the global transmission network of SARS-CoV-2 is essential to design and put in place efficient and globally coordinated interventions. METHODS. We employ molecular surveillance data of SARS-CoV-2 epidemics for inference and comprehensive analysis of its global transmission network before the pandemic declaration. Our goal was to characterize the spatial-temporal transmission pathways that led to the establishment of the pandemic. We exploited a network-based approach specifically tailored to emerging outbreak settings. Specifically, it traces the accumulation of mutations in viral genomic variants via mutation trees, which are then used to infer transmission networks, revealing an up-to-date picture of the spread of SARS-CoV-2 between and within countries and geographic regions. RESULTS AND CONCLUSIONS. The analysis suggest multiple introductions of SARS-CoV-2 into the majority of world regions by means of heterogeneous transmission pathways. The transmission network is scale-free, with a few genomic variants responsible for the majority of possible transmissions. The network structure is in line with the available temporal information represented by sample collection times and suggest the expected sampling time difference of few days between potential transmission pairs. The inferred network structural properties, transmission clusters and pathways and virus introduction routes emphasize the extent of the global epidemiological linkage and demonstrate the importance of internationally coordinated public health measures.

negative: Contact tracing with a real-time location system: A case study of increasing relative effectiveness in an emergency department BACKGROUND: Contact tracing is the systematic method of identifying individuals potentially exposed to infectious diseases. Electronic medical record (EMR) use for contact tracing is time-consuming and may miss exposed individuals. Real-time location systems (RTLSs) may improve contact identification. Therefore, the relative effectiveness of these 2 contact tracing methodologies were evaluated. METHODS: During a pertussis outbreak in the United States, a retrospective case study was conducted between June 14 and August 31, 2016, to identify the contacts of confirmed pertussis cases, using EMR and RTLS data in the emergency department of a tertiary care medical center. Descriptive statistics and a paired t test (α = 0.05) were performed to compare contacts identified by EMR versus RTLS, as was correlation between pertussis patient length of stay and the number of potential contacts. RESULTS: Nine cases of pertussis presented to the emergency department during the identified time period. RTLS doubled the potential exposure list (P < .01). Length of stay had significant positive correlation with contacts identified by RTLS (ρ = 0.79; P = .01) but not with EMR (ρ = 0.43; P = .25). CONCLUSIONS: RTLS doubled the potential pertussis exposures beyond EMR-based contact identification. Thus, RTLS may be a valuable addition to the practice of contact tracing and infectious disease monitoring.

negative: The 2003 SARS outbreak and its impact on infection control practices Summary Severe Acute Respiratory Syndrome (SARS) emerged recently as a new infectious disease that was transmitted efficiently in the healthcare setting and particularly affected healthcare workers (HCWs), patients and visitors. The efficiency of transmission within healthcare facilities was recognised following significant hospital outbreaks of SARS in Canada, China, Hong Kong, Singapore, Taiwan and Vietnam. The causative agent of SARS was identified as a novel coronavirus, the SARS coronavirus. This was largely spread by direct or indirect contact with large respiratory droplets, although airborne transmission has also been reported. High infection rates among HCWs led initially to the theory that SARS was highly contagious and the concept of ‘super-spreading events’. Such events illustrated that lack of infection control (IC) measures or failure to comply with IC precautions could lead to large-scale hospital outbreaks. SARS was eventually contained by the stringent application of IC measures that limited exposure of HCWs to potentially infectious individuals. As the ‘global village’ becomes smaller and other microbial threats to health emerge, or re-emerge, there is an urgent need to develop a global strategy for infection control in hospitals. This paper provides an overview of the main IC practices employed during the 2003 SARS outbreak, including management measures, dedicated SARS hospitals, personal protective equipment, isolation, handwashing, environmental decontamination, education and training. The psychological and psychosocial impact on HCWs during the outbreak are also discussed. Requirements for IC programmes in the post-SARS period are proposed based on the major lessons learnt from the SARS outbreak.

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: A Critical Appraisal of the World Health Organization’s International Health Regulations (2005) in Times of Pandemic: It Is Time for Revision

negative: SARS: future research and vaccine Summary Severe acute respiratory syndrome (SARS) is a new infectious disease of the 21st century that has pandemic potential. A novel coronavirus (CoV) was identified as its aetiological agent and its genome was sequenced within months of the World Health Organisation issuing a global threat on SARS. The high morbidity and mortality of this potentially pandemic infection demands a rapid research response to develop effective antiviral treatment and vaccine. This will depend on understanding the pathogenesis and immune response to SARS CoV. Further understanding of the ecology of SARS CoV in human and animals will help prevent future cross species transmission. Likewise for the super-spreading events, clarification of the underlying reasons will be important to prevent a large scale outbreak of SARS. Lastly it is of utmost importance that international research collaboration should be strengthened to deal with SARS and any other emerging infectious disease that can seriously threaten our future.

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: Covid-19 spreads in US Multiple outbreaks worldwide have led to countries stepping up their responses. By Debora MacKenzie and Press Association

negative: 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.

negative: Severe Acute Respiratory Syndrome (SARS) and the GDP. Part I: Epidemiology, virology, pathology and general health issues The health profession faces a new challenge with the emergence of a novel viral disease Severe Acute Respiratory Syndrome (SARS), a form of atypical pneumonia caused by a coronavirus termed SARS-CoV. This highly infectious disease has spread through 32 countries, infecting more than 8,400 patients with over 790 deaths in just over 6 months. Over one quarter of those infected were unsuspecting healthcare workers. The major transmission mode of SARS-coronavirus appears to be through droplet spread with other minor subsidiary modes of transmission such as close contact and fomites although air borne transmission has not been ruled out. There is as yet no definitive treatment protocol. Although the peak period of the outbreak is likely to have passed and the risk of SARS in the UK is therefore assessed to be low, the World Health Organisation has asked all countries to remain vigilant lest SARS re-emerges. Recent laboratory acquired cases of SARS reported from Taiwan and Beijing, China are a testimony to this risk. Until reliable diagnostic tests, vaccine and medications are available, control of SARS outbreaks depends on close surveillance, early identification of index cases, quick isolation of carriers and effective infection control and public health measures.

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: General Model for COVID-19 Spreading with Consideration of Intercity Migration, Insufficient Testing and Active Intervention: Application to Study of Pandemic Progression in Japan and USA A new Susceptible-Exposed-Infected-Confirmed-Removed (SEICR) model with consideration of intercity travel and active intervention is proposed for predicting the spreading progression of the 2019 New Coronavirus Disease (COVID-19). The model takes into account the known or reported number of infected cases being fewer than the actual number of infected individuals due to insufficient testing. The model integrates intercity travel data to track the movement of exposed and infected individuals among cities, and allows different levels of active intervention to be considered so that realistic prediction of the number of infected individuals can be performed. The data of the COVID-19 infection cases and the intercity travel data for Japan (January 15 to March 20, 2020) and the USA (February 20 to March 20, 2020) are used to illustrate the prediction of the pandemic progression in 47 regions of Japan and 50 states (plus a federal district) in the USA. By fitting the model with the data, we reveal that, as of March 19, 2020, the number of infected individuals in Japan and the USA could be twenty-fold and five-fold as many as the number of confirmed cases, respectively. Moreover, the model generates future progression profiles for different levels of intervention by setting the parameters relative to the values found from the data fitting. Results show that without tightening the implementation of active intervention, Japan and the USA will see about 6.55% and 18.2% of the population eventually infected, and with drastic ten-fold elevated active intervention, the number of people eventually infected can be reduced by up to 95% in Japan and 70% in the USA. Finally, an assessment of the relative effectiveness of active intervention and personal protective measures is discussed. With a highly vigilant public maintaining personal hygiene and exercising strict protective measures, the percentage of population infected can be further reduced to 0.23% in Japan and 2.7% in the USA.

negative: Temporal dynamics of Middle East respiratory syndrome coronavirus in the Arabian Peninsula, 2012–2017 Middle East respiratory syndrome coronavirus (MERS-CoV) remains a notable disease and poses a significant threat to global public health. The Arabian Peninsula is considered a major global epicentre for the disease and the virus has crossed regional and continental boundaries since 2012. In this study, we focused on exploring the temporal dynamics of MERS-CoV in human populations in the Arabian Peninsula between 2012 and 2017, using publicly available data on case counts and combining two analytical methods. Disease progression was assessed by quantifying the time-dependent reproductive number (TD-Rs), while case series temporal pattern was modelled using the AutoRegressive Integrated Moving Average (ARIMA). We accounted for geographical variability between three major affected regions in Saudi Arabia including Eastern Province, Riyadh and Makkah. In Saudi Arabia, the epidemic size was large with TD-Rs >1, indicating significant spread until 2017. In both Makkah and Riyadh regions, the epidemic progression reached its peak in April 2014 (TD-Rs > 7), during the highest incidence period of MERS-CoV cases. In Eastern Province, one unique super-spreading event (TD-R > 10) was identified in May 2013, which comprised of the most notable cases of human-to-human transmission. Best-fitting ARIMA model inferred statistically significant biannual seasonality in Riyadh region, a region characterised by heavy seasonal camel-related activities. However, no statistical evidence of seasonality was identified in Eastern Province and Makkah. Instead, both areas were marked by an endemic pattern of cases with sporadic outbreaks. Our study suggested new insights into the epidemiology of the virus, including inferences about epidemic progression and evidence for seasonality. Despite the inherent limitations of the available data, our conclusions provide further guidance to currently implement risk-based surveillance in high-risk populations and, subsequently, improve related interventions strategies against the epidemic at country and regional levels.

negative: Perfusion-ventilation imaging in an era of COVID-19

negative: Simulation-based Estimation of the Spread of COVID-19 in Iran Background: The 2019 Coronavirus (COVID-19) has turned into a global pandemic with unprecedented challenges for the global community. Understanding the state of the disease and planning for future trajectories relies heavily on data on the spread and mortality. Yet official data coming from various countries are highly unreliable: symptoms similar to common cold in majority of cases and limited screening resources and delayed testing procedures may contribute to under-estimation of the burden of disease. Anecdotal and more limited data are available, but few have systematically combined those with official statistics into a coherent view of the epidemic. This study is a modeling-in-real-time of the emerging outbreak for understanding the state of the disease. Our focus is on the case of the spread of disease in Iran, as one of the epicenters of the disease in the first months of 2020. Method: We develop a simple dynamic model of the epidemic to provide a more reliable picture of the state of the disease based on existing data. Building on the generic SEIR (Susceptible, Exposed, Infected, and Recovered) framework we incorporate two behavioral and logistical considerations. First we capture the endogenous changes in contact rate (average contact per person) as more death are reported. As a result the reproduction number changes endogenously in the model. Second we differentiate reported and true cases by including simple formulations for how only a fraction of cases might be diagnosed, and how that fraction changes in response to epidemic's progression. In estimating the model we use both the official data as well as the discovered infected travelers and unofficial medical community estimates and triangulate these sources to build a more complete picture. Calibration is completed by forming a likelihood function for observing the actual time series data conditional on model parameters, and conducting a Markov Chain Monte Carlo simulations. The model is used to estimate current "true" cases of infection and death. We analyze the future trajectory of the disease under six conditions related to the seasonal effects and policy measures targeting social distancing. Findings: The model closely replicates the past data but also shows the true number of cases is likely far larger. We estimate about 493,000 current infected cases (90% CI: 271K-810K) as of March 20th, 2020. Our estimate for cumulative cases of infection until that date is 916,000 (90% CI: 508K, 1.5M), and for total death is 15,485 (90% CI: 8.4K, 25.8K). These numbers are significantly (more than one order of magnitude) higher than official statistics. The trajectory of the epidemic until the end of June could take various paths depending on the impact of seasonality and policies targeting social distancing. In the most optimistic scenario for seasonal effects, depending on policy measures, 1.6 million Iranians (90% CI: 0.9M-2.6M) are likely to get infected, and death toll will reach about 58,000 cases (90% CI: 32K-97K), while in the more pessimistic scenarios, death toll may exceed 103,000 cases (90% CI: 56K-172K). Implication: Our results suggest that the number of cases and deaths may be over an order of magnitude larger than official statistics in Iran. Absent extended testing capacity other countries may face a significant under-count of existing cases and thus be caught off guard about the actual toll of the epidemic.

negative: Coronavirus disease (COVID-19) and fertility: viral host entry protein expression in male and female reproductive tissues Abstract Objective To identify cell types in the male and female reproductive systems at risk of SARS-CoV-2 infection due to expression of host genes and proteins used by the virus for cell entry. Design Descriptive analysis of transcriptomic and proteomic data. Setting Academic research department and clinical diagnostic laboratory. Patients/Animals None. Focused on previously generated gene and protein expression data. Intervention(s) None. Main Outcome Measure(s) Identification of cell types co-expressing the key ACE2 and TMPRSS2 genes and proteins, as well as other candidates potentially involved in SARS-CoV-2 cell entry. Results Based on single cell RNA sequencing data, co-expression of ACE2 and TMPRSS2 was not detected in testicular cells, including sperm. A subpopulation of oocytes in non-human primate ovarian tissue were found to express ACE2 and TMPRSS2, but co-expression was not observed in ovarian somatic cells. RNA expression of TMPRSS2 in 18 samples of human cumulus cells was shown to be low or absent. There was general agreement between publicly available bulk RNA and protein datasets in terms of ACE2 and TMPRSS2 expression patterns in testis, ovary, endometrial and placental cells. Conclusion These analyses suggest that SARS-CoV-2 infection is unlikely to have long-term effects on male and female reproductive function. While the results cannot be considered definitive they imply that procedures in which oocytes are collected and fertilized in vitro are associated with very little risk of viral transmission from gametes to embryos and may indeed have the potential to minimize exposure of susceptible reproductive cell types to infection when compared to natural conception.

negative: Restructured society and environment: A review on potential technological strategies to control the COVID-19 pandemic Abstract The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in China at December 2019 had led to a global outbreak of coronavirus disease 2019 (COVID-19) and the disease started to spread all over the world and became an international public health issue. The entire humanity has to fight in this war against the unexpected and each and every individual role is important. Healthcare system is doing exceptional work and the government is taking various measures that help the society to control the spread. Public, on the other hand, coordinates with the policies and act accordingly in most state of affairs. But the role of technologies in assisting different social bodies to fight against the pandemic remains hidden. The intention of our study is to uncover the hidden roles of technologies that ultimately help for controlling the pandemic. On investigating, it is found that the strategies utilizing potential technologies would yield better benefits and these technological strategies can be framed either to control the pandemic or to support the confinement of the society during pandemic which in turn aids in controlling the spreading of infection. This study enlightens the various implemented technologies that assists the healthcare systems, government and public in diverse aspects for fighting against COVID-19. Furthermore, the technological swift that happened during the pandemic and their influence in the environment and society is discussed. Besides the implemented technologies, this work also deals with untapped potential technologies that have prospective applications in controlling the pandemic circumstances. Alongside the various discussion, our suggested solution for certain situational issues is also presented.

negative: Analysis of Spatiotemporal Characteristics of Pandemic SARS Spread in Mainland China Severe acute respiratory syndrome (SARS) is one of the most severe emerging infectious diseases of the 21st century so far. SARS caused a pandemic that spread throughout mainland China for 7 months, infecting 5318 persons in 194 administrative regions. Using detailed mainland China epidemiological data, we study spatiotemporal aspects of this person-to-person contagious disease and simulate its spatiotemporal transmission dynamics via the Bayesian Maximum Entropy (BME) method. The BME reveals that SARS outbreaks show autocorrelation within certain spatial and temporal distances. We use BME to fit a theoretical covariance model that has a sine hole spatial component and exponential temporal component and obtain the weights of geographical and temporal autocorrelation factors. Using the covariance model, SARS dynamics were estimated and simulated under the most probable conditions. Our study suggests that SARS transmission varies in its epidemiological characteristics and SARS outbreak distributions exhibit palpable clusters on both spatial and temporal scales. In addition, the BME modelling demonstrates that SARS transmission features are affected by spatial heterogeneity, so we analyze potential causes. This may benefit epidemiological control of pandemic infectious diseases.

negative: Interrupting COVID-19 transmission by implementing enhanced traffic control bundling: Implications for global prevention and control efforts Abstract We argue that enhanced Traffic Control Bundling (eTCB) can interrupt the community-hospital-community transmission cycle, thereby limiting COVID-19’s impact. Enhanced TCB is an expansion of the traditional TCB that proved highly effective during Taiwan’s 2003 SARS outbreak. TCB’s success derived from ensuring that Health Care Workers (HCWs) and patients were protected from fomite, contact and droplet transmission within hospitals. Although TCB proved successful during SARS, achieving a similar level of success with the COVID-19 outbreak requires adapting TCB to the unique manifestations of this new disease. These manifestations include asymptomatic infection, a hyper-affinity to ACE2 receptors resulting in high transmissibility, false negatives, and an incubation period of up to 22 days. Enhanced TCB incorporates the necessary adaptations. In particular, eTCB includes expanding the TCB transition zone to incorporate a new sector – the quarantine ward. This ward houses patients exhibiting atypical manifestations or awaiting definitive diagnosis. A second adaptation involves enhancing the checkpoint hand disinfection and gowning up with Personal Protective Equipment deployed in traditional TCB. Under eTCB, checkpoint hand disinfection and donning of face masks are now required of all visitors who seek to enter hospitals. These enhancements ensure that transmissions by droplets, fomites and contact are disrupted both within hospitals and between hospitals and the broader community. Evidencing eTCB effectiveness is Taiwan’s success to date in containing and controlling the community-hospital-community transmission cycle.

negative: Geographical tracking and mapping of coronavirus disease COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics In December 2019, a new virus (initially called ‘Novel Coronavirus 2019-nCoV’ and later renamed to SARS-CoV-2) causing severe acute respiratory syndrome (coronavirus disease COVID-19) emerged in Wuhan, Hubei Province, China, and rapidly spread to other parts of China and other countries around the world, despite China’s massive efforts to contain the disease within Hubei. As with the original SARS-CoV epidemic of 2002/2003 and with seasonal influenza, geographic information systems and methods, including, among other application possibilities, online real-or near-real-time mapping of disease cases and of social media reactions to disease spread, predictive risk mapping using population travel data, and tracing and mapping super-spreader trajectories and contacts across space and time, are proving indispensable for timely and effective epidemic monitoring and response. This paper offers pointers to, and describes, a range of practical online/mobile GIS and mapping dashboards and applications for tracking the 2019/2020 coronavirus epidemic and associated events as they unfold around the world. Some of these dashboards and applications are receiving data updates in near-real-time (at the time of writing), and one of them is meant for individual users (in China) to check if the app user has had any close contact with a person confirmed or suspected to have been infected with SARS-CoV-2 in the recent past. We also discuss additional ways GIS can support the fight against infectious disease outbreaks and epidemics.

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: A Letter to the Future AWWA Dear Future AWWA Members, I'm writing to you on the 139th birthday of the American Water Works Association, and what a strange time it is We are in the midst of a global pandemic A disease called COVID‐19 is spreading so quickly that we are running short on hospital beds and people are hoarding toilet paper At this moment, the United States has more confirmed cases than any other country and Canada is ranked 15th But I am not writing to tell you about the tragedy of COVID‐19;I imagine the history books will capture that This is a letter about how today's water professionals are rising to the challenge through their selfless and often uncelebrated acts of courage They are building on the legacy of water professionals throughout AWWA's history, and I wish you were here to witness it As you—the future AWWA—look back on spring 2020, you will clearly see how access to safe, reliable water was critical in halting the spread of COVID‐19 The simplest example I can provide is handwashing The practice of handwashing for at least 20 seconds, with plenty of soap, has never seemed so important Now, we are a society uniformly obsessed with washing our hands Because tap water is critical to personal hygiene and protecting the public's health, the US Environmental Protection Agency this week sent a letter to all governors, reminding them that water utility workers and water sector businesses that support water utilities should be considered “essential” as communities impose orders to keep people at home And in another sign of the essential nature of water service in a public health crisis, utilities are suspending water shutoffs and, in many cases, restoring service to customers who had previously been shut off But it isn't these policy decisions I hope you'll remember It's the exemplary—and yes, courageous—commitment of your predecessors in the water profession Each day, water professionals are delivering safe water to their communities and then cleaning the wastewater before returning it to the environment Never has this daily routine seemed more extraordinary These days, we are all being asked to participate in “social distancing,” a term that most had never heard of before COVID‐19 As schools and restaurants close and citizens are ordered to stay at home, your predecessors in the water profession continue to do what it takes to keep the water flowing, whether that is repairing mains, unclogging sewer lines (you can't imagine what some people do in the absence of toilet paper!), or ensuring treatment equipment is functioning properly Many water professionals are stationed 24/7 at treatment plants They are living apart from their own families so they can protect all of our families The ongoing pandemic has given our society new appreciation for the work of health professionals, police, and other first responders I would say that water professionals are not only first responders, but “everyday” responders They are the super‐heroes we don't need to summon because they are already on the scene I am certain that in time we will be able to return to a more normal state, where a handshake is a handshake and not an elbow bump And when we do, I hope that we—and the people who live in the communities we serve—remember that water is critical to everything we care about and that it played a crucial role in eliminating COVID‐19 It is not an overstatement to say that others’ lives were in the hands of water professionals during the pandemic Poet and philosopher George Santayana is known for saying, “Those who cannot remember the past are condemned to repeat it ” In this case, however, it would be wise to remember and repeat selfless acts like those of water professionals facing COVID‐19 in the spring of 2020 In closing, Happy Birthday, AWWA, and my thanks to all who are members today and in the future Your commitment to the legacy of safe and reliable water service is, quite literally, life‐saving Sincerely, David B LaFrance Chief Executive Officer, American Water orks Association

negative: 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.

negative: Disease contact tracing in random and clustered networks. The efficacy of contact tracing, be it between individuals (e.g. sexually transmitted diseases or severe acute respiratory syndrome) or between groups of individuals (e.g. foot-and-mouth disease; FMD), is difficult to evaluate without precise knowledge of the underlying contact structure; i.e. who is connected to whom? Motivated by the 2001 FMD epidemic in the UK, we determine, using stochastic simulations and deterministic 'moment closure' models of disease transmission on networks of premises (nodes), network and disease properties that are important for contact tracing efficiency. For random networks with a high average number of connections per node, little clustering of connections and short latency periods, contact tracing is typically ineffective. In this case, isolation of infected nodes is the dominant factor in determining disease epidemic size and duration. If the latency period is longer and the average number of connections per node small, or if the network is spatially clustered, then the contact tracing performs better and an overall reduction in the proportion of nodes that are removed during an epidemic is observed.

negative: Myocardial injury and COVID-19: Possible mechanisms Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.

negative: Chapter 8 The Middle East Respiratory Syndrome Coronavirus: An Emerging Virus of Global Threat Abstract Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (CoV), first identified in Saudi Arabia in 2012. Since then, almost 2000 cases have been reported from 27 countries, with Saudi Arabia being the epicenter. This newly emerging virus is highly pathogenic and has a case mortality rate of 35%. It is similar to the CoV causing severe acute respiratory syndrome CoV (SARS-CoV) in that both belong to the genus beta CoVs that are of zoonotic origin and cause lower respiratory infection. The natural reservoir for MERS-CoV remains unknown. Serological studies indicate that most dromedary camels in the Middle East have been infected with this virus, and they maybe the potential intermediate host. However, the mode of transmission from camels to humans is poorly understood. The majority of confirmed human cases have resulted from human-to-human transmission, most probably via respiratory route. Patients most at risk of developing severe MERS-CoV infection appear to be those with underlying conditions such as diabetes, hypertension, obesity, cardiac diseases, chronic respiratory diseases, and cancer. Unlike SARS-CoV, MERS-CoV is considered an ongoing public health problem, particularly for the Middle East region. In this chapter, we outline the prevailing information regarding the emergence and epidemiology of this virus, its mode of transmission and pathogenicity, its clinical features, and the potential strategies for prevention.

negative: New technologies in computer-aided drug design: Toward target identification and new chemical entity discovery In the postgenomic era, computer-aided drug design (CADD) has considerably extended its range of applications, spanning almost all stages in the drug discovery pipeline, from target identification to lead discovery, from lead optimization to preclinical or clinical trials. Two new technologies of CADD associated with target identification and new chemical entity discovery will be the focus of this review. Section editors: Li-he Zhang – School of Pharmaceutical Science, Peking University, Beijing, China Kaixian Chen – Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

negative: Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal human coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

negative: Assessing the risks of "infodemics" in response to COVID-19 epidemics Our society is built on a complex web of interdependencies whose effects become manifest during extraordinary events such as the COVID-19 pandemic, with shocks in one system propagating to the others to an exceptional extent. We analyzed more than 100 millions Twitter messages posted worldwide in 64 languages during the epidemic emergency due to SARS-CoV-2 and classified the reliability of news diffused. We found that waves of unreliable and low-quality information anticipate the epidemic ones, exposing entire countries to irrational social behavior and serious threats for public health. When the epidemics hit the same area, reliable information is quickly inoculated, like antibodies, and the system shifts focus towards certified informational sources. Contrary to mainstream beliefs, we show that human response to falsehood exhibits early-warning signals that might be mitigated with adequate communication strategies.

negative: Current management and outcome of tracheobronchial malacia and stenosis presenting to the paediatric intensive care unit Objective: To identify factors associated with mortality and prolonged ventilatory requirements in patients admitted to our paediatric intensive care unit (PICU) with tracheobronchial malacia and stenosis diagnosed by dynamic contrast bronchograms. Design: Retrospective review. Setting: Tertiary paediatric intensive care unit. Patients: Forty-eight cases admitted to our PICU over a 5-year period in whom a diagnosis of tracheobronchial malacia or stenosis was made by dynamic contrast bronchography (1994–1999). Interventions: Conservative management, tracheostomy and long-term ventilation, surgical correction, internal or external airway stenting. Measurements and results: Recording of clinical details, length of invasive ventilation and appearance at contrast bronchography. Five groups of patients were defined: isolated primary airway pathology (n=7), ex-premature infants (n=11), vascular rings (n=9), complex cardiac and/or syndromic pathology (n=17) and tracheo-oesophageal fistulae (n=4). The overall mortality was 29%. Median length of invasive ventilation in survivors was 38 days and in patients who died 45. Mortality was highest in the patients with complex cardiac and/or syndromic pathology (p=0.039 Cox regression analysis) but was not related to any other factor. Patients with stenosis required a significantly longer period of ventilatory support (median length of ventilation 59 days) than patients with malacia (39 days). Conclusions: Length of ventilation and bronchographic diagnosis did not predict survival. The only factor found to contribute significantly to mortality was the presence of complex cardiac and/or syndromic pathology. However, patients with stenosis required longer ventilatory support than patients with malacia.

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: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea In 2015, we experienced the largest in-hospital Middle East respiratory syndrome (MERS) outbreak outside the Arabian Peninsula. We share the infection prevention measures for surgical procedures during the unexpected outbreak at our hospital. We reviewed all forms of related documents and collected information through interviews with healthcare workers of our hospital. After the onset of outbreak, a multidisciplinary team devised institutional MERS-control guidelines. Two standard operating rooms were converted to temporary negative-pressure rooms by physically decreasing the inflow air volume (−4.7 Pa in the main room and −1.2 Pa in the anteroom). Healthcare workers were equipped with standard or enhanced personal protective equipment according to the MERS-related patient’s profile and symptoms. Six MERS-related patients underwent emergency surgery, including four MERS-exposed and two MERS-confirmed patients. Negative conversion of MERS-CoV polymerase chain reaction tests was noticed for MERS-confirmed patients before surgery. MERS-exposed patients were also tested twice preoperatively, all of which were negative. All operative procedures in MERS-related patients were performed without specific adverse events or perioperative MERS transmission. Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries.

negative: Self-isolation or borders closing: what prevents epidemic spreading better? Pandemic distribution of COVID-19 in the world has motivated us to discuss combined effects of network clustering and adaptivity on epidemic spreading. We address the question concerning the choice of optimal mechanism for most effective prohibiting disease propagation in a connected network: adaptive clustering, which mimics self-isolation (SI) in local communities, or sharp instant clustering, which looks like frontiers closing (FC) between cities and countries. SI-networks are"adaptively grown"under condition of maximization of small cliques in the entire network, while FC-networks are"instantly created". Running the standard SIR model on clustered SI- and FC-networks, we demonstrate that the adaptive network clustering prohibits the epidemic spreading better than the instant clustering in the network with similar parameters. We found that SI model has scale-free property for degree distribution $P(k)\sim k^{\eta}$ with small critical exponent $-2<\eta<-1$ and argue that scale-free behavior emerges due to the randomness in the initial degree distributions and is absent for random regular graphs.

negative: COVID-19 Myocarditis and Severity Factors： An Adult Cohort Study Background Notwithstanding the clinical hallmarks of COVID-19 patients were reported, several critical issues still remain mysterious, i.e., prognostic factors for COVID-19 including extrinsic factors as viral load of SARS-CoV-2 and intrinsic factors as individual's health conditions; myocarditis incidence rate and hallmarks. Methods Demographic, epidemiologic, radiologic and laboratory data were collected by medical record reviews of adult hospitalized patients diagnosed as COVID-19. Cycle threshold (Ct) value data of real-time PCR (RT-PCR) were collected. The time duration was from 21 January to 2 March, 2020. Pulmonary inflammation index (PII) values were used for chest CT findings. Multivariate logistic regression analysis was used to identify independent severity risk factors. RESULTS In total, 84 hospitalized adult patients diagnosed as COVID-19 were included, including 20 severe and 64 nonsevere cases. The viral load of the severe group was significantly higher than that of the non-severe group, regardless of the Ct values for N or ORF1ab gene of virus (all p<0.05).Typical CT abnormalities was more likely existing in the severe group than in the nonsevere group in patchy shadows or ground glass opacities, consolidation, and interlobular septal thickening (all p<0.05). In addition, the PII values in the severe group was significantly higher than that in the nonsevere group (52.5 [42.5-62.5] vs 20 [5.0-31.6]; p<0.001). Amongst 84 patients, 13 patients (15.48%) were noted with abnormal electrocardiograms (ECGs) and serum myocardial enzyme levels; whereas 4 (4.8%) were clinically diagnosed as SARS-CoV-2 myocarditis. Multivariable logistic regress analysis distinguished three key independent risk factors for the severity of COVID-19, including age [OR 2.350; 95% CI (1.206 to 4.580); p=0.012], Ct value [OR 0.158; 95% CI (0.025 to 0.987); p=0.048] and PII [OR 1.912; 95% CI (1.187 to 3.079); p=0.008]. Interpretation Three key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions.

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: 4S-DT: Self Supervised Super Sample Decomposition for Transfer learning with application to COVID-19 detection

negative: A dynamic compartmental model for the Middle East respiratory syndrome outbreak in the Republic of Korea: A retrospective analysis on control interventions and superspreading events Abstract The 2015 Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea has provided an opportunity to improve our understanding of the spread of MERS linked to healthcare settings. Here we designed a dynamic transmission model to analyze the MERS outbreak in the Republic of Korea based on confirmed cases reported during the period May 20–July 4, 2015. Our model explicitly incorporates superspreading events and time-dependent transmission and isolation rates. Our model was able to provide a good fit to the trajectory of the outbreak and was useful to analyze the role of hypothetical control scenarios. Specifically, we assessed the impact of the timing of control measures, especially associated with a reduction of the transmission rate and diagnostic delays on outbreak size and duration. Early interventions within 1week after the epidemic onset, for instance, including the initial government announcement to the public about the list of hospitals exposed to MERS coronavirus (MERS-CoV), show a promising means to reduce the size ( > 71 % ) and duration ( > 35 % ) of the MERS epidemic. Finally, we also present results of an uncertainty analysis focused on the role of superspreading events.

negative: Panthera pardus (Carnivora: Felidae) Panthera pardus (leopard; Linnaeus, 1758) is the smallest of the 4 large felids in the genus Panthera. A solitary and adaptable species, P. pardus is the widest ranging of all wild felids, inhabiting rain forests, mountains, semiarid environments, and suburban areas throughout sub-Saharan Africa, the Middle East, and South Asia to the Russian Far East. Despite this distribution, P. pardus is listed as “Near Threatened” by the International Union for Conservation of Nature and Natural Resources and several Asian subspecies are listed as endangered. P. pardus primarily feeds on small to medium-sized ungulates, but has a varied diet including fish, reptiles, birds, and small mammals.

negative: Detection of 20 respiratory viruses and bacteria by influenza-like illness surveillance in Beijing, China, 2016–2018

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: Using a novel rapid viral test to improve triage of emergency department patients with acute respiratory illness during flu season Abstract Background Acute respiratory illnesses (ARI) are mostly viral in etiology and cause significant morbidity and mortality. Point of care PCR (POC-PCR) is a promising new technology for rapid virus identification but utility in the Emergency Department (ED) is not yet defined. Objectives Primarily, to investigate the value of POC-PCR in rapidly identifying RSV and influenza in the setting of ED triage. Additionally, to assess whether rapid knowledge of accurate test results would improve patient management by preventing nosocomial transmission and optimizing the prescription of antimicrobials for ARIs. Study Design A prospective cohort study of consecutive ED patients with ARI symptoms during peak flu season was conducted. Patient nasopharyngeal swabs were collected and tested using a POC-PCR device; physicians and patients were blinded to results. Virus positive and negative groups were compared by ED patient room placement and antimicrobial therapy ordered. Specificity and sensitivity were calculated using laboratory-PCR as the gold standard. Results Of 119 participants, 52.9% were POC-PCR positive - Influenza A (42.9%), RSV (41.3%), influenza B (15.9%). Nearly 70% of virus positive patients were placed rooms shared with non-ARI patients. Antibiotics were prescribed for 27.3% of virus positive patients, and 77.8% of oseltamivir-eligible patients did not receive therapy. POC-PCR was 100% sensitive (95% CI, 80.5–100.0%) and 95.2% specific (95% CI, 76.2–99.9%). Conclusions Rapid POC-PCR for influenza and RSV in ED triage has excellent sensitivity and specificity and the potential to improve social distancing practices through better triage and increase appropriate prescription of antimicrobials.

negative: Tabagisme et maladie à coronavirus 2019 (COVID-19)

negative: Letter to the Editor: Wastewater-Based Epidemiology Can Overcome Representativeness and Stigma Issues Related to COVID-19

negative: Public health concerns and unsubstantiated claims at the intersection of vaping and COVID-19

negative: Mathematical model of infection kinetics and its analysis for COVID-19, SARS and MERS Abstract The purpose of this paper is to reveal the spread rules of the three pneumonia: COVID-19, SARS and MERS. We compare the new spread characteristics of COVID-19 with those of SARS and MERS. By considering the growth rate and inhibition constant of infectious diseases, their propagation growth model is established. The parameters of the three coronavirus transmission growth models are obtained by nonlinear fitting. Parametric analysis shows that the growth rate of COVID-19 is about twice that of the SARS and MERS, and the COVID-19 doubling cycle is two to three days, suggesting that the number of COVID-19 patients would double in two to three days without human intervention. The infection inhibition constant in Hubei is two orders of magnitude lower than in other regions, which reasonably explains the situation of the COVID-19 outbreak in Hubei.

negative: Preventing Airborne Disease Transmission: Implications for Patients During Mechanical Ventilation The organisms causing respiratory infections such as influenza are spread in droplets or aerosols or by direct or indirect contact with contaminated surfaces. Certain medical procedures have been termed aerosol generating because they are associated with high or augmented inspiratory and expiratory flows, which can increase microbial dissemination. Invasive ventilation maneuvers and noninvasive ventilation (NIV) fall into that category. We discuss the risk of transmitting these procedures and the strategies for mechanical ventilation in future airborne epidemics with special consideration given to the issue of protecting health care workers (HCWs).

negative: A systematic review of Anakinra, Tocilizumab, Sarilumab and Siltuximab for coronavirus-related infections Background There is accumulating evidence for an overly activated immune response characterised by the release of pro-inflammatory cytokines in severe Covid-19. Suppression of the inflammatory response with immunomodulatory therapies may be a potential therapeutic strategy. We systematically review and assess the effectiveness of specific interleukin-1 and -6 inhibitors for the treatment of coronavirus-related infections. Methods Electronic databases, pre-print servers and clinical trial registries were searched to identify current and ongoing studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of Covid-19 and other coronavirus related super infections. The co-primary outcome was time to hospital discharge (days) and severity on an ordinal scale measured at day 15. Results Five retrospective studies (tocilizumab, two case series and two case reports; siltuximab, one case series) were shortlisted for inclusion, totalling 59 patients. All studies had a moderate or high risk of bias, with multiple limitations. Insufficient data and inter-study heterogeneity prevented meta-analysis. Primary outcomes were inconsistently reported but suggest many patients experienced an improvement in status seven days following therapy. The case fatality ratio (CFR) of patients with severe Covid-19 included in our review was 6.8%, a figure substantially lower than that estimated in non-interventional case series. Of the studies measuring IL-6, all reported elevated baseline levels. Twenty-five ongoing registered clinical trials exploring immunomodulatory agents in Covid-19 were identified, although inconsistency in participants and endpoints are noted. Conclusion Inhibition of IL-6 with tocilizumab and siltuximab requires further evaluation in managing the assumed hyperinflammatory response associated with severe Covid-19. These early data are considered hypothesis generating and justify the need for well-designed randomised clinical studies.

negative: COVID-19: what has been learned and to be learned about the novel coronavirus disease The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.

negative: 新型冠状病毒肺炎流行期肺部手术的初步建议 In December 2019, China diagnosed the first patient with 2019 novel coronavirus disease (COVID-19), and the following development of the epidemic had a huge impact on China and the whole world. For patients with lung occupying lesions, the whole process of diagnosis and treatment can not be carried out as usual due to the epidemic. For thoracic surgeons, the timing of surgical intervention should be very carefully considered. All thoracic surgeons in China should work together to develop the proper procedures for the diagnosis and treatment in this special situation, and continuously update the recommendations based on epidemic changes and further understanding of COVID-19. Here, we only offer some preliminary suggestions based on our own knowledge for further reference and discussion.

negative: Return of the Coronavirus: 2019-nCoV The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.

negative: Interactome Mapping: Using Protein Microarray Technology to Reconstruct Diverse Protein Networks A major focus of systems biology is to characterize interactions between cellular components, in order to develop an accurate picture of the intricate networks within biological systems. Over the past decade, protein microarrays have greatly contributed to advances in proteomics and are becoming an important platform for systems biology. Protein microarrays are highly flexible, ranging from large-scale proteome microarrays to smaller customizable microarrays, making the technology amenable for detection of a broad spectrum of biochemical properties of proteins. In this article, we will focus on the numerous studies that have utilized protein microarrays to reconstruct biological networks including protein–DNA interactions, posttranslational protein modifications (PTMs), lectin–glycan recognition, pathogen–host interactions and hierarchical signaling cascades. The diversity in applications allows for integration of interaction data from numerous molecular classes and cellular states, providing insight into the structure of complex biological systems. We will also discuss emerging applications and future directions of protein microarray technology in the global frontier.

negative: Factors influencing the epidemiological characteristics of pandemic COVID 19: A TISM approach The COVID 19 is a pandemic having an epidemic nature influencing the human health and economy in a global level. The major limitation to overcome the issue is the lack of potential vaccines or effective medicines to treat or control the disease. Considering the shortness of time to act, the purpose of the paper was to identify and categorise the climatic, socio-biological factors that influence the global super-spread of the epidemic using a theory building approach, ‘Total Interpretive Structural Modelling’ (TISM). MICMAC analysis of the identified factors, based on their interdependence categorized the triggering factors, air temperature, humidity, age, airflow and ventilation, responsible for the increased mortality rate of COVID 19 compared to SARS and MERS. So the model explains why the temperate countries of similar climatic zones and aged people are more vulnerable. It also predicts the susceptibility of countries based on their geographic locations and upcoming climatic conditions which were found to be influential in sustaining longevity and aerosol spread of the virus. Since many of these factors remain unaltered or out of human control, the linkage factors identified in this paper; change in host behaviour and number of contacts can be given priorities in order to overcome the situation. Furthermore, this is the first attempt made to understand epidemiological characteristics of COVID 19 using TISM approach.

negative: On the impact of epidemic severity on network immunization algorithms Abstract There has been much recent interest in the prevention and mitigation of epidemics spreading through contact networks of host populations. Here, we investigate how the severity of epidemics, measured by its infection rate, influences the efficiency of well-known vaccination strategies. In order to assess the impact of severity, we simulate the SIR model at different infection rates on various real and model immunized networks. An extensive analysis of our simulation results reveals that immunization algorithms, which efficiently reduce the nodes’ average degree, are more effective in the mitigation of weak and slow epidemics, whereas vaccination strategies that fragment networks to small components, are more successful in suppressing severe epidemics.

negative: Social and administrative issues related to the COVID-19 pandemic in Pakistan: better late than never The study critically reviewed Pakistan’s provincial updates of coronavirus disease 2019 (COVID-19) and discussed the current challenges faced by the government in a given context. The coronavirus-associated death tolls have been increasing rapidly in a country. The provincial status of confirmed cases of coronavirus is higher in Punjab, followed by the Sindh, Khyber Pakhtunkhwa (KPK), and Balochistan. The case fatality ratio shows that KPK has a higher ratio, i.e., 5.11%, followed by the Punjab, i.e., 1.82%; Sindh, i.e., 1.80%; Balochistan, i.e., 1.28%; Gilgit-Baltistan, i.e., 0.71%; and Federal territory, i.e., 0.66%. The country has a less testing capacity to identify more suspected coronavirus patients. The study calculated that if we increase five times our testing capacity from the current date, the total registered cases will be reached to 137,370 and death tolls will increase up to 3090. It is highly needed to increase testing capacity across Pakistan in order to minimize the outbreak of coronavirus. The provincial government should follow the Federal Government instructions to contain coronavirus by increasing testing capacities, tracing suspected patients, smart lockdowns, emergency relief to the poor, and vigilant monitoring system.

negative: Tomar medidas preventivas inmediatamente: evidencia de China sobre el COVID-19

negative: Perspectives on Surgery in the time of COVID-19: Safety First

negative: Myocardial injury and COVID-19: Possible mechanisms Abstract Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.

negative: Why are pregnant women susceptible to COVID-19? An immunological viewpoint Abstract The 2019 novel coronavirus disease (COVID-19) was first detected in December 2019 and became epidemic in Wuhan, Hubei Province, China. COVID-19 has been rapidly spreading out in China and all over the world. The virus causing COVID-19, SARS-CoV-2 has been known to be genetically similar to severe acute respiratory syndrome coronavirus (SARS-CoV) but distinct from it. Clinical manifestation of COVID-19 can be characterized by mild upper respiratory tract infection, lower respiratory tract infection involving non-life threatening pneumonia, and life-threatening pneumonia with acute respiratory distress syndrome. It affects all age groups, including newborns, to the elders. Particularly, pregnant women may be more susceptible to COVID-19 since pregnant women, in general, are vulnerable to respiratory infection. In pregnant women with COVID-19, there is no evidence for vertical transmission of the virus, but an increased prevalence of preterm deliveries has been noticed. The COVID-19 may alter immune responses at the maternal-fetal interface, and affect the well-being of mothers and infants. In this review, we focused on the reason why pregnant women are more susceptible to COVID-19 and the potential maternal and fetal complications from an immunological viewpoint.

negative: 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: SARS Coronavirus and Lung Fibrosis Severe acute respiratory syndrome (SARS) is an acute infectious disease with significant mortality. A novel coronavirus (SARS-CoV) has been shown to be the causative agent of SARS. The typical clinical feature associated with SARS is diffuse alveolar damage in lung, and lung fibrosis is evident in patients who died from this disease. The mechanisms by which SARS-CoV infection causes lung fibrosis are not fully understood, but transforming growth factor-β (TGF-β) and angiotensin-converting enzyme 2 (ACE2)-mediated lung fibrosis are among the most documented ones. The activation of the TGF-β/Smad pathway is critical to lung fibrosis. SARS-CoV infection not only enhances the expression of TGF-β, but also facilitates its signaling activity. The SARS-CoV receptor ACE2 is a negative regulator of lung fibrosis, and SARS-CoV infection decreases ACE2 expression. Therefore, SARS-CoV infection may lead to lung fibrosis through multiple signaling pathways and TGF-β activation is one of the major contributors.

negative: Similarities and Evolutionary Relationships of COVID-19 and Related Viruses Today, we are all threatened by an unprecedented pandemic: COVID-19. How different is it from other coronaviruses? Will it be attenuated or become more virulent? Which animals may be its original host? In this study, we analyzed 377 publicly available complete genome sequences for the COVID-19 virus, the previously known flu-causing coronaviruses (HCov-229E, HCov-OC43, HCov-NL63 and HCov-HKU1) and the lethal, pathogenic viruses, SARS, MERS, Victoria, Lassa, Yamagata, Ebola, and Dengue. We found strong similarities between the current circulating COVID-19 and SARS and MERS, as well as COVID-19 in rhinolophines and pangolins. On the contrary, COVID-19 shares little similarity with the flu-causing coronaviruses and the other known viruses. Strikingly, we observed divergence of COVID-19 strains isolated from human hosts has steadily increased from December 2019 to March 2020, suggesting COVID-19 is actively evolving in human hosts. From all existing human COVID-19 genome sequences, we calculated the first common model that represents the shared sequences of the human COVID-19 strains, which provides important information for vaccine and antibody development. Geographic and time -course analysis of the evolutionary trees of the human COVID-19 reveals possible evolutional paths among strains from 21 countries. This finding has important implications to the management of COVID-19 and the development of vaccines.

negative: 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.

negative: Epidemiologic Characteristics of COVID-19 in Guizhou, China At the end of 2019, a coronavirus disease 2019 (COVID-19) outbroke in Wuhan, China, and spread to Guizhou province on January of 2020. To acquire the epidemiologic characteristics of COVID-19 in Guizhou, China, we collected data on 162 laboratory-confirmed cases related to COVID-19. We described the demographic characteristics of the cases and estimated the incubation period, serial interval and basic reproduction number. We also presented two representative case studies in Guizhou province -- Case Study 1 was an example of asymptomatic carrier; and Case Study 2 was an example of a large and complex infection chain that involved four different districts spanning three provinces and eight families. With an estimation of 8 days incubation period and 6 days serial interval, our results indicate that there may exist infectiousness during the incubation period for 2019-nCoV. This increases the difficulty of screening or identifying cases related to COVID-19.

negative: Temperature, Humidity, and Latitude Analysis to Estimate Potential Spread and Seasonality of Coronavirus Disease 2019 (COVID-19) IMPORTANCE: Coronavirus disease 2019 (COVID-19) infection has resulted in a global crisis. Investigating the potential association of climate and seasonality with the spread of this infection could aid in preventive and surveillance strategies. OBJECTIVE: To examine the association of climate with the spread of COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined climate data from 50 cities worldwide with and without substantial community spread of COVID-19. Eight cities with substantial spread of COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain) were compared with 42 cities that have not been affected or did not have substantial community spread. Data were collected from January to March 10, 2020. MAIN OUTCOMES AND MEASURES: Substantial community transmission was defined as at least 10 reported deaths in a country as of March 10, 2020. Climate data (latitude, mean 2-m temperature, mean specific humidity, and mean relative humidity) were obtained from ERA-5 reanalysis. RESULTS: The 8 cities with substantial community spread as of March 10, 2020, were located on a narrow band, roughly on the 30° N to 50° N corridor. They had consistently similar weather patterns, consisting of mean temperatures of between 5 and 11 °C, combined with low specific humidity (3-6 g/kg) and low absolute humidity (4-7 g/m(3)). There was a lack of substantial community establishment in expected locations based on proximity. For example, while Wuhan, China (30.8° N) had 3136 deaths and 80 757 cases, Moscow, Russia (56.0° N), had 0 deaths and 10 cases and Hanoi, Vietnam (21.2° N), had 0 deaths and 31 cases. CONCLUSIONS AND RELEVANCE: In this study, the distribution of substantial community outbreaks of COVID-19 along restricted latitude, temperature, and humidity measurements was consistent with the behavior of a seasonal respiratory virus. Using weather modeling, it may be possible to estimate the regions most likely to be at a higher risk of substantial community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.

negative: Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015 The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several “superspreading” events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology. We found sequential emergence of the spike mutations in 2 superspreaders. In vivo virulence of the mutant viruses seems to decline in human patients, as assessed by fever duration in affected persons. In addition, neutralizing activity against these 2 mutant viruses in serum samples from mice immunized with wild-type spike antigen were gradually reduced, suggesting emergence and wide spread of neutralization escapers during the outbreak.

negative: 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.

negative: Fatality risks for nosocomial outbreaks of Middle East respiratory syndrome coronavirus in the Middle East and South Korea Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012. The largest known outbreak outside the Middle East occurred in South Korea in 2015. As of 29 June 2016, 1769 laboratory-confirmed cases (630 deaths; 35.6 % case fatality rate [CFR]) had been reported from 26 countries, particularly in the Middle East. However, the CFR for hospital outbreaks was higher than that of family clusters in the Middle East and Korea. Here, we compared the mortality rates for 51 nosocomial outbreaks in the Middle East and one outbreak of MERS-CoV in South Korea. Our findings showed the CFR in the Middle East was much higher than that in South Korea (25.9 % [56/216] vs. 13.8 % [24/174], p = 0.003). Infected individuals who died were, on average, older than those who survived in both the Middle East (64 years [25–98] vs. 46 years [2–85], p = 0.000) and South Korea (68 years [49–82] vs. 53.5 years [16–87], p = 0.000). Similarly, the co-morbidity rates for the fatal cases were statistically higher than for the nonfatal cases in both the Middle East (64.3 % [36/56] vs. 28.1 % [45/160], p = 0.000) and South Korea (45.8 % [11/24] vs. 12.0 % [18/150], p = 0.000). The median number of days from onset to confirmation of infection in the fatal cases was longer than that for survivors from the Middle East (8 days [1–47] vs. 4 days [0–14], p = 0.009). Thus, older age, pre-existing concurrent diseases, and delayed confirmation increase the odds of a fatal outcome in nosocomial MERS-CoV outbreaks in the Middle East and South Korea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-016-3062-x) contains supplementary material, which is available to authorized users.

negative: Understanding of guidance for acupuncture and moxibustion interventions on COVID-19 (Second edition) issued by CAAM Abstract At present, the situation of global fight against COVID-19 is serious. WHO (World Health Organization)-China Joint Mission fully confirms the success of “China's model” against COVID-19 in the report. In fact, one particular power in “China's model” is acupuncture and moxibustion of traditional Chinese medicine. To better apply “non-pharmaceutic measures”—the external technique of traditional Chinese medicine, in the article, the main content of Guidance for acupuncture and moxibustion interventions on COVID-19 (Second edition) issued by China Association of Acupuncture–Moxibution is introduced and the discussion is stressed on the selection of moxibustion device and the duration of its exertion.

negative: 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.

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: Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example Emerging and re-emerging infections such as SARS (2003) and pandemic H1N1 (2009) have caused concern for public health researchers and policy makers due to the increased burden of these diseases on health care systems. This concern has prompted the use of mathematical models to evaluate strategies to control disease spread, making these models invaluable tools to identify optimal intervention strategies. A particularly important quantity in infectious disease epidemiology is the basic reproduction number, R(0.) Estimation of this quantity is crucial for effective control responses in the early phase of an epidemic. In our previous study, an approach for estimating the basic reproduction number in real time was developed. This approach uses case notification data and the structure of potential transmission contacts to accurately estimate R(0) from the limited amount of information available at the early stage of an outbreak. Based on this approach, we extend the existing methodology; the most recent method features intra- and inter-age groups contact heterogeneity. Given the number of newly reported cases at the early stage of the outbreak, with parsimony assumptions on removal distribution and infectivity profile of the diseases, experiments to estimate real time R(0) under different levels of intra- and inter-group contact heterogeneity using two age groups are presented. We show that the new method converges more quickly to the actual value of R(0) than the previous one, in particular when there is high-level intra-group and inter-group contact heterogeneity. With the age specific contact patterns, number of newly reported cases, removal distribution, and information about the natural history of the 2009 pandemic influenza in Hong Kong, we also use the extended model to estimate R(0) and age-specific R(0).

negative: The Characteristics of Middle Eastern Respiratory Syndrome Coronavirus Transmission Dynamics in South Korea OBJECTIVES: The outbreak of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) was one of the major events in South Korea in 2015. In particular, this study pays attention to formulating a mathematical model for MERS transmission dynamics and estimating transmission rates. METHODS: Incidence data of MERS-CoV from the government authority was analyzed for the first aim and a mathematical model was built and analyzed for the second aim of the study. A mathematical model for MERS-CoV transmission dynamics is used to estimate the transmission rates in two periods due to the implementation of intensive interventions. RESULTS: Using the estimates of the transmission rates, the basic reproduction number was estimated in two periods. Due to the superspreader, the basic reproduction number was very large in the first period; however, the basic reproduction number of the second period has reduced significantly after intensive interventions. CONCLUSION: It turned out to be the intensive isolation and quarantine interventions that were the most critical factors that prevented the spread of the MERS outbreak. The results are expected to be useful to devise more efficient intervention strategies in the future.

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 2019 Novel Coronavirus Outbreak - A Global Threat. The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international significance. There are significant knowledge gaps in the epidemiology, transmission dynamics, investigation tools and management. In this article, we review the available evidence about this disease. Every decade has witnessed the evolution of a new coronavirus epidemic since the last three decades. The varying transmission patterns, namely, nosocomial transmission and spread through mildly symptomatic cases is an area of concern. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, ARDS, acute cardiac injury and septic shock. Presence of bilateral ground glass opacity and consolidation on imaging in appropriate clinical background should raise a suspicion about COVID 19. Poor prognostic factors include Multilobular infiltration on chest imaging, Lymphopenia, Bacterial co-infection, Smoking history, Chronic medical conditions like Hypertension and age >60 years (MuLBSTA score). Diagnosis is confirmed with PCR based testing of appropriate respiratory samples. Management is primarily supportive, with newer antivirals (lopinavir ritonavir and Remdesivir) under investigation. Role of steroids is still inconclusive. Standard infection control and prevention techniques should be followed. Vigilant screening of suspected cases and their contacts is important. Isolation of symptomatic cases and home quarantine of asymptomatic contacts is recommended. To conclude, controlling this highly transmissible disease requires international co-ordination.

negative: Wireless Monitoring System for Oral-Feeding Evaluation of Preterm Infants. The oral feeding disorder is one of the important indicators for the high risk group of neurodevelopment delay. The procedure of oral feeding requires the coordination of sucking, swallowing, and breathing activities, and it is the most complex sensorimotor process for newborn infants. Premature infants often uneasily complete the procedure of oral feeding. However, the evaluation of the oral feeding disorders and severity are usually dependent on the subjective clinical experience of the physician. Monitoring the sucking-swallowing-breathing activities directly is difficult for preterm infants. In this study, a wireless monitoring system for oral-feeding evaluation of full term and preterm infants was proposed to objectively and quantitatively evaluate the coordination of suck-swallow-respiration function during oral feeding. Moreover, the ratios of the swallowing and breathing event numbers to the sucking event number were defined to evaluate the coordination of suck-swallow-respiration function during oral feeding. Finally, the system performance was validated and the coordination of suck-swallow-respiration function for full term and preterm infants during oral feeding was also investigated.

negative: Efficacy of Houttuynia eye drops for the treatment of vernal keratoconjunctivitis: A systemic review and meta-analysis protocol BACKGROUND: Vernal keratoconjunctivitis (VKC) is a common eye disease and can result in permanent decrease or loss of vision. Houttuynia eye drops (HED) is used for the treatment of VKC. However, the clinical evidence of HED has not been well concluded. Herein, we described a proposed systemic review and meta-analysis to evaluate the clinical efficacy of HED for the treatment of VKC. METHODS: Six electronic databases (Medline, Embase, the Cochrane database, Chinese National Knowledge Infrastructure, Wanfang database, and Chinese Biology and Medicine database) will be searched for randomized controlled trials (RCTs) which evaluating the clinical efficacy of HED for the treatment of VKC. Studies meet the eligibility criteria will be included. Data of the included studies will be extracted and the quality will also be evaluated. Data synthesis will be performed using RevMan software. Sensitivity analysis and publication bias will also be investigated. RESULTS: This study will provide high-quality systemic review and synthesis of RCTs on efficacy of HED for the treatment of VKC. CONCLUSION: This systemic review and meta-analysis will conclude the efficacy of HED for the treatment of VKC. REGISTRATION: PROSPERO CRD42019124737

negative: Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts BACKGROUND: Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. METHODS: We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R(0)), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FINDINGS: Simulated outbreaks starting with five initial cases, an R(0) of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R(0) was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R(0) of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R(0) of 2·5 more than 70% of contacts had to be traced, and for an R(0) of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R(0) was 1·5. For R(0) values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. INTERPRETATION: In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FUNDING: Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.

negative: Data-based analysis, modelling and forecasting of the COVID-19 outbreak Since the first suspected case of coronavirus disease-2019 (COVID-19) on December 1st, 2019, in Wuhan, Hubei Province, China, a total of 40,235 confirmed cases and 909 deaths have been reported in China up to February 10, 2020, evoking fear locally and internationally. Here, based on the publicly available epidemiological data for Hubei, China from January 11 to February 10, 2020, we provide estimates of the main epidemiological parameters. In particular, we provide an estimation of the case fatality and case recovery ratios, along with their 90% confidence intervals as the outbreak evolves. On the basis of a Susceptible-Infectious-Recovered-Dead (SIDR) model, we provide estimations of the basic reproduction number (R(0)), and the per day infection mortality and recovery rates. By calibrating the parameters of the SIRD model to the reported data, we also attempt to forecast the evolution of the outbreak at the epicenter three weeks ahead, i.e. until February 29. As the number of infected individuals, especially of those with asymptomatic or mild courses, is suspected to be much higher than the official numbers, which can be considered only as a subset of the actual numbers of infected and recovered cases in the total population, we have repeated the calculations under a second scenario that considers twenty times the number of confirmed infected cases and forty times the number of recovered, leaving the number of deaths unchanged. Based on the reported data, the expected value of R(0) as computed considering the period from the 11th of January until the 18th of January, using the official counts of confirmed cases was found to be ∼4.6, while the one computed under the second scenario was found to be ∼3.2. Thus, based on the SIRD simulations, the estimated average value of R(0) was found to be ∼2.6 based on confirmed cases and ∼2 based on the second scenario. Our forecasting flashes a note of caution for the presently unfolding outbreak in China. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of infected could reach 180,000 (with a lower bound of 45,000) by February 29. Regarding the number of deaths, simulations forecast that on the basis of the up to the 10th of February reported data, the death toll might exceed 2,700 (as a lower bound) by February 29. Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Thus, in a scenario where we have taken twenty times the confirmed number of infected and forty times the confirmed number of recovered cases, the case fatality ratio is around ∼0.15% in the total population. Importantly, based on this scenario, simulations suggest a slow down of the outbreak in Hubei at the end of February.

negative: Prediction of Number of Cases of 2019 Novel Coronavirus (COVID-19) Using Social Media Search Index Predicting the number of new suspected or confirmed cases of novel coronavirus disease 2019 (COVID-19) is crucial in the prevention and control of the COVID-19 outbreak. Social media search indexes (SMSI) for dry cough, fever, chest distress, coronavirus, and pneumonia were collected from 31 December 2019 to 9 February 2020. The new suspected cases of COVID-19 data were collected from 20 January 2020 to 9 February 2020. We used the lagged series of SMSI to predict new suspected COVID-19 case numbers during this period. To avoid overfitting, five methods, namely subset selection, forward selection, lasso regression, ridge regression, and elastic net, were used to estimate coefficients. We selected the optimal method to predict new suspected COVID-19 case numbers from 20 January 2020 to 9 February 2020. We further validated the optimal method for new confirmed cases of COVID-19 from 31 December 2019 to 17 February 2020. The new suspected COVID-19 case numbers correlated significantly with the lagged series of SMSI. SMSI could be detected 6–9 days earlier than new suspected cases of COVID-19. The optimal method was the subset selection method, which had the lowest estimation error and a moderate number of predictors. The subset selection method also significantly correlated with the new confirmed COVID-19 cases after validation. SMSI findings on lag day 10 were significantly correlated with new confirmed COVID-19 cases. SMSI could be a significant predictor of the number of COVID-19 infections. SMSI could be an effective early predictor, which would enable governments’ health departments to locate potential and high-risk outbreak areas.

negative: Modeling Epidemic Spreading through Public Transit using Time-Varying Encounter Network Passenger contact in public transit (PT) networks can be a key mediate in the spreading of infectious diseases. This paper proposes a time-varying weighted PT encounter network to model the spreading of infectious diseases through the PT systems. Social activity contacts at both local and global levels are also considered. We select the epidemiological characteristics of coronavirus disease 2019 (COVID-19) as a case study along with smart card data from Singapore to illustrate the model at the metropolitan level. A scalable and lightweight theoretical framework is derived to capture the time-varying and heterogeneous network structures, which enables to solve the problem at the whole population level with low computational costs. Different control policies from both the public health side and the transportation side are evaluated. We find that people's preventative behavior is one of the most effective measures to control the spreading of epidemics. From the transportation side, partial closure of bus routes helps to slow down but cannot fully contain the spreading of epidemics. Identifying"influential passengers"using the smart card data and isolating them at an early stage can also effectively reduce the epidemic spreading.

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: epiDMS: Data Management and Analytics for Decision-Making From Epidemic Spread Simulation Ensembles BACKGROUND: Carefully calibrated large-scale computational models of epidemic spread represent a powerful tool to support the decision-making process during epidemic emergencies. Epidemic models are being increasingly used for generating forecasts of the spatial-temporal progression of epidemics at different spatial scales and for assessing the likely impact of different intervention strategies. However, the management and analysis of simulation ensembles stemming from large-scale computational models pose challenges, particularly when dealing with multiple interdependent parameters, spanning multiple layers and geospatial frames, affected by complex dynamic processes operating at different resolutions. METHODS: We describe and illustrate with examples a novel epidemic simulation data management system, epiDMS, that was developed to address the challenges that arise from the need to generate, search, visualize, and analyze, in a scalable manner, large volumes of epidemic simulation ensembles and observations during the progression of an epidemic. RESULTS AND CONCLUSIONS: epiDMS is a publicly available system that facilitates management and analysis of large epidemic simulation ensembles. epiDMS aims to fill an important hole in decision-making during healthcare emergencies by enabling critical services with significant economic and health impact.

negative: Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review Background: Since early December 2019, the Coronavirus Disease 19 (COVID-19) infection has been prevalent in China and eventually spread to other countries. There are a few published cases of COVID-19 occurring during pregnancy and due the possibility of mother-fetal vertical transmission, there is a concern that the fetuses may be at risk of congenital COVID-19. Methods: We reviewed the risk of vertical transmission of COVID-19 to the fetus of infected mothers by using data of published articles or official websites up to March 4, 2020. Results: A total of 31 infected pregnant mothers with COVID-19 were reported. No COVID-19 infection was detected in their neonates or placentas. Two mothers died from COVID-19-related respiratory complications after delivery. Conclusions: Currently, based on limited data, there is no evidence for intrauterine transmission of COVID-19 from infected pregnant women to their fetuses. Mothers may be at increased risk for more severe respiratory complications.

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: Phase adjusted estimation of the number of 2019 novel coronavirus cases in Wuhan, China An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV / SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R0 of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of Rt. In the first assumption, Rt was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with Rt = 1.9, 2.6 or 3.1. The number of infections would reach 11,044, 70,258 and 227,989, respectively, by 29 February 2020. In the second assumption, Rt was assumed to gradually decrease at different phases from high level of transmission (Rt = 3.1, 2.6 and 1.9) to below 1 (Rt = 0.9 or 0.5) owing to increasingly implemented public heath intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077-84,520 or 55,869-81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce Rt to an ideal level and control the infection.

negative: Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. METHODS: We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (R(t)) at the provincial level. FINDINGS: We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33–56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4·4 days (95% CI 0·0–14·0) for the period of Dec 24 to Jan 27, to 2·6 days (0·0–9·0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5·2 days (1·8–12·4) and the mean serial interval at 5·1 days (1·3–11·6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1·08 (95% CI 0·74–1·54) in Shenzhen city of Guangdong province and 1·71 (1·32–2·17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, <1) after Jan 30. INTERPRETATION: Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province. FUNDING: National Science Fund for Distinguished Young Scholars, National Institute of General Medical Sciences, and European Commission Horizon 2020.

negative: The impact of unplanned school closure on children's social contact: Rapid evidence review Background Emergency school closures are often used as public health interventions during infectious disease outbreaks in an attempt to minimise the spread of infection. However, if children continue to mix with others outside the home during the closures, these measures are unlikely to be effective. Objectives This review aimed to summarise existing literature on children's activities and contacts made outside the home during unplanned school closures. Methods We searched four databases from inception to February 2020 for relevant literature. Main findings were extracted. Results 3,343 citations were screened and 19 included in the review. Activities and social contacts appeared to decrease during closures but contact was still common. All studies reported children leaving the house or being looked after by non-household members. There was some evidence that older child age and parental disagreement with closure were predictive of children leaving the house, and mixed evidence regarding the relationship between infection status and leaving the home. Parental agreement with closure was generally high, but some parents disagreed due to perceived low risk of infection and practical issues regarding childcare and financial impact. Conclusions Evidence suggests that many children continue to leave the house and mix with others during school closures despite public health recommendations to avoid social contact. This review of behaviour during unplanned school closures could be used to improve infectious disease modelling.

negative: Analysis of IFITM-IFITM Interactions by a Flow Cytometry-Based FRET Assay The interferon-induced transmembrane proteins 1–3 (IFITM1–3) inhibit host cell entry of several viruses. However, it is incompletely understood how IFITM1–3 exert antiviral activity. Two phenylalanine residues, F75 and F78, within the intramembrane domain 1 (IM1) were previously shown to be required for IFITM3/IFITM3 interactions and for inhibition of viral entry, suggesting that IFITM/IFITM interactions might be pivotal to antiviral activity. Here, we employed a fluorescence resonance energy transfer (FRET) assay to analyze IFITM/IFITM interactions. For assay calibration, we equipped two cytosolic, non-interacting proteins, super yellow fluorescent protein (SYFP) and super cyan fluorescent protein (SCFP), with signals that target proteins to membrane rafts and also analyzed a SCFP-SYFP fusion protein. This strategy allowed us to discriminate background signals resulting from colocalization of proteins at membrane subdomains from signals elicited by protein–protein interactions. Coexpression of IFITM1–3 and IFITM5 fused to fluorescent proteins elicited strong FRET signals, and mutation of F75 and F78 in IFITM3 (mutant IFITM3-FF) abrogated antiviral activity, as expected, but did not alter cellular localization and FRET signals. Moreover, IFITM3-FF co-immunoprecipitated efficiently with wild type (wt) IFITM3, lending further support to the finding that lack of antiviral activity of IFITM3-FF was not due to altered membrane targeting or abrogated IFITM3-IFITM3 interactions. Collectively, we report an assay that allows quantifying IFITM/IFITM interactions. Moreover, we confirm residues F75 and F78 as critical for antiviral activity but also show that these residues are dispensable for IFITM3 membrane localization and IFITM3/IFITM3 interactions.

negative: Novel Corona virus Disease infection in Tunisia: Mathematical model and the impact of the quarantine strategy In this paper, we propose a new model for the dynamics of COVID-19 infections. Our approach consists of seven phenotypes: the susceptible humans, exposed humans, infectious humans, the recovered humans, the quarantine population, the recovered-exposed and deceased population. We proved first through mathematical approach the positivity, boundness and existence of a solution to considered model. We also studied the existence of the disease free equilibrium and corresp onding stability. Hence, the actual reproduction number was calculated . We analyzed the dependence of basic reproductions R_0 on the confidence of our model. Our work shows, in particular, that the disease will decrease out if the number of reproduction was less than one. Moreover, the impact of the quarantine strategies to reduce the spread of this disease is discussed. The theoretical results are validated by some numerical simulations of the system of the epidemic's differential equations.

negative: Comparative genomics suggests limited variability and similar evolutionary patterns between major clades of SARS-CoV-2 Phylogenomic analysis of SARS-CoV-2 as available from publicly available repositories suggests the presence of 3 prevalent groups of viral episomes (super-clades), which are mostly associated with outbreaks in distinct geographic locations (China, USA and Europe). While levels of genomic variability between SARS-CoV-2 isolates are limited, to our knowledge, it is not clear whether the observed patterns of variability in viral super-clades reflect ongoing adaptation of SARS-CoV-2, or merely genetic drift and founder effects. Here, we analyze more than 1100 complete, high quality SARS-CoV-2 genome sequences, and provide evidence for the absence of distinct evolutionary patterns/signatures in the genomes of the currently known major clades of SARS-CoV-2. Our analyses suggest that the presence of distinct viral episomes at different geographic locations are consistent with founder effects, coupled with the rapid spread of this novel virus. We observe that while cross species adaptation of the virus is associated with hypervariability of specific protein coding regions (including the RDB domain of the spike protein), the more variable genomic regions between extant SARS-CoV-2 episomes correspond with the 3’ and 5’ UTRs, suggesting that at present viral protein coding genes should not be subjected to different adaptive evolutionary pressures in different viral strains. Although this study can not be conclusive, we believe that the evidence presented here is strongly consistent with the notion that the biased geographic distribution of SARS-CoV-2 isolates should not be associated with adaptive evolution of this novel pathogen.

negative: Recognition of Lys48-linked di-ubiquitin and deubiquitinating activities of the SARS coronavirus papain-like protease Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific poly-ubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The Severe Acute Respiratory Syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1–S1′ preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections.

negative: COVID-19 testing and patients in mental health facilities

negative: Protecting Health Care Workers during the COVID-19 Coronavirus Outbreak –Lessons from Taiwan's SARS response During major epidemic outbreaks, demand for health care workers grows even as the extreme pressures they face cause declining availability. We draw on Taiwan’s SARS experience to argue that a modified form of Traffic Control Bundling protects health care worker safety and by extension strengthens overall COVID-19 epidemic control.

negative: Neurocritical Care Society 14(th) Annual Meeting

negative: Assessing the risk of spread of COVID-19 to the Asia Pacific region During the early stages of an emerging disease outbreak, governments are required to make critical decisions on how to respond appropriately, despite limited data being available to inform these decisions. Analytical risk assessment is a valuable approach to guide decision-making on travel restrictions and border measures during the early phase of an outbreak, when transmission is primarily contained within a source country. Here we introduce a modular framework for estimating the importation risk of an emerging disease when the direct travel route is restricted and the risk stems from indirect importation via intermediary countries. This was the situation for Australia in February 2020. The framework was specifically developed to assess the importation risk of COVID-19 into Australia during the early stages of the outbreak from late January to mid-February 2020. The dominant importation risk to Australia at the time of analysis was directly from China, as the only country reporting uncontained transmission. However, with travel restrictions from mainland China to Australia imposed from February 1, our framework was designed to consider the importation risk from China into Australia via potential intermediary countries in the Asia Pacific region. The framework was successfully used to contribute to the evidence base for decisions on border measures and case definitions in the Australian context during the early phase of COVID-19 emergence and is adaptable to other contexts for future outbreak response.

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

negative: Feasibility of single-access laparoscopic sleeve gastrectomy in super-super obese patients. BACKGROUND The sleeve gastrectomy procedure has been gaining popularity because of its simplicity and favorable outcomes. This study reports the experience with a single-access approach to laparoscopic sleeve gastrectomy in super-super obese patients. METHODS Four super-super obese patients having a mean body mass index of 62.7 kg/m(2) underwent single-access laparoscopic sleeve gastrectomy. The same perioperative protocol and operative techniques were implemented for all 4 patients. RESULTS A total of 4 single-access laparoscopic sleeve gastrectomies in super-super obese patients were successfully performed using this technique. Mean operating time was 126 minutes. One patient required the insertion of an additional trocar. There were no mortalities or postoperative complications noted. Most comorbidities either improved or resolved during a mean follow-up of 5.3 months. CONCLUSION Single-access laparoscopic sleeve gastrectomy in the super-super obese is safe, feasible, and reproducible.

negative: Bacteriophages as model organisms for virus emergence research Viruses fully emerge by gaining the ability to sustainably infect new host populations. When the hosts are humans, emerging viruses can present major public health issues, as exemplified by the AIDS pandemic. Therefore, heuristic approaches to identify nascent diseases before they become pandemic would be valuable. Unfortunately, the current patient-based and epidemiological approaches are ill-suited in this regard because they are largely responsive and not predictive. Alternative approaches based on virus evolutionary ecology might have greater potential to predict virus emergence. However, given the difficulties encountered when studying metazoan viruses in this context, the development of new model systems is greatly desirable. Here, I highlight studies that show that bacteriophages are appropriate model organisms for virus emergence research because of the ease in which important population parameters can be manipulated. Ideally this research will permit identifying major factors determining the persistence or extinction of emerging viruses. If such viruses could be recognized in advance, patient-based and epidemiological strategies could be better mobilized to deal with them.

negative: A Smartphone enabled Approach to Manage COVID-19 Lockdown and Economic Crisis The emergence of novel COVID-19 causing an overload in health system and high mortality rate. The key priority is to contain the epidemic and prevent the infection rate. In this context, many countries are now in some degree of lockdown to ensure extreme social distancing of entire population and hence slowing down the epidemic spread. Further, authorities use case quarantine strategy and manual second/third contact-tracing to contain the COVID-19 disease. However, manual contact tracing is time consuming and labor-intensive task which tremendously overload public health systems. In this paper, we developed a smartphone-based approach to automatically and widely trace the contacts for confirmed COVID-19 cases. Particularly, contact-tracing approach creates a list of individuals in the vicinity and notifying contacts or officials of confirmed COVID-19 cases. This approach is not only providing awareness to individuals they are in the proximity to the infected area, but also tracks the incidental contacts that the COVID-19 carrier might not recall. Thereafter, we developed a dashboard to provide a plan for government officials on how lockdown/mass quarantine can be safely lifted, and hence tackling the economic crisis. The dashboard used to predict the level of lockdown area based on collected positions and distance measurements of the registered users in the vicinity. The prediction model uses K-means algorithm as an unsupervised machine learning technique for lockdown management.

negative: Asymptomatic carriers of COVID-19 as a concern for disease prevention and control: more testing, more follow-up. Following a containment phase of two months, China has transitioned to the mitigation phase. However, China still faces the risk of COVID-19 spreading due to not only to sporadic new cases and imported cases but also asymptomatic carriers. According to daily reports from the National Health Commission of the People's Republic of China from March 31, 2020 to April 7, 2020, the number of new asymptomatic cases reported daily greatly exceeded that of new imported cases. As of 24:00 on April 7, there were a total of 1,095 asymptomatic cases with COVID-19 under medical observation on the Chinese mainland, including 358 imported cases. A growing number of studies have indicated that asymptomatic carriers are infectious to an extent and can potentially transmit COVID-19. At present, China's measures for managing asymptomatic carriers are 14 days of centralized quarantine and observation; in principle, people with two consecutive negative nucleic acid tests (at an interval of at least 24 hours) can be released from quarantine. However, asymptomatic carriers will not be included in confirmed cases unless they develop clinical manifestations while in quarantine. As "silent spreaders", asymptomatic carriers warrant attention as part of disease prevention and control. The testing and follow-up of asymptomatic carriers should be expanded to include people in close contact with patients with confirmed COVID-19 and asymptomatic cases, clusters of outbreaks, and key areas and populations with a high risk of infection.

negative: Evidence Based Management Guideline for the COVID-19 Pandemic - Review article ABSTRACT COVID-19 has now been declared a pandemic. To date, COVID-19 has affected over 944,181 people worldwide, resulting in over 47,312 reported deaths. Numerous preventative strategies and non-pharmaceutical interventions have been employed to mitigate the spread of disease including careful infection control, the isolation of patients, and social distancing. Management is predominantly focused on the provision of supportive care, with oxygen therapy representing the major treatment intervention. Medical therapy involving corticosteroids and antivirals have also been encouraged as part of critical management schemes. However, there is at present no specific antiviral recommended for the treatment of COVID-19, and no vaccine is currently available. Despite the strategic implementation of these measures, the number of new reported cases continues to rise at a profoundly alarming rate. As new findings emerge, there is an urgent need for up-to-date management guidelines. In response to this call, we review what is currently known regarding the management of COVID-19, and offer an evidence-based review of current practice.

negative: The Impact of Contact Tracing in Clustered Populations The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease.

negative: Super-Gau: Ausrottung der Menschheit durch Krieg und Naturkatastrophen Die Vernichtung der Menschheit durch Krieg oder Naturkatastrophen weist in ihren Konsequenzen große Überschneidungen auf, weshalb ich sie auch zu einem übergeordneten Typus „Super-Gau – Ausrottung der Menschheit“ zusammengefasst habe. Im Prinzip lehren uns die dystopischen Filme generell, dass die Menschheit stets selbst an ihrem Unheil schuld ist. Dies unterscheidet auch die von Giddens als high-consequence risks bezeichneten modernen Risiken von früheren Katastrophen wie Sintfluten, Dürren oder Epidemien, die der Mensch nicht beeinfl ussen konnte. Wenn man jedoch genauer hinsieht, dann ist die Zuschreibung der Verantwortlichkeit des Menschen für das, was in der Umwelt passiert, keine moderne Erfindung.

negative: Chapter Three Dances with Membranes: Breakthroughs from Super-resolution Imaging Abstract Biological membrane organization mediates numerous cellular functions and has also been connected with an immense number of human diseases. However, until recently, experimental methodologies have been unable to directly visualize the nanoscale details of biological membranes, particularly in intact living cells. Numerous models explaining membrane organization have been proposed, but testing those models has required indirect methods; the desire to directly image proteins and lipids in living cell membranes is a strong motivation for the advancement of technology. The development of super-resolution microscopy has provided powerful tools for quantification of membrane organization at the level of individual proteins and lipids, and many of these tools are compatible with living cells. Previously inaccessible questions are now being addressed, and the field of membrane biology is developing rapidly. This chapter discusses how the development of super-resolution microscopy has led to fundamental advances in the field of biological membrane organization. We summarize the history and some models explaining how proteins are organized in cell membranes, and give an overview of various super-resolution techniques and methods of quantifying super-resolution data. We discuss the application of super-resolution techniques to membrane biology in general, and also with specific reference to the fields of actin and actin-binding proteins, virus infection, mitochondria, immune cell biology, and phosphoinositide signaling. Finally, we present our hopes and expectations for the future of super-resolution microscopy in the field of membrane biology.

negative: ICU management of severe acute respiratory syndrome BACKGROUND: Severe acute respiratory syndrome (SARS) is a contagious viral illness first recognized in late 2002. It has now been documented in 26 countries worldwide, with significant outbreaks in China, Hong Kong, Singapore, and Toronto. Research into identifying the etiological agent, evaluating modes of disease transmission, and treatment options is currently ongoing. DISCUSSION: The disease can produce a severe bilateral pneumonia, with progressive hypoxemia. Up to 20% of patients require mechanical ventilatory support, with a fatal outcome occurring in about 5% of cases. CONCLUSIONS: We review the current knowledge about this disease, with particular emphasis on ICU management and infection control precautions to prevent disease transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available if you access this article at http://dx.doi.org/10.1007/s00134-003-1821-0. On that page (frame on the left side) a link takes you directly to the supplementary material.

negative: COVID-19, SARS and MERS: are they closely related? BACKGROUND: The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. AIMS: To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. SOURCES: The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. CONTENT: COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0-2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7-1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. IMPLICATIONS: There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.

negative: Dynamic basic reproduction number based evaluation for current prevention and control of COVID-19 outbreak in China/ 中华流行病学杂志 Objective@#To evaluate the current status of the prevention and control of coronavirus disease (COVID-19) outbreak in China, establish a predictive model to evaluate the effects of the current prevention and control strategies, and provide scientific information for decision- making departments.@*Methods@#Based on the epidemic data of COVID-19 openly accessed from national health authorities, we estimated the dynamic basic reproduction number R0(t) to evaluate the effects of the current COVID-19 prevention and control strategies in all the provinces (municipalities and autonomous regions) as well as in Wuhan and the changes in infectivity of COVID-19 over time.@*Results@#For the stability of the results, 24 provinces (municipality) with more than 100 confirmed COVID-19 cases were included in the analysis. At the beginning of the outbreak, the R0(t) showed unstable trend with big variances. As the strengthening of the prevention and control strategies, R0(t) began to show a downward trend in late January, and became stable in February. By the time of data analysis, 18 provinces (municipality) (75%) had the R0(t)s less than 1. The results could be used for the decision making to free population floating conditionally.@* Conclusions@#Dynamic R0(t) is useful in the evaluation of the change in infectivity of COVID-19, the prevention and control strategies for the COVID-19 outbreak have shown preliminary effects, if continues, it is expected to control the COVID-19 outbreak in China in near future.

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: Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease with lack of established laboratory markers available to evaluate illness severity. In this study, we investigate whether platelet count could differentiate between COVID-19 patients with or without severe disease. Additionally, we evaluate if thrombocytopenia is associated with severe COVID-19. METHODS: An electronic search in Medline, Scopus and Web of Science was performed to identify studies reporting data on platelet count in COVID-19 patients. A meta-analysis was performed, with calculation of weighted mean difference (WMD) of platelet number in COVID-19 patients with or without severe disease and odds ratio (OR) of thrombocytopenia for severe form of COVID-19. RESULTS: Nine studies with 1779 COVID-19 patients, 399 (22.4%) with severe disease, were included in the meta-analysis. The pooled analysis revealed that platelet count was significantly lower in patients with more severe COVID-19 (WMD -31×10(9)/L; 95% CI, from -35 to -29×10(9)/L). A subgroup analysis comparing patients by survival, found an even lower platelet count was observed with mortality (WMD, -48×10(9)/L; 95% CI, -57 to -39×10(9)/L. In the four studies (n=1427) which reported data on rate of thrombocytopenia, a low platelet count was associated with over fivefold enhanced risk of severe COVID-19 (OR, 5.1; 95% CI, 1.8-14.6). CONCLUSIONS: Low platelet count is associated with increased risk of severe disease and mortality in patients with COVID-19, and thus should serve as clinical indicator of worsening illness during hospitalization.

negative: Structure‐Based Design and Synthesis of Highly Potent SARS‐CoV 3CL Protease Inhibitors In a successful example of lead optimization by computer modeling prediction, computational technology was used to optimize a lead inhibitor (TL‐3) of the SARS‐CoV 3CL protease. A novel C (2)‐symmetric diol (1) was then designed and synthesized, and displayed higher affinity than the original lead compound by one order of magnitude in its inhibition constant (0.6→0.073 μm). We believe that this approach has provided a platform for further lead optimization.[Image: see text]

negative: Systematic review and meta-analysis of predictive symptoms and comorbidities for severe COVID-19 infection Background/introduction COVID−19, a novel coronavirus outbreak starting in China, is now a rapidly developing public health emergency of international concern. The clinical spectrum of COVID−19 disease is varied, and identifying factors associated with severe disease has been described as an urgent research priority. It has been noted that elderly patients with pre-existing comorbidities are more vulnerable to more severe disease. However, the specific symptoms and comorbidities that most strongly predict disease severity are unclear. We performed a systematic review and meta-analysis to identify the symptoms and comorbidities predictive of COVID−19 severity. Method This study was prospectively registered on PROSPERO. A literature search was performed in three databases (MEDLINE, EMBASE and Global Health) for studies indexed up to 5th March 2020. Two reviewers independently screened the literature and both also completed data extraction. Quality appraisal of studies was performed using the STROBE checklist. Random effects meta-analysis was performed for selected symptoms and comorbidities to identify those most associated with severe COVID−19 infection or ICU admission. Results Of the 2259 studies identified, 42 were selected after title and abstract analysis, and 7 studies (including 1813 COVID−19 patients) were chosen for inclusion. The ICU group were older (62.4 years) compared to the non-ICU group (46 years), with a significantly higher proportion of males (67.2% vs. 57.1%, p=0.04). Dyspnoea was the only significant symptom predictive for both severe disease (pOR 3.70, 95% CI 1.83 − 7.46) and ICU admission (pOR 6.55, 95% CI 4.28 − 10.0). Notwithstanding the low prevalence of COPD in severe disease and ICU-admitted groups (4.5% and 9.7%, respectively), COPD was the most strongly predictive comorbidity for both severe disease (pOR 6.42, 95% CI 2.44 − 16.9) and ICU admission (pOR 17.8, 95% CI 6.56 − 48.2). Cardiovascular disease and hypertension were also strongly predictive for both severe disease and ICU admission. Those with CVD and hypertension were 4.4 (95% CI 2.64 − 7.47) and 3.7 (95% CI 2.22 − 5.99) times more likely to have an ICU admission respectively, compared to patients without the comorbidity. Conclusions Dyspnoea was the only symptom strongly predictive for both severe disease and ICU admission, and could be useful in guiding clinical management decisions early in the course of illness. When looking at ICU-admitted patients, who represent the more severe end of the spectrum of clinical severity, COPD patients are particularly vulnerable, and those with cardiovascular disease and hypertension are also at a high-risk of severe illness. To aid clinical assessment, risk stratification, efficient resource allocation, and targeted public health interventions, future research must aim to further define those at high-risk of severe illness with COVID−19.

negative: Usefulness of national respiratory virus surveillance data for clinicians who manage adult patients The Korean Centers for Disease Control and Prevention (KCDC) provides weekly respiratory virus (RV) surveillance reports on its website (the KCDC data). Clinicians in clinical settings wherein the use of PCR for RVs is not a routine laboratory test for adult patients with acute respiratory illness (ARI) may question the clinical utility of such a national RV surveillance dataset in predicting RV outbreaks among their adult patients. We compared the KCDC data to the RV PCR data of adult patients who visited a tertiary care center. During a period of 108 weeks, a total of 6955 (5598 pediatric and 1257 adult) patients underwent RV PCR tests for ARI; most of these tests were administered while the patients were admitted (n = 6,920; 99.5%). From the KCDC website, we collected the RV PCR test results of 22 540 patients. Three graphs of weekly positivity rates were made for adults, children, and the KCDC data per each RV, and these graphs were then compared with one another. Whereas RV outbreaks were coincident between the KCDC and the adult graph with respect to influenza virus, respiratory syncytial virus, human metapneumovirus, and human coronavirus, the same was not true for human bocavirus, parainfluenza virus, rhinovirus, and adenovirus. However, a negative predictive value of the KCDC data in the prediction of the occurrence of an outbreak in the adult graph was high for the respective eight RVs (85‐100%). A national RV surveillance dataset may be useful in identifying RV outbreaks in adult patients with severe ARI.

negative: Forecasting the novel coronavirus COVID-19 What will be the global impact of the novel coronavirus (COVID-19)? Answering this question requires accurate forecasting the spread of confirmed cases as well as analysis of the number of deaths and recoveries. Forecasting, however, requires ample historical data. At the same time, no prediction is certain as the future rarely repeats itself in the same way as the past. Moreover, forecasts are influenced by the reliability of the data, vested interests, and what variables are being predicted. Also, psychological factors play a significant role in how people perceive and react to the danger from the disease and the fear that it may affect them personally. This paper introduces an objective approach to predicting the continuation of the COVID-19 using a simple, but powerful method to do so. Assuming that the data used is reliable and that the future will continue to follow the past pattern of the disease, our forecasts suggest a continuing increase in the confirmed COVID-19 cases with sizable associated uncertainty. The risks are far from symmetric as underestimating its spread like a pandemic and not doing enough to contain it is much more severe than overspending and being over careful when it will not be needed. This paper describes the timeline of a live forecasting exercise with massive potential implications for planning and decision making and provides objective forecasts for the confirmed cases of COVID-19.

negative: 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.

negative: 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.

negative: Porcine Deltacoronavirus Accessory Protein NS6 Antagonizes Interferon Beta Production by Interfering with the Binding of RIG-I/MDA5 to Double-Stranded RNA. Porcine deltacoronavirus (PDCoV) has recently emerged as an enteric pathogen that can cause serious vomiting and diarrhea in suckling piglets. The first outbreak of PDCoV occurred in the United States in 2014 and was followed by reports of PDCoV in South Korea, China, Thailand, Lao People's Democratic Republic, and Vietnam, leading to economic losses for pig farms and posing a considerable threat to the swine industry worldwide. Our previous studies have shown that PDCoV encodes three accessory proteins, NS6, NS7, and NS7a, but the functions of these proteins in viral replication, pathogenesis, and immune regulation remain unclear. Here, we found that ectopic expression of accessory protein NS6 significantly inhibits Sendai virus-induced interferon beta (IFN-β) production as well as the activation of transcription factors IRF3 and NF-κB. Interestingly, NS6 does not impede the IFN-β promoter activation mediated via key molecules in the RIG-I-like receptor (RLR) signaling pathway, specifically RIG-I, MDA5, and their downstream molecules MAVS, TBK1, IKKε, and IRF3. Further analyses revealed that NS6 is not an RNA-binding protein; however, it interacts with RIG-I/MDA5. This interaction attenuates the binding of double-stranded RNA by RIG-I/MDA5, resulting in the reduction of RLR-mediated IFN-β production. Taken together, our results demonstrate that ectopic expression of NS6 antagonizes IFN-β production by interfering with the binding of RIG-I/MDA5 to double-stranded RNA, revealing a new strategy employed by PDCoV accessory proteins to counteract the host innate antiviral immune response.IMPORTANCE Coronavirus accessory proteins are species specific, and they perform multiple functions in viral pathogenicity and immunity, such as acting as IFN antagonists and cell death inducers. Our previous studies have shown that PDCoV encodes three accessory proteins. Here, we demonstrated for the first time that PDCoV accessory protein NS6 antagonizes IFN-β production by interacting with RIG-I and MDA5 to impede their association with double-stranded RNA. This is an efficient strategy of antagonizing type I IFN production by disrupting the binding of host pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs). These findings deepen our understanding of the function of accessory protein NS6, and they may direct us toward novel therapeutic targets and lead to the development of more effective vaccines against PDCoV infection.

negative: Can mathematical modelling solve the current Covid-19 crisis? Since COVID-19 transmission started in late January, mathematical modelling has been at the forefront of shaping the decisions around different non-pharmaceutical interventions to confine its’ spread in the UK and worldwide. This Editorial discusses the importance of modelling in understanding Covid-19 spread, highlights different modelling approaches and suggests that while modelling is important, no one model can give all the answers.

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

negative: Epidemiological and Clinical Aspects of COVID-19; a Narrative Review There are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of COVID-19 as a new emerging epidemic. In addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable. However, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic. Accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities.

negative: Why is it difficult to accurately predict the COVID-19 epidemic? Since the COVID-19 outbreak in Wuhan City in December of 2019, numerous model predictions on the COVID-19 epidemics in Wuhan and other parts of China have been reported. These model predictions have shown a wide range of variations. In our study, we demonstrate that nonidentifiability in model calibrations using the confirmed-case data is the main reason for such wide variations. Using the Akaike Information Criterion (AIC) for model selection, we show that an SIR model performs much better than an SEIR model in representing the information contained in the confirmed-case data. This indicates that predictions using more complex models may not be more reliable compared to using a simpler model. We present our model predictions for the COVID-19 epidemic in Wuhan after the lockdown and quarantine of the city on January 23, 2020. We also report our results of modeling the impacts of the strict quarantine measures undertaken in the city after February 7 on the time course of the epidemic, and modeling the potential of a second outbreak after the return-to-work in the city.

negative: Early Prediction of the 2019 Novel Coronavirus Outbreak in the Mainland China Based on Simple Mathematical Model The 2019 novel coronavirus (2019-nCoV) outbreak has been treated as a Public Health Emergency of International Concern by the World Health Organization. This work made an early prediction of the 2019-nCoV outbreak in China based on a simple mathematical model and limited epidemiological data. Combing characteristics of the historical epidemic, we found part of the released data is unreasonable. Through ruling out the unreasonable data, the model predictions exhibit that the number of the cumulative 2019-nCoV cases may reach 76,000 to 230,000, with a peak of the unrecovered infectives (22,000-74,000) occurring in late February to early March. After that, the infected cases will rapidly monotonically decrease until early May to late June, when the 2019-nCoV outbreak will fade out. Strong anti-epidemic measures may reduce the cumulative infected cases by 40%-49%. The improvement of medical care can also lead to about one-half transmission decrease and effectively shorten the duration of the 2019-nCoV.

negative: Outbreak of Middle East respiratory syndrome coronavirus in Saudi Arabia: a retrospective study BACKGROUND: The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease. Dromedary camels have been implicated due to reports that some confirmed cases were exposed to camels. Risk factors for MERS coronavirus (MERS-CoV) infections in humans are incompletely understood. This study aimed to describe the demographic characteristics, mortality rate, clinical manifestations and comorbidities with confirmed cases of MERS-CoV. METHODS: Retrospective chart review were performed to identify all laboratory-confirmed cases of MERS-CoV in Saudi Arabia who reported to the Ministry of Health (MOH) of Saudi Arabia and WHO between April 23, 2014 and August 31, 2015. Patients’ charts were also reviewed for demographic information, mortality, comorbidities, clinical presentations, health care facility and presented with descriptive and comparative statistics using non parametric binomial test and Chi-square test. RESULTS: Confirmed cases of male patients (61.1%) exceeded those of female patients (38.9%). Infections among Saudi patients (62.6%) exceeded those among non-Saudi patients (37.4%; P = 0.001). The majority of the patients were aged 21–40 years (37.4%) or 41–60 years (35.8%); 43 (22.6%) were aged >61 years, and (8) 4.2% were aged 0–20 years. There was a difference in mortality between confirmed MERS-CoV cases (63.7% alive versus 36.3% dead cases, respectively). Furthermore, fever with cough and shortness of breath (SOB) (n = 39; 20.5%), fever with cough (n = 29; 15.3%), fever (n = 18; 9.5%), and fever with SOB (n = 13; 6.8%), were the most common clinical manifestations associated with confirmed MERS-CoV cases. CONCLUSION: MERS-CoV is considered an epidemic in Saudi Arabia. The results of the present study showed that the frequency of cases is higher among men than women, in Saudi patients than non-Saudi, and those between 21 to 60 years are most affected. Further studies are required to improve the surveillance associated with MERS-CoV to get definite and clear answers and better understanding of the MERS-CoV outbreak as well the source, and route of infection transmission in Saudi Arabia.

negative: Control Strategies to Curtail Transmission of COVID-19 Recently, the World Health Organization has declared the outbreak of a severe acute respiratory syndrome coronavirius as a pandemic, and declared it as Public Health Emergency of International Concern. More than 6,83,536 positive cases and 32,139 deaths caused by coronavirus 2019 affecting 199 countries and territories. This pandemic can transform into an extremely destructive form if we still do not take it seriously. In this present study, we propose a generalized SEIR model of COVID-2019 to study the behavior of its transmission under different control strategies.

negative: 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.

negative: The roles of chemokines in rabies virus infection: overexpression may not always be beneficial. It was found previously that induction of innate immunity, particularly chemokines, is an important mechanism of rabies virus (RABV) attenuation. To evaluate the effect of overexpression of chemokines on RABV infection, chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), RANTES, and IP-10 were individually cloned into the genome of attenuated RABV strain HEP-Flury. These recombinant RABVs were characterized in vitro for growth properties and expression of chemokines. It was found that all the recombinant viruses grew as well as the parent virus, and each of the viruses expressed the intended chemokine in a dose-dependent manner. When these viruses were evaluated for pathogenicity in the mouse model, it was found that overexpression of MIP-1alpha further decreased RABV pathogenicity by inducing a transient innate immune response. In contrast, overexpression of RANTES or IP-10 increased RABV pathogenicity by causing neurological diseases, which is due to persistent and high-level expression of chemokines, excessive infiltration and accumulation of inflammatory cells in the central nervous system, and severe enhancement of blood-brain barrier permeability. These studies indicate that overexpression of chemokines, although important in controlling virus infection, may not always be beneficial to the host.

negative: Medical imaging informatics research and development trends—an editorial

negative: Current epidemiological status of Middle East respiratory syndrome coronavirus in the world from 1.1.2017 to 17.1.2018: a cross-sectional study BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is considered to be responsible for a new viral epidemic and an emergent threat to global health security. This study describes the current epidemiological status of MERS-CoV in the world. METHODS: Epidemiological analysis was performed on data derived from all MERS-CoV cases recorded in the disease outbreak news on WHO website between 1.1.2017 and 17.1.2018. Demographic and clinical information as well as potential contacts and probable risk factors for mortality were extracted based on laboratory-confirmed MERS-CoV cases. RESULTS: A total of 229 MERS-CoV cases, including 70 deaths (30.5%), were recorded in the disease outbreak news on world health organization website over the study period. Based on available details in this study, the case fatality rate in both genders was 30.5% (70/229) [32.1% (55/171) for males and 25.8% (15/58) for females]. The disease occurrence was higher among men [171 cases (74.7%)] than women [58 cases (25.3%)]. Variables such as comorbidities and exposure to MERS-CoV cases were significantly associated with mortality in people affected with MERS-CoV infections, and adjusted odds ratio estimates were 2.2 (95% CI: 1.16, 7.03) and 2.3 (95% CI: 1.35, 8.20), respectively. All age groups had an equal chance of mortality. CONCLUSIONS: In today’s “global village”, there is probability of MERS-CoV epidemic at any time and in any place without prior notice. Thus, health systems in all countries should implement better triage systems for potentially imported cases of MERS-CoV to prevent large epidemics.

negative: Middle East respiratory syndrome coronavirus: a comprehensive review The Middle East respiratory syndrome coronavirus was first identified in 2012 and has since then remained uncontrolled. Cases have been mostly reported in the Middle East, however travel-associated cases and outbreaks have also occurred. Nosocomial and zoonotic transmission of the virus appear to be the most important routes. The infection is severe and highly fatal thus necessitating rapid and efficacious interventions. Here, we performed a comprehensive review of published literature and summarized the epidemiology of the virus. In addition, we summarized the virological aspects of the infection and reviewed the animal models used as well as vaccination and antiviral tested against it.

negative: Privacy Guidelines for Contact Tracing Applications Contact tracing is a very powerful method to implement and enforce social distancing to avoid spreading of infectious diseases. The traditional approach of contact tracing is time consuming, manpower intensive, dangerous and prone to error due to fatigue or lack of skill. Due to this there is an emergence of mobile based applications for contact tracing. These applications primarily utilize a combination of GPS based absolute location and Bluetooth based relative location remitted from user's smartphone to infer various insights. These applications have eased the task of contact tracing; however, they also have severe implication on user's privacy, for example, mass surveillance, personal information leakage and additionally revealing the behavioral patterns of the user. This impact on user's privacy leads to trust deficit in these applications, and hence defeats their purpose. In this work we discuss the various scenarios which a contact tracing application should be able to handle. We highlight the privacy handling of some of the prominent contact tracing applications. Additionally, we describe the various threat actors who can disrupt its working, or misuse end user's data, or hamper its mass adoption. Finally, we present privacy guidelines for contact tracing applications from different stakeholder's perspective. To best of our knowledge, this is the first generic work which provides privacy guidelines for contact tracing applications.

negative: Sentinel Event Surveillance to Estimate Total SARS-CoV-2 Infections, United States Human infections with a novel coronavirus (SARS-CoV-2) were first identified via syndromic surveillance in December of 2019 in Wuhan China. Since identification, infections (coronavirus disease-2019; COVID-19) caused by this novel pathogen have spread globally, with more than 180,000 confirmed cases as of March 16, 2020. Effective public health interventions, including social distancing, contact tracing, and isolation/quarantine rely on the rapid and accurate identification of confirmed cases. However, testing capacity (having sufficient tests and laboratory throughput) to support these non-pharmaceutical interventions remains a challenge for containment and mitigation of COVID-19 infections. We undertook a sentinel event strategy (where single health events signal emerging trends) to estimate the incidence of COVID-19 in the US. Data from a recent national conference, the Conservative Political Action Conference, (CPAC) near Washington, DC and from the outbreak in Wuhan, China were used to fit a simple exponential growth model to estimate the total number of incident SARS- CoV-2 infections in the United States on March 1, 2020, and to forecast subsequent infections potentially undetected by current testing strategies. Our analysis and forecasting estimates a total of 54,100 SARS-CoV-2 infections (80 % CI 5,600 to 125,300) have occurred in the United States to March 12, 2020. Our forecast predicts that a very substantial number of infections are undetected, and without extensive and far-reaching non-pharmaceutical interventions, the number of infections should be expected to grow at an exponential rate.

negative: 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: Plausible models for propagation of the SARS virus Using daily infection data for Hong Kong we explore the validity of a variety of models of disease propagation when applied to the SARS epidemic. Surrogate data methods show that simple random models are insufficient and that the standard epidemic susceptible-infected-removed model does not fully account for the underlying variability in the observed data. As an alternative, we consider a more complex small world network model and show that such a structure can be applied to reliably produce simulations quantitative similar to the true data. The small world network model not only captures the apparently random fluctuation in the reported data, but can also reproduces mini-outbreaks such as those caused by so-called ``super-spreaders'' and in the Hong Kong housing estate Amoy Gardens.

negative: Contact among healthcare workers in the hospital setting: developing the evidence base for innovative approaches to infection control BACKGROUND: Nosocomial, or healthcare-associated infections (HAI), exact a high medical and financial toll on patients, healthcare workers, caretakers, and the health system. Interpersonal contact patterns play a large role in infectious disease spread, but little is known about the relationship between health care workers’ (HCW) movements and contact patterns within a heath care facility and HAI. Quantitatively capturing these patterns will aid in understanding the dynamics of HAI and may lead to more targeted and effective control strategies in the hospital setting. METHODS: Staff at 3 urban university-based tertiary care hospitals in Canada completed a detailed questionnaire on demographics, interpersonal contacts, in-hospital movement, and infection prevention and control practices. Staff were divided into categories of administrative/support, nurses, physicians, and “Other HCWs” - a fourth distinct category, which excludes physicians and nurses. Using quantitative network modeling tools, we constructed the resulting HCW “co-location network” to illustrate contacts among different occupations and with locations in hospital settings. RESULTS: Among 3048 respondents (response rate 38%) an average of 3.79, 3.69 and 3.88 floors were visited by each HCW each week in the 3 hospitals, with a standard deviation of 2.63, 1.74 and 2.08, respectively. Physicians reported the highest rate of direct patient contacts (> 20 patients/day) but the lowest rate of contacts with other HCWs; nurses had the most extended (> 20 min) periods of direct patient contact. “Other HCWs” had the most direct daily contact with all other HCWs. Physicians also reported significantly more locations visited per week than nurses, other HCW, or administrators; nurses visited the fewest. Public spaces such as the cafeteria had the most staff visits per week, but the least mean hours spent per visit. Inpatient settings had significantly more HCW interactions per week than outpatient settings. CONCLUSIONS: HCW contact patterns and spatial movement demonstrate significant heterogeneity by occupation. Control strategies that address this diversity among health care workers may be more effective than “one-strategy-fits-all” HAI prevention and control programs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3093-x) contains supplementary material, which is available to authorized users.

negative: Epidemiology The common cold is the result of an upper respiratory tract infection causing an acute syndrome characterised by a combination of non-specific symptoms, including sore throat, cough, fever, rhinorrhoea, malaise, headache, and myalgia. Respiratory viruses, alone or in combination, are the most common cause. The course f illness can be complicated by bacterial agents, causing pharyngitis or sinusitis, but the are a rare cause of cold and flu-like illnesses (CFLIs). Our understanding of CFLI epidemiology has been enhanced by molecular detection methods, particularly polymerase chain reaction (PCR) testing. PCR has not only improved detection of previously known viruses, but within the last decade has resulted in the detection of many divergent novel respiratory virus species. Human rhinovirus (HRV) infections cause nearly all CFLIs and they can be responsible for asthma and chronic obstructive pulmonary disease exacerbations. HRVs are co-detected with other respiratory viruses in statistically significant patterns, with HRVs occurring in the lowest proportion of co-detections, compared to most other respiratory viruses. Some recently identified rhinoviruses may populate an entirely new putative HRV species; HRV C. Further work is required to confirm a causal role for these newly identified viruses in CFLIs. The burden of illness associated with CFLIs is poorly documented, but where data are available, the impact of CFLIs is considerable. Individual infections, although they do not commonly result in more severe respiratory tract illness, are associated with substantial direct and indirect resource use. The product of frequency and burden for CFLIs is likely to be greater in magnitude than for any other respiratory syndrome, but further work is required to document this. Our understanding of the viral causes of CLFIs, although incomplete, has improved in recent years. Documenting burden is also an important step in progress towards improved control and management of these illnesses.

negative: NCI’s Work to Advance Cancer Research while Responding to the COVID-19 Pandemic Abstract During the COVID-19 pandemic, the National Cancer Institute (NCI) is bringing to bear its considerable expertise and capabilities to understand, treat, and prevent the disease. While responding to the pandemic, NCI’s priority remains the advancement of cancer research. NCI has implemented many flexibilities for grantees and trainees.

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: Information Diffusion on Social Media During Natural Disasters Social media analytics has drawn new quantitative insights of human activity patterns. Many applications of social media analytics, from pandemic prediction to earthquake response, require an in-depth understanding of how these patterns change when human encounter unfamiliar conditions. In this paper, we select two earthquakes in China as the social context in Sina-Weibo (or Weibo for short), the largest Chinese microblog site. After proposing a formalized Weibo information flow model to represent the information spread on Weibo, we study the information spread from three main perspectives: individual characteristics, the types of social relationships between interactive participants, and the topology of real interaction networks. The quantitative analyses draw the following conclusions. First, the shadow of Dunbar’s number is evident in the “declared friends/followers” distributions, and the number of each participant’s friends/followers who also participated in the earthquake information dissemination show the typical power-law distribution, indicating a rich-gets-richer phenomenon. Second, an individual’s number of followers is the most critical factor in user influence. Strangers are very important forces for disseminating real-time news after an earthquake. Third, two types of real interaction networks share the scale-free and small-world property, but with a looser organizational structure. In addition, correlations between different influence groups indicate that when compared with other online social media, the discussion on Weibo is mainly dominated and influenced by verified users.

negative: The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated The novel coronavirus (2019-nCoV) is a recently emerged human pathogen that has spread widely since January 2020. Initially, the basic reproductive number, R0, was estimated to be 2.2 to 2.7. Here we provide a new estimate of this quantity. We collected extensive individual case reports and estimated key epidemiology parameters, including the incubation period. Integrating these estimates and high-resolution real-time human travel and infection data with mathematical models, we estimated that the number of infected individuals during early epidemic double every 2.4 days, and the R0 value is likely to be between 4.7 and 6.6. We further show that quarantine and contact tracing of symptomatic individuals alone may not be effective and early, strong control measures are needed to stop transmission of the virus.

negative: The Same Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) yet Different Outbreak Patterns and Public Health Impacts on the Far East Expert Opinion from the Rapid Response Team of the Republic of Korea A Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) outbreak, the largest outbreak outside the Middle East in 2012, occurred in the Republic of Korea and resulted in a large number of cases, with 186 infected people, including 38 deaths. A Rapid Response Team (RRT) was appointed after a request from the Korean government on June 8, 2015 calling for specialists to manage and control the MERS-CoV outbreak. This report presents the opinion of the RRT who worked to manage this healthcare-associated MERS-CoV outbreak in Korea.

negative: Reproducibility and reporting practices in COVID-19 preprint manuscripts The novel coronavirus, COVID-19, has sparked an outflow of scientific research seeking to understand the virus, its spread, and best practices in prevention and treatment. If this international research effort is going to be as swift and effective as possible, it will need to rely on a principle of open science. When researchers share data, code, and software and generally make their work as transparent as possible, it allows other researchers to verify and expand upon their work. Furthermore, it allows public officials to make informed decisions. In this study, we analyzed 535 preprint articles related to COVID-19 for eight transparency criteria and recorded study location and funding information. We found that individual researchers have lined up to help during this crisis, quickly tackling important public health questions, often without funding or support from outside organizations. However, most authors could improve their data sharing and scientific reporting practices. The contrast between the commitment of researchers to doing important research and their reporting practices reveals underlying weaknesses in reporting habits, but not necessarily their science.

negative: MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans with a case fatality rate of over 39%, and poses a considerable threat to public health. A lack of approved vaccine or drugs currently constitutes a roadblock in controlling disease outbreak and spread. In this study, we generated MERS-CoV VLPs using the baculovirus expression system. Electron microscopy and immunoelectron microscopy results demonstrate that MERS-CoV VLPs are structurally similar to the native virus. Rhesus macaques inoculated with MERS-CoV VLPs and Alum adjuvant induced virus-neutralizing antibodies titers up to 1:40 and induced specific IgG antibodies against the receptor binding domain (RBD), with endpoint titers reaching 1:1,280. MERS-CoV VLPs also elicited T-helper 1 cell (Th1)-mediated immunity, as measured by ELISpot. These data demonstrate that MERS-CoV VLPs have excellent immunogenicity in rhesus macaques, and represent a promising vaccine candidate.

negative: A few thoughts and evidence on the COViD-19 pandemic

negative: Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review INTRODUCTION: Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies. METHODS: We searched five general, three Chinese and four coronavirus disease (COVID-19)–specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments. RESULTS: We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps. CONCLUSION: While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.

negative: Super Refractory Status Epilepticus Earlier definitions of status epilepticus (SE) were based on the duration of seizures, but newer definitions rely more on a pragmatic staging based on treatment failures (Table 23.1). Refractory status epilepticus (RSE) is defined as SE that continues despite administration of both benzodiazepines and an appropriately dosed second-line antiseizure drug. Depending on the semiology of the seizures and comorbidities of the patient, this stage may be treated with further antiseizure drugs or anesthesia. When seizures recur upon weaning the anesthetic agent, typically after 24 h of seizure suppression, or in the rare cases where seizure control cannot be achieved with anesthesia, status epilepticus is considered to be super refractory (SRSE). The incidence of status epilepticus has been increasing, from 3.5 to 12.5/100,000 population between 1979 and 2010. During this time hospital mortality has not changed [1].

negative: A model for the spread of an epidemic from local to global: A case study of COVID-19 in India In this paper we propose an epidemiological model for the spread of COVID-19. The dynamics of the spread is based on four fundamental categories of people in a population: Tested and infected, Non-Tested but infected, Tested but not infected, and non-Tested and not infected. The model is based on two levels of dynamics of spread in the population: at local level and at the global level. The local level growth is described with data and parameters which include testing statistics for COVID-19, preventive measures such as nationwide lockdown, and the migration of people across neighboring locations. In the context of India, the local locations are considered as districts and migration or traffic flow across districts are defined by normalized edge weight of the metapopulation network of districts which are infected with COVID-19. Based on this local growth, state level predictions for number of people tested with COVID-19 positive are made. Further, considering the local locations as states, prediction is made for the country level. The values of the model parameters are determined using grid search and minimizing an error function while training the model with real data. The predictions are made based on the present statistics of testing, and certain linear and log-linear growth of testing at state and country level. Finally, it is shown that the spread can be contained if number of testing can be increased linearly or log-linearly by certain factors along with the preventive measures in near future. This is also necessary to prevent the sharp growth in the count of infected and to get rid of the second wave of pandemic.

negative: Super-factors associated with transmission of occupational COVID-2019 infection among healthcare staff in Wuhan , China BACKGROUND: Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM: To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS: A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS: A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3·23). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0·37). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5·64). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION: High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working.

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

negative: The threat of climate change to non-dengue-endemic countries: increasing risk of dengue transmission potential using climate and non-climate datasets BACKGROUND: Dengue is a major public health problem in the tropics and sub-tropics, but the disease is less known to non-dengue-endemic countries including in Northeast Asia. However, an unexpected dengue outbreak occurred in 2014 in Japan. Given that autochthonous (domestic) dengue cases had not been reported for the past 70 years in Japan, this outbreak was highly unusual and suggests that several environmental factors might have changed in a way that favors vector mosquitoes in the Northeast Asian region. METHODS: A Climate Risk Factor (CRF) index, as validated in previous work, was constructed using climate and non-climate factors. This CRF index was compared to the number of reported dengue cases in Tokyo, Japan where the outbreak was observed in 2014. In order to identify high-risk areas, the CRF index was further estimated at the 5 km by 5 km resolution and mapped for Japan and South Korea. RESULTS: The high-risk areas determined by the CRF index corresponded well to the provinces where a high number of autochthonous cases were reported during the outbreak in Japan. At the provincial-level, high-risk areas for dengue fever were the Eastern part of Tokyo and Kanakawa, the South-Eastern part of Saitama, and the North-Western part of Chiba. While a relatively small number of high-risk areas were identified in South Korea compared with Japan, the high-risk areas in South Korea include popular tourist destinations where international visitors have been increasing. CONCLUSION: The recent dengue outbreak in Japan may signal that the two adjacent non-dengue-endemic countries are also exposed to the risk of temporal and sporadic behavior of dengue fever. It is critical to understand potential high-risk areas for future outbreaks and to set up appropriate prevention activities at the governmental-level.

negative: Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2) Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness. We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases. These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging.

negative: The immune vulnerability landscape of the 2019 Novel Coronavirus, SARS-CoV-2 The outbreak of the 2019 Novel Coronavirus (SARS-CoV-2) rapidly spread from Wuhan, China to more than 150 countries, areas or territories, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of SARS-CoV-2, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development, is lacking. In this study, we investigated the potential of the SARS-CoV-2 viral proteins to induce class I and II MHC presentation and to form linear antibody epitopes. We created an online database to broadly share the predictions as a resource for the research community. Using this resource, we showed that genetic variations in SARS- CoV-2, though still few for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus. Importantly, we discovered evidence that SARS-CoV-2, along with related coronaviruses, used mutations to evade attack from the human immune system. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development and mechanistic research.

negative: Assessing functional propagation patterns in COVID-19 Among the many efforts done by the scientific community to help coping with the COVID-19 pandemic, one of the most important has been the creation of models to describe its propagation, as these are expected to guide the deployment of containment and health policies. These models are commonly based on exogenous information, as e.g. mobility data, whose limitedness always compromise the reliability of obtained results. In this contribution we propose a different approach, based on extracting relationships between the evolution of the disease in different regions through information theoretical metrics. In a way similar to what is commonly done in neuroscience, propagation is understood as information transfer, and the resulting propagation patterns are represented and studied as functional networks. By applying this methodology to the dynamics of COVID-19 in several countries and regions thereof, we were able to reconstruct static and time-varying propagation graphs. We further discuss the advantages, promises and open research questions associated with this functional approach.

negative: One world, one health: The novel coronavirus COVID-19 epidemic()

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: Airborne rhinovirus detection and effect of ultraviolet irradiation on detection by a semi-nested RT-PCR assay BACKGROUND: Rhinovirus, the most common cause of upper respiratory tract infections, has been implicated in asthma exacerbations and possibly asthma deaths. Although the method of transmission of rhinoviruses is disputed, several studies have demonstrated that aerosol transmission is a likely method of transmission among adults. As a first step in studies of possible airborne rhinovirus transmission, we developed methods to detect aerosolized rhinovirus by extending existing technology for detecting infectious agents in nasal specimens. METHODS: We aerosolized rhinovirus in a small aerosol chamber. Experiments were conducted with decreasing concentrations of rhinovirus. To determine the effect of UV irradiation on detection of rhinoviral aerosols, we also conducted experiments in which we exposed aerosols to a UV dose of 684 mJ/m(2). Aerosols were collected on Teflon filters and rhinovirus recovered in Qiagen AVL buffer using the Qiagen QIAamp Viral RNA Kit (Qiagen Corp., Valencia, California) followed by semi-nested RT-PCR and detection by gel electrophoresis. RESULTS: We obtained positive results from filter samples that had collected at least 1.3 TCID(50 )of aerosolized rhinovirus. Ultraviolet irradiation of airborne virus at doses much greater than those used in upper-room UV germicidal irradiation applications did not inhibit subsequent detection with the RT-PCR assay. CONCLUSION: The air sampling and extraction methodology developed in this study should be applicable to the detection of rhinovirus and other airborne viruses in the indoor air of offices and schools. This method, however, cannot distinguish UV inactivated virus from infectious viral particles.

negative: Trying Times and Trying Out Solutions: Intimate Partner Violence Screening and Support for Women Veterans During COVID-19 Initial reports indicate widespread increases in intimate partner violence (IPV) rates during the coronavirus disease 2019 (COVID-19) pandemic. Women veterans are at particular risk for experiencing IPV, and the COVID-19 pandemic and resulting stay-at-home orders may be exacerbating this risk. IPV screening and intervention are an integral part of the care provided to women veterans in the Veteran’s Health Administration (VHA). Current changes in healthcare delivery during COVID-19 may present challenges to the VHA’s standard methods of initiating IPV screening and intervention with women veterans. We discuss the potential challenges VHA healthcare providers may be encountering when conducting routine IPV screening during the COVID-19 pandemic and when providing resources and support to women veterans experiencing IPV. We describe solutions to these challenges, including existing efforts led by the VHA IPV Assistance Program (IPVAP) as well as additional potential solutions. New ideas and partnerships will be critical for helping the VHA continue to assist women veterans experiencing IPV as the COVID-19 pandemic evolves. Though our focus is on women veterans and the VHA, the challenges and solutions we discuss are likely applicable to other populations experiencing IPV and other health care systems screening for IPV.

negative: Novel coronavirus 2019, an emerging public health emergency

negative: The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak Abstract Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.

negative: Updated understanding of the outbreak of 2019 novel coronavirus (2019‐nCoV) in Wuhan, China To help health workers and the public recognize and deal with the 2019 novel coronavirus (2019‐nCoV) quickly, effectively, and calmly with an updated understanding. A comprehensive search from Chinese and worldwide official websites and announcements was performed between 1 December 2019 and 9:30 am 26 January 2020 (Beijing time). A latest summary of 2019‐nCoV and the current outbreak was drawn. Up to 24 pm, 25 January 2020, a total of 1975 cases of 2019‐nCoV infection were confirmed in mainland China with a total of 56 deaths having occurred. The latest mortality was approximately 2.84% with a total of 2684 cases still suspected. The China National Health Commission reported the details of the first 17 deaths up to 24 pm, 22 January 2020. The deaths included 13 males and 4 females. The median age of the people who died was 75 (range 48‐89) years. Fever (64.7%) and cough (52.9%) were the most common first symptoms among those who died. The median number of days from the occurence of the first symptom to death was 14.0 (range 6‐41) days, and it tended to be shorter among people aged 70 years or more (11.5 [range 6‐19] days) than those aged less than 70 years (20 [range 10‐41] days; P = .033). The 2019‐nCoV infection is spreading and its incidence is increasing nationwide. The first deaths occurred mostly in elderly people, among whom the disease might progress faster. The public should still be cautious in dealing with the virus and pay more attention to protecting the elderly people from the virus.

negative: On the probability of strain invasion in endemic settings: Accounting for individual heterogeneity and control in multi-strain dynamics Abstract Pathogen evolution is an imminent threat to global health that has warranted, and duly received, considerable attention within the medical, microbiological and modelling communities. Outbreaks of new pathogens are often ignited by the emergence and transmission of mutant variants descended from wild-type strains circulating in the community. In this work we investigate the stochastic dynamics of the emergence of a novel disease strain, introduced into a population in which it must compete with an existing endemic strain. In analogy with past work on single-strain epidemic outbreaks, we apply a branching process approximation to calculate the probability that the new strain becomes established. As expected, a critical determinant of the survival prospects of any invading strain is the magnitude of its reproduction number relative to that of the background endemic strain. Whilst in most circumstances this ratio must exceed unity in order for invasion to be viable, we show that differential control scenarios can lead to less-fit novel strains invading populations hosting a fitter endemic one. This analysis and the accompanying findings will inform our understanding of the mechanisms that have led to past instances of successful strain invasion, and provide valuable lessons for thwarting future drug-resistant strain incursions.

negative: A Novel Coronavirus (COVID-19) Outbreak A Call for Action

negative: Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis Background/Purpose Current studies on pediatric coronavirus disease 2019 (COVID-19) are rare. The clinical characteristics and spectrum are still unknown. Facing this unknown and emerging pathogen, we aimed to collect current evidence about COVID-19 in children. Methods We performed a systematic review in PubMed and Embase to find relevant case series. Because some reports were published in Chinese journals, the journals and publications of the Chinese Medical Association related to COVID-19 were completely reviewed. A random effects model was used to pool clinical data in the meta-analysis. Results Nine case series were included. In the pooled data, most of patients (75%) had a household contact history. The disease severity was mainly mild to moderate (98%). Only 2 children (2%) received intensive care. Fever occurred in 59% of the patients, while cough in 46%. Gastrointestinal symptoms (12%) were uncommon. There are 26% children are asymptomatic. The most common radiographic finding was ground glass opacities (48%). Currently, there is no evidence of vertical transmission to neonates born to mothers with COVID-19. Compared with the most relevant virus, SARS-CoV, SARS-CoV-2 causes less severe disease. Conclusion COVID-19 has distinct features in children. The disease severity is mild. Current diagnosis is based mainly on typical ground glass opacities on chest CT, epidemiological suspicion and contact tracing.

negative: Insights into Cross-species Evolution of Novel Human Coronavirus 2019-nCoV and Defining Immune Determinants for Vaccine Development Novel Coronavirus (nCoV) outbreak in the city of Wuhan, China during December 2019, has now spread to various countries across the globe triggering a heightened containment effort. This human pathogen is a member of betacoronavirus genus carrying 30 kilobase of single positive-sense RNA genome. Understanding the evolution, zoonotic transmission, and source of this novel virus would help accelerating containment and prevention efforts. The present study reported detailed analysis of 2019-nCoV genome evolution and potential candidate peptides for vaccine development. This nCoV genotype might have been evolved from a bat-CoV by accumulating non-synonymous mutations, indels, and recombination events. Structural proteins Spike (S), and Membrane (M) had extensive mutational changes, whereas Envelope (E) and Nucleocapsid (N) proteins were very conserved suggesting differential selection pressures exerted on 2019-nCoV during evolution. Interestingly, 2019-nCoV Spike protein contains a 39 nucleotide (5’-aAT GGT GTT GAA GGT TTT AAT TGT TAC TTT CCT TTA CAA Tca-3’) sequence insertion, which shares homology to fish genomic sequence of Myripristis murdjan, an abundant fish type in Indo-Pacific Ocean. Furthermore, we identified eight high binding affinity (HBA) CD4 T-cell epitopes in the S, E, M and N proteins, which can be commonly recognized by HLA-DR alleles of Asia and Asia-Pacific Region population. These immunodominant epitopes can be incorporated in universal subunit CoV vaccine. Diverse HLA types and variations in the epitope binding affinity may contribute to the wide range of immunopathological outcomes of circulating virus in humans. Our findings emphasize the requirement for continuous surveillance of CoV strains in live animal markets to better understand the viral adaptation to human host and to develop practical solutions to prevent the emergence of novel pathogenic CoV strains.

negative: COVID-19 in cardiac arrest and infection risk to rescuers: a systematic review Abstract Background There may be a risk of COVID-19 transmission to rescuers delivering treatment for cardiac arrest. The aim of this review was to identify the potential risk of transmission associated with key interventions (chest compressions, defibrillation, cardiopulmonary resuscitation) to inform international treatment recommendations. Methods We undertook a systematic review comprising three questions: 1) aerosol generation associated with key interventions; 2) risk of airborne infection transmission associated with key interventions; and 3) the effect of different personal protective equipment strategies. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the World Health Organisation COVID-19 database on 24th March 2020. Eligibility criteria were developed individually for each question. We assessed risk of bias for individual studies, and used the GRADE process to assess evidence certainty by outcome. Results We included eleven studies: two cohort studies, one case control study, five case reports, and three manikin randomised controlled trials. We did not find any direct evidence that chest compressions or defibrillation either are or are not associated with aerosol generation or transmission of infection. Data from manikin studies indicates that donning of personal protective equipment delays treatment delivery. Studies provided only indirect evidence, with no study describing patients with COVID-19. Evidence certainty was low or very low for all outcomes. Conclusion It is uncertain whether chest compressions or defibrillation cause aerosol generation or transmission of COVID-19 to rescuers. There is very limited evidence and a rapid need for further studies. Review registration: PROSPERO CRD42020175594

negative: School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2–4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.

negative: 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.

negative: 2,500-year Evolution of the Term Epidemic The term epidemic (from the Greek epi [on] plus demos [people]), first used by Homer, took its medical meaning when Hippocrates used it as the title of one of his famous treatises. At that time, epidemic was the name given to a collection of clinical syndromes, such as coughs or diarrheas, occurring and propagating in a given period at a given location. Over centuries, the form and meaning of the term have changed. Successive epidemics of plague in the Middle Ages contributed to the definition of an epidemic as the propagation of a single, well-defined disease. The meaning of the term continued to evolve in the 19th-century era of microbiology. Its most recent semantic evolution dates from the last quarter of the 20th century, and this evolution is likely to continue in the future.

negative: The impact of 2019 novel coronavirus on heart injury: A systemic review and Meta-analysis Abstract Background Evidence about COVID-19 on cardiac injury is inconsistent. Objectives We aimed to summarize available data on severity differences in acute cardiac injury and acute cardiac injury with mortality during the COVID-19 outbreak. Methods We performed a systematic literature search across Pubmed, Embase and pre-print from December 1, 2019 to March 27, 2020, to identify all observational studies that reported cardiac specific biomarkers (troponin, creatine kinase–MB fraction, myoglobin, or NT-proBNP) during COVID-19 infection. We extracted data on patient demographics, infection severity, comorbidity history, and biomarkers during COVID-19 infection. Where possible, data were pooled for meta-analysis with standard (SMD) or weighted (WMD) mean difference and corresponding 95% confidence intervals (CI). Results We included 4189 confirmed COVID-19 infected patients from 28 studies. More severe COVID-19 infection is associated with higher mean troponin (SMD 0.53, 95% CI 0.30 to 0.75, p < 0.001), with a similar trend for creatine kinase–MB, myoglobin, and NT-proBNP. Acute cardiac injury was more frequent in those with severe, compared to milder, disease (risk ratio 5.99, 3.04 to 11.80; p < 0.001). Meta regression suggested that cardiac injury biomarker differences of severity are related to history of hypertension (p = 0.030). Also COVID19-related cardiac injury is associated with higher mortality (summary risk ratio 3.85, 2.13 to 6.96; p < 0.001). hsTnI and NT-proBNP levels increased during the course of hospitalization only in non-survivors. Conclusion The severity of COVID-19 is associated with acute cardiac injury, and acute cardiac injury is associated with death. Cardiac injury biomarkers mainly increase in non-survivors. This highlights the need to effectively monitor heart health to prevent myocarditis in patients infected with COVID-19.

negative: A mathematical modelling approach in the spread of the novel 2019 coronavirus SARS-COV-2 (COVID-19) pandemic The novel 2019 coronavirus, SARS-CoV-2 (COVID-19), emerged towards the end of 2019 in the city of Wuhan in the province of Hubei in the People’s Republic of China, and it has spread to the entire world very fast and in a very short time. This study aimed to investigate the course of the pandemic by mathematical modelling based on the information that the time-dependent change (spreading) rate of the H number of individuals who have caught a contagious disease is proportional to the multiplication of the numbers of those who have caught the disease and those who have not. According to the results of the mathematical modelling in our study, in the case that sufficient precautions are not taken, or precautions are reduced, the course of the pandemic may show a very fast change in the negative direction. For this reason, every precaution, individual or social, will be significant in terms of the course of the COVID-19 pandemic.

negative: 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.

negative: Extended SIR prediction of the epidemics trend of COVID-19 in Italy and compared with Hunan, China Background: Coronavirus Disease 2019 (COVID19) is currently a global public health threat. Outside of China, Italy is one of the most suffering countries with the COVID19 epidemic. It is important to predict the epidemics trend of COVID19 epidemic in Italy to help develop public health strategies. Methods: We used time series data of COVID 19 from Jan 22,2020 to Mar 16,2020. An infectious disease dynamic extended susceptible infected removed (eSIR) model, which covers the effects of different intervention measures in dissimilar periods, was applied to estimate the epidemic trend in Italy. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credible interval (CI). Hunan, with similar total number of populations in Italy, was used as a comparative item. Results: In the eSIR model, we estimated that the basic reproductive number for COVID 19 was respectively 4.10 (95% CI: 2.15 to 6.77) in Italy and 3.15(95% CI: 1.71 to 5.21) in Hunan. There would be totally 30 086 infected cases (95%CI:7920-81 869) under the current country blockade and the endpoint would be Apr 25 (95%CI: Mar 30 to Aug 07) in Italy. If the country blockade is imposed 5 day later, the total number of infected cases would expand the infection scale 1.50 times. Conclusion: Italy's current strict measures can efficaciously prevent the further spread of COVID19 and should be maintained. Necessary strict public health measures be implemented as soon as possible in other European countries with a high number of COVID19 cases. The most effective strategy needs to be confirmed in further studies.

negative: Speculation is not evidence: antihypertensive therapy and COVID-19

negative: What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review Background: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps. Materials and Methods: We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV. Results: Dipeptidyl peptidase 4 (DPP4/CD26) was identified as the human receptor for MERS-CoV, and a variety of molecular and serological assays developed. Dromedary camels remain the only documented zoonotic source of human infection, but MERS-like CoVs have been detected in bat species globally, as well as in dromedary camels throughout the Middle East and Africa. However, despite evidence of camel-to-human MERS-CoV transmission and cases apparently related to camel contact, the source of many primary cases remains unknown. There have been sustained health care-associated human outbreaks in Saudi Arabia and South Korea, the latter originating from one traveler returning from the Middle East. Transmission mechanisms are poorly understood; for health care, this may include environmental contamination. Various potential therapeutics have been identified, but not yet evaluated in human clinical trials. At least one candidate vaccine has progressed to Phase I trials. Conclusions: There has been substantial MERS-CoV research since 2012, but significant knowledge gaps persist, especially in epidemiology and natural history of the infection. There have been few rigorous studies of baseline prevalence, transmission, and spectrum of disease. Terms such as “camel exposure” and the epidemiological relationships of cases should be clearly defined and standardized. We strongly recommend a shared and accessible registry or database. Coronaviruses will likely continue to emerge, arguing for a unified “One Health” approach.

negative: Hong Kong bears brunt of latest outbreak

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: 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.

negative: Virus emergentes y reemergentes: un nuevo reto para la salud mundial del milenio

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: An investigation of the questions posted on medical consultation websites. BACKGROUND Online medical consultation has recently become a more and more popular alternative venue for healthcare. It allows patients and caregivers to discuss their health problems and symptoms with qualified medical health professionals via the Internet. OBJECTIVE This study investigates the questions posted on an asynchronous online medical consultation website, Taiwan eDoctor. Five research themes are explored: (1) length of questions, (2) moment of seeking consultation, (3) strategies of communicating chief complaints, (4) purpose of seeking consultation and (5) identity disclosure. METHODS Data collection was conducted by randomly selecting 50 resolved consultation Q&As for each of 24 medical specialties, resulting in a total of 1200 entries in the primary data set. Data analysis was conducted qualitatively and quantitatively. RESULTS Average length of questions was 161.21 words. Online medical consultation was sought when healthy, healthy but not robust, when suspicious of illness, when diagnosed as ill and during treatment/recovery. In communicating chief complaints, consultation seekers were engaged in contextual, focal or emotional communication styles. Nine distinct purposes to seek online consultation were identified and can be broadly interpreted as intellectual, social and emotional. The finding also suggests that more than two-third of questions were asked for by the patients themselves. CONCLUSION Through content analysis of questions posted on an online medical consultation website, this study characterises communication patterns during the health information seeking process. These findings can help guide the design of more effective patient-centred online medical consultation services.

negative: SARS-CoV-2 infection in children: Transmission dynamics and clinical characteristics

negative: Influenza estacional en adultos y niños—Diagnóstico, tratamiento, quimioprofilaxis y control de brotes institucionales: Guías de práctica clínica de la Sociedad de Enfermedades Infecciosas de Estados Unidos de América Un Grupo de Expertos de la Sociedad de Enfermedades Infecciosas de los Estados Unidos de América elaboró las guias para el tratamiento de personas infectadas por el virus de la influenza. Estas guias basadas en datos y pruebas cientificas comprenden el diagnóstico, el tratamiento y la quimioprofilaxis con medicamentos antivirales, además de temas relacionados con el control de brotes de influenza estacional (interpandémicas) en ámbitos institucionales. Están destinadas a los médicos de todas las especialidades a cargo de la atención directa de pacientes porque los médicos generales que atienden una gran variedad de casos son los que se enfrentan con la influenza, frecuente en el ámbito comunitario durante la temporada de influenza.

negative: Comparative genomics provides an operational classification system and reveals early emergence and biased spatio-temporal distribution of SARS-CoV-2 Effective systems for the analysis of molecular data are of fundamental importance for real-time monitoring of the spread of infectious diseases and the study of pathogen evolution. While the Nextstrain and GISAID portals offer widely used systems for the classification of SARS-CoV-2 genomes, both present relevant limitations. Here we propose a highly reproducible method for the systematic classification of SARS-CoV-2 viral types. To demonstrate the validity of our approach, we conduct an extensive comparative genomic analysis of more than 20,000 SARS-CoV-2 genomes. Our classification system delineates 12 clusters and 4 super-clusters in SARS-CoV-2, with a highly biased spatio-temporal distribution worldwide, and provides important observations concerning the evolutionary processes associated with the emergence of novel viral types. Based on the estimates of SARS-CoV-2 evolutionary rate and genetic distances of genomes of the early pandemic phase, we infer that SARS-CoV-2 could have been circulating in humans since August-November 2019. The observed pattern of genomic variability is remarkably similar between all clusters and super-clusters, being UTRs and the s2m element, a highly conserved secondary structure element, the most variable genomic regions. While several polymorphic sites that are specific to one or more clusters were predicted to be under positive or negative selection, overall, our analyses also suggest that the emergence of novel genome types is unlikely to be driven by widespread convergent evolution and independent fixation of advantageous substitutions. While, in the absence of rigorous experimental validation, several questions concerning the evolutionary processes and the phenotypic characteristics (increased/decreased virulence) remain open, we believe that the approach outlined in this study can be of relevance for the tracking and functional characterization of different types of SARS-CoV-2 genomes.

negative: Molecular characterization of a novel cryptic virus infecting pigeonpea plants A new member of the genus Deltapartitivirus was identified containing three dsRNAs with an estimated size of 1.71, 1.49 and 1.43 kb. The dsRNAs were extracted from symptomless pigeonpea [Cajanus cajan (L.) Millspaugh] plants cv. Erra Kandulu. This new virus with 4.64 kb genome was tentatively named Arhar cryptic virus-1 (ArCV-1). The genomic RNAs were amplified and characterized by sequence independent single primer amplification. The dsRNAs shared a highly conserved 16 nt 5’ non-coding region (5’-GATAATGATCCAAGGA-3’). The largest dsRNA (dsRNA-1) was identified as the viral RNA dependent RNA polymerase (replicase), predicted to encode a putative 55.34 kDa protein (P1). The two other smaller dsRNAs (dsRNA-2 and dsRNA-3) predicted to encode for putative capsid proteins of 38.50kDa (P2) and 38.51kDa (P3), respectively. Phylogenetic analysis indicated that ArCV-1 formed a clade together with Fragaria chiloensis cryptic virus, Rosa multiflora cryptic virus and Rose cryptic virus-1, indicating that ArCV-1 could be a new member of the genus Deltapartitivirus. ArCV-1 3D(pol) structure revealed several interesting features. The 3D(pol) in its full-length shares structural similarities with members of the family Caliciviridaeand family Picornaviridae. In addition, fourth dsRNA molecule (dsRNA-2A), not related to ArCV-1 genome, was found in the same plant tissue. The dsRNA-2A (1.6 kb) encodes a protein (P4), with a predicted size of 44.5 kDa. P4 shares similarity with coat protein genes of several cryptic viruses, in particular the bipartite cryptic viruses including Raphanus sativus cryptic virus-3. This is the first report of occurrence of a cryptic virus in pigeonpea plants.

negative: Novel corona virus disease (COVID-19) in pregnancy: What clinical recommendations to follow?

negative: 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.

negative: Evidence-Based Process for Prioritizing Positive Behaviors for Promotion: Zika Prevention in Latin America and the Caribbean and Applicability to Future Health Emergency Responses Since the 2015 Zika outbreak in Latin America and the Caribbean, a plethora of behavior change messages have been promoted to reduce Zika transmission. One year after the United States Agency for International Development (USAID) initiated its Zika response, more than 30 variants of preventive behaviors were being promoted. This situation challenged social and behavior change (SBC) programming efforts that require a coordinated response and agreed upon set of focus behaviors to be effective. To support USAID implementing partners in harmonizing prevention efforts to reduce Zika infection, we developed an evidence-based process to identify behaviors with the highest potential to reduce Zika infection and transmission. We compiled a full list of behaviors and selected the most promising for a full evidence review. The review included systematic keyword searches on Google Scholar, extraction of all relevant published articles on Aedes-borne diseases between 2012 and 2018, review of seminal papers, and review of gray literature. We examined articles to determine each behavior's potential effectiveness in preventing Zika transmission or reducing the Aedes aegypti population. We also developed assessment criteria to delineate the ease with which the target population could adopt each behavior, including: (1) required frequency; (2) feasibility of the behavior; and (3) accessibility and cost of the necessary materials in the setting. These behaviors were refined through a consensus-building process with USAID's Zika implementing partners, considering contextual factors. The resulting 7 evidence-based preventive behaviors have high potential to strengthen SBC programming's impact in USAID's Zika response: (1) apply mosquito repellent, (2) use condoms during pregnancy, (3) remove standing water, (4) cover water storage containers, (5) clean/remove mosquito eggs from water containers, (6) seek antenatal care, and (7) seek family planning counseling. This case study documents a flexible process that can be adapted to inform the prioritization of behaviors when there is limited evidence available, as during many emergency responses.

negative: Human Coronaviruses: A Review of Virus–Host Interactions Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.

negative: 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: An analysis of spatiotemporal pattern for COIVD-19 in China based on space-time cube This study seeks to examine and analyze the spatial and temporal patterns of 2019 novel coronavirus disease (COVID-19) outbreaks and identify the spatiotemporal distribution characteristics and changing trends of cases. Hence, local outlier analysis and emerging spatiotemporal hot spot analysis were performed to analyze the spatiotemporal clustering pattern and cold/hot spot trends of COVID-19 cases based on space-time cube during the period from 23 January 2020 to 24 February 2020. The main findings are as follows: (1) The outbreak had spread rapidly throughout the country within a short time and the current totality incidence rate has decreased. (2) The spatiotemporal distribution of cases was uneven. In terms of the spatiotemporal clustering pattern, Wuhan and Shiyan city were the center as both cities had high-high clustering pattern with a surrounding unstable multiple-type pattern in partial areas of Henan, Anhui, Jiangxi, and Hunan provinces, and Chongqing city. Those regions are continuously in the hot spot on the spatiotemporal tendency. (3) The spatiotemporal analysis technology based on the space-time cube can analyze comprehensively the spatiotemporal pattern of epidemiological data and produce a visual output of the consequences, which can reflect intuitively the distribution and trend of data in space-time. Therefore, the Chinese government should strengthen the prevention and control efforts in a targeted manner to cope with a highly changeable situation.

negative: Coronavirus derived expression systems Abstract Both helper dependent expression systems, based on two components, and single genomes constructed by targeted recombination, or by using infectious cDNA clones, have been developed. The sequences that regulate transcription have been characterized mainly using helper dependent expression systems and it will now be possible to validate them using single genomes. The genome of coronaviruses has been engineered by modification of the infectious cDNA leading to an efficient (>20 μg ml−1) and stable (>20 passages) expression of the foreign gene. The possibility of engineering the tissue and species tropism to target expression to different organs and animal species, including humans, increases the potential of coronaviruses as vectors. Thus, coronaviruses are promising virus vectors for vaccine development and, possibly, for gene therapy.

negative: 8 INFECTIOUS DISEASES Publisher Summary The emergence of new pathogens, or the concern about bioterrorism, has brought an added urgency to the development of more efficient and rapid methods to detect pathogens and predict their potential virulence. Till date, DNA testing in microbiology has been directed predominantly to the detection of organisms that are difficult to culture in vitro, or for various reasons the growth is unlikely. DNA analysis can be used successfully in infections in which there is a mix of pathogens. Apart from the straightforward diagnostic applications, DNA microbiological testing has been used to detect antimicrobial resistance or toxigenic forms of E. coli. More recently, the availability of DNA technology to quantitate HCV and HIV has been useful in planning and monitoring treatment. The pathogenesis of many infections, particularly viral ones, can also be realized from experimental strategies based on light and electron microscopy, cell culture and immunoassay. The advantages that are provided by DNA techniques include the ability to detect latent (non-replicating) viruses and to localize their genomes to nuclear or cytoplasmic regions within cells. Nucleic acid probe techniques (NAT) can also be manipulated to enable a broad spectrum of serotypes to be detectable. This is particularly valuable in those emerging infections where the underlying serotypes are unknown.

negative: Emerging Influenza and Psychosis: An Important Story in Psychological Medicine

negative: Viral Pneumonias Other Than Cytomegalovirus in Transplant Recipients Community-acquired respiratory viruses (CARVs) are frequent causes of upper and lower respiratory tract infections in tranplant recipients. In most series, respiratory syncytial virus and parainfluenza are the most common CARVs, followed by influenza and adenovirus. Significant morbidity and mortality are associated with these infections, particularly when they progress to pneumonia or when they are associated with bacterial or fungal coinfections. Outcomes are also poor with adenovirus, frequently reflecting disseminated infection. Efforts to prevent morbidity and mortality from CARV infection should focus on prevention, because treatment options are limited with inconclusive data to support their efficacy.

negative: Common Viral Pneumonia Common respiratory viruses are now recognised as true opportunistic respiratory pathogens in patients with haematological malignancies. The epidemiology of these viruses has not been extensively studied in immunocompromised hosts, but is probably closely related to viral activity in immunocompetent hosts, who constitute the virus reservoir for immunocompromised patients. In these patients, common respiratory viruses may cause severe infections with higher rates of progression to pneumonia and mortality compared to immunocompetent individuals. Prolonged high-titre viral shedding is common in patients with haematological malignancies and may enhance not only viral transmission, but also the selection of resistant strains. Influenza and respiratory syncytial virus (RSV) infections have been particularly well studied. They are associated with pneumonia rates of about one-third for influenza and 30–40% for RSV. Both viruses are responsible for mortality rates ranging from 15% to 30%. The exact mechanisms of pneumonia related to these viruses remains unknown, but bacterial and fungal co-infections are frequent and must be carefully investigated. Parainfluenza viruses (PIV) and RSV have also been linked to late airflow obstruction in haematopoietic stem cell transplant recipients. Neuraminidase inhibitor therapy has been suggested for influenza, ribavirin for RSV, and cidofovir for adenovirus infections. However, there is no evidence supporting the use of these drugs, and randomised controlled trials are urgently needed to better define the optimal management of common viral pneumonia in patients with haematological malignancies. The absence of proven effective treatments highlights the critical importance of prevention. Viral transmission may be interrupted by contact isolation with droplet precautions for infected patients and by having patients and health care workers with suspected infection, and their relatives, refrain from visits and work. Immunisation remains the cornerstone of influenza prevention and is recommended for patients with haematological malignancies, their relatives, and health care workers.

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: Transmission potential of COVID-19 in South Korea Since the first identified individual of 2019 novel coronavirus (COVID-19) infection on Jan 20, 2020 in South Korea, the number of confirmed cases rapidly increased. As of Feb 26, 2020, 1,261 cases of COVID-19 including 12 deaths were confirmed in South Korea. Using the incidence data of COVID-19, we estimate the reproduction number at 1.5 (95% CI: 1.4-1.6), which indicates sustained transmission and support the implementation of social distancing measures to rapidly control the outbreak.

negative: Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study Since SARS-CoV-2 infection was first identified in December 2019, it spread rapidly and a global pandemic of COVID-19 has occurred. ACE2, the receptor for entry into the target cells by SARS-CoV-2, was found to abundantly express in testes, including spermatogonia, Leydig and Sertoli cells. However, there is no clinical evidence about whether SARS-CoV-2 infection can affect male gonadal function so far. In this study, we compared the sex-related hormones between 81 reproductive-aged men with SARS-CoV-2 infection and 100 age-matched healthy men, and found that serum luteinizing hormone (LH) was significantly increased, but the ratio of testosterone (T) to LH and the ratio of follicle stimulating hormone (FSH) to LH were dramatically decreased in males with COVID-19. Besides, multivariable regression analysis indicated that c-reactive protein (CRP) level was significantly associated with serum T:LH ratio in COVID-19 patients. This study provides the first direct evidence about the influence of medical condition of COVID-19 on male sex hormones, alerting more attention to gonadal function evaluation among patients recovered from SARS-CoV-2 infection, especially the reproductive-aged men.

negative: Mining Text Patterns over Fake and Real Tweets With the exponential growth of users and user-generated content present on online social networks, fake news and its detection have become a major problem. Through these, smear campaigns can be generated, aimed for example at trying to change the political orientation of some people. Twitter has become one of the main spreaders of fake news in the network. Therefore, in this paper, we present a solution based on Text Mining that tries to find which text patterns are related to tweets that refer to fake news and which patterns in the tweets are related to true news. To test and validate the results, the system faces a pre-labelled dataset of fake and real tweets during the U.S. presidential election in 2016. In terms of results interesting patterns are obtained that relate the size and subtle changes of the real news to create fake news. Finally, different ways to visualize the results are provided.

negative: Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence BACKGROUND: Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19. METHODS: Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig. RESULTS: 89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19. CONCLUSION: The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.

negative: Disease Outbreaks: Critical Biological Factors and Control Strategies Disease outbreaks remain a major threat to human health and welfare especially in urban areas in both developed and developing countries. A large body of theoretical work has been devoted to modeling disease emergence, and critical factors that predict outbreak occurrence and severity have been proposed. In this chapter, we focus on biological factors that underlie both theoretical models and urban planning. We describe the SARS 2002–2003 pandemic as a case study of epidemic control of a human infectious disease. We then describe theoretical analyses of disease dynamics and control strategies. An important conclusion is that epidemic control will be strongly dependent on particular aspects of pathogen biology including host breadth, virulence, incubation time, and/or mutation rate. The probability, and potential cost, of future outbreaks, may be high and lessons from both past cases and theoretical work should inform urban design and policy. Interdisciplinary collaboration in planning, swiftness of information dissemination and response, and willingness to forgo personal liberties during a crisis may be key factors in resilience to infectious disease outbreaks.

negative: Novel coronavirus infection and pregnancy

negative: COVID-19, SARS and MERS: are they closely related? Abstract Background The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. Aims To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. Sources The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. Content COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0–2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7–1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. Implications There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.

negative: Investigating the cases of novel coronavirus disease (COVID-19) in China using dynamic statistical techniques The initial investigation by local hospital attributed the outbreak of the novel coronavirus disease (COVID-19) to pneumonia with unknown cause that appeared like the 2003 severe acute respiratory syndrome (SARS). The World Health Organization declared COVID-19 as public health emergency after it spread outside China to several countries. Thus, an assessment of the novel coronavirus disease (COVID-19) with novel estimation approaches is essential to the global debate. This study is the first to develop both time series and panel data models to construct conceptual tools that examine the nexus between death from COVID-19 and confirmed cases. We collected daily data on four health indicators namely deaths, confirmed cases, suspected cases, and recovered cases across 31 Provinces/States in China. Due to the complexities of the COVID-19, we investigated the unobserved factors including environmental exposures accounting for the spread of the disease through human-to-human transmission. We used estimation methods capable of controlling for cross-sectional dependence, endogeneity, and unobserved heterogeneity. We predicted the impulse-response between confirmed cases of COVID-19 and COVID-19-attributable deaths. Our study revealed that the effect of confirmed cases on the novel coronavirus attributable deaths is heterogeneous across Provinces/States in China. We found a linear relationship between COVID-19 attributable deaths and confirmed cases whereas a nonlinear relationship was confirmed for the nexus between recovery cases and confirmed cases. The empirical evidence revealed that an increase in confirmed cases by 1% increases coronavirus attributable deaths by ~0.10%–~1.71% (95% CI). Our empirical results confirmed the presence of unobserved heterogeneity and common factors that facilitates the novel coronavirus attributable deaths caused by increased levels of confirmed cases. Yet, the role of such a medium that facilitates the transmission of COVID-19 remains unclear. We highlight safety precaution and preventive measures to circumvent the human-to-human transmission.

negative: Computed tomography manifestations in super early stage 2019 novel coronavirus pneumonia. BACKGROUND The recent outbreak of pneumonia cases in Wuhan, PR China, was caused by a novel beta coronavirus, the 2019 novel coronavirus (COVID-19). PURPOSE To summarize chest computed tomography (CT) manifestations of the early stage of COVID-19 infection and provide a piece of reliable imaging evidence for initial screening and diagnosis. MATERIAL AND METHODS From 10 January 2020 to 10 February 2020, we continuously observed chest CT imaging of 14 patients with clinically suspected new coronavirus infection in the two weeks after onset of symptoms. Ground-glass opacity (GGO), consolidation, reticular pattern, and ground-glass mimic nodules in each patient's chest CT image were recorded. RESULTS We enrolled 14 patients, of which nine patients had the infection confirmed by reverse transcription polymerase chain reaction (RT-PCR). Five patients were highly suspected of infection. All cases had epidemiological evidence. GGO was a dominant imaging manifestation in the initial days of infection. GGO performance accounts for 40% in 1- 2 days, 90% in 3- 6 days, and 85% in 7- 10 days. With disease progression, consolidation appeared on follow-up CT. Consolidation performance accounts for 0% in 1- 2 days, 40% in 3- 6 days, and 71% in 7- 10 days. The lesions are mostly near the pleura. The number of lesions and the extent of the lesions increased as the disease progressed. CONCLUSION Patients with novel coronavirus pneumonia have characteristic CT features in the initial stage of infection, which can be used as an essential supplement for nucleic acid examination.

negative: Coronavirus Disease 2019 (COVID-19) and pregnancy: what obstetricians need to know Coronavirus disease 2019 is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, in December 2019. Limited data are available about coronavirus disease 2019 during pregnancy; however, information on illnesses associated with other highly pathogenic coronaviruses (ie, severe acute respiratory syndrome and the Middle East respiratory syndrome) might provide insights into coronavirus disease 2019’s effects during pregnancy. Coronaviruses cause illness ranging in severity from the common cold to severe respiratory illness and death. Currently the primary epidemiologic risk factors for coronavirus disease 2019 include travel from mainland China (especially Hubei Province) or close contact with infected individuals within 14 days of symptom onset. Data suggest an incubation period of ∼5 days (range, 2–14 days). Average age of hospitalized patients has been 49–56 years, with a third to half with an underlying illness. Children have been rarely reported. Men were more frequent among hospitalized cases (54–73%). Frequent manifestations include fever, cough, myalgia, headache, and diarrhea. Abnormal testing includes abnormalities on chest radiographic imaging, lymphopenia, leukopenia, and thrombocytopenia. Initial reports suggest that acute respiratory distress syndrome develops in 17–29% of hospitalized patients. Overall case fatality rate appears to be ∼1%; however, early data may overestimate this rate. In 2 reports describing 18 pregnancies with coronavirus disease 2019, all were infected in the third trimester, and clinical findings were similar to those in nonpregnant adults. Fetal distress and preterm delivery were seen in some cases. All but 2 pregnancies were cesarean deliveries and no evidence of in utero transmission was seen. Data on severe acute respiratory syndrome and Middle East respiratory syndrome in pregnancy are sparse. For severe acute respiratory syndrome, the largest series of 12 pregnancies had a case-fatality rate of 25%. Complications included acute respiratory distress syndrome in 4, disseminated intravascular coagulopathy in 3, renal failure in 3, secondary bacterial pneumonia in 2, and sepsis in 2 patients. Mechanical ventilation was 3 times more likely among pregnant compared with nonpregnant women. Among 7 first-trimester infections, 4 ended in spontaneous abortion. Four of 5 women with severe acute respiratory syndrome after 24 weeks’ gestation delivered preterm. For Middle East respiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contact investigation; 3 patients (23%) died. Two pregnancies ended in fetal demise and 2 were born preterm. No evidence of in utero transmission was seen in severe acute respiratory syndrome or Middle East respiratory syndrome. Currently no coronavirus-specific treatments have been approved by the US Food and Drug Administration. Because coronavirus disease 2019 might increase the risk for pregnancy complications, management should optimally be in a health care facility with close maternal and fetal monitoring. Principles of management of coronavirus disease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. Information on coronavirus disease 2019 is increasing rapidly. Clinicians should continue to follow the Centers for Disease Control and Prevention website to stay up to date with the latest information (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html).

negative: Anosmia and ageusia are emerging as symptoms in patients with COVID-19: What does the current evidence say? There have been several reports noting anosmia and ageusia as possible symptoms of COVID-19. This is of particular interest in oncology since patients receiving some cancer treatments such as chemotherapy or immune therapy often experience similar symptoms as side-effects. The purpose of this report was to summarise the evidence on the existence of anosmia and ageusia an emerging COVID-19 symptoms in order to better inform both oncology patients and clinicians. Currently, there is no published evidence or case reports noting anosmia or ageusia as symptoms of COVID-19. Nevertheless, experts in rhinology have suggested that the onset of such symptoms could either act as a trigger for testing for the disease where possible, or could be a new criterion to self-isolate. Whilst more data is currently needed to strengthen our knowledge of the symptoms of COVID-19, oncology patients who are concerned about anosmia or ageusia in the context of their systemic anti-cancer therapy should contact their acute oncology support line for advice.

negative: The epidemiology of the outbreak of severe acute respiratory syndrome (SARS) in Hong Kong--what we do know and what we don't. Severe acute respiratory syndrome (SARS) struck Hong Kong bitterly in the spring of 2003, infecting 1755 persons and claiming nearly 300 lives. The epidemic was introduced by travellers from southern China, where the disease had originated. It started in late February and lasted until early June. Two notable 'super-spreading' events were reported, one inside a teaching hospital and the other in a private housing estate. Other than in the super-spreading events, the infectivity in the community appeared to be low, and there were few, if any, asymptomatic or subclinical infections. Health-care workers were at particular risk and accounted for 22 % of all probable cases. The main modes of transmission were through droplet spread and close/direct contacts, but situations conducive to aerosol generation appeared to be associated with higher risk. Our review suggests that there are still many unknown factors concerning the mode of transmission and environmental risk that need to be clarified.

negative: Managing Cancer Care during the COVID-19 Pandemic and Beyond Abstract COVID-19 pandemic has posed insurmountable challenges to health care systems globally. Cancer therapy is complex, and outcomes are centered on timing. Many oncology societies and health ministries have issued guidelines for cancer care to enable oncologists and patients navigate the crisis. Lessons learned should inform care models for future pandemics.

negative: Bootstrap Bias Corrected Cross Validation Applied to Super Learning Super learner algorithm can be applied to combine results of multiple base learners to improve quality of predictions. The default method for verification of super learner results is by nested cross validation; however, this technique is very expensive computationally. It has been proposed by Tsamardinos et al., that nested cross validation can be replaced by resampling for tuning hyper-parameters of the learning algorithms. The main contribution of this study is to apply this idea to verification of super learner. We compare the new method with other verification methods, including nested cross validation. Tests were performed on artificial data sets of diverse size and on seven real, biomedical data sets. The resampling method, called Bootstrap Bias Correction, proved to be a reasonably precise and very cost-efficient alternative for nested cross validation.

negative: A Review of Coronavirus Disease-2019 (COVID-19) There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

negative: On the probability of strain invasion in endemic settings: accounting for individual heterogeneity and control in multi-strain dynamics The rise of antimicrobial drug resistance is an imminent threat to global health that has warranted, and duly received, considerable attention within the medical, microbiological and modelling communities. Outbreaks of drug-resistant pathogens are ignited by the emergence and transmission of mutant variants descended from wild-type strains circulating in the community. In this work we investigate the stochastic dynamics of the emergence of a novel disease strain, introduced into a population in which it must compete with an existing endemic strain. In analogy with past work on single-strain epidemic outbreaks, we apply a branching process approximation to calculate the probability that the new strain becomes established. As expected, a critical determinant of the survival prospects of any invading strain is the magnitude of its reproduction number relative to that of the background endemic strain. Whilst in most circumstances this ratio must exceed unity in order for invasion to be viable, we show that differential control scenarios can lead to less-fit novel strains invading populations hosting a fitter endemic one. This analysis and the accompanying findings will inform our understanding of the mechanisms that have led to past instances of successful strain invasion, and provide valuable lessons for thwarting future drug-resistant strain incursions.

negative: How to obtain evidence of vertical transmission in viral infected pregnant women: Reflection on COVID-19 epidemic/ 中华围产医学杂志 During the COVID-19 epidemic, there have been many misconceptions concerning vertical transmission between the mother and fetus/baby, which has caused much discussion and controversy. However, there is no strong evidence to indicate that this novel coronavirus could be vertically transmitted from infected mothers to their fetuses/infants. Several easily confused concepts are clarified in this paper, including vertical transmission, intrauterine transmission, mother-to-infant transmission, intrapartum or postpartum transmission. Well-designed protocols and a disciplined research team are essential for both basic and clinical research, in order to contribute to obtaining more scientific evidence for better understanding of the characteristics of this novel coronavirus. Proper handling and disposal of the body fluids and tissue are critical for safety. We highlight the significant value of relevant research, and suggest future research directions, such as investigating the impact of COVID-19 in different trimesters. Furthermore, China has the most experience of treating pregnant women exposed to the COVID-19 virus, and it would be a great service to the rest of the world, for all centers in China to collaborate to report this collective experience.

negative: Brain on FIRES: Super Refractory Seizure in a 7 yr Old Boy We present a 7 yr old boy afflicted with super-refractory seizure that responded poorly to antiepileptic drugs and sustained a long course of hospitalization and complications of high doses of medications as well as longstanding stay in hospital. The differential diagnoses were, fever-induced refractory epileptic encephalopathy (FIRES), and infectious and autoimmune encephalitis. However, work-ups had not revealed any evidence of any specific diagnosis, so we assumed that he was afflicted by viral infectious encephalitis as he had, fever, vomiting, and prodromal symptoms of infectious (most probably viral) disease prior to onset of the seizure attacks.

negative: Children are not COVID-19 super spreaders: time to go back to school