query: what is the origin of COVID-19

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

positive: 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.

positive: 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.

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

positive: Evidence for zoonotic origins of Middle East respiratory syndrome coronavirus Middle East respiratory syndrome (MERS) is an emerging infectious disease, caused by Middle East respiratory syndrome coronavirus (MERS-CoV) and is considered to be a zoonosis. However, the natural reservoirs of MERS-CoV remain obscure, with bats and camels as the most suspected sources. In this article, we review the evidence supporting a bat/camel origin of human MERS-CoV infection and current knowledge on the modes of camel-to-human transmission of MERS-CoV.

positive: Deadly virus effortlessly hops species Genetic engineering helps reveal origin of deadly 'flu

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

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

positive: Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans RNA viruses are proficient at switching to novel host species due to their fast mutation rates. Implicit in this assumption is the need to evolve adaptations in the new host species to exploit their cells efficiently. However, SARS-CoV-2 has required no significant adaptation to humans since the pandemic began, with no observed selective sweeps to date. Here we contrast the role of positive selection and recombination in the Sarbecoviruses in horseshoe bats to SARS-CoV-2 evolution in humans. While methods can detect some evidence for positive selection in SARS-CoV-2, we demonstrate these are mostly due to recombination and sequencing artefacts. Purifying selection is also substantially weaker in SARS-CoV-2 than in the related bat Sarbecoviruses. In comparison, our results show evidence for positive, specifically episodic selection, acting on the bat virus lineage SARS-CoV-2 emerged from. This signature of selection can also be observed among synonymous substitutions, for example, linked to ancestral CpG depletion on this bat lineage. We show the bat virus RmYN02 has recombinant CpG content in Spike pointing to coinfection and evolution in bats without involvement of other species. Our results suggest the non-human progenitor of SARS-CoV-2 was capable of human-human transmission as a consequence of its natural evolution in bats.

positive: Emerging infectious diseases The spectrum of human pathogens and the infectious diseases they cause is continuously changing through evolution and changes in the way human populations interact with their environment and each other. New human pathogens most often emerge from an animal reservoir, emphasizing the central role that non-human reservoirs play in human infectious diseases. Pathogens may also re-emerge with new characteristics, such as multidrug-resistance, or in different places, such as West Nile virus in the USA in 1999, to cause new epidemics. Most human pathogens have a history of evolution in which they first emerge and cause epidemics, become unstably adapted, re-emerge periodically, and eventually become endemic with the potential for future outbreaks.

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

positive: Investigation of three clusters of COVID-19 in Singapore: implications for surveillance and response measures BACKGROUND: Three clusters of coronavirus disease 2019 (COVID-19) linked to a tour group from China, a company conference, and a church were identified in Singapore in February, 2020. METHODS: We gathered epidemiological and clinical data from individuals with confirmed COVID-19, via interviews and inpatient medical records, and we did field investigations to assess interactions and possible modes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Open source reports were obtained for overseas cases. We reported the median (IQR) incubation period of SARS-CoV-2. FINDINGS: As of Feb 15, 2020, 36 cases of COVID-19 were linked epidemiologically to the first three clusters of circumscribed local transmission in Singapore. 425 close contacts were quarantined. Direct or prolonged close contact was reported among affected individuals, although indirect transmission (eg, via fomites and shared food) could not be excluded. The median incubation period of SARS-CoV-2 was 4 days (IQR 3–6). The serial interval between transmission pairs ranged between 3 days and 8 days. INTERPRETATION: SARS-CoV-2 is transmissible in community settings, and local clusters of COVID-19 are expected in countries with high travel volume from China before the lockdown of Wuhan and institution of travel restrictions. Enhanced surveillance and contact tracing is essential to minimise the risk of widespread transmission in the community. FUNDING: None.

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

positive: 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.

positive: 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.

positive: Intraspecies diversity of SARS-like coronaviruses in Rhinolophus sinicus and its implications for the origin of SARS coronaviruses in humans. The Chinese rufous horseshoe bat (Rhinolophus sinicus) has been suggested to carry the direct ancestor of severe acute respiratory syndrome (SARS) coronavirus (SCoV), and the diversity of SARS-like CoVs (SLCoV) within this Rhinolophus species is therefore worth investigating. Here, we demonstrate the remarkable diversity of SLCoVs in R. sinicus and identify a strain with the same pattern of phylogenetic incongruence (i.e. an indication of recombination) as reported previously in another SLCoV strain. Moreover, this strain possesses a distinctive 579 nt deletion in the nsp3 region that was also found in a human SCoV from the late-phase epidemic. Phylogenetic analysis of the Orf1 region suggested that the human SCoVs are phylogenetically closer to SLCoVs in R. sinicus than to SLCoVs in other Rhinolophus species. These findings reveal a closer evolutionary linkage between SCoV in humans and SLCoVs in R. sinicus, defining the scope of surveillance to search for the direct ancestor of human SCoVs.

positive: Lessons from a rapid systematic review of early SARS-CoV-2 serosurveys Background. As the world grapples with the COVID-19 pandemic, there is increasing global interest in the role of serological testing for population monitoring and to inform public policy. However, limitations in serological study designs and test standards raise concerns about the validity of seroprevalence estimates and their utility in decision-making. There is now a critical window of opportunity to learn from early SARS-CoV-2 serology studies. We aimed to synthesize the results of SARS-CoV-2 serosurveillance projects from around the world and provide recommendations to improve the coordination, strategy, and methodology of future serosurveillance efforts. Methods. This was a rapid systematic review of cross-sectional and cohort studies reporting seroprevalence outcomes for SARS-CoV 2. We included completed, ongoing, and proposed serosurveys. The search included electronic databases (PubMed, MedRXIV, BioRXIV, and WHO ICTPR); five medical journals (NEJM, BMJ, JAMA, The Lancet, Annals of Internal Medicine); reports by governments, NGOs, and health systems; and media reports (Google News) from December 1, 2019 to May 1, 2020. We extracted data on study characteristics and critically appraised prevalence estimates using Joanna Briggs Institute criteria. Results. Seventy records met inclusion criteria, describing 73 studies. Of these, 23 reported prevalence estimates: eight preprints, 14 news articles, and one government report. These studies had a total sample size of 35,784 and reported 42 prevalence estimates. Seroprevalence estimates ranged from 0.4% to 59.3%. No estimates were found to have a low risk of bias (43% high risk, 21% moderate risk, 36% unclear). Fifty records reported characteristics of ongoing or proposed serosurveys. Overall, twenty countries have completed, ongoing, or proposed serosurveys. Discussion. Study design, quality, and prevalence estimates of early SARS-CoV2 serosurveys are heterogeneous, suggesting that the urgency to examine seroprevalence may have compromised methodological rigour. Based on the limitations of included studies, future serosurvey investigators and stakeholders should ensure that: i) serological tests used undergo high-quality independent evaluations that include cross-reactivity; ii) all reports of serosurvey results, including media, describe the test used, sample size, and sampling method; and iii) initiatives are coordinated to prevent test fatigue, minimize redundant efforts, and encourage better study methodology. Other. PROSPERO: CRD42020183634. No third-party funding.

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

positive: Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.

positive: Predicting the evolution Of SARS-Covid-2 in Portugal using an adapted SIR Model previously used in South Korea for the MERS outbreak The new coronavirus covid-19 has spread very quickly worldwide, leading the World Health Organization (WHO) to declare a state of pandemic. One of the questions many policy makers, and governments are asking themselves is how the spread is going to evolve in time. In this study, I applied an adapted SIR model previously used in South Korea to model the MERS outbreak, which is also caused by a coronavirus, to estimate the evolution of the curve of active cases in the case of the Portuguese situation, using Italian dara. I then construct five different scenarios for the evolution of covid-19 in Portugal. In the out of control scenario, the number of active cases could reach as much as ~40,000 people on the 5th of April (out-of-control scenario). If the self-protective and control are taken in the same level as what was considered for the South Korean model, this number could have be reduced to about 800 cases (scenario 1). Considering that this scenario is now unrealistic, three other scenarios were devised. In all these scenarios, the government measures had a 50\% effectiveness when compared to the measures in Korea. But in scenario 2 the transmission rate $\beta$ was effectively reduced to 50\%, In this scenario active cases could reach circa 7,000 people. In scenario 3, the transmission rate $\beta$ was reduced to 70\% of its initial value, in which the number of cases would reach a peak of ~11,000 people. And finally in scenario 4, $\beta$ was reduced to 80\%. In this scenario, the peak would be reached at about ~13,000 cases. This study shows the importance of control and self-protecting measure to bring down the number of affected people by following the recommendations of the WHO and health authorities. With the appropriate measures, this number can be brought down to ~7,000-13,000 people. Hopefully that will be the case not just in Portugal, but in the rest of the World.

positive: The Story behind COVID-19: Animal Diseases at the Crossroads of Wildlife, Livestock and Human Health A number of virological, epidemiological and ethnographic arguments suggest that COVID-19 has a zoonotic origin. The pangolin, a species threatened with extinction due to poaching for both culinary purposes and traditional Chinese pharmacopoeia, is now suspected of being the “missing link” in the transmission to humans of a virus that probably originated in a species of bat. Our predation of wild fauna and the reduction in their habitats have thus ended up creating new interfaces that favour the transmission of pathogens (mainly viruses) to humans. Domesticated animals and wild fauna thus constitute a reservoir for almost 80% of emerging human diseases (SARS-CoV, MERS-CoV, Ebola). These diseases are all zoonotic in origin. As if out of a Chinese fairy tale, the bat and the pangolin have taught us a lesson: within an increasingly interdependent world, environmental crises will become ever more intertwined with health crises. Questions relating to public health will no longer be confined to the secrecy of the physician’s consulting room or the sanitised environment of the hospital. They are now being played out in the arena of international trade, ports and airports and distribution networks. Simply put, all human activity creates new interfaces that facilitate the transmission of pathogens from an animal reservoir to humans. This pluri-disciplinary article highlights that environmental changes, such as the reduction in habitats for wild fauna and the intemperate trade in fauna, are the biggest causes of the emergence of new diseases. Against this background, it reviews the different measures taken to control, eradicate and prevent the emergence of animal diseases in a globalised world.

positive: Comparison of SARS-CoV-2 spike protein binding to ACE2 receptors from human, pets, farm animals, and putative intermediate hosts The emergence of a novel coronavirus, SARS-CoV-2, resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptor allows to define residues important for binding. From the 20 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S-binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites located near the S-interface. Of note, Pigs and dogs, which are not or not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with viruses from Bat-CoV-RaTG13 and Pangolin-CoV revealed that the latter contains only one substitution, whereas the Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2.IMPORTANCE SARS-CoV-2 is threatening people worldwide and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the species barrier might be low. An exception are dogs and especially pigs, which, however, revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.

positive: 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.

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: Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2 We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. Its genome is closest to that of severe acute respiratory syndrome–related coronaviruses from horseshoe bats, and its receptor-binding domain is closest to that of pangolin viruses. Its origin and direct ancestral viruses have not been identified.

positive: Comparative genomic signature representations of the emerging COVID-19 coronavirus and other coronaviruses: High identity and possible recombination between Bat and Pangolin coronaviruses Abstract Coronaviruses are responsible on respiratory diseases in animal and human. The combination of numerical encoding techniques and digital signal processing methods are becoming increasingly important in handling large genomic data. In this paper, we propose to analyze the SARS-CoV-2 genomic signature using the combination of different nucleotide representations and signal processing tools in the aim to identify its genetic origin. The sequence of SARS-CoV-2 was compared with 21 relevant sequences including bat, yak and pangolin coronavirus sequences. In addition, we developed a new algorithm to locate the nucleotide modifications. The results show that the Bat and Pangolin coronaviruses were the most related to SARS-CoV-2 with 96% and 86% of identity all along the genome. Within the S gene sequence, the Pangolin sequence presents local highest nucleotide identity. Those findings suggest genesis of SARS-Cov-2 through evolution from bat and pangolin strains. This study offers new ways to automatically characterize viruses.

positive: Phylogenetic analysis and sequence comparisons of structural and non-structural SARS coronavirus proteins in Taiwan Abstract Taiwan experienced a large number of severe acute respiratory syndrome (SARS) viral infections between March and July 2003; by September of that year, 346 SARS cases were confirmed by RT-PCR or serological tests. In order to better understand evolutionary relationships among SARS coronaviruses (SCoVs) from different international regions, we performed phylogenetic comparisons of full-length genomic and protein sequences from 45 human SCoVs (including 12 from Taiwan) and two civet SCoVs. All the Taiwanese SARS-CoV strains which associated with nosocomial infection formed a monophyletic clade within the late phase of the SARS epidemic. This Taiwanese clade could be further divided into two epidemic waves. Taiwan SCoVs in the first wave clustered with three isolates from the Amoy Gardens housing complex in Hong Kong indicating their possible origin. Of the 45 human SCoVs, one isolate from Guangdong province, China, exhibited an extra 29-nucleotide fragment between Orf 10 and Orf 11—similar to the civet SCoV genome. Nucleotide and protein sequence comparisons suggested that all SCoVs of late epidemic came from human-to-human transmission, while certain SCoVs of early epidemic might have originated in animals.

positive: Coronaviruses: a paradigm of new emerging zoonotic diseases A novel type of coronavirus (2019-nCoV) infecting humans appeared in Wuhan, China, at the end of December 2019. Since the identification of the outbreak the infection quickly spread involving in one month more than 31,000 confirmed cases with 638 death. Molecular analysis suggest that 2019-nCoV could be originated from bats after passaging in intermediate hosts, highlighting the high zoonotic potential of coronaviruses.

positive: Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19) The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions.

positive: The emergence of SARS, MERS and novel SARS-2 coronaviruses in the 21st century At the beginning of the 21st century, a new deadly infectious disease known as severe acute respiratory syndrome (SARS) was recognized as a global public health threat. Subsequently, ten years after the initial SARS cases occurred in 2002, new cases of another atypical respiratory disease caused worldwide concern. This disease became known as Middle East respiratory syndrome (MERS) and was even more lethal than SARS. Currently, history has repeated itself with the emergence of a new Chinese epidemic at the end of 2019. For this respiratory disease, called COVID-19, a novel coronavirus (SARS-CoV-2) was identified as the etiologic agent. In sum, SARS, MERS and COVID-19 are caused by recently discovered coronaviruses that cause flu-like illnesses, but with a clinical outcome that tends to be more severe. As a result of the current importance of coronaviruses in global public health, we conducted a review to summarize and update, above all, the epidemiological historical aspects of the three major diseases in humans caused by coronaviral infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04628-0) contains supplementary material, which is available to authorized users.

positive: Coronavirus Disease 2019-COVID-19 SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.

positive: 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.

positive: Current epidemiological and clinical features of COVID-19; a global perspective from China 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: Might the many positive COVID19 subjects in Italy have been caused by resident bat-derived zoonotic ß-coronaviruses instead of the Wuhan (China) outbreak?

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

positive: 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.

positive: Assessing the Epidemic Potential of RNA and DNA Viruses Many new and emerging RNA and DNA viruses are zoonotic or have zoonotic origins in an animal reservoir that is usually mammalian and sometimes avian. Not all zoonotic viruses are transmissible (directly or by an arthropod vector) between human hosts. Virus genome sequence data provide the best evidence of transmission. Of human transmissible virus, 37 species have so far been restricted to self-limiting outbreaks. These viruses are priorities for surveillance because relatively minor changes in their epidemiologies can potentially lead to major changes in the threat they pose to public health. On the basis of comparisons across all recognized human viruses, we consider the characteristics of these priority viruses and assess the likelihood that they will further emerge in human populations. We also assess the likelihood that a virus that can infect humans but is not capable of transmission (directly or by a vector) between human hosts can acquire that capability.

positive: Molecular aspects of MERS-CoV Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus which can cause acute respiratory distress in humans and is associated with a relatively high mortality rate. Since it was first identified in a patient who died in a Jeddah hospital in 2012, the World Health Organization has been notified of 1735 laboratory-confirmed cases from 27 countries, including 628 deaths. Most cases have occurred in Saudi Arabia. MERS-CoVancestors may be found in OldWorld bats of the Vespertilionidae family. After a proposed bat to camel switching event, transmission of MERS-CoV to humans is likely to have been the result of multiple zoonotic transfers from dromedary camels. Human-to-human transmission appears to require close contact with infected persons, with outbreaks mainly occurring in hospital environments. Outbreaks have been associated with inadequate infection prevention and control implementation, resulting in recommendations on basic and more advanced infection prevention and control measures by the World Health Organization, and issuing of government guidelines based on these recommendations in affected countries including Saudi Arabia. Evolutionary changes in the virus, particularly in the viral spike protein which mediates virus-host cell contact may potentially increase transmission of this virus. Efforts are on-going to identify specific evidence-based therapies or vaccines. The broad-spectrum antiviral nitazoxanide has been shown to have in vitro activity against MERS-CoV. Synthetic peptides and candidate vaccines based on regions of the spike protein have shown promise in rodent and non-human primate models. GLS-5300, a prophylactic DNA-plasmid vaccine encoding S protein, is the first MERS-CoV vaccine to be tested in humans, while monoclonal antibody, m336 has given promising results in animal models and has potential for use in outbreak situations.

positive: Molecular Evolution of MERS Coronavirus: Dromedaries as a Recent Intermediate Host or Long-Time Animal Reservoir? While dromedary camels are the immediate animal source of MERS coronavirus (MERS-CoV) infection, the evolutionary origin of MERS-CoV remains obscure. We analyzed 219 camel and human MERS-CoV genome sequences available in GenBank. Phylogenetic analysis showed that 5 and 214 strains belong to clade A and B, respectively, with clade A further divided into lineage A1 (3 human strains) and lineage A2 (2 camel strains), and clade B divided into B1 to B6 (each containing both human and camel strains). Recombination analysis showed potential recombination events in five strains from dromedaries in Saudi Arabia, with recombination between lineage B5 and B3 in four strains, and between lineage B3 and B4 in one strain. The spike protein showed the highest number of amino acid substitutions, especially between A2 and other lineages, and contained positively selected codons. Notably, codon 1020 was positively selected among B and B5 strains, and can distinguish between clade A (Q1020) and B (R1020/H1020) strains, suggesting that this residue may play a role in the evolution of S protein during divergence of different lineages. The time of the most recent common ancestor of all MERS-CoV was dated to approximately 2010. The implications on the role of camels in the evolution of MERS-CoV are discussed.

positive: The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike SUMMARY The ongoing outbreak of the novel coronavirus pneumonia COVID-19 has caused great number of cases and deaths, but our understanding about the pathogen SARS-CoV-2 remains largely unclear. The attachment of the virus with the cell-surface receptor and a co-factor is the first step for the infection. Here, bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures have revealed the high affinity between human dipeptidyl peptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 are identical to those as bound to the MERS-CoV-S. Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with SARS-CoV-S. This potential utilization of DPP4 as a binding target for SARS-CoV-2 may offer novel insight into the viral pathogenesis, and help the surveillance and therapeutics strategy for meeting the challenge of COVID-19.

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

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

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

positive: Non-Molecular-Clock-Like Evolution following Viral Origins in Homo sapiens Researchers routinely adopt molecular clock assumptions in conducting sequence analyses to estimate dates for viral origins in humans. We used computational methods to examine the extent to which this practice can result in inaccurate ‘retrodiction.’ Failing to account for dynamic molecular evolution can affect greatly estimating index case dates, resulting in an overestimated age for the SARS-CoV-human infection, for instance.

positive: A Unique Clade of SARS-CoV-2 Viruses is Associated with Lower Viral Loads in Patient Upper Airways The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we examined the genome sequences of 88 SARS-CoV-2 viruses from COVID-19 patients in Chicago, USA and identified three distinct phylogenetic clades. Clade 1 was most closely related to clades centered in New York, and showed evidence of rapid expansion across the USA, while Clade 3 was most closely related to those in Washington. Clade 2 was localized primarily to the Chicago area with limited evidence of expansion elsewhere. Average viral loads in the airways of patients infected with the rapidly spreading Clade 1 viruses were significantly higher than those of the poorly spreading Clade 2. These results show that multiple variants of SARS-CoV-2 are circulating in the USA that differ in their relative airway viral loads and potential for expansion.

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

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

positive: Cross-species transmission of the newly identified coronavirus 2019-nCoV The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019-nCoV sequence. Results obtained from our analyses suggest that the 2019-nCoV may appear to be a recombinant virus between the bat coronavirus and an origin-unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019-nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019-nCoV cross-species transmission.

positive: Phylogenetic Analysis and Structural Modeling of SARS-CoV-2 Spike Protein Reveals an Evolutionary Distinct and Proteolytically Sensitive Activation Loop The 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) originally arose as part of a major outbreak of respiratory disease centered on Hubei province, China. It is now a global pandemic and is a major public health concern. Taxonomically, SARS-CoV-2 was shown to be a Betacoronavirus (lineage B) closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been reported to share a common receptor with SARS-CoV (ACE-2). Subsequently, betacoronaviruses from pangolins were identified as close relatives to SARS-CoV-2. Here, we perform structural modeling of the SARS-CoV-2 spike glycoprotein. Our data provide support for the similar receptor utilization between SARS-CoV-2 and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV and all other coronaviruses in Betacoronavirus lineage B, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains. We suggest this loop confers fusion activation and entry properties more in line with betacoronaviruses in lineages A and C, and be a key component in the evolution of SARS-CoV-2 with this structural loop affecting virus stability and transmission.

positive: Wildlife Trade and the Emergence of Infectious Diseases Most recent emerging infectious diseases have been zoonotic in origin. It is our contention that one of the factors responsible for such emergence is the trade in wildlife and bushmeat in particular. This article considers the effect of increasing diversity in the species hunted on the probability of global epidemics such as SARS. In particular, we develop a mathematical model of the probability of such an outbreak in terms of the number of species hunted, the number of susceptibles, and the rate of contact. Hence, we postulate that local biodiversity loss and increasing rates of animal trafficking, and trade and transportation of animals to large cities—where there is a greater potential for person-to-person transmission—may increase the probability of such outbreaks dramatically.

positive: Molecular conservation and Differential mutation on ORF3a gene in Indian SARS-CoV2 genomes A global emergency due to the COVID-19 pandemic demands various studies related to genes and genomes of the SARS-CoV2. Among other important proteins, the role of accessory proteins are of immense importance in replication, regulation of infections of the coronavirus in the hosts. The largest accessory proteins in the SARS-CoV2 genome is ORF3a which modulates the host response to the virus infection and consequently it plays an important role in pathogenesis. In this study, an attempt is made to decipher the conservation of nucleotides, dimers, codons and amino acids in the ORF3a genes across thirty two genomes of Indian patients. ORF3a gene possesses single and double point mutations in Indian SARS-CoV2 genomes suggesting the change of SARS-CoV2’s virulence property in Indian patients. We find that the parental origin of the ORF3a gene over the genomes of SARS-CoV2 and Pangolin-CoV is same from the phylogenetic analysis based on conservations of nucleotides and so on. This study highlights the accumulation of mutation on ORF3a in Indian SARS-CoV2 genomes which may provide the designing therapeutic approach against SARS-CoV2.

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

positive: 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.

positive: Common RNA replication signals exist among group 2 coronaviruses: evidence for in vivo recombination between animal and human coronavius molecules Abstract 5′ and 3′ UTR sequences on the coronavirus genome are known to carry cis-acting elements for DI RNA replication and presumably also virus genome replication. 5′ UTR-adjacent coding sequences are also thought to harbor cis-acting elements. Here we have determined the 5′ UTR and adjacent 289-nt sequences, and 3′ UTR sequences, for six group 2 coronaviruses and have compared them to each other and to three previously reported group 2 members. Extensive regions of highly similar UTR sequences were found but small regions of divergence were also found indicating group 2 coronaviruses could be subdivided into those that are bovine coronavirus (BCoV)-like (BCoV, human respiratory coronavirus-OC43, human enteric coronavirus, porcine hemagglutinating encephalomyelitis virus, and equine coronavirus) and those that are murine hepatitis virus (MHV)-like (A59, 2, and JHM strains of MHV, puffinosis virus, and rat sialodacryoadenitis virus). The 3′ UTRs of BCoV and MHV have been previously shown to be interchangeable. Here, a reporter-containing BCoV DI RNA was shown to be replicated by all five BCoV-like helper viruses and by MHV-H2 (a human cell-adapted MHV strain), a representative of the MHV-like subgroup, demonstrating group 2 common 5′ and 3′ replication signaling elements. BCoV DI RNA, furthermore, acquired the leader of HCoV-OC43 by leader switching, demonstrating for the first time in vivo recombination between animal and human coronavirus molecules. These results indicate that common replication signaling elements exist among group 2 coronaviruses despite a two-cluster pattern within the group and imply there could exist a high potential for recombination among group members.

positive: The outbreak of Coronavirus Disease 2019 (COVID-19)—An emerging global health threat Abstract The outbreak of Coronavirus Disease 2019 (COVID-19) causing novel coronavirus-infected pneumonia (NCIP), has affected the lives of 71,429 people globally. Originating in China, the disease has a rapid progression to other countries. Research suggests remarkable genomic resemblance of 2019-nCoV with Severe Acute Respiratory Syndrome (SARS) which has a history of a pandemic in 2002. With evidence of nosocomial spread, a number of diligent measures are being employed to constrain its propagation. Hence, the Public Health Emergency of International Concern (PHEIC) has been established by the World Health Organization (WHO) with strategic objectives for public health to curtail its impact on global health and economy.

positive: SARS – Unprecedented global response to a newly emerging disease Abstract No Abstract

positive: The COVID-19 pandemic In December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei Province, China. Pneumonia cases were epidemiologically linked to the Huanan Seafood Wholesale Market. Inoculation of respiratory samples into human airway epithelial cells, Vero E6 and Huh7 cell lines, led to the isolation of a novel respiratory virus whose genome analysis showed it to be a novel coronavirus related to SARS-CoV, and therefore named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus belonging to the subgenus Sarbecovirus. The global spread of SARS-CoV-2 and the thousands of deaths caused by coronavirus disease (COVID-19) led the World Health Organization to declare a pandemic on 12 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. In this review, we provide information regarding the epidemiology, serological and molecular diagnosis, origin of SARS-CoV-2 and its ability to infect human cells, and safety issues. Then we focus on the available therapies to fight COVID-19, the development of vaccines, the role of artificial intelligence in the management of the pandemic and limiting the spread of the virus, the impact of the COVID-19 epidemic on our lifestyle, and preparation for a possible second wave.

positive: Human coronaviruses with emphasis on the COVID-19 outbreak Human coronaviruses are known as respiratory pathogens mainly associated with a range of respiratory diseases. In the past 18 years, the beginning of severe acute respiratory syndrome human coronavirus (SARS-HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and now the (COVID-19) have driven the HCoV into the platform of the scientific community due to their high pathogenicity in humans. Our study about the HCoV has contributed extensively to the understanding of HCoV pathogenesis its outbreak and precautionary measurements mainly COVID-19. By the 16-February 2020, total existing diagnosis cases of COVID-19, in china now numbered around 57,255, total cumulative diagnosis is about 68,592, total existing suspicion is about 8228, a total severe existing disease 11,272, the total cumulative cure is about 9671 with more than 1666 cumulative deaths have been reported. The purpose of the review is to summarize the present knowledge on the viral diversity, reservoir hosts, and geographical distributions of Human coronavirus (COVID-19) in China.

positive: The novel coronavirus 2019-nCoV: Its evolution and transmission into humans causing global COVID-19 pandemic A novel coronavirus strain 2019-nCoV has caused a rapid global pandemic-COVID-19. Scientists have taken onto the task of characterizing this new virus and understanding how this virus has transmitted to humans. All preliminary studies have found some striking similarities between this new virus and the SARS-CoV that caused a similar kind of epidemic in 2002–2003. Through bioinformatics tools, a great deal of information has been gathered about the origin, evolution and zoonosis of this virus. We, in this review, report the symptoms, mode of transmission and available and putative treatments to tackle 2019-nCoV infections. We also comprehensively summarize all the information so far made available regarding the genome, evolution and zoonosis of this virus.

positive: The first three months of the COVID-19 epidemic: Epidemiological evidence for two separate strains of SARS-CoV-2 viruses spreading and implications for prevention strategies About one month after the COVID-19 epidemic peaked in Mainland China and SARS-CoV-2 migrated from China westward to Europe and then the U.S., the epidemiological data begin to provide important insights into the risks associated with the disease and the effectiveness of intervention strategies. Like other respiratory diseases, including the 2003 SARS epidemic, the virus remains only about two months in any given population, yet the peak incidence and the lethality can vary. The data suggest that at least two strains of the 2020 SARS-CoV-2 virus have evolved during its migration from Mainland China to Europe. South Korea, Iran, and Italy were hit by the more dangerous "SKII" variant. While the epidemic in China is about to end, and in Europe about to level off, the course of the epidemic in the younger US population is still increasing and the peak level will likely depend on which of the strains has entered the US first. The same models that help us to understand the epidemic also help us to choose prevention strategies. While containment merely prolongs the time the disease circulates until the proportion of immune people is high enough for "herd immunity", reducing disease severity, either by vaccination or by early treatment of complications, is the best strategy against a respiratory virus disease.

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

positive: Covid‐19 and neurodegeneration. What can we learn from the past? Coronaviridae (CoVs) are single stranded RNA viruses. βeta‐CoVs encompasses Bat coronavirus (BCoV), the human Severe Acute Respiratory Syndrome (SARS) virus and the Middle Eastern Respiratory Syndrome (MERS) virus. In December 2019, a new βeta‐CoVs was identified in Wuhan, China, SARS‐CoV‐2. The genome sequencing demonstrated a 79.5% and 96.2% identity to SARS‐CoV and a bat CoV genome, respectively, supporting the interspecies transmission and the origin of this new pandemia.

positive: Emerging Animal Coronaviruses: First SARS and Now MERS The first major pandemic of the new millennium that arose from southern China in 2002 was of zoonotic origin from wild game animals, called severe acute respiratory syndrome [SARS]. The culprit was determined to be a coronavirus of animal origin [SARS-CoV]. The discovery of the SARS-CoV, which caused an outbreak of >8000 people in >30 countries with fatality of about 10%, resulted in intense search for novel coronaviruses with potentially high pathogenicity. Ten years later after the SARS pandemic, another novel coronavirus crossed the species barrier from bats to humans through an intermediate camel host, to produce a severe lower respiratory infection labeled the Middle East respiratory syndrome [MERS]. A novel coronavirus [MERS-CoV] was first identified in September 2012, from patients who resided or traveled to Saudi Arabia. The MERS-CoV spread through contacts with camel and subsequently from human to human via droplet transmission. MERS cases occurred in several other countries including in Europe and the United States, mainly from residence or travel to the Arabian Peninsula, but was not of pandemic potential. However, in the spring of 2015, a MERS outbreak started in South Korea which was initiated by a returning traveler from Saudi Arabia, and subsequently secondary infection of over 186 local residents occurred. Recent estimate in May 2015 indicates that the MERS-CoV have afflicted 1167 patients with MERS worldwide with 479 deaths [41% fatality]. Thus MERS is more deadly than SARS but appears to be less contagious. However, unlike SARS which has not reappeared since 2002–2003, MERS-CoV have the potential to cause sporadic or local outbreaks for many years as the virus may now be entrenched endemically in dromedary camels of the Middle East.

positive: Introduction—Panspermia, 2020 This current volume is, in many ways, a 2020 update to the important 1999–2000 compendium by Sir Fed Hoyle and Professor N. Chandra Wickramasinghe's “Astronomical Origins of life: Steps towards Panspermia.” The emerging new paradigm of biology that connects life on Earth with the wider cosmos is covered in considerable depth showing that terrestrial biological evolution is best understood as a cosmically derived habitat and an interconnected genetic system. The various chapters here discuss all aspects of this interconnectedness, particularly relevant now in this time of the coronavirus pandemic (COVID-19) as the human race reacts to the many microbes and viral pathogens that arrive regularly from space.

positive: Virus–Host Coevolution with a Focus on Animal and Human DNA Viruses Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life. It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus. The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants. In this literature review we try to give a short insight into some general consequences or traits of virus–host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses.

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

positive: Mystery deepens over animal source of coronavirus

positive: Evolutionary perspectives on novel coronaviruses identified in pneumonia cases in China

positive: Understanding the possible origin and genotyping of first Bangladeshi SARS-CoV-2 strain The novel coronavirus, SARS-CoV-2, causes the unfathomable pandemic in the history of humankind. Bangladesh is also a victim of this critical situation. To investigate the genomic features of the pathogen, the first complete genome of the virus has very recently been published. Therefore, the long awaiting questions regarding the possible origin and typing of the strain(s) can now be answered. Here, we endeavor to mainly discuss the published reports or online-accessed data (results) regarding those issues and presented a comprehensive picture of the typing of the virus alongside the probable origin of the sub-clade containing Bangladeshi strain. Our observation suggested that this strain might have originated from the United Kingdom (UK) or other European countries epidemiologically linked to the UK. According to different genotyping classification schemes, this strain belongs to A2a clade under G major clade, is of B and/or L type, and is a SARS-CoV-2a sub-strain. In the forwarding days, randomized genome data will certainly voluminate in Bangladesh, however because of globalization and immigrant movements, we urgently need a mass regional sequencing approach targeting the partial or complete genome that can link the epidemiological data and may help in further clinical interventions. This article is protected by copyright. All rights reserved.

positive: Effect of a wet market on coronavirus disease (COVID-19) transmission dynamics in China, 2019-2020 OBJECTIVES: The novel coronavirus (SARS-CoV-2) originating from Wuhan spread rapidly throughout China. While its origin remains uncertain, accumulating evidence links a wet market with the early spread of SARS-CoV-2 in Wuhan. Similarly, the influence of the marketplace on the early transmission dynamics is yet to be investigated. METHODS: Using the daily series of COVID-19 incidence, stratified according to contact history with the market, we have conducted quantitative modeling analyses to estimate the reproduction numbers (R) for market-to-human and human-to-human transmission, the reporting probability, and the early effects of public health interventions. RESULTS: We estimated R at 0.24 (95% CrI: 0.01-1.38) for market-to-human transmission and 2.37 (95% CrI: 2.08-2.71) for human-to-human transmission during the early spread in China (2019-2020). Moreover, we estimated that the reporting rate for cases stemming from market-to-human transmission was 2-34 fold higher than that for cases stemming from human-to-human transmission, suggesting that contact history with the wet market played a key role in identifying COVID-19 cases. CONCLUSIONS: Our R estimate tied to market-to-human transmission had substantial uncertainty, but it was significantly lower compared with the reproduction number driving human-to-human transmission. Our results also suggest that asymptomatic and subclinical infections constitute a substantial component of the COVID-19 morbidity burden.

positive: Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13 The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3’-to-5’ exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.

positive: COVID-19 and veterinarians for one health, zoonotic- and reverse-zoonotic transmissions A novel coronavirus emerged in human populations and spread rapidly to cause the global coronavirus disease 2019 pandemic. Although the origin of the associated virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) remains unclear, genetic evidence suggests that bats are a reservoir host of the virus, and pangolins are a probable intermediate. SARS-CoV-2 has crossed the species barrier to infect humans and other animal species, and infected humans can facilitate reverse-zoonotic transmission to animals. Considering the rapidly changing interconnections among people, animals, and ecosystems, traditional roles of veterinarians should evolve to include transdisciplinary roles.

positive: Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19) Coronavirus has emerged as a global health threat due to its accelerated geographic spread over the last two decades. This article reviews the current state of knowledge concerning the origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Historically, it has caused two pandemics: severe acute respiratory syndrome and Middle East respiratory syndrome followed by the present COVID-19 that emerged from China. The virus is believed to be acquired from zoonotic source and spreads through direct and contact transmission. The symptomatic phase manifests with fever, cough and myalgia to severe respiratory failure. The diagnosis is confirmed using reverse transcriptase PCR. Management of COVID-19 is mainly by supportive therapy along with mechanical ventilation in severe cases. Preventive strategies form the major role in reducing the public spread of virus along with successful disease isolation and community containment. Development of a vaccine to eliminate the virus from the host still remains an ongoing challenge.

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

positive: Multivariate analyses of codon usage of SARS-CoV-2 and other betacoronaviruses Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus, which also includes severe acute respiratory syndrome-related coronavirus (SARSr-CoV) and Middle East respiratory syndrome-related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses helped identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, we compared the codon usage bias using global correspondence analysis (CA), within-group CA and between-group CA. We found that the bat RaTG13 virus best matched the overall codon usage pattern of SARS-CoV-2 in orf1ab, spike and nucleocapsid genes, while the pangolin P1E virus had a more similar codon usage in membrane gene. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.

positive: COVID-19: animals, veterinary and zoonotic links. Coronavirus disease 2019 (COVID-19), has spread over 210 countries and territories beyond China shortly. On February 29, 2020, the World Health Organization (WHO) denoted it in a high-risk category, and on March 11, 2020, this virus was designated pandemic, after its declaration being a Public Health International Emergency on January 30, 2020. World over high efforts are being made to counter and contain this virus. The COVID-19 outbreak once again proves the potential of the animal-human interface to act as the primary source of emerging zoonotic diseases. Even though the circumstantial evidence suggests the possibility of an initial zoonotic emergence, it is too early to confirm the role of intermediate hosts such as snakes, pangolins, turtles, and other wild animals in the origin of SARS-CoV-2, in addition to bats, the natural hosts of multiple coronaviruses such as SARS-CoV and MERS-CoV. The lessons learned from past episodes of MERS-CoV and SARS-CoV are being exploited to retort this virus. Best efforts are being taken up by worldwide nations to implement effective diagnosis, strict vigilance, heightened surveillance, and monitoring, along with adopting appropriate preventive and control strategies. Identifying the possible zoonotic emergence and the exact mechanism responsible for its initial transmission will help us to design and implement appropriate preventive barriers against the further transmission of SARS-CoV-2. This review discusses in brief about the COVID-19/SARS-CoV-2 with a particular focus on the role of animals, the veterinary and associated zoonotic links along with prevention and control strategies based on One-health approaches.

positive: Response to "Comments on "Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human" and "Codon bias analysis alone is uninformative for identifying host(s) of new virus" We have recently reported for the first time that SARS-CoV-2 maybe a bat-originated coronavirus with a recombination occurred within the spike (S) protein gene based on phylogenetic and simplot analyses1 . These two conclusions are supported by findings recently reported by others and are well accepted in the field of SARS-CoV-2 research2-4 . This article is protected by copyright. All rights reserved.

positive: Getting Insights from a Large Corpus of Scientific Papers on Specialisted Comprehensive Topics -- the Case of COVID-19 COVID-19 is one of the most important topic these days, specifically on search engines and news. While fake news are easily shared, scientific papers are reliable sources where information can be extracted. With about 24,000 scientific publications on COVID-19 and related research on PUBMED, automatic computer-assisted analysis is required. In this paper, we develop two methodologies to get insights on specific sub-topics of interest and latest research sub-topics. They rely on natural language processing and graph-based visualizations. We run these methodologies on two cases: the virus origin and the uses of existing drugs.

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

positive: 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.

positive: A generalized overview of SARS-COV-2: Where does the current knowledge stand? The novel coronavirus known to have brought the world to a standstill is responsible for many deaths throughout the globe as of now. The causative agent (SARS-CoV-2) for coronavirus disease 2019 (COVID-19) has been recognized as a zoonotic transfer. Although, the medium of animal-human transmission is still unknown, bats maybe a potential reservoir of this novel strain. Due to its high rate of transmission the most favorable way of limiting the outbreak’s extent is by early diagnosis followed by isolation of the infected individuals. So far, the most widely used diagnosis methods are RT-qPCR which detects specific sequences of the viral RNA. Some other methods include serological tests and the recently introduced CRISPR-CAS-12 based assays. As of now, no specific therapeutic treatments are known for COVID-19 however the use of some broad-spectrum antiviral drugs and convalescent plasma therapy have demonstrated positive outcomes. Apart from these treatments, vaccine development for SARS-CoV-2 is also in progress by 17 known companies. This article provides a comprehensive insight on the recently emerged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) including its origin, transmission mechanism, pathophysiology and updated treatment methods.

positive: Cell entry of SARS-CoV-2 conferred by angiotensin-converting enzyme 2 (ACE2) of different species The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a huge threat to many countries around the world. However, where is it origin and which animals are sensitive to cross-species transmission is unclear. The interaction of virus and cell receptor is a key determinant of host range for the novel coronavirus. Angiotensin-converting enzyme 2 (ACE2) is demonstrated as the primary entry receptor for SARS-CoV-2. In this study, we evaluated the SARS-CoV-2 entry mediated by ACE2 of 11 different species of animals, and discovered that ACE2 of Rhinolophus sinicus (Chinese horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (pig), Capra hircus (goat) and especially Manis javanica (Malayan pangolin) were able to render SARS-CoV-2 entry in non-susceptible cells. This is the first report that ACE2 of Pangolin could mediate SARS-CoV-2 entry which increases the presume that SARS-CoV-2 may have a pangolin origin. However, none of the ACE2 proteins from Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (chicken), Notechis scutatus (mainland tiger snake), Mus musculus (house mouse) rendered SARS-CoV-2 entry. Specifically, a natural isoform of Macaca mulatta (Rhesus monkey) ACE2 with a mutation of Y217N was resistance to infection, which rises the possible impact of this type of ACE2 during monkey studies of SARS-CoV-2. Overall, these results clarify that SARS-CoV-2 could engage receptors of multiple species of animals and it is a perplexed work to track SARS-CoV-2 origin and its intermediate hosts. IMPORTANCE In this study, we illustrated that SARS-CoV-2 is able to engage receptors of multiple species of animals. This indicated that it may be a perplexed work to track SARS-CoV-2 origin and discover its intermediate hosts. This feature of virus is considered to potentiate its diverse cross-species transmissibility. Of note, here is the first report that ACE2 of Pangolin could mediate SARS-CoV-2 entry which increases the possibility that SARS-CoV-2 may have a pangolin origin. And we also demonstrated that not all species of bat were sensitive to SARS-CoV-2 infection. At last, it is also important to detect the expression ratio of the Y217N ACE2 to the prototype in Rhesus monkeys to be recruited for studies on SARS-CoV-2 infection.

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

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: A phylogenomic data-driven exploration of viral origins and evolution The origin of viruses remains mysterious because of their diverse and patchy molecular and functional makeup. Although numerous hypotheses have attempted to explain viral origins, none is backed by substantive data. We take full advantage of the wealth of available protein structural and functional data to explore the evolution of the proteomic makeup of thousands of cells and viruses. Despite the extremely reduced nature of viral proteomes, we established an ancient origin of the “viral supergroup” and the existence of widespread episodes of horizontal transfer of genetic information. Viruses harboring different replicon types and infecting distantly related hosts shared many metabolic and informational protein structural domains of ancient origin that were also widespread in cellular proteomes. Phylogenomic analysis uncovered a universal tree of life and revealed that modern viruses reduced from multiple ancient cells that harbored segmented RNA genomes and coexisted with the ancestors of modern cells. The model for the origin and evolution of viruses and cells is backed by strong genomic and structural evidence and can be reconciled with existing models of viral evolution if one considers viruses to have originated from ancient cells and not from modern counterparts.

positive: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence Origin of the COVID-19 virus has been intensely debated in the scientific community since the first infected cases were detected in December 2019. The disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic. Recent research results suggest that bats or pangolins might be the original hosts for the virus based on comparative studies using its genomic sequences. This paper investigates the COVID-19 virus origin by using artificial intelligence (AI) and raw genomic sequences of the virus. More than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods. The results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined COVID-19 virus genomes belong to a cluster that also contains bat and pangolin coronavirus genomes. This provides evidences strongly supporting scientific hypotheses that bats and pangolins are probable hosts for the COVID-19 virus. At the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins.

positive: Zoonotic origins of human coronavirus 2019 (HCoV-19 / SARS-CoV-2): why is this work important? The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19 / SARS-CoV-2 / 2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARS-CoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.

positive: Strong evolutionary convergence of receptor-binding protein spike between COVID-19 and SARS-related coronaviruses Coronavirus Disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS)-related coronaviruses (e.g., 2019-nCoV and SARS-CoV) are phylogenetically distantly related, but both are capable of infecting human hosts via the same receptor, angiotensin-converting enzyme 2, and cause similar clinical and pathological features, suggesting their phenotypic convergence. Yet, the molecular basis that underlies their phenotypic convergence remains unknown. Here, we used a recently developed molecular phyloecological approach to examine the molecular basis leading to their phenotypic convergence. Our genome-level analyses show that the spike protein, which is responsible for receptor binding, has undergone significant Darwinian selection along the branches related to 2019-nCoV and SARS-CoV. Further examination shows an unusually high proportion of evolutionary convergent amino acid sites in the receptor binding domain (RBD) of the spike protein between COVID-19 and SARS-related CoV clades, leading to the phylogenetic uniting of their RBD protein sequences. In addition to the spike protein, we also find the evolutionary convergence of its partner protein, ORF3a, suggesting their possible co-evolutionary convergence. Our results demonstrate a strong adaptive evolutionary convergence between COVID-19 and SARS-related CoV, possibly facilitating their adaptation to similar or identical receptors. Finally, it should be noted that many observed bat SARS-like CoVs that have an evolutionary convergent RBD sequence with 2019-nCoV and SARS-CoV may be pre-adapted to human host receptor ACE2, and hence would be potential new coronavirus sources to infect humans in the future.

positive: One Health, emerging infectious diseases and wildlife: two decades of progress? Infectious diseases affect people, domestic animals and wildlife alike, with many pathogens being able to infect multiple species. Fifty years ago, following the wide-scale manufacture and use of antibiotics and vaccines, it seemed that the battle against infections was being won for the human population. Since then, however, and in addition to increasing antimicrobial resistance among bacterial pathogens, there has been an increase in the emergence of, mostly viral, zoonotic diseases from wildlife, sometimes causing fatal outbreaks of epidemic proportions. Concurrently, infectious disease has been identified as an increasing threat to wildlife conservation. A synthesis published in 2000 showed common anthropogenic drivers of disease threats to biodiversity and human health, including encroachment and destruction of wildlife habitat and the human-assisted spread of pathogens. Almost two decades later, the situation has not changed and, despite improved knowledge of the underlying causes, little has been done at the policy level to address these threats. For the sake of public health and wellbeing, human-kind needs to work better to conserve nature and preserve the ecosystem services, including disease regulation, that biodiversity provides while also understanding and mitigating activities which lead to disease emergence. We consider that holistic, One Health approaches to the management and mitigation of the risks of emerging infectious diseases have the greatest chance of success. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.

positive: Animal source of the coronavirus continues to elude scientists.

positive: MERS Coronavirus: An Emerging Zoonotic Virus Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus that was first reported in humans in June 2012 [...].

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

positive: Comparison of SARS-CoV-2 spike protein binding to ACE2 receptors from human, pets, farm animals, and putative intermediate hosts. The emergence of a novel coronavirus, SARS-CoV-2, resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptor allows to define residues important for binding. From the 20 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S-binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites located near the S-interface. Of note, Pigs and dogs, which are not or not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with viruses from Bat-CoV-RaTG13 and Pangolin-CoV revealed that the latter contains only one substitution, whereas the Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2.IMPORTANCE SARS-CoV-2 is threatening people worldwide and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the species barrier might be low. An exception are dogs and especially pigs, which, however, revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.

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

positive: Genomic variance of the 2019-nCoV coronavirus There is a rising global concern for the recently emerged novel coronavirus (2019-nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches.

positive: The Novel Coronavirus SARS‐CoV‐2: From a Zoonotic Infection to Coronavirus Disease‐19 (COVID19) OBJECTIVE: The novel coronavirus, SARS‐CoV‐2 is an international public health emergency. Until now, the intermediate host and mechanisms of interspecies jump of this virus are unknown. METHODS: Phylogenetic analysis of all available bat coronavirus (CoV) complete genomes was performed in order to analyze the relationships between bat CoV and SARS‐CoV‐2. In order to suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals which were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions which may have permitted the adaptation of SARS‐CoV‐2 to the human host. RESULTS: The phylogenetic analysis demonstrated that SARS‐CoV‐2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS‐CoV‐2, bat RaTG13 and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS‐CoV‐2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS‐CoV‐2 tropism to human cells. CONCLUSIONS: Our analysis shows the tight relationship between SARS‐CoV‐2 and bat SARS‐like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function. This article is protected by copyright. All rights reserved.

positive: Outbreak of a new coronavirus: what anaesthetists should know

positive: Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are likely reservoir hosts for SARS-CoV-2, the identity of any intermediate host that might have facilitated transfer to humans is unknown. Here, we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity to SARS-CoV-2 in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of novel coronaviruses and should be removed from wet markets to prevent zoonotic transmission.

positive: Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human.

positive: From SARS coronavirus to novel animal and human coronaviruses. In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) caused one of the most devastating epidemics known to the developed world. There were two important lessons from this epidemic. Firstly, coronaviruses, in addition to influenza viruses, can cause severe and rapidly spreading human infections. Secondly, bats can serve as the origin and natural animal reservoir of deadly human viruses. Since then, researchers around the world, especially those in Asia where SARS-CoV was first identified, have turned their focus to find novel coronaviruses infecting humans, bats, and other animals. Two human coronaviruses, HCoV-HKU1 and HCoV-NL63, were identified shortly after the SARS-CoV epidemic as common causes of human respiratory tract infections. In 2012, a novel human coronavirus, now called Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in the Middle East to cause fatal human infections in three continents. MERS-CoV human infection is similar to SARS-CoV in having a high fatality rate and the ability to spread from person to person which resulted in secondary cases among close contacts including healthcare workers without travel history to the Middle East. Both viruses also have close relationships with bat coronaviruses. New cases of MERS-CoV infection in humans continue to occur with the origins of the virus still unknown in many cases. A multifaceted approach is necessary to control this evolving MERS-CoV outbreak. Source identification requires detailed epidemiological studies of the infected patients and enhanced surveillance of MERS-CoV or similar coronaviruses in humans and animals. Early diagnosis of infected patients and appropriate infection control measures will limit the spread in hospitals, while social distancing strategies may be necessary to control the outbreak in communities if it remained uncontrolled as in the SARS epidemic.

positive: Assessing uncertainty in the rooting of the SARS-CoV-2 phylogeny The rooting of the SARS-CoV-2 phylogeny is important for understanding the origin and early spread of the virus. Previously published phylogenies have used different rootings that do not always provide consistent results. We use several different strategies for rooting the SARS-CoV-2 tree and provide measures of statistical uncertainty for all methods. We show that methods based on the molecular clock tend to place the root in the B clade, while methods based on outgroup rooting tend to place the root in the A clade. The results from the two approaches are statistically incompatible, possibly as a consequence of deviations from a molecular clock or excess back-mutations. We also show that none of the methods provide strong statistical support for the placement of the root in any particular edge of the tree. Our results suggest that inferences on the origin and early spread of SARS-CoV-2 based on rooted trees should be interpreted with caution.

positive: The origin and underlying driving forces of the SARS-CoV-2 outbreak BACKGROUND: SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. METHOD: Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. RESULT: After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019–12/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. CONCLUSION: SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.

positive: SARS-CoV-2 variants: Relevance for symptom granularity, epidemiology, immunity (herd, vaccines), virus origin and containment? The origin of the SARS-CoV-2 virus remains enigmatic. It is likely to be a continuum resulting from inevitable mutations and recombination events. These genetic changes keep developing in the present epidemic. Mutations tending to deplete the genome in its cytosine content will progressively lead to attenuation as a consequence of Muller's ratchet, but this is counteracted by recombination when different mutants co-infect the same host, in particular, in clusters of infection. Monitoring as a function of time the genome sequences in closely related cases is critical to anticipate the future of SARS-CoV-2 and hence of COVID-19.

positive: Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of any intermediate host facilitating transfer to humans is unknown. Here, we report the identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, including one very closely related to 2019-nCoV in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV suggests that pangolins should be considered as possible intermediate hosts for this novel human virus and should be removed from wet markets to prevent zoonotic transmission.

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

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

positive: A Genomic Perspective on the Origin and Emergence of SARS-CoV-2 The ongoing pandemic of a new human coronavirus, SARS-CoV-2, has generated enormous global concern. We and others in China were involved in the initial genome sequencing of the virus. Herein, we describe what genomic data reveal about the emergence SARS-CoV-2 and discuss the gaps in our understanding of its origins.

positive: The 2019 novel coronavirus resource. An ongoing outbreak of a novel coronavirus infection in Wuhan, China since December 2019 has led to 31,516 infected persons and 638 deaths across 25 countries (till 16:00 on February 7, 2020). The virus causing this pneumonia was then named as the 2019 novel coronavirus (2019-nCoV) by the World Health Organization. To promote the data sharing and make all relevant information of 2019-nCoV publicly available, we construct the 2019 Novel Coronavirus Resource (2019nCoVR, https://bigd.big.ac.cn/ncov). 2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC). It also incorporates a wide range of relevant information including scientific literatures, news, and popular articles for science dissemination, and provides visualization functionalities for genome variation analysis results based on all collected 2019-nCoV strains. Moreover, by linking seamlessly with related databases in CNCB/NGDC, 2019nCoVR offers virus data submission and sharing services for raw sequence reads and assembled sequences. In this report, we provide comprehensive descriptions on data deposition, management, release and utility in 2019nCoVR, laying important foundations in aid of studies on virus classification and origin, genome variation and evolution, fast detection, drug development and pneumonia precision prevention and therapy.

positive: SARS, MERS and COVID-19—new threats; old lessons

positive: Identification of a common deletion in the spike protein of SARS-CoV-2 Two notable features have been identified in the SARS-CoV-2 genome: (1) the receptor binding domain of SARS-CoV-2; (2) a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1 and S2 boundary. For the first feature, the similar RBD identified in SARs-like virus from pangolin suggests the RBD in SARS-CoV-2 may already exist in animal host(s) before it transmitted into human. The left puzzle is the history and function of the insertion at S1/S2 boundary, which is uniquely identified in SARS-CoV-2. In this study, we identified two variants from the first Guangdong SARS-CoV-2 cell strain, with deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. More extensive screening indicates the deletion at the flank sites of PRRAR could be detected in 3 of 68 clinical samples and half of 22 in vitro isolated viral strains. These data indicate (1) the deletion of QTQTN, at the flank of polybasic cleavage site, is likely benefit the SARS-CoV-2 replication or infection in vitro but under strong purification selection in vivo since it is rarely identified in clinical samples; (2) there could be a very efficient mechanism for deleting this region from viral genome as the variants losing 23585-23599 is commonly detected after two rounds of cell passage. The mechanistic explanation for this in vitro adaptation and in vivo purification processes (or reverse) that led to such genomic changes in SARS-CoV-2 requires further work. Nonetheless, this study has provided valuable clues to aid further investigation of spike protein function and virus evolution. The deletion mutation identified in vitro isolation should be also noted for current vaccine development.

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

positive: Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study BACKGROUND: Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin. METHODS: Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85–95%, and four 30–50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done. FINDINGS: Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction. INTERPRETATION: We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R(0) values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed. FUNDING: Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.

positive: Phylogeny of Viruses Biological species, including viruses, change through generations and over time in the process known as evolution. Viruses may evolve at high, uneven, and fluctuating rates among genome sites. The accumulated changes, through either mutation or recombination with other species, are first fixed in the genome of successful individuals that give rise to genetic lineages. The relationship between biological lineages related by common descent is called ‘phylogeny’. For inferring phylogeny, the differences between aligned sequences of genomes and proteins are quantified and depicted in the form of a tree, in which contemporary species and their intermediate and common ancestors occupy, respectively, the terminal nodes, internal nodes, and the root. The tree is characterized by a topology, length of branches, shape, and the root position. A complex mathematical apparatus has been developed for phylogeny inference that can evaluate inter-species differences, facilitate tree building and comparison of trees, and assess the fit between data and tree through, typically, computationally intensive calculations. A reconstructed tree is an approximation of the true phylogeny that practically remains unknown. The phylogenetic analysis is used in applied and fundamental virus research, including epidemiology, diagnostics, forensic studies, phylogeography, evolutionary studies, and virus taxonomy. It can provide an evolutionary perspective on variation of any trait that can be measured for a group of viruses.

positive: Coronavirus Genomics and Bioinformatics Analysis The drastic increase in the number of coronaviruses discovered and coronavirus genomes being sequenced have given us an unprecedented opportunity to perform genomics and bioinformatics analysis on this family of viruses. Coronaviruses possess the largest genomes (26.4 to 31.7 kb) among all known RNA viruses, with G + C contents varying from 32% to 43%. Variable numbers of small ORFs are present between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid) and downstream to nucleocapsid gene in different coronavirus lineages. Phylogenetically, three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, with Betacoronavirus consisting of subgroups A, B, C and D, exist. A fourth genus, Deltacoronavirus, which includes bulbul coronavirus HKU11, thrush coronavirus HKU12 and munia coronavirus HKU13, is emerging. Molecular clock analysis using various gene loci revealed that the time of most recent common ancestor of human/civet SARS related coronavirus to be 1999–2002, with estimated substitution rate of 4×10(−4) to 2×10(−2) substitutions per site per year. Recombination in coronaviruses was most notable between different strains of murine hepatitis virus (MHV), between different strains of infectious bronchitis virus, between MHV and bovine coronavirus, between feline coronavirus (FCoV) type I and canine coronavirus generating FCoV type II, and between the three genotypes of human coronavirus HKU1 (HCoV-HKU1). Codon usage bias in coronaviruses were observed, with HCoV-HKU1 showing the most extreme bias, and cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape such codon usage bias in coronaviruses.

positive: Evolution of Viral Proteins Originated De Novo by Overprinting New protein-coding genes can originate either through modification of existing genes or de novo. Recently, the importance of de novo origination has been recognized in eukaryotes, although eukaryotic genes originated de novo are relatively rare and difficult to identify. In contrast, viruses contain many de novo genes, namely those in which an existing gene has been “overprinted” by a new open reading frame, a process that generates a new protein-coding gene overlapping the ancestral gene. We analyzed the evolution of 12 experimentally validated viral genes that originated de novo and estimated their relative ages. We found that young de novo genes have a different codon usage from the rest of the genome. They evolve rapidly and are under positive or weak purifying selection. Thus, young de novo genes might have strain-specific functions, or no function, and would be difficult to detect using current genome annotation methods that rely on the sequence signature of purifying selection. In contrast to young de novo genes, older de novo genes have a codon usage that is similar to the rest of the genome. They evolve slowly and are under stronger purifying selection. Some of the oldest de novo genes evolve under stronger selection pressure than the ancestral gene they overlap, suggesting an evolutionary tug of war between the ancestral and the de novo gene.

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

positive: [Source of the COVID-19 pandemic: ecology and genetics of coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS-CoV (subgenus Merbecovirus).] Since the early 2000s, three novel zooanthroponous coronaviruses (Betacoronavirus) have emerged. The first outbreak of infection (SARS) caused by SARS-CoV virus occurred in the fall of 2002 in China (Guangdong Province). A second outbreak (MERS) associated with the new MERS-CoV virus appeared in Saudi Arabia in autumn 2012. The third epidemic, which turned into a COVID-19 pandemic caused by SARS-CoV-2 virus, emerged in China (Hubei Province) in the autumn 2019. This review focuses on ecological and genetic aspects that lead to the emergence of new human zoanthroponous coronaviruses. The main mechanism of adaptation of zoonotic betacoronaviruses to humans is to changes in the receptor-binding domain of surface protein (S), as a result of which it gains the ability to bind human cellular receptors of epithelial cells in respiratory and gastrointestinal tract. This process is caused by the high genetic diversity and variability combined with frequent recombination, during virus circulation in their natural reservoir - bats (Microchiroptera, Chiroptera). Appearance of SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS (subgenus Merbecovirus) viruses is a result of evolutionary events occurring in bat populations with further transfer of viruses to the human directly or through the intermediate vertebrate hosts, ecologically connected with bats. This review is based on the report at the meeting «Coronavirus - a global challenge to science» of the Scientific Council «Life Science» of the Russian Academy of Science: Lvov D.K., Alkhovsky S.V., Burtseva E.I. COVID-19 pandemic sources: origin, biology and genetics of coronaviruses of SARS-CoV, SARS-CoV-2, MERS-CoV (Conference hall of Presidium of RAS, 14 Leninsky Prospect, Moscow, Russia. April 16, 2020).

positive: Understanding the possible origin and genotyping of first Bangladeshi SARS‐CoV‐2 strain The novel coronavirus, SARS‐CoV‐2, causes the unfathomable pandemic in the history of humankind. Bangladesh is also a victim of this critical situation. To investigate the genomic features of the pathogen, the first complete genome of the virus has very recently been published. Therefore, the long awaiting questions regarding the possible origin and typing of the strain(s) can now be answered. Here, we endeavor to mainly discuss the published reports or online‐accessed data (results) regarding those issues and presented a comprehensive picture of the typing of the virus alongside the probable origin of the sub‐clade containing Bangladeshi strain. Our observation suggested that this strain might have originated from the United Kingdom (UK) or other European countries epidemiologically linked to the UK. According to different genotyping classification schemes, this strain belongs to A2a clade under G major clade, is of B and/or L type, and is a SARS‐CoV‐2a sub‐strain. In the forwarding days, randomized genome data will certainly voluminate in Bangladesh, however because of globalization and immigrant movements, we urgently need a mass regional sequencing approach targeting the partial or complete genome that can link the epidemiological data and may help in further clinical interventions. This article is protected by copyright. All rights reserved.

positive: Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)? The outbreak of a novel corona Virus Disease 2019 (COVID-19) in the city of Wuhan, China has resulted in more than 1.7 million laboratory confirmed cases all over the world. Recent studies showed that SARS-CoV-2 was likely originated from bats, but its intermediate hosts are still largely unknown. In this study, we assembled the complete genome of a coronavirus identified in 3 sick Malayan pangolins. The molecular and phylogenetic analyses showed that this pangolin coronavirus (pangolin-CoV-2020) is genetically related to the SARS-CoV-2 as well as a group of bat coronaviruses but do not support the SARS-CoV-2 emerged directly from the pangolin-CoV-2020. Our study suggests that pangolins are natural hosts of Betacoronaviruses. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. In addition to conservation of wildlife, minimizing the exposures of humans to wildlife will be important to reduce the spillover risks of coronaviruses from wild animals to humans.

positive: The COVID-19 pandemic: biological evolution, treatment options and consequences The spread of novel coronavirus SARS-CoV-2, the cause of the pandemic COVID-19 has emerged as a global matter of concern in the last couple of months. It has rapidly spread around the globe, which initially began in the city of Wuhan, People’s Republic of China and is hypothesized to originate from the group of Rhinolophus bats. Till date, there has been no clinically proven vaccine against the SARS-CoV-2 and thus the doctors are employing the other well-known techniques, which have previously successfully tackled similar other human coronaviruses. To prevent the further spread of COVID-19, doctors are advising isolation of the infected patients, and also regular washing of hands and the use of face mask for the common people. In the wake of the COVID-19 outbreak, the countries are going for nationwide lockdown as the only preventive measure to avert community transmission of this disease, which is having economic, social and psychological effect on the general mass. Therefore, this comprehensive review article encapsulates the biological evolution of human coronaviruses, probable treatment and control strategies to combat COVID-19 and, its impact on human life.

positive: Genetic relatedness of the novel human group C betacoronavirus to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5 The recent outbreak of severe respiratory infections associated with a novel group C betacoronavirus (HCoV-EMC) from Saudi Arabia has drawn global attention to another highly probable “SARS-like” animal-to-human interspecies jumping event in coronavirus (CoV). The genome of HCoV-EMC is most closely related to Tylonycteris bat coronavirus HKU4 (Ty-BatCoV HKU4) and Pipistrellus bat coronavirus HKU5 (Pi-BatCoV HKU5) we discovered in 2006. Phylogenetically, HCoV-EMC is clustered with Ty-BatCoV HKU4/Pi-BatCoV HKU5 with high bootstrap supports, indicating that HCoV-EMC is a group C betaCoV. The major difference between HCoV-EMC and Ty-BatCoV HKU4/Pi-BatCoV HKU5 is in the region between S and E, where HCoV-EMC possesses five ORFs (NS3a-NS3e) instead of four, with low (31%–62%) amino acid identities to Ty-BatCoV HKU4/Pi-BatCoV HKU5. Comparison of the seven conserved replicase domains for species demarcation shows that HCoV-EMC is a novel CoV species. More intensive surveillance studies in bats and other animals may reveal the natural host of HCoV-EMC.

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

positive: Diversity of Coronaviruses in Bats: Insights Into Origin of SARS Coronavirus

positive: Alphacoronavirus in urban Molossidae and Phyllostomidae bats, Brazil BACKGROUND: Bats have been implicated as the main reservoir of coronavirus (CoV). Thus the role of these hosts on the evolution and spread of CoVs currently deserve the attention of emerging diseases surveillance programs. On the view of the interest on and importance of CoVs in bats the occurrence and molecular characterization of CoV were conducted in bats from Brazil. FINDINGS: Three hundred five enteric contents of 29 bat species were tested using a panCoV nested RT-PCR. Nine specimens were positive and eight was suitable for RdRp gene sequencing. RdRp gene phylogeny showed that all CoVs strains from this study cluster in Alphacoronavirus genus, with one Molossidae and one Phlyllostomidae-CoV specific groups. Phylogenetic analyses of two S gene sequences showed a large diversity within the Alphacoronavirus genus. CONCLUSIONS: This study indicated a CoV-to-host specificity and draws attention for CoV detection in Cynomops sp, a potential new reservoir. The phylogenetic analyses indicate that diversity of CoV in bats is higher than previously known.

positive: Novel SARS-CoV-2/COVID-19: Origin, pathogenesis, genes and genetic variations, immune responses and phylogenetic analysis In this review, we focused on the origins of the novel coronavirus (SARS-CoV-2), origin, pathogenesis, immune responses, genes and genetic variations, phylogenetic analyses, and potential therapeutic strategies to summarize approaches for developing broadly effective preventions and vaccines to cope COVID-19. Towards the end of 2019, SARS-CoV-2 has emerged in association with the SARS, later was named COVID-19 caused an environment of chaos worldwide and infected a massive number of lives. Since these epidemics or pandemics had spread to 210 countries and territories around the world and 2 international conveyances with 6,467,229 confirmed cases, including, 382,766 deaths, as of June 03, 2020 (https://www.worldometers.info/coronavirus/), hence the World Health Organization declared it as a global Public Health Emergency. There are no clinically approved vaccines or antiviral drugs available for either of new or old corona infections; thus, the development of effective therapeutic and preventive strategies that can be readily available to cope with these strains.

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

positive: The diversity of viruses infecting humans Most human viruses have been discovered through the diseases they cause in animals, plants, bacteria or fungi. Recent finds include human bocaviruses, which now seem to have a global distribution, and cause respiratory tract disease in infants, and several new pathogenic human coronaviruses. The SARS coronavirus, genetically distinct from all previously known coronaviruses, caused a disease which was highly transmissible and very severe, eventually leading to 8000 cases worldwide with over 800 deaths. Many viruses which are transmitted to humans by invertebrates, such as insects or ticks, have the ability to infect and replicate in cells of both vertebrate and invertebrate origin. However human virology is a rapidly expanding field and recent technologies such as the polymerase chain reaction (PCR) amplification system have made it possible to look for previously unrecognized viruses which may or may not be involved in pathogenesis. For example viruses in the genus Anellovirus are found in 80% of human blood samples yet do not seem to cause any disease. This paper overviews known human vertebrate viruses, more recent discoveries, and recommends a systematic search for viruses which may already infect the human population but have so far remained undetected.

positive: [Source of the COVID-19 pandemic: ecology and genetics of coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS-CoV (subgenus Merbecovirus).] Since the early 2000s, three novel zooanthroponous coronaviruses (Betacoronavirus) have emerged. The first outbreak of infection (SARS) caused by SARS-CoV virus occurred in the fall of 2002 in China (Guangdong Province). A second outbreak (MERS) associated with the new MERS-CoV virus appeared in Saudi Arabia in autumn 2012. The third epidemic, which turned into a COVID-19 pandemic caused by SARS-CoV-2 virus, emerged in China (Hubei Province) in the autumn 2019. This review focuses on ecological and genetic aspects that lead to the emergence of new human zoanthroponous coronaviruses. The main mechanism of adaptation of zoonotic betacoronaviruses to humans is to changes in the receptor-binding domain of surface protein (S), as a result of which it gains the ability to bind human cellular receptors of epithelial cells in respiratory and gastrointestinal tract. This process is caused by the high genetic diversity and variability combined with frequent recombination, during virus circulation in their natural reservoir - bats (Microchiroptera, Chiroptera). Appearance of SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS (subgenus Merbecovirus) viruses is a result of evolutionary events occurring in bat populations with further transfer of viruses to the human directly or through the intermediate vertebrate hosts, ecologically connected with bats. This review is based on the report at the meeting «Coronavirus - a global challenge to science¼ of the Scientific Council «Life Science¼ of the Russian Academy of Science: Lvov D.K., Alkhovsky S.V., Burtseva E.I. COVID-19 pandemic sources: origin, biology and genetics of coronaviruses of SARS-CoV, SARS-CoV-2, MERS-CoV (Conference hall of Presidium of RAS, 14 Leninsky Prospect, Moscow, Russia. April 16, 2020).

positive: Going viral – Covid-19 impact assessment: A perspective beyond clinical practice In the realm of infectious diseases, a global outbreak is a worst-case scenario In the past, outbreaks such as plague, Spanish flu, severe acute respiratory syndrome, and H1N1 (swine flu) have caused great human suffering The novel coronavirus, christened as Covid-19, is a zoonotic disease which originated from the Wuhan province in China and spread like wildfire killing people and devastating the global economy Mammoth efforts are still on to control this viral strain from further spread Cities have been blocked, air travel banned, ships have been quarantined, and panic-stricken people have been evacuated from China As Covid-19 continues to ravage countries across the globe, this article is an effort to provide an overview of the impact of Covid-19 and tickle wits of intellectuals to think how easily a nanometer organism can virtually bring down superpowers of the world

positive: Sampling bias and incorrect rooting make phylogenetic network tracing of SARS-COV-2 infections unreliable

positive: Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus. Bats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant of the direct ancestor of SCoV, based on their relatively distant phylogenetic relationship. In this study, evidence of the recombinant origin of the genome of a bat SLCoV is demonstrated. We identified a potential recombination breakpoint immediately after the consensus intergenic sequence between open reading frame 1 and the S coding region, suggesting the replication intermediates may participate in the recombination event, as previously speculated for other CoVs. Phylogenetic analysis of its parental regions suggests the presence of an uncharacterized SLCoV lineage that is phylogenetically closer to SCoVs than any of the currently sampled bat SLCoVs. Using various Bayesian molecular-clock models, interspecies transfer of this SLCoV lineage from bats to the amplifying host (e.g., civets) was estimated to have happened a median of 4.08 years before the SARS outbreak. Based on this relatively short window period, we speculate that this uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study sheds light on the possible host bat species of the direct ancestor of SCoV, providing valuable information on the scope and focus of surveillance for the origin of SCoV.

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

positive: Bat origin of a new human coronavirus: there and back again

positive: Chapter 1 Introduction to Virus Origins and Their Role in Biological Evolution Abstract Viruses are extremely abundant and diverse parasites of cells. They might have arisen during an early phase of the evolution of life on Earth dominated by RNA or RNA-like macromolecules, or when a cellular world was already well established. The theories of the origin of life on Earth shed light on the possible origin of primitive viruses or virus-like genetic elements in our biosphere. Some features of present day viruses, notably error-prone replication, might be a consequence of the selective forces that mediated their ancestral origin. Two views on the role of viruses in our biosphere predominate: viruses considered as opportunistic, selfish elements, and viruses considered as active participants in the construction of the cellular world via lateral transfers of genes. These two models bear on considering viruses predominantly as disease agents or predominantly as cooperators in the shaping of differentiated cellular organisms.

positive: Is A Problem Shared, A Problem Halved? Not Always! The Novel Coronavirus COVID-19 Outbreak How to cite this article: Bhosale S, Kulkarni AP. Is A Problem Shared, A Problem Halved? Not Always! The Novel Coronavirus COVID-19 Outbreak. Indian J Crit Care Med 2020;24(2):88–89.

positive: Molecular evolution and phylogenetic analysis of SARS-CoV-2 and hosts ACE2 protein suggest Malayan pangolin as intermediary host An emergence of a novel coronavirus, causative agent of COVID19, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred due to cross-species transmission. Coronaviruses are a large family of viruses able to infect a great number of hosts. Entrance of SARS-CoV-2 depends on the surface (S) protein interaction with host ACE2 protein and cleavage by TMPRSS2. ACE2 could be a species-specific barrier that interferes with bat-to-human coronavirus cross-species transmission. Molecular analysis supported bats as natural hosts for SARS-CoV and involved them in MERS-CoV origin. The genomic similarity between bat RaTG13 CoV strain and SARS-CoV-2 implicates bats in the origin of the new outbreak. Additionally, there is a hypothesis for the zoonotic transmission based on contact with Malayan pangolins by humans in Huanan seafood market in Wuhan, China. To investigate bats and pangolin as hosts in SARS-CoV-2 cross-species transmission, we perform an evolutionary analysis combining viral and host phylogenies and divergence of ACE2 and TMPRSS2 amino acid sequences between CoV hosts. Phylogeny showed SARS-like-CoV-2 strains that infected pangolin and bats are close to SARS-CoV-2. In contrast to TMPRSS2, pangolin ACE2 amino acid sequence has low evolutionary divergence compared with humans and is more divergent from bats. Comparing SARS-CoV with SARS-CoV-2 origins, pangolin has yet lower ACE2 evolutionary divergence with humans than civet-the main intermediary host of SARS-CoV. Thus, pangolin has become an opportune host to intermediates bat-to-human SARS-CoV-2 jump and entry.

positive: 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.

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

positive: Deciphering MERS-CoV Evolution in Dromedary Camels The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) poses a potential threat to global public health. Many aspects of the evolution and transmission of MERS-CoV in its animal reservoir remain unclear. A recent study provides new insights into the evolution and transmission of MERS-CoV in dromedary camels.

positive: Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.

positive: Emergence of SARS-CoV-2 through Recombination and Strong Purifying Selection COVID-19 has become a global pandemic caused by a novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis and for drug discovery and vaccine development. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike gene and in other genes among bat, pangolin and human coronaviruses, indicating similar strong evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. Similar purifying selection in different host species and frequent recombination among coronaviruses suggest a common evolutionary mechanism that could lead to new emerging human coronaviruses. One Sentence Summary Extensive Recombination and Strong Purifying Selection among coronaviruses from different hosts facilitate the emergence of SARS-CoV-2

positive: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses However, the external subdomain of Spike's receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses Remarkably, its orf3b encodes a completely novel short protein Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection FAU - Chan, Jasper Fuk-Woo

positive: Molecular tracing of SARS-CoV-2 in Italy in the first three months of the epidemic The aim of this study is the characterization and genomic tracing by phylogenetic analyses of 59 new SARS-CoV-2 Italian isolates obtained from patients attending clinical centres in North and Central Italy until the end of April 2020. All but one of the newly characterized genomes belonged to the lineage B.1, the most frequently identified in European countries, including Italy. Only a single sequence was found to belong to lineage B. A mean of 6 nucleotide substitutions per viral genome was observed, without significant differences between synonymous and non-synonymous mutations, indicating genetic drift as a major source for virus evolution. tMRCA estimation confirmed the probable origin of the epidemic between the end of January and the beginning of February with a rapid increase in the number of infections between the end of February and mid-March. Since early February, an effective reproduction number (Re) greater than 1 was estimated, which then increased reaching the peak of 2.3 in early March, confirming the circulation of the virus before the first COVID-19 cases were documented. Continuous use of state-of-the-art methods for molecular surveillance is warranted to trace virus circulation and evolution and inform effective prevention and containment of future SARS-CoV-2 outbreaks.

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

positive: COVID-19: animals, veterinary and zoonotic links Coronavirus disease 2019 (COVID-19), has spread over 210 countries and territories beyond China shortly. On February 29, 2020, the World Health Organization (WHO) denoted it in a high-risk category, and on March 11, 2020, this virus was designated pandemic, after its declaration being a Public Health International Emergency on January 30, 2020. World over high efforts are being made to counter and contain this virus. The COVID-19 outbreak once again proves the potential of the animal-human interface to act as the primary source of emerging zoonotic diseases. Even though the circumstantial evidence suggests the possibility of an initial zoonotic emergence, it is too early to confirm the role of intermediate hosts such as snakes, pangolins, turtles, and other wild animals in the origin of SARS-CoV-2, in addition to bats, the natural hosts of multiple coronaviruses such as SARS-CoV and MERS-CoV. The lessons learned from past episodes of MERS-CoV and SARS-CoV are being exploited to retort this virus. Best efforts are being taken up by worldwide nations to implement effective diagnosis, strict vigilance, heightened surveillance, and monitoring, along with adopting appropriate preventive and control strategies. Identifying the possible zoonotic emergence and the exact mechanism responsible for its initial transmission will help us to design and implement appropriate preventive barriers against the further transmission of SARS-CoV-2. This review discusses in brief about the COVID-19/SARS-CoV-2 with a particular focus on the role of animals, the veterinary and associated zoonotic links along with prevention and control strategies based on One-health approaches.

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

positive: 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.

positive: Origin and cross-species transmission of bat coronaviruses in China Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. We used a Bayesian statistical framework and sequence data from all known bat-CoVs (including 630 novel CoV sequences) to study their macroevolution, cross-species transmission, and dispersal in China. We find that host-switching was more frequent and across more distantly related host taxa in alpha-than beta-CoVs, and more highly constrained by phylogenetic distance for beta-CoVs. We show that inter-family and -genus switching is most common in Rhinolophidae and the genus Rhinolophus. Our analyses identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance. Finally, we present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats.

positive: Molecular Evolution of Human Coronavirus Genomes Human coronaviruses (HCoVs), including SARS-CoV and MERS-CoV, are zoonotic pathogens that originated in wild animals. HCoVs have large genomes that encode a fixed array of structural and nonstructural components, as well as a variety of accessory proteins that differ in number and sequence even among closely related CoVs. Thus, in addition to recombination and mutation, HCoV genomes evolve through gene gains and losses. In this review we summarize recent findings on the molecular evolution of HCoV genomes, with special attention to recombination and adaptive events that generated new viral species and contributed to host shifts and to HCoV emergence. Video Abstract

positive: Mosaic evolution of the severe acute respiratory syndrome coronavirus. Severe acute respiratory syndrome (SARS) is a deadly form of pneumonia caused by a novel coronavirus, a viral family responsible for mild respiratory tract infections in a wide variety of animals including humans, pigs, cows, mice, cats, and birds. Analyses to date have been unable to identify the precise origin of the SARS coronavirus. We used Bayesian, neighbor-joining, and split decomposition phylogenetic techniques on the SARS virus replicase, surface spike, matrix, and nucleocapsid proteins to reveal the evolutionary origin of this recently emerging infectious agent. The analyses support a mammalian-like origin for the replicase protein, an avian-like origin for the matrix and nucleocapsid proteins, and a mammalian-avian mosaic origin for the host-determining spike protein. A bootscan recombination analysis of the spike gene revealed high nucleotide identity between the SARS virus and a feline infectious peritonitis virus throughout the gene, except for a 200- base-pair region of high identity to an avian sequence. These data support the phylogenetic analyses and suggest a possible past recombination event between mammalian-like and avian-like parent viruses. This event occurred near a region that has been implicated to be the human receptor binding site and may have been directly responsible for the switch of host of the SARS coronavirus from animals to humans.

positive: SARS-CoV-2 and COVID-19: A genetic, epidemiological, and evolutionary perspective In less than five months, COVID-19 has spread from a small focus in Wuhan, China, to more than 5 million people in almost every country in the world, dominating the concern of most governments and public health systems. The social and political distresses caused by this epidemic will certainly impact our world for a long time to come. Here, we synthesize lessons from a range of scientific perspectives rooted in epidemiology, virology, genetics, ecology and evolutionary biology so as to provide perspective on how this pandemic started, how it is developing, and how best we can stop it.

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

positive: Chasing the origin of SARS-CoV-2 in Canada’s COVID-19 cases: A genomics study The emergence and global spread of SARS-CoV-2 has had profound social and economic consequences and has shed light on the importance of continued and additional investment in global health and infectious disease surveillance. Identifying changes in viral genomes provides key insights into viral diversity, how viruses spread within populations, and viral strategies for evasion of host immune systems. Here we report twenty-five SARS-CoV-2 genome sequences collected from some of the first COVID-19 cases in eastern Ontario, Canada (March 18-30, 2020). The reported genomes belong to the S-clade (n=2) and G-clade (n=23) of SARS-CoV-2 and contain 45 polymorphic sites including one shared missense and three unique synonymous variants in the gene encoding the spike protein. A phylogenetic analysis enabled the tracing of viral origin and potential transmission into and within Canada. There may be as many as sixteen unique infection events represented in these samples, including at least three that were likely introduced from Europe and seven from the USA. In addition, four separate genomes are each shared by multiple patients, suggesting a common origin or community spread even during this early stage of infection. These results demonstrate how molecular epidemiology and evolutionary phylogenetics can help local health units track origins and vectors of spread for emerging diseases like SARS-CoV-2. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to prevent future pandemics.

positive: Middle East respiratory syndrome coronavirus (MERS-CoV): evidence and speculations In 2012, a novel human coronavirus emerged and was tentatively named “Middle East respiratory syndrome coronavirus” (MERS-CoV). The high mortality rate of MERS-CoV focused attention on the ecology of the virus. It has been found that MERS-CoV belongs to the group C lineage of the genus Betacoronavirus. Coronavirus surveillance studies in different populations of bats have suggested that they are probable reservoirs for this novel virus, and phylogenetic analysis of both the spike (S1) and RNA-dependent RNA polymerase proteins of MERS-CoV have revealed that it is related to bat viruses. Recently, the MERS-CoV and its neutralizing antibodies were detected in dromedary camels. Despite the limited number of reported cases of person-to-person transmission, the rapid evolution of the virus poses a continuous threat to humans worldwide. This paper reviews the current state of knowledge regarding the virology, clinical spectrum, evolution, diagnosis and treatment of MERS-CoV infections.

positive: SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission Background With the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2 Whole Genome Sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, practical and cost considerations of cWGS should be addressed before it can be widely implemented. Methods We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences. Results We show a significant improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome compared to an average of 0.63% without enrichment. Consequently, a dramatic increase in genome coverage was obtained using significantly less sequencing data, enabling higher scalability and significant cost reductions. We also demonstrate how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains. Conclusions SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic.

positive: 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.

positive: Coast-to-coast spread of SARS-CoV-2 in the United States revealed by genomic epidemiology Since its emergence and detection in Wuhan, China in late 2019, the novel coronavirus SARS-CoV-2 has spread to nearly every country around the world, resulting in hundreds of thousands of infections to date. The virus was first detected in the Pacific Northwest region of the United States in January, 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the U.S., we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated impacts of federal travel restrictions. This study provides evidence for widespread, sustained transmission of SARS-CoV-2 within the U.S. and highlights the critical need for local surveillance.

positive: Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism As the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rages across the world, killing hundreds of thousands and infecting millions, researchers are racing against time to elucidate the viral genome. Some Bangladeshi institutes are also in this race, sequenced a few isolates of the virus collected from Bangladesh. Here, we present a genomic analysis of 14 isolates. The analysis revealed that SARS-CoV-2 isolates sequenced from Dhaka and Chittagong were the lineage of Europe and the Middle East, respectively. Our analysis identified a total of 42 mutations, including three large deletions, half of which were synonymous. Most of the missense mutations in Bangladeshi isolates found to have weak effects on the pathogenesis. Some mutations may lead the virus to be less pathogenic than the other countries. Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh.

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

positive: Host range of SARS-CoV-2 and implications for public health

positive: The Italian Outbreak of COVID-19: Conditions, Contributors, and Concerns

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

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

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

positive: The novel Coronavirus enigma: Phylogeny and mutation analyses of SARS-CoV-2 viruses circulating in India during early 2020 Background This is a comprehensive analysis of 46 Indian SARS-CoV-2 genome sequences available from the NCBI and GISAID repository during early 2020. Evolutionary dynamics, gene-specific phylogeny and emergence of the novel co-evolving mutations in nine structural and non-structural genes among circulating SARS-CoV-2 strains in ten states of India have been assessed. Materials and methods 46 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID (39/46) or from NCBI (7/46) database. Phylogenetic study and analyses of mutation were based on the nine structural and non-structural genes of SARS-CoV-2 strains. Secondary structure of RdRP/NSP12 protein was predicted with respect to the novel A97V mutation. Results Phylogenetic analyses revealed the evolution of “genome-type clusters” and adaptive selection of “L” type SARS-CoV-2 strains with genetic closeness to the bat SARS-like coronaviruses than pangolin or MERS-CoVs. With regards to the novel co-evolving mutations, 2 groups are seen to circulate in India at present: the “major group” (52.2%) and the “minor group” (30.4%), harboring four and five co-existing mutations, respectively. The “major group” mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6) were unique to the Indian isolates. Conclusion The study highlights rapidly evolving SARS-CoV-2 virus and co-circulation of multiple clades and sub-clades, driving this pandemic worldwide. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, changes in viral pathogenesis, for designing vaccines and other therapeutics.

positive: 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.

positive: Transmission dynamics and evolutionary history of 2019-nCoV To investigate the time origin, genetic diversity, and transmission dynamics of the recent 2019-nCoV outbreak in China and beyond, a total of 32 genomes of virus strains sampled from China, Thailand, and the USA with sampling dates between 24 December 2019 and 23 January 2020 were analyzed. Phylogenetic, transmission network, and likelihood-mapping analyses of the genome sequences were performed. On the basis of the likelihood-mapping analysis, the increasing tree-like signals (from 0% to 8.2%, 18.2%, and 25.4%) over time may be indicative of increasing genetic diversity of 2019-nCoV in human hosts. We identified three phylogenetic clusters using the Bayesian inference framework and three transmission clusters using transmission network analysis, with only one cluster identified by both methods using the above genome sequences of 2019-nCoV strains. The estimated mean evolutionary rate for 2019-nCoV ranged from 1.7926 × 10-3 to 1.8266 × 10-3 substitutions per site per year. On the basis of our study, undertaking epidemiological investigations and genomic data surveillance could positively impact public health in terms of guiding prevention efforts to reduce 2019-nCOV transmission in real-time.

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

positive: Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19

positive: An Extensive Meta-Metagenomic Search Identifies SARS-CoV-2-Homologous Sequences in Pangolin Lung Viromes In numerous instances, tracking the biological significance of a nucleic acid sequence can be augmented through the identification of environmental niches in which the sequence of interest is present. Many metagenomic data sets are now available, with deep sequencing of samples from diverse biological niches. While any individual metagenomic data set can be readily queried using web-based tools, meta-searches through all such data sets are less accessible. In this brief communication, we demonstrate such a meta-metagenomic approach, examining close matches to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in all high-throughput sequencing data sets in the NCBI Sequence Read Archive accessible with the “virome” keyword. In addition to the homology to bat coronaviruses observed in descriptions of the SARS-CoV-2 sequence (F. Wu, S. Zhao, B. Yu, Y. M. Chen, et al., Nature 579:265–269, 2020, https://doi.org/10.1038/s41586-020-2008-3; P. Zhou, X. L. Yang, X. G. Wang, B. Hu, et al., Nature 579:270–273, 2020, https://doi.org/10.1038/s41586-020-2012-7), we note a strong homology to numerous sequence reads in metavirome data sets generated from the lungs of deceased pangolins reported by Liu et al. (P. Liu, W. Chen, and J. P. Chen, Viruses 11:979, 2019, https://doi.org/10.3390/v11110979). While analysis of these reads indicates the presence of a similar viral sequence in pangolin lung, the similarity is not sufficient to either confirm or rule out a role for pangolins as an intermediate host in the recent emergence of SARS-CoV-2. In addition to the implications for SARS-CoV-2 emergence, this study illustrates the utility and limitations of meta-metagenomic search tools in effective and rapid characterization of potentially significant nucleic acid sequences. IMPORTANCE Meta-metagenomic searches allow for high-speed, low-cost identification of potentially significant biological niches for sequences of interest.

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

positive: 2019 Novel Coronavirus Disease Outbreak and Molecular Genetic Characteristics of Severe Acute Respiratory Syndrome-coronavirus-2 The 2019 novel coronavirus disease (COVID-19) outbreaks that emerged in Wuhan city, Hubei province, have led to a formidable number of confirmed cases that resulted in >5,700 deaths globally, including 143 countries in all 6 continents. The World Health Organization declared a Public Health Emergency of International Concern with a very high level of global risk assessment. Severe acute respiratory syndrome (SARS)-coronavirus-2 (SARS-CoV-2), the agent of COVID-19, has >79% nucleotide sequence homology to SARS-CoV; therefore, both belong to the genus betacoronavirus and subgenus sarbecovirus. The S1 domains of the two appeared to share the cellular receptor ACE2, but revealed a much higher S1-ACE2 binding affinity. As seen in many other human coronaviruses, SARS-CoV-2 also shows respiratory infection, but the basic reproductive number (R0) in transmission and the clinical latency are quite dissimilar from those of SARS-or MERS-CoVs. Many scientists infer that the time point of cross-barrier transfer from bats to mediate animals or to humans should be a rather recent event based on the full-length genome analyses obtained from the very first patients. Copy-choice polymerization, which often leads to a significant genome recombination rate in most coronaviruses, predicts the continued emergence of novel coronaviruses.

positive: Opinion paper: Severe Acute Respiratory Syndrome Coronavirus 2 and domestic animals: what relation?

positive: Origin, Evolution, and Genotyping of Emergent Porcine Epidemic Diarrhea Virus Strains in the United States Coronaviruses are known to infect humans and other animals and cause respiratory and gastrointestinal diseases. Here we report the emergence of porcine epidemic diarrhea virus (PEDV) in the United States and determination of its origin, evolution, and genotypes based on temporal and geographical evidence. Histological lesions in small intestine sections of affected pigs and the complete genomic sequences of three emergent strains of PEDV isolated from outbreaks in Minnesota and Iowa were characterized. Genetic and phylogenetic analyses of the three U.S. strains revealed a close relationship with Chinese PEDV strains and their likely Chinese origin. The U.S. PEDV strains underwent evolutionary divergence, which can be classified into two sublineages. The three emergent U.S. strains are most closely related to a strain isolated in 2012 from Anhui Province in China, which might be the result of multiple recombination events between different genetic lineages or sublineages of PEDV. Molecular clock analysis of the divergent time based on the complete genomic sequences is consistent with the actual time difference, approximately 2 to 3 years, of the PED outbreaks between China (December 2010) and the United States (May 2013). The finding that the emergent U.S. PEDV strains share unique genetic features at the 5′-untranslated region with a bat coronavirus provided further support of the evolutionary origin of PEDV from bats and potential cross-species transmission. The data from this study have important implications for understanding the ongoing PEDV outbreaks in the United States and will guide future efforts to develop effective preventive and control measures against PEDV.

positive: Global Epidemiology of Bat Coronaviruses Bats are a unique group of mammals of the order Chiroptera. They are highly diversified and are the group of mammals with the second largest number of species. Such highly diversified cell types and receptors facilitate them to be potential hosts of a large variety of viruses. Bats are the only group of mammals capable of sustained flight, which enables them to disseminate the viruses they harbor and enhance the chance of interspecies transmission. This article aims at reviewing the various aspects of the global epidemiology of bat coronaviruses (CoVs). Before the SARS epidemic, bats were not known to be hosts for CoVs. In the last 15 years, bats have been found to be hosts of >30 CoVs with complete genomes sequenced, and many more if those without genome sequences are included. Among the four CoV genera, only alphaCoVs and betaCoVs have been found in bats. As a whole, both alphaCoVs and betaCoVs have been detected from bats in Asia, Europe, Africa, North and South America and Australasia; but alphaCoVs seem to be more widespread than betaCoVs, and their detection rate is also higher. For betaCoVs, only those from subgenera Sarbecovirus, Merbecovirus, Nobecovirus and Hibecovirus have been detected in bats. Most notably, horseshoe bats are the reservoir of SARS-CoV, and several betaCoVs from subgenus Merbecovirus are closely related to MERS-CoV. In addition to the interactions among various bat species themselves, bat–animal and bat–human interactions, such as the presence of live bats in wildlife wet markets and restaurants in Southern China, are important for interspecies transmission of CoVs and may lead to devastating global outbreaks.

positive: COVID-19: a review. The enduring epidemic outbreak which started in Wuhan city of China, in December 2019 caused by the 2019 novel coronavirus (COVID- 19) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a dangerous and deadly Public Health disaster of International apprehension, with cases confirmed in several countries. This novel community health trouble is frightening the universe with clinical, psychological, emotional, collapse of health system and economical slowdown in each and every part of the world infecting nearly 200 countries. A highly virulent and pathogenic COVID-19 viral infection with incubation period ranging from two to fourteen days, transmitted by breathing of infected droplets or contact with infected droplets, belongs to the genus Coronavirus with its high mutation rate in the Coronaviridae. The likely probable primary reservoir could be bats, because genomic analysis discovered that SARSCoV-2 is phylogenetically interrelated to SARS-like bat viruses. The transitional resource of origin and transfer to humans is not known, however, the rapidly developing pandemic has confirmed human to human transfer. Approximately 1,016,128 reported cases, 211,615 recovered cases and 53,069 deaths of COVID-2019 have been reported to date (April 2, 2020). The symptoms vary from asymptomatic, low grade pyrexia, dry cough, sore throat, breathlessness, tiredness, body aches, fatigue, myalgia, nausea, vomiting, diarrhea, to severe consolidation and pneumonia, acute respiratory distress syndrome (ARDS) and multiple organ dysfunction leading to death with case fatality rate ranging from 2 to 3%.

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

positive: COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives The recent outbreak of COVID-19 in Wuhan turned into a public health emergency of international concern. With no antiviral drugs nor vaccines, and the presence of carriers without obvious symptoms, traditional public health intervention measures are significantly less effective. Here, we report the epidemiological and virological characteristics of the COVID-19 outbreak. Originated in bats, 2019-nCoV/ severe acute respiratory syndrome coronavirus (SARS-CoV)-2 likely experienced adaptive evolution in intermediate hosts before transfer to humans at a concentrated source of transmission. Similarities of receptor sequence binding to 2019-nCoV between humans and animals suggest a low species barrier for transmission of the virus to farm animals. We propose, based on the One Health model, that veterinarians and animal specialists should be involved in a cross-disciplinary collaboration in the fight against this epidemic.

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

positive: The origin of SARS-CoV-2 in Istanbul: Sequencing findings from the epicenter of the pandemic in Turkey OBJECTIVE: Turkey is one of the latest countries that COVID-19 disease was reported, with the first case on March 11, 2020, and since then, Istanbul became the epicenter of the pandemic in Turkey. Here, we reveal sequences of the virus isolated from three different patients with various clinical presentations. METHODS: Nasopharyngeal swab specimens of the patients were tested positive for the COVID-19 by qRT-PCR. Viral RNA extraction was performed from the same swab samples. Amplicon based libraries were prepared and sequenced using the Illumina NextSeq platform. Raw sequencing data were processed for variant calling and generating near-complete genome sequences. All three genomes were evaluated and compared with other worldwide isolates. RESULTS: The patients showed various clinics (an asymptomatic patient, patient with mild disease, and with severe pulmonary infiltration). Amplicon-based next-generation sequencing approach successfully applied to generate near-complete genomes with an average depth of 2.616. All three viral genomes carried the D614G variant (G clade according to GISAID classification) with implications for the origin of a spread first through China to Europe then to Istanbul. CONCLUSION: Here, we report the viral genomes circulating in Istanbul for the first time. Further sequencing of the virus isolates may enable us to understand variations in disease presentation and association with viral factors if there is any. In addition, the sequencing of more viral genomes will delineate the spread of disease and will guide and ease the necessary measures taken to stem the spread of the novel coronavirus.

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

positive: Predicting wildlife hosts of betacoronaviruses for SARS-CoV-2 sampling prioritization Despite massive investment in research on reservoirs of emerging pathogens, it remains difficult to rapidly identify the wildlife origins of novel zoonotic viruses. Viral surveillance is costly but rarely optimized using model-guided prioritization strategies, and predictions from a single model may be highly uncertain. Here, we generate an ensemble of eight network- and trait-based statistical models that predict mammal-virus associations, and we use model predictions to develop a set of priority recommendations for sampling potential bat reservoirs and intermediate hosts for SARS-CoV-2 and related betacoronaviruses. We find over 200 bat species globally could be undetected hosts of betacoronaviruses. Although over a dozen species of Asian horseshoe bats (Rhinolophus spp.) are known to harbor SARS-like coronaviruses, we find at least two thirds of betacoronavirus reservoirs in this bat genus might still be undetected. Although identification of other probable mammal reservoirs is likely beyond existing predictive capacity, some of our findings are surprisingly plausible; for example, several civet and pangolin species were highlighted as high-priority species for viral sampling. Our results should not be over-interpreted as novel information about the plausibility or likelihood of SARS-CoV-2’s ultimate origin, but rather these predictions could help guide sampling for novel potentially zoonotic viruses; immunological research to characterize key receptors (e.g., ACE2) and identify mechanisms of viral tolerance; and experimental infections to quantify competence of suspected host species.

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

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

positive: Genetic Grouping of SARS-CoV-2 Coronavirus Sequences using Informative Subtype Markers for Pandemic Spread Visualization We propose an efficient framework for genetic subtyping of SARS-CoV-2, the novel coronavirus that causes the COVID-19 pandemic. Efficient viral subtyping enables visualization and modeling of the geographic distribution and temporal dynamics of disease spread. Subtyping thereby advances the development of effective containment strategies and, potentially, therapeutic and vaccine strategies. However, identifying viral subtypes in real-time is challenging: SARS-CoV-2 is a novel virus, and the pandemic is rapidly expanding. Viral subtypes may be difficult to detect due to rapid evolution; founder effects are more significant than selection pressure; and the clustering threshold for subtyping is not standardized. We propose to identify mutational signatures of available SARS-CoV-2 sequences using a population-based approach: an entropy measure followed by frequency analysis. These signatures, Informative Subtype Markers (ISMs), define a compact set of nucleotide sites that characterize the most variable (and thus most informative) positions in the viral genomes sequenced from different individuals. Through ISM compression, we find that certain distant nucleotide variants covary, including non-coding and ORF1ab sites covarying with the D614G spike protein mutation which has become increasingly prevalent as the pandemic has spread. ISMs are also useful for downstream analyses, such as spatiotemporal visualization of viral dynamics. By analyzing sequence data available in the GISAID database, we validate the utility of ISM-based subtyping by comparing spatiotemporal analyses using ISMs to epidemiological studies of viral transmission in Asia, Europe, and the United States. In addition, we show the relationship of ISMs to phylogenetic reconstructions of SARS-CoV-2 evolution, and therefore, ISMs can play an important complementary role to phylogenetic tree-based analysis, such as is done in the Nextstrain [1] project. The developed pipeline dynamically generates ISMs for newly added SARS-CoV-2 sequences and updates the visualization of pandemic spatiotemporal dynamics, and is available on Github at https://github.com/EESI/ISM and via an interactive website at https://covid19-ism.coe.drexel.edu/. Author Summary The novel coronavirus responsible for COVID-19, SARS-CoV-2, expanded to reportedly 8.7 million confirmed cases worldwide by June 21, 2020. The global SARS-CoV-2 pandemic highlights the importance of tracking viral transmission dynamics in real-time. Through June 2020, researchers have obtained genetic sequences of SARS-CoV-2 from over 47,000 samples from infected individuals worldwide. Since the virus readily mutates, each sequence of an infected individual contains useful information linked to the individual’s exposure location and sample date. But, there are over 30,000 bases in the full SARS-CoV-2 genome—so tracking genetic variants on a whole-sequence basis becomes unwieldy. We describe a method to instead efficiently identify and label genetic variants, or “subtypes” of SARS-CoV-2. Applying this method results in a compact, 11 base-long compressed label, called an Informative Subtype Marker or “ISM”. We define viral subtypes for each ISM, and show how regional distribution of subtypes track the progress of the pandemic. Major findings include (1) covarying nucleotides with the spike protein which has spread rapidly and (2) tracking emergence of a local subtype across the United States connected to Asia and distinct from the outbreak in New York, which is found to be connected to Europe.

positive: Phylogenetic clustering of the Indian SARS-CoV-2 genomes reveals the presence of distinct clades of viral haplotypes among states The first Indian cases of COVID-19 caused by SARS-Cov-2 were reported in February 29, 2020 with a history of travel from Wuhan, China and so far above 4500 deaths have been attributed to this pandemic. The objectives of this study were to characterize Indian SARS-CoV-2 genome-wide nucleotide variations, trace ancestries using phylogenetic networks and correlate state-wise distribution of viral haplotypes with differences in mortality rates. A total of 305 whole genome sequences from 19 Indian states were downloaded from GISAID. Sequences were aligned using the ancestral Wuhan-Hu genome sequence (NC_045512.2). A total of 633 variants resulting in 388 amino acid substitutions were identified. Allele frequency spectrum, and nucleotide diversity (π) values revealed the presence of higher proportions of low frequency variants and negative Tajima’s D values across ORFs indicated the presence of population expansion. Network analysis highlighted the presence of two major clusters of viral haplotypes, namely, clade G with the S:D614G, RdRp: P323L variants and a variant of clade L [Lv] having the RdRp:A97V variant. Clade G genomes were found to be evolving more rapidly into multiple sub-clusters including clade GH and GR and were also found in higher proportions in three states with highest mortality rates namely, Gujarat, Madhya Pradesh and West Bengal.

positive: Evolution of genomes, host shifts and the geographic spread of SARS‐CoV and related coronaviruses Severe acute respiratory syndrome (SARS) is a novel human illness caused by a previously unrecognized coronavirus (CoV) termed SARS‐CoV. There are conflicting reports on the animal reservoir of SARS‐CoV. Many of the groups that argue carnivores are the original reservoir of SARS‐CoV use a phylogeny to support their argument. However, the phylogenies in these studies often lack outgroup and rooting criteria necessary to determine the origins of SARS‐CoV. Recently, SARS‐CoV has been isolated from various species of Chiroptera from China (e.g., Rhinolophus sinicus) thus leading to reconsideration of the original reservoir of SARS‐CoV. We evaluated the hypothesis that SARS‐CoV isolated from Chiroptera are the original zoonotic source for SARS‐CoV by sampling SARS‐CoV and non‐SARS‐CoV from diverse hosts including Chiroptera, as well as carnivores, artiodactyls, rodents, birds and humans. Regardless of alignment parameters, optimality criteria, or isolate sampling, the resulting phylogenies clearly show that the SARS‐CoV was transmitted to small carnivores well after the epidemic of SARS in humans that began in late 2002. The SARS‐CoV isolates from small carnivores in Shenzhen markets form a terminal clade that emerged recently from within the radiation of human SARS‐CoV. There is evidence of subsequent exchange of SARS‐CoV between humans and carnivores. In addition SARS‐CoV was transmitted independently from humans to farmed pigs (Sus scrofa). The position of SARS‐CoV isolates from Chiroptera are basal to the SARS‐CoV clade isolated from humans and carnivores. Although sequence data indicate that Chiroptera are a good candidate for the original reservoir of SARS‐CoV, the structural biology of the spike protein of SARS‐CoV isolated from Chiroptera suggests that these viruses are not able to interact with the human variant of the receptor of SARS‐CoV, angiotensin‐converting enzyme 2 (ACE2). In SARS‐CoV we study, both visually and statistically, labile genomic fragments and, putative key mutations of the spike protein that may be associated with host shifts. We display host shifts and candidate mutations on trees projected in virtual globes depicting the spread of SARS‐CoV. These results suggest that more sampling of coronaviruses from diverse hosts, especially Chiroptera, carnivores and primates, will be required to understand the genomic and biochemical evolution of coronaviruses, including SARS‐CoV. © The Willi Hennig Society 2008.

positive: Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes The Chinese horseshoe bat (Rhinolophus sinicus), reservoir host of severe acute respiratory syndrome coronavirus (SARS-CoV), carries many bat SARS-related CoVs (SARSr-CoVs) with high genetic diversity, particularly in the spike gene. Despite these variations, some bat SARSr-CoVs can utilize the orthologs of human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry. It is speculated that the interaction between bat ACE2 and SARSr-CoV spike proteins drives diversity. Here, we have identified a series of R. sinicus ACE2 variants with some polymorphic sites involved in the interaction with the SARS-CoV spike protein. Pseudoviruses or SARSr-CoVs carrying different spike proteins showed different infection efficiency in cells transiently expressing bat ACE2 variants. Consistent results were observed by binding affinity assays between SARS- and SARSr-CoV spike proteins and receptor molecules from bats and humans. All tested bat SARSr-CoV spike proteins had a higher binding affinity to human ACE2 than to bat ACE2, although they showed a 10-fold lower binding affinity to human ACE2 compared with their SARS-CoV counterpart. Structure modeling revealed that the difference in binding affinity between spike and ACE2 might be caused by the alteration of some key residues in the interface of these two molecules. Molecular evolution analysis indicates that these residues were under strong positive selection. These results suggest that the SARSr-CoV spike protein and R. sinicus ACE2 may have coevolved over time and experienced selection pressure from each other, triggering the evolutionary arms race dynamics. It further proves that R. sinicus is the natural host of SARSr-CoVs. Importance Evolutionary arms race dynamics shape the diversity of viruses and their receptors. Identification of key residues which are involved in interspecies transmission is important to predict potential pathogen spillover from wildlife to humans. Previously, we have identified genetically diverse SARSr-CoV in Chinese horseshoe bats. Here, we show the highly polymorphic ACE2 in Chinese horseshoe bat populations. These ACE2 variants support SARS- and SARSr-CoV infection but with different binding affinity to different spike proteins. The higher binding affinity of SARSr-CoV spike to human ACE2 suggests that these viruses have the capacity of spillover to humans. The positive selection of residues at the interface between ACE2 and SARSr-CoV spike protein suggests a long-term and ongoing coevolutionary dynamics between them. Continued surveillance of this group of viruses in bats is necessary for the prevention of the next SARS-like disease.

positive: Three adjacent nucleotide changes spanning two residues in SARS-CoV-2 nucleoprotein: possible homologous recombination from the transcription-regulating sequence The COVID-19 pandemic is caused by the single-stranded RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus of zoonotic origin that was first detected in Wuhan, China in December 2019. There is evidence that homologous recombination contributed to this cross-species transmission. Since that time the virus has demonstrated a high propensity for human-to-human transmission. Here we report two newly identified adjacent amino acid polymorphisms in the nucleocapsid at positions 203 and 204 (R203K/G204R) due to three adjacent nucleotide changes across the two codons (i.e. AGG GGA to AAA CGA). This new strain within the LGG clade may have arisen by a form of homologous recombination from the core sequence (CS-B) of the transcription-regulating sequences of SAS-CoV-2 itself and has rapidly increased to approximately one third of reported sequences from Europe during the month of March 2020. We note that these polymorphisms are predicted to reduce the binding of an overlying putative HLA-C*07-restricted epitope and that HLA-C*07 is prevalent in Caucasians being carried by >40% of the population. The findings suggest that homologous recombination may have occurred since its introduction into humans and be a mechanism for increased viral fitness and adaptation of SARS-CoV-2 to human populations.

positive: Origins of major human infectious diseases Many of the major human infectious diseases, including some now confined to humans and absent from animals, are ‘new’ ones that arose only after the origins of agriculture. Where did they come from? Why are they overwhelmingly of Old World origins? Here we show that answers to these questions are different for tropical and temperate diseases; for instance, in the relative importance of domestic animals and wild primates as sources. We identify five intermediate stages through which a pathogen exclusively infecting animals may become transformed into a pathogen exclusively infecting humans. We propose an initiative to resolve disputed origins of major diseases, and a global early warning system to monitor pathogens infecting individuals exposed to wild animals. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature05775) contains supplementary material, which is available to authorized users.

positive: 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.

positive: Ancestral origin, antigenic resemblance and epidemiological insights of novel coronavirus (SARS-CoV-2): Global burden and Bangladesh perspective SARS-CoV-2, a new coronavirus strain responsible for COVID-19 has emerged in Wuhan City, China and still continuing its worldwide pandemic nature. Considering the severity of the disease, a number of studies are underway, and full genomic sequences have already been released in the last few weeks to enable the understanding of the evolutionary origin and molecular characteristics of this virus. Bioinformatics analysis, satellite derived imaging data and epidemiological attributes were employed to investigate origin, immunogenic resemblance and global threat of newly pandemic SARS-CoV-2 including Bangladesh perspective. Based on currently available genomic information, a phylogeny study was employed focusing four types of representative viral proteins (spike, membrane, envelope and nucleoprotein) of SARS-CoV-2, HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HKU1, MERS-CoV, HKU4, HKU5 and BufCoV-HKU26. The findings clearly demonstrated that SARS-CoV-2 exhibited evolutionary convergent relation with previously reported SARS-CoV. It was also found that SARS-CoV-2 proteins were highly similar and identical to SARS-CoV proteins, though proteins from other coronaviruses showed lower level of similarity and identical patterns. The cross-checked conservancy analysis of SARS-CoV-2 antigenic epitopes showed significant conservancy with antigenic epitopes derived from SARS-CoV. The study also prioritized the temperature comparison through satellite imaging alongside compiling and analyzing the epidemiological outbreak information on the 2019 novel coronavirus based on several open datasets on COVID-19 (SARS-CoV-2) and discussed possible threats to Bangladesh.

positive: The origin and early spread of SARS-CoV-2 in Europe The investigation of migratory patterns of the SARS-CoV-2 pandemic before border closures in Europe is a crucial first step towards an in-depth evaluation of border closure policies. Here we analyze viral genome sequences using a phylodynamic model with geographic structure to estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures. Based on SARS-CoV-2 genomes, we reconstruct a partial transmission tree of the early pandemic, including inferences of the geographic location of ancestral lineages and the number of migration events into and between European regions. We find that the predominant lineage spreading in Europe has a most recent common ancestor in Italy and was probably seeded by a transmission event in either Hubei or Germany. We do not find evidence for preferential migration paths from Hubei into different European regions or from each European region to the others. Sustained local transmission is first evident in Italy and then shortly thereafter in the other European regions considered. Before the first border closures in Europe, we estimate that the rate of occurrence of new cases from within-country transmission was within the bounds of the estimated rate of new cases from migration. In summary, our analysis offers a view on the early state of the epidemic in Europe and on migration patterns of the virus before border closures. This information will enable further study of the necessity and timeliness of border closures.

positive: First 12 patients with coronavirus disease 2019 (COVID-19) in the United States Introduction: More than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. Methods: We collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. Results: Among the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. Conclusions: In 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

positive: Emergence of a Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2: Biology and Therapeutic Options The new decade of the 21st century (2020) started with the emergence of a novel coronavirus known as SARS-CoV-2 that caused an epidemic of coronavirus disease (COVID-19) in Wuhan, China. It is the third highly pathogenic and transmissible coronavirus after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in humans. The source of origin, transmission to humans, and mechanisms associated with the pathogenicity of SARS-CoV-2 are not yet clear, however, its resemblance to SARS-CoV and several other bat coronaviruses was recently confirmed through genome sequencing-related studies. The development of therapeutic strategies is necessary in order to prevent further epidemics and cure infections. In this review, we summarize current information about the emergence, origin, diversity, and epidemiology of three pathogenic coronaviruses with a specific focus on the current outbreak in Wuhan, China. Furthermore, we discuss the clinical features and potential therapeutic options that may be effective against SARS-CoV-2.

positive: CoV Genome Tracker: tracing genomic footprints of Covid-19 pandemic Summary Genome sequences constitute the primary evidence on the origin and spread of the 2019-2020 Covid-19 pandemic. Rapid comparative analysis of coronavirus SARS-CoV-2 genomes is critical for disease control, outbreak forecasting, and developing clinical interventions. CoV Genome Tracker is a web portal dedicated to trace Covid-19 outbreaks in real time using a haplotype network, an accurate and scalable representation of genomic changes in a rapidly evolving population. We resolve the direction of mutations by using a bat-associated genome as outgroup. At a broader evolutionary time scale, a companion browser provides gene-by-gene and codon-by-codon evolutionary rates to facilitate the search for molecular targets of clinical interventions. Availability and Implementation CoV Genome Tracker is publicly available at http://cov.genometracker.org and updated weekly with the data downloaded from GISAID (http://gisaid.org). The website is implemented with a custom JavaScript script based on jQuery (https://jquery.com) and D3-force (https://github.com/d3/d3-force). Contact weigang@genectr.hunter.cuny.edu, City University of New York, Hunter College Supplementary Information All supporting scripts developed in JavaScript, Python, BASH, and PERL programming languages are available as Open Source at the GitHub repository https://github.com/weigangq/cov-browser.

positive: Phyloevolutionary analysis of SARS-CoV-2 in Nigeria Abstract Background Phyloepidemiologic approaches have given specific insight to understanding emergence and evolution of infection. Knowledge on the outbreak and spread of SARS-CoV-2 in Nigeria would assist in providing preventive measures to reduce transmission among populations at risk. Therefore, this study aimed at investigating the evolution of SARS-CoV-2 in Nigeria. Materials and Method A total of 39 complete genomes of SARS-CoV-2 were retrieved from the GISAID EpiFluTM database on March 29th 2020 to investigate its evolution in Nigeria. Sequences were selected based on the travel history of the patient and the collection date. Other sequences were not selected because they were short, contained artefacts, not from original source or had insufficient information. Evolutionary history was inferred using Maximum Likelihood method based on the General Time Reversible model. Phylogenetic tree was constructed to determine the common ancestor of each strain. Results The phylogenetic analysis showed the strain in Nigeria clustered in a monophyletic clade with a Wuhan sublineage. Nucleotide alignment also showed a 100% similarity indicating a common origin of evolution. Comparative analysis showed 27,972 (93.6%) identical sites and 97.6% pairwise identity with the consensus. Conclusion The study evidently showed the entire outbreak of COVID-19 infection in Nigeria stemmed from a single introduction sharing consensus similarity with the reference SARS-CoV-2 human genome from Wuhan. Preventive measures that can limit the spread of the infection among populations at risk should be implemented.

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

positive: deepMINE - Natural Language Processing based Automatic Literature Mining and Research Summarization for Early-Stage Comprehension in Pandemic Situations specifically for COVID-19 The recent pandemic created due to Novel Coronavirus (nCOV-2019) from Wuhan, China demanding a large scale of a general health emergency. This demands novel research on the vaccine to fight against this pandemic situation, re-purposing of the existing drugs, phylogenetic analysis to identify the origin and determine the similarity with other known viruses, etc. The very preliminary task from the research community is to analyze the wide verities of existing related research articles, which is very much time-consuming in such situations where each minute counts for saving hundreds of human lives. The entire manual processing is even lower down the efficiency in mining the information. We have developed a complete automatic literature mining system that delivers efficient and fast mining from existing biomedical literature databases. With the help of modern-day deep learning algorithms, our system also delivers a summarization of important research articles that provides ease and fast comprehension of critical research articles. The system is currently scanning nearly 1,46,115,136 English words from 29,315 research articles in not greater than 1.5 seconds with multiple search keywords. Our research article presents the criticality of literature mining, especially in pandemic situations with the implementation and online deployment of the system.

positive: Transmission dynamics and evolutionary history of 2019‐nCoV To investigate the time origin, genetic diversity, and transmission dynamics of the recent 2019‐nCoV outbreak in China and beyond, a total of 32 genomes of virus strains sampled from China, Thailand, and the USA with sampling dates between 24 December 2019 and 23 January 2020 were analyzed. Phylogenetic, transmission network, and likelihood‐mapping analyses of the genome sequences were performed. On the basis of the likelihood‐mapping analysis, the increasing tree‐like signals (from 0% to 8.2%, 18.2%, and 25.4%) over time may be indicative of increasing genetic diversity of 2019‐nCoV in human hosts. We identified three phylogenetic clusters using the Bayesian inference framework and three transmission clusters using transmission network analysis, with only one cluster identified by both methods using the above genome sequences of 2019‐nCoV strains. The estimated mean evolutionary rate for 2019‐nCoV ranged from 1.7926 × 10(−3) to 1.8266 × 10(−3) substitutions per site per year. On the basis of our study, undertaking epidemiological investigations and genomic data surveillance could positively impact public health in terms of guiding prevention efforts to reduce 2019‐nCOV transmission in real‐time.

positive: A Mathematical Model of the Evolution and Spread of Pathogenic Coronaviruses from Natural Host to Human Host Coronaviruses are highly transmissible and are pathogenic viruses of the 21(st) century worldwide. In general, these viruses are originated in bats or rodents. At the same time, the transmission of the infection to the human host is caused by domestic animals that represent in the habitat the intermediate host. In this study, we review the currently collected information about coronaviruses and establish a model of differential equations with piecewise constant arguments to discuss the spread of the infection from the natural host to the intermediate, and from them to the human host, while we focus on the potential spillover of bat-borne coronaviruses. The local stability of the positive equilibrium point of the model is considered via the Linearized Stability Theorem. Besides, we discuss global stability by employing an appropriate Lyapunov function. To analyze the outbreak in early detection, we incorporate the Allee effect at time t and obtain stability conditions for the dynamical behavior. Furthermore, it is shown that the model demonstrates the Neimark-Sacker Bifurcation. Finally, we conduct numerical simulations to support the theoretical findings.

positive: SARS-CoV-2 (COVID-19): Zoonotic Origin and Susceptibility of Domestic and Wild Animals Coronaviruses (CoVs) are responsible for causing economically significant diseases both in animals and humans The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing Coronavirus Diseases (COVID-19), outbreak has become the first pandemic of the 21st century and is the deadliest pandemic after the 1918 Spanish Flu Except, the two previous epidemics, SARS-CoV (2002 epidemic, China) and MERS-CoV (2012 epidemic, Middle Eastern region), CoVs are known the world over as the mild pathogens of humans and animals Despite several measures to control the COVID-19 pandemic, it has affected more than 210 countries and regional territories distressing more than 5 3 million people and claiming nearly 0 34 million lives globally Several findings point towards the appearance of the SARS-CoV-2 virus in the humans through animals, especially the wild animals of the Chinese live seafood wet market The ongoing COVID-19 pandemic is another example of diseases originating from the human-animal interface and spreading through international borders causing global health emergencies Most of the countries around the globe are stumbling due to the COVID-19 pandemic with severe threats and panic among the mass population World Health Organization ( WHO), international and national health authorities are working with excessive efforts for effective and impactful interventions to contain the virus It is significant to comprehend the inclination of these viruses to jump between different species, and the establishment of infection in the entirely new host, identification of significant reservoirs of coronaviruses Several animal species such as cats, dogs, tiger, and minks have been confirmed to get SARS-CoV-2 infections from COVID-19 infected person Laboratory investigations point out those cats are the most susceptible species for SARS-CoV-2, and it can evidence with clinical disease The studies carried out on animal's susceptibility to SARS-CoV-2 further support the human-to-animal spread of the virus In this review, we focus on addressing COVID-19 infections in domestic and wild animals

positive: History and Philosophy of Science and the Teaching of Macroevolution Although macroevolution has been the subject of sustained attention in the history and philosophy of science (HPS) community, only in recent years have science educators begun to more fully engage with the topic. This chapter first explores how science educators have conceptualized macroevolution and how their perspectives align with the views from HPS. Second, it illustrates how science educators’ limited engagement with HPS scholarship on macroevolution has influenced construct delineation, measurement instrument development, and educational arguments about which aspects of macroevolution are most important for students to learn. Third, it discusses how scientific debates about the causal factors responsible for macroevolutionary patterns have been exploited by creationists and have impacted the teaching of evolution. Finally, it emphasizes that the rich perspectives that HPS has to offer on the important topic of macroevolution have yet to be integrated into science education scholarship.

positive: 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.

positive: Public Exposure to Live Animals, Behavioural Change, and Support in Containment Measures in response to COVID-19 Outbreak: a population-based cross sectional survey in China Background In response to the COVID-19 outbreak, we aimed to investigate behavioural change on exposure to live animals before and during the outbreak, and public support and confidence for governmental containment measures. Methods A population-based cross-sectional telephone survey via random dialing was conducted in Wuhan (the epicentre) and Shanghai (an affected city with imported cases) between 1 and 10 February, 2020. 510 residents in Wuhan and 501 residents in Shanghai were randomly sampled. Differences of outcome measures were compared before and during the outbreak, and between two cities. Findings Proportion of respondents visiting wet markets at usual was 23.3% (119/510) in Wuhan and 20.4% (102/501) in Shanghai. During the outbreak, it decreased to 3.1% (16) in Wuhan (p<0.001), and 4.4% (22) in Shanghai (p<0.001). Proportion of those consuming wild animal products declined from 10.2% (52) to 0.6% (3) in Wuhan (p<0.001), and from 5.2% (26) to 0.8% (4) in Shanghai (p<0.001). 79.0% (403) of respondents in Wuhan and 66.9% (335) of respondents in Shanghai supported permanent closure of wet markets (P<0.001). 95% and 92% of respondents supported banning wild animal trade and quarantining Wuhan, and 75% were confident towards containment measures. Females and the more educated were more supportive for the above containment measures. Interpretation The public responded quickly to the outbreak, and reduced exposure to live animals, especially in Wuhan. With high public support in containment measures, better regulation of wet markets and healthy diets should be promoted.

positive: 26 Evolution of SARS Coronavirus and the Relevance of Modern Molecular Epidemiology Abstract The severe acute respiratory syndrome (SARS) is the first major zoonotic infectious disease of the 21st Century. The disease, originally termed “atypical pneumonia,” was first recognized in November 2002 in Guangdong Province, China, which spread rapidly to 26 countries within 5months and eventually led to 8096 human infection cases and 774 deaths. A previously unrecognized coronavirus, named SARS coronavirus (SARS-CoV), was later identified as the causative agent of SARS. Subsequent investigation indicated that the source of the human infections originated most likely from infected wildlife animals traded in the live animal markets, with masked palm civets considered the most prominent and important carrier. Large-scale culling of civets appeared to be effective in preventing further outbreaks in the region. Subsequent epidemiological studies showed that civets are intermediate host of SARS-CoV and bats are the likely natural reservoir of SARS-CoV and a large number of SARS-like coronaviruses (SL-CoVs). Detailed analysis of the massive SARS-CoV genomic sequence data indicated that SARS-CoV experienced a strong selection pressure during different outbreak phases in humans as well as interspecies transmission from animals to humans. The spike glycoprotein (S) of SARS-CoV plays a key role in virus–host interaction and hence is a key determinant of interspecies transmission. It has been shown that minor changes of amino acid (aa) residues in the S protein could lead to dramatic changes in virus susceptibility in animal and human hosts. This chapter focuses on the genetics and evolution of SARS-CoVs and SL-CoVs in humans, civets, and bats. The events of SARS outbreaks and the accompanying response activities highlight the importance of modern molecular epidemiology in disease investigation and the urgent need to broaden the screening and investigation of unknown viruses in wildlife animals.

positive: Bioinformatic analysis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses OBJECTIVE: SARS-CoV-2 is responsible for the present coronavirus pandemic and some suggestions were made about its possible artificial origin. We, therefore, compared SARS-CoV-2 with such known viruses that were prepared in the laboratory and other relevant natural strains to estimate their genetic relatedness. MATERIALS AND METHODS: BLAST and clustalW were used to identify and align viral sequences of SARS-CoV-2 to other animal coronaviruses (human, bat, mouse, pangolin) and related artificial constructs. Phylogenetics trees were then prepared using iTOL. RESULTS: Our study supports the notion that known artificial coronaviruses, including the chimeric SL-SHC014-MA15 synthesized in 2015, differ too much from SARS-CoV-2 to hypothesize an artificial origin of the latter. On the contrary, our data support the natural origin of the COVID-19 virus, likely derived from bats, possibly transferred to pangolins, before spreading to man. CONCLUSIONS: Speculations about the artificial origin of SARS-CoV-2 are most likely unfounded. On the contrary, when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears.

positive: Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV

positive: The current understanding and potential therapeutic options to combat COVID-19 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.

positive: 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.

positive: Close relationship between SARS-coronavirus and group 2 coronavirus. The sudden appearance and potential lethality of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in humans has resulted in a focusing of new attention on the determination of both its origins and evolution. The relationship existing between SARS-CoV and other groups of coronaviruses was determined via analyses of phylogenetic trees and comparative genomic analyses of the coronavirus genes: polymerase (Orf1ab), spike (S), envelope (E), membrane (M) and nucleocapsid (N). Although the coronaviruses are traditionally classed into 3 groups, with SARS-CoV forming a 4th group, the phylogenetic position and origins of SARS-CoV remain a matter of some controversy. Thus, we conducted extensive phylogenetic analyses of the genes common to all coronavirus groups, using the Neighbor-joining, Maximum-likelihood, and Bayesian methods. Our data evidenced largely identical topology for all of the obtained phylogenetic trees, thus supporting the hypothesis that the relationship existing between SARS-CoV and group 2 coronavirus is a monophyletic one. Additional comparative genomic studies, including sequence similarity and protein secondary structure analyses, suggested that SARS-CoV may bear a closer relationship with group 2 than with the other coronavirus groups. Although our data strongly suggest that group 2 coronaviruses are most closely related with SARS-CoV, further and more detailed analyses may provide us with an increased amount of information regarding the origins and evolution of the coronaviruses, most notably SARS-CoV.

positive: SARS‐CoV‐2: Structural diversity, phylogeny, and potential animal host identification of spike glycoprotein To investigate the evolutionary history of the current pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a total of 137 genomes of coronavirus strains with release dates between January 2019 and 25 March 2020, were analyzed. To investigate the potential intermediate host of the SARS‐CoV‐2, we analyzed spike glycoprotein sequences from different animals, with particular emphasis on bats. We performed phylogenetic analysis and structural reconstruction of the spike glycoproteins with subsequent alignment and comparison. Our phylogenetic results revealed that SARS‐CoV‐2 was more similar to the bats' betacoronavirus isolates: HKU5‐related from Pipistrellus abramus and HKU4‐related from Tylonycteris pachypus. We also identified a yak betacoronavirus strain, YAK/HY24/CH/2017, as the closest match in the comparison of the structural models of spike glycoproteins. Interestingly, a set of unique features has been described for this particular strain of the yak betacoronavirus. Therefore, our results suggest that the human SARS‐CoV‐2, responsible for the current outbreak of COVID‐19, could also come from yak as an intermediate host.

positive: Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV) The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.

positive: Effect of the Wet Market on the coronavirus disease (COVID-19) transmission dynamics in China, 2019-2020 Abstract Objectives The novel coronavirus (SARS-CoV-2) originating from Wuhan rapidly spread throughout China. While its origin remains uncertain, accumulating evidence links a wet market for the early SARS-CoV-2 spread in Wuhan. Similarly, the influence of the marketplace on the early transmission dynamics is yet to be investigated. Methods Using the daily series of COVID-19 incidence stratified according to contact history with the market, we have conducted quantitative modeling analyses to estimate the reproduction numbers (R) for the market-to-human and human-to-human transmission, the reporting probability and the early effects of public health interventions. Results We estimated R at 0.24 (95%CrI: 0.01-1.38) for market-to-human transmission, and 2.37 (95%CrI: 2.08-2.71) for human-to-human transmission during the early spread in China (2019-2020). Moreover, we estimated that the reporting rate for cases stemming from market-to-human transmission was 2-34 fold higher than that for cases stemming from human-to-human transmission, suggesting that contact history with the wet market played a key role in identifying COVID-19 cases. Conclusions Our R estimate tied to market-to-human transmission has substantial uncertainty, but it was significantly lower compared to the reproduction number driving human-to-human transmission. Our results also suggest that asymptomatic and subclinical infections constitute a substantial component of the COVID-19 morbidity burden.

positive: PhEVER: a database for the global exploration of virus–host evolutionary relationships Fast viral adaptation and the implication of this rapid evolution in the emergence of several new infectious diseases have turned this issue into a major challenge for various research domains. Indeed, viruses are involved in the development of a wide range of pathologies and understanding how viruses and host cells interact in the context of adaptation remains an open question. In order to provide insights into the complex interactions between viruses and their host organisms and namely in the acquisition of novel functions through exchanges of genetic material, we developed the PhEVER database. This database aims at providing accurate evolutionary and phylogenetic information to analyse the nature of virus–virus and virus–host lateral gene transfers. PhEVER (http://pbil.univ-lyon1.fr/databases/phever) is a unique database of homologous families both (i) between sequences from different viruses and (ii) between viral sequences and sequences from cellular organisms. PhEVER integrates extensive data from up-to-date completely sequenced genomes (2426 non-redundant viral genomes, 1007 non-redundant prokaryotic genomes, 43 eukaryotic genomes ranging from plants to vertebrates) and offers a clustering of proteins into homologous families containing at least one viral sequences, as well as alignments and phylogenies for each of these families. Public access to PhEVER is available through its webpage and through all dedicated ACNUC retrieval systems.

positive: Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

positive: The origin and underlying driving forces of the SARS-CoV-2 outbreak The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China. SUMMARY In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.

positive: Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2 The recent outbreak of a new coronavirus (SARS-CoV-2) in Wuhan, China, underscores the need for understanding the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. Here, we show that recombination in betacoronaviruses, including human-infecting viruses like SARS-CoV and MERS-CoV, frequently encompasses the Receptor Binding Domain (RBD) in the Spike gene. We find that this common process likely led to a recombination event at least 11 years ago in an ancestor of the SARS-CoV-2 involving the RBD. As a result of this recombination event, SARS-CoV and SARS-CoV-2 share a similar genotype in RBD, including two insertions (positions 432-436 and 460-472), and alleles 427N and 436Y. Both 427N and 436Y belong to a helix that interacts with the human ACE2 receptor. Ancestral state analyses revealed that SARS-CoV-2 differentiated from its most recent common ancestor with RaTG13 by accumulating a significant number of amino acid changes in the RBD. In sum, we propose a two-hit scenario in the emergence of the SARS-CoV-2 virus whereby the SARS-CoV-2 ancestors in bats first acquired genetic characteristics of SARS-CoV by incorporation of a SARS-like RBD through recombination before 2009, and subsequently, the lineage that led to SARS-CoV-2 accumulated further, unique changes specifically in the RBD.

positive: An exclusive 42 amino acid signature in pp1ab protein provides insights into the evolutive history of the 2019 novel human‐pathogenic coronavirus (SARS‐CoV‐2) The city of Wuhan, Hubei province, China, was the origin of a severe pneumonia outbreak in December 2019, attributed to a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]), causing a total of 2761 deaths and 81109 cases (25 February 2020). SARS‐CoV‐2 belongs to genus Betacoronavirus, subgenus Sarbecovirus. The polyprotein 1ab (pp1ab) remains unstudied thoroughly since it is similar to other sarbecoviruses. In this short communication, we performed phylogenetic‐structural sequence analysis of pp1ab protein of SARS‐CoV‐2. The analysis showed that the viral pp1ab has not changed in most isolates throughout the outbreak time, but interestingly a deletion of 8 aa in the virulence factor nonstructural protein 1 was found in a virus isolated from a Japanese patient that did not display critical symptoms. While comparing pp1ab protein with other betacoronaviruses, we found a 42 amino acid signature that is only present in SARS‐CoV‐2 (AS‐SCoV2). Members from clade 2 of sarbecoviruses have traces of this signature. The AS‐SCoV2 located in the acidic‐domain of papain‐like protein of SARS‐CoV‐2 and bat‐SL‐CoV‐RatG13 guided us to suggest that the novel 2019 coronavirus probably emerged by genetic drift from bat‐SL‐CoV‐RaTG13. The implication of this amino acid signature in papain‐like protein structure arrangement and function is something worth to be explored.

positive: COVID-19, a worldwide public health emergency Abstract A new coronavirus outbreak emerged on the 31st of December 2019 in Wuhan, China, causing commotion among the medical community and the rest of the world. This new species of coronavirus has been termed 2019-nCoV and has caused a considerable number of cases of infection and deaths in China and, to a growing degree, beyond China, becoming a worldwide public health emergency. 2019-nCoV has high homology to other pathogenic coronaviruses, such as those originating from bat-related zoonosis (SARS-CoV), which caused approximately 646 deaths in China at the start of the decade. The mortality rate for 2019-nCoV is not as high (approximately 2–3%), but its rapid propagation has resulted in the activation of protocols to stop its spread. This pathogen has the potential to become a pandemic. It is therefore vital to follow the personal care recommendations issued by the World Health Organization.

positive: Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route In the epidemic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues of mutation, origin, typing and the effect of mutation on molecular detection remain to be unrevealed. In order to identify the evolutionary relationship of SARS-CoV-2 and evaluate the detection efficiency of primers that are currently used in different countries, we retrieved genomic sequences of 373 SARS-CoV-2 strains from multiple databases and performed genome-wide variation analysis. According to the nucleotide C28144T variation, the SARS-CoV-2 can be divided into group A (117 strains) and group B (256 strains). The spike protein gene (S gene) coding region 1841 (total 23403) A1841G, formed a B1 subgroup (40 strains) in group B, of which 30 strains were from European and American countries in March (especially Washington, USA). These mutations are likely to be influenced by the environment or the immunization selection pressure of different populations. Although the mutation is not in the receptor binding region (RBD) and alkaline cleavage region, it may also affect the ability of transmission and pathogenicity; however, the significance is not yet clear. As the ratio of A / B strains in the epidemic months showed an increasing trend (0.35: 1 in January, 0.62: 1 in February and 0.76: 1 in March), it seems that the transmissibility of group A strains becomes stronger with time. Based on the variation of 11 nucleotide sites during the epidemic process, it is speculated that the Washington strain is more like an ancestor type, and the Wuhan strain is the offspring of the group A virus strain. By comparing the detection capabilities of primers in different countries, the SARS-CoV-2 nucleotide variation may only affect molecular detection of very few strains. The differences in the transmissibility, pathogenicity and clinical manifestations of different types of strains require further investigations.

positive: In-silico nucleotide and protein analyses of S-gene region in selected zoonotic coronaviruses reveal conserved domains and evolutionary emergence with trajectory course of viral entry from SARS-CoV2 genomic data The recent zoonotic coronavirus virus outbreak of a novel type [COVID 19] has necessitated the adequate understanding of the evolutionary pathway of zoonotic viruses which adversely affects human populations for therapeutic constructs to combat the pandemic now and in the future. We analyzed conserved domains of the severe acute respiratory coronavirus 2 [SARS-CoV2] for possible targets of viral entry inhibition in host cells, evolutionary relationship of human coronavirus [229E] and zoonotic coronaviruses with SAR-CoV2 as well as evolutionary relationship between selected SARS-CoV 2 genomic data. Conserved domains with antagonistic action on host innate antiviral cellular mechanisms in SARS-CoV 2 include nsp 11, nsp 13 etc. Also, multiple sequence alignments of the spike [S] gene protein of selected candidate zoonotic coronaviruses alongside the S gene protein of the SARs-CoV2 revealed closest evolutionary relationship [95.6%] with pangolin coronaviruses [S] gene. Clades formed between Wuhan SARS-CoV2 phylogeny data and five others suggests viral entry trajectory while revealing genomic and protein SARS CoV 2 data from Philippines as early ancestors. Therefore, phylogeny of SARS-CoV 2 genomic data suggests profiling in diverse populations with and without the outbreak alongside migration history and racial background for mutation tracking and dating of viral subtype divergence which is essential for effective management of present and future zoonotic coronavirus outbreaks.

positive: [Editorial] Possibility of transmission through dogs being a contributing factor to the extreme Covid19 outbreak in North Italy Covid19 origin and transmission to humans. Covid19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARSCoV2 transmission. However, the source(s) and transmission routine(s) of SARSCoV2 remain elusive' (1).

positive: Identification of Diverse Bat Alphacoronaviruses and Betacoronaviruses in China Provides New Insights Into the Evolution and Origin of Coronavirus-Related Diseases Outbreaks of severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome in 2012 and fatal swine acute diarrhea syndrome in 2017 caused serious infectious diseases in humans and in livestock, resulting in serious public health threats and huge economic losses. All such coronaviruses (CoVs) were confirmed to originate from bats. To continuously monitor the epidemic-related CoVs in bats, virome analysis was used to classify CoVs from 831 bats of 15 species in Yunnan, Guangxi, and Sichuan Provinces between August 2016 and May 2017. We identified 11 CoV strains from 22 individual samples of four bat species. Identification of four alpha-CoVs from Scotophilus kuhlii in Guangxi, which was closely related to a previously reported bat CoV and porcine epidemic diarrhea virus (PEDV), revealed a bat-swine lineage under the genus Alphacoronavirus. A recombinant CoV showed that the PEDV probably originated from the CoV of S. kuhlii. Another alpha-CoV, α-YN2018, from Rhinolophus affinis in Yunnan, suggested that this alpha-CoV lineage had multiple host origins, and α-YN2018 had recombined with CoVs of other bat species over time. We identified five SARS-related CoVs (SARSr-CoVs) in Rhinolophus bats from Sichuan and Yunnan and confirmed that angiotensin-converting enzyme 2 usable SARSr-CoVs were continuously circulating in Rhinolophus spp. in Yunnan. The other beta-CoV, strain β-GX2018, found in Cynopterus sphinx of Guangxi, represented an independently evolved lineage different from known CoVs of Rousettus and Eonycteris bats. The identification of diverse CoVs here provides new genetic data for understanding the distribution and source of pathogenic CoVs in China.

positive: One Health—One Medicine: unifying human and animal medicine within an evolutionary paradigm One health is a concept since early civilization, which promoted the view that there was no major distinction between animal and human medicine. Although persisting through the 19th century, this common vision was then all but forgotten in the early 20th century. It is now experiencing a renaissance, coincident with an awakening of the role that evolutionary biology plays in human and animal health, including sexually transmitted infections (STIs). A number of STIs in humans have comparable infections in animals; likewise, both humans and animals have STIs unique to each mammalian camp. These similarities and differences offer opportunities for basic medical and public health studies, including evolutionary insights that can be gleaned from ongoing interdisciplinary investigation—especially with the molecular analytical tools available—in what can become a golden age of mutually helpful discovery.

positive: Emerging infectious diseases Abstract The spectrum of human pathogens and the infectious diseases they cause is continuously changing through evolution, selection and changes in the way human populations interact with their environment and each other. New human pathogens often emerge or re-emerge from an animal reservoir, emphasizing the central role that non-human reservoirs play in human infectious diseases. Pathogens can also re-emerge with new characteristics, such as multidrug resistance, or in different places, such as Ebola virus in West Africa in 2013 and Zika virus in Brazil in 2015, to cause new epidemics. Most human pathogens have a history of evolution in which they first emerge and cause epidemics, become unstably adapted, re-emerge periodically and then – without intervention – eventually become endemic, with the potential for future outbreaks.

positive: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2 Abstract SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.

positive: Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission

positive: Broad reception for coronavirus The discovery that a new coronavirus associated with lethal respiratory infections binds to an evolutionarily conserved receptor on airway cells suggests that direct transmission from bats to humans may occur. See Letter p.251

positive: 2019 Novel coronavirus (COVID-19) overview Novel coronaviruses (CoVs) are zoonotic pathogens, but the first human-to-human transmission has been reported. CoVs have the best known genome of all RNA viruses, and mutations in the genome have now been found. A pneumonia of unknown cause detected in Wuhan, China, was first reported to the WHO Country Office in China on 31 December 2019. This study aims to report early findings related to COVID-19 and provide methods to prevent and treat it.

positive: Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease Abstract Aims In December 2019, the Coronavirus disease-2019 (COVID-19) virus has emerged in Wuhan, China. In this research, the first resolved COVID-19 crystal structure (main protease) was targeted in a virtual screening study by of FDA approved drugs dataset. In addition, a knowledge gap in relations of COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS and MERS CoVs, was covered by investigation of sequence statistics and phylogenetics. Materials and methods Molecular modeling, virtual screening, docking, sequence comparison statistics and phylogenetics of the COVID-19 main protease were investigated. Key findings COVID-19 Mpro formed a phylogenetic group with SARS CoV that was distant from MERS CoV. The identity% was 96.061 and 51.61 for COVID-19/SARS and COVID-19/MERS CoV sequence comparisons, respectively. The top 20 drugs in the virtual screening studies comprised a broad-spectrum antiviral (ribavirin), anti-hepatitis B virus (telbivudine), two vitamins (vitamin B12 and nicotinamide) and other miscellaneous systemically acting drugs. Of special interest, ribavirin had been used in treating cases of SARS CoV. Significance The present study provided a comprehensive targeting of the first resolved COVID+19 structure of Mpro and found a suitable save drugs for repurposing against the viral Mpro. Ribavirin, telbivudine, vitamin B12 and nicotinamide can be combined and used for COVID treatment. This initiative relocates already marketed and approved safe drugs for potential use in COVID-treatment.

positive: Human Coronaviruses: General Features Abstract Human coronaviruses (HCoVs), including HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, are traditionally known to cause symptoms of common cold with only moderate clinical impact. Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), on the other hand, have strike humans in the past two decades as highly fatal human pathogens leading to considerable mortality and economic loss. This article summaries the updates on the structure, genome organization, replication and clinical features of human coronaviruses. Recent studies also shed light upon the zoonotic origin of emerging human pathogens including SARS-CoV and MERS-CoV, providing insight for future surveillance and intervention.

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

positive: The role of wildlife in emerging and re-emerging zoonoses. There are huge numbers of wild animals distributed throughout the world and the diversity of wildlife species is immense. Each landscape and habitat has a kaleidoscope of niches supporting an enormous variety of vertebrate and invertebrate species, and each species or taxon supports an even more impressive array of macro- and micro-parasites. Infectious pathogens that originate in wild animals have become increasingly important throughout the world in recent decades, as they have had substantial impacts on human health, agricultural production, wildlife-based economies and wildlife conservation. The emergence of these pathogens as significant health issues is associated with a range of causal factors, most of them linked to the sharp and exponential rise of global human activity. Among these causal factors are the burgeoning human population, the increased frequency and speed of local and international travel, the increase in human-assisted movement of animals and animal products, changing agricultural practices that favour the transfer of pathogens between wild and domestic animals, and a range of environmental changes that alter the distribution of wild hosts and vectors and thus facilitate the transmission of infectious agents. Two different patterns of transmission of pathogens from wild animals to humans are evident among these emerging zoonotic diseases. In one pattern, actual transmission of the pathogen to humans is a rare event but, once it has occurred, human-to-human transmission maintains the infection for some period of time or permanently. Some examples of pathogens with this pattern of transmission are human immunodeficiency virus/acquired immune deficiency syndrome, influenza A, Ebola virus and severe acute respiratory syndrome. In the second pattern, direct or vector-mediated animal-to-human transmission is the usual source of human infection. Wild animal populations are the principal reservoirs of the pathogen and human-to-human disease transmission is rare. Examples of pathogens with this pattern of transmission include rabies and other lyssaviruses, Nipah virus, West Nile virus, Hantavirus, and the agents of Lyme borreliosis, plague, tularemia, leptospirosis and ehrlichiosis. These zoonotic diseases from wild animal sources all have trends that are rising sharply upwards. In this paper, the authors discuss the causal factors associated with the emergence or re-emergence of these zoonoses, and highlight a selection to provide a composite view of their range, variety and origins. However, most of these diseases are covered in more detail in dedicated papers elsewhere in this Review.

positive: The COVID-19 Pandemic and Paradigm Change in Global Scientific Research. The current pandemic has rocked the lives of human beings every-where in ways never imagined, forcing us to question where our civilization is headed. In this article, we explore and discuss scien-tifi c evidence that helps explain recent events in the context of the COVID-19 pandemic.COVID-19 is caused by infection with a zoonotic-origin novel virus, SARS-CoV-2, that is genetically close to two coronavirus types iso-lated in bats. The transmission dynamics to humans from the original and intermediary hosts remain poorly understood, but it is highly likely that the SARS-CoV-2 virus infected humans after undergoing an inter-species transfer from bats to an intermediate species, and from there to human beings. Crossing the species barrier is largely fostered by industrial-scale agricultural practices that simplify original ecosystem connections by reducing biodiversity, facilitating the emergence of new infectious diseases. The scientifi c community has played an exemplary role in responding to this global emergency, working to fi nd timely, relevant solutions for governments and society as a whole. We need to take this opportunity to promote a global and open science that delves into the interrelation-ships of the biological, environmental, social and economic dimen-sions of this and other diseases while questioning current modes of production and their impact on the environment, and thus on human health worldwide. Keywords: Coronavirus infections; communicable diseases; zoonoses; ecosystems; technology, industry, and agriculture; pandemics; global health; Mexico.

positive: The risk of SARS-CoV-2 transmission to pets and other wild and domestic animals strongly mandates a one-health strategy to control the COVID-19 pandemic

positive: Full-Genome Deep Sequencing and Phylogenetic Analysis of Novel Human Betacoronavirus A novel betacoronavirus associated with lethal respiratory and renal complications was recently identified in patients from several countries in the Middle East. We report the deep genome sequencing of the virus directly from a patient’s sputum sample. Our high-throughput sequencing yielded a substantial depth of genome sequence assembly and showed the minority viral variants in the specimen. Detailed phylogenetic analysis of the virus genome (England/Qatar/2012) revealed its close relationship to European bat coronaviruses circulating among the bat species of the Vespertilionidae family. Molecular clock analysis showed that the 2 human infections of this betacoronavirus in June 2012 (EMC/2012) and September 2012 (England/Qatar/2012) share a common virus ancestor most likely considerably before early 2012, suggesting the human diversity is the result of multiple zoonotic events.

positive: Could India be the origin of next COVID-19 like epidemic? The COVID-19 global pandemic is not even over yet but it has already taught us a lot of lessons - the hard way. The vast majority of the global community has blamed the Chinese Illegal wildlife markets for the origin of this pandemic. Through careful scientific analysis, I have explained in this article that we don't need such wildlife markets for these kinds of outbreaks to occur in the future. I have also explained how India which is the second-most populous country in the world, could be the origin of the next outbreak, even though such wildlife markets are either very rare or do not exist at all in India.

positive: The divergence between SARS-CoV-2 and RaTG13 might be overestimated due to the extensive RNA modification Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. There is urgent need to understand the phylogeny, divergence and origin of SARS-CoV-2. Materials & methods: A recent study claimed that there was 17% divergence between SARS-CoV-2 and RaTG13 (a SARS-related coronaviruses) on synonymous sites by using sequence alignment. We re-analyzed the sequences of the two coronaviruses with the same methodology. Results: We found that 87% of the synonymous substitutions between the two coronaviruses could be potentially explained by the RNA modification system in hosts, with 65% contributed by deamination on cytidines (C-T mismatches) and 22% contributed by deamination on adenosines (A-G mismatches). Conclusion: Our results demonstrate that the divergence between SARS-CoV-2 and RaTG13 has been overestimated.

positive: Commentary: Origin and evolution of pathogenic coronaviruses

positive: Influenza A virus transmission via respiratory aerosols or droplets as it relates to pandemic potential Many respiratory viruses of humans originate from animals. For instance, there are now eight paramyxoviruses, four coronaviruses and four orthomxoviruses that cause recurrent epidemics in humans but were once confined to other hosts. In the last decade, several members of the same virus families have jumped the species barrier from animals to humans. Fortunately, these viruses have not become established in humans, because they lacked the ability of sustained transmission between humans. However, these outbreaks highlighted the lack of understanding of what makes a virus transmissible. In part triggered by the relatively high frequency of occurrence of influenza A virus zoonoses and pandemics, the influenza research community has started to investigate the viral genetic and biological traits that drive virus transmission via aerosols or respiratory droplets between mammals. Here we summarize recent discoveries on the genetic and phenotypic traits required for airborne transmission of zoonotic influenza viruses of subtypes H5, H7 and H9 and pandemic viruses of subtypes H1, H2 and H3. Increased understanding of the determinants and mechanisms of respiratory virus transmission is not only key from a basic scientific perspective, but may also aid in assessing the risks posed by zoonotic viruses to human health, and preparedness for such risks.

positive: Coronavirus Infection and Diversity in Bats in the Australasian Region Following the SARS outbreak, extensive surveillance was undertaken globally to detect and identify coronavirus diversity in bats. This study sought to identify the diversity and prevalence of coronaviruses in bats in the Australasian region. We identified four different genotypes of coronavirus, three of which (an alphacoronavirus and two betacoronaviruses) are potentially new species, having less than 90% nucleotide sequence identity with the most closely related described viruses. We did not detect any SARS-like betacoronaviruses, despite targeting rhinolophid bats, the putative natural host taxa. Our findings support the virus-host co-evolution hypothesis, with the detection of Miniopterus bat coronavirus HKU8 (previously reported in Miniopterus species in China, Hong Kong and Bulgaria) in Australian Miniopterus species. Similarly, we detected a novel betacoronavirus genotype from Pteropus alecto which is most closely related to Bat coronavirus HKU9 identified in other pteropodid bats in China, Kenya and the Philippines. We also detected possible cross-species transmission of bat coronaviruses, and the apparent enteric tropism of these viruses. Thus, our findings are consistent with a scenario wherein the current diversity and host specificity of coronaviruses reflects co-evolution with the occasional host shift.

positive: SARS‐CoV‐2, the Virus that Causes COVID‐19: Cytometry and the New Challenge for Global Health

positive: Variant analysis of SARS-CoV-2 strains in Middle Eastern countries Background SARS-CoV-2 is diverging from the initial Wuhan serotype, and different variants of the virus are reported. Mapping the variant strains and studying their pattern of evolution will provide better insights into the pandemic spread Methods Data on different SARS-CoV2 for WHO EMRO countries were obtained from the Chinese National Genomics Data Center (NGDC), Genbank and the Global Initiative on Sharing All Influenza Data (GISAID). Multiple sequence alignments (MSA) was performed to study the evolutionary relationship between the genomes. Variant calling, genome and variant alignment were performed to track the strains in each country. Evolutionary and phylogenetic analysis is used to explore the evolutionary hypothesis. Findings Of the total 50 samples, 4 samples did not contain any variants. Variant calling identified 379 variants. Earliest strains are found in Iranian samples. Variant alignment indicates Iran samples have a low variant frequency. Saudi Arabia has formed an outgroup. Saudi Arabia, Qatar and Kuwait were the most evolved genomes and are the countries with the highest number of cases per million. Interpretation Iran was exposed to the virus earlier than other countries in the Eastern Mediterranean Region. Funding None

positive: Binding Ability Prediction between Spike Protein and Human ACE2 Reveals the Adaptive Strategy of SARS-CoV-2 in Humans SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing an outbreak of COVID-19 globally in the past six months. A relatively higher divergence on the spike protein of SASR-CoV-2 enables it to transmit across species efficiently. We particularly believe that the adaptive mutations of the receptor-binding domain (RBD) of spike protein in SARS-CoV-2 might be essential to its high transmissibility among humans. Thus here we collected 2,142 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny, and also analyzed the interaction between the polymorphisms of spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 and coronavirus in other hosts show SARS-CoV-2 is highly possible originated from Bat-CoV (RaTG13) found in horseshoe bat and a recombination event may occur on the spike protein of Pangolin-CoV to imbue it the ability to infect humans. Moreover, compared to the S gene of SARS-CoV-2, it is more conserved in the direct-binding sites of RBD and we noticed that spike protein of SARS-CoV-2 may under a consensus evolution to adapt to human hosts better. 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 were simulated and their stability and affinity binding to hACE2 (S19-D615) were calculated. Our analysis indicates SARS-CoV-2 could infect humans from different populations with no preference, and a higher divergence in the spike protein of SARS-CoV-2 at the early stage of this pandemic may be a good indicator that could show the pathway of SARS-CoV-2 transmitting from the natural reservoir to human beings.

positive: Emergence of a Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2: Biology and Therapeutic Options The new decade of the 21(st) century (2020) started with the emergence of a novel coronavirus known as SARS-CoV-2 that caused an epidemic of coronavirus disease (COVID-19) in Wuhan, China. It is the third highly pathogenic and transmissible coronavirus after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in humans. The source of origin, transmission to humans, and mechanisms associated with the pathogenicity of SARS-CoV-2 are not yet clear, however, its resemblance to SARS-CoV and several other bat coronaviruses was recently confirmed through genome sequencing-related studies. The development of therapeutic strategies is necessary in order to prevent further epidemics and cure infections. In this review, we summarize current information about the emergence, origin, diversity, and epidemiology of three pathogenic coronaviruses with a specific focus on the current outbreak in Wuhan, China. Furthermore, we discuss the clinical features and potential therapeutic options that may be effective against SARS-CoV-2.

positive: Whole Genome Analysis and Targeted Drug Discovery Using Computational Methods and High Throughput Screening Tools for Emerged Novel Coronavirus (2019-nCoV) A novel coronavirus designated as SARS-CoV-2 in February 2020 by World Health organization (WHO) was identified as main cause of SARS like pneumonia cases in Wuhan city in Hubei Province of China at the end of 2019 This been recently declared as Global Pandemic by WHO There is a global emergency to identify potential drugs to treat the SARS-CoV-2 Currently, there is no specific treatment against the new virus There is a urgency to identifying potential antiviral agents to combat the disease is urgently needed An effective and quick approach is to test existing antiviral drugs against Whole genome analysis and alignment carried out using BLASTn, SMART BLAST and WebDSV 2 0 had shown more than 238 ORF's coding for proteins mostly origin from Bat SARS coronavirus and root genomic origin from Archaea Molecular docking results against protein targets Furin, papain like proteases, RdRp and Spike glycoprotein had shown paritaprevir, ritonavir, entecavir and chloroquine derivatives are the best drugs to inhibit multi targets of coronavirus infection including natural compounds corosolic acid, baicalin and glycyrrhizic acid with minimal inhibitory concentrations Thus we propose use of paritaprevir, entecavir, ritonavir and chloroquine derivatives as best drug combination along with niacinamide, folic acid and zinc supplements to treat novel coronavirus infection We also propose use of plant protease inhibitors (PI's) and Anti-IL8, IL-6, IL-2 as future drug models against coronavirus

positive: Global genetic patterns reveal host tropism versus cross-taxon transmission of bat Betacoronaviruses Emerging infectious diseases due to coronavirus (CoV) infections have received significant global attention in the past decade and have been linked to bats as the original source. The diversity, distribution, and host associations of bat CoVs were investigated to assess their potential for zoonotic transmission. Phylogenetic, network, and principal coordinate analysis confirmed the classification of betacoronaviruses (BetaCoVs) into five groups (2A to 2E) and a potentially novel group, with further division of 2D into five subgroups. The genetic co-clustering of BetaCoVs among closely related bats reflects host taxon-specificity with each bat family as the host for a specific BetaCoV group, potentially a natural barrier against random transmission. The divergent pathway of BetaCoV and host evolution suggests that the viruses were introduced just prior to bat dispersal and speciation. As such, deviant patterns were observed such as for 2D-IV, wherein cross-taxon transmission due to overlap in bat habitats and geographic range among genetically divergent African bat hosts could have played a strong role on their shared CoV lineages. In fact, a few bat taxa especially the subfamily Pteropodinae were shown to host diverse groups of BetaCoVs. Therefore, ecological imbalances that disturb bat distribution may lead to loss of host specificity through cross-taxon transmission and multi-CoV infection. Hence, initiatives that minimize the destruction of wildlife habitats and limit wildlife-livestock-human interfaces are encouraged to help maintain the natural state of bat BetaCoVs in the wild. Importance Bat Betacoronaviruses (BetaCoVs) pose a significant threat to global public health and have been implicated in several epidemics such as the recent pandemic by severe acute respiratory syndrome coronavirus 2. Here, we show that bat BetaCoVs are predominantly host-specific, which could be a natural barrier against infection of other host types. However, a strong overlap in bat habitat and geographic range may facilitate viral transmission to unrelated hosts, and a few bat families have already been shown to host multi-CoV variants. We predict that continued disturbances on the ecological balance may eventually lead to loss of host specificity. When combined with enhanced wildlife-livestock-human interfaces, spillover to humans may be further facilitated. We should therefore start to define the ecological mechanisms surrounding zoonotic events. Global surveillance should be expanded and strengthened to assess the complete picture of bat coronavirus diversity and distribution and their potential to cause spillover infections.

positive: Potential host range of multiple SARS-like coronaviruses and an improved ACE2-Fc variant that is potent against both SARS-CoV-2 and SARS-CoV-1 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a currently uncontrolled pandemic and the etiological agent of coronavirus disease 2019 (COVID-19). It is important to study the host range of SARS-CoV-2 because some domestic species might harbor the virus and transmit it back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. Here we show that ACE2 orthologs of a wide range of domestic and wild animals support entry of SARS-CoV-2, as well as that of SARS-CoV-1, bat coronavirus RaTG13, and a coronavirus isolated from pangolins. Some of these species, including camels, cattle, horses, goats, sheep, pigs, cats, and rabbits may serve as potential intermediate hosts for new human transmission, and rabbits in particular may serve as a useful experimental model of COVID-19. We show that SARS-CoV-2 and SARS-CoV-1 entry could be potently blocked by recombinant IgG Fc-fusion proteins of viral spike protein receptor-binding domains (RBD-Fc) and soluble ACE2 (ACE2-Fc). Moreover, an ACE2-Fc variant, which carries a D30E mutation and has ACE2 truncated at its residue 740 but not 615, outperforms all the other ACE2-Fc variants on blocking entry of both viruses. Our data suggest that RBD-Fc and ACE2-Fc could be used to treat and prevent infection of SARS-CoV-2 and any new viral variants that emerge over the course of the pandemic.

positive: A novel bat coronavirus reveals natural insertions at the S1/S2 cleavage site of the Spike protein and a possible recombinant origin of HCoV-19 The unprecedented epidemic of pneumonia caused by a novel coronavirus, HCoV-19, in China and beyond has caused public health concern at a global scale. Although bats are regarded as the most likely natural hosts for HCoV-191,2, the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. RmYN02 shared 93.3% nucleotide identity with HCoV-19 at the scale of the complete virus genome and 97.2% identity in the 1ab gene in which it was the closest relative of HCoV-19. In contrast, RmYN02 showed low sequence identity (61.3%) to HCoV-19 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, however, and in a similar manner to HCoV-19, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the Spike (S) protein. This provides strong evidence that such insertion events can occur in nature. Together, these data suggest that HCoV-19 originated from multiple naturally occurring recombination events among those viruses present in bats and other wildlife species.

positive: Bioinformatic analysis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses. OBJECTIVE SARS-CoV-2 is responsible for the present coronavirus pandemic and some suggestions were made about its possible artificial origin. We, therefore, compared SARS-CoV-2 with such known viruses that were prepared in the laboratory and other relevant natural strains to estimate their genetic relatedness. MATERIALS AND METHODS BLAST and clustalW were used to identify and align viral sequences of SARS-CoV-2 to other animal coronaviruses (human, bat, mouse, pangolin) and related artificial constructs. Phylogenetics trees were then prepared using iTOL. RESULTS Our study supports the notion that known artificial coronaviruses, including the chimeric SL-SHC014-MA15 synthesized in 2015, differ too much from SARS-CoV-2 to hypothesize an artificial origin of the latter. On the contrary, our data support the natural origin of the COVID-19 virus, likely derived from bats, possibly transferred to pangolins, before spreading to man. CONCLUSIONS Speculations about the artificial origin of SARS-CoV-2 are most likely unfounded. On the contrary, when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears.

positive: COVID-19 and the clinical hematology laboratory The ongoing COVID-19 pandemic originated in Wuhan, Hubei Province, China, in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID-19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID-19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to (a) provide background context about the origins and course of the pandemic, (b) discuss the laboratory's role in the diagnosis of COVID-19 infection, (c) summarize the current state of biomarker analysis in COVID-19 infection, with an emphasis on markers derived from the hematology laboratory, (d) comment on the impact of COVID-19 on hematology laboratory safety, and (e) describe the impact the pandemic has had on organized national and international educational activities worldwide.

positive: In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs Coronavirus disease-2019 (COVID-19) outbreak due to novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has come out as a major threat for mankind in recent times. It is continually taking an enormous toll on mankind by means of increasing number of deaths, associated comorbidities, and socioeconomic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to scientists and doctors for developing an urgent therapeutic strategy. In this connection, the present in silico study aims to understand the sequence divergence of spike protein (the major infective protein of SARS-CoV-2), its mode of interaction with the angiotensin-converting enzyme-2 receptor (ACE2) receptor of human and related animal hosts/reservoir. Moreover, the involvement of the human Toll-like receptors (TLRs) against the spike protein has also been demonstrated. Our data indicated that the spike glycoprotein of SARS-CoV-2 is phylogenetically close to bat coronavirus and strongly binds with ACE2 receptor protein from both human and bat origin. We have also found that cell surface TLRs, especially TLR4 is most likely to be involved in recognizing molecular patterns from SARS-CoV-2 to induce inflammatory responses. The present study supported the zoonotic origin of SARS-CoV-2 from a bat and also revealed that TLR4 may have a crucial role in the virus-induced inflammatory consequences associated with COVID-19. Therefore, selective targeting of TLR4-spike protein interaction by designing competitive TLR4-antagonists could pave a new way to treat COVID-19. Finally, this study is expected to improve our understanding on the immunobiology of SARS-CoV-2 and could be useful in adopting spike protein, ACE2, or TLR-guided intervention strategy against COVID-19 shortly.

positive: Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection Summary Background The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus. Whole genome sequence analysis of various isolates might provide an indication of potential strain differences of this new virus. Moreover, mutation analysis will help to develop effective vaccines. Methods We sequenced the entire SARS viral genome of cultured isolates from the index case (SIN2500) presenting in Singapore, from three primary contacts (SIN2774, SIN2748, and SIN2677), and one secondary contact (SIN2679). These sequences were compared with the isolates from Canada (TOR2), Hong Kong (CUHK-W1 and HKU39849), Hanoi (URBANI), Guangzhou (GZ01), and Beijing (BJ01, BJ02, BJ03, BJ04). Findings We identified 129 sequence variations among the 14 isolates, with 16 recurrent variant sequences. Common variant sequences at four loci define two distinct genotypes of the SARS virus. One genotype was linked with infections originating in Hotel M in Hong Kong, the second contained isolates from Hong Kong, Guangzhou, and Beijing with no association with Hotel M (p<0.0001). Moreover, other common sequence variants further distinguished the geographical origins of the isolates, especially between Singapore and Beijing. Interpretation Despite the recent onset of the SARS epidemic, genetic signatures are emerging that partition the worldwide SARS viral isolates into groups on the basis of contact source history and geography. These signatures can be used to trace sources of infection. In addition, a common variant associated with a non-conservative aminoacid change in the S1 region of the spike protein, suggests that immunological pressures might be starting to influence the evolution of the SARS virus in human populations. Published online May 9, 2003 http://image.thelancet.com/extras/03art4454web.pdf

positive: Genetic characterization of Betacoronavirus lineage C viruses in bats reveals marked sequence divergence in the spike protein of pipistrellus bat coronavirus HKU5 in Japanese pipistrelle: implications for the origin of the novel Middle East respiratory syndrome coronavirus. While the novel Middle East respiratory syndrome coronavirus (MERS-CoV) is closely related to Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) and Pipistrellus bat CoV HKU5 (Pi-BatCoV HKU5) in bats from Hong Kong, and other potential lineage C betacoronaviruses in bats from Africa, Europe, and America, its animal origin remains obscure. To better understand the role of bats in its origin, we examined the molecular epidemiology and evolution of lineage C betacoronaviruses among bats. Ty-BatCoV HKU4 and Pi-BatCoV HKU5 were detected in 29% and 25% of alimentary samples from lesser bamboo bat (Tylonycteris pachypus) and Japanese pipistrelle (Pipistrellus abramus), respectively. Sequencing of their RNA polymerase (RdRp), spike (S), and nucleocapsid (N) genes revealed that MERS-CoV is more closely related to Pi-BatCoV HKU5 in RdRp (92.1% to 92.3% amino acid [aa] identity) but is more closely related to Ty-BatCoV HKU4 in S (66.8% to 67.4% aa identity) and N (71.9% to 72.3% aa identity). Although both viruses were under purifying selection, the S of Pi-BatCoV HKU5 displayed marked sequence polymorphisms and more positively selected sites than that of Ty-BatCoV HKU4, suggesting that Pi-BatCoV HKU5 may generate variants to occupy new ecological niches along with its host in diverse habitats. Molecular clock analysis showed that they diverged from a common ancestor with MERS-CoV at least several centuries ago. Although MERS-CoV may have diverged from potential lineage C betacoronaviruses in European bats more recently, these bat viruses were unlikely to be the direct ancestor of MERS-CoV. Intensive surveillance for lineage C betaCoVs in Pipistrellus and related bats with diverse habitats and other animals in the Middle East may fill the evolutionary gap.

positive: Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019 A novel coronavirus (nCoV-2019) was the cause of an outbreak of respiratory illness detected in Wuhan, Hubei Province, China in December of 2019. Genomic analyses of nCoV-2019 determined a 96% resemblance with a coronavirus isolated from a bat in 2013 (RaTG13); however, the receptor binding motif (RBM) of these two genomes share low sequence similarity. This divergence suggests a possible alternative source for the RBM coding sequence in nCoV-2019. We identified high sequence similarity in the RBM between nCoV-2019 and a coronavirus genome reconstructed from a viral metagenomic dataset from pangolins possibly indicating a more complex origin for nCoV-2019.

positive: Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in the city of Wuhan in China and has widely spread worldwide. Currently, it is vital to explore potential intermediate hosts of SARS-CoV-2 to control COVID-19 spread. Therefore, we reinvestigated published data from pangolin lung samples from which SARS-CoV-like CoVs were detected by Liu et al. [1]. We found genomic and evolutionary evidence of the occurrence of a SARS-CoV-2-like CoV (named Pangolin-CoV) in dead Malayan pangolins. Pangolin-CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the whole-genome level. Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Five key amino acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and SARS-CoV-2, but four amino acid mutations are present in RaTG13. Both Pangolin-CoV and RaTG13 lost the putative furin recognition sequence motif at S1/S2 cleavage site that can be observed in the SARS-CoV-2. Conclusively, this study suggests that pangolin species are a natural reservoir of SARS-CoV-2-like CoVs.

positive: COVID-19: the First Documented Coronavirus Pandemic in History Abstract The novel human coronavirus disease COVID-19 has become the fifth documented pandemic since the 1918 flu pandemic. COVID-19 was first reported in Wuhan, China, and subsequently spread worldwide. The coronavirus was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses based on phylogenetic analysis. SARS-CoV-2 is believed to be a spillover of an animal coronavirus and later adapted the ability of human-to-human transmission. Because the virus is highly contagious, it rapidly spreads and continuously evolves in the human population. In this review article, we discuss the basic properties, potential origin, and evolution of the novel human coronavirus. These factors may be critical for studies of pathogenicity, antiviral designs, and vaccine development against the virus.

positive: [What is the origin of SARS-CoV-2?] Every time a pandemic occurs, dozens of theories emerge to attribute the origin of the event to different facts. The COVID-19 pandemic that has hit virtually all the globe has been no exception. What is known so far about the origin of the virus that causes COVID 19? The first investigations on the origin of this disease have determined that it is a new type of virus, the origin of which is most likely zoonotic.

positive: Coronaviruses in cats and other companion animals: Where does SARS-CoV-2/COVID-19 fit? • Coronaviruses are wide-ranging diseases in humans and animals. • SARS-CoV-2 is a bat-origin zoonotic coronavirus causing the COViD-19 pandemic. • SARS-CoV-2 can also infect cats and ferrets and has been detected in dogs. • The SARS-CoV-2 receptor ACE2 is highly similar between cats and humans.

positive: Broad and differential animal ACE2 receptor usage by SARS-CoV-2. The COVID-19 pandemic has caused an unprecedented global public health and economy crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, comparing to the SARS-CoV-2-like CoVs identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human ACE2 as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2 from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activity, respectively. Among the remaining species, ACE2 from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.IMPORTANCE SARS-CoV-2 uses human ACE2 as primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologues and found that wild type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models and molecular basis of receptor binding for SARS-CoV-2.

positive: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus BACKGROUND: As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus. METHODS: In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R(0)) from the RP model to assess the transmissibility of the SARS-CoV-2. RESULTS: The value of R(0) was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. CONCLUSIONS: Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.

positive: Master Regulator Analysis of the SARS-CoV-2/Human Interactome The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we set out to shed light on the SARS-CoV-2/host receptor recognition, a crucial factor for successful virus infection. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, we performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus.

positive: The novel Chinese coronavirus (2019‐nCoV) infections: Challenges for fighting the storm Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. They shared a connection with the Huanan South China Seafood Market in Wuhan, and now it has been confirmed that the disease is caused by a novel coronavirus (provisionally named 2019-nCoV). As of today (30 January 2020), 7734 cases have been confirmed in China, and 90 cases have also been cumulatively reported from Taiwan, Thailand, Vietnam, Malaysia, Nepal, Sri Lanka, Cambodia, Japan, Singapore, Republic of Korea, United Arab Emirate, United States, The Philippines, India, Australia, Canada, Finland, France, and Germany (Finland, France and Germany are the only European countries in which cases [n= 1, n = 5, and n = 4, respectively] have been reported up to date). According to the released news, the case rate fatality is 2.2% (170/7824).

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

positive: Betacoronavirus Adaptation to Humans Involved Progressive Loss of Hemagglutinin-Esterase Lectin Activity Human beta1-coronavirus (β1CoV) OC43 emerged relatively recently through a single zoonotic introduction. Like related animal β1CoVs, OC43 uses 9-O-acetylated sialic acid as receptor determinant. β1CoV receptor binding is typically controlled by attachment/fusion spike protein S and receptor-binding/receptor-destroying hemagglutinin-esterase protein HE. We show that following OC43’s introduction into humans, HE-mediated receptor binding was selected against and ultimately lost through progressive accumulation of mutations in the HE lectin domain. Consequently, virion-associated receptor-destroying activity toward multivalent glycoconjugates was reduced and altered such that some clustered receptor populations are no longer cleaved. Loss of HE lectin function was also observed for another respiratory human coronavirus, HKU1. This thus appears to be an adaptation to the sialoglycome of the human respiratory tract and for replication in human airways. The findings suggest that the dynamics of virion-glycan interactions contribute to host tropism. Our observations are relevant also to other human respiratory viruses of zoonotic origin, particularly influenza A virus.

positive: The first two cases of 2019‐nCoV in Italy: Where they come from? A novel Coronavirus, 2019‐nCoV, has been identified as the causal pathogen of an ongoing epidemic, with the first cases reported in Wuhan, China, last December 2019, and has since spread to other countries worldwide, included Europe and very recently Italy. In this short report, phylogenetic reconstruction was used to better understand the transmission dynamics of the virus from its first introduction in China focusing on the more recent evidence of infection in a couple of Chinese tourists arrived in Italy on 23rd January 2020 and labeled as Coronavirus Italian cases. A maximum clade credibility tree has been built using a dataset of 54 genome sequences of 2019‐nCoV plus two closely related bat strains (SARS‐like CoV) available in GenBank. Bayesian time‐scaled phylogenetic analysis was implemented in BEAST 1.10.4. The Bayesian phylogenetic reconstruction showed that 2019‐2020 nCoV firstly introduced in Wuhan on 25 November 2019, started epidemic transmission reaching many countries worldwide, including Europe and Italy where the two strains isolated dated back 19 January 2020, the same that the Chinese tourists arrived in Italy. Strains isolated outside China were intermixed with strains isolated in China as evidence of likely imported cases in Rome, Italy, and Europe, as well. In conclusion, this report suggests that further spread of 2019‐nCoV epidemic was supported by human mobility and that quarantine of suspected or diagnosed cases is useful to prevent further transmission. Viral genome phylogenetic analysis represents a useful tool for the evaluation of transmission dynamics and preventive action.

positive: Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Coronavirus has emerged as a global health treat due to its accelerated geographic spread over the last two decades. This article reviews the current state of knowledge concerning the origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Historically, it has caused two pandemics: severe acute respiratory syndrome and Middle East respiratory syndrome followed by the present COVID-19 that emerged from China. The virus is believed to be acquired from zoonotic source and spreads through direct and contact transmission. The symptomatic phase manifests with fever, cough and myalgia to severe respiratory failure. The diagnosis is confirmed using reverse transcriptase PCR. Management of COVID-19 is mainly by supportive therapy along with mechanical ventilation in severe cases. Preventive strategies form the major role in reducing the public spread of virus along with successful disease isolation and community containment. Development of a vaccine to eliminate the virus from the host still remains an ongoing challenge.

positive: COVID-19 Outbreak: An Overview BACKGROUND: In late December 2019, Chinese health authorities reported an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province. SUMMARY: A few days later, the genome of a novel coronavirus was released (http://viro-logical.org/t/novel-2019-coronavirus-genome/319; Wuhan-Hu-1, GenBank accession No. MN908947) and made publicly available to the scientific community. This novel coronavirus was provisionally named 2019-nCoV, now SARS-CoV-2 according to the Coronavirus Study Group of the International Committee on Taxonomy of Viruses. SARS-CoV-2 belongs to the Coronaviridae family, Betacoronavirus genus, subgenus Sarbecovirus. Since its discovery, the virus has spread globally, causing thousands of deaths and having an enormous impact on our health systems and economies. In this review, we summarize the current knowledge about the epidemiology, phylogenesis, homology modeling, and molecular diagnostics of SARS-CoV-2. Key Messages: Phylogenetic analysis is essential to understand viral evolution, whereas homology modeling is important for vaccine strategies and therapies. Highly sensitive and specific diagnostic assays are key to case identification, contact tracing, identification of the animal source, and implementation of control measures.

positive: Data analytics for novel coronavirus disease This paper describes different aspects of novel coronavirus disease (COVID-19), presents visualization of the spread of the infection, and discusses the potential applications of data analytics on this viral infection. Firstly, a literature survey is done on COVID-19 highlighting a number of factors including its origin, its similarity with previous coronaviruses, its transmission capacity, its symptoms, etc. Secondly, data analytics is applied on a dataset of Johns Hopkins University to find out the spread of the viral infection. It is shown here that although the disease started in China in December 2019, the highest number of confirmed cases up to June 04, 2020 is in the USA. Thirdly, the worldwide increase in the number of confirmed cases over time is modelled here using a polynomial regression algorithm with degree 2. Fourthly, classification algorithms are applied on a dataset of 5644 samples provided by Hospital Israelita Albert Einstein of Brazil in order to diagnose COVID-19. It is shown here that multilayer perceptron (MLP), XGBoost and logistic regression can classify COVID-19 patients at an accuracy above 91%. Finally, a discussion is presented on the potential applications of data analytics in several important factors of COVID-19.

positive: The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins SARS-CoV-2 emerged in late 2019, leading to the COVID-19 pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as well as related coronaviruses circulating in bats, SARS-CoV-2 is thought to have originated in Chiroptera species in China. However, whether the virus spread directly to humans or through an intermediate host is currently unclear, as is the potential for this virus to infect companion animals, livestock and wildlife that could act as viral reservoirs. Using a combination of surrogate entry assays and live virus we demonstrate that, in addition to human ACE2, the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins. Of the twenty-two different hosts we investigated, ACE2 proteins from dog, cat and rabbit were the most permissive to SARS-CoV-2, while bat and bird ACE2 proteins were the least efficiently used receptors. The absence of a significant tropism for any of the three genetically distinct bat ACE2 proteins we examined indicates that SARS-CoV-2 receptor usage likely shifted during zoonotic transmission from bats into people, possibly in an intermediate reservoir. Interestingly, while SARS-CoV-2 pseudoparticle entry was inefficient in cells bearing the ACE2 receptor from bats or birds the live virus was still able to enter these cells, albeit with markedly lower efficiency. The apparently broad tropism of SARS-CoV-2 at the point of viral entry confirms the potential risk of infection to a wide range of companion animals, livestock and wildlife.

positive: Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV) The outbreaks of 2002/2003 SARS, 2012/2015 MERS and 2019/2020 Wuhan respiratory syndrome clearly indicate that genome evolution of an animal coronavirus (CoV) may enable it to acquire human transmission ability, and thereby to cause serious threats to global public health. It is widely accepted that CoV human transmission is driven by the interactions of its spike protein (S-protein) with human receptor on host cell surface; so, quantitative evaluation of these interactions may be used to assess the human transmission capability of CoVs. However, quantitative methods directly using viral genome data are still lacking. Here, we perform large-scale protein-protein docking to quantify the interactions of 2019-nCoV S-protein receptor-binding domain (S-RBD) with human receptor ACE2, based on experimental SARS-CoV S-RBD-ACE2 complex structure. By sampling a large number of thermodynamically probable binding conformations with Monte Carlo algorithm, this approach successfully identified the experimental complex structure as the lowest-energy receptor-binding conformations, and hence established an experiment-based strength reference for evaluating the receptor-binding affinity of 2019-nCoV via comparison with SARS-CoV. Our results show that this binding affinity is about 73% of that of SARS-CoV, supporting that 2019-nCoV may cause human transmission similar to that of SARS-CoV. Thus, this study presents a method for rapidly assessing the human transmission capability of a newly emerged CoV and its mutant strains, and demonstrates that post-genome analysis of protein-protein interactions may provide early scientific guidance for viral prevention and control.

positive: The First 75 Days of Novel Coronavirus (SARS-CoV-2) Outbreak: Recent Advances, Prevention, and Treatment The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) outbreak has engulfed an unprepared world amidst a festive season. The zoonotic SARS-CoV-2, believed to have originated from infected bats, is the seventh member of enveloped RNA coronavirus. Specifically, the overall genome sequence of the SARS-CoV-2 is 96.2% identical to that of bat coronavirus termed BatCoV RaTG13. Although the current mortality rate of 2% is significantly lower than that of SARS (9.6%) and Middle East respiratory syndrome (MERS) (35%), SARS-CoV-2 is highly contagious and transmissible from human to human with an incubation period of up to 24 days. Some statistical studies have shown that, on average, one infected patient may lead to a subsequent 5.7 confirmed cases. Since the first reported case of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 on December 1, 2019, in Wuhan, China, there has been a total of 60,412 confirmed cases with 1370 fatalities reported in 25 different countries as of February 13, 2020. The outbreak has led to severe impacts on social health and the economy at various levels. This paper is a review of the significant, continuous global effort that was made to respond to the outbreak in the first 75 days. Although no vaccines have been discovered yet, a series of containment measures have been implemented by various governments, especially in China, in the effort to prevent further outbreak, whilst various medical treatment approaches have been used to successfully treat infected patients. On the basis of current studies, it would appear that the combined antiviral treatment has shown the highest success rate. This review aims to critically summarize the most recent advances in understanding the coronavirus, as well as the strategies in prevention and treatment.

positive: Chapter 19 Species Inquirendae in the Carnivora Abstract There are at least 483 reports of carnivore apicomplexans in the literature citing 17 genera or generic categoriesthat have not been described sufficiently or there was so little information provided by the author(s), that their validity, and sometimes even their identity is in question. These include: 2 “Apicomplexa protozoa,” 1 Besnoitia sp., 34 Coccidia-like or Coccidia spp., 135 Cryptosporidium spp., 2 Cyclospora spp., 26 Cystoisospora spp., 36 Eimeria spp., 3 Hammondia-like forms; 7 Hammondia–Neospora-like forms; 7 Hammondia–Toxoplasma-like forms; 14 Hepatozoon spp., 1 Hoareosporidium sp., 72 Isospora spp., 1 Klossia sp., 1 “oocysts,” 135 Sarcocystis spp., and 3 Toxoplasma-like forms. All are considered species inquirendae. In addition, two names, Isospora novocati of Pellérdy, 1974b and Isospora mustelae of Galli-Valerio, 1932, are considered nomen nuda, by definition. There is no record that 37/72 (51%) Caniformia genera, and all their 60 species, and 37/54 (68.5%) Feliformia genera, and all their 49 species, have any of these abbreviated identifications attached to them because most, if not all, likely were never surveyed for intestinal coccidian parasites. And, in the 52 genera that have been surveyed, the vast majority of their 177 species have not yet been looked at for coccidia.

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

positive: The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1 COVID-19 pandemic is a global crisis that threatens our way of life. As of April 29, 2020, COVID-19 has claimed more than 200,000 lives, with a global mortality rate of ~7% and recovery rate of ~30%. Understanding the interaction of cellular targets to the SARS-CoV2 infection is crucial for therapeutic development. Therefore, the aim of this study was to perform a comparative analysis of transcriptomic signatures of infection of COVID-19 compared to different respiratory viruses (Ebola, H1N1, MERS-CoV, and SARS-CoV), to determine unique anti-COVID1-19 gene signature. We identified for the first time molecular pathways for Heparin-binding, RAGE, miRNA, and PLA2 inhibitors, to be associated with SARS-CoV2 infection. The NRCAM and SAA2 that are involved in severe inflammatory response, and FGF1 and FOXO1 genes, which are associated with immune regulation, were found to be associated with a cellular gene response to COVID-19 infection. Moreover, several cytokines, most significantly the IL-8, IL-6, demonstrated key associations with COVID-19 infection. Interestingly, the only response gene that was shared between the five viral infections was SERPINB1. The PPI study sheds light on genes with high interaction activity that COVID-19 shares with other viral infections. The findings showed that the genetic pathways associated with Rheumatoid arthritis, AGE-RAGE signaling system, Malaria, Hepatitis B, and Influenza A were of high significance. We found that the virogenomic transcriptome of infection, gene modulation of host antiviral responses, and GO terms of both COVID-19 and Ebola are more similar compared to SARS, H1N1, and MERS. This work compares the virogenomic signatures of highly pathogenic viruses and provides valid targets for potential therapy against COVID-19.

positive: Virology, Epidemiology, Pathogenesis, and Control of COVID-19 The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Scientific advancements since the pandemic of severe acute respiratory syndrome (SARS) in 2002~2003 and Middle East respiratory syndrome (MERS) in 2012 have accelerated our understanding of the epidemiology and pathogenesis of SARS-CoV-2 and the development of therapeutics to treat viral infection. As no specific therapeutics and vaccines are available for disease control, the epidemic of COVID-19 is posing a great threat for global public health. To provide a comprehensive summary to public health authorities and potential readers worldwide, we detail the present understanding of COVID-19 and introduce the current state of development of measures in this review.

positive: Evidence for a common evolutionary origin of coronavirus spike protein receptor-binding subunits. Among different coronavirus genera, the receptor-binding S1 subunits of their spike proteins differ in primary, secondary, and tertiary structures. This study identified shared structural topologies (connectivity of secondary structural elements) in S1 domains of different coronavirus genera. The results suggest that coronavirus S1 subunits share a common evolutionary origin but have attained diverse sequences and structures following extensive divergent evolution. The results also increase understanding of the structures and functions of coronavirus S1 domains whose tertiary structures are currently unknown.

positive: Recommendations on the clinical management of the COVID-19 infection by the «new coronavirus» SARS-CoV2. Spanish Paediatric Association working group Abstract On 31 December 2019, the Wuhan Municipal Committee of Health and Healthcare (Hubei Province, China) reported that there were 27 cases of pneumonia of unknown origin with symptoms starting on the 8 December. There were 7 serious cases with common exposure in market with shellfish, fish, and live animals, in the city of Wuhan. On 7 January 2020, the Chinese authorities identified that the agent causing the outbreak was a new type of virus of the Coronaviridae family, temporarily called «new coronavirus», 2019-nCoV. On January 30th, 2020, the World Health Organisation (WHO) declared the outbreak an International Emergency. On 11 February 2020 the WHO assigned it the name of SARS-CoV2 and COVID-19 (SARS-CoV2 and COVID-19). The Ministry of Health summoned the Specialties Societies to prepare a clinical protocol for the management of COVID-19. The Spanish Paediatric Association appointed a Working Group of the Societies of Paediatric Infectious Diseases and Paediatric Intensive Care to prepare the present recommendations with the evidence available at the time of preparing them.

positive: Phylogenetic and recombination analysis of coronavirus HKU1, a novel coronavirus from patients with pneumonia Phylogenetic trees constructed using predicted amino acid sequences of putative proteins of coronavirus HKU1 (CoV-HKU1) revealed that CoV-HKU1 formed a distinct branch among group 2 coronaviruses. Of the 14 trees from p65 to nsp10, nine showed that CoV-HKU1 was clustered with murine hepatitis virus. From nsp11, the topologies of the trees changed dramatically. For the eight trees from nsp11 to N, seven showed that the CoV-HKU1 branch was the first branch. The codon usage patterns of CoV-HKU1 differed significantly from those in other group 2 coronaviruses. Split decomposition analysis revealed that recombination events had occurred between CoV-HKU1 and other coronaviruses.

positive: Evidence of Increasing Diversification of Emerging SARS‐CoV‐2 Strains BACKGROUND: On January 30th, 2020, an outbreak of atypical pneumonia caused by a novel Betacoronavirus (βCoV), named SARS‐CoV‐2, was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS‐CoV‐2 strains currently circulating in different geographic regions of the world was performed. METHODS: A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS‐CoV‐2 strains recently isolated in Europe, North America, South America and Asia was performed. RESULTS: The results of these studies revealed a diversification of SARS‐CoV‐2 strains in three different genetic clades. Co‐circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor (tMRCA) was established to be around November 1, 2019. A mean rate of evolution of 6.57 x 10(‐4) substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. CONCLUSION: The results of these studies revealed an increasing diversification of SARS‐CoV‐2 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS‐CoV‐2 strains. This article is protected by copyright. All rights reserved.

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: Broad and differential animal ACE2 receptor usage by SARS-CoV-2 The COVID-19 pandemic has caused an unprecedented global public health and economy crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, comparing to the SARS-CoV-2-like CoVs identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human ACE2 as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2 from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activity, respectively. Among the remaining species, ACE2 from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.

positive: A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein Summary The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1,2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.

positive: Animal coronaviruses: what can they teach us about the severe acute respiratory syndrome? In 2002, a new coronavirus (CoV) emerged in the People's Republic of China, associated with a severe acute respiratory syndrome (SARS) and mortality in humans. The epidemic rapidly spread throughout the world before being contained in 2003, although sporadic cases occurred thereafter in Asia. The virus is thought to be of zoonotic origin from a wild animal reservoir (Himalayan palm civets [Paguma larvata] are suspected), but the definitive host is unknown. There is concern about possible transmission of SARS CoV to rodents or domestic cats (as proven experimentally) with perpetuation of the disease in these species. In livestock and poultry, CoVs are recognised causes of enteric and respiratory infections that are often fatal in young animals. Although the emergence of SARS surprised the medical community, veterinary coronavirologists had previously isolated CoVs from wildlife and documented their interspecies transmission to livestock. Furthermore, scientists were aware of compelling evidence pointing to the emergence of new CoV strains and the mutation of existing strains resulting in new disease syndromes in animals, but the evolution and disease impact of CoVs was not widely appreciated before SARS. This review focuses on the comparative pathogenesis of CoV infections, including the factors that accentuate CoV respiratory disease, with emphasis on livestock and poultry. The goal is to provide insights into CoV transmission and disease mechanisms that could potentially be applicable to SARS, highlighting the contributions of veterinary scientists to this area of study. Such examples illustrate the need for communication and collaboration between the veterinary and medical communities to understand and control emerging zoonotic diseases of the 21st Century.

positive: Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel enzootic betacoronavirus that was first described in September 2012. The clinical spectrum of MERS-CoV infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. Bats harbour several betacoronaviruses that are closely related to MERS-CoV but more research is needed to establish the relationship between bats and MERS-CoV. The seroprevalence of MERS-CoV antibodies is very high in dromedary camels in Eastern Africa and the Arabian Peninsula. MERS-CoV RNA and viable virus have been isolated from dromedary camels, including some with respiratory symptoms. Furthermore, near-identical strains of MERS-CoV have been isolated from epidemiologically linked humans and camels, confirming inter-transmission, most probably from camels to humans. Though inter-human spread within health care settings is responsible for the majority of reported MERS-CoV cases, the virus is incapable at present of causing sustained human-to-human transmission. Clusters can be readily controlled with implementation of appropriate infection control procedures. Phylogenetic and sequencing data strongly suggest that MERS-CoV originated from bat ancestors after undergoing a recombination event in the spike protein, possibly in dromedary camels in Africa, before its exportation to the Arabian Peninsula along the camel trading routes. MERS-CoV serosurveys are needed to investigate possible unrecognized human infections in Africa. Amongst the important measures to control MERS-CoV spread are strict regulation of camel movement, regular herd screening and isolation of infected camels, use of personal protective equipment by camel handlers and enforcing rules banning all consumption of unpasteurized camel milk and urine.

positive: Comparative pathogenesis of bovine and porcine respiratory coronaviruses in the animal host species and SARS-CoV-2 in humans. Discovery of bats with severe acute respiratory syndrome (SARS)-related coronaviruses (CoVs) raised the spector of potential future outbreaks of zoonotic SARS-CoV-like disease in humans, which largely went unheeded. Nevertheless, the novel SARS-CoV-2 of bat ancestoral origin emerged to infect humans in Wuhan, China in late 2019 and then became a global pandemic. Less than 5 months after its emergence, millions of people worldwide have been infected asymptomatically or symptomatically and at least 360,000 have died. Coronavirus disease 2019 (COVID-19) in severely affected patients includes atypical pneumonia characterized by a dry cough, persistent fever, and progressive dyspnea and hypoxia, sometimes accompanied by diarrhea and often followed by multiple organ failure, especially, the respiratory and cardiovascular systems. In this mini-review, we focus on two endemic respiratory CoV infections of livestock: Bovine coronavirus (BCoV) and porcine respiratory coronavirus (PRCV). Both animal respiratory CoVs share some common features with SARS-CoV and SARS-CoV-2. BCoV has a broad host range including wild ruminants and a zoonotic potential. BCoV also has a dual tropism for the respiratory and gastrointestinal tracts. These aspects, their interspecies transmission and certain factors that impact disease severity in cattle parallel related facets of SARS-CoV or SARS-CoV-2 in humans. PRCV has a tissue tropism for the upper and lower respiratory tracts and a cellular tropism for type 1 and 2 pneumocytes in lung, but is generally a mild infection unless complicated by other exacerbating factors, such as bacterial or viral co-infections and immunosuppression (corticosteroids).

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

positive: Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2) Since December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan, Central China and rapidly spread throughout China. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests). The results showed that 80 haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain mutations abundance in the genomes of SARS-CoV-2, which may be explaining the existing widespread and high adaptation of the deadly virus. Phylogenetic analysis showed that the view, pangolin acted as an intermediate host, may be controversial. The network indicated that, in the original haplotype (H14), one patient sample lived near the Huanan seafood market (approximate 2 km), indicating high possibility of the patient having a history of unconscious contact with this market. However, based on this clue, we cannot accurately concluded that whether this market was the origin center of SARS-CoV-2. Additionally, 16 genomes, collected from this market, assigned to 10 haplotypes, indicated a circulating infection within the market in a short term and then leading to the outbreak of SARS-CoV-2 in Wuhan and other areas. The EBSP results showed that the first estimated expansion date of SARS-CoV-2 began from 7 December 2019, which may indicated that the transmission could have begun from person to person in mid to late November.

positive: The global spread of 2019-nCoV: a molecular evolutionary analysis The global spread of the 2019-nCoV is continuing and is fast moving, as indicated by the WHO raising the risk assessment to high. In this article, we provide a preliminary phylodynamic and phylogeographic analysis of this new virus. A Maximum Clade Credibility tree has been built using the 29 available whole genome sequences of 2019-nCoV and two whole genome sequences that are highly similar sequences from Bat SARS-like Coronavirus available in GeneBank. We are able to clarify the mechanism of transmission among the countries which have provided the 2019-nCoV sequence isolates from their patients. The Bayesian phylogeographic reconstruction shows that the 2019-2020 nCoV most probably originated from the Bat SARS-like Coronavirus circulating in the Rhinolophus bat family. In agreement with epidemiological observations, the most likely geographic origin of the new outbreak was the city of Wuhan, China, where 2019-nCoV time of the most recent common ancestor emerged, according to molecular clock analysis, around November 25th, 2019. These results, together with previously recorded epidemics, suggest a recurring pattern of periodical epizootic outbreaks due to Betacoronavirus. Moreover, our study describes the same population genetic dynamic underlying the SARS 2003 epidemic, and suggests the urgent need for the development of effective molecular surveillance strategies of Betacoronavirus among animals and Rhinolophus of the bat family.

positive: [Analysis of variation and evolution of SARS-CoV-2 genome] OBJECTIVE: To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019. METHODS: We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution. RESULTS: The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of ß Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic. CONCLUSIONS: SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.

positive: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.

positive: Deep phylogenetic analysis of Orthocoronavirinae genomes traces the origin, evolution and transmission route of 2019 novel coronavirus The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan city, China in December 2019 and thereafter its spillover across the world has created a global pandemic and public health crisis. Today, it appears as a threat to human civilization. Scientists and medical practitioners across the world are involved to trace out the origin and evolution of SARS-CoV-2 (also called 2019 novel coronavirus and referred as 2019-nCoV), its transmission route, cause of pathogenicity, and possible remedial action. In this work, we aim to find out the origin, evolutionary patternthat led to its pathogenicity and possible transmission pathway of 2019-nCoV. To achieve the aims we conducted a large-scale deep phylogenetic analysis on the 162 complete Orthocoronavirinae genomes consisting of four genera namely Alphacoronavirus, Betacoronavirus, Deltacoronavirus and Gammacoronavirus, their gene trees analysis and subsequently genome and gene recombination analyses. Our analyses revealed that i) bat, pangolin and anteater are the natural hosts of 2019-nCoV, ii) outbreak of 2019-nCoV took place via inter-intra species transmission mode, iii) host-specific adaptive mutation made 2019-nCoV more virulent, and the presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity. Highlights Orthocoronavirinae genome phylogeny revealed that bat, pangolin and anteater are natural reservoir hosts of novel coronavirus (2019-nCoV/SARS-CoV-2). Host-specific adaptive mutation occurred among the coronaviruses. Transmission of 2019-nCoV to human took place by inter-intra species mode of transmission. Presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity.

positive: The COVID-19 pandemic. In December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei Province, China. Pneumonia cases were epidemiologically linked to the Huanan Seafood Wholesale Market. Inoculation of respiratory samples into human airway epithelial cells, Vero E6 and Huh7 cell lines, led to the isolation of a novel respiratory virus whose genome analysis showed it to be a novel coronavirus related to SARS-CoV, and therefore named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus belonging to the subgenus Sarbecovirus. The global spread of SARS-CoV-2 and the thousands of deaths caused by coronavirus disease (COVID-19) led the World Health Organization to declare a pandemic on 12 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. In this review, we provide information regarding the epidemiology, serological and molecular diagnosis, origin of SARS-CoV-2 and its ability to infect human cells, and safety issues. Then we focus on the available therapies to fight COVID-19, the development of vaccines, the role of artificial intelligence in the management of the pandemic and limiting the spread of the virus, the impact of the COVID-19 epidemic on our lifestyle, and preparation for a possible second wave.

positive: 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.

positive: Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates Severe acute respiratory syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a fatal disease. Prevention of future outbreaks is essential and requires understanding pathogenesis and evolution of the virus. We have isolated a SARS-CoV in China and analyzed 47 SARS-CoV genomes with the aims to reveal the evolution trends of the virus and provide insights into understanding pathogenesis and SARS epidemic. Specimen from a SARS patient was inoculated into cell culture. The presence of SARS-CoV was determined by RT-PCR and confirmed by electron microscopy. Virus was isolated followed by the determination of its genome sequences, which were then analyzed by comparing with other 46 SARS-CoV genomes. Genetic mutations with potential implications to pathogenesis and the epidemic were characterized. This viral genome consists of 29,728 nucleotides with overall organization in agreement with that of published isolates. A total of 348 positions were mutated on 47 viral genomes. Among them 22 had mutations in more than three genomes. Hot spots of nucleotide variations and unique trends of mutations were identified on the viral genomes. Mutation rates were different from gene to gene and were correlated well with periodical or geographic characteristics of the epidemic.

positive: Initial success in the identification and management of the coronavirus disease 2019 (COVID-19) indicates human-to-human transmission in Wuhan, China Coronavirus (CoV) has been one of the major pandemic threats to human health in the last two decades. The human coronavirus was first identified in 1960s. CoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV have caused numerous disasters or human deaths worldwide. Recently, an outbreak of the previously unknown deadly CoV disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome CoV 2 (SARS-CoV-2, early named 2019-nCoV) occurred in Wuhan, China, and it had caused 81238 cases of confirmed infection, including 3250 deaths until March 19, 2020. Its risks and pandemic potential have brought global consideration. We summarized epidemiology, virological characteristics, clinical symptoms, diagnostic methods, clinical treatments, and prevention methods for COVID-19 to present a reference for the future wave of probable CoV outbreaks.

positive: Stochastic dynamics of an epidemic with recurrent spillovers from an endemic reservoir Abstract Most emerging human infectious diseases have an animal origin. While zoonotic diseases originate from a reservoir, most theoretical studies have principally focused on single-host processes, either exclusively humans or exclusively animals, without considering the importance of animal to human transmission (i.e. spillover transmission) for understanding the dynamics of emerging infectious diseases. Here we aim to investigate the importance of spillover transmission for explaining the number and the size of outbreaks. We propose a simple continuous time stochastic Susceptible-Infected-Recovered model with a recurrent infection of an incidental host from a reservoir (e.g. humans by a zoonotic species), considering two modes of transmission, (1) animal-to-human and (2) human-to-human. The model assumes that (i) epidemiological processes are faster than other processes such as demographics or pathogen evolution and that (ii) an epidemic occurs until there are no susceptible individuals left. The results show that during an epidemic, even when the pathogens are barely contagious, multiple outbreaks are observed due to spillover transmission. Overall, the findings demonstrate that the only consideration of direct transmission between individuals is not sufficient to explain the dynamics of zoonotic pathogens in an incidental host.

positive: Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission.

positive: Voice from China: nomenclature of the novel coronavirus and related diseases

positive: Comparative pathogenesis of bovine and porcine respiratory coronaviruses in the animal host species and SARS-CoV-2 in humans Discovery of bats with severe acute respiratory syndrome (SARS)-related coronaviruses (CoVs) raised the spector of potential future outbreaks of zoonotic SARS-CoV-like disease in humans, which largely went unheeded. Nevertheless, the novel SARS-CoV-2 of bat ancestoral origin emerged to infect humans in Wuhan, China in late 2019 and then became a global pandemic. Less than 5 months after its emergence, millions of people worldwide have been infected asymptomatically or symptomatically and at least 360,000 have died. Coronavirus disease 2019 (COVID-19) in severely affected patients includes atypical pneumonia characterized by a dry cough, persistent fever, and progressive dyspnea and hypoxia, sometimes accompanied by diarrhea and often followed by multiple organ failure, especially, the respiratory and cardiovascular systems. In this mini-review, we focus on two endemic respiratory CoV infections of livestock: Bovine coronavirus (BCoV) and porcine respiratory coronavirus (PRCV). Both animal respiratory CoVs share some common features with SARS-CoV and SARS-CoV-2. BCoV has a broad host range including wild ruminants and a zoonotic potential. BCoV also has a dual tropism for the respiratory and gastrointestinal tracts. These aspects, their interspecies transmission and certain factors that impact disease severity in cattle parallel related facets of SARS-CoV or SARS-CoV-2 in humans. PRCV has a tissue tropism for the upper and lower respiratory tracts and a cellular tropism for type 1 and 2 pneumocytes in lung, but is generally a mild infection unless complicated by other exacerbating factors, such as bacterial or viral co-infections and immunosuppression (corticosteroids).

positive: Insight into 2019 novel coronavirus - An updated interim review and lessons from SARS-CoV and MERS-CoV 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 literature, 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 indicated 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.

positive: Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.

positive: Phylogeny of Viruses☆ Abstract Biological species, including viruses, change through generations and over time in the process known as evolution. Viruses may evolve at high, uneven, and fluctuating rates among genome sites. The accumulated changes, through either mutation or recombination with other species, are first fixed in the genome of successful individuals that give rise to genetic lineages. The relationship between biological lineages related by common descent is called ‘phylogeny’. For inferring phylogeny, the differences between aligned sequences of genomes and proteins are quantified and depicted in the form of a tree, in which contemporary species and their intermediate and common ancestors occupy, respectively, the terminal nodes, internal nodes, and the root. The tree is characterized by a topology, length of branches, shape, and the root position. A complex mathematical apparatus has been developed for phylogeny inference that can evaluate inter-species differences, facilitate tree building and comparison of trees, and assess the fit between data and tree through, typically, computationally intensive calculations. A reconstructed tree is an approximation of the true phylogeny that practically remains unknown. The phylogenetic analysis is used in applied and fundamental virus research, including epidemiology, diagnostics, forensic studies, phylogeography, evolutionary studies, and virus taxonomy. It can provide an evolutionary perspective on variation of any trait that can be measured for a group of viruses.

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

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

positive: Betacoronavirus Genomes: How Genomic Information has been Used to Deal with Past Outbreaks and the COVID-19 Pandemic In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002-2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2. We focus on shared genomic features of the betacoronaviruses and the application of genomic information to phylogenetic analysis, molecular epidemiology and the design of diagnostic systems, potential drugs and vaccine candidates.

positive: Strategies to trace back the origin of COVID-19

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/2 u. 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: The Origin and Evolution of Viruses The lecture covers three main topics: (i) Viruses: properties, place in the living world, and possible origin; (ii) Molecular basis of viral variability and evolution; and (iii) Evolution of viral pathogenicity and emerging viral infections.

positive: Origins of MERS-CoV, and lessons for 2019-nCoV

positive: Phylogenetic study of 2019-nCoV by using alignment-free method The origin and early spread of 2019-nCoV is studied by phylogenetic analysis using IC-PIC alignment-free method based on DNA/RNA sequence information correlation (IC) and partial information correlation (PIC). The topology of phylogenetic tree of Betacoronavirus is remarkably consistent with biologist's systematics, classifies 2019-nCoV as Sarbecovirus of Betacoronavirus and supports the assumption that these novel viruses are of bat origin with pangolin as one of the possible intermediate hosts. The novel virus branch of phylogenetic tree shows location-virus linkage. The placement of root of the early 2019-nCoV tree is studied carefully in Neighbor Joining consensus algorithm by introducing different out-groups (Bat-related coronaviruses, Pangolin coronaviruses and HIV viruses etc.) and comparing with UPGMA consensus trees. Several oldest branches (lineages) of the 2019-nCoV tree are deduced that means the COVID-19 may begin to spread in several regions in the world before its outbreak in Wuhan.

positive: Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic There are outstanding evolutionary questions on the recent emergence of coronavirus SARS-CoV-2/hCoV-19 in Hubei province that caused the COVID-19 pandemic, including (1) the relationship of the new virus to the SARS-related coronaviruses, (2) the role of bats as a reservoir species, (3) the potential role of other mammals in the emergence event, and (4) the role of recombination in viral emergence. Here, we address these questions and find that the sarbecoviruses – the viral subgenus responsible for the emergence of SARS-CoV and SARS-CoV-2 – exhibit frequent recombination, but the SARS-CoV-2 lineage itself is not a recombinant of any viruses detected to date. In order to employ phylogenetic methods to date the divergence events between SARS-CoV-2 and the bat sarbecovirus reservoir, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were consistent for all three recombination-free alignments and robust to two different prior specifications based on HCoV-OC43 and MERS-CoV evolutionary rates. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% HPD: 1879-1999), 1969 (95% HPD: 1930-2000), and 1982 (95% HPD: 1948-2009). Despite intensified characterization of sarbecoviruses since SARS, the lineage giving rise to SARS-CoV-2 has been circulating unnoticed for decades in bats and been transmitted to other hosts such as pangolins. The occurrence of a third significant coronavirus emergence in 17 years together with the high prevalence and virus diversity in bats implies that these viruses are likely to cross species boundaries again. In Brief The Betacoronavirus SARS-CoV-2 is a member of the sarbecovirus subgenus which shows frequent recombination in its evolutionary history. We characterize the extent of this genetic exchange and identify non-recombining regions of the sarbecovirus genome using three independent methods to remove the effects of recombination. Using these non-recombining genome regions and prior information on coronavirus evolutionary rates, we obtain estimates from three approaches that the most likely divergence date of SARS-CoV-2 from its most closely related available bat sequences ranges from 1948 to 1982. Key Points RaTG13 is the closest available bat virus to SARS-CoV-2; a sub-lineage of these bat viruses is able to infect humans. Two sister lineages of the RaTG13/SARS-CoV-2 lineage infect Malayan pangolins. The sarbecoviruses show a pattern of deep recombination events, indicating that there are high levels of co-infection in horseshoe bats and that the viral pool can generate novel allele combinations and substantial genetic diversity; the sarbecoviruses are efficient ‘explorers’ of phenotype space. The SARS-CoV-2 lineage is not a recent recombinant, at least not involving any of the bat or pangolin viruses sampled to date. Non-recombinant regions of the sarbecoviruses can be identified, allowing for phylogenetic inference and dating to be performed. We constructed three such regions using different methods. We estimate that RaTG13 and SARS-CoV-2 diverged 40 to 70 years ago. There is a diverse unsampled reservoir of generalist viruses established in horseshoe bats. While an intermediate host responsible for the zoonotic event cannot be ruled out, the relevant evolution for spillover to humans very likely occurred in horseshoe bats.

positive: Newly identified viral genomes in pangolins with fatal disease Epizootic pathogens pose a major threat to many wildlife species, particularly in the context of rapidly changing environments. Pangolins (order Pholidota) are highly threatened mammals, in large part due to the trade in illegal wildlife. During July to August 2018 four sick wild pangolins (three Manis javanica and one Manis pentadactyla) exhibiting a variety of clinical symptoms were rescued by the Jinhua Wildlife Protection Station in Zhejiang province, China. Although three of these animals died, fortunately one recovered after 2 weeks of symptomatic treatment. Using meta-transcriptomics combined with reverse transcription polymerase chain reaction (RT-PCR), we identified two novel RNA viruses in two of the dead pangolins. Genomic analysis revealed that these viruses were most closely related to pestiviruses and coltiviruses, although still highly genetically distinct, with more than 48 and 25 per cent sequence divergence at the amino acid level, respectively. We named these Dongyang pangolin virus (DYPV) and Lishui pangolin virus (LSPV) based on the sampling site and hosts. Although coltiviruses (LSPV) are known to be transmitted by ticks, we found no evidence of LSPV in ticks sampled close to where the pangolins were collected. In addition, although DYPV was present in nymph ticks (Amblyomma javanense) collected from a diseased pangolin, they were not found in the local tick population. Epidemiological investigation revealed that both novel viruses might have been imported following the illegal international trade of pangolins. Hence, these data indicate that illegal wildlife trafficking not only threatens the status of pangolin populations, but may also spread epizootic pathogens.

positive: [Analysis of variation and evolution of SARS-CoV-2 genome]. OBJECTIVE To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019. METHODS We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution. RESULTS The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of β Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic. CONCLUSIONS SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.

positive: Origin and Evolution of the 2019 Novel Coronavirus

positive: Selection of and recombination between minor variants lead to the adaptation of an avian coronavirus to primate cells Abstract An interesting question posed by the current evidence that severe acute respiratory syndrome coronavirus may be originated from an animal coronavirus is how such an animal coronavirus breaks the host species barrier and becomes zoonotic. In this report, we study the chronological order of genotypic changes in the spike protein of avian coronavirus infectious bronchitis virus (IBV) during its adaptation to a primate cell line. Adaptation of the Beaudette strain of IBV from chicken embryo to Vero cells showed the accumulation of 49 amino acid mutations. Among them, 26 (53.06%) substitutions were located in the S protein. Sequencing analysis and comparison of the S gene demonstrated that the majority of the mutations were accumulated and fixed at passage 7 on Vero cells and minor variants were isolated in several passages. Evidence present suggests that the dominant Vero cell-adapted IBV strain may be derived from the chicken embryo passages by selection of and potential recombination between the minor variants. This may explain why adaptation is a rapid process and the dominant strain, once adapted to a new host cell, becomes relatively stable.

positive: Lessons from SARS-CoV-2 Pandemic: Evolution, Disease Dynamics and Future The COVID-19 pandemic is rising at an unprecedented rate. The surging number of deaths every day, global lockdown and travel restrictions have resulted in huge losses to society. The impact is massive and will leave a historical footprint. The Spanish Flu of 1918, which was the last pandemic that had a similar impact, was shadowed under the consequences of World War I. All the brilliance, strength and economies of countries worldwide are aimed at fighting the COVID-19 pandemic. The knowledge about coronavirus dynamics, its nature and epidemiology are expanding every day. The present review aims to summarize the structure, epidemiology, symptoms, statistical status of the disease status, intervention strategies and deliberates the lessons learnt during the pandemic. The intervention approaches, antiviral drug repurposing and vaccine trials are intensified now. Statistical interpretations of disease dynamics and their projections may help the decision-makers.

positive: 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.

positive: SARS-CoV-2 and COVID-19: The most important research questions Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.

positive: Characterization of the substitution hotspots in SARS-CoV-2 genome using BioAider and detection of a SR-rich region in N protein providing further evidence of its animal origin The novel human coronavirus (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic worldwide. The increasing sequencing data have shown abundant single nucleotide variations in SARS-CoV-2 genome. However, it is difficult to quickly analyze genomic variation and screen key mutations of SARS-CoV-2. In this study, we developed a visual program, named BioAider, for quick and convenient sequence annotation and mutation analysis on multiple genome-sequencing data. Using BioAider, we conducted a comprehensive genome variation analysis on 3,240 sequences of SARS-CoV-2 genome. Herein, we detected 14 substitution hotspots within SARS-CoV-2 genome, including 10 non-synonymous and 4 synonymous ones. Among these hotspots, NSP13-Y541C was predicted to be a crucial substitution which might affect the unwinding activity of NSP13, a key protein for viral replication. Besides, we also found 3 groups of potentially linked substitution hotspots which were worth further study. In particular, we discovered a SR-rich region (aa 184-204) on the N protein of SARS-CoV-2 distinct from SARS-CoV, indicating more complex replication mechanism and unique N-M interaction of SARS-CoV-2. Interestingly, the quantity of SRXX repeat fragments in the SR-rich region well reflected the evolutionary relationship among SARS-CoV-2 and SARS-CoV-2 related animal coronaviruses, providing further evidence of its animal origin. Overall, we developed an efficient tool for rapid identification of mutations, identified substitution hotspots in SARS-CoV-2 genomes, and detected a distinctive polymorphism SR-rich region in N protein. This tool and the detected hotspots could facilitate the viral genomic study and may contribute for screening antiviral target sites.

positive: Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV) Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.

positive: Genotyping SARS-CoV-2 through an interactive web application

positive: Understanding Coronavirus Since the identification of the first cases of the coronavirus in December 2019 in Wuhan, China, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', officially named SARS-CoV-2, and the cause of the disease COVID-19 Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the newly emerging virus and the inconsistent public health measures across different countries, have all served to increase the level of anxiety in the population Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? What can we do to stop its spread? Written by a leading expert, this concise and accessible introduction provides answers to the most common questions surrounding coronavirus for a general audience

positive: Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses Seven coronaviruses (CoVs) have been isolated from humans so far. Among them, three emerging pathogenic CoVs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and a newly identified CoV (2019-nCoV), once caused or continue to cause severe infections in humans, posing significant threats to global public health. SARS-CoV infection in humans (with about 10% case fatality rate) was first reported from China in 2002, while MERS-CoV infection in humans (with about 34.4% case fatality rate) was first reported from Saudi Arabia in June 2012. 2019-nCoV was first reported from China in December 2019, and is currently infecting more than 70000 people (with about 2.7% case fatality rate). Both SARS-CoV and MERS-CoV are zoonotic viruses, using bats as their natural reservoirs, and then transmitting through intermediate hosts, leading to human infections. Nevertheless, the intermediate host for 2019-nCoV is still under investigation and the vaccines against this new CoV have not been available. Although a variety of vaccines have been developed against infections of SARS-CoV and MERS-CoV, none of them has been approved for use in humans. In this review, we have described the structure and function of key proteins of emerging human CoVs, overviewed the current vaccine types to be developed against SARS-CoV and MERS-CoV, and summarized recent advances in subunit vaccines against these two pathogenic human CoVs. These subunit vaccines are introduced on the basis of full-length spike (S) protein, receptor-binding domain (RBD), non-RBD S protein fragments, and non-S structural proteins, and the potential factors affecting these subunit vaccines are also illustrated. Overall, this review will be helpful for rapid design and development of vaccines against the new 2019-nCoV and any future CoVs with pandemic potential. This review was written for the topic of Antivirals for Emerging Viruses: Vaccines and Therapeutics in the Virology section of Frontiers in Microbiology.

positive: Origin of new emergent Coronavirus and Candida fungal diseases—Terrestrial or cosmic? The origins and global spread of two recent, yet quite different, pandemic diseases is discussed and reviewed in depth: Candida auris, a eukaryotic fungal disease, and COVID-19 (SARS-CoV-2), a positive strand RNA viral respiratory disease. Both these diseases display highly distinctive patterns of sudden emergence and global spread, which are not easy to understand by conventional epidemiological analysis based on simple infection-driven human- to-human spread of an infectious disease (assumed to jump suddenly and thus genetically, from an animal reservoir). Both these enigmatic diseases make sense however under a Panspermia in-fall model and the evidence consistent with such a model is critically reviewed.

positive: Novel Bat Alphacoronaviruses in Southern China Support Chinese Horseshoe Bats as an Important Reservoir for Potential Novel Coronaviruses While bats are increasingly recognized as a source of coronavirus epidemics, the diversity and emergence potential of bat coronaviruses remains to be fully understood. Among 1779 bat samples collected in China, diverse coronaviruses were detected in 32 samples from five different bat species by RT-PCR. Two novel alphacoronaviruses, Rhinolophus sinicus bat coronavirus HKU32 (Rs-BatCoV HKU32) and Tylonycteris robustula bat coronavirus HKU33 (Tr-BatCoV HKU33), were discovered from Chinese horseshoe bats in Hong Kong and greater bamboo bats in Guizhou Province, respectively. Genome analyses showed that Rs-BatCoV HKU32 is closely related to BatCoV HKU10 and related viruses from diverse bat families, whereas Tr-BatCoV HKU33 is closely related to BtNv-AlphaCoV and similar viruses exclusively from bats of Vespertilionidae family. The close relatedness of Rs-BatCoV HKU32 to BatCoV HKU10 which was also detected in Pomona roundleaf bats from the same country park suggests that these viruses may have the tendency of infecting genetically distant bat populations of close geographical proximity with subsequent genetic divergence. Moreover, the presence of SARSr-CoV ORF7a-like protein in Rs-BatCoV HKU32 suggests a common evolutionary origin of this accessory protein with SARS-CoV, also from Chinese horseshoe bats, an apparent reservoir for coronavirus epidemics. The emergence potential of Rs-BatCoV HKU32 should be explored.

positive: Analysis of the Hosts and Transmission Paths of SARS-CoV-2 in the COVID-19 Outbreak The severe respiratory disease COVID-19 was initially reported in Wuhan, China, in December 2019, and spread into many provinces from Wuhan. The corresponding pathogen was soon identified as a novel coronavirus named SARS-CoV-2 (formerly, 2019-nCoV). As of 2 May, 2020, over 3 million COVID-19 cases had been confirmed, and 235,290 deaths had been reported globally, and the numbers are still increasing. It is important to understand the phylogenetic relationship between SARS-CoV-2 and known coronaviruses, and to identify its hosts for preventing the next round of emergency outbreak. In this study, we employ an effective alignment-free approach, the Natural Vector method, to analyze the phylogeny and classify the coronaviruses based on genomic and protein data. Our results show that SARS-CoV-2 is closely related to, but distinct from the SARS-CoV branch. By analyzing the genetic distances from the SARS-CoV-2 strain to the coronaviruses residing in animal hosts, we establish that the most possible transmission path originates from bats to pangolins to humans.

positive: Genomics of Indian SARS-CoV-2: Implications in genetic diversity, possible origin and spread of virus World Health Organization (WHO) declared COVID-19 as a pandemic disease on March 11, 2020. Comparison of genome sequences from diverse locations allows us to identify the genetic diversity among viruses which would help in ascertaining viral virulence, disease pathogenicity, origin and spread of the SARS-CoV-2 between countries. The aim of this study is to ascertain the genetic diversity among Indian SARS-CoV-2 isolates. Initial examination of the phylogenetic data of SARS-CoV-2 genomes (n=3123) from different continents deposited at GISAID (Global Initiative on Sharing All Influenza Data) revealed multiple origin for Indian isolates. An in-depth analysis of 449 viral genomes derived from samples representing countries from USA, Europe, China, East Asia, South Asia, Oceania, Middle East regions and India revealed that most Indian samples are divided into two clusters (A and B) with cluster A showing more similarity to samples from Oceania and Kuwait and the cluster B grouping with countries from Europe, Middle East and South Asia. Diversity analysis of viral clades, which are characterized by specific non-synonymous mutations in viral proteins, discovered that the cluster A Indian samples belong to I clade (V378I in ORF1ab), which is an Oceania clade with samples having Iran connections and the cluster B Indian samples belong to G clade (D614G in Spike protein), which is an European clade. Thus our study identifies that the Indian SARS-CoV-2 viruses belong to I and G clades with potential origin to be countries mainly from Oceania, Europe, Middle East and South Asia regions, which strongly implying the spread of virus through most travelled countries. The study also emphasizes the importance of pathogen genomics through phylogenetic analysis to discover viral genetic diversity and understand the viral transmission dynamics with eventual grasp on viral virulence and disease pathogenesis.

positive: 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 ß-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.

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

positive: 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.

positive: 89 Severe Acute Respiratory Syndrome (SARS) Abstract Severe acute respiratory syndrome (SARS) first appeared in November 2002 and ultimately resulted in 8096 probable human infections and 774 deaths worldwide. By July 2003, the global outbreak was declared over. A new coronavirus, SARS-associated coronavirus (SARS-CoV), was identified as the causative agent; this virus appeared to have a zoonotic origin, as genetically similar coronaviruses have been identified in several animal species. The global response to the outbreak was extensive. Within a short period, the pathogen had been identified, new diagnostic tests were developed, surveillance systems were created, infection control and prevention measures were instituted, and transmission among humans stopped. It is unclear if and when person-to-person SARS-CoV transmission will reappear. However, procedures have been established by public health organizations, including the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), to help guide diagnosis, reporting, surveillance, and prevention.

positive: Exceptional diversity and selection pressure on SARS-CoV and SARS-CoV-2 host receptor in bats compared to other mammals Pandemics originating from pathogen transmission between animals and humans highlight the broader need to understand how natural hosts have evolved in response to emerging human pathogens and which groups may be susceptible to infection. Here, we investigate angiotensin-converting enzyme 2 (ACE2), the host protein bound by SARS-CoV and SARS-CoV-2. We find that the ACE2 gene is under strong selection pressure in bats, the group in which the progenitors of SARS-CoV and SARS-CoV-2 are hypothesized to have evolved, particularly in residues that contact SARS-CoV and SARS-CoV-2. We detect positive selection in non-bat mammals in ACE2 but in a smaller proportion of branches than in bats, without enrichment of selection in residues that contact SARS-CoV or SARS-CoV-2. Additionally, we evaluate similarity between humans and other species in residues that contact SARS-CoV or SARS-CoV-2, revealing potential susceptible species but also highlighting the difficulties of predicting spillover events. This work increases our understanding of the relationship between mammals, particularly bats, and coronaviruses, and provides data that can be used in functional studies of how host proteins are bound by SARS-CoV and SARS-CoV-2 strains.

positive: A glimpse into the origins of genetic diversity in SARS-CoV-2

positive: An update on the origin of SARS‐CoV‐2: Despite closest identity, bat (RaTG13) and pangolin derived coronaviruses varied in the critical binding site and O‐linked glycan residues The initial cases of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) occurred in Wuhan, China, in December 2019 and swept the world by 23 June 2020 with 8 993 659 active cases, 469 587 deaths across 216 countries, areas or territories. This strongly implies global transmission occurred before the lockdown of China. However, the initial source's transmission routes of SARS‐CoV‐2 remain obscure and controversial. Research data suggest bat (RaTG13) and pangolin carried CoV were the proximal source of SARS‐CoV‐2. In this study, we used systematic phylogenetic analysis of Coronavirinae subfamily along with wild type human SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 strains. The key residues of the receptor‐binding domain (RBD) and O‐linked glycan were compared. SARS‐CoV‐2 strains were clustered with RaTG13 (97.41% identity), Pangolin‐CoV (92.22% identity) and Bat‐SL‐CoV (80.36% identity), forms a new clade‐2 in lineage B of beta‐CoV. The alignments of RBD contact residues to ACE2 justified? Those SARS‐CoV‐2 strains sequences were 100% identical by each other, significantly varied in RaTG13 and pangolin‐CoV. SARS‐CoV‐2 has a polybasic cleavage site with an inserted sequence of PRRA compared to RaTG13 and only PRR to pangolin. Only serine (Ser) in pangolin and both threonine (Thr) and serine (Ser) O‐linked glycans were seen in RaTG13, suggesting that a detailed study needed in pangolin (Manis javanica) and bat (Rhinolophus affinis) related CoV.

positive: Coronavirus: origins, signs, prevention and management of patients

positive: Drivers of MERS-CoV transmission: what do we know? Middle East Respiratory Syndrome coronavirus (MERS-CoV) emerged in 2012 has since resulted in sporadic cases, intra-familial transmission and major outbreaks in healthcare settings. The clinical picture of MERS-CoV includes asymptomatic infections, mild or moderately symptomatic cases and fatal disease. Transmissions of MERS-CoV within healthcare settings are facilitated by overcrowding, poor compliance with basic infection control measures, unrecognized infections, the superspreaders phenomenon and poor triage systems. The actual contributing factors to the spread of MERS-CoV are yet to be systematically studied, but data to date suggest viral, host and environmental factors play a major role. Here, we summarize the known factors for the diverse transmission of MERS-CoV.

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

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

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

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

positive: On the origin and continuing evolution of SARS-CoV-2 The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19).

positive: The genetic landscape of COVID-19: A South Asian perspective. COVID-19 has taken the world by storm in the ongoing pandemic. The virus responsible for COVID-19 disease is 'severe acute respiratory syndrome coronavirus-2' SARS-CoV-2, an enveloped RNA beta-coronavirus from the family Coronaviridae. There have been similar beta-coronavirus disease outbreaks previously: Severe acute respiratory syndrome (SARS - 2002) and Middle East respiratory syndrome (MERS - 2012) epidemics. SARS-CoV-2 origins have been traced to bat reservoirs. A virus with a high capacity for mutation, SARS-CoV-2 poses unique challenges both in the current form of disease control and management, while also leaving the door open for future novel diseases and pandemics. An understanding of the virion structure and genomic organisation will help us in understanding their origins and likely course of future evolution. Moreover, novel cost-effective methodologies for genetic surveillance may help in mitigating the emergence of these viral infections in future. In this manuscript, the authors have detailed the unique aspects of the SARS-CoV-2 virus genome and its clinical implications.

positive: 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.

positive: Recombination in Avian Gamma-Coronavirus Infectious Bronchitis Virus Recombination in the family Coronaviridae has been well documented and is thought to be a contributing factor in the emergence and evolution of different coronaviral genotypes as well as different species of coronavirus. However, there are limited data available on the frequency and extent of recombination in coronaviruses in nature and particularly for the avian gamma-coronaviruses where only recently the emergence of a turkey coronavirus has been attributed solely to recombination. In this study, the full-length genomes of eight avian gamma-coronavirus infectious bronchitis virus (IBV) isolates were sequenced and along with other full-length IBV genomes available from GenBank were analyzed for recombination. Evidence of recombination was found in every sequence analyzed and was distributed throughout the entire genome. Areas that have the highest occurrence of recombination are located in regions of the genome that code for nonstructural proteins 2, 3 and 16, and the structural spike glycoprotein. The extent of the recombination observed, suggests that this may be one of the principal mechanisms for generating genetic and antigenic diversity within IBV. These data indicate that reticulate evolutionary change due to recombination in IBV, likely plays a major role in the origin and adaptation of the virus leading to new genetic types and strains of the virus.

positive: SARS coronavirus without reservoir originated from an unnatural evolution, experienced the reverse evolution, and finally disappeared in the world.

positive: Coronaviruses Coronaviruses of humans were first identified more than 60 years ago from individuals with respiratory infections, mainly mild. Two different viruses, 229E and OC43 were initially recognized. Because of difficulty in isolating them using standard techniques, many of the early studies of their occurrence were seroepidemiologic. They were confirmed to be worldwide in distribution, and, in the North Temperate Zone, mainly occurring in the winter season. With the development of the reverse transcriptase polymerase chain reaction (PCR) technique, two additional distinct viruses have been identified, HKU1 and NL63. The four viruses have now been recognized as important in the etiology of common respiratory infections, second only to the rhinoviruses. In 2002, a previously unrecognized betacoronavirus emerged from a zoonotic reservoir in Southern China and spread during the following year to several major cities of the world. The resulting illness was termed Severe Acute Respiratory Syndrome (SARS) because of its potential lethality. More than 8,000 probable cases were reported during 2003, mainly from Hong Kong and mainland China, producing social and economic disruption in those areas affected. A constant feature of the outbreak was the importance of nosocomial spread. In spite of an estimated basic reproductive number higher than influenza, the outbreak was ended, in large part because of control of in-hospital transmission. In 2012, another betacoronavirus has emerged in the Arabian peninsula which is producing a somewhat similar illness, termed Middle East Respiratory Syndrome (MERS), also marked by extensive nosocomial transmission. The outcome of this emergence is currently unknown.

positive: Mystery deepens over animal source of coronavirus.

positive: Genetic variants and source of introduction of SARS‐CoV‐2 in South America After more than four months of the COVID‐19 pandemics with genomic information of SARS‐CoV‐2 around the globe, there are more than 1000 complete genomes of this virus. We used 691 genomes from the GISAID database. Several studies have been reporting mutations and hotspots according to the viral evolution. Our work intends to show and compare positions that have variants in 30 complete viral genomes from South American countries. We classified strains according to point alterations and portray the source where strains came into this region. Most viruses entered to South America from Europe, followed by Oceania. Only Chilean isolates demonstrated a relationship to Asian isolates. Some changes in South American genomes are near to specific domains related to replication or S protein. Our work contributes to global understanding of which sort of strains are spreading throughout South American countries, and the differences among them according to the first isolates introduced in this region. This article is protected by copyright. All rights reserved.

positive: Molecular mechanisms of severe acute respiratory syndrome (SARS) Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease.

positive: Computational analysis suggests putative intermediate animal hosts of the SARS-CoV-2 The authors have withdrawn their manuscript whilst they wish to perform additional experiments to validate their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author for more details.

positive: SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. However, as SARS-CoV-2 is an emerging virus, we know little about it. In this review, we summarize the key events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the pathogen, the signs and symptoms of the infected patients as well as the possible transmission pathways of the virus. Furthermore, we also review the current knowledge on the origin and evolution of the SARS-CoV-2. We highlight bats as the potential natural reservoir and pangolins as the possible intermediate host of the virus, but their roles are waiting for further investigation. Finally, the advances in the development of chemotherapeutic options are also briefly summarized.

positive: Genomic epidemiology of SARS-CoV-2 in Colombia Coronavirus disease 2019 (COVID-19) was first diagnosed in Colombia from a traveler arriving from Italy on February 26, 2020. To date, available data on the origins and number or introductions of SARS-CoV-2 into the country are limited. Here, we sequenced SARS-CoV-2 from 43 clinical samples and-together with another 73 genomes sequences available from the country-we investigated the emergence and the routes of importation of COVID-19 into Colombia using epidemiological, historical air travel and phylogenetic observations. Our study provided evidence of multiple introductions, mostly from Europe, with at least 12 lineages being documented. Phylogenetic findings validated the linkage of epidemiologically-linked transmission chains. Our results demonstrate the advantages of genome sequencing to complement COVID-19 outbreak investigation and underscores that human mobility and genetic data are relevant to complete epidemiological investigation and better characterize virus transmission dynamics at local scales.

positive: Mutations, Recombination and Insertion in the Evolution of 2019-nCoV The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

positive: Evolution and Emergence of Pathogenic Viruses: Past, Present, and Future Incidences of emerging/re-emerging deadly viral infections have significantly affected human health despite extraordinary progress in the area of biomedical knowledge. The best examples are the recurring outbreaks of dengue and chikungunya fever in tropical and sub-tropical regions, the recent epidemic of Zika in the Americas and the Caribbean, and the SARS, MERS, and influenza A outbreaks across the globe. The established natural reservoirs of human viruses are mainly farm animals, and, to a lesser extent, wild animals and arthropods. The intricate “host-pathogen-environment” relationship remains the key to understanding the emergence/re-emergence of pathogenic viruses. High population density, rampant constructions, poor sanitation, changing climate, and the introduction of anthropophilic vectors create selective pressure on host-pathogen reservoirs. Nevertheless, the knowledge and understanding of such zoonoses and pathogen diversity in their known non-human reservoirs are very limited. Prevention of arboviral infections using vector control methods has not been very successful. Currently, new approaches to protect against food-borne infections, such as consuming only properly cooked meats and animal products, are the most effective control measures. Though significant progress in controlling human immunodeficiency virus and hepatitis viruses has been achieved, the unpredictable nature of evolving viruses and the rare occasions of outbreaks severely hamper control and preventive modalities.

positive: Emergence and Reemergence of Severe Acute Respiratory Syndrome (SARS) Coronaviruses The positive-strand RNA viruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and recently emerged COVID-19 epidemics, demonstrated the transmission capability of the coronaviruses by crossing the species barrier and emergence in humans. The source of coronavirus disease 2019 (COVID-19) is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), firstly reported in December 2019 at Wuhan, China. COVID-19 is a kind of viral pneumonia. The outbreak of SARS-CoV-2 (COVID-19) has been reported as the introduction of the third highly pathogenic coronavirus which crossed the species barrier and spread into the human population. Severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) were the first two epidemic viruses, respectively, in the twenty-first century. Introduction of the 2019 novel coronaviruses (2019-nCoV) in human population is a worldwide concern, and this might have generated via RNA recombination among the previous reported coronaviruses. The COVID-19 is spreading in an alarming rate, and till date no vaccine or specific medicines are available in the market. The newly emerged coronavirus COVID-19 is strongly related to SARS-CoV except little dissimilarity. In this chapter, we will discuss about the alterations and variations in antigenicity, structural changes, and RNA recombination which might be responsible for the COVID-19 emergence.

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

positive: Genotyping coronavirus SARS-CoV-2: Methods and implications Abstract The emerging global infectious COVID-19 disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. To understand the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. This study presents an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The single-nucleotide polymorphism (SNP) genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. The proposed method serves an effective tool for monitoring and tracking the epidemic of pathogenic viruses in their global and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.

positive: 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.

positive: Pathogen genomic surveillance elucidates the origins, transmission and evolution of emerging viral agents in China In the past twenty years, numerous novel zoonotic viral agents with pandemic potential have emerged in China, such as the severe acute respiratory syndrome (SARS) coronavirus and, more recently, the avian-origin influenza A/H7N9 virus, which have caused outbreaks among humans with high morbidity and mortality. In addition, several emerging and re-emerging viral pathogens have also been imported into China from travelers, e.g. the Middle East respiratory syndrome (MERS) coronavirus and Zika virus (ZIKV). Herein, we review these emerging viral pathogens in China and focus on how surveillance by pathogen genomics has been employed to discover and annotate novel pathogenic agents, identify natural reservoirs, monitor the transmission events and delineate their evolution and adaption to the human host. We also highlight the application of genomic sequencing in the recent Ebola epidemics in Western Africa. In summary, genomic sequencing has become a standard research tool in the field of emerging infectious diseases which has been proven invaluable in containing these viral infections and reducing burden of disease in humans and animals. Genomic surveillance of pathogenic agents will serve as a key epidemiological and research tool in the modern era of precision infectious diseases and in the future studies of virosphere.

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

positive: On spatial molecular arrangements of SARS-CoV2 genomes of Indian patients A pandemic caused by the SARS-CoV2 is being experienced by the whole world since December, 2019. A thorough understanding beyond just sequential similarities among the protein coding genes of SARS-CoV2 is important in order to differentiate or relate to the other known CoVs of the same genus. In this study, we compare three genomes namely MT012098 (India-Kerala), MT050493 (India-Kerala), MT358637 (India-Gujrat) from India with NC_045512 (China-Wuhan) to view the spatial as well as molecular arrangements of nucleotide bases of all the genes embedded in these four genomes. Based on different features extracted for each gene embedded in these genomes, corresponding phylogenetic relationships have been built up. Differences in phylogenetic tree arrangement with individual gene suggest that three genomes of Indian origin have come from three different origins or the evolution of viral genome is very fast process. This study would also help to understand the virulence factors, disease pathogenicity, origin and transmission of the SARS-CoV2.

positive: Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event Background A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus. Methods Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods. Results Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat-SARS-like coronavirus sequences. Specifically, in the 5’-part spanning the first 11,498 nucleotides and the last 3’-part spanning 24,341-30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat-SARS-like coronavirus sequences, whereas in the middle region spanning the 3’-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch. Conclusions The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.

positive: Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.

positive: Coronavirus: origins, signs, prevention and management of patients.

positive: Possibility of transmission through dogs being a contributing factor to the extreme Covid-19 outbreak in North Italy Covid‑19 origin and transmission to humans. Covid‑19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid‑19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS‑CoV‑2 transmission. However, the source(s) and transmission routine(s) of SARS‑CoV‑2 remain elusive' (1).

positive: 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.

positive: The genetic landscape of COVID-19: A South Asian perspective COVID-19 has taken the world by storm in the ongoing pandemic. The virus responsible for COVID-19 disease is 'severe acute respiratory syndrome coronavirus-2' SARS-CoV-2, an enveloped RNA beta-coronavirus from the family Coronaviridae. There have been similar beta-coronavirus disease outbreaks previously: Severe acute respiratory syndrome (SARS - 2002) and Middle East respiratory syndrome (MERS - 2012) epidemics. SARS-CoV-2 origins have been traced to bat reservoirs. A virus with a high capacity for mutation, SARS-CoV-2 poses unique challenges both in the current form of disease control and management, while also leaving the door open for future novel diseases and pandemics. An understanding of the virion structure and genomic organisation will help us in understanding their origins and likely course of future evolution. Moreover, novel cost-effective methodologies for genetic surveillance may help in mitigating the emergence of these viral infections in future. In this manuscript, the authors have detailed the unique aspects of the SARS-CoV-2 virus genome and its clinical implications.

positive: Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19. Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world. To date, seven known strains of HCoVs belonging to four genera (i.e., α?, β?, γ, and δ-CoV) have been recognized; the latest one has been identified as the SARS-CoV-2. Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body. Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19. Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19. There is a greater need to better understand the mechanisms and risk factors of transmission routes. To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear. Therefore, there is an urgent need for update data on SARS-CoV-2. Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020.

positive: Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

positive: Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2 We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. Its genome is closest to that of severe acute respiratory syndrome-related coronaviruses from horseshoe bats, and its receptor-binding domain is closest to that of pangolin viruses. Its origin and direct ancestral viruses have not been identified.

positive: Interspecies transmission and emergence of novel viruses: lessons from bats and birds As exemplified by coronaviruses and influenza viruses, bats and birds are natural reservoirs for providing viral genes during evolution of new virus species and viruses for interspecies transmission. These warm-blooded vertebrates display high species biodiversity, roosting and migratory behavior, and a unique adaptive immune system, which are favorable characteristics for asymptomatic shedding, dissemination, and mixing of different viruses for the generation of novel mutant, recombinant, or reassortant RNA viruses. The increased intrusion of humans into wildlife habitats and overcrowding of different wildlife species in wet markets and farms have also facilitated the interspecies transmission between different animal species.

positive: 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.

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

positive: Are Animals a Neglected Transmission Route of SARS-CoV-2? Little information on the SARS-CoV-2 virus in animals is available to date. Whereas no one husbandry animal case has been reported to date, which would have significant implications in food safety, companion animals play a role in COVID-19 epidemiology that opens up new questions. There is evidence that SARS-CoV-2 can infect felines, dogs and minks, and there is evidence of human-to-animal infection. Likewise, the S protein nucleotide sequence of the SARS-CoV-2 virus isolated in domestic animals and humans is identical, and the replication of the SARS-CoV-2 in cats is efficient. Besides, the epidemiological evidence for this current pandemic indicates that the spillover to humans was associated with close contact between man and exotic animals, very probably in Chinese wet markets, thus there is a growing general consensus that the exotic animal markets, should be strictly regulated. The examination of these findings and the particular role of animals in COVID-19 should be carefully analyzed in order to establish preparation and containment measures. Animal management and epidemiological surveillance must be also considered for COVID-19 control, and it can open up new questions regarding COVID-19 epidemiology and the role that animals play in it.

positive: Receptor utilization of angiotensin converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV Coronavirus pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, SARS-CoV caused SARS pandemic in 2003 and SARS-CoV-2 caused the COVID-19 pandemic recently. Both viruses have been reported to originate from bats. Thus, direct or indirect interspecies transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the interspecies transmission. Angiotensin converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. Meanwhile, pangolin CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20th and 42nd amino acids that may determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin CoV. Our studies promote the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.

positive: Coronaviruses and SARS-CoV-2: A Brief Overview In late December 2019, several cases of pneumonia of unknown origin were reported from China, which in early January 2020 were announced to be caused by a novel coronavirus. The virus was later denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and defined as the causal agent of Coronavirus Disease 2019 (COVID-19). Despite massive attempts to contain the disease in China, the virus has spread globally, and COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. Here we provide a short background on coronaviruses, and describe in more detail the novel SARS-CoV-2 and attempts to identify effective therapies against COVID-19.

positive: Bats as a continuing source of emerging infections in humans Amongst the 60 viral species reported to be associated with bats, 59 are RNA viruses, which are potentially important in the generation of emerging and re‐emerging infections in humans. The prime examples of these are the lyssaviruses and Henipavirus. The transmission of Nipah, Hendra and perhaps SARS coronavirus and Ebola virus to humans may involve intermediate amplification hosts such as pigs, horses, civets and primates, respectively. Understanding of the natural reservoir or introductory host, the amplifying host, the epidemic centre and at‐risk human populations are crucial in the control of emerging zoonosis. The association between the bat coronaviruses and certain lyssaviruses with particular bat species implies co‐evolution between specific viruses and bat hosts. Cross‐infection between the huge number of bat species may generate new viruses which are able to jump the trans‐mammalian species barrier more efficiently. The currently known viruses that have been found in bats are reviewed and the risks of transmission to humans are highlighted. Certain families of bats including the Pteropodidae, Molossidae, Phyllostomidae, and Vespertilionidae are most frequently associated with known human pathogens. A systematic survey of bats is warranted to better understand the ecology of these viruses. Copyright © 2006 John Wiley & Sons, Ltd.

positive: COVID-19 breakthroughs: separating fact from fiction The newly recognised coronavirus SARS-CoV-2, causative agent of COVID-19, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.

positive: The 2019 novel coronavirus disease (COVID-19) pandemic: A zoonotic prospective Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus (CoV), has recently emerged as a significant pathogen for humans and the cause for the recent outbreak of the 2019 novel coronavirus disease (COVID-19) throughout the globe For developing any preventive measure, an understanding of the zoonotic pattern for this virus is a necessity We should have a clear knowledge of its reservoir host, its distribution pattern and spreading routes Information about zoonotic reservoirs and its transmission among them can help to understand the COVID-19 outbreaks In this article, we discuss about the bats as the zoonotic reservoir of several CoV strains, co-existence of bats and CoV/viruses, the sequence similarity of SARS-CoV-2 with bat SARS-like CoV, the probable source of the origin of SARS-CoV-2 strain and COVID-19 outbreak, intermediate host of CoVs and SARS-CoV-2, human to human transmission and the possibility to maintain the zoonotic barriers Our knowledge about the zoonotic reservoir of SARS-CoV-2 and its transmission ability may help develop the preventive measures and control for the future outbreak of CoV

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

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

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

positive: Genomic analysis of early SARS-CoV-2 strains introduced in Mexico The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described in the country. Within this Mexican cluster, we also identified an H49Y amino acid change in the spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts. This work is the result of the collaboration of five institutions into one research consortium: three public health institutes and two universities. From the beginning of this work, it was agreed that the experimental leader of each institution would share the first authorship. Those were the criteria followed to assign first co-first authorship in this manuscript. The order of the other authors was randomly assigned. IMPORTANCE Understanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.

positive: The First Disease X is Caused by a Highly Transmissible Acute Respiratory Syndrome Coronavirus Based on the announcement of the World Health Organization (WHO) in 2018, the Wuhan pneumonia caused by an unknown etiology should be recognized as the first Disease X. Later, the pathogen was identified to be a novel coronavirus denoted 2019-nCoV, which has 79.5% and 96% whole genome sequence identify to SARS-CoV and bat SARS-related coronavirus (SARSr-CoV-RaTG13), respectively, suggesting its potential bat origin. With high human-to-human transmission rate (R0), 2019-nCoV has quickly spread in China and other countries, resulting in 34,953 confirmed cases and 725 deaths as of 8 February 2020, thus calling for urgent development of therapeutics and prophylactics. Here we suggest renaming 2019-nCoV as “transmissible acute respiratory syndrome coronavirus (TARS-CoV)” and briefly review the advancement of research and development of neutralizing antibodies and vaccines targeting the receptor-binding domain (RBD) and viral fusion inhibitors targeting the heptad repeat 1 (HR1) domain in spike protein of 2019-nCoV.

positive: Bat Coronaviruses in China During the past two decades, three zoonotic coronaviruses have been identified as the cause of large-scale disease outbreaks–Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Swine Acute Diarrhea Syndrome (SADS). SARS and MERS emerged in 2003 and 2012, respectively, and caused a worldwide pandemic that claimed thousands of human lives, while SADS struck the swine industry in 2017. They have common characteristics, such as they are all highly pathogenic to humans or livestock, their agents originated from bats, and two of them originated in China. Thus, it is highly likely that future SARS- or MERS-like coronavirus outbreaks will originate from bats, and there is an increased probability that this will occur in China. Therefore, the investigation of bat coronaviruses becomes an urgent issue for the detection of early warning signs, which in turn minimizes the impact of such future outbreaks in China. The purpose of the review is to summarize the current knowledge on viral diversity, reservoir hosts, and the geographical distributions of bat coronaviruses in China, and eventually we aim to predict virus hotspots and their cross-species transmission potential.

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

positive: SARS‐CoV‐2 variants: Relevance for symptom granularity, epidemiology, immunity (herd, vaccines), virus origin and containment? The origin of the SARS‐CoV‐2 virus remains enigmatic. It is likely to be a continuum resulting from inevitable mutations and recombination events. These genetic changes keep developing in the present epidemic. Mutations tending to deplete the genome in its cytosine content will progressively lead to attenuation as a consequence of Muller's ratchet, but this is counteracted by recombination when different mutants co‐infect the same host, in particular, in clusters of infection. Monitoring as a function of time the genome sequences in closely related cases is critical to anticipate the future of SARS‐CoV‐2 and hence of COVID‐19.

positive: Using the spike protein feature to predict infection risk and monitor the evolutionary dynamic of coronavirus BACKGROUND: Coronavirus can cross the species barrier and infect humans with a severe respiratory syndrome. SARS-CoV-2 with potential origin of bat is still circulating in China. In this study, a prediction model is proposed to evaluate the infection risk of non-human-origin coronavirus for early warning. METHODS: The spike protein sequences of 2666 coronaviruses were collected from 2019 Novel Coronavirus Resource (2019nCoVR) Database of China National Genomics Data Center on Jan 29, 2020. A total of 507 human-origin viruses were regarded as positive samples, whereas 2159 non-human-origin viruses were regarded as negative. To capture the key information of the spike protein, three feature encoding algorithms (amino acid composition, AAC; parallel correlation-based pseudo-amino-acid composition, PC-PseAAC and G-gap dipeptide composition, GGAP) were used to train 41 random forest models. The optimal feature with the best performance was identified by the multidimensional scaling method, which was used to explore the pattern of human coronavirus. RESULTS: The 10-fold cross-validation results showed that well performance was achieved with the use of the GGAP (g = 3) feature. The predictive model achieved the maximum ACC of 98.18% coupled with the Matthews correlation coefficient (MCC) of 0.9638. Seven clusters for human coronaviruses (229E, NL63, OC43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2) were found. The cluster for SARS-CoV-2 was very close to that for SARS-CoV, which suggests that both of viruses have the same human receptor (angiotensin converting enzyme II). The big gap in the distance curve suggests that the origin of SARS-CoV-2 is not clear and further surveillance in the field should be made continuously. The smooth distance curve for SARS-CoV suggests that its close relatives still exist in nature and public health is challenged as usual. CONCLUSIONS: The optimal feature (GGAP, g = 3) performed well in terms of predicting infection risk and could be used to explore the evolutionary dynamic in a simple, fast and large-scale manner. The study may be beneficial for the surveillance of the genome mutation of coronavirus in the field.

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

positive: Dinucleotide repeats in coronavirus SARS-CoV-2 genome: evolutionary implications The ongoing global pandemic of infection disease COVID-19 caused by the 2019 novel coronavirus (SARS-COV-2, formerly 2019-nCoV) presents critical threats to public health and the economy since it was identified in China, December 2019. The genome of SARS-CoV-2 had been sequenced and structurally annotated, yet little is known of the intrinsic organization and evolution of the genome. To this end, we present a mathematical method for the genomic spectrum, a kind of barcode, of SARS-CoV-2 and common human coronaviruses. The genomic spectrum is constructed according to the periodic distributions of nucleotides, and therefore reflects the unique characteristics of the genome. The results demonstrate that coronavirus SARS-CoV-2 exhibits dinucleotide TT islands in the non-structural proteins 3, 4, 5, and 6. Further analysis of the dinucleotide regions suggests that the dinucleotide repeats are increased during evolution and may confer the evolutionary fitness of the virus. The special dinucleotide regions in the SARS-CoV-2 genome identified in this study may become diagnostic and pharmaceutical targets in monitoring and curing the COVID-19 disease.

positive: Phylogenomic proximity and comparative proteomic analysis of SARS-CoV-2 The coronavirus disease (COVID-19) belongs to the family Severe Acute Respiratory Syndrome (SARS-CoV). It can be more severe for some persons and can lead to pneumonia or breathing difficulties resulting in the death of immune-compromised patients. We performed a phylogenomic and phylogeographic tree from the collected datasets. Phylogenomic analysis or sequence-based phylogeny showed an evolutionary relationship between the geographical strains. The phylogenomic tree grouped into two major clades consists of various isolates of SARS-CoV-2 and Bat SARS-like coronavirus, Bat coronavirus, and Pangolin coronavirus. The phylogenetic neighbor of newly sequenced Indian strains (Accession: MT012098.1, MT050493.1) was revealed to identify the variations between the nCoV-19 strains. The results showed keen evidence that SARS-CoV-2 has evolved from Bat SARS-like coronavirus. The evolutionary history and comparative proteomic analysis provide a new avenue for the current scientific research related to the coronavirus.

positive: From SARS to COVID-19: A previously unknown SARS- related coronavirus (SARS-CoV-2) of pandemic potential infecting humans – Call for a One Health approach Human coronaviruses continue to pose a threat to human health. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 which causes coronavirus disease-2019 (COVID-19), an acute respiratory disease marked the third introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. This recent emergence of a previously unknown coronavirus in China leads to huge impacts on humans globally. Covid-19 is a challenge to global public health. Here, we discuss the COVID-19 outbreak in a one health context, highlighting the need for the implementation of one health measures and practices to improve human health and reduce the emergence of pandemic viruses.

positive: Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat.

positive: 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.

positive: 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.

positive: Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

positive: SARS-CoV-2 host diversity: An update of natural infections and experimental evidences Abstract Coronavirus disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now a pandemic threat. This virus is supposed to be spread by human to human transmission. Cellular angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans. Moreover, a recent study predicted that dog might be secondary host during the evolution of SARS-CoV-2 from bat to human. Therefore, there is a possibility of spreading SARS-CoV-2 through domestic pets. There are now many reports of SARS-CoV-2 positive cases in dogs, cats, tigers, lion, and minks. Experimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne route. Based on these natural infection reports and experimental data, whether the pets are responsible for SARS-CoV-2 spread to human; needs to be deeply investigated. Humans showing clinical symptoms of respiratory infections have been undergoing for COVID-19 diagnostic test but many infected people and few pets confirmed with SARS-CoV-2 remained asymptomatic. In this review, we summarize the natural cases of SARS-CoV-2 in animals with the latest researches conducted in this field. This review will be helpful to think insights of SARS-CoV-2 transmissions, spread, and demand for sero-prevalence studies especially in companion animals.

positive: Might the many positive COVID19 subjects in Italy have been caused by resident bat‐derived zoonotic β‐coronaviruses instead of the Wuhan (China) outbreak?

positive: Emergence of Novel Coronavirus and COVID-19: whether to stay or die out? The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus “SARS-CoV-2” (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect naïve, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.

positive: Astroviruses☆ Abstract Astroviruses are positive-sense, single-stranded RNA viruses. Their genomes contain three open reading frames, but the exact number of encoded proteins remains unknown. Astroviruses were originally identified in association with childhood diarrhea; subsequently, they have been identified as a common enteric virus infecting children under the age of 2. Infection is not restricted to humans, however, and astroviruses have been found in widespread mammalian and avian species. Generally, infection causes a mild, self-limiting gastroenteritis, although infection can result in nephritis, hepatitis, and encephalitis in certain host species. Astrovirus pathogenicity and immune response is only poorly characterized and may differ between mammalian and avian species. In this article, the current knowledge of astroviruses is reviewed, including their molecular virology, viral evolution, pathogenesis, and immune response.

positive: Susceptibility of ferrets, cats, dogs, and different domestic animals to SARS-coronavirus-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19, which was first reported in Wuhan, China in December, 2019. Despite the tremendous efforts to control the disease, COVID-19 has now spread to over 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are completely unknown. Here, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2. We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but efficiently in ferrets and cats. We found that the virus transmits in cats via respiratory droplets. Our study provides important insights into the animal reservoirs of SARS-CoV-2 and animal management for COVID-19 control.

positive: A case for the ancient origin of coronaviruses. Coronaviruses are found in a diverse array of bat and bird species, which are believed to act as natural hosts. Molecular clock dating analyses of coronaviruses suggest that the most recent common ancestor of these viruses existed around 10,000 years ago. This relatively young age is in sharp contrast to the ancient evolutionary history of their putative natural hosts, which began diversifying tens of millions of years ago. Here, we attempted to resolve this discrepancy by applying more realistic evolutionary models that have previously revealed the ancient evolutionary history of other RNA viruses. By explicitly modeling variation in the strength of natural selection over time and thereby improving the modeling of substitution saturation, we found that the time to the most recent ancestor common for all coronaviruses is likely far greater (millions of years) than the previously inferred range.

positive: Potential Intermediate Hosts for Coronavirus Transmission: No Evidence of Clade 2c Coronaviruses in Domestic Livestock from Ghana The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), nearly a decade ago with worldwide distribution, was believed to be of zoonotic origin from bats with dromedary camels as intermediate hosts. There is a likelihood of other domestic livestock serving as intermediate hosts for this virus. The presence of coronaviruses, closely related to MERS-CoV in Ghanaian bats, presented the opportunity to test the hypothesis of transmissibility of this virus through domestic livestock species. The possible interactions between livestock and bats in 31 household farms were accessed by observation and interviews with farmers. Rectal swabs and serum from cattle, sheep, goats, donkeys, and swine from commercial and household farms were tested for MERS-CoV and a Nycteris sp. bat coronavirus, previously detected in Ghana. A pan-PCR assay to detect clade 2c viruses and recombinant immunofluorescence assay to detect anti-spike IgG antibodies against the target viruses were used. Likely contact between livestock and bats was determined for 13 farms (41.9%) that reported confining their livestock and also observing bats in their homes. Livestock were left unconfined on eight farms (25.8%) that also observed bats roosting in trees close to their homes. No viral RNA or antibodies against the two coronaviruses were detected in any of the livestock species tested. Cattle, sheep, goats, donkeys, and swine are not likely hosts of clade 2c coronaviruses.

positive: Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2 The outbreak of a novel coronavirus, which was later formally named the severe acute respiratory coronavirus 2 (SARS-CoV-2), has caused a worldwide public health crisis. Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. Here, we have systematically studied the molecular mechanisms of human infection with SARS-CoV-2 and SARS-CoV by protein-protein docking and MD simulations. It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. In addition, the spike protein of SARS-CoV-2 has a significantly lower free energy than that of SARS-CoV, suggesting that SARS-CoV-2 is more stable and may survive a higher temperature than SARS-CoV. This provides insights into the evolution of SARS-CoV-2 because SARS-like coronaviruses have originated in bats. Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV. Thus, it is expected that SARS-CoV-2 would decrease its infection ability much faster than SARS-CoV when the temperature rises. These findings would be beneficial for the disease prevention and drug/vaccine development of SARS-CoV-2.

positive: 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.

positive: Detection of Severe Acute Respiratory Syndrome‐Like, Middle East Respiratory Syndrome‐Like Bat Coronaviruses and Group H Rotavirus in Faeces of Korean Bats Bat species around the world have recently been recognized as major reservoirs of several zoonotic viruses, such as severe acute respiratory syndrome coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV), Nipah virus and Hendra virus. In this study, consensus primer‐based reverse transcriptase polymerase chain reactions (RT‐PCRs) and high‐throughput sequencing were performed to investigate viruses in bat faecal samples collected at 11 natural bat habitat sites from July to December 2015 in Korea. Diverse coronaviruses were first detected in Korean bat faeces, including alphacoronaviruses, SARS‐CoV‐like and MERS‐CoV‐like betacoronaviruses. In addition, we identified a novel bat rotavirus belonging to group H rotavirus which has only been described in human and pigs until now. Therefore, our results suggest the need for continuing surveillance and additional virological studies in domestic bat.

positive: Protein structure and sequence re-analysis of 2019-nCoV genome does not indicate snakes as its intermediate host or the unique similarity between its spike protein insertions and HIV-1 As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, careful analysis of its transmission and cellular mechanisms is sorely needed. In this report, we re-analyzed the computational approaches and findings presented in two recent manuscripts by Ji et al. (https://doi.org/10.1002/jmv.25682) and by Pradhan et al. (https://doi.org/10.1101/2020.01.30.927871), which concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions shared a unique similarity to HIV-1. Results from our re-implementation of the analyses, built on larger-scale datasets using state-of-the-art bioinformatics methods and databases, do not support the conclusions proposed by these manuscripts. Based on our analyses and existing data of coronaviruses, we concluded that the intermediate hosts of 2019-nCoV are more likely to be mammals and birds than snakes, and that the “novel insertions” observed in the spike protein are naturally evolved from bat coronaviruses.

positive: Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins The outbreak of 2019-nCoV in the central Chinese city of Wuhan at the end of 2019 poses unprecedent public health challenges to both China and the rest world1. The new coronavirus shares high sequence identity to SARS-CoV and a newly identified bat coronavirus2. While bats may be the reservoir host for various coronaviruses, whether 2019-nCoV has other hosts is still ambiguous. In this study, one coronavirus isolated from Malayan pangolins showed 100%, 98.2%, 96.7% and 90.4% amino acid identity with 2019-nCoV in the E, M, N and S genes, respectively. In particular, the receptor-binding domain of the S protein of the Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference. Comparison of available genomes suggests 2019-nCoV might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. Infected pangolins showed clinical signs and histopathological changes, and the circulating antibodies reacted with the S protein of 2019-nCoV. The isolation of a coronavirus that is highly related to 2019-nCoV in the pangolins suggests that these animals have the potential to act as the intermediate host of 2019-nCoV. The newly identified coronavirus in the most-trafficked mammal could represent a continuous threat to public health if wildlife trade is not effectively controlled.

positive: Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history(1). An ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV)(2) suggests that this group of viruses remains a major threat and that their distribution is wider than previously recognized. Although bats have been suggested as the natural reservoirs of both viruses(3–5), attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa(5–8), but none are considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins (S) to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2)(9,10). Here, we report whole genome sequences of two novel bat CoVs from Chinese horseshoe bats (Family: Rhinolophidae) in Yunnan, China; RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat CoVs, particularly in the receptor binding domain (RDB) of the S protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat fecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses the ACE2s from human, civet and Chinese horseshoe bat for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.

positive: 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.

positive: Information Mining for COVID-19 Research From a Large Volume of Scientific Literature The year 2020 has seen an unprecedented COVID-19 pandemic due to the outbreak of a novel strain of coronavirus in 180 countries. In a desperate effort to discover new drugs and vaccines for COVID-19, many scientists are working around the clock. Their valuable time and effort may benefit from computer-based mining of a large volume of health science literature that is a treasure trove of information. In this paper, we have developed a graph-based model using abstracts of 10,683 scientific articles to find key information on three topics: transmission, drug types, and genome research related to coronavirus. A subgraph is built for each of the three topics to extract more topic-focused information. Within each subgraph, we use a betweenness centrality measurement to rank order the importance of keywords related to drugs, diseases, pathogens, hosts of pathogens, and biomolecules. The results reveal intriguing information about antiviral drugs (Chloroquine, Amantadine, Dexamethasone), pathogen-hosts (pigs, bats, macaque, cynomolgus), viral pathogens (zika, dengue, malaria, and several viruses in the coronaviridae virus family), and proteins and therapeutic mechanisms (oligonucleotide, interferon, glycoprotein) in connection with the core topic of coronavirus. The categorical summary of these keywords and topics may be a useful reference to expedite and recommend new and alternative directions for COVID-19 research.

positive: Comparative sequence analysis of the distal one-third of the genomes of a systemic and an enteric ferret coronavirus Abstract Ferret systemic coronavirus (FRSCV) infection is associated with an emerging, highly fatal disease of ferrets. Enhanced macrophage tropism and the resulting induction of pyogranulomatous lesions are shared with feline infectious peritonitis virus (FIPV) infection in cats, but are not features of ferret enteric coronavirus (FRECV) infection. Comparative sequence analysis of the distal one-third of the genomes of one FRSCV and one FRECV strain showed that these two ferret coronaviruses share >96% nucleotide sequence identities in the membrane (M), nucleocapsid (N) and non-structural protein genes (partial polymerase, open reading frames [ORFs] 3 and 7b). The envelope (E) protein gene showed a moderate nucleotide sequence similarity of 91.6%. In contrast, nucleotide and amino acid sequence similarities observed with the spike (S) protein were only 79.5 and 79.6%, respectively. Twenty-one amino acid differences within a 195–199-amino acid C-terminal portion of the S protein were conserved between 3 strains each of FRSCV and FRECV. Both systemic and enteric strains were found to carry a single ORF 3 gene with truncated proteins observed in two out of three FRSCV strains examined. The two enteric strains analyzed each contained an intact ORF 3 gene. Phylogenetically, FRSCV is more closely related to FRECV than to other group 1 coronaviruses.

positive: 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.

positive: Evidence for an Ancestral Association of Human Coronavirus 229E with Bats. UNLABELLED We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5- and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3' end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E. IMPORTANCE The ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus.

positive: New Virus, New Challenge The ongoing COVID-19 pandemic has made us to consider the emergence of potential viral diseases in the future. Animals can carry vast and diverse virus species, most of which we do not understand yet, and the spillover events of the viruses from the unknown pool in animals to human population always occurred in the past. To effectively prevent and control the emerging viral diseases, we should make efforts to explore the unknown virus species in nature and prepare in advance.

positive: 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

positive: Machine learning using intrinsic genomic signatures for rapid classification of novel pathogens: COVID-19 case study The 2019 novel coronavirus (renamed SARS-CoV-2, and generally referred to as the COVID-19 virus) has spread to 184 countries with over 1.5 million confirmed cases. Such major viral outbreaks demand early elucidation of taxonomic classification and origin of the virus genomic sequence, for strategic planning, containment, and treatment. This paper identifies an intrinsic COVID-19 virus genomic signature and uses it together with a machine learning-based alignment-free approach for an ultra-fast, scalable, and highly accurate classification of whole COVID-19 virus genomes. The proposed method combines supervised machine learning with digital signal processing (MLDSP) for genome analyses, augmented by a decision tree approach to the machine learning component, and a Spearman’s rank correlation coefficient analysis for result validation. These tools are used to analyze a large dataset of over 5000 unique viral genomic sequences, totalling 61.8 million bp, including the 29 COVID-19 virus sequences available on January 27, 2020. Our results support a hypothesis of a bat origin and classify the COVID-19 virus as Sarbecovirus, within Betacoronavirus. Our method achieves 100% accurate classification of the COVID-19 virus sequences, and discovers the most relevant relationships among over 5000 viral genomes within a few minutes, ab initio, using raw DNA sequence data alone, and without any specialized biological knowledge, training, gene or genome annotations. This suggests that, for novel viral and pathogen genome sequences, this alignment-free whole-genome machine-learning approach can provide a reliable real-time option for taxonomic classification.

positive: When Darkness Becomes a Ray of Light in the Dark Times: Understanding the COVID-19 via the Comparative Analysis of the Dark Proteomes of SARS-CoV-2, Human SARS and Bat SARS-Like Coronaviruses Recently emerged coronavirus designated as SARS-CoV-2 (also known as 2019 novel coronavirus (2019-nCoV) or Wuhan coronavirus) is a causative agent of coronavirus disease 2019 (COVID-19), which is rapidly spreading throughout the world now. More than 9,00,000 cases of SARS-CoV-2 infection and more than 47,000 COVID-19-associated mortalities have been reported worldwide till the writing of this article, and these numbers are increasing every passing hour. World Health Organization (WHO) has declared the SARS-CoV-2 spread as a global public health emergency and admitted that the COVID-19 is a pandemic now. The multiple sequence alignment data correlated with the already published reports on the SARS-CoV-2 evolution and indicated that this virus is closely related to the bat Severe Acute Respiratory Syndrome-like coronavirus (bat SARS-like CoV) and the well-studied Human SARS coronavirus (SARS CoV). The disordered regions in viral proteins are associated with the viral infectivity and pathogenicity. Therefore, in this study, we have exploited a set of complementary computational approaches to examine the dark proteomes of SARS-CoV-2, bat SARS-like, and human SARS CoVs by analysing the prevalence of intrinsic disorder in their proteins. According to our findings, SARS-CoV-2 proteome contains very significant levels of structural order. In fact, except for Nucleocapsid, Nsp8, and ORF6, the vast majority of SARS-CoV-2 proteins are mostly ordered proteins containing less intrinsically disordered protein regions (IDPRs). However, IDPRs found in SARS-CoV-2 proteins are functionally important. For example, cleavage sites in its replicase 1ab polyprotein are found to be highly disordered, and almost all SARS-CoV-2 proteins were shown to contain molecular recognition features (MoRFs), which are intrinsic disorder-based protein-protein interaction sites that are commonly utilized by proteins for interaction with specific partners. The results of our extensive investigation of the dark side of the SARS-CoV-2 proteome will have important implications for the structural and non-structural biology of SARS or SARS-like coronaviruses. Significance The infection caused by a novel coronavirus (SARS-CoV-2) that causes severe respiratory disease with pneumonia-like symptoms in humans is responsible for the current COVID-19 pandemic. No in-depth information on structures and functions of SARS-CoV-2 proteins is currently available in the public domain, and no effective anti-viral drugs and/or vaccines are designed for the treatment of this infection. Our study provides the first comparative analysis of the order- and disorder-based features of the SARS-CoV-2 proteome relative to human SARS and bat CoV that may be useful for structure-based drug discovery.

positive: COVID-19: a novel zoonotic disease caused by a coronavirus from China: what we know and what we don’t

positive: The diversity, evolution and origins of vertebrate RNA viruses Despite a substantial increase in our knowledge of the biodiversity and evolution of vertebrate RNA viruses, far less is known about the diversity, evolution and origin of RNA viruses across the diverse phylogenetic range of viruses, and particularly in healthy animals that are often only rarely utilized for virological sampling. Fortunately, recent advances in virus discovery using metagenomic approaches are beginning to reveal a multitude of RNA viruses in vertebrates other than birds and mammals. In particular, fish harbor a remarkable array of RNA viruses, including the relatives of important pathogens. In addition, despite frequent cross-species transmission, the RNA viruses in vertebrates generally follow the evolutionary history of their hosts, which began in the oceans and then moved to terrestrial habitats over timescales covering hundreds of millions of years.

positive: Betacoronavirus Genomes: How Genomic Information has been Used to Deal with Past Outbreaks and the COVID-19 Pandemic. In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002-2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2. We focus on shared genomic features of the betacoronaviruses and the application of genomic information to phylogenetic analysis, molecular epidemiology and the design of diagnostic systems, potential drugs and vaccine candidates.

positive: Do pets protect their owners in the COVID-19 era?

positive: The hallmarks of COVID-19 disease Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that has caused a worldwide pandemic of the human respiratory illness COVID-19, resulting in a severe threat to public health and safety. Analysis of the genetic tree suggests that SARS-CoV-2 belongs to the same Betacoronavirus group as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Although the route for viral transmission remains a mystery, SARS-CoV-2 may have originated in an animal reservoir, likely that of bat. The clinical features of COVID-19, such as fever, cough, shortness of breath, and fatigue, are similar to those of many acute respiratory infections. There is currently no specific treatment for COVID-19, but antiviral therapy combined with supportive care is the main strategy. Here, we summarize recent progress in understanding the epidemiological, virological, and clinical characteristics of COVID-19 and discuss potential targets with existing drugs for the treatment of this emerging zoonotic disease.

positive: History is repeating itself: Probable zoonotic spillover as the cause of the 2019 novel Coronavirus Epidemic Pathogen transmission from a vertebrate animal to a human, also known as zoonotic spillover, represents a global public health burden, which while associated with multiple outbreaks, still remains a poorly understood phenomenon. Coronaviruses, like influenza viruses, circulate in nature in various animal species. Alpha-coronaviruses and beta-coronaviruses can infect mammals and gamma-coronaviruses and delta-coronaviruses tend to infect birds, but some of them can also be transmitted to mammals. Although still preliminary, current data suggest that bats are the most probable initial source of the current 2019 novel CoV (2019nCoV) outbreak, that begun on December 2019 in Wuhan, China, apparently spreading from a "wet market" to multiple cities and provinces in China. This epidemic of 2019nCoV, already reaching more than 6,000 cases to-day (end of January 2020) (>90% in China), will not be the last one linked to zoonotic spillover events.

positive: Comprehensive evolution and molecular characteristics of a large number of SARS-CoV-2 genomes revealed its epidemic trend and possible origins Objectives To reveal epidemic trend and possible origins of SARS-CoV-2 by exploring its evolution and molecular characteristics based on a large number of genomes since it has infected millions of people and spread quickly all over the world. Methods Various evolution analysis methods were employed. Results The estimated Ka/Ks ratio of SARS-CoV-2 is 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes, and the time to the most recent common ancestor (tMRCA) was inferred in late September 2019. Further 9 key specific sites of highly linkage and four major haplotypes H1, H2, H3 and H4 were found. The Ka/Ks, detected population size and development trends of each major haplotype showed H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating H3 and H4 might have existed for a long time, while H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time. Notably the frequency of H1 was generally high in Europe and correlated to death rate (r>0.37). Conclusions In this study, the evolution and molecular characteristics of more than 16000 genomic sequences provided a new perspective for revealing epidemiology of SARS-CoV-2.

positive: Detection of novel coronaviruses in bats in Myanmar The recent emergence of bat-borne zoonotic viruses warrants vigilant surveillance in their natural hosts. Of particular concern is the family of coronaviruses, which includes the causative agents of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and most recently, Coronavirus Disease 2019 (COVID-19), an epidemic of acute respiratory illness originating from Wuhan, China in December 2019. Viral detection, discovery, and surveillance activities were undertaken in Myanmar to identify viruses in animals at high risk contact interfaces with people. Free-ranging bats were captured, and rectal and oral swabs and guano samples collected for coronaviral screening using broadly reactive consensus conventional polymerase chain reaction. Sequences from positives were compared to known coronaviruses. Three novel alphacoronaviruses, three novel betacoronaviruses, and one known alphacoronavirus previously identified in other southeast Asian countries were detected for the first time in bats in Myanmar. Ongoing land use change remains a prominent driver of zoonotic disease emergence in Myanmar, bringing humans into ever closer contact with wildlife, and justifying continued surveillance and vigilance at broad scales.

positive: Coronavirus disease 2019 (COVID‐19) outbreak: Could pigs be vectors for human infections?

positive: The virus whose family expanded The discovery of many new species of hepaciviruses and pegiviruses, which exhibit enormous genetic diversity, in wild rodent and bat populations might help us to understand the origins of the hepatitis C virus.

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

positive: The 2019-new coronavirus epidemic: Evidence for virus evolution There is a worldwide concern about the new coronavirus 2019-nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequences of 2019-nCoV, 12 whole genome sequences of 2019-nCoV, and 12 highly similar whole genome sequences available in gene bank (five from the severe acute respiratory syndrome, two from Middle East respiratory syndrome, and five from bat SARS-like coronavirus). Fast unconstrained Bayesian approximation analysis shows that the nucleocapsid and the spike glycoprotein have some sites under positive pressure, whereas homology modeling revealed some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019-nCoV significantly clustered with bat SARS-like coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. From these results, the new 2019-nCoV is distinct from SARS virus, probably trasmitted from bats after mutation conferring ability to infect humans.

positive: In silico studies on the comparative characterization of the interactions of SARS‐CoV‐2 spike glycoprotein with ACE‐2 receptor homologs and human TLRs Coronavirus disease‐2019 (COVID‐19) outbreak due to novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has come out as a major threat for mankind in recent times. It is continually taking an enormous toll on mankind by means of increasing number of deaths, associated comorbidities, and socioeconomic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to scientists and doctors for developing an urgent therapeutic strategy. In this connection, the present in silico study aims to understand the sequence divergence of spike protein (the major infective protein of SARS‐CoV‐2), its mode of interaction with the angiotensin‐converting enzyme‐2 receptor (ACE2) receptor of human and related animal hosts/reservoir. Moreover, the involvement of the human Toll‐like receptors (TLRs) against the spike protein has also been demonstrated. Our data indicated that the spike glycoprotein of SARS‐CoV‐2 is phylogenetically close to bat coronavirus and strongly binds with ACE2 receptor protein from both human and bat origin. We have also found that cell surface TLRs, especially TLR4 is most likely to be involved in recognizing molecular patterns from SARS‐CoV‐2 to induce inflammatory responses. The present study supported the zoonotic origin of SARS‐CoV‐2 from a bat and also revealed that TLR4 may have a crucial role in the virus‐induced inflammatory consequences associated with COVID‐19. Therefore, selective targeting of TLR4‐spike protein interaction by designing competitive TLR4‐antagonists could pave a new way to treat COVID‐19. Finally, this study is expected to improve our understanding on the immunobiology of SARS‐CoV‐2 and could be useful in adopting spike protein, ACE2, or TLR‐guided intervention strategy against COVID‐19 shortly.

positive: Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.

positive: A pneumonia outbreak associated with a new coronavirus of probable bat origin Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats(1–4). Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans(5–7). Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

positive: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that has caused the global COVID-19 pandemic. Tracing the evolution and transmission of the virus is crucial to respond to and control the pandemic through appropriate intervention strategies. This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. Prediction results suggest that mutation D614G in the virus spike protein, which has attracted much attention from researchers, is unlikely to make changes in protein secondary structure and relative solvent accessibility. Based on 6,324 viral genome sequences, we create a spreadsheet dataset of point mutations that can facilitate the investigation of SARS-CoV-2 in many perspectives, especially in tracing the evolution and worldwide spread of the virus. Our analysis results also show that coding genes E, M, ORF6, ORF7a, ORF7b and ORF10 are most stable, potentially suitable to be targeted for vaccine and drug development.

positive: Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible.

positive: Bats and Coronaviruses Bats are speculated to be reservoirs of several emerging viruses including coronaviruses (CoVs) that cause serious disease in humans and agricultural animals. These include CoVs that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), porcine epidemic diarrhea (PED) and severe acute diarrhea syndrome (SADS). Bats that are naturally infected or experimentally infected do not demonstrate clinical signs of disease. These observations have allowed researchers to speculate that bats are the likely reservoirs or ancestral hosts for several CoVs. In this review, we follow the CoV outbreaks that are speculated to have originated in bats. We review studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease. We speculate about future studies that are critical to identify how bats can harbor multiple strains of CoVs and factors that enable these viruses to “jump” from bats to other mammals. We hope that this review will enable readers to identify gaps in knowledge that currently exist and initiate a dialogue amongst bat researchers to share resources to overcome present limitations.

positive: Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19) has rapidly spread to the entire world within a few months. The origin of SARS-CoV-2 has been related to the lineage B Betacoronavirus SARS-CoV and SARS-related coronaviruses found in bats. Early characterizations of the SARS-CoV-2 genome revealed the existence of a distinct 4 amino acid insert within the spike (S) protein (underlined, SPRRAR↓S), at the S1/S2 site located at the interface between the S1 receptor binding subunit and the S2 fusion subunit. Notably, this insert appears to be a distinguishing feature among SARS-related sequences and introduces a potential cleavage site for the protease furin. Here, we investigate the potential role of this novel S1/S2 cleavage site and present direct biochemical evidence for proteolytic processing by a variety of proteases. We discuss these findings in the context of the origin of SARS-CoV-2, viral stability and transmission.

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

positive: The novel Coronavirus (SARS-CoV-2) is a one health issue

positive: Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.

positive: Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts. The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.

positive: Phylogenetic perspectives on the epidemiology and origins of SARS and SARS-like coronaviruses Abstract Severe Acute Respiratory Syndrome (SARS) is a respiratory disease caused by a zoonotic coronavirus (CoV) named SARS-CoV (SCoV), which rapidly swept the globe after its emergence in rural China during late 2002. The origins of SCoV have been mysterious and controversial, until the recent discovery of SARS-like CoV (SLCoV) in bats and the proposal of bats as the natural reservior of the Coronaviridae family. In this article, we focused on discussing how phylogenetics contributed to our understanding towards the emergence and transmission of SCoV. We first reviewed the epidemiology of SCoV from a phylogenetic perspective and discussed the controversies over its phylogenetic origins. Then, we summarized the phylogenetic findings in relation to its zoonotic origins and the proposed inter-species viral transmission events. Finally, we also discussed how the discoveries of SCoV and SLCoV expanded our knowledge on the evolution of the Coronaviridae family as well as its implications on the possible future re-emergence of SCoV.

positive: Is There a Guarantee That the Crisis of COVID-19 Will not Be Repeated?

positive: Evolution and epidemic spread of SARS-CoV-2 in Brazil Brazil currently has one of the fastest growing SARS-CoV-2 epidemics in the world. Due to limited available data, assessments of the impact of non-pharmaceutical interventions (NPIs) on virus transmission and epidemic spread remain challenging. We investigate the impact of NPIs in Brazil using epidemiological, mobility and genomic data. Mobility-driven transmission models for Sao Paulo and Rio de Janeiro cities show that the reproduction number (Rt) reached below 1 following NPIs but slowly increased to values between 1 to 1.3 (1.0 - -1.6). Genome sequencing of 427 new genomes and analysis of a geographically representative genomic dataset from 21 of the 27 Brazilian states identified >100 international introductions of SARS-CoV-2 in Brazil. We estimate that three clades introduced from Europe emerged between 22 and 27 February 2020, and were already well-established before the implementation of NPIs and travel bans. During this first phase of the epidemic establishment of SARS-CoV-2 in Brazil, we find that the virus spread mostly locally and within-state borders. Despite sharp decreases in national air travel during this period, we detected a 25% increase in the average distance travelled by air passengers during this time period. This coincided with the spread of SARS-CoV-2 from large urban centers to the rest of the country. In conclusion, our results shed light on the role of large and highly connected populated centres in the rapid ignition and establishment of SARS-CoV-2, and provide evidence that current interventions remain insufficient to keep virus transmission under control in Brazil.

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

positive: The Novel Coronavirus Outbreak: What We Know and What We Don’t

positive: 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.

positive: 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.

positive: Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination. UNLABELLED Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission. IMPORTANCE Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination.

positive: Origin and evolution of the 2019 novel coronavirus

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

positive: In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus The devastating impact of the COVID19 pandemic caused by SARS coronavirus 2 (SARSCoV2) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in susceptibilities across animal species. Traditional lab-based methods will ultimately answer many of these questions but take considerable time. In silico modeling methods provide the opportunity to rapidly generate information on newly emerged pathogens to aid countermeasure development and also to predict potential future behaviors. We used a structural homology modeling approach to characterize the SARSCoV2 spike protein and predict its binding strength to the human ACE2 receptor. We then explored the possible transmission path by which SARSCoV2 might have crossed to humans by constructing models of ACE2 receptors of relevant species, and calculating the binding energy of SARSCoV2 spike protein to each. Notably, SARSCoV2 spike protein had the highest overall binding energy for human ACE2, greater than all the other tested species including bat, the postulated source of the virus. This indicates that SARSCoV2 is a highly adapted human pathogen. Of the species studied, the next highest binding affinity after human was pangolin, which is most likely explained by a process of convergent evolution. Binding of SARSCoV2 for dog and cat ACE2 was similar to affinity for bat ACE2, all being lower than for human ACE2, and is consistent with only occasional observations of infections of these domestic animals. Overall, the data indicates that SARSCoV2 is uniquely adapted to infect humans, raising questions as to whether it arose in nature by a rare chance event or whether its origins lie elsewhere.

positive: Identification of the hyper-variable genomic hotspot for the novel coronavirus SARS-CoV-2

positive: COVID-19: The Conjunction of Events Leading to the Coronavirus Pandemic and Lessons to Learn for Future Threats

positive: Cross‐species transmission of the newly identified coronavirus 2019‐nCoV The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.

positive: Q&A: The novel coronavirus outbreak causing COVID-19

positive: Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. The source of the severe acute respiratory syndrome (SARS) epidemic was traced to wildlife market civets and ultimately to bats. Subsequent hunting for novel coronaviruses (CoVs) led to the discovery of two additional human and over 40 animal CoVs, including the prototype lineage C betacoronaviruses, Tylonycteris bat CoV HKU4 and Pipistrellus bat CoV HKU5; these are phylogenetically closely related to the Middle East respiratory syndrome (MERS) CoV, which has affected more than 1,000 patients with over 35% fatality since its emergence in 2012. All primary cases of MERS are epidemiologically linked to the Middle East. Some of these patients had contacted camels which shed virus and/or had positive serology. Most secondary cases are related to health care-associated clusters. The disease is especially severe in elderly men with comorbidities. Clinical severity may be related to MERS-CoV's ability to infect a broad range of cells with DPP4 expression, evade the host innate immune response, and induce cytokine dysregulation. Reverse transcription-PCR on respiratory and/or extrapulmonary specimens rapidly establishes diagnosis. Supportive treatment with extracorporeal membrane oxygenation and dialysis is often required in patients with organ failure. Antivirals with potent in vitro activities include neutralizing monoclonal antibodies, antiviral peptides, interferons, mycophenolic acid, and lopinavir. They should be evaluated in suitable animal models before clinical trials. Developing an effective camel MERS-CoV vaccine and implementing appropriate infection control measures may control the continuing epidemic.

positive: Mapping the genomic landscape & diversity of COVID-19 based on >3950 clinical isolates of SARS-CoV-2: Likely origin & transmission dynamics of isolates sequenced in India

positive: History is repeating itself, a probable zoonotic spillover as a cause of an epidemic: the case of 2019 novel Coronavirus. Pathogen transmission from a vertebrate animal to a human, also known as zoonotic spillover, represents a global public health burden, which while associated with multiple outbreaks, still remains a poorly understood phenomenon. Coronaviruses, like influenza viruses, circulate in nature in various animal species. Alpha-coronaviruses and beta-coronaviruses can infect mammals and gamma-coronaviruses and delta-coronaviruses tend to infect birds, but some of them can also be transmitted to mammals. Although still preliminary, current data suggest that bats are the most probable initial source of the current 2019 novel CoV (2019nCoV) outbreak, that begun on December 2019 in Wuhan, China, apparently spreading from a "wet market" to multiple cities and provinces in China. This epidemic of 2019nCoV, already reaching more than 6,000 cases to-day (end of January 2020) (>90% in China), will not be the last one linked to zoonotic spillover events.

positive: [Spike protein in the detection and treatment of novel coronavirus] Recently a COVID-19 pneumonia pandemic caused by a novel coronavirus 2019-nCoV has broken out over the world. In order to better control the spread of the pandemic, there's an urgent need to extensively study the virus' origin and the mechanisms for its infectivity and pathogenicity. Spike protein is a special structural protein on the surface of coronavirus. It contains important information about the evolution of the virus and plays critical roles in the processes of cellular recognition and entry. In the past decades, spike protein has always been one of the most important objects in research works on coronaviruses closely related to human life. In this review we introduce these research works related to spike proteins, hoping it will provide reasonable ideas for the control of the current pandemic, as well as for the diagnosis and treatment of COVID-19.

positive: Detection of alpha- and betacoronaviruses in rodents from Yunnan, China BACKGROUND: Rodents represent the most diverse mammals on the planet and are important reservoirs of human pathogens. Coronaviruses infect various animals, but to date, relatively few coronaviruses have been identified in rodents worldwide. The evolution and ecology of coronaviruses in rodent have not been fully investigated. RESULTS: In this study, we collected 177 intestinal samples from thress species of rodents in Jianchuan County, Yunnan Province, China. Alphacoronavirus and betacoronavirus were detected in 23 rodent samples from three species, namely Apodemus chevrieri (21/98), Eothenomys fidelis (1/62), and Apodemus ilex (1/17). We further characterized the full-length genome of an alphacoronavirus from the A. chevrieri rat and named it as AcCoV-JC34. The AcCoV-JC34 genome was 27,649 nucleotides long and showed a structure similar to the HKU2 bat coronavirus. Comparing the normal transcription regulatory sequence (TRS), 3 variant TRS sequences upstream the spike (S), ORF3, and ORF8 genes were found in the genome of AcCoV-JC34. In the conserved replicase domains, AcCoV-JC34 was most closely related to Rattus norvegicus coronavirus LNRV but diverged from other alphacoronaviruses, indicating that AcCoV-JC34 and LNRV may represent a novel alphacoronavirus species. However, the S and nucleocapsid proteins showed low similarity to those of LRNV, with 66.5 and 77.4% identities, respectively. Phylogenetic analysis revealed that the S genes of AcCoV-JC34, LRNV, and HKU2 formed a distinct lineage with all known coronaviruses. CONCLUSIONS: Both alphacoronaviruses and betacoronaviruses were detected in Apodemus chevrieri in the Yunnan Province of China, indicating that Apodemus chevrieri is an important host for coronavirus. Several new features were identified in the genome of an Apodemus chevrieri coronavirus. The phylogenetic distance to other coronaviruses suggests a variable origin and evolutionary route of the S genes of AcCoV-JC34, LRNV, and HKU2. These results indicate that the diversity of rodent coronaviruses is much higher than previously expected. Further surveillance and functional studies of these coronaviruses will help to better understand the importance of rodent as host for coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0766-9) contains supplementary material, which is available to authorized users.

positive: Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event Abstract Background A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus. Methods Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods. Results Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat_SARS-like coronavirus sequences. Specifically, in the 5′-part spanning the first 11,498 nucleotides and the last 3′-part spanning 24,341–30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat_SARS-like coronavirus sequences, whereas in the middle region spanning the 3′-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch. Conclusions The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.

positive: Introductions and early spread of SARS-CoV-2 in the New York City area New York City (NYC) has emerged as one of the epicenters of the current SARS-CoV2 pandemic. To identify the early events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus causing COVID19 in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV2 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. Moreover, we find evidence for community transmission of SARS-CoV2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.

positive: A new coronavirus associated with human respiratory disease in China Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health(1–3). Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing(4) of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China(5). This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.

positive: Coronaviruses pandemics: Can neutralizing antibodies help? For the first time in Homo sapiens history, possibly, most of human activities is stopped by coronavirus disease 2019 (COVID-19). Nearly eight billion people of this world are facing a great challenge, maybe not “to be or not to be” yet, but unpredictable. What happens to other major pandemics in the past, and how human beings went through these hurdles? The human body is equipped with the immune system that can recognize, respond and fight against pathogens such as viruses. Following the innate response, immune system processes the adaptive response by which each pathogen is encoded and recorded in memory system. The humoral reaction containing cytokines and antibodies is expected to activate when the pathogens come back. Exploiting this nature of body protection, neutralizing antibodies have been investigated. Learning from past, in parallel to SARS-CoV-2, other coronaviruses SARS-CoV and MERS-CoV who caused previous pandemics, are recalled in this review. We here propose insights of origin and characteristics and perspective for the future of antibodies development.

positive: Tracking the onset date of the community spread of SARS-CoV-2 in Western Countries The SARS-CoV-2 rapidly spread around the world during 2020, but the precise time in which the virus began to spread locally is currently unknown for most countries. Here, we estimate the probable onset date of the community spread of SARS-CoV-2 from the cumulative number of deaths reported during the early stage of the epidemic in Western Europe and the Americas. Our results support that SARS-CoV-2 probably started to spread locally in all western countries analyzed between the middle of January and early February 2020, thus long before community transmission was officially recognized and control measures were implemented.

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

positive: COVID-19-A Novel Zoonotic Disease: A Review of the Disease, the Virus, and Public Health Measures. A cluster of cases of pneumonia of unknown etiology emerged in Wuhan, China, at the end of December 2019. The cluster was largely associated with a seafood and animal market. A novel Betacoronavirus was quickly identified as the causative agent, and it is shown to be related genetically to SARS-CoV and other bat-borne SARS-related Betacoronaviruses. The number of cases increased rapidly and spread to other provinces in China, as well as to another 4 countries. To help control the spread of the virus, a "cordon sanitaire" was instituted for Wuhan on January 23, 2020, and subsequently extended to other cities in Hubei Province, and the outbreak declared a Public Health Emergency of International Concern by the Director General of the World Health Organization on January 30, 2020. The virus was named SARS-CoV-2 by the International Committee for the Taxonomy of Viruses, and the disease it causes was named COVID-19 by the World Health Organization. This article described the evolution of the outbreak, and the known properties of the novel virus, SARS-CoV-2 and the clinical disease it causes, and the major public health measures being used to help control it's spread. These measures include social distancing, intensive surveillance and quarantining of cases, contact tracing and isolation, cancellation of mass gatherings, and community containment. The virus is the third zoonotic coronavirus, after SARS-CoV and MERS-CoV, but appears to be the only one with pandemic potential. However, a number of important properties of the virus are still not well understood, and there is an urgent need to learn more about its transmission dynamics, its spectrum of clinical severity, its wildlife origin, and its genetic stability. In addition, more research is needed on possible interventions, particularly therapeutic and vaccines.

positive: Mutated COVID-19 may foretell a great risk for mankind in the future Coronavirus disease 2019 SARS-CoV-2 (COVID-19) is a zoonotic virus causing a variety of severe respiratory diseases. SARS-CoV-2 is closest to SARS-CoV and MERS-CoV in structure. The high prevalence of COVID-19 is a result of a lack of symptoms at onset. Our study aimed to present an overview of the virus in terms of structure, epidemiology, symptoms, treatment and prevention. Whole genome sequences and some viral proteins were investigated to determine gaps and changes in alternation of nucleotides and amino acid sequences. We evaluate 11 complete genome sequences of different coronaviruses using BAST and MAFFT software. We also selected seven types of structural proteins. We conclude that COVID-19 might produce new mutations, specifically in glycoproteins, so caution and complete preparation by health authorities is required.

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

positive: 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.

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

positive: Molecular epidemiology, evolution and phylogeny of SARS coronavirus Abstract Shortly after its emergence in southern China in 2002/2003, Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) was confirmed to be the cause of SARS. Subsequently, SARS-related CoVs (SARSr-CoVs) were found in palm civets from live animal markets in Guangdong and in various horseshoe bat species, which were believed to be the ultimate reservoir of SARSr-CoV. Till November 2018, 339 SARSr-CoV genomes have been sequenced, including 274 from human, 18 from civets and 47 from bats [mostly from Chinese horseshoe bats (Rhinolophus sinicus), n = 30; and greater horseshoe bats (Rhinolophus ferrumequinum), n = 9]. The human SARS-CoVs and civet SARSr-CoVs were collected in 2003/2004, while bat SARSr-CoVs were continuously isolated in the past 13 years even after the cessation of the SARS epidemic. SARSr-CoVs belong to the subgenus Sarbecovirus (previously lineage B) of genus Betacoronavirus and occupy a unique phylogenetic position. Overall, it is observed that the SARSr-CoV genomes from bats in Yunnan province of China possess the highest nucleotide identity to those from civets. It is evident from both multiple alignment and phylogenetic analyses that some genes of a particular SARSr-CoV from bats may possess higher while other genes possess much lower nucleotide identity to the corresponding genes of SARSr-CoV from human/civets, resulting in the shift of phylogenetic position in different phylogenetic trees. Our current model on the origin of SARS is that the human SARS-CoV that caused the epidemic in 2002/2003 was probably a result of multiple recombination events from a number of SARSr-CoV ancestors in different horseshoe bat species.

positive: Middle East Respiratory Syndrome Coronavirus “MERS-CoV”: Current Knowledge Gaps Summary The Middle East respiratory syndrome coronavirus (MERS-CoV) that causes a severe lower respiratory tract infection in humans is now considered a pandemic threat to the Gulf region. Since its discovery in 2012, MERS-CoV has reached 23 countries affecting about 1100 people, including a dozen children, and claiming over 400 lives. Compared to SARS (severe acute respiratory syndrome), MERS-CoV appears to kill more people (40% versus 10%), more quickly, and is especially more severe in those with pre-existing medical conditions. Most MERS-CoV cases (>85%) reported thus far have a history of residence in, or travel to the Middle East. The current epidemiology is characterised by slow and sustained transmission with occasional sparks. The dromedary camel is the intermediate host of MERS-CoV, but the transmission cycle is not fully understood. In this current review, we have briefly summarised the latest information on the epidemiology, clinical features, diagnosis, treatment and prevention of MERS-CoV especially highlighting the knowledge gaps in its transmission dynamics, diagnosis and preventive strategy.

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: 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.

positive: Evidence for SARS-CoV-2 Infection of Animal Hosts COVID-19 is the first known pandemic caused by a coronavirus, SARS-CoV-2, which is the third virus in the family Coronaviridae to cause fatal infections in humans after SARS-CoV and MERS-CoV Animals are involved in the COVID-19 pandemic This review summarizes the role of animals as reservoirs, natural hosts and experimental models SARS-CoV-2 originated from animal reservoir, most likely bats and/or pangolins Anthroponotic transmission has been reported in cats, dogs, tigers, lions and minks As of now, there is no a strong evidence for natural animal-to-human transmission or sustained animal-to-animal transmission of SARS-CoV-2 Experimental infections conducted by several research groups have shown that monkeys, hamsters, ferrets, cats, tree shrews, transgenic mice and fruit bats were permissive, while dogs, pigs and poultry were resistant There is an urgent need to understand the zoonotic potential of different viruses in animals, particularly in bats, before they transmit to humans Vaccines or antivirals against SARS-CoV-2 should be evaluated not only for humans, but also for the protection of companion animals (particularly cats) and susceptible zoo and farm animals

positive: COVID-19 Variants Database: A repository for Human SARS-CoV-2 Polymorphism Data COVID-19 is a newly communicable disease with a catastrophe outbreak that affects all over the world. We retrieved about 8,781 nucleotide fragments and complete genomes of SARS-CoV-2 reported from sixty-four countries. The CoV-2 reference genome was obtained from the National Genomics Data Center (NGDC), GISAID, and NCBI Genbank. All the sequences were aligned against reference genomes using Clustal Omega and variants were called using in-house built Python script. We intend to establish a user-friendly online resource to visualize the variants in the viral genome along with the Primer Infopedia. After analyzing and filtering the data globally, it was made available to the public. The detail of data available to the public includes mutations from 5688 SARS-CoV-2 sequences curated from 91 regions. This database incorporated 39920 mutations over 3990 unique positions. According to the translational impact, these mutations include 11829 synonymous mutations including 681 synonymous frameshifts and 21701 nonsynonymous mutations including 10 nonsynonymous frameshifts. Development of SARS-CoV-2 mutation genome browsers is a fundamental step obliging towards the virus surveillance, viral detection, and development of vaccine and therapeutic drugs. The SARS-COV-2 mutation browser is available at http://covid-19.dnageography.com.

positive: Revealing COVID-19 Transmission by SARS-CoV-2 Genome Sequencing and Agent Based Modelling Community transmission of the new coronavirus SARS-CoV-2 is a major public health concern that remains difficult to assess. We present a genomic survey of SARS-CoV-2 from a during the first 10 weeks of COVID-19 activity in New South Wales, Australia. Transmission events were monitored prospectively during the critical period of implementation of national control measures. SARS-CoV-2 genomes were sequenced from 209 patients diagnosed with COVID-19 infection between January and March 2020. Only a quarter of cases appeared to be locally acquired and genomic-based estimates of local transmission rates were concordant with predictions from a computational agent-based model. This convergent assessment indicates that genome sequencing provides key information to inform public health action and has improved our understanding of the COVID-19 evolution from outbreak to epidemic.

positive: Molecular basis of genetic variation of viruses: error-prone replication Genetic variation is a necessity of all biological systems. Viruses use all known mechanisms of variation; mutation, several forms of recombination, and segment reassortment in the case of viruses with a segmented genome. These processes are intimately connected with the replicative machineries of viruses, as well as with fundamental physical-chemical properties of nucleotides when acting as template or substrate residues. Recombination has been viewed as a means to rescue viable genomes from unfit parents or to produce large modifications for the exploration of phenotypic novelty. All types of genetic variation can act conjointly as blind processes to provide the raw materials for adaptation to the changing environments in which viruses must replicate. A distinction is made between mechanistically unavoidable and evolutionarily relevant mutation and recombination.

positive: A previously uncharacterized gene in SARS-CoV-2 and the origins of the COVID-19 pandemic Understanding the emergence of novel viruses requires an accurate and comprehensive annotation of their genomes. Overlapping genes (OLGs) are common in viruses and have been associated with the origins of pandemics, but are still widely overlooked. We identify ORF3c, a novel OLG in SARS-CoV-2 that is also present in Guangxi pangolin-CoVs but not more closely related pangolin-CoVs (Guangdong) or bat-CoVs (RaTG13 and RmYN02). We then document evidence of translation from ribosome profiling and conduct an evolutionary analysis at three levels: between-species (n=21 betacoronavirus genomes), between-host (n=3,978 SARS-CoV-2 consensus sequences), and within-host (401 deeply sequenced SARS-CoV-2 samples). ORF3c has been independently identified and shown to elicit a strong antibody response in COVID-19 patients. However, it has been misclassified as ORF3b, an unrelated gene in other SARS-related betacoronaviruses, leading to confusion and unfounded functional inferences. Our results liken ORF3c to other viral accessory genes and stress the importance of studying OLGs.

positive: Computational Inference of Selection Underlying the Evolution of the Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that recently emerged in China is thought to have a bat origin, as its closest known relative (BatCoV RaTG13) was described previously in horseshoe bats. We analyzed the selective events that accompanied the divergence of SARS-CoV-2 from BatCoV RaTG13. To this end, we applied a population genetics-phylogenetics approach, which leverages within-population variation and divergence from an outgroup. Results indicated that most sites in the viral open reading frames (ORFs) evolved under conditions of strong to moderate purifying selection. The most highly constrained sequences corresponded to some nonstructural proteins (nsps) and to the M protein. Conversely, nsp1 and accessory ORFs, particularly ORF8, had a nonnegligible proportion of codons evolving under conditions of very weak purifying selection or close to selective neutrality. Overall, limited evidence of positive selection was detected. The 6 bona fide positively selected sites were located in the N protein, in ORF8, and in nsp1. A signal of positive selection was also detected in the receptor-binding motif (RBM) of the spike protein but most likely resulted from a recombination event that involved the BatCoV RaTG13 sequence. In line with previous data, we suggest that the common ancestor of SARS-CoV-2 and BatCoV RaTG13 encoded/encodes an RBM similar to that observed in SARS-CoV-2 itself and in some pangolin viruses. It is presently unknown whether the common ancestor still exists and, if so, which animals it infects. Our data, however, indicate that divergence of SARS-CoV-2 from BatCoV RaTG13 was accompanied by limited episodes of positive selection, suggesting that the common ancestor of the two viruses was poised for human infection. IMPORTANCE Coronaviruses are dangerous zoonotic pathogens; in the last 2 decades, three coronaviruses have crossed the species barrier and caused human epidemics. One of these is the recently emerged SARS-CoV-2. We investigated how, since its divergence from a closely related bat virus, natural selection shaped the genome of SARS-CoV-2. We found that distinct coding regions in the SARS-CoV-2 genome evolved under conditions of different degrees of constraint and are consequently more or less prone to tolerate amino acid substitutions. In practical terms, the level of constraint provides indications about which proteins/protein regions are better suited as possible targets for the development of antivirals or vaccines. We also detected limited signals of positive selection in three viral ORFs. However, we warn that, in the absence of knowledge about the chain of events that determined the human spillover, these signals should not be necessarily interpreted as evidence of an adaptation to our species.

positive: SARS-CoV-2: Combating Coronavirus Emergence Summary The emergence and rapid global spread of SARS-CoV-2 mark the third such identification of a novel coronavirus capable of causing severe, potentially fatal disease in humans in the 21st century. As noted by Andersen et al. (Nature Medicine), the sequencing of proximal zoonotic ancestors to SARS-CoV-2 has aided in the identification of alleles that may contribute to the virus’ virulence in humans.

positive: Lions, Tigers and Kittens too: ACE2 and susceptibility to CoVID-19 SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has been reported to infect domesticated animals in a species-specific manner, where cats were susceptible but not dogs. Using the recently published crystal structure of the SARS-CoV-2 spike protein complexed with the human host cell receptor ACE2, we characterized the structure and evolution of ACE2 in several of these species and identify a single interacting amino acid residue conserved between human and Felidae ACE2 but not in Canidae that correlates with virus susceptibility. Using computational analyses we describe how this site likely affects ACE2 targeting by the virus. Thus, we highlight how evolution-based approaches can be used to form hypotheses and study animal transmission of such viruses in the future. Lay summary: Recently, the virus that causes COVID-19 was shown to transmit to companion animals. A single genetic change in the host receptor for the virus inherited in cats, but not dogs, correlates with feline susceptibility. With human-to-cat transmission of COVID-19 confirmed, such information can inform public health policy regarding companion animals.

positive: The COVID-19 Pandemic and Paradigm Change in Global Scientific Research The current pandemic has rocked the lives of human beings every-where in ways never imagined, forcing us to question where our civilization is headed. In this article, we explore and discuss scien-tifi c evidence that helps explain recent events in the context of the COVID-19 pandemic.COVID-19 is caused by infection with a zoonotic-origin novel virus, SARS-CoV-2, that is genetically close to two coronavirus types iso-lated in bats. The transmission dynamics to humans from the original and intermediary hosts remain poorly understood, but it is highly likely that the SARS-CoV-2 virus infected humans after undergoing an inter-species transfer from bats to an intermediate species, and from there to human beings. Crossing the species barrier is largely fostered by industrial-scale agricultural practices that simplify original ecosystem connections by reducing biodiversity, facilitating the emergence of new infectious diseases. The scientifi c community has played an exemplary role in responding to this global emergency, working to fi nd timely, relevant solutions for governments and society as a whole. We need to take this opportunity to promote a global and open science that delves into the interrelation-ships of the biological, environmental, social and economic dimen-sions of this and other diseases while questioning current modes of production and their impact on the environment, and thus on human health worldwide. Keywords: Coronavirus infections; communicable diseases; zoonoses; ecosystems; technology, industry, and agriculture; pandemics; global health; Mexico.

positive: Origins and evolution of viruses of eukaryotes: The ultimate modularity Abstract Viruses and other selfish genetic elements are dominant entities in the biosphere, with respect to both physical abundance and genetic diversity. Various selfish elements parasitize on all cellular life forms. The relative abundances of different classes of viruses are dramatically different between prokaryotes and eukaryotes. In prokaryotes, the great majority of viruses possess double-stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss) DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes, RNA viruses account for the majority of the virome diversity although ssDNA and dsDNA viruses are common as well. Phylogenomic analysis yields tangible clues for the origins of major classes of eukaryotic viruses and in particular their likely roots in prokaryotes. Specifically, the ancestral genome of positive-strand RNA viruses of eukaryotes might have been assembled de novo from genes derived from prokaryotic retroelements and bacteria although a primordial origin of this class of viruses cannot be ruled out. Different groups of double-stranded RNA viruses derive either from dsRNA bacteriophages or from positive-strand RNA viruses. The eukaryotic ssDNA viruses apparently evolved via a fusion of genes from prokaryotic rolling circle-replicating plasmids and positive-strand RNA viruses. Different families of eukaryotic dsDNA viruses appear to have originated from specific groups of bacteriophages on at least two independent occasions. Polintons, the largest known eukaryotic transposons, predicted to also form virus particles, most likely, were the evolutionary intermediates between bacterial tectiviruses and several groups of eukaryotic dsDNA viruses including the proposed order “Megavirales” that unites diverse families of large and giant viruses. Strikingly, evolution of all classes of eukaryotic viruses appears to have involved fusion between structural and replicative gene modules derived from different sources along with additional acquisitions of diverse genes.

positive: Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals a Broad Potential Host Range of SARS-CoV-2 The pandemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health threat. Epidemiological studies suggest that bats are the natural zoonotic reservoir for SARS-CoV-2. However, the host range of SARS-CoV-2 and intermediate hosts that facilitate its transmission to humans remain unknown. The interaction of coronavirus with its host receptor is a key genetic determinant of host range and cross-species transmission. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor to enter host cells in a species-dependent manner. It has been shown that human, palm civet, pig and bat ACE2 can support virus entry, while the murine ortholog cannot. In this study, we characterized the ability of ACE2 from diverse species to support viral entry. We found that ACE2 is expressed in a wide range of species, with especially high conservation in mammals. By analyzing amino acid residues of ACE2 critical for virus entry, based on structure of SARS-CoV spike protein interaction with human, bat, palm civet, pig and ferret ACE2, we identified approximately eighty ACE2 proteins from mammals that could potentially mediate SARS-CoV-2 entry. Functional assays showed that 44 of these mammalian ACE2 orthologs, including those of domestic animals, pets, livestock, and animals commonly found in zoos and aquaria, could bind SARS-CoV-2 spike protein and support viral entry. In contrast, New World monkey ACE2 orthologs could not bind SARS-CoV-2 spike protein and support viral entry. We further identified the genetic determinant of New World monkey ACE2 that restricts viral entry using genetic and functional analyses. In summary, our study demonstrates that ACE2 from a remarkably broad range of species can facilitate SARS-CoV-2 entry. These findings highlight a potentially broad host tropism of SARS-CoV-2 and suggest that SARS-CoV-2 might be distributed much more widely than previously recognized, underscoring the necessity to monitor susceptible hosts to prevent future outbreaks.

positive: First genome sequences of buffalo coronavirus from water buffaloes in Bangladesh We report the complete genome sequences of a buffalo coronavirus (BufCoV HKU26) detected from the faecal samples of two domestic water buffaloes (Bubalus bubalis) in Bangladesh. They possessed 98–99% nucleotide identities to bovine coronavirus (BCoV) genomes, supporting BufCoV HKU26 as a member of Betacoronavirus 1. Nevertheless, BufCoV HKU26 possessed distinct accessory proteins between spike and envelope compared to BCoV. Sugar-binding residues in the N-terminal domain of S protein in BCoV are conserved in BufCoV HKU26.

positive: 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.

positive: Characterizing the transmission and identifying the control strategy for COVID-19 through epidemiological modeling The outbreak of the novel coronavirus disease, COVID-19, originating from Wuhan, China in early December, has infected more than 70,000 people in China and other countries and has caused more than 2,000 deaths. As the disease continues to spread, the biomedical society urgently began identifying effective approaches to prevent further outbreaks. Through rigorous epidemiological analysis, we characterized the fast transmission of COVID-19 with a basic reproductive number 5.6 and proved a sole zoonotic source to originate in Wuhan. No changes in transmission have been noted across generations. By evaluating different control strategies through predictive modeling and Monte carlo simulations, a comprehensive quarantine in hospitals and quarantine stations has been found to be the most effective approach. Government action to immediately enforce this quarantine is highly recommended.

positive: Predicting zoonoses As the line dividing human and wild habitats becomes thinner, we might be brewing the world's next big pandemic. Zoonoses are diseases that are naturally transmitted between animals and humans, and a new project aims to predict their occurrence.

positive: Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2 To investigate the evolutionary history of the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. To explore the potential intermediate animal host of the SARS-CoV-2 virus, we reanalyzed virome data sets from pangolins and representative SARS-related coronaviruses isolates from bats, with particular attention paid to the spike glycoprotein gene. We performed phylogenetic, split network, transmission network, likelihood-mapping, and comparative analyses of the genomes. Based on Bayesian time-scaled phylogenetic analysis using the tip-dating method, we estimated the time to the most recent common ancestor and evolutionary rate of SARS-CoV-2, which ranged from 22 to 24 November 2019 and 1.19 to 1.31 × 10-3 substitutions per site per year, respectively. Our results also revealed that the BetaCoV/bat/Yunnan/RaTG13/2013 virus was more similar to the SARS-CoV-2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378). We also identified a unique peptide (PRRA) insertion in the human SARS-CoV-2 virus, which may be involved in the proteolytic cleavage of the spike protein by cellular proteases, and thus could impact host range and transmissibility. Interestingly, the coronavirus carried by pangolins did not have the RRAR motif. Therefore, we concluded that the human SARS-CoV-2 virus, which is responsible for the recent outbreak of COVID-19, did not come directly from pangolins.

positive: Understanding evolution of SARS‐CoV‐2: a perspective from analysis of genetic diversity of RdRp gene BACKGROUND & OBJECTIVES: COVID‐19 emerged as the first example of “Disease X”, a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as SARS‐CoV‐2. The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS‐CoV‐2 using RdRp gene, a stable genetic marker. METHODS: Phylogenetic and population stratification analyses were carried out using Maximum likelihood and Bayesian methods, respectively. RESULTS: Molecular phylogeny using RdRp, showed that SARS‐CoV‐2 isolates cluster together. Bat‐CoV isolate RaTG13 and Pangolin‐CoVs are observed to branch off prior to SARS‐CoV‐2 cluster. While SARS‐CoV form a single cluster, Bat‐CoVs form multiple clusters. Population‐based analyses revealed that both SARS‐CoV‐2 and SARS‐CoV form separate clusters with no admixture. Bat‐CoVs were found to have single and mixed ancestry and clustered as four sub‐populations. CONCLUSIONS: Population‐based analyses of Betacoronaviruses using RdRp, revealed that SARS‐CoV‐2 is a homogeneous population. SARS‐CoV‐2 appears to have evolved from Bat‐CoV isolate RaTG13, which diversified from a common ancestor from which Pangolin‐CoVs have also evolved. The admixed Bat‐CoV sub‐populations indicate that bats serve as reservoirs harboring virus ensembles that are responsible for zoonotic spillovers such as SARS‐CoV and SARS‐CoV‐2. The extent of admixed isolates of Bat‐CoVs observed in population diversification studies underline the need for periodic surveillance of bats and other animal reservoirs for potential spillovers as a measure towards preparedness for emergence of zoonosis. This article is protected by copyright. All rights reserved.

positive: 2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine readiness. On 31 December 2019 the Wuhan Health Commission reported a cluster of atypical pneumonia cases that was linked to a wet market in the city of Wuhan, China. The first patients began experiencing symptoms of illness in mid-December 2019. Clinical isolates were found to contain a novel coronavirus with similarity to bat coronaviruses. As of 28 January 2020, there are in excess of 4,500 laboratory-confirmed cases, with > 100 known deaths. As with the SARS-CoV, infections in children appear to be rare. Travel-related cases have been confirmed in multiple countries and regions outside mainland China including Germany, France, Thailand, Japan, South Korea, Vietnam, Canada, and the United States, as well as Hong Kong and Taiwan. Domestically in China, the virus has also been noted in several cities and provinces with cases in all but one provinence. While zoonotic transmission appears to be the original source of infections, the most alarming development is that human-to-human transmission is now prevelant. Of particular concern is that many healthcare workers have been infected in the current epidemic. There are several critical clinical questions that need to be resolved, including how efficient is human-to-human transmission? What is the animal reservoir? Is there an intermediate animal reservoir? Do the vaccines generated to the SARS-CoV or MERS-CoV or their proteins offer protection against 2019-nCoV? We offer a research perspective on the next steps for the generation of vaccines. We also present data on the use of in silico docking in gaining insight into 2019-nCoV Spike-receptor binding to aid in therapeutic development. Diagnostic PCR protocols can be found at https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus.

positive: Tracing Back the Temporal Change of SARS-CoV-2 with Genomic Signatures The coronavirus disease (COVID-19) outbreak starting from China at the end of 2019 and its subsequent spread in many countries have given rise to thousands of coronavirus samples being collected and sequenced till date. To trace back the initial temporal change of SARS-CoV-2, the coronavirus implicated in COVID-19, we study the limited genomic sequences that were available within the first couple of months of its spread. These samples were collected under varying circumstances and highlight wide variations in their genomic compositions. In this paper, we explore whether these variations characterize the initial temporal change of SARS-CoV-2 sequences. We observe that n-mer distributions in the SARS-CoV-2 samples, which were collected at an earlier period of time, predict its collection timeline with approximately 78% accuracy. However, such a distinctive pattern disappears with the inclusion of samples collected at a later time. We further observe that isolation sources (e.g., oronasopharynx, saliva, feces, etc.) could not be predicted by the n-mer patterns in these sequences. Finally, the phylogenetic and protein-alignment analyses highlight interesting associations between SARS-CoV-2 and other coronaviruses.

positive: 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.

positive: Transmissibility of 2019 Novel Coronavirus: zoonotic vs. human to human transmission, China, 2019-2020 Objectives: The novel coronavirus (2019-nCoV) originating from Wuhan has rapidly spread throughout China. While the origin of the outbreak remains uncertain, accumulating evidence links a wet market in Wuhan for the early spread of 2019-nCoV. Similarly, the influence of the marketplace on the early transmission dynamics is yet to be investigated. Methods: Using the daily series of COVID-19 incidenceincluding contact history with the market, we have conducted quantitative modeling analyses to estimate the reproduction numbers (R) for the market-to-human and human-to-human transmission together with the reporting probability and the early effects of public health interventions. Results: Our mean R estimates for China in 2019-2020 are estimated at 0.37 (95%CrI: 0.02-1.78) for market-to-human transmission, and 3.87 (95%CrI: 3.18-4.78) for human-to-human transmission, respectively. Moreover we estimated that the reporting rate cases stemming from market-to-human transmission was 3-31 fold higher than that for cases stemming from human-to-human transmission, suggesting that contact history with the wet market played a key role in identifying COVID-19 cases. Conclusions: Our findings suggest that the proportions of asymptomatic and subclinical patients constitute a substantial component of the epidemic's magnitude. Findings suggest that the development of rapid diagnostic tests could help bring the epidemic more rapidly under control.

positive: Understanding evolution of SARS-CoV-2: A perspective from analysis of genetic diversity of RdRp gene Coronavirus disease 2019 emerged as the first example of "Disease X", a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS-CoV-2 using RNA dependent RNA polymerase (RdRp) gene, a stable genetic marker. Phylogenetic and population stratification analyses were carried out using maximum likelihood and Bayesian methods, respectively. Molecular phylogeny using RdRp showed that SARS-CoV-2 isolates cluster together. Bat-CoV isolate RaTG13 and Pangolin-CoVs are observed to branch off prior to SARS-CoV-2 cluster. While SARS-CoV form a single cluster, Bat-CoVs form multiple clusters. Population-based analyses revealed that both SARS-CoV-2 and SARS-CoV form separate clusters with no admixture. Bat-CoVs were found to have single and mixed ancestry and clustered as four sub-populations. Population-based analyses of Betacoronaviruses using RdRp revealed that SARS-CoV-2 is a homogeneous population. SARS-CoV-2 appears to have evolved from Bat-CoV isolate RaTG13, which diversified from a common ancestor from which Pangolin-CoVs have also evolved. The admixed Bat-CoV sub-populations indicate that bats serve as reservoirs harboring virus ensembles that are responsible for zoonotic spillovers such as SARS-CoV and SARS-CoV-2. The extent of admixed isolates of Bat-CoVs observed in population diversification studies underline the need for periodic surveillance of bats and other animal reservoirs for potential spillovers as a measure towards preparedness for emergence of zoonosis.

positive: Novel coronavirus: From discovery to clinical diagnostics Abstract A novel coronavirus designated as 2019-nCoV first appeared in Wuhan, China in late December 2019. Dozens of people died in China, and thousands of people infected as 2019-nCoV continues to spread around the world. We have described the discovery, emergence, genomic characteristics, and clinical diagnostics of 2019-nCoV.

positive: SARS-CoV-2: Camazotz's Curse The world is currently face to face with a pandemic which is spreading rapidly across the globe caused by SARS-CoV-2, a strain of Coronaviruses (CoVs) belonging to subgenus Sarbecovirus of genus Betacoronavirus. World Health Organisation (WHO) on 11 Feb 20 named this disease caused by SARS-CoV-2 as Covid-19. This pandemic is spreading rapidly and more than 20,00,000 cases have occurred globally. The human Coronaviruses discovered in 1960s were considered potentially harmless endemic viruses with seasonal distribution before late 2002. The CoVs are found in a large number of domestic and wild animals and birds. The first pandemic caused by Coronavirus caused by SARS-CoV was recognized in the late 2002 in Guangdong Province and resulted in widespread morbidity and mortality. This was followed by MERS-CoV which began in 2012 in the Arabian peninsula with multiple outbreaks related to it in various parts of the globe. Various studies have suggested how these viruses made their entry from their natural reservoir bats via intermediate host like civets and camels in case of SARS-CoV and MERS-CoV respectively. The intermediate host of the SARS-CoV-2 still needs to be established. The SARS-CoV-2 has 96.2% similarity to the bat Severe Acute Respiratory Syndrome related-Coronavirus (SARSr-CoV RaTG13). SARS-CoV-2 has been found to be more distant in relation to SARS-CoV (79%) and MERS-CoV (50%). At the whole genome sequence level pangolin CoV and SARSr-CoV RaTG13 show 91.02% and 96.2% similarity with SARS-CoV-2 but the S1 subunit of spike protein of pangolin CoV is more closely related to SARS-CoV-2 than SARSr-CoV RaTG13. The genetic analysis of the currently circulating strains of the pandemic have shown 99.98-100% similarity in their genomes implying a recent shift to humans. The animal source of SARS-CoV-2 needs to be identified to implement control measures in the present pandemic. Also, how the virus moves interspecies will help predict and prevent future pandemics.

positive: Geographical structure of bat SARS-related coronaviruses Abstract Bats are the natural reservoirs of severe acute respiratory syndrome coronavirus (SARS-CoV) which caused the outbreak of human SARS in 2002–2003. We introduce the genetic diversity of SARS-related coronaviruses (SARSr-CoVs) discovered in bats and provide insights on the bat origin of human SARS. We also analyze the viral geographical structure that may improve our understanding of the evolution of bat SARSr-CoVs.

positive: SARS-like virus in the Middle East: A truly bat-related coronavirus causing human diseases

positive: [Etiology of epidemic outbreaks COVID-19 on Wuhan, Hubei province, Chinese People Republic associated with 2019-nCoV (Nidovirales, Coronaviridae, Coronavirinae, Betacoronavirus, Subgenus Sarbecovirus): lessons of SARS-CoV outbreak.] Results of analysis of phylogenetic, virological, epidemiological, ecological, clinical data of COVID-19 outbreaks in Wuhan, China (PRC) in comparison with SARS-2002 and MERS-2012 outbreaks allow to conclude: - the etiological agent of COVID-19 is coronavirus (2019-CoV), phylogenetically close to the SARS-CoV, isolated from human, and SARS-related viruses isolated from bats (SARS-related bat CoV viruses). These viruses belong to the Sarbecovirus subgenus, Betacoronavirus genus, Orthocoronavirinae subfamily, Coronaviridae family (Cornidovirinea: Nidovirales). COVID-19 is a variant of SARS-2002 and is different from MERS-2012 outbreak, which were caused by coronavirus belonged to the subgenus Merbecovirus of the same genus; - according to the results of phylogenetic analysis of 35 different betacoronaviruses, isolated from human and from wild animals in 2002-2019, the natural source of COVID-19 and SARS-CoV (2002) is bats of Rhinolophus genus (Rhinolophidae) and, probably, some species of other genera. An additional reservoir of the virus could be an intermediate animal species (snakes, civet, hedgehogs, badgers, etc.) that are infected by eating of infected bats. SARS-like coronaviruses circulated in bats in the interepidemic period (2003-2019); - seasonal coronaviruses (subgenus Duvinacovirus, Alphacoronavirus) are currently circulating (November 2019 - January 2020) in the European part of Russia, Urals, Siberia and the Far East of Russia, along with the influenza viruses A(H1N1)pdm09, A(H3N2), and Ð, as well as six other respiratory viruses (HPIV, HAdV, HRSV, HRV, HBoV, and HMPV).

positive: The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak 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.

positive: Molecular evolution and phylogenetic analysis of SARS-CoV-2 and hosts ACE2 protein suggest Malayan pangolin as intermediary host An emergence of a novel coronavirus, causative agent of COVID19, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred due to cross-species transmission. Coronaviruses are a large family of viruses able to infect a great number of hosts. Entrance of SARS-CoV-2 depends on the surface (S) protein interaction with host ACE2 protein and cleavage by TMPRSS2. ACE2 could be a species-specific barrier that interferes with bat-to-human coronavirus cross-species transmission. Molecular analysis supported bats as natural hosts for SARS-CoV and involved them in MERS-CoV origin. The genomic similarity between bat RaTG13 CoV strain and SARS-CoV-2 implicates bats in the origin of the new outbreak. Additionally, there is a hypothesis for the zoonotic transmission based on contact with Malayan pangolins by humans in Huanan seafood market in Wuhan, China. To investigate bats and pangolin as hosts in SARS-CoV-2 cross-species transmission, we perform an evolutionary analysis combining viral and host phylogenies and divergence of ACE2 and TMPRSS2 amino acid sequences between CoV hosts. Phylogeny showed SARS-like-CoV-2 strains that infected pangolin and bats are close to SARS-CoV-2. In contrast to TMPRSS2, pangolin ACE2 amino acid sequence has low evolutionary divergence compared with humans and is more divergent from bats. Comparing SARS-CoV with SARS-CoV-2 origins, pangolin has yet lower ACE2 evolutionary divergence with humans than civet—the main intermediary host of SARS-CoV. Thus, pangolin has become an opportune host to intermediates bat-to-human SARS-CoV-2 jump and entry. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42770-020-00321-1) contains supplementary material, which is available to authorized users.

positive: Machine learning using intrinsic genomic signatures for rapid classification of novel pathogens: COVID-19 case study The 2019 novel coronavirus (renamed SARS-CoV-2, and generally referred to as the COVID-19 virus) has spread to 184 countries with over 1.5 million confirmed cases. Such major viral outbreaks demand early elucidation of taxonomic classification and origin of the virus genomic sequence, for strategic planning, containment, and treatment. This paper identifies an intrinsic COVID-19 virus genomic signature and uses it together with a machine learning-based alignment-free approach for an ultra-fast, scalable, and highly accurate classification of whole COVID-19 virus genomes. The proposed method combines supervised machine learning with digital signal processing (MLDSP) for genome analyses, augmented by a decision tree approach to the machine learning component, and a Spearman's rank correlation coefficient analysis for result validation. These tools are used to analyze a large dataset of over 5000 unique viral genomic sequences, totalling 61.8 million bp, including the 29 COVID-19 virus sequences available on January 27, 2020. Our results support a hypothesis of a bat origin and classify the COVID-19 virus as Sarbecovirus, within Betacoronavirus. Our method achieves 100% accurate classification of the COVID-19 virus sequences, and discovers the most relevant relationships among over 5000 viral genomes within a few minutes, ab initio, using raw DNA sequence data alone, and without any specialized biological knowledge, training, gene or genome annotations. This suggests that, for novel viral and pathogen genome sequences, this alignment-free whole-genome machine-learning approach can provide a reliable real-time option for taxonomic classification.

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

positive: 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.

positive: SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence? In a side-by-side comparison of evolutionary dynamics between the 2019/2020 SARS-CoV-2 and the 2003 SARS-CoV, we were surprised to find that SARS-CoV-2 resembles SARS-CoV in the late phase of the 2003 epidemic after SARS-CoV had developed several advantageous adaptations for human transmission. Our observations suggest that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV. However, no precursors or branches of evolution stemming from a less human-adapted SARS-CoV-2-like virus have been detected. The sudden appearance of a highly infectious SARS-CoV-2 presents a major cause for concern that should motivate stronger international efforts to identify the source and prevent near future re-emergence. Any existing pools of SARS-CoV-2 progenitors would be particularly dangerous if similarly well adapted for human transmission. To look for clues regarding intermediate hosts, we analyze recent key findings relating to how SARS-CoV-2 could have evolved and adapted for human transmission, and examine the environmental samples from the Wuhan Huanan seafood market. Importantly, the market samples are genetically identical to human SARS-CoV-2 isolates and were therefore most likely from human sources. We conclude by describing and advocating for measured and effective approaches implemented in the 2002-2004 SARS outbreaks to identify lingering population(s) of progenitor virus.

positive: Molecular diversity of coronaviruses in bats Abstract The existence of coronaviruses in bats is unknown until the recent discovery of bat-SARS-CoV in Chinese horseshoe bats and a novel group 1 coronavirus in other bat species. Among 309 bats of 13 species captured from 20 different locations in rural areas of Hong Kong over a 16-month period, coronaviruses were amplified from anal swabs of 37 (12%) bats by RT-PCR. Phylogenetic analysis of RNA-dependent-RNA-polymerase (pol) and helicase genes revealed six novel coronaviruses from six different bat species, in addition to the two previously described coronaviruses. Among the six novel coronaviruses, four were group 1 coronaviruses (bat-CoV HKU2 from Chinese horseshoe bat, bat-CoV HKU6 from rickett's big-footed bat, bat-CoV HKU7 from greater bent-winged bat and bat-CoV HKU8 from lesser bent-winged bat) and two were group 2 coronaviruses (bat-CoV HKU4 from lesser bamboo bats and bat-CoV HKU5 from Japanese pipistrelles). An astonishing diversity of coronaviruses was observed in bats.

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

positive: Virus strain of a mild COVID-19 patient in Hangzhou representing a new trend in SARS-CoV-2 evolution related to Furin cleavage site We found, in our 788 confirmed COVID-19 patients, the decreased rate of severe/critical type, increased liver/kidney damage and prolonged period of nuclear acid positivity during virus dissemination, when compared with Wuhan. To investigate the underlining mechanism, we isolated one strain of SARS- CoV-2 (ZJ01) in mild COVID-19 patient and found the existence of 35 specific gene mutation by gene alignment. Further phylogenetic analysis and RSCU heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 strains of viruses worldwide (C/T type) based on the base (C or T) at positions 8824 and 28247. ZJ01 were both T at these two sites, becoming the only TT type currently identified in the world. The prediction of Furin cleavage site (FCS) and the sequence alignment of virus family indicated that FCS may be an important site of coronavirus evolution. ZJ01 had mutations near FCS (F1-2), which caused changes in the structure and the electrostatic distribution of the S protein surface, further affecting the binding capacity of Furin. Single cell sequencing and ACE2-Furin co-expression results confirmed that Furin level was higher in the whole body, especially in glands, liver, kidney and colon while FCS may help SARS-CoV-2 infect these organs. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 (the source of FCS sequence-PRRA) caused influenza, further showing potential in differentiating into mild COVID-19 subtypes.

positive: Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS Abstract In 2002/2003, a novel coronavirus (CoV) caused a pandemic, infecting more than 8000 people, of whom nearly 10% died. This virus, termed severe acute respiratory syndrome-CoV was linked to a zoonotic origin from rhinolophid bats in 2005. Since then, numerous studies have described novel bat CoVs, including close relatives of the newly emerging Middle East respiratory syndrome (MERS)-CoV. In this paper we discuss CoV genomic properties and compare different taxonomic approaches in light of the technical difficulties of obtaining full genomic sequences directly from bat specimens. We first present an overview of the available studies on bat CoVs, with details on their chiropteran hosts, then comparatively analyze the increase in bat CoV studies and novel genomic sequences obtained since the SARS pandemic. We then conduct a comprehensive phylogenetic analysis of the genera Alpha- and Betacoronavirus, to show that bats harbour more CoV diversity than other mammalian hosts and are widely represented in most, but not all parts of the tree of mammalian CoVs. We next discuss preliminary evidence for phylogenetic co-segregation of CoVs and bat hosts encompassing the Betacoronavirus clades b and d, with an emphasis on the sampling bias that exists among bat species and other mammals, then present examples of CoVs infecting different hosts on the one hand and viruses apparently confined to host genera on the other. We also demonstrate a geographic bias within available studies on bat CoVs, and identify a critical lack of information from biodiversity hotspots in Africa, Asia and Latin America. We then present evidence for a zoonotic origin of four of the six known human CoVs (HCoV), three of which likely involved bats, namely SARS-CoV, MERS-CoV and HCoV-229E; compare the available data on CoV pathogenesis in bats to that in other mammalian hosts; and discuss hypotheses on the putative insect origins of CoV ancestors. Finally, we suggest caution with conclusions on the zoonotic potential of bat viruses, based only on genomic sequence data, and emphasize the need to preserve these ecologically highly relevant animals. This paper forms part of a symposium in Antiviral Research on “from SARS to MERS: 10years of research on highly pathogenic human coronaviruses”.

positive: Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.

positive: SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.

positive: Regaining perspective on SARS-CoV-2 molecular tracing and its implications During the past three months, a new coronavirus (SARS-CoV-2) epidemic has been growing exponentially, affecting over 100 thousand people worldwide, and causing enormous distress to economies and societies of affected countries. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined all full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies. Our analysis clearly shows severe limitations in the present data, in light of which any finding should be considered, at the very best, preliminary and hypothesis-generating. Hence the need for avoiding stigmatization based on partial information, and for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic.

positive: 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.

positive: Morphology, Genome Organization, Replication, and Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) SARS-CoV-2 is a single-stranded RNA virus of ~30 kb genome size which belongs to genus Coronavirus and family Coronaviridae. SARS-CoV-2 has recently emerged and has been declared as a pandemic by the World Health Organization. Genomic characterization of SARS-CoV-2 has shown that it is of zoonotic origin. The structure of SARS-CoV-2 is found to be similar to SARS-CoV with virion size ranging from 70 to 90 nm. Spike, membrane, and envelope surface viral proteins of coronavirus are embedded in host membrane-derived lipid bilayer encapsulating the helical nucleocapsid comprising viral RNA. The genome comprises of 6–11 open reading frames (ORFs) with 5′ and 3′ flanking untranslated regions (UTRs). Sequence variation among SARS-CoV-2 and SARS-CoV revealed no significant difference in ORFs and nsps. The nsps includes two viral cysteine proteases including papain-like protease (nsp3), chymotrypsin-like, 3C-like, or main protease (nsp5), RNA-dependent RNA polymerase (nsp12), helicase (nsp13), and others likely to be involved in the transcription and replication of SARS-CoV-2. The structure of spike glycoprotein structure of SARS-CoV-2 resembles that of the spike protein of SARS-CoV with an root-mean-square deviation (RMSD) of 3.8 Å. Like SARS-CoV, SARS-CoV-2 uses the ACE2 receptor for internalization and TMPRSS2 serine proteases for S protein priming. Histopathological investigation of tissues from SARS-CoV-2 infected patients showed virus-induced cytopathic effect with signs of acute respiratory distress syndrome in lung cells. This chapter discusses about the morphology, genome organization, replication, and pathogenesis of SARS-CoV-2 that may help us understand the disease that may leads to identification of effective antiviral drugs and vaccines.

positive: Origin time and epidemic dynamics of the 2019 novel coronavirus The 2019 novel coronavirus (2019-nCoV) have emerged from Wuhan, China. Studying the epidemic dynamics is crucial for further surveillance and control of the outbreak. We employed a Bayesian framework to infer the time-calibrated phylogeny and the epidemic dynamics represented by the effective reproductive number (Re) changing over time from the genomic sequences available from GISAID. The origin time is estimated to be December 17, 2019 (95% CI: December 5, 2019 – December 23, 2019). The median estimate of Re ranges from 0.2 to 2.2 and changes drastically over time. This study provides an early insight of the 2019-nCoV epidemic.

positive: A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJ01) The genome sequence of the Severe Acute Respiratory Syndrome (SARS)-associated virus provides essential information for the identification of pathogen(s), exploration of etiology and evolution, interpretation of transmission and pathogenesis, development of diagnostics, prevention by future vaccination, and treatment by developing new drugs. We report the complete genome sequence and comparative analysis of an isolate (BJ01) of the coronavirus that has been recognized as a pathogen for SARS. The genome is 29725 nt in size and has 11 ORFs (Open Reading Frames). It is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 2 ORFs) and a variable region representing 4 CDSs (coding sequences) for viral structural genes (the S, E, M, N proteins) and 5 PUPs (putative uncharacterized proteins). Its gene order is identical to that of other known coronaviruses. The sequence alignment with all known RNA viruses places this virus as a member in the family of Coronaviridae. Thirty putative substitutions have been identified by comparative analysis of the 5 SARS-associated virus genome sequences in GenBank. Fifteen of them lead to possible amino acid changes (non-synonymous mutations) in the proteins. Three amino acid changes, with predicted alteration of physical and chemical features, have been detected in the S protein that is postulated to be involved in the immunoreactions between the virus and its host. Two amino acid changes have been detected in the M protein, which could be related to viral envelope formation. Phylogenetic analysis suggests the possibility of non-human origin of the SARS-associated viruses but provides no evidence that they are man-made. Further efforts should focus on identifying the etiology of the SARS-associated virus and ruling out conclusively the existence of other possible SARS-related pathogen(s).

positive: Pros and cons of the application of evolutionary theories to the evolution of SARS-CoV-2 The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused severe damage to the world. With the support of classic evolutionary theories and population genetics principles, many studies on the origin of SARS-CoV-2 have revealed encouraging results but meanwhile some are still under debate. We are concerned with the validity of applying classic evolutionary theories and formula to the evolution of RNA viruses. We have raised several confounding factors like the RNA replication feature and the RNA modification systems of the hosts, which might jeopardize the validity of the application of classic methods to analyze the SARS-CoV-2 data.

positive: The Novel Coronavirus – A Snapshot of Current Knowledge Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.

positive: Unveiling the Origin and Transmission of 2019-nCoV A novel coronavirus has caused thousands of human infections in China since December 2019, raising a global public health concern. Recent studies (Huang et al ., Chan et al ., and Zhou et al .) have provided timely insights into its origin and ability to spread among humans, informing infection prevention and control practices.

positive: COVID-19: what has been learned and to be learned about the novel coronavirus disease The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.

positive: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified. Highlights Based on the currently available genome sequence data, we proved that SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.

positive: 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.

positive: Transmission Cycle of SARS-CoV and SARS-CoV-2 Severe acute respiratory syndrome (SARS) is a pandemic that has shocked the world twice over the last two decades caused by a highly transmissible and pathogenic coronavirus (CoV). It causes disease in the lower respiratory tract in humans that was first reported in late 2002 in Guangdong province, China, and later on in December 2019 in Wuhan, China. The two viruses designated as SARS-CoV and SARS-CoV-2, respectively, originated probably from the bat and infected humans via carrier animals. The constant recombination and evolution in the CoV genome may have facilitated their cross-species transmission resulting in recurrent emergence as a pandemic. This chapter intends to accumulate recent findings related to CoV transmission and tentative molecular mechanisms governing the process.

positive: Epidemiology of CoViD-19 Pandemic: Recovery and mortality ratio around the globe Coronavirus Disease 2019 (CoViD-19) is the third type of coronavirus disease after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) that appears in human population from the past two decades. It is highly contagious and rapidly spread in the human population and compelled global public health institutions on high alert. Due to genetic similarity of this novel coronavirus 2019 with bat virus its emergence from bat to humans is possible. The virus survive in the droplets of coughing and sneezing and spread around the large areas through infected person resulting in its rapid spread among people. Clinical symptoms of CoViD-19 include fever, dry cough, dyspnea, loose stool, nausea and vomiting. The present review discuss the origin of CoViD-19, its rapid spread, mortality rate and recoveries ratio around the world. Since its origin from Wuhan, the CoViD-19 spread very rapidly all across the countries, on April 17, 2020 this disease has affected 210 countries of the globe. The data obtained showed over 2.4 million confirmed cases of CoViD-19. Higher mortality rate was found in Algeria and Belgium as 15% and 13.95%, respectively. Lower mortality rate was found in Qatar 0.17% and Singapore 0.2%. Recovery versus deceased ratio showed that recovery was 68, 59 and 35 times higher than the death in Singapore, Qatar and Thailand respectively. It is concluded that 2019-novel corona virus is a zoonotic pathogen similar to MERS and SARS. Therefore, a barrier should be maintained between and across the human, household and wild animals to avoid such pandemics.

positive: 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.

positive: Molecular characterization of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China BACKGROUND: Novel Muscovy duck reovirus (N-MDRV), emerged in southeast China in 2002, which can infect a wide range of waterfowl and induces clinical signs and cytopathic effects that are distinct from those of classical MDRV, and continues to cause high morbidity and 5–50% mortality in ducklings. The present study aimed to investigate the characteristics of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China. RESULTS: Two novel MDRV strains, designated as MDRV-SH12 and MDRV-DH13, were isolated from two diseased Muscovy ducklings in Guangdong province, China in June 2012 and September 2013, respectively. Sequencing of the complete genomes of these two viruses showed that they consisted of 23,418 bp and were divided into 10 segments, ranging from 1191 bp (S4) to 3959 bp (L1) in length, and all segments contained conserved sequences in the 5′ non-coding region (GCUUUU) and 3′ non-coding region (UCAUC). Pairwise sequence comparisons demonstrated that MDRV-SH12 and MDRV-DH13 showed the highest similarity with novel MDRVs. Phylogenetic analyses of the nucleotide sequences of all 10 segments revealed that MDRV-SH12 and MDRV-DH13 were clustered together with other novel waterfowl-origin reoviruses and were distinct from classical waterfowl-origin and chicken-origin reoviruses. The analyses also showed possible genetic re-assortment events in segment M2 between waterfowl-origin and chicken-origin reoviruses and the segments encoding λA, μA, μNS, σA, and σNS between classical and novel waterfowl-origin reoviruses. Potential recombination events detection in segment S2 suggests that MDRV-SH12 and MDRV-DH13 may be recombinants of classical and novel WRVs. CONCLUSIONS: The results presented in this study, the full genomic data for two novel MDRV strains, will improve our understanding of the evolutionary relationships among the waterfowl-origin reoviruses circulating in China, and may aid in the development of more effective vaccines against various waterfowl-origin reoviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1877-x) contains supplementary material, which is available to authorized users.

positive: 27 Evolution of SARS Coronavirus and the Relevance of Modern Molecular Epidemiology Severe acute respiratory syndrome (SARS) is the first major zoonotic infectious disease of the twenty-first century. The disease, originally termed “atypical pneumonia,” was first recognized in November 2002 in Guangdong Province, China, which spread rapidly to 26 countries within 5 months and eventually led to 8096 human infection cases and 774 deaths. A previously unrecognized coronavirus, SARS coronavirus (SARS-CoV), was later identified as the causative agent of the SARS. Subsequent investigation indicated that the source of the human infections was most likely originated from infected wildlife animals traded in the live animal markets, with masked palm civets being considered the most prominent and important carrier. Large-scale culling of civets appeared to have prevented further outbreaks in the region. Further epidemiological studies showed that civets are intermediate hosts of SARS-CoV, and bats are the likely natural reservoir of SARS-CoV and a large number of SARS-like coronaviruses (SL-CoVs). Detailed analysis of the massive SARS-CoV genomic sequence data accumulated indicated that SARS-CoV experienced a strong selection pressure during different outbreak phases in humans as well as interspecies transmission from animals to humans. The spike glycoprotein (S) of SARS-CoV plays a key role in virus–host interaction and hence is a key determinant of interspecies transmission. It has been shown that minor changes of amino acid (aa) residues in the S protein could lead to dramatic changes in virus susceptibility in animal and human hosts. This chapter will focus on the genetics and evolution of SARS-CoVs and SL-CoVs in humans, civets, and bats. The events of SARS outbreaks and the accompanying response activities highlight the importance of modern molecular epidemiology in disease investigation and the urgent need to broaden the screening and investigation of unknown viruses in wildlife animals.

positive: Overselling wildlife trade bans will not bolster conservation or pandemic preparedness

positive: COVID-19-A Novel Zoonotic Disease: A Review of the Disease, the Virus, and Public Health Measures A cluster of cases of pneumonia of unknown etiology emerged in Wuhan, China, at the end of December 2019. The cluster was largely associated with a seafood and animal market. A novel Betacoronavirus was quickly identified as the causative agent, and it is shown to be related genetically to SARS-CoV and other bat-borne SARS-related Betacoronaviruses. The number of cases increased rapidly and spread to other provinces in China, as well as to another 4 countries. To help control the spread of the virus, a "cordon sanitaire" was instituted for Wuhan on January 23, 2020, and subsequently extended to other cities in Hubei Province, and the outbreak declared a Public Health Emergency of International Concern by the Director General of the World Health Organization on January 30, 2020. The virus was named SARS-CoV-2 by the International Committee for the Taxonomy of Viruses, and the disease it causes was named COVID-19 by the World Health Organization. This article described the evolution of the outbreak, and the known properties of the novel virus, SARS-CoV-2 and the clinical disease it causes, and the major public health measures being used to help control it's spread. These measures include social distancing, intensive surveillance and quarantining of cases, contact tracing and isolation, cancellation of mass gatherings, and community containment. The virus is the third zoonotic coronavirus, after SARS-CoV and MERS-CoV, but appears to be the only one with pandemic potential. However, a number of important properties of the virus are still not well understood, and there is an urgent need to learn more about its transmission dynamics, its spectrum of clinical severity, its wildlife origin, and its genetic stability. In addition, more research is needed on possible interventions, particularly therapeutic and vaccines.

positive: The 2019‐new coronavirus epidemic: Evidence for virus evolution There is a worldwide concern about the new coronavirus 2019‐nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequences of 2019‐nCoV, 12 whole genome sequences of 2019‐nCoV, and 12 highly similar whole genome sequences available in gene bank (five from the severe acute respiratory syndrome, two from Middle East respiratory syndrome, and five from bat SARS‐like coronavirus). Fast unconstrained Bayesian approximation analysis shows that the nucleocapsid and the spike glycoprotein have some sites under positive pressure, whereas homology modeling revealed some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019‐nCoV significantly clustered with bat SARS‐like coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. From these results, the new 2019‐nCoV is distinct from SARS virus, probably trasmitted from bats after mutation conferring ability to infect humans.

positive: The 2019-new coronavirus epidemic: evidence for virus evolution There is concern about a new coronavirus, the 2019-nCoV, as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequence of 2019-nCoV and 12 whole genome sequences highly similar sequences available in gene bank (5 from SARS, 2 from MERS and 5 from Bat SARS-like Coronavirus). FUBAR analysis shows that the Nucleocapsid and the Spike Glycoprotein has some sites under positive pressure while homology modelling helped to explain some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019.nCoV significantly clustered with Bat SARS-like Coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in S and nucleocapsid proteins. From these results, 2019nCoV could be considered a coronavirus distinct from SARS virus, probably transmitted from bats or another host where mutations conferred upon it the ability to infect humans.

positive: Classical Coronaviruses In the last week of December 2019, few patients with the history of pyrexia of unknown origin and symptoms of lower respiratory tract infections were detected in Wuhan, a well-known area as the largest metropolitan city located in the province of Hubei, China. On further investigation, a novel coronavirus was identified as the causative pathogen, which later on provisionally named as 2019 novel coronavirus (2019-nCoV). Coronaviruses are predominantly found in warm-blooded animals and birds and cause various respiratory complications and multiorgan failure in the immunocompromised individuals. Human coronaviruses were first identified in 1965 and are responsible for the respiratory tract infections in major proportion of population worldwide; at least five new human coronaviruses have been identified, including severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002–2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The background related to the origin and classification of coronaviruses is reviewed here.

positive: Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. We introduce mutation ratio and mutation $h$-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively non-conservative. In particular, the nucleocapsid protein has more than half its genes changed in the past few months, signaling devastating impacts on the ongoing development of COVID-19 diagnosis, vaccines, and drugs.

positive: COVID-19 Outbreak: An Overview BACKGROUND: In late December 2019, Chinese health authorities reported an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province. SUMMARY: A few days later, the genome of a novel coronavirus was released (http://virological.org/t/novel-2019-coronavirus-genome/319; Wuhan-Hu-1, GenBank accession No. MN908947) and made publicly available to the scientific community. This novel coronavirus was provisionally named 2019-nCoV, now SARS-CoV-2 according to the Coronavirus Study Group of the International Committee on Taxonomy of Viruses. SARS-CoV-2 belongs to the Coronaviridae family, Betacoronavirus genus, subgenus Sarbecovirus. Since its discovery, the virus has spread globally, causing thousands of deaths and having an enormous impact on our health systems and economies. In this review, we summarize the current knowledge about the epidemiology, phylogenesis, homology modeling, and molecular diagnostics of SARS-CoV-2. KEY MESSAGES: Phylogenetic analysis is essential to understand viral evolution, whereas homology modeling is important for vaccine strategies and therapies. Highly sensitive and specific diagnostic assays are key to case identification, contact tracing, identification of the animal source, and implementation of control measures.

positive: Evolution and variation of 2019-novel coronavirus Background The current outbreak caused by novel coronavirus (2019-nCoV) in China has become a worldwide concern. As of 28 January 2020, there were 4631 confirmed cases and 106 deaths, and 11 countries or regions were affected. Methods We downloaded the genomes of 2019-nCoVs and similar isolates from the Global Initiative on Sharing Avian Influenza Database (GISAID and nucleotide database of the National Center for Biotechnology Information (NCBI). Lasergene 7.0 and MEGA 6.0 softwares were used to calculate genetic distances of the sequences, to construct phylogenetic trees, and to align amino acid sequences. Bayesian coalescent phylogenetic analysis, implemented in the BEAST software package, was used to calculate the molecular clock related characteristics such as the nucleotide substitution rate and the most recent common ancestor (tMRCA) of 2019-nCoVs. Results An isolate numbered EPI_ISL_403928 showed different phylogenetic trees and genetic distances of the whole length genome, the coding sequences (CDS) of ployprotein (P), spike protein (S), and nucleoprotein (N) from other 2019-nCoVs. There are 22, 4, 2 variations in P, S, and N at the level of amino acid residues. The nucleotide substitution rates from high to low are 1·05 × 10−2 (nucleotide substitutions/site/year, with 95% HPD interval being 6.27 × 10−4 to 2.72 × 10−2) for N, 5.34 × 10−3 (5.10 × 10−4, 1.28 × 10−2) for S, 1.69 × 10−3 (3.94 × 10−4, 3.60 × 10−3) for P, 1.65 × 10−3 (4.47 × 10−4, 3.24 × 10−3) for the whole genome, respectively. At this nucleotide substitution rate, the most recent common ancestor (tMRCA) of 2019-nCoVs appeared about 0.253-0.594 year before the epidemic. Conclusion Our analysis suggests that at least two different viral strains of 2019-nCoV are involved in this outbreak that might occur a few months earlier before it was officially reported.

positive: Testing the hypothesis of a recombinant origin of the SARS-associated coronavirus The origin of severe acute respiratory syndrome-associated corona-virus (SARS-CoV) is still a matter of speculation, although more than one year has passed since the onset of the SARS outbreak. In this study, we implemented a 3-step strategy to test the intriguing hypothesis that SARS-CoV might have been derived from a recombinant virus. First, we blasted the whole SARS-CoV genome against a virus database to search viruses of interest. Second, we employed 7 recombination detection techniques well documented in successfully detecting recombination events to explore the presence of recombination in SARS-CoV genome. Finally, we conducted phylogenetic analyses to further explore whether recombination has indeed occurred in the course of coronaviruses history predating the emergence of SARS-CoV. Surprisingly, we found that 7 putative recombination regions, located in Replicase 1ab and Spike protein, exist between SARS-CoV and other 6 coronaviruses: porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), bovine coronavirus (BCoV), human coronavirus 229E (HCoV), murine hepatitis virus (MHV), and avian infectious bronchitis virus (IBV). Thus, our analyses substantiate the presence of recombination events in history that led to the SARS-CoV genome. Like the other coronaviruses used in the analysis, SARS-CoV is also a mosaic structure.

positive: Understanding bat SARS-like coronaviruses for the preparation of future coronavirus outbreaks — Implications for coronavirus vaccine development The severe acute respiratory syndrome coronavirus (SARS-CoV) first emerged in 2003, causing the SARS epidemic which resulted in a 10% fatality rate. The advancements in metagenomic techniques have allowed the identification of SARS-like coronaviruses (SL-CoVs) sequences that share high homology to the human SARS-CoV epidemic strains from wildlife bats, presenting concrete evidence that bats are the origin and natural reservoir of SARS-CoV. The application of reverse genetics further enabled that characterization of these bat CoVs and the prediction of their potential to cause disease in humans. The knowledge gained from such studies is valuable in the surveillance and preparation of a possible future outbreak caused by a spill-over of these bat SL-CoVs.

positive: Genotyping coronavirus SARS-CoV-2: methods and implications The emerging global infectious COVID-19 coronavirus disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. For understanding the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. We present an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The SNP genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. Our method serves a promising tool for monitoring and tracking the epidemic of pathogenic viruses in their gradual and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.

positive: The continuous evolution and dissemination of 2019 novel human coronavirus

positive: Emergence of RBD mutations in circulating SARS-CoV-2 strains enhancing the structural stability and human ACE2 receptor affinity of the spike protein A novel coronavirus SARS-CoV-2 is associated with the current global pandemic of Coronavirus Disease 2019 (COVID-19). Spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the critical determinant of viral tropism and infectivity. To investigate whether the mutations in the RBD have altered the receptor binding affinity and caused these strains more infectious, we performed molecular dynamics simulations of the binding affinity between the mutant SARS-CoV-2 RBDs to date and the human ACE2 receptor. Among 1609 genomes of global SARS-CoV-2 strains, 32 non-synonymous RBD mutants were identified and clustered into 9 mutant types under high positive selection pressure. Three mutant types (V367F, W436R, and D364Y) emerging in Wuhan, Shenzhen, Hong Kong, and France, displayed higher human ACE2 affinity, and probably higher infectivity. This is due to the enhanced structural stabilization of the RBD beta-sheet scaffold. High frequencies of RBD mutations were identified: V367F from five France and one Hong Kong mutants, 13 V483A and 7 G476S mutants from the U.S.A. This suggested they originated as novel sub-lineages. The enhancement of the binding affinity of the mutant type (V367F) was further validated by the receptor-ligand binding ELISA assay. The molecular dynamics simulations also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The analysis of critical RBD mutations provides further insights into the evolutionary history of SARS-CoV-2 under high selection pressure. An enhancement of the SARS-CoV-2 binding affinity to human ACE2 receptor reveals higher infectivity of the mutant strains. Importance A novel coronavirus SARS-CoV-2 has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether the mutations in the RBD of the circulating SARS-CoV-2 strains have altered the receptor binding affinity and caused these strains more infectious, should be paid more attentions to. Here, 32 non-synonymous RBD mutants were identified and clustered into 9 mutant types under high positive selection pressure, suggesting they originated as novel sub-lineages. Three mutant types displayed higher human ACE2 affinity, and probably higher infectivity, one of which (V367F) was validated by wet bench. The RBD mutation analysis provides insights into SARS-CoV-2 evolution. The emergence of RBD mutations with increased human ACE2 affinity reveals higher risk of severe morbidity and mortality during a sustained COVID-19 pandemic, particularly if no effective precautions are implemented.

positive: Genomic variance of the 2019-nCoV coronavirus There is rising global concern for the recently emerged novel Coronavirus (2019-nCov). Full genomic sequences have been released by the worldwide scientific community in the last few weeks in order to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and SARS. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hyper-variable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches.

positive: Animal origins of SARS coronavirus: possible links with the international trade in small carnivores. The search for animal host origins of severe acute respiratory syndrome (SARS) coronavirus has so far remained focused on wildlife markets, restaurants and farms within China. A significant proportion of this wildlife enters China through an expanding regional network of illegal, international wildlife trade. We present the case for extending the search for ancestral coronaviruses and their hosts across international borders into countries such as Vietnam and Lao People's Democratic Republic, where the same guilds of species are found on sale in similar wildlife markets or food outlets. The three species that have so far been implicated, a viverrid, a mustelid and a canid, are part of a large suite of small carnivores distributed across this region currently overexploited by this international wildlife trade. A major lesson from SARS is that the underlying roots of newly emergent zoonotic diseases may lie in the parallel biodiversity crisis of massive species loss as a result of overexploitation of wild animal populations and the destruction of their natural habitats by increasing human populations. To address these dual threats to the long-term future of biodiversity, including man, requires a less anthropocentric and more interdisciplinary approach to problems that require the combined research expertise of ecologists, conservation biologists, veterinarians, epidemiologists, virologists, as well as human health professionals.

positive: Molecular characterization of a novel coronavirus associated with epizootic catarrhal enteritis (ECE) in ferrets Abstract A novel coronavirus, designated as ferret enteric coronavirus (FECV), was identified in feces of domestic ferrets clinically diagnosed with epizootic catarrhal enteritis (ECE). Initially, partial sequences of the polymerase, spike, membrane protein, and nucleocapsid genes were generated using coronavirus consensus PCR assays. Subsequently, the complete sequences of the nucleocapsid gene and the last two open reading frames at the 3′ terminus of the FECV genome were obtained. Phylogenetic analyses based on predicted partial amino acid sequences of the polymerase, spike, and membrane proteins, and full sequence of the nucleocapsid protein showed that FECV is genetically most closely related to group 1 coronaviruses. FECV is more similar to feline coronavirus, porcine transmissible gastroenteritis virus, and canine coronavirus than to porcine epidemic diarrhea virus and human coronavirus 229E. Molecular data presented in this study provide the first genetic evidence for a new coronavirus associated with clinical cases of ECE.

positive: The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms The emerging coronavirus disease (COVID-19) swept across the world, affecting more than 200 countries and territories. Genomic analysis suggests that the COVID-19 virus originated in bats and transmitted to humans through unknown intermediate hosts in the Wuhan seafood market, China, in December of 2019. This virus belongs to the Betacoronavirus group, the same group of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), and for the similarity, it was named SARS-CoV-2. Given the lack of registered clinical therapies or vaccines, many physicians and scientists are investigating previously used clinical drugs for COVID-19 treatment. In this review, we aim to provide an overview of the CoVs origin, pathogenicity, and genomic structure, with a focus on SARS-CoV-2. Besides, we summarize the recently investigated drugs that constitute an option for COVID-19 treatment.

positive: Identification of Coronavirus Isolated from a Patient in Korea with COVID-19 OBJECTIVES: Following reports of patients with unexplained pneumonia at the end of December 2019 in Wuhan, China, the causative agent was identified as coronavirus (SARS-CoV-2), and the 2019 novel coronavirus disease was named COVID-19 by the World Health Organization. Putative patients with COVID-19 have been identified in South Korea, and attempts have been made to isolate the pathogen from these patients. METHODS: Upper and lower respiratory tract secretion samples from putative patients with COVID-19 were inoculated onto cells to isolate the virus. Full genome sequencing and electron microscopy were used to identify the virus. RESULTS: The virus replicated in Vero cells and cytopathic effects were observed. Full genome sequencing showed that the virus genome exhibited sequence homology of more than 99.9% with SARS-CoV-2 which was isolated from patients from other countries, for instance China. Sequence homology of SARS-CoV-2 with SARS-CoV, and MERS-CoV was 77.5% and 50%, respectively. Coronavirus-specific morphology was observed by electron microscopy in virus-infected Vero cells. CONCLUSION: SARS-CoV-2 was isolated from putative patients with unexplained pneumonia and intermittent coughing and fever. The isolated virus was named BetaCoV/Korea/KCDC03/2020.

positive: Review of Bats and SARS Bats have been identified as a natural reservoir for an increasing number of emerging zoonotic viruses, including henipaviruses and variants of rabies viruses. Recently, we and another group independently identified several horseshoe bat species (genus Rhinolophus) as the reservoir host for a large number of viruses that have a close genetic relationship with the coronavirus associated with severe acute respiratory syndrome (SARS). Our current research focused on the identification of the reservoir species for the progenitor virus of the SARS coronaviruses responsible for outbreaks during 2002–2003 and 2003–2004. In addition to SARS-like coronaviruses, many other novel bat coronaviruses, which belong to groups 1 and 2 of the 3 existing coronavirus groups, have been detected by PCR. The discovery of bat SARS-like coronaviruses and the great genetic diversity of coronaviruses in bats have shed new light on the origin and transmission of SARS coronaviruses.

positive: Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV Abstract The seventh novel human infecting Betacoronavirus that causes pneumonia (2019 novel coronavirus, 2019-nCoV) originated in Wuhan, China. The evolutionary relationship between 2019-nCoV and the other human respiratory illness-causing coronavirus is not closely related. We sought to characterize the relationship of the translated proteins of 2019-nCoV with other species of Orthocoronavirinae. A phylogenetic tree was constructed from the genome sequences. A cluster tree was developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The combined data were used to characterize the relationship of the translated proteins of 2019-nCoV to other species of Orthocoronavirinae. Our analysis reliably suggests that 2019-nCoV is most closely related to BatCoV RaTG13 and belongs to subgenus Sarbecovirus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus. The phylogenetic profiling cluster of homolog proteins of one annotated 2019-nCoV protein against other genome sequences revealed two clades of ten 2019-nCoV proteins. Clade 1 consisted of a group of conserved proteins in Orthocoronavirinae comprising Orf1ab polyprotein, Nucleocapsid protein, Spike glycoprotein, and Membrane protein. Clade 2 comprised six proteins exclusive to Sarbecovirus and Hibecovirus. Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. Thus, we speculated that knowledge of the functional changes in the NS7b and NS8 proteins during evolution may provide important information to explore the human infective property of 2019-nCoV.

positive: Chapter 1 Introduction to virus origins and their role in biological evolution Abstract Viruses are diverse parasites of cells and extremely abundant. They might have arisen during an early phase of the evolution of life on Earth dominated by ribonucleic acid or RNA-like macromolecules, or when a cellular world was already well established. The theories of the origin of life on Earth shed light on the possible origin of primitive viruses or virus-like genetic elements in our biosphere. Some features of present-day viruses, notably error-prone replication, might be a consequence of the selective forces that mediated their ancestral origin. Two views on the role of viruses in our biosphere predominate; viruses considered as opportunistic, selfish elements, and viruses considered as active participants in the construction of the cellular world via the lateral transfer of genes. These two models have a bearing on viruses being considered predominantly as disease agents or predominantly as cooperators in the shaping of differentiated cellular organisms.

positive: Coronavirus Disease 2019-COVID-19. SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.

positive: Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19). First identified in Wuhan (Hubei, China) in December of 2019, it has since been declared a pandemic by the World Health Organization in March of 2020. In this study, we will provide a brief review of viral origin, identification, symptoms, transmission, diagnosis, and potential treatment strategies for the newly identified SARS-CoV-2 strain.

positive: The origin and underlying driving forces of the SARS-CoV-2 outbreak BACKGROUND: SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. METHOD: Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. RESULT: After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019-12/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. CONCLUSION: SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.

positive: [Etiology of epidemic outbreaks COVID-19 on Wuhan, Hubei province, Chinese People Republic associated with 2019-nCoV (Nidovirales, Coronaviridae, Coronavirinae, Betacoronavirus, Subgenus Sarbecovirus): lessons of SARS-CoV outbreak.] Results of analysis of phylogenetic, virological, epidemiological, ecological, clinical data of COVID-19 outbreaks in Wuhan, China (PRC) in comparison with SARS-2002 and MERS-2012 outbreaks allow to conclude: - the etiological agent of COVID-19 is coronavirus (2019-CoV), phylogenetically close to the SARS-CoV, isolated from human, and SARS-related viruses isolated from bats (SARS-related bat CoV viruses). These viruses belong to the Sarbecovirus subgenus, Betacoronavirus genus, Orthocoronavirinae subfamily, Coronaviridae family (Cornidovirinea: Nidovirales). COVID-19 is a variant of SARS-2002 and is different from MERS-2012 outbreak, which were caused by coronavirus belonged to the subgenus Merbecovirus of the same genus; - according to the results of phylogenetic analysis of 35 different betacoronaviruses, isolated from human and from wild animals in 2002-2019, the natural source of COVID-19 and SARS-CoV (2002) is bats of Rhinolophus genus (Rhinolophidae) and, probably, some species of other genera. An additional reservoir of the virus could be an intermediate animal species (snakes, civet, hedgehogs, badgers, etc.) that are infected by eating of infected bats. SARS-like coronaviruses circulated in bats in the interepidemic period (2003-2019); - seasonal coronaviruses (subgenus Duvinacovirus, Alphacoronavirus) are currently circulating (November 2019 - January 2020) in the European part of Russia, Urals, Siberia and the Far East of Russia, along with the influenza viruses A(H1N1)pdm09, A(H3N2), and В, as well as six other respiratory viruses (HPIV, HAdV, HRSV, HRV, HBoV, and HMPV).

positive: Identification and Characterization of a Novel Alpaca Respiratory Coronavirus Most Closely Related to the Human Coronavirus 229E In 2007, a novel coronavirus associated with an acute respiratory disease in alpacas (Alpaca Coronavirus, ACoV) was isolated. Full-length genomic sequencing of the ACoV demonstrated the genome to be consistent with other Alphacoronaviruses. A putative additional open-reading frame was identified between the nucleocapsid gene and 3'UTR. The ACoV was genetically most similar to the common human coronavirus (HCoV) 229E with 92.2% nucleotide identity over the entire genome. A comparison of spike gene sequences from ACoV and from HCoV-229E isolates recovered over a span of five decades showed the ACoV to be most similar to viruses isolated in the 1960’s to early 1980’s. The true origin of the ACoV is unknown, however a common ancestor between the ACoV and HCoV-229E appears to have existed prior to the 1960’s, suggesting virus transmission, either as a zoonosis or anthroponosis, has occurred between alpacas and humans.

positive: Host-related nucleotide composition and codon usage as driving forces in the recent evolution of the Astroviridae Abstract The evolutionary history of the Astroviridae comprises the ancient separation between avian and mammalian astrovirus lineages followed by diversification among mammalian astroviruses. The latter process included several cross-species transmissions. We found that the recent, but not the ancient, evolution of astroviruses was associated with a switch in nucleotide composition and codon usage among non-human mammalian versus human/avian astroviruses. Virus and hosts phylogenies based on codon usage agreed with each other and matched the hosts' evolutionary emergence order. This recent switch in driving forces acting at the synonymous level points to the adaptation of codon usage by viruses to that of their hosts after cross-species transmissions. This is the first demonstration of nucleotide composition and codon usage being active driving forces during the recent evolutionary history of a virus group in the host–parasite system.

positive: Natural transmission of bat-like SARS-CoV-2ïPRRA variants in COVID-19 patients BACKGROUND: SARS-CoV-2 contains the furin cleavage PRRA motif in the S1/S2 region, which enhances viral pathogenicity but is absent in closely related bat and pangolin coronaviruses. It remains unknown if bat-like coronaviral variants without PRRA (ΔPRRA) can establish natural infection in humans. METHODS: Here, we developed a duplex digital PCR assay to examine ΔPRRA variants in Vero-E6-propagated isolates, human organoids, experimentally infected hamsters and COVID-19 patients. RESULTS: We found that currently transmitting SARS-CoV-2 contained a quasispecies of wildtype, ΔPRRA variants and upstream variants that have mutations upstream the PRRA motif. Moreover, the ΔPRRA variants were readily detected despite at a low intra-host frequency in transmitted founder viruses in hamsters and in COVID-19 patients including acute cases and a family cluster with a prevalence rate of 52.9%. CONCLUSIONS: Our findings demonstrate that bat-like SARS-CoV-2ΔPRRA not only naturally exists but remains transmissible in COVID-19 patients, which have significant implications to zoonotic origin and natural evolution of SARS-CoV-2.

positive: Genomic characterization and infectivity of a novel SARS-like coronavirus in Chinese bats SARS coronavirus (SARS-CoV), the causative agent of the large SARS outbreak in 2003, originated in bats. Many SARS-like coronaviruses (SL-CoVs) have been detected in bats, particularly those that reside in China, Europe, and Africa. To further understand the evolutionary relationship between SARS-CoV and its reservoirs, 334 bats were collected from Zhoushan city, Zhejiang province, China, between 2015 and 2017. PCR amplification of the conserved coronaviral protein RdRp detected coronaviruses in 26.65% of bats belonging to this region, and this number was influenced by seasonal changes. Full genomic analyses of the two new SL-CoVs from Zhoushan (ZXC21 and ZC45) showed that their genomes were 29,732 nucleotides (nt) and 29,802 nt in length, respectively, with 13 open reading frames (ORFs). These results revealed 81% shared nucleotide identity with human/civet SARS CoVs, which was more distant than that observed previously for bat SL-CoVs in China. Importantly, using pathogenic tests, we found that the virus can reproduce and cause disease in suckling rats, and further studies showed that the virus-like particles can be observed in the brains of suckling rats by electron microscopy. Thus, this study increased our understanding of the genetic diversity of the SL-CoVs carried by bats and also provided a new perspective to study the possibility of cross-species transmission of SL-CoVs using suckling rats as an animal model.

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

positive: The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.

positive: Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

positive: Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event BACKGROUND: A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus. METHODS: Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods. RESULTS: Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat_SARS-like coronavirus sequences. Specifically, in the 5'-part spanning the first 11,498 nucleotides and the last 3'-part spanning 24,341-30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat_SARS-like coronavirus sequences, whereas in the middle region spanning the 3'-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch. CONCLUSIONS: The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.

positive: A pneumonia outbreak associated with a new coronavirus of probable bat origin Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.

positive: SARS-Coronavirus ancestor’s foot-prints in South-East Asian bat colonies and the refuge theory Abstract One of the great challenges in the ecology of infectious diseases is to understand what drives the emergence of new pathogens including the relationship between viruses and their hosts. In the case of the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), several studies have shown coronavirus diversity in bats as well as the existence of SARS-CoV infection in apparently healthy bats, suggesting that bats may be a crucial host in the genesis of this disease. To elucidate the biogeographic origin of SARS-CoV and investigate the role that bats played in its emergence, we amplified coronavirus sequences from bat species captured throughout Thailand and assessed the phylogenetic relationships to each other and to other published coronavirus sequences. To this end, RdRp sequence of Coronavirinae was targeted by RT-PCR in non-invasive samples from bats collected in Thailand. Two new coronaviruses were detected in two bat species: one Betacoronavirus in Hipposideros larvatus and one Alphacoronavirus in Hipposideros armiger. Interestingly, these viruses from South-East Asia are related to those previously detected in Africa (Betacoronavirus-b) or in Europe (Alphacoronavirus & Betacoronavirus-b). These findings illuminate the origin and the evolutionary history of the SARS-CoV group found in bats by pushing forward the hypothesis of a Betacoronavirus spill-over from Hipposideridae to Rhinolophidae and then from Rhinolophidae to civets and Human. All reported Betacoronaviruses-b (SARS-CoV group) of Hipposideridae and Rhinolophidae respectively cluster in two groups despite their broad geographic distribution and the sympatry of their hosts, which is in favor of an ancient and genetically independent evolution of Betacoronavirus-b clusters in these families. Moreover, despite its probable pathogenicity, we found that a Betacoronavirus-b can persistently infect a medium-sized hipposiderid bat colony. These findings illustrate the importance of the host phylogeny and the host/pathogen ecological interactions in the description and the understanding of pathogen emergence. The host’s phylogeny, biogeography and behaviour, combined with already described roles of pathogen plasticity and anthropic changes are likely to be co-factors of disease emergence. Elucidating the common ancestor of Hipposideridae and Rhinolophidae is key to understanding the evolutionary history of actual betacoronaviruses and therefore to get an insight of the deep origin of SARS-CoV.

positive: Cryptic transmission of SARS-CoV-2 in Washington State Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

positive: COVID‐19 and the clinical hematology laboratory The ongoing COVID‐19 pandemic originated in Wuhan, Hubei Province, China in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID‐19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID‐19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to 1) provide background context about the origins and course of the pandemic 2) discuss the laboratory’s role in the diagnosis of COVID‐19 infection 3) summarize the current state of biomarker analysis in COVID‐19 infection, with an emphasis on markers derived from the hematology laboratory 4) comment on the impact of COVID‐19 on hematology laboratory safety, and 5) describe the impact the pandemic has had on organized national and international educational activities worldwide.

positive: Phylodynamics of SARS-CoV-2 transmission in Spain Objectives SARS-CoV-2 whole-genome analysis has identified three large clades spreading worldwide, designated G, V and S. This study aims to analyze the diffusion of SARS-CoV-2 in Spain/Europe. Methods Maximum likelihood phylogenetic and Bayesian phylodynamic analyses have been performed to estimate the most probable temporal and geographic origin of different phylogenetic clusters and the diffusion pathways of SARS-CoV-2. Results Phylogenetic analyses of the first 28 SARS-CoV-2 whole genome sequences obtained from patients in Spain revealed that most of them are distributed in G and S clades (13 sequences in each) with the remaining two sequences branching in the V clade. Eleven of the Spanish viruses of the S clade and six of the G clade grouped in two different monophyletic clusters (S-Spain and G-Spain, respectively), with the S-Spain cluster also comprising 8 sequences from 6 other countries from Europe and the Americas. The most recent common ancestor (MRCA) of the SARS-CoV-2 pandemic was estimated in the city of Wuhan, China, around November 24, 2019, with a 95% highest posterior density (HPD) interval from October 30-December 17, 2019. The origin of S-Spain and G-Spain clusters were estimated in Spain around February 14 and 18, 2020, respectively, with a possible ancestry of S-Spain in Shanghai. Conclusions Multiple SARS-CoV-2 introductions have been detected in Spain and at least two resulted in the emergence of locally transmitted clusters, with further dissemination of one of them to at least 6 other countries. These results highlight the extraordinary potential of SARS-CoV-2 for rapid and widespread geographic dissemination.

positive: Insights into molecular evolution recombination of pandemic SARS-CoV-2 using Saudi Arabian sequences The recently emerged SARS-CoV-2 (Coronaviridae; Betacoronavirus) is the underlying cause of COVID-19 disease. Here we assessed SARS-CoV2 from the Kingdom of Saudi Arabia alongside sequences of SARS-CoV, bat SARS-like CoVs and MERS-CoV, the latter currently detected in this region. Phylogenetic analysis, natural selection investigation and genome recombination analysis were performed. Our analysis showed that all Saudi SARS-CoV-2 sequences are of the same origin and closer proximity to bat SARS-like CoVs, followed by SARS-CoVs, however quite distant to MERS-CoV. Moreover, genome recombination analysis revealed two recombination events between SARS-CoV-2 and bat SARS-like CoVs. This was further assessed by S gene recombination analysis. These recombination events may be relevant to the emergence of this novel virus. Moreover, positive selection pressure was detected between SARS-CoV-2, bat SL-CoV isolates and human SARS-CoV isolates. However, the highest positive selection occurred between SARS-CoV-2 isolates and 2 bat-SL-CoV isolates (Bat-SL-RsSHC014 and Bat-SL-CoVZC45). This further indicates that SARS-CoV-2 isolates were adaptively evolved from bat SARS-like isolates, and that a virus with originating from bats triggered this pandemic. This study thuds sheds further light on the origin of this virus. AUTHOR SUMMARY The emergence and subsequent pandemic of SARS-CoV-2 is a unique challenge to countries all over the world, including Saudi Arabia where cases of the related MERS are still being reported. Saudi SARS-CoV-2 sequences were found to be likely of the same or similar origin. In our analysis, SARS-CoV-2 were more closely related to bat SARS-like CoVs rather than to MERS-CoV (which originated in Saudi Arabia) or SARS-CoV, confirming other phylogenetic efforts on this pathogen. Recombination and positive selection analysis further suggest that bat coronaviruses may be at the origin of SARS-CoV-2 sequences. The data shown here give hints on the origin of this virus and may inform efforts on transmissibility, host adaptation and other biological aspects of this virus.

positive: Molecular immune pathogenesis and diagnosis of COVID-19 Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.

positive: Tracking the origin of early COVID-19 cases in Canada Abstract The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country’s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world’s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada’s first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.

positive: Natural transmission of bat-like SARS-CoV-2PRRA variants in COVID-19 patients. BACKGROUND SARS-CoV-2 contains the furin cleavage PRRA motif in the S1/S2 region, which enhances viral pathogenicity but is absent in closely related bat and pangolin coronaviruses. It remains unknown if bat-like coronaviral variants without PRRA (ΔPRRA) can establish natural infection in humans. METHODS Here, we developed a duplex digital PCR assay to examine ΔPRRA variants in Vero-E6-propagated isolates, human organoids, experimentally infected hamsters and COVID-19 patients. RESULTS We found that currently transmitting SARS-CoV-2 contained a quasispecies of wildtype, ΔPRRA variants and upstream variants that have mutations upstream the PRRA motif. Moreover, the ΔPRRA variants were readily detected despite at a low intra-host frequency in transmitted founder viruses in hamsters and in COVID-19 patients including acute cases and a family cluster with a prevalence rate of 52.9%. CONCLUSIONS Our findings demonstrate that bat-like SARS-CoV-2ΔPRRA not only naturally exists but remains transmissible in COVID-19 patients, which have significant implications to zoonotic origin and natural evolution of SARS-CoV-2.

positive: Computational Inference of Selection Underlying the Evolution of the Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that recently emerged in China is thought to have a bat origin, as its closest known relative (BatCoV RaTG13) was described previously in horseshoe bats. We analyzed the selective events that accompanied the divergence of SARS-CoV-2 from BatCoV RaTG13. To this end, we applied a population genetics-phylogenetics approach, which leverages within-population variation and divergence from an outgroup. Results indicated that most sites in the viral open reading frames (ORFs) evolved under conditions of strong to moderate purifying selection. The most highly constrained sequences corresponded to some nonstructural proteins (nsps) and to the M protein. Conversely, nsp1 and accessory ORFs, particularly ORF8, had a nonnegligible proportion of codons evolving under conditions of very weak purifying selection or close to selective neutrality. Overall, limited evidence of positive selection was detected. The 6 bona fide positively selected sites were located in the N protein, in ORF8, and in nsp1. A signal of positive selection was also detected in the receptor-binding motif (RBM) of the spike protein but most likely resulted from a recombination event that involved the BatCoV RaTG13 sequence. In line with previous data, we suggest that the common ancestor of SARS-CoV-2 and BatCoV RaTG13 encoded/encodes an RBM similar to that observed in SARS-CoV-2 itself and in some pangolin viruses. It is presently unknown whether the common ancestor still exists and, if so, which animals it infects. Our data, however, indicate that divergence of SARS-CoV-2 from BatCoV RaTG13 was accompanied by limited episodes of positive selection, suggesting that the common ancestor of the two viruses was poised for human infection.IMPORTANCE Coronaviruses are dangerous zoonotic pathogens; in the last 2 decades, three coronaviruses have crossed the species barrier and caused human epidemics. One of these is the recently emerged SARS-CoV-2. We investigated how, since its divergence from a closely related bat virus, natural selection shaped the genome of SARS-CoV-2. We found that distinct coding regions in the SARS-CoV-2 genome evolved under conditions of different degrees of constraint and are consequently more or less prone to tolerate amino acid substitutions. In practical terms, the level of constraint provides indications about which proteins/protein regions are better suited as possible targets for the development of antivirals or vaccines. We also detected limited signals of positive selection in three viral ORFs. However, we warn that, in the absence of knowledge about the chain of events that determined the human spillover, these signals should not be necessarily interpreted as evidence of an adaptation to our species.

positive: Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China Abstract Among 489 bats of 11 species in China, three novel paramyxoviruses [Tuhokovirus 1, 2 and 3 (ThkPV-1, ThkPV-2 and ThkPV-3)] were discovered in 15 Leschenault's rousettes. Phylogenetically, the three viruses are most closely related to Menangle and Tioman virus. Genome analysis showed that their 3'-leader sequences are unique by possessing GA instead of AG at the 5th and 6th positions. Unlike Menangle and Tioman virus, key amino acids for neuraminidase activity characteristic of rubulavirus attachment proteins are present. The genome of ThkPV-1 represents the largest rubulavirus genome. Unique features between the three viruses include perfect complementary 5'-trailer and 3'-leader sequence and a unique cysteine pair in attachment protein of ThkPV-1, G at +1 position in all predicted mRNA sequences of ThkPV-2, and amino acid substitutions in the conserved N-terminal motif of nucleocapsid of ThkPV-3. Analysis of phosphoprotein gene mRNA products confirmed mRNA editing. Antibodies to the viruses were detected in 48–60% of Leschenault's rousettes.

positive: Prevent and predict As the COVID-19 outbreak continues, the next pandemic could be prevented by ending the wildlife trade and reinvesting in the monitoring of potential zoonoses.

positive: 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.

positive: Comments to the predecessor of human SARS coronavirus in 2003–2004 epidemic

positive: The epidemiology and clinical information about COVID-19 In December 2019, pneumonia of unknown cause occurred in Wuhan, Hubei Province, China. On 7 January 2020, a novel coronavirus, named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was identified in the throat swab sample of one patient. The World Health Organization (WHO) announced the epidemic disease caused by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). Currently, COVID-19 has spread widely around the world, affecting more than seventy countries. China, with a huge burden of this disease, has taken strong measures to control the spread and improve the curative rate of COVID-19. In this review, we summarized the epidemiological characteristics, clinical features, diagnosis, treatment, and prognosis of COVID-19. A comprehensive understanding will help to control the disease.

positive: Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. The outbreak of COVID-19 poses unprecedent challenges to global health1. The new coronavirus, SARS-CoV-2, shares high sequence identity to SARS-CoV and a bat coronavirus RaTG132. While bats may be the reservoir host for various coronaviruses3,4, whether SARS-CoV-2 has other hosts remains ambiguous. In this study, one coronavirus isolated from a Malayan pangolin showed 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S genes, respectively. In particular, the receptor-binding domain within the S protein of the Pangolin-CoV is virtually identical to that of SARS-CoV-2, with one noncritical amino acid difference. Results of comparative genomic analysis suggest that SARS-CoV-2 might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. The Pangolin-CoV was detected in 17 of 25 Malayan pangolins analyzed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against Pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus that is highly related to SARS-CoV-2 in pangolins suggests that they have the potential to act as the intermediate host of SARS-CoV-2. The newly identified coronavirus in the most-trafficked mammal could represent a future threat to public health if wildlife trade is not effectively controlled.

positive: Hypothesized behavioral host manipulation by SARS-CoV2 / COVID-19 infection Abstract Although not widely studied, behavioral host manipulation by various pathogens has been documented. Host manipulation is the process by which a pathogen evolves adaptations to manipulate the behavior of the host to maximize reproduction (Ro) of the pathogen. The most notable example is rabies. When a host is infected with the rabies virus it gets into the host’s central nervous system and triggers hyper aggression. The virus is also present in the rabid animal’s saliva so being bitten transmits the infection to a new host and the old host is left to eventually die if untreated. Toxoplasmosis is another example. When mice are infected they demonstrate a fearlessness toward cats, thus increasing their chances of being eaten. Toxoplasmosis needs the digestive tract of the feline to survive. Recent studies have shown that exposure to toxoplasmosis in humans (e.g., through cat feces) has also been associated with behavioral changes that are predicted to enhance the spread of the pathogen. Even the common influenza virus has been shown to selectively increase in-person sociality during the 48-hour incubation period, thus producing an obvious vector for transmission. Here we hypothesize that the novel coronavirus, SARS-CoV2, which produces the COVID-19 disease may produce similar host manipulations that maximize its transmission between humans.

positive: Distinct genetic spectrums and evolution patterns of SARS-CoV-2 Four signature groups of single-nucleotide variants (SNVs) were identified using two-way clustering method in about twenty thousand high quality and high coverage SARS-CoV-2 complete genome sequences. Some frequently occurred SNVs predominate but are mutually exclusively presented in patients from different countries and areas. These major SNV signatures exhibited distinguished evolution patterns overtime. Although it was rare, our data indicated possible cross-infections with multiple groups of SNVs existed simultaneously in some patients, suggesting infections from different SARS-CoV-2 clades or potential re-combination of SARS-CoV-2 sequences. Interestingly nucleotide substitutions among SARS-CoV-2 genomes tend to occur at the sites where one bat RaTG13 coronavirus sequences differ from Wuhan-Hu-1 genome, indicating the tolerance of mutations on those sites or suggesting that major viral strains might exist between Wuhan-Hu-1 and RaTG13 coronavirus.

positive: Comparing the binding interactions in the receptor binding domains of SARS-CoV-2 and SARS-CoV COVID-19, since emerged in Wuhan, China, has been a major concern due to its high infection rate, leaving more than one million infected people around the world. Huge number of studies tried to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV-1, in order to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV-1 Spike protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the spike proteins of SARS-CoV and SARS-CoV-2 to the ACE2. We found that the SARS-CoV-2 binds to ACE2 stronger than SARS-CoV by 7 kcal/mol, due to enhanced electrostatic interactions. The major contributions to the electrostatic binding energies are resulting from the salt-bridges formed between R426 and ACE2-E329 in case of SARS-CoV and K417 and ACE2-D30 for SARS-CoV2. In addition, there is no significant contribution from a single mutant to the binding energies. However, these mutations induce sophisticated structural changes that enhance the binding energies. Our results also indicate that the SARS-CoV-2 is unlikely a lab engineered virus.

positive: World Heart Federation Briefing on Prevention: Coronavirus Disease 2019 (COVID-19) in Low-Income Countries In December 2019, the novel coronavirus Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan, the capital of Hubei province in China. Since then it has spread to many other regions, including low-income countries.

positive: Recombination and purifying selection preserves covariant movements of mosaic SARS-CoV-2 protein S In depth evolutionary and structural analyses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from bats, pangolins, and humans are necessary to assess the role of natural selection and recombination in the emergence of the current pandemic strain. The SARS-CoV-2 S glycoprotein unique features have been associated with efficient viral spread in the human population. Phylogeny-based and genetic algorithm methods clearly show that recombination events between viral progenitors infecting animal hosts led to a mosaic structure in the S gene. We identified recombination coldspots in the S glycoprotein and strong purifying selection. Moreover, although there is little evidence of diversifying positive selection during host-switching, structural analysis suggests that some of the residues emerged along the ancestral lineage of current pandemic strains may contribute to enhanced ability to infect human cells. Interestingly, recombination did not affect the long-range covariant movements of SARS-CoV-2 S glycoprotein monomer in pre-fusion conformation but, on the contrary, could contribute to the observed overall viral efficiency. Our dynamic simulations revealed that the movements between the host cell receptor binding domain (RBD) and the novel furin-like cleavage site are correlated. We identified threonine 333 (under purifying selection), at the beginning of the RBD, as the hinge of the opening/closing mechanism of the SARS-CoV-2 S glycoprotein monomer functional to hACE2 binding. Our findings support a scenario where ancestral recombination and fixation of amino acid residues in the RBD of the S glycoprotein generated a virus with unique features, capable of extremely efficient infection of the human host.

positive: Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5 and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P=0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin.

positive: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics.

positive: 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.

positive: Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identification of the agent represented an important breakthrough, our understanding of the deadly virus remains limited. Detailed biological knowledge is crucial for the development of effective countermeasures, diagnostic tests, vaccines and antiviral drugs against the SARS-CoV. This article reviews the present state of molecular knowledge about SARS-CoV, from the aspects of comparative genomics, molecular biology of viral genes, evolution, and epidemiology, and describes the diagnostic tests and the anti-viral drugs derived so far based on the available molecular information.

positive: Extensive diversity of coronaviruses in bats from China Abstract To help reveal the diversity and evolution of bat coronaviruses we collected 1067 bats from 21 species in China. A total of 73 coronaviruses (32 alphacoronaviruses and 41 betacoronaviruses) were identified in these bats, with an overall prevalence of 6.84%. All newly-identified betacoronaviruses were SARS-related Rhinolophus bat coronaviruses (SARSr-Rh-BatCoV). Importantly, with the exception of the S gene, the genome sequences of the SARSr-Rh-BatCoVs sampled in Guizhou province were closely related to SARS-related human coronavirus. Additionally, the newly-identified alphacoronaviruses exhibited high genetic diversity and some may represent novel species. Our phylogenetic analyses also provided insights into the transmission of these viruses among bat species, revealing a general clustering by geographic location rather than by bat species. Inter-species transmission among bats from the same genus was also commonplace in both the alphacoronaviruses and betacoronaviruses. Overall, these data suggest that high contact rates among specific bat species enable the acquisition and spread of coronaviruses.

positive: 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.

positive: No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2

positive: COVID-19 under spotlight: A close look at the origin, transmission, diagnosis, and treatment of the 2019-nCoV disease Months after the outbreak of a new flu-like disease in China, the entire world is now in a state of caution. The subsequent less-anticipated propagation of the novel coronavirus disease, formally known as COVID-19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS-CoV-2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID-19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.

positive: SARS-CoV originated from bats in 1998 and may still exist in humans SARS-CoV is believed to originate from civets and was thought to have been eliminated as a threat after the 2003 outbreak. Here, we show that human SARS-CoV (huSARS-CoV) originated directly from bats, rather than civets, by a cross-species jump in 1991, and formed a human-adapted strain in 1998. Since then huSARS-CoV has evolved further into highly virulent strains with genotype T and a 29-nt deletion mutation, and weakly virulent strains with genotype C but without the 29-nt deletion. The former can cause pneumonia in humans and could be the major causative pathogen of the SARS outbreak, whereas the latter might not cause pneumonia in humans, but evolved the ability to co-utilize civet ACE2 as an entry receptor, leading to interspecies transmission between humans and civets. Three crucial time points - 1991, for the cross-species jump from bats to humans; 1998, for the formation of the human-adapted SARS-CoV; and 2003, when there was an outbreak of SARS in humans - were found to associate with anomalously low annual precipitation and high temperatures in Guangdong. Anti-SARS-CoV sero-positivity was detected in 20% of all the samples tested from Guangzhou children who were born after 2005, suggesting that weakly virulent huSARS-CoVs might still exist in humans. These existing but undetected SARS-CoVs have a large potential to evolve into highly virulent strains when favorable climate conditions occur, highlighting a potential risk for the reemergence of SARS.

positive: 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.

positive: Molecular evolution and multilocus sequence typing of 145 strains of SARS-CoV Abstract In this study, we have identified 876 polymorphism sites in 145 complete or partial genomes of SARS-CoV available in the NCBI GenBank. One hundred and seventy-four of these sites existed in two or more SARS-CoV genome sequences. According to the sequence polymorphism, all SARS-CoVs can be divided into three groups: (I) group 1, animal-origin viruses (such as SARS-CoV SZ1, SZ3, SZ13 and SZ16); (II) group 2, all viruses with clinical origin during first epidemic; and (III) group 3, SARS-CoV GD03T0013. According to 10 special loci, group 2 again can be divided into genotypes C and T, which can be further divided into sub-genotypes C1–C4 and T1–T4. Positive Darwinian selections were identified between any pair of these three groups. Genotype C gives neutral selection. Genotype T, however, shows negative selection. By comparing the death rates of SARS patients in the different regions, it was found that the death rate caused by the viruses of the genotype C was lower than that of the genotype T. SARS-CoVs might originate from an unknown ancestor.

positive: Evolutionary Relationships between Bat Coronaviruses and Their Hosts Recent studies have suggested that bats are the natural reservoir of a range of coronaviruses (CoVs), and that rhinolophid bats harbor viruses closely related to the severe acute respiratory syndrome (SARS) CoV, which caused an outbreak of respiratory illness in humans during 2002–2003. We examined the evolutionary relationships between bat CoVs and their hosts by using sequence data of the virus RNA-dependent RNA polymerase gene and the bat cytochrome b gene. Phylogenetic analyses showed multiple incongruent associations between the phylogenies of rhinolophid bats and their CoVs, which suggested that host shifts have occurred in the recent evolutionary history of this group. These shifts may be due to either virus biologic traits or host behavioral traits. This finding has implications for the emergence of SARS and for the potential future emergence of SARS-CoVs or related viruses.

positive: Coronavirus Disease (COVID-19): A primer for emergency physicians INTRODUCTION: Rapid worldwide spread of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic. OBJECTIVE: This review article provides emergency physicians with an overview of the most current understanding of COVID-19 and recommendations on the evaluation and management of patients with suspected COVID-19. DISCUSSION: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing COVID-19, is primarily transmitted from person-to-person through close contact (approximately 6 ft) by respiratory droplets. Symptoms of COVID-19 are similar to other viral upper respiratory illnesses. Three major trajectories include mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ARDS). Emergency physicians should focus on identifying patients at risk, isolating suspected patients, and informing hospital infection prevention and public health authorities. Patients with suspected COVID-19 should be asked to wear a facemask. Respiratory etiquette, hand washing, and personal protective equipment are recommended for all healthcare personnel caring for suspected cases. Disposition depends on patient symptoms, hemodynamic status, and patient ability to self-quarantine. CONCLUSION: This narrative review provides clinicians with an updated approach to the evaluation and management of patients presenting to the emergency department with suspected COVID-19.

positive: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans. Though not confirmed yet, multiple surveillance and phylogenetic studies suggest a bat origin. The disease is heavily endemic in dromedary camel populations of East Africa and the Middle East. It is unclear as to when the virus was introduced to dromedary camels, but data from studies that investigated stored dromedary camel sera and geographical distribution of involved dromedary camel populations suggested that the virus was present in dromedary camels several decades ago. Though bats and alpacas can serve as potential reservoirs for MERS-CoV, dromedary camels seem to be the only animal host responsible for the spill over human infections.

positive: The global emergence of severe acute respiratory syndrome coronavirus 2 in human Coronaviruses are spherical and enveloped RNA viruses that infect diverse vertebrates like mammals, birds and fish. There are five human coronavirus species and all of their origin is linked to animal like bat and rodent. The two coronavirus species, Middle East respiratory syndrome-related coronavirus and Severe acute respiratory syndrome-related coronavirus are lethal to human. In the second week of December 2019, there was an outbreak of pneumonia of unknown cause in the people associated with a seafood market in Wuhan, China. The disease was designated as coronavirus disease 2019 (COVID-19) and the virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of the genus Betacoronavirus. SARS-CoV-2 being highly transmissible and pathogenic, soon it has spread to 213 countries killing > 0.47 million people. The information on the research findings of SARS-CoC-2 are pouring from all over the world. In a special issue of VirusDisease, “The global emergence of coronavirus in human”, various topics relating to emergence, potential cases, transmission dynamics, diagnosis, pathogenesis, food safety, therapeutic strategies and antiviral properties of Ayurveda products are covered.

positive: Synonymous mutations and the molecular evolution of SARS-Cov-2 origins Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of non-synonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively.

positive: The Evolutionary Processes of Canine Coronaviruses Since the first identification of the virus in 1971, the disease caused by canine coronavirus (CCoV) has not been adequately investigated, and the role that the virus plays in canine enteric illness has not been well established. Only after the emergence in 2002 of SARS in human has new attention been focused on coronaviruses. As a consequence of the relatively high mutation frequency of RNA-positive stranded viruses, CCoV has evolved and, with the biomolecular techniques developed over the last two decades, new virus strains, serotypes, and subtypes have been identified in infected dogs. Considering the widespread nature of CCoV infections among dog populations, several studies have been carried out, focusing upon the epidemiological relevance of these viruses and underlining the need for further investigation into the biology of CCoVs and into the pathogenetic role of the infections. This paper reports the evolutionary processes of CCoVs with a note onto recent diagnostic methods.

positive: Origin of imported SARS-CoV-2 strains in The Gambia identified from Whole Genome Sequences Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a positive-sense single stranded RNA virus with high human transmissibility. This study generated Whole Genome data to determine the origin and pattern of transmission of SARS-CoV-2 from the first six cases tested in The Gambia. Total RNA from SARS-CoV-2 was extracted from inactivated nasopharyngeal-oropharyngeal swabs of six cases and converted to cDNA following the ARTIC COVID-19 sequencing protocol. Libraries were constructed with the NEBNext ultra II DNA library prep kit for Illumina and Oxford Nanopore Ligation sequencing kit and sequenced on Illumina MiSeq and Nanopore GridION, respectively. Sequencing reads were mapped to the Wuhan reference genome and compared to eleven other SARS-CoV-2 strains of Asian, European and American origins. A phylogenetic tree was constructed with the consensus genomes for local and non-African strains. Three of the Gambian strains had a European origin (UK and Spain), two strains were of Asian origin (Japan). In The Gambia, Nanopore and Illumina sequencers were successfully used to identify the sources of SARS-CoV-2 infection in COVID-19 cases.

positive: Complete genome sequence of bat coronavirus HKU2 from Chinese horseshoe bats revealed a much smaller spike gene with a different evolutionary lineage from the rest of the genome Abstract Apart from bat-SARS-CoV, we have identified a novel group 1 coronavirus, bat-CoV HKU2, in Rhinolophus sinicus (Chinese horseshoe bats). Since it has been suggested that the receptor-binding motif (RBM) of SARS-CoV may have been acquired from a group 1 coronavirus, we conducted a surveillance study and identified bat-SARS-CoV and bat-CoV HKU2 in 8.7% and 7.5% respectively of R. sinicus in Hong Kong and Guangdong. Complete genome sequencing of four strains of bat-CoV HKU2 revealed the smallest coronavirus genome (27164 nucleotides) and a unique spike protein evolutionarily distinct from the rest of the genome. This spike protein, sharing similar deletions with other group 2 coronaviruses in its C-terminus, also contained a 15-amino acid peptide homologous to a corresponding peptide within the RBM of spike protein of SARS-CoV, which was absent in other coronaviruses except bat-SARS-CoV. These suggest a common evolutionary origin in the spike protein of bat-CoV HKU2, bat-SARS-CoV, and SARS-CoV.

positive: Evidence from the evolutionary analysis of nucleotide sequences for a recombinant history of SARS-CoV Abstract The origins and evolutionary history of the Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS-CoV) remain an issue of uncertainty and debate. Based on evolutionary analyses of coronavirus DNA sequences, encompassing an approximately 13kb stretch of the SARS-TOR2 genome, we provide evidence that SARS-CoV has a recombinant history with lineages of types I and III coronavirus. We identified a minimum of five recombinant regions ranging from 83 to 863bp in length and including the polymerase, nsp9, nsp10, and nsp14. Our results are consistent with a hypothesis of viral host jumping events, concomitant with the reassortment of bird and mammalian coronaviruses, a scenario analogous to earlier outbreaks of influenzae.

positive: Initial Cluster of Novel Coronavirus (2019-nCoV) Infections in Wuhan, China Is Consistent with Substantial Human-to-Human Transmission Reanalysis of the epidemic curve from the initial cluster of cases with novel coronavirus (2019-nCoV) in December 2019 indicates substantial human-to-human transmission. It is possible that the common exposure history at a seafood market in Wuhan originated from the human-to-human transmission events within the market, and the early, strong emphasis that market exposure indicated animal-to-human transmission was potentially the result of observer bias. To support the hypothesis of zoonotic origin of 2019-nCoV stemming from the Huanan seafood market, the index case should have had exposure history related to the market and the virus should have been identified from animals sold at the market. As these requirements remain unmet, zoonotic spillover at the market must not be overemphasized.

positive: Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses Abstract In December 2019, a novel human-infecting coronavirus (SARS-CoV-2) was recognized in China. In a few months, SARS-CoV-2 has caused thousands of disease cases and deaths in several countries. Phylogenetic analyses indicated that SARS-CoV-2 clusters with SARS-CoV in the Sarbecovirus subgenus and viruses related to SARS-CoV-2 were identified from bats and pangolins. Coronaviruses have long and complex genomes with high plasticity in terms of gene content. To date, the coding potential of SARS-CoV-2 remains partially unknown. We thus used available sequences of bat and pangolin viruses to determine the selective events that shaped the genome structure of SARS-CoV-2 and to assess its coding potential. By searching for signals of significantly reduced variability at synonymous sites (dS), we identified six genomic regions, one of these corresponding to the programmed −1 ribosomal frameshift. The most prominent signal of dS reduction was observed within the E gene. A genome-wide analysis of conserved RNA structures indicated that this region harbors a putative functional RNA element that is shared with the SARS-CoV lineage. Additional signals of reduced dS indicated the presence of internal ORFs. Whereas the presence ORF9a (internal to N) was previously proposed by homology with a well characterized protein of SARS-CoV, ORF3h (for hypothetical, within ORF3a) was not previously described. The predicted product of ORF3h has 90% identity with the corresponding predicted product of SARS-CoV and displays features suggestive of a viroporin. Finally, analysis of the putative ORF10 revealed high dN/dS (3.82) in SARS-CoV-2 and related coronaviruses. In the SARS-CoV lineage, the ORF is predicted to encode a truncated protein and is neutrally evolving. These data suggest that ORF10 encodes a functional protein in SARS-CoV-2 and that positive selection is driving its evolution. Experimental analyses will be necessary to validate and characterize the coding and non-coding functional elements we identified.

positive: Game consumption and the 2019 novel coronavirus

positive: Could India be the origin of next COVID-19 like epidemic? Abstract The COVID-19 global pandemic is not even over yet but it has already taught us a lot of lessons - the hard way. The vast majority of the global community has blamed the Chinese Illegal wildlife markets for the origin of this pandemic. Through careful scientific analysis, I have explained in this article that we don't need such wildlife markets for these kinds of outbreaks to occur in the future. I have also explained how India which is the second-most populous country in the world, could be the origin of the next outbreak, even though such wildlife markets are either very rare or do not exist at all in India.

positive: COVID-19: An Update on the Epidemiological, Genomic Origin, Phylogenetic study, India centric to Worldwide current status The pandemic spread of novel coronavirus, (SARS-CoV-2) causing CoronaVirus Infectious Diseases (COVID-19) emerged into a global threat for human life causing serious death rates and economic crunch all over the globe. As on April 17, 2020 at 2:00am CEST, there include a total of 2,034,802 confirmed cases for Corona and 1,35,163 deaths worldwide have been reported which includes 212 countries, areas or territories reported by World Health Organization (WHO), in which USA tops 6,32,781 confirmed cases (28,221 deaths) followed by Italy 1,65,155 (21,647 deaths), Spain 1,77,633 (18,579 deaths) and China 84,149 (4,642 deaths). This study aims to compare the genomic nature of SARS-CoV-2 genome reported from Wuhan, China with two Indian isolate genome reported by ICMR-NIV, India. Further Phylogenetic studies performed with coronavirus infecting non-human species like Bats, Duck, and sparrow were compared with Indian and other country whole genome sequences of SARS-CoV2 using MegaX and traced out the association between the human coronavirus with the other species viral genome. In addition, epidemiological reports on COVID-19 among Worldwide and India centric data were compared between April 7, 2020 to April 17, 2020 global data and the number of active cases were increased dramatically in this 10 days period studied, highlighted in the current study.

positive: Genomic variance of the 2019‐nCoV coronavirus There is a rising global concern for the recently emerged novel coronavirus (2019‐nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019‐nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019‐nCoV. Despite the low heterogeneity of the 2019‐nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8‐encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti‐coronavirus approaches.

positive: Coronaviruses: emerging and re-emerging pathogens in humans and animals The severe acute respiratory syndrome coronavirus (SARS-CoV) and recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) epidemics have proven the ability of coronaviruses to cross species barrier and emerge rapidly in humans. Other coronaviruses such as porcine epidemic diarrhea virus (PEDV) are also known to cause major disease epidemics in animals wiith huge economic loss. This special issue in Virology Journal aims to highlight the advances and key discoveries in the animal origin, viral evolution, epidemiology, diagnostics and pathogenesis of the emerging and re-emerging coronaviruses in both humans and animals.

positive: An exclusive 42 amino acid signature in pp1ab protein provides insights into the evolutive history of the 2019 novel human-pathogenic coronavirus (SARS-CoV-2) The city of Wuhan, Hubei province, China, was the origin of a severe pneumonia outbreak in December 2019, attributed to a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), causing a total of 2761 deaths and 81109 cases (25 February 2020). SARS-CoV-2 belongs to genus Betacoronavirus, subgenus Sarbecovirus. The polyprotein 1ab (pp1ab) remains unstudied thoroughly since it is similar to other sarbecoviruses. In this short communication, we performed phylogenetic-structural sequence analysis of pp1ab protein of SARS-CoV-2. The analysis showed that the viral pp1ab has not changed in most isolates throughout the outbreak time, but interestingly a deletion of 8 aa in the virulence factor nonstructural protein 1 was found in a virus isolated from a Japanese patient that did not display critical symptoms. While comparing pp1ab protein with other betacoronaviruses, we found a 42 amino acid signature that is only present in SARS-CoV-2 (AS-SCoV2). Members from clade 2 of sarbecoviruses have traces of this signature. The AS-SCoV2 located in the acidic-domain of papain-like protein of SARS-CoV-2 and bat-SL-CoV-RatG13 guided us to suggest that the novel 2019 coronavirus probably emerged by genetic drift from bat-SL-CoV-RaTG13. The implication of this amino acid signature in papain-like protein structure arrangement and function is something worth to be explored.

positive: 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.

positive: Genetic drift of human coronavirus OC43 spike gene during adaptive evolution Coronaviruses (CoVs) continuously threaten human health. However, to date, the evolutionary mechanisms that govern CoV strain persistence in human populations have not been fully understood. In this study, we characterized the evolution of the major antigen-spike (S) gene in the most prevalent human coronavirus (HCoV) OC43 using phylogenetic and phylodynamic analysis. Among the five known HCoV-OC43 genotypes (A to E), higher substitution rates and dN/dS values as well as more positive selection sites were detected in the S gene of genotype D, corresponding to the most dominant HCoV epidemic in recent years. Further analysis showed that the majority of substitutions were located in the S1 subunit. Among them, seven positive selection sites were chronologically traced in the temporal evolution routes of genotype D, and six were located around the critical sugar binding region in the N-terminal domain (NTD) of S protein, an important sugar binding domain of CoV. These findings suggest that the genetic drift of the S gene may play an important role in genotype persistence in human populations, providing insights into the mechanisms of HCoV-OC43 adaptive evolution.

positive: Evolutionary history, potential intermediate animal host, and cross‐species analyses of SARS‐CoV‐2 To investigate the evolutionary history of the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. To explore the potential intermediate animal host of the SARS‐CoV‐2 virus, we reanalyzed virome data sets from pangolins and representative SARS‐related coronaviruses isolates from bats, with particular attention paid to the spike glycoprotein gene. We performed phylogenetic, split network, transmission network, likelihood‐mapping, and comparative analyses of the genomes. Based on Bayesian time‐scaled phylogenetic analysis using the tip‐dating method, we estimated the time to the most recent common ancestor and evolutionary rate of SARS‐CoV‐2, which ranged from 22 to 24 November 2019 and 1.19 to 1.31 × 10(−3) substitutions per site per year, respectively. Our results also revealed that the BetaCoV/bat/Yunnan/RaTG13/2013 virus was more similar to the SARS‐CoV‐2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378). We also identified a unique peptide (PRRA) insertion in the human SARS‐CoV‐2 virus, which may be involved in the proteolytic cleavage of the spike protein by cellular proteases, and thus could impact host range and transmissibility. Interestingly, the coronavirus carried by pangolins did not have the RRAR motif. Therefore, we concluded that the human SARS‐CoV‐2 virus, which is responsible for the recent outbreak of COVID‐19, did not come directly from pangolins.

positive: COVID-19: Knowns, Unknowns, and Questions The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months highlights the transmissibility of this family of viruses and the significant morbidity and mortality that they can cause. We highlight the current state of knowledge of coronavirus biology while answering questions concerning the current outbreak of SARS-CoV-2.

positive: A Bat-Derived Putative Cross-Family Recombinant Coronavirus with a Reovirus Gene The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 has generated enormous interest in the biodiversity, genomics and cross-species transmission potential of coronaviruses, especially those from bats, the second most speciose order of mammals. Herein, we identified a novel coronavirus, provisionally designated Rousettus bat coronavirus GCCDC1 (Ro-BatCoV GCCDC1), in the rectal swab samples of Rousettus leschenaulti bats by using pan-coronavirus RT-PCR and next-generation sequencing. Although the virus is similar to Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9) in genome characteristics, it is sufficiently distinct to be classified as a new species according to the criteria defined by the International Committee of Taxonomy of Viruses (ICTV). More striking was that Ro-BatCoV GCCDC1 contained a unique gene integrated into the 3’-end of the genome that has no homologs in any known coronavirus, but which sequence and phylogeny analyses indicated most likely originated from the p10 gene of a bat orthoreovirus. Subgenomic mRNA and cellular-level observations demonstrated that the p10 gene is functional and induces the formation of cell syncytia. Therefore, here we report a putative heterologous inter-family recombination event between a single-stranded, positive-sense RNA virus and a double-stranded segmented RNA virus, providing insights into the fundamental mechanisms of viral evolution.

positive: Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses Human coronaviruses (HCoVs) were first described in the 1960s for patients with the common cold. Since then, more HCoVs have been discovered, including those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two pathogens that, upon infection, can cause fatal respiratory disease in humans. It was recently discovered that dromedary camels in Saudi Arabia harbor three different HCoV species, including a dominant MERS HCoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015. In this review we aim to compare and contrast the different HCoVs with regard to epidemiology and pathogenesis, in addition to the virus evolution and recombination events which have, on occasion, resulted in outbreaks amongst humans.

positive: A Review of Coronavirus Disease-2019 (COVID-19) There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

positive: Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10 - 25 January) 2020. We also applied structural bioinformatics to assess D614G potential impact on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.

positive: Current Insight into the Novel Coronavirus Disease 2019 (COVID-19) SARS-CoV-2 is a novel strain of coronavirus that has not been previously identified in humans. It has been declared a pandemic and has infected at least 1,844,683 individuals and caused 117,021 deaths as of 14th April 2020. Transmission among humans occurs via close contact with an infected individual that produces respiratory droplets. Patients have been shown to undergo acute respiratory distress syndrome, which is defined as cytokine storm. The diagnosis relies on detection of nucleic acid, IgG/IgM antibodies, and a chest radiograph of the suspected individuals. The genome of SARS-CoV-2 is similar to other coronaviruses that comprise of ten open reading frames (ORFs). SARS-CoV-2 spike protein exhibits higher affinity to ACE2 receptor as compared with SARS-CoV. Repurposing drugs like favipiravir, remdesivir, chloroquine, and TMPRSS2 protease inhibitors have been shown to be effective for the treatment of COVID-19. Personal protective measures should be followed to prevent SARS-CoV-2 infection. In addition, a clinical trial of SARS-CoV-2 vaccine, mRNA-1273, has been started. This chapter provides a glimpse of advancements made in the area of SARS-CoV-2 infection by proving recent clinical and research trials in the field.

positive: The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus (SARS‐CoV) and the emerging Middle East respiratory syndrome coronavirus (MERS‐CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.

negative: Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease A novel coronavirus SARS-CoV-2, also called novel coronavirus 2019 (nCoV-19), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.96% as of May 4, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (M(pro)). Using the FRET-based enzymatic assay, several inhibitors including boceprevir, GC-376, and calpain inhibitors II, and XII were identified to have potent activity with single-digit to submicromolar IC(50) values in the enzymatic assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies, thermal shift binding assays, and native mass spectrometry. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC(50) values ranging from 0.49 to 3.37 μM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known M(pro) inhibitors. A complex crystal structure of SARS-CoV-2 M(pro) with GC-376, determined at 2.15 Å resolution with three monomers per asymmetric unit, revealed two unique binding configurations, shedding light on the molecular interactions and protein conformational flexibility underlying substrate and inhibitor binding by M(pro). Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.

negative: Current issue in tourism: The evolution of travel medicine research: A new research agenda for tourism? There has been considerable growth in interest in the field of travel medicine and the intersection with Tourism Studies since the 1990s. Yet this interest from a medical perspective is not new as a review of The Lancet, one of the most well-established medical journals, shows. What is new is the way in which the interest in travel medicine has developed across the science–social science divide and has now become one strand of a wider practitioner and academic interest in tourist well-being. With the exception of studies on technology and tourism and environmental science and tourism (e.g. climate change), this science–social science intersection has been comparatively absent from research in Tourism Studies. For this reason, this current issue's paper seeks to broadly outline the evolution of this area of study and some of the influential studies published to date along with some of the research agendas now emerging in this new area of study.

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

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

negative: Chapter 4 Human Viruses: Emergence and Evolution Abstract Many new viruses have emerged in the last five decades. These newer genetically active agents have a major impact on the public health systems worldwide. Most emerging infections appear to be caused by pathogens already present in the environment, brought out of obscurity or given a selective advantage by changing conditions and afforded an opportunity to infect new host populations. Also on rare occasions, a new variant may evolve and cause a new disease. Altered virus transmission because of deforestation and environment change, ecological changes and agricultural development, commerce, technology, microbial adaptation and change, breakdown of public health measures, and deficiencies in public health infrastructure are the reasons for emergence and reemergence of infectious diseases in general and viral infections in particular. Specific factors precipitating disease emergence can be identified in virtually all cases. Moreover, these factors are increasing in prevalence. This increase, together with the ongoing evolution of viral and microbial variants and selection for drug resistance, suggests that infections will continue to emerge and probably increase and emphasize the urgent need for effective surveillance and control. These viruses are rich source of emerging diseases due to the introduction of infections from other species in the zoonotic pool. In the near future, there is an urgent need to monitor collaboration between human–animal interface so that public health risks can be understood. A number of activities increase microbial traffic from animals to humans or disseminate microbes from isolated groups into new populations and as a result promote emergence and epidemics. In some cases, including many of the most novel infections, the agents are zoonotic crossing from their natural hosts into the human population because of many similarities. Vector-borne diseases also have a natural advantage of dissemination.

negative: Sonographic signs and patterns of COVID-19 pneumonia The pandemic of COVID-19 is seriously challenging the medical organization in many parts of the world. This novel corona virus SARS-CoV-2 has a specific tropism for the low respiratory airways, but causes severe pneumonia in a low percentage of patients. However, the rapid spread of the infection during this pandemic is causing the need to hospitalize a high number of patients. Pneumonia in COVID-19 has peculiar features and can be studied by lung ultrasound in the early approach to suspected patients. The sonographic signs are non-specific when considered alone, but observation of some aspects of vertical artifacts can enhance the diagnostic power of the ultrasound examination. Also, the combination of sonographic signs in patterns and their correlation with blood exams in different phenotypes of the disease may allow for a reliable characterization and be of help in triaging and admitting patients.

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

negative: A simple statistical physics model for the epidemic with incubation period Based on the classical SIR model, we derive a simple modification for the dynamics of epidemics with a known incubation period of infection. The model is described by a system of integro-differential equations. Parameters of our model directly related to epidemiological data. We derive some analytical results, as well as perform numerical simulations. We use the proposed model to analyze COVID-19 epidemic data in Armenia. We propose a strategy: organize a quarantine, and then conduct extensive testing of risk groups during the quarantine, evaluating the percentage of the population among risk groups and people with symptoms.

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: Power of Artificial Intelligence to Diagnose and Prevent Further COVID-19 Outbreak: A Short Communication Novel coronavirus-19 (2019-nCoV or COVID-19) is by far the most dangerous coronavirus ever identified for the third time in the three decades capable of infecting not only the animals but also the humans across the globe. Nearly 6000 deaths have been recorded due mainly to COVID-19 outbreak worldwide and more than 50% of these deaths appeared to have evolved from China where the virus was thought to originate. The endemicity of COVID-19 dramatically surpassed severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) that were so far discovered in 2003 and 2012 respectively. Thus, the World Health Organization (WHO) has declared the 2019-nCoV outbreak not only a public health emergency but also pandemic in nature. Currently, over 120 countries including Nigeria were reported to have more than 157,844 confirmed cases and 5,846 deaths due mainly to COVID-19 outbreak as of March 15, 2020, 10:55 GMT. Artificial Intelligence (AI) is widely used to aid in the prediction, detection, response, recovery of disease and making clinical diagnosis. In this study, we highlighted the power of AI in the containment and mitigation of the spread of COVID-19 outbreak in African countries such as Nigeria where human to human contact is apparently inevitable.

negative: Orthogonal genome-wide screenings in bat cells identify MTHFD1 as a target of broad antiviral therapy Bats are responsible for the zoonotic transmission of several major viral diseases including the 2003 SARS outbreak and the ongoing COVID-19 pandemic. While bat genomic sequencing studies have revealed characteristic adaptations of the innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the tolerance of viral infections in bats. Here we report the establishment and screening of genome-wide RNAi library and CRISPR library for the model megabat, Pteropus Alecto. We used the complementary RNAi and CRISPR libraries to interrogate Pteropus Alecto cells for infection with two different viruses, mumps virus and Influenza A virus, respectively. Screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C-1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells as well as in human cells. MTHFD1 inhibitor carolacton potently blocked replication of several RNA viruses including SARS-CoV-2. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad spectrum antiviral therapy.

negative: Study of knowledge, attitude, anxiety & perceived mental healthcare need in Indian population during COVID-19 pandemic Abstract Novel Corona Virus Disease (COVID-19) originating from China has rapidly crossed borders, infecting people throughout the whole world. This phenomenon has led to a massive public reaction; the media has been reporting continuously across borders to keep all informed about the pandemic situation. All these things are creating a lot of concern for people leading to heightened levels of anxiety. Pandemics can lead to heightened levels of stress; Anxiety is a common response to any stressful situation. This study attempted to assess the knowledge, attitude, anxiety experience, and perceived mental healthcare need among adult Indian population during the COVID-19 pandemic. An online survey was conducted using a semi-structured questionnaire using a non-probability snowball sampling technique. A total of 662 responses were received. The responders had a moderate level of knowledge about the COVID-19 infection and adequate knowledge about its preventive aspects. The attitude towards COVID-19 showed peoples' willingness to follow government guidelines on quarantine and social distancing. The anxiety levels identified in the study were high. More than 80 % of the people were preoccupied with the thoughts of COVID-19 and 72 % reported the need to use gloves, and sanitizers. In this study, sleep difficulties, paranoia about acquiring COVID-19 infection and distress related social media were reported in 12.5 %, 37.8 %, and 36.4 % participants respectively. The perceived mental healthcare need was seen in more than 80 % of participants. There is a need to intensify the awareness and address the mental health issues of people during this COVID-19 pandemic.

negative: Potential of age distribution profiles for the prediction of COVID-19 infection origin in a patient group The COVID-19 pandemic is a serious and global public health concern. It is now well known that COVID-19 cases may result in mild symptoms leading to patient recovery. However, severity of infection, fatality rates, and treatment responses across different countries, age groups, and demographic groups suggest that the nature of infection is diverse, and a timely investigation of the same is needed for evolving sound treatment and preventive strategies. This paper reports an the analysis of age distribution patterns in six groups of Indian COVID-19 patient populations based on their likely geographical origin of infection viz. the United Kingdom, North America, the European Union, the Middle East, and Asian countries. It was observed that patient groups stratified in this way had a distinct age profile and that some of these groups e.g. patient groups from Asia, the European Union, and the United Kingdom formed a different cluster than those from North America, the Middle East, and other regions. Patient age profiles of a population were found to be highly predictive of the group they belong to, and there are indications of their distinct recovery and fatality rates across gender. Altogether this study provides a scalable framework to estimate the source of infection in a new population of COVID-19 patients with unknown origin. It is also concluded that greater public availability of age and other demographic profile details of patients may be helpful in gaining robust insights into COVID-19 infection origins. Datasets and scripts used in this work are shared at http://covid.sciwhylab.org.

negative: To alert coinfection of COVID-19 and dengue virus in developing countries in the dengue-endemic area Coronavirus disease 2019 (CoVID-19) is a new outbreak infectious disease caused by SARS-CoV-2, which was originated from Wuhan in China and has now spread to the whole world. At the meantime, dengue was endemic in the Southeast Asia and South America, and a part of the patients shared the same symptoms, so, we write this paper to alert the clinicians to distinguish these two diseases.

negative: Anesthesia and COVID-19: What We Should Know and What We Should Do. Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, Hubei, China, and has spread to more than 200 other countries around the world. COVID-19 is a highly contagious disease with continuous human-to-human transmission. The origin of the virus is unknown. Airway manipulations and intubations, which are common during anesthesia procedures may increasingly expose anesthesia providers and intensive care unit team members to SARS-CoV-2. Through a comprehensive review of existing studies on COVID-19, this article presents the epidemiological and clinical characteristics of COVID-19, reviews current medical management, and suggests ways to improve the safety of anesthetic procedures. Owing to the highly contagious nature of the virus and the lack of therapeutic drugs or vaccines, precautions should be taken to prevent medical staff from COVID-19.

negative: A framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation.

negative: A double epidemic model for the SARS propagation BACKGROUND: An epidemic of a Severe Acute Respiratory Syndrome (SARS) caused by a new coronavirus has spread from the Guangdong province to the rest of China and to the world, with a puzzling contagion behavior. It is important both for predicting the future of the present outbreak and for implementing effective prophylactic measures, to identify the causes of this behavior. RESULTS: In this report, we show first that the standard Susceptible-Infected-Removed (SIR) model cannot account for the patterns observed in various regions where the disease spread. We develop a model involving two superimposed epidemics to study the recent spread of the SARS in Hong Kong and in the region. We explore the situation where these epidemics may be caused either by a virus and one or several mutants that changed its tropism, or by two unrelated viruses. This has important consequences for the future: the innocuous epidemic might still be there and generate, from time to time, variants that would have properties similar to those of SARS. CONCLUSION: We find that, in order to reconcile the existing data and the spread of the disease, it is convenient to suggest that a first milder outbreak protected against the SARS. Regions that had not seen the first epidemic, or that were affected simultaneously with the SARS suffered much more, with a very high percentage of persons affected. We also find regions where the data appear to be inconsistent, suggesting that they are incomplete or do not reflect an appropriate identification of SARS patients. Finally, we could, within the framework of the model, fix limits to the future development of the epidemic, allowing us to identify landmarks that may be useful to set up a monitoring system to follow the evolution of the epidemic. The model also suggests that there might exist a SARS precursor in a large reservoir, prompting for implementation of precautionary measures when the weather cools down.

negative: Moral Obligation, Public Leadership, and Collective Action for Epidemic Prevention and Control: Evidence from the Corona Virus Disease 2019 (COVID-19) Emergency To investigate the effect of villagers' moral obligation and village cadres' public leadership on villagers' collective action for epidemic prevention and control, against the background of the corona virus disease 2019 (COVID-19) emergency in China, we constructed models based on the institutional analysis and development (IAD) framework and employed principal component analysis (PCA) and ordered probit regression, drawing on survey data from 533 villagers in Henan province adjacent to the COVID-19 origin province, Hubei, China. The results indicate that: (1) generally, both moral obligation and public leadership as well as their constituent indicators contributed positively to collective action for COVID-19 prevention and control; (2) moreover, moral obligation and public leadership can strengthen each other's positive role in collective action for COVID-19 prevention and control. Based on the above findings, this paper suggests that villagers' moral obligation can be perfected through internalizing epidemic prevention and control norms into the villagers' moral norms by the way of villagers mastering the rural public health governance scheme. In addition, public leadership can be improved through professional training of village cadres and by motivating village elites to run for village cadres. With improved villagers' moral obligation and village cadres' public leadership, collective action for epidemic prevention and control could be more likely to be realized.

negative: Diseases of the Liver and Hepatobiliary System

negative: Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus Abstract This paper concerns study of the genome of the Wuhan Seafood Market isolate believed to represent the causative agent of the disease COVID-19. This is to find a short section or sections of viral protein sequence suitable for preliminary design proposal for a peptide synthetic vaccine and a peptidomimetic therapeutic, and to explore some design possibilities. The project was originally directed towards a use case for the Q-UEL language and its implementation in a knowledge management and automated inference system for medicine called the BioIngine, but focus here remains mostly on the virus itself. However, using Q-UEL systems to access relevant and emerging literature, and to interact with standard publically available bioinformatics tools on the Internet, did help quickly identify sequences of amino acids that are well conserved across many coronaviruses including 2019-nCoV. KRSFIEDLLFNKV was found to be particularly well conserved in this study and corresponds to the region around one of the known cleavage sites of the SARS virus that are believed to be required for virus activation for cell entry. This sequence motif and surrounding variations formed the basis for proposing a specific synthetic vaccine epitope and peptidomimetic agent. The work can, nonetheless, be described in traditional bioinformatics terms, and readily reproduced by others, albeit with the caveat that new data and research into 2019-nCoV is emerging and evolving at an explosive pace. Preliminary studies using molecular modeling and docking, and in that context the potential value of certain known herbal extracts, are also described.

negative: Coronavirus Disease-19: Summary of 2,370 Contact Investigations of the First 30 Cases in the Republic of Korea Between January 24(th) and March 10(th), a total of 2,370 individuals had contact with the first 30 cases of COVID-19. There were 13 individuals who contracted COVID-19 resulting in a secondary attack rate of 0.55% (95% CI 0.31–0.96). There were 119 household contacts, of which 9 individuals developed COVID-19 resulting in a secondary attack rate of 7.56% (95% CI 3.7–14.26).

negative: First COVID-19 suicide case in Bangladesh due to fear of COVID-19 and xenophobia: Possible suicide prevention strategies

negative: COVID-19 and what pediatric rheumatologists should know: a review from a highly affected country On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of the infection and a very high number of victims. Person-to-person spread mainly occurs via respiratory droplets and contact. The median incubation period is 5 days. The spectrum of respiratory symptoms may range from mild to severe, strictly depending on the age of the patient and the underlying comorbidities. In children COVID-19 related disease is less frequent and less aggressive. In Italy 1% of positive cases are under 18 years of age, and no deaths have been recorded before 29 years of age. For patients affected by rheumatic disease, despite the concerns related to the imbalance of their immune response and the effect of immunosuppressive treatments, there are still few data to understand the real consequences of this infection. Major scientific societies have issued recommendations to help rheumatologists in caring their patients. Interestingly, some of the drugs mostly used by rheumatologists appear to be promising in critical COVID-19 infected patients, where the hyperinflammation and cytokine storm seem to drive to the multiorgan failure. Pediatric rheumatologists are expected to play a supporting role in this new front of COVID-19 pandemic, both as general pediatricians treating infected children, and as rheumatologists taking care of their rheumatic patients, as well as offering their experience in the possible alternative use of immunomodulatory drugs.

negative: Pediatric SARS, H1N1, MERS, EVALI, and Now Coronavirus Disease (COVID-19) Pneumonia: What Radiologists Need to Know. OBJECTIVE. The purpose of this article is to review new pediatric lung disorders-including disorders that have occurred in recent years years such as severe acute respiratory syndrome (SARS), swine-origin influenza A (H1N1), Middle East respiratory syndrome (MERS), e-cigarette or vaping product use-associated lung injury (EVALI), and coronavirus disease (COVID-19) pneumonia-to enhance understanding of the characteristic imaging findings. CONCLUSION. Although the clinical symptoms of SARS, H1N1, MERS, EVALI, and COVID-19 pneumonia in pediatric patients may be nonspecific, some characteristic imaging findings have emerged or are currently emerging. It is essential for radiologists to have a clear understanding of the characteristic imaging appearances of these lung disorders in pediatric patients to ensure optimal patient care.

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: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) —a homologue of ACE—to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin–angiotensin–aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

negative: Erratum to: Bat origin of a new human coronavirus: there and back again We miscalculated identities of several genes, and the corrected Table 1 should be as follows.

negative: Tracking the Twitter attention around the research efforts on the COVID-19 pandemic The outbreak of the COVID-19 pandemic has been accompanied by a bulk of scientific research and related Twitter discussions. To unravel the public concerns about the COVID-19 crisis reflected in the science-based Twitter conversations, this study tracked the Twitter attention around the COVID-19 research efforts during the first three months of 2020. On the basis of nearly 1.4 million Twitter mentions of 6,162 COVID-19-related scientific publications, we investigated the temporal tweeting dynamic and the Twitter users involved in the online discussions around COVID-19-related research. The results show that the quantity of Twitter mentions of COVID-19-related publications was on rising. Scholarly-oriented Twitter users played an influential role in disseminating research outputs on COVID-19, with their tweets being frequently retweeted. Over time, a change in the focus of the Twitter discussions can be observed, from the initial attention to virological and clinical research to more practical topics, such as the potential treatments, the countermeasures by the governments, the healthcare measures, and the influences on the economy and society, in more recent times.

negative: A high frequency of allopolyploid speciation in the gymnospermous genus Ephedra and its possible association with some biological and ecological features The origin and evolution of polyploids have been studied extensively in angiosperms and ferns but very rarely in gymnosperms. With the exception of three species of conifers, all natural polyploid species of gymnosperms belong to Ephedra, in which more than half of the species show polyploid cytotypes. Here, we investigated the origin and evolution of polyploids of Ephedra distributed in the Qinghai–Tibetan Plateau (QTP) and neighbouring areas. Flow cytometry (FCM) was used to measure the ploidy levels of the sampled species that are represented by multiple individuals from different populations, and then, two single‐copy nuclear genes (LFY and DDB2) and two chloroplast DNA fragments were used to unravel the possible origins and maternal donors of the polyploids. The results indicate that the studied polyploid species are allopolyploids, and suggest that allotetraploidy is a dominant mode of speciation in Ephedra. The high percentage of polyploids in the genus could be related to some of its biological attributes such as vegetative propagation, a relatively high rate of unreduced gamete formation, and a small genome size relative to most other gymnosperms. Significant ecological divergences between allotetraploids and their putative progenitors were detected by PCAs and anova and Tukey's tests, with the exception of E. saxatilis. The overlap of geographical distributions and ecological niches of some diploid species could have provided opportunities for interspecific hybridization and allopolyploid speciation.

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

negative: Insights into the cross-species evolution of 2019 novel coronavirus

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: COVID-19: what is next for public health?

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

negative: An expanded One Health model: Integrating social science and One Health to inform study of the human-animal interface Abstract Zoonotic disease emergence is not a purely biological process mediated only by ecologic factors; opportunities for transmission of zoonoses from animals to humans also depend on how people interact with animals. While exposure is conditioned by the type of animal and the location in which interactions occur, these in turn are influenced by human activity. The activities people engage in are determined by social as well as contextual factors including gender, age, socio-economic status, occupation, social norms, settlement patterns and livelihood systems, family and community dynamics, as well as national and global influences. This paper proposes an expanded “One Health” conceptual model for human-animal exposure that accounts for social as well as epidemiologic factors. The expanded model informed a new study approach to document the extent of human exposure to animals and explore the interplay of social and environmental factors that influence risk of transmission at the individual and community level. The approach includes a formative phase using qualitative and participatory methods, and a representative, random sample survey to quantify exposure to animals in a variety of settings. The paper discusses the different factors that were considered in developing the approach, including the range of animals asked about and the parameters of exposure that are included, as well as factors to be considered in local adaptation of the generic instruments. Illustrative results from research using this approach in Lao PDR are presented to demonstrate the effect of social factors on how people interact with animals. We believe that the expanded model can be similarly operationalized to explore the interactions of other social and policy-level determinants that may influence transmission of zoonoses.

negative: Estimation of global case fatality rate of coronavirus disease 2019 (COVID-19) using meta-analyses: Comparison between calendar date and days since the outbreak of the first confirmed case. Since the outbreak of the coronavirus disease 2019 (COVID-19) in December of 2019 in China, the estimation of the pandemic case fatality rate (CFR) has been the focus and interest of many stakeholders. In this manuscript, we prove that the method of using the cumulative CFR is static and does not reflect the trend according to the daily change per unit of time. A proportion meta-analysis was carried out on CFR in every country reporting COVID-19 cases. Based on the results, we performed a meta-analysis for global COVID-19 CFR. Each analysis was performed on two different calculations of CFR: according to calendar date and according to days since the outbreak of the first confirmed case. We thus explored an innovative and original calculation of CFR concurrently based on the date of the first confirmed case as well as on a daily basis. For the first time, we showed that using meta-analyses, according to calendar date and days since the outbreak of the first confirmed case were different. We propose that CFR according to days since the outbreak of the first confirmed case might be a better predictor of the current CFR of COVID-19 and its kinetics. Keywords: COVID-19, case fatality rate, proportion meta-analysis, calendar date, days since first confirmed case.

negative: COVID-19 and gender-specific difference: Analysis of public surveillance data in Hong Kong and Shenzhen, China, from January 10 to February 15, 2020

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: 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: Feline coronavirus isolates from a part of Brazil: insights into molecular epidemiology and phylogeny inferred from the 7b gene The Feline coronavirus (FCoV) can lead to Feline infectious peritonitis (FIP), which the precise cause is still unknown. The theory of internal mutation suggests that a less virulent biotype of FCoV (FECV) would lead to another more pathogenic biotype (FIPV) capable of causing FIP. In this work, the 7b gene was amplified from 51 domestic cat plasma samples by semi-nested PCR and tested through phylogenetic and phylogeographical approaches. The 7b gene of Brazilian isolates displayed high conservation, a strong correlation between the geographic origin of the viral isolates and their genealogy, and its evolution was possibly shaped by a combination of high rates of nucleotide substitution and purifying selection.

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: 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: Pandemia COVID-19, la nueva emergencia sanitaria de preocupación internacional: una revisión./ [Pandemic COVID-19, the new health emergency of international concern: a review] In late December 2019, some cases of atypical pneumonia, at that time of unknown origin, were reported in Wuhan, China. Days later, the etiologic agent was identified as a new coronavirus. This new coronavirus was called SARS-CoV-2 and the disease it produces was named COVID-19. The origin of this new virus is presumed zoonotic, with bats being its probable vector. Due to the rapid number of infections and deaths that occurred first in China and later around the world, the infection of this virus quickly went from being an isolated outbreak in a Chinese region to becoming a health emergency of international concern and later, a pandemic. The purpose of this review is to study the most relevant and current information on the pathogen, as well as epidemiology, pathology, clinical features, transmission, prevention, and treatment of the disease.

negative: A large-scale COVID-19 Twitter chatter dataset for open scientific research -- an international collaboration As the COVID-19 pandemic continues its march around the world, an unprecedented amount of open data is being generated for genetics and epidemiological research. The unparalleled rate at which many research groups around the world are releasing data and publications on the ongoing pandemic is allowing other scientists to learn from local experiences and data generated in the front lines of the COVID-19 pandemic. However, there is a need to integrate additional data sources that map and measure the role of social dynamics of such a unique world-wide event into biomedical, biological, and epidemiological analyses. For this purpose, we present a large-scale curated dataset of over 152 million tweets, growing daily, related to COVID-19 chatter generated from January 1st to April 4th at the time of writing. This open dataset will allow researchers to conduct a number of research projects relating to the emotional and mental responses to social distancing measures, the identification of sources of misinformation, and the stratified measurement of sentiment towards the pandemic in near real time.

negative: Belief in Conspiracy Theory about COVID-19 Predicts Mental Health and Well-being -- A Study of Healthcare Staff in Ecuador Abstract Objective: We aim to provide the first evidence of belief in conspiracy theory regarding the COVID-19 virus as a predictor of the mental health and well-being of healthcare workers. Methods: We conducted a survey of 252 healthcare workers in Ecuador from April 10 to May 2, 2020. Results: In Ecuador, 32.54% of the sampled healthcare workers experienced distress disorder, and 28.17% had anxiety disorder. Compared to healthcare workers who were not sure where the virus originated, those who believed the virus was developed intentionally in a lab reported higher levels of distress and anxiety, and lower levels of job satisfaction and life satisfaction. Older healthcare workers and those who exercise more reported higher job satisfaction. Married healthcare workers, those who exercise more, and those not infected reported higher life satisfaction. Conclusion: This paper identifies belief in a COVID-19 conspiracy theory as an important predictor of distress, anxiety, and job and life satisfaction of healthcare workers. It enables mental health services to better target and help mentally vulnerable healthcare workers during the ongoing COVID-19 pandemic.

negative: SARS‐CoV‐2 viral spike G614 mutation exhibits higher case fatality rate AIM: The COVID pandemic is caused by infection with the SARS‐CoV‐2 virus. The major mutation detected to date in the SARS‐CoV‐2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation. RESULT: Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible. CONCLUSION: These results imply that G614 is a more pathogenic strain of SARS‐CoV‐2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID‐19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection.

negative: Why does the coronavirus spread so easily between people?

negative: Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world to cause thousands of mortalities each day. Poor responses from the authorities to the spread of infection, lack of effective measures for prevention, unavailability of promising treatment options, and sufficient diagnostic options have created an alarming for the world. The transmission routes from human to human of SARS-CoV-2 can be the direct transmission, droplet inhalation transmission, contact transmission, transmission through saliva, and transmission via fecal–oral routes. Due to the asymptomatic spread of SARS-CoV-2's, developing control and prevention measures is challenging. Implementing proper strategies addressing the infection control and clinical supplies, understanding the mechanism associated with pathogenesis, advancing in preventive measures and effective treatment and diagnostic options are necessary to control the ongoing pandemic. In this article, we briefly discuss the features, entry mechanism, infectiousness, and health consequences related to the COVID-19 outbreak.

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

negative: 2019 Novel coronavirus infection and gastrointestinal tract Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. As of Feb 17th, 2020, statistical data show that the outbreak constitutes an epidemic threat in China, where the exponential increase in patients has reached 75114 confirmed cases, with 2239 deaths. Different from SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus) infection, the initial presentations or the chief complain of some patients with the 2019 novel coronavirus (COVID-19) were gastrointestinal symptoms. So we call upon all the first-line medical staff to be cautious and pay more attention to those untypical patients especially from the epidemic area. Besides, as the viral nucleic acids could be found in the fecal samples and anal swabs of some patients with COVID-19 infection, the possibility of fecal-oral transmission need to be took into account. Based on the previously and recently studies, we speculate that COVID-19 may have some relationship with the gut microbiota through angiotensin-converting enzyme 2 (ACE2) receptor, thus targeting gut microbiota might be a new therapeutic option for the treatment of virus-related pneumonia. This article is protected by copyright. All rights reserved.

negative: Double-Quencher Probes Improved the Detection Sensitivity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by One-Step RT-PCR Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerges in Wuhan City, Hubei Province, spreads worldwide, and threats the human life. The detection of SARS-CoV-2 is important for the prevention of the outbreak and management of patients. Real-time reverse-transcription polymerase chain reaction (RT-PCR) assay detected the virus in clinical laboratory. Methods: This study utilized primers and single-quencher probes in accordance with the Centers for Disease Control and Prevention (CDC) in the USA and the National Institute of Infectious Diseases (NIID) in Japan. Moreover, we designed the double-quencher probes (YCH assay) according to the oligonucleotide sequence established by NIID. Using these assays, we conducted a one-step real-time RT-PCR with serial DNA positive control to assess the detection sensitivity. Results: The threshold cycle (Ct) value of RT-PCR was relatively low in CDC and YCH assays compared to NIID assay. Serial dilution assay showed that both CDC and YCH assays could detect a low-copy number of DNA positive control. The background fluorescent signal at the baseline was lower in YCH than that of NIID. Conclusion: Double-quencher probes decreased background fluorescent signal and improved detection sensitivity of SARS-CoV-2.

negative: Experimental infection of a US spike-insertion deletion porcine epidemic diarrhea virus in conventional nursing piglets and cross-protection to the original US PEDV infection Although the original US porcine epidemic diarrhea virus (PEDV) was confirmed as highly virulent by multiple studies, the virulence of spike-insertion deletion (S-INDEL) PEDV strains is undefined. In this study, 3–4 day-old conventional suckling piglets were inoculated with S-INDEL PEDV Iowa106 (4 pig litters) to study its virulence. Two litters of age-matched piglets were inoculated with either the original US PEDV PC21A or mock as positive and negative controls, respectively. Subsequently, all pigs were challenged with the original US PEDV PC21A on 21–29 days post-inoculation (dpi) to assess cross-protection. All S-INDEL Iowa106- and the original US PC21A-inoculated piglets developed diarrhea. However, the severity of clinical signs, mortality (0–75%) and fecal PEDV RNA shedding titers varied among the four S-INDEL Iowa106-inoculated litters. Compared with the original PC21A, piglets euthanized/died acutely from S-INDEL Iowa106 infection had relatively milder villous atrophy, lower antigen scores and more limited intestinal infection. Two of four S-INDEL Iowa106-infected sows and the original PC21A-infected sow showed anorexia and watery diarrhea for 1–4 days. After the original PC21A challenge, a subset (13/16) of S-INDEL Iowa106-inoculated piglets developed diarrhea, whereas all (5/5) and no (0/4) pigs in the mock and original PC21A-inoculated pigs had diarrhea, respectively. Our results suggest that the virulence of S-INDEL PEDV Iowa106 was less than the original US PEDV PC21A in suckling pigs, with 100% morbidity and 18% (6/33) overall (0–75%) mortality in suckling pigs depending on factors such as the sow’s health and lactation and the piglets’ birth weight. Prior infection by S-INDEL Iowa106 provided partial cross-protection to piglets against the original PC21A challenge at 21–29 dpi.

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

negative: Management of rheumatic diseases in the times of COVID-19 pandemic- perspectives of rheumatology practitioners from India Background. The Coronavirus disease 19 (COVID-19) pandemic has led to widespread concerns about the risk of infection in patients with rheumatic diseases (RD) receiving disease modifying ant-rheumatic drugs (DMARDs) and other immunosuppressants (IS). Methods. A SurveyMonkey based electronic survey was conducted amongst members of the Indian Rheumatology Association to understand the need for changes in prevailing practices. Results. Of the 861 invitees, 221 responded. In the wake of the pandemic, 47.5% would reduce biological DMARDs (bDMARDs) while only 12.2% would reduce the use of conventional synthetic DMARDs. 64.2% were likely to defer change in IS, the reluctance being most with rituximab (58.3%) followed by cyclophosphamide (53.3%), anti-tumor necrosis factor alpha agents (52.4%) and Janus kinase inhibitors (34.39%). Hydroxychloroquine was the preferred choice (81.9%) for the treatment of COVID-19 followed by protease inhibitors (22.1%) and intravenous immunoglobulin (8.1%). Chloroquine was less preferred (19%). More than two-thirds (70.5%) believed that COVID-19 might trigger macrophage activation syndrome. Social distancing (98.1%) and hand hygiene (74.6%) were recommended by majority. 62.8% would avoid touch for clinical examination whenever feasible. Conclusion. Most rheumatologists perceived the need to change treatment of RDs during the COVID-19 pandemic; reduce immunosuppression and defer the usage of rituximab and bDMARDs.

negative: Top Concerns of Tweeters During the COVID-19 Pandemic: Infoveillance Study BACKGROUND: The recent coronavirus disease (COVID-19) pandemic is taking a toll on the world’s health care infrastructure as well as the social, economic, and psychological well-being of humanity. Individuals, organizations, and governments are using social media to communicate with each other on a number of issues relating to the COVID-19 pandemic. Not much is known about the topics being shared on social media platforms relating to COVID-19. Analyzing such information can help policy makers and health care organizations assess the needs of their stakeholders and address them appropriately. OBJECTIVE: This study aims to identify the main topics posted by Twitter users related to the COVID-19 pandemic. METHODS: Leveraging a set of tools (Twitter’s search application programming interface (API), Tweepy Python library, and PostgreSQL database) and using a set of predefined search terms (“corona,” “2019-nCov,” and “COVID-19”), we extracted the text and metadata (number of likes and retweets, and user profile information including the number of followers) of public English language tweets from February 2, 2020, to March 15, 2020. We analyzed the collected tweets using word frequencies of single (unigrams) and double words (bigrams). We leveraged latent Dirichlet allocation for topic modeling to identify topics discussed in the tweets. We also performed sentiment analysis and extracted the mean number of retweets, likes, and followers for each topic and calculated the interaction rate per topic. RESULTS: Out of approximately 2.8 million tweets included, 167,073 unique tweets from 160,829 unique users met the inclusion criteria. Our analysis identified 12 topics, which were grouped into four main themes: origin of the virus; its sources; its impact on people, countries, and the economy; and ways of mitigating the risk of infection. The mean sentiment was positive for 10 topics and negative for 2 topics (deaths caused by COVID-19 and increased racism). The mean for tweet topics of account followers ranged from 2722 (increased racism) to 13,413 (economic losses). The highest mean of likes for the tweets was 15.4 (economic loss), while the lowest was 3.94 (travel bans and warnings). CONCLUSIONS: Public health crisis response activities on the ground and online are becoming increasingly simultaneous and intertwined. Social media provides an opportunity to directly communicate health information to the public. Health systems should work on building national and international disease detection and surveillance systems through monitoring social media. There is also a need for a more proactive and agile public health presence on social media to combat the spread of fake news.

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: Characteristics of Metazoan DNA Replication Origins DNA replication in metazoan cells initiates at multiple discrete chromosomal sites called replication origins. Recent genome-wide studies have mapped thousands of origins in animal and plant cells, but without yielding a distinct and universal consensus sequence. However, origin-associated regions with particular base composition features have been identified, such as the G-rich OGRE motif, predicted to form G-quadruplexes. Epigenetic marks such as histone modifications that promote open chromatin also favor origin formation. Before DNA replication can initiate at origins, they need to be “licensed” by the binding of the origin recognition complex (ORC) and other proteins to form pre-replication and pre-initiation complexes. Origin-associated proteins are themselves subject to multilayered regulation, notably by posttranslational modification and proteasomal degradation. Origins are organized into replicons and replicon clusters, whose firing occurs at discrete subnuclear bodies known as replication foci. A still poorly characterized nuclear matrix structure might be involved in the attachment of replication units and the formation of replication foci. Preferential genomic sequences responsible for these attachments have been reported, as well as factors playing roles in their regulation. There appears to be great flexibility in the choice of origins used in each S-phase, being affected by factors including cell identity and replication stresses. Origin selection also changes dramatically during embryogenesis in concert with developmental signaling pathways. Dysregulation of origin positioning and recognition are implicated in human disease, as mutations in origin-binding proteins have been found in developmental disorders, and expansions in repeat-containing genomic regions promote genome instability. This chapter summarizes current understanding about replication origins, the most recent discoveries, and outlines key unanswered questions in this exciting field.

negative: COVID-19: Disease, management, treatment, and social impact 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: Peptide-like and small-molecule inhibitors against Covid-19 Coronavirus disease strain (SARS-CoV-2) was discovered in 2019, and it is spreading very fast around the world causing the disease Covid-19. Currently, more than 1.6 million individuals are infected, and several thousand are dead across the globe because of Covid-19. Here, we utilized the in-silico approaches to identify possible protease inhibitors against SARS-CoV-2. Potential compounds were screened from the CHEMBL database, ZINC database, FDA approved drugs and molecules under clinical trials. Our study is based on 6Y2F and 6W63 co-crystallized structures available in the protein data bank (PDB). Seven hundred compounds from ZINC/CHEMBL databases and fourteen hundred compounds from drug-bank were selected based on positive interactions with the reported binding site. All the selected compounds were subjected to standard-precision (SP) and extra-precision (XP) mode of docking. Generated docked poses were carefully visualized for known interactions within the binding site. Molecular mechanics-generalized born surface area (MM-GBSA) calculations were performed to screen the best compounds based on docking scores and binding energy values. Molecular dynamics (MD) simulations were carried out on four selected compounds from the CHEMBL database to validate the stability and interactions. MD simulations were also performed on the PDB structure 6YF2F to understand the differences between screened molecules and co-crystallized ligand. We screened 300 potential compounds from various databases, and 66 potential compounds from FDA approved drugs. Cobicistat, ritonavir, lopinavir, and darunavir are in the top screened molecules from FDA approved drugs. The screened drugs and molecules may be helpful in fighting with SARS-CoV-2 after further studies.

negative: Canadian Geriatrics Society COVID-19 Recommendations for Older Adults. What Do Older Adults Need To Know?

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

negative: Highlights of traditional Chinese medicine frontline expert advice in the China national guideline for COVID-19 Abstract Introduction The World Health Organization has declared the coronavirus disease (COVID-19) as a pandemic on 11 March 2020, after the number of confirmed cases outside China increased 13-fold. As the epicentre of the initial outbreak, China has been updating the National COVID-19 Diagnostic and Treatment Guideline with up-to-date information about the disease. To facilitate the implementation of integrative Chinese–Western Medicine in COVID-19 management, Traditional Chinese medicine (TCM) has been recommended in recent editions of the national guideline. Methods The national guideline summarised the opinions and frontline experience of medical experts across the country to provide by far the best management for COVID-19. We extracted the case definition and clinical classifications of COVID-19 in China along with relevant TCM treatments cited in the seventh edition of the guideline, with an intend to disseminate practical information to TCM practitioners and researchers around the world. Results We presented the most recent case definition, clinical classifications, and relevant TCM treatments of COVID-19 in accordance to recommendations of the Chinese guideline. TCM treatments are stratified into two groups based on patients’ disease status. Four types of Chinese patent medicines are recommended for suspected COVID-19 cases. Several herbal formulae are recommended for confirmed COVID-19 cases according to their clinical classification and TCM pattern diagnoses. Two herbal formulae are also recommended for rehabilitation of recovering cases. Conclusion To control the waves of COVID-19 outbreak, countries must ensure the adherence of their citizens to local public health measures. Medical professionals should diagnose and treat patients according to up-to-date guidelines. Future evaluation of the outcomes of implementing TCM recommendations will strengthen the evidence base for COVID-19 management for the sake of public health and the internationalisation of TCM.

negative: Lessons from China When Performing Neurosurgical Procedures During the Coronavirus Disease 2019 (COVID-19) Pandemic The novel coronavirus disease 2019 (COVID-19) pandemic poses a substantial threat to the health of health care personnel on the front line of caring for patients with COVID-19. The Centers for Medicare and Medicaid Services have announced that all nonessential planned surgeries and procedures should be postponed until further notice and only urgent procedures should proceed. Neurologic surgeries and procedures should not be delayed under the circumstance in which it is essential at saving a life or preserving functioning of the central nervous system. With the intent to advise the neurosurgery team on how to adequately prepare and safely perform neurosurgical procedures on confirmed and suspected patients with COVID-19, we discuss considerations and recommendations based on the lessons and experience shared by neurosurgeons in China. Perioperative and intraoperative strategies, considerations, as well as challenges arisen under the specific circumstance have been discussed. In addition, a case of a ruptured aneurysm in a suspected patient with COVID-19 is reported. It is advised that all health care personnel who immediately participate in neurosurgical surgeries and procedures for confirmed and suspected patients with COVID-19 should take airborne precautions and wear enhanced personal protective equipment. Following the proposed guidance, urgent neurosurgical surgeries and procedures can be safely performed for the benefit of critical patients with or suspected for COVID-19.

negative: The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 215,461 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers. Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses. Acute hemorrhagic necrotizing encephalopathy is associated to the cytokine storm. A frontal hypoperfusion syndrome has been identified. There are isolated reports of seizures, encephalopathy, meningitis, encephalitis, and myelitis. The neurological diseases affecting the PNS and muscle in COVID-19 are less frequent and include Guillain-Barré syndrome; Miller Fisher syndrome; polyneuritis cranialis; and rare instances of viral myopathy with rhabdomyolysis. The main conclusion of this review is the pressing need to define the neurology of COVID-19, its frequency, manifestations, neuropathology and pathogenesis. On behalf of the World Federation of Neurology we invite national and regional neurological associations to create local databases to report cases with neurological manifestations observed during the on-going pandemic. International neuroepidemiological collaboration may help define the natural history of this worldwide problem.

negative: Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.

negative: SARS-CoV-2 is sensitive to type I interferon pretreatment. SARS-CoV-2, a novel coronavirus (CoV), has recently emerged causing an ongoing outbreak of viral pneumonia around the world. While genetically distinct from the original SARS-CoV, both group 2B CoVs share similar genome organization and origins to coronaviruses harbored in bats. Importantly, initial guidance has used insights from SARS-CoV infection to inform treatment and public health strategies. In this report, we evaluate type-I Interferon (IFN-I) sensitivity of SARS-CoV-2 relative to the original SARS-CoV. Our results indicate that while SARS-CoV-2 maintains similar viral replication kinetics to SARS-CoV in Vero cell, the novel CoV is much more sensitive to IFN-I pretreatment. Examining transcriptional factor activation and interferon stimulated gene (ISG) induction, SARS-CoV-2 in the context of type I IFN induces phosphorylation of STAT1 and increased ISG proteins. In contrast, the original SARS-CoV has no evidence for STAT1 phosphorylation or ISG protein increases even in the presence of type I IFN pretreatment. Next, we examined IFN competent Calu3 2B4 cells finding SARS-CoV-2 had reduced viral replication relative to SARS-CoV and induced STAT1 phosphorylation late during infection. Finally, we examined homology between SARS-CoV and SARS-CoV-2 in viral proteins shown to be interferon antagonist. The absence of open reading frame (ORF) 3b and significant changes to ORF6 suggest the two key IFN antagonists may not maintain equivalent function in SARS-CoV-2. Together, the results identify key differences in susceptibility to the IFN-I response between SARS-CoV and SARS-CoV-2. that could help inform disease progression, treatment options, and animal model development.

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

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

negative: Human and novel coronavirus infections in children: a review Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. ABBREVIATIONS: 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Guérin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization.

negative: When will the battle against novel coronavirus end in Wuhan: a SEIR modeling analysis Recent outbreak of 2019-nCoV in Wuhan raised serious public health concerns. By February 15, 2020 in Wuhan, the total number of confirmed infection cases has reached 37,914, and the number of deaths has reached 1123, accounting for 56.9% of the total confirmed cases and 73.7% of the total deaths in China. People are eager to know when the epidemic will be completely controlled and when people's work and life will be on the right track. In this study we analyzed the epidemic dynamics and trend of 2019-nCoV in Wuhan by using the data after the closure of Wuhan city till February 12, 2020 based on the SEIR modeling method. The optimal parameters were estimated as R0=1.44 (interquartile range: 1.40-1.47)，TI=14 (interquartile range: 14-14) and TE=3.0 (interquartile range: 2.8-3.1). Based on these parameters, the number of infected individuals in Wuhan city may reach the peak around February 19 at about 45,000 people. Once entering March, the epidemic would gradually decline, and end around the late March. It is worth noting that the above prediction is based on the assumption that the number of susceptible population N = 200,000 will not increase. If the epidemic situation is not properly controlled, the peak of infected number can be further increased and the peak time will be a little postponed. It was expected that the epidemic would subside in early March, and disappear gradually towards the late March.

negative: The Second Worldwide Wave of Interest in Coronavirus since the COVID-19 Outbreaks in South Korea, Italy and Iran: A Google Trends Study The recent emergence of a new coronavirus, COVID-19, has gained extensive coverage in public media and global news. As of 24 March 2020, the virus has caused viral pneumonia in tens of thousands of people in Wuhan, China, and thousands of cases in 184 other countries and territories. This study explores the potential use of Google Trends (GT) to monitor worldwide interest in this COVID-19 epidemic. GT was chosen as a source of reverse engineering data, given the interest in the topic. Current data on COVID-19 is retrieved from (GT) using one main search topic: Coronavirus. Geographical settings for GT are worldwide, China, South Korea, Italy and Iran. The reported period is 15 January 2020 to 24 March 2020. The results show that the highest worldwide peak in the first wave of demand for information was on 31 January 2020. After the first peak, the number of new cases reported daily rose for 6 days. A second wave started on 21 February 2020 after the outbreaks were reported in Italy, with the highest peak on 16 March 2020. The second wave is six times as big as the first wave. The number of new cases reported daily is rising day by day. This short communication gives a brief introduction to how the demand for information on coronavirus epidemic is reported through GT.

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

negative: First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model BACKGROUND: Similar to outbreaks of many other infectious diseases, success in controlling the novel 2019 coronavirus infection requires a timely and accurate monitoring of the epidemic, particularly during its early period with rather limited data while the need for information increases explosively. METHODS: In this study, we used a second derivative model to characterize the coronavirus epidemic in China with cumulatively diagnosed cases during the first 2 months. The analysis was further enhanced by an exponential model with a close-population assumption. This model was built with the data and used to assess the detection rate during the study period, considering the differences between the true infections, detectable and detected cases. RESULTS: Results from the second derivative modeling suggest the coronavirus epidemic as nonlinear and chaotic in nature. Although it emerged gradually, the epidemic was highly responsive to massive interventions initiated on January 21, 2020, as indicated by results from both second derivative and exponential modeling analyses. The epidemic started to decelerate immediately after the massive actions. The results derived from our analysis signaled the decline of the epidemic 14 days before it eventually occurred on February 4, 2020. Study findings further signaled an accelerated decline in the epidemic starting in 14 days on February 18, 2020. CONCLUSIONS: The coronavirus epidemic appeared to be nonlinear and chaotic, and was responsive to effective interventions. The methods used in this study can be applied in surveillance to inform and encourage the general public, public health professionals, clinicians and decision-makers to take coordinative and collaborative efforts to control the epidemic.

negative: Building a COVID-19 Vulnerability Index COVID-19 is an acute respiratory disease that has been classified as a pandemic by the World Health Organization. Information regarding this particular disease is limited, however, it is known to have high mortality rates, particularly among individuals with preexisting medical conditions. Creating models to identify individuals who are at the greatest risk for severe complications due to COVID-19 will be useful to help for outreach campaigns in mitigating the diseases worst effects. While information specific to COVID-19 is limited, a model using complications due to other upper respiratory infections can be used as a proxy to help identify those individuals who are at the greatest risk. We present the results for three models predicting such complications, with each model having varying levels of predictive effectiveness at the expense of ease of implementation.

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

negative: COVID-19: a crash test for biomedical publishing? The effect of COVID-19 on biomedical publishing (BP) (i.e. scientific biomedical periodicals continuously published by research communities or commercial publishers) has not been deeply explored. To estimate the immediate COVID-19 impact on BP, we have assessed PubMed-indexed articles about COVID-19 (PMIAC) from December 2019 to April 2020. PMIAC have been classified according to publication date, country, and journals for evaluation of time-, region- and scientometric-dependant impact of COVID-19 on BP and have been curated manually (i.e. each entry has been individually analyzed). PMIAC analysis reflects geographic and temporal parameters of outbreak spread. A major BP problem is related to the fact that only 40% of articles report/review/analyze data. Another BP weakness is the clusterization of "highly-trusted" publications according to countries of origin and "highly impacting" journals. Finally, a problem highlighted by COVID-19 crisis is the increased specification of biomedical research. To solve the problem, analytical reviews integrating data from different areas of biology and medicine are required. The data on PMIAC suggest priority of "what is published" over "where it is published" and "who are the authors". We believe that our brief analysis may help to shape forthcoming BP to become more effective in solving immediate problems resulted from global threats.

negative: 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.

negative: Mode and tempo of human hepatitis virus evolution Human viral hepatitis, a major cause of morbidity and mortality worldwide, is caused by highly diverse viruses with different genetic, ecological, and pathogenetic features. Technological advances that allow throughput sequencing of viral genomes, as well as the development of computational tools to analyze such genome data, have largely expanded our knowledge on the host range and evolutionary history of human hepatitis viruses. Thus, with the exclusion of hepatitis D virus, close or distant relatives of these human pathogens were identified in a number of domestic and wild mammals. Also, sequences of human viral strains isolated from different geographic locations and over different time-spans have allowed the application of phylogeographic and molecular dating approaches to large viral phylogenies. In this review, we summarize the most recent insights into our understanding of the evolutionary events and ecological contexts that determined the origin and spread of human hepatitis viruses.

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: Looming threat of COVID-19 infection in Africa: act collectively, and fast

negative: COVID-19: The first documented coronavirus pandemic in history The novel human coronavirus disease COVID-19 has become the fifth documented pandemic since the 1918 flu pandemic. COVID-19 was first reported in Wuhan, China, and subsequently spread worldwide. The coronavirus was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses based on phylogenetic analysis. SARS-CoV-2 is believed to be a spillover of an animal coronavirus and later adapted the ability of human-to-human transmission. Because the virus is highly contagious, it rapidly spreads and continuously evolves in the human population. In this review article, we discuss the basic properties, potential origin, and evolution of the novel human coronavirus. These factors may be critical for studies of pathogenicity, antiviral designs, and vaccine development against the virus.

negative: 新型冠状病毒肺炎疫情期间肺癌患者临床管理 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: Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.

negative: Therapeutic strategies for critically ill patients with COVID-19 Since the 2019 novel coronavirus disease (COVID-19) outbreak originated from Wuhan, Hubei Province, China, at the end of 2019, it has become a clinical threat to the general population worldwide. Among people infected with the novel coronavirus (2019-nCoV), the intensive management of the critically ill patients in intensive care unit (ICU) needs substantial medical resource. In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and influenza. These treatments are referable before the vaccine and specific drugs are available for COVID-19.

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

negative: Monoclonal Antibody as a Potential Anti-COVID-19 Coronavirus disease 2019 (COVID-19) is expanding rapidly, which made it as one of top priorities for scientists to develop novel treatment strategies. Researchers are racing to develop treatments based on antibodies to block and/or neutralize the coronavirus in affected patients. Initially, the genetic and structural similarity of the virus to severe acute respiratory syndrome coronavirus (SARS-CoV) created the potential for understanding disease pathogenesis. Researchers have published reports of specific monoclonal antibodies against to COVID-19 (B38, H4, 47D11) and hope that this method is effective. As well as studies on patients who are plasma therapy, the patient's condition shows improvement. The evidence for these studies is very promising and demonstrates the potential of monoclonal antibody therapy as a therapeutic approach and prevention of covid-19 infection.

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: Correction to: Venous thromboembolism and heparin use in COVID-19 patients: juggling between pragmatic choices, suggestions of medical societies and the lack of guidelines In the original version of the article, the article title was processed incorrectly. The correct article title is "Venous Thromboembolism and Heparin Use in COVID-19 Patients: Juggling between Pragmatic Choices, Suggestions of Medical Societies and the Lack of Guidelines". This has been corrected with this erratum and the original article has also been updated to reflect the change in article title.

negative: An alternative approach to minimize the risk of coronavirus (Covid-19) and similar infections. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain that was discovered in 2019 and has not been previously identified in humans. On December 31st 2019 World Health Organization (WHO) was informed of a cluster of cases with pneumonia of unknown origin from Wuhan City, Hubei province of China. The WHO announced in February 2020 that COVID-19 is the official name of the coronavirus diseases. A total of 519,899 confirmed cases with 23,592 deaths linked to this pathogen as on March 27, 2020 have been reported. Due to increasing number of infected people across the continents and huge loss to human life, the WHO has declared the novel COVID-19 outbreak a pandemic. A pandemic is defined as the "worldwide spread" of a new disease. Currently, no COVID-19 specific treatments have been approved by the United States Food and Drug Administration (US-FDA). However, the current treatment options include hydroxychloroquine, tocilizumab, remdesivir, lopinavir-ritonavir (Kaletra®), and nitazoxanide. In recent past, some natural herbal compounds have demonstrated encouraging anti-viral properties. This article attempted to summarize available information on the reported anti-viral activity of some natural products.

negative: Rice endosperm is cost‐effective for the production of recombinant griffithsin with potent activity against HIV Protein microbicides containing neutralizing antibodies and antiviral lectins may help to reduce the rate of infection with human immunodeficiency virus (HIV) if it is possible to manufacture the components in large quantities at a cost affordable in HIV‐endemic regions such as sub‐Saharan Africa. We expressed the antiviral lectin griffithsin (GRFT), which shows potent neutralizing activity against HIV, in the endosperm of transgenic rice plants (Oryza sativa), to determine whether rice can be used to produce inexpensive GRFT as a microbicide ingredient. The yield of (OS)GRFT in the best‐performing plants was 223 μg/g dry seed weight. We also established a one‐step purification protocol, achieving a recovery of 74% and a purity of 80%, which potentially could be developed into a larger‐scale process to facilitate inexpensive downstream processing. (OS)GRFT bound to HIV glycans with similar efficiency to GRFT produced in Escherichia coli. Whole‐cell assays using purified (OS)GRFT and infectivity assays using crude extracts of transgenic rice endosperm confirmed that both crude and pure (OS)GRFT showed potent activity against HIV and the crude extracts were not toxic towards human cell lines, suggesting they could be administered as a microbicide with only minimal processing. A freedom‐to‐operate analysis confirmed that GRFT produced in rice is suitable for commercial development, and an economic evaluation suggested that 1.8 kg/ha of pure GRFT could be produced from rice seeds. Our data therefore indicate that rice could be developed as an inexpensive production platform for GRFT as a microbicide component.

negative: Epidemiological Characteristics of Coronavirus Disease 2019 (COVID-19) Patients in IRAN: A single Center Study • The majority of cases were in the age group of 50 to 60 years of old. • A total of 2964 cases of COVID-19 were investigated. • The male-to-female ratio was 1.93:1. • A significant effect of age, gender and comorbidities on the mortality. • The Case Fatality Rate among understudy cases was 8.06%.

negative: One size does not fit all – Patterns of vulnerability and resilience in the COVID-19 pandemic and why heterogeneity of disease matters

negative: Caring for persons in detention suffering with mental illness during the Covid-19 outbreak

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

negative: 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: Introduction: Conceptualizing and Partitioning the Emergence Process of Zoonotic Viruses from Wildlife to Humans This introduction provides a telegraphic overview of the processes of zoonotic viral emergence, the intricacies of host–virus interactions, and the distinct role of biological transitions and modifying factors. The process of emergence is conceptualized as two transition stages which are common and required for all disease emergence, (1) human contact with the infectious agent and (2) cross-species transmission of the agent, and two transition stages which are not required for emergence and appear unavailable to many zoonotic pathogens, (3) sustained human-to-human transmission and (4) genetic adaptation to the human host. The latter two transitions are presumably prerequisites for the pandemic emergence of a pathogen. The themes introduced herein are amplified and explored in detail by the contributors to this volume. Each author explores the mechanisms and unique circumstances by which evolution, biology, history, and current context have contrived to drive the emergence of different zoonotic agents by a series of related events; although recognizable similarities exist among the events leading to emergence the details and circumstances are never repetitive.

negative: MERS-coronavirus: From discovery to intervention Middle East respiratory syndrome coronavirus (MERS-CoV) still causes outbreaks despite public awareness and implementation of health care measures, such as rapid viral diagnosis and patient quarantine. Here we describe the current epidemiological picture of MERS-CoV, focusing on humans and animals affected by this virus and propose specific intervention strategies that would be appropriate to control MERS-CoV. One-third of MERS-CoV patients develop severe lower respiratory tract infection and succumb to a fatal outcome; these patients would require effective therapeutic antiviral therapy. Because of the lack of such intervention strategies, supportive care is the best that can be offered at the moment. Limiting viral spread from symptomatic human cases to health care workers and family members, on the other hand, could be achieved through prophylactic administration of MERS-CoV neutralizing antibodies and vaccines. To ultimately prevent spread of the virus into the human population, however, vaccination of dromedary camels – currently the only confirmed animal host for MERS-CoV – may be the best option to achieve a sustained drop in human MERS cases in time. In the end, a One Health approach combining all these different efforts is needed to tackle this zoonotic outbreak.

negative: Estimating pre-symptomatic transmission of COVID-19: a secondary analysis using published data Background: Understanding the extent of virus transmission that can occur before symptom onset is vital for targeting control measures against the global pandemic of COVID-19. Objective: Estimation of (1) the proportion of pre-symptomatic transmission of COVID-19 that can occur and (2) timing of transmission relative to symptom onset. Design: Secondary analysis of published data Data sources: Meta-analysis of COVID-19 incubation period and a rapid systematic review of serial interval and generation time, which are published separately. Methods: Simulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset were calculated and the proportion of pre-symptomatic transmission was estimated. Results: A total of 23 estimates of serial interval and five estimates of generation time from 17 publications were included. These came from nine different data source categories (presented here in descending order of the proportion of pre-symptomatic transmission): Hong Kong, Tianjin, pooled data from Hong Kong and Shenzhen, Singapore, Mainland China excluding Hubei, mixed sources, Shenzhen, northern Italy and Wuhan. Transmission time relative to symptom onset ranged from a mean of 2.05 days before symptom onset for Hong Kong to 1.72 days after symptom onset for Wuhan. Proportion of pre-symptomatic transmission ranged from 33.7% in Wuhan to 72.7% in Hong Kong. Based on individual estimates, transmission time relative to symptom onset ranged from mean of 2.95 days before symptom onset to 1.72 days after symptom onset and proportion of pre-symptomatic transmission ranged from 33.7% to 79.9%. Simple unweighted pooling of estimates based on serial intervals resulted in a mean time of transmission of 0.67 days before symptoms, and an estimated 56.1% of transmission occurring in the pre-symptomatic period. Conclusions: Contact rates between symptomatic infectious and susceptible people are likely to influence the proportion of pre-symptomatic transmission. There is substantial potential for pre-symptomatic transmission of COVID-19 in a range of different contexts. Our work suggests that transmission of SARS-CoV-2 is most likely in the day before symptom onset whereas estimates suggesting most pre-symptomatic transmission highlighted a mean transmission times almost 3 days before symptom onset. These findings highlight the urgent need for extremely rapid and effective case detection, contact tracing and quarantine measures if strict social distancing measures are to be eased.

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

negative: SARS-CoV-2 IgG Antibody Responses in New York City Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a strain of coronavirus that causes coronavirus disease 2019 (Covid-19) and has been declared a global pandemic by the World Health Organization. Total cases of SARS-CoV-2 worldwide exceed 4.8 million, with over 320,000 deaths recorded. Little is known about the body's immune response to SARS-CoV-2 infection. In this paper, we describe SARS-CoV-2 IgG antibody responses in 11,092 patients from the New York City metropolitan area and report a SARS-CoV-2 IgG positivity rate of nearly 50%, indicating the widespread nature of the pandemic in the city and state of New York. Additionally, we report on the correlation between SARS-CoV-2 patient symptom severity and level of SARS-CoV-2 IgG antibody found in the patient sample.

negative: Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19

negative: COVID-19 breakthroughs: separating fact from fiction The newly recognised coronavirus SARS-CoV-2, causative agent of coronavirus disease (COVID-19), has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.

negative: Pharmacy practice in times of civil crisis: The experience of SARS and “the blackout” in Ontario, Canada Abstract Background Crises affecting civilian infrastructure (including electricity supply, clean water, and access to institutional health services) may have an effect on the delivery of pharmacy services in the community. Objectives The objectives were to describe and analyze the impact of 2 major crises (the severe acute respiratory syndrome [SARS] outbreak, and the electrical system failure [“blackout”]) on pharmacy practice and pharmacists in Toronto, Canada. Methods An exploratory, qualitative study was undertaken. Pharmacists were recruited, provided informed consent, and were interviewed. Data from transcripts were coded and categorized to identify themes related to adaptive strategies undertaken by pharmacists during times of civil crisis. Results Five key themes emerged from this research: (1) during times of crisis, pharmacies become frontline health care facilities, (2) a vacuity of leadership/lack of utility of emergency preparedness guidelines and policies, (3) role of and reliance on experience and professional judgment, (4) importance of documentation, and (5) the importance of “teamness” in enabling successful adaptation during times of crisis. Conclusions Emergencies and civil crises will continue to occur. Findings of this study include the importance of effective documentation systems and teamwork practices, as well as confident reliance on professional judgment and experience, as determinants of successful adaptation to civil crises.

negative: Rôle des animaux vertébrés dans l’épidémiologie des zoonoses Résumé Les zoonoses, distinguées ici des maladies humaines d’origine animale, représentent un ensemble d’entités pathologiques dont les agents responsables circulent régulièrement entre l’espèce humaine et de nombreuses espèces de vertébrés. L’analyse de divers exemples, quelles que soient les voies de transmission et les causes favorisantes de la contamination, met en avant une régulière rareté du passage direct du réservoir animal vers l’espèce humaine, à opposer à la diversité et surtout à la gravité possible des évolutions sanitaires ultérieures possibles, parfois liées à des comportements humains peu adaptés. D’un point de vue pratique, il semblerait plus pertinent de se pencher d’abord sur un meilleur contrôle de la diffusion des agents pathogènes au sein des populations humaines que d’agir a priori sur le réservoir animal, qu’il soit domestique ou sauvage, source potentielle de ces agents pathogènes mais selon des modalités difficiles à anticiper. La relation entre biodiversité et santé est abordée à l’occasion de la discussion. Summary Zoonoses, to be distinguished here from human diseases with an animal origin, represent a large quantity of pathological entities the corresponding pathogens of which are regularly shared between human beings and many different vertebrates species. Working on selected examples and situations, whatever the contamination routes and the facilitating reasons, puts into light a real rarity of a direct transmission from the animal reservoir to human beings. On the opposite, the diversity and the possible severity of some of the sanitary consequences, quite often in relation to human behaviours, must be stressed. On a practical point of view, it seems more adapted to try first to improve the control of pathogens diffusion within human populations after a contamination than to try to start to work first on the reservoir, be it domestic or wild, the potential source of these pathogens, but following routes quite difficult to anticipate. The relationship between biodiversity and health is discussed.

negative: Evaluating the effect of public health intervention on the global-wide spread trajectory of Covid-19 As COVID-19 evolves rapidly, the issues the governments of affected countries facing are whether and when to take public health interventions and what levels of strictness of these interventions should be, as well as when the COVID-19 spread reaches the stopping point after interventions are taken. To help governments with policy-making, we developed modified auto-encoders (MAE) method to forecast spread trajectory of Covid-19 of countries affected, under different levels and timing of intervention strategies. Our analysis showed public health interventions should be executed as soon as possible. Delaying intervention 4 weeks after March 8, 2020 would cause the maximum number of cumulative cases of death increase from 7,174 to 133,608 and the ending points of the epidemic postponed from Jun 25 to Aug 22.

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

negative: Diagnostic value of triggering receptor expressed on myeloid cells-1 and C-reactive protein for patients with lung infiltrates: an observational study BACKGROUND: Differential diagnosis of patients with lung infiltrates remains a challenge. Triggering receptor expressed on myeloid cells (TREM)-1 is a neutrophil and monocyte receptor up-regulated during infection. The aim of this study was to evaluate the diagnostic accuracy of TREM-1 and of C-reactive protein (CRP) from patients with lung infiltrates to discern community acquired lung infections. METHODS: 68 patients admitted to a medical ward with acute respiratory illness were enrolled in the study. Neutrophil and monocyte TREM-1 expression were measured by flow cytometry, sTREM-1 by an enzyme immunoassay and C-reactive protein by nephelometry. Clinical pulmonary infection score was recorded. RESULTS: 34 patients were diagnosed with bacterial community acquired pneumonia (group A) and 34 with non-bacterial pulmonary disease (group B). Median serum TREM-1 concentration was 102.09 pg/ml in group A and lower than 15.10 pg/ml (p < 0.0001) in group B. Mean±SE neutrophil TREM-1 expression was 4.67 ± 0.53 MFI in group A and 2.64 ± 0.25 MFI (p = 0.001) in group B. Monocyte TREM-1 expression was 4.2 ± 0.42 MFI in group A and 2.64 ± 0.35 MFI (p = 0.007) in group B and mean±SE CRP was 18.03 ± 2 mg/ml in group A and 7.1 ± 1.54 mg/ml (p < 0.001) in group B. A cut-off of 19.53 pg/ml of sTREM-1 with sensitivity 82.6% and specificity 63% to discriminate between infectious and non-infectious pulmonary infiltrates was found. sTREM-1 at admission greater than 180 pg/ml was accompanied with unfavourable outcome. CONCLUSION: TREM-1 myeloid expression and sTREM-1 are reliable markers of bacterial infection among patients with pulmonary infiltrates; sTREM-1 is a predictor of final outcome.

negative: Pandemia COVID-19, la nueva emergencia sanitaria de preocupación internacional: una revisión Resumen A finales de diciembre del 2019, se reportaron una serie de casos de neumonía atípica, en ese momento, de origen desconocido en Wuhan, China. Días más tarde se identificó al agente etiológico como un nuevo coronavirus. A este nuevo coronavirus, se le llamó SARS-CoV-2 y a la enfermedad que produce se le denominó COVID-19. El origen de este nuevo virus se presume zoonótico siendo los murciélagos su probable vector. Debido al acelerado número de contagios y muertes que se produjeron primero en China y posteriormente alrededor del mundo, la infección de este virus pasó rápidamente de ser un brote aislado en una región china, a convertirse en una emergencia sanitaria de preocupación internacional y posteriormente, en una pandemia. El propósito de esta revisión es estudiar la información más relevante y actual del patógeno, así como la epidemiología, patología, características clínicas, transmisión, prevención y tratamiento de la enfermedad. Abstract In late December 2019, some cases of atypical pneumonia, at that time of unknown origin, were reported in Wuhan, China. Days later, the etiologic agent was identified as a new coronavirus. This new coronavirus was called SARS-CoV-2 and the disease it produces was named COVID-19. The origin of this new virus is presumed zoonotic, with bats being its probable vector. Due to the rapid number of infections and deaths that occurred first in China and later around the world, the infection of this virus quickly went from being an isolated outbreak in a Chinese region to becoming a health emergency of international concern and later, a pandemic. The purpose of this review is to study the most relevant and current information on the pathogen, as well as epidemiology, pathology, clinical features, transmission, prevention, and treatment of the disease.

negative: Statistical investigation of relationship between spread of coronavirus disease (COVID-19) and environmental factors based on study of four mostly affected places of China and five mostly affected places of Italy COVID-19 is a new type of coronavirus disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It originated in China in the month of December 2019 and quickly started to spread within the country. On 31st December 2019, it was first reported to country office of World Health Organization (WHO) in China. Since then, it has spread to most of the countries around the globe. However, there has been a recent rise in trend in believing that it would go away during summer days, which has not yet been properly investigated. In this paper, relationship of daily number of confirmed cases of COVID-19 with three environmental factors, viz. maximum relative humidity (RH_max), maximum temperature (T_max) and highest wind speed (WS_max), considering the incubation period, have been investigated statistically, for four of the most affected places of China, viz. Beijing, Chongqing, Shanghai, Wuhan and five of the most affected places of Italy, viz. Bergamo, Cremona, Lodi, Milano. It has been found that the relationship with maximum relative humidity and highest wind is mostly negligible, whereas relationship with maximum temperature is ranging between negligible to moderate.

negative: Whole Genome Analysis and Targeted Drug Discovery Using Computational Methods and High Throughput Screening Tools for Emerged Novel Coronavirus (2019-nCoV). A novel coronavirus designated as SARS-CoV-2 in February 2020 by World Health organization (WHO) was identified as main cause of SARS like pneumonia cases in Wuhan city in Hubei Province of China at the end of 2019. This been recently declared as Global Pandemic by WHO. There is a global emergency to identify potential drugs to treat the SARS-CoV-2. Currently, there is no specific treatment against the new virus. There is a urgency to identifying potential antiviral agents to combat the disease is urgently needed. An effective and quick approach is to test existing antiviral drugs against. Whole genome analysis and alignment carried out using BLASTn, SMART BLAST and WebDSV 2.0 had shown more than 238 ORF's coding for proteins mostly origin from Bat SARS coronavirus and root genomic origin from Archaea. Molecular docking results against protein targets Furin, papain like proteases, RdRp and Spike glycoprotein had shown paritaprevir, ritonavir, entecavir and chloroquine derivatives are the best drugs to inhibit multi targets of coronavirus infection including natural compounds corosolic acid, baicalin and glycyrrhizic acid with minimal inhibitory concentrations. Thus we propose use of paritaprevir, entecavir, ritonavir and chloroquine derivatives as best drug combination along with niacinamide, folic acid and zinc supplements to treat novel coronavirus infection. We also propose use of plant protease inhibitors (PI's) and Anti-IL8, IL-6, IL-2 as future drug models against coronavirus.

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: 2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus 2019 Novel Coronavirus (2019-nCoV) is an emerging infectious disease closely related to MERS-CoV and SARS-CoV that was first reported in Wuhan City, Hubei Province, China in December 2019. As of January 2020, cases of 2019-nCoV are continuing to be reported in other Eastern Asian countries as well as in the United States, Europe, Australia, and numerous other countries. An unusually high volume of domestic and international travel corresponding to the beginning of the 2020 Chinese New Year complicated initial identification and containment of infected persons. Due to the rapidly rising number of cases and reported deaths, all countries should be considered at risk of imported 2019-nCoV. Therefore, it is essential for prehospital, clinic, and emergency department personnel to be able to rapidly assess 2019-nCoV risk and take immediate actions if indicated. The Identify-Isolate-Inform (3I) Tool, originally conceived for the initial detection and management of Ebola virus and later adjusted for other infectious agents, can be adapted for any emerging infectious disease. This paper reports a modification of the 3I Tool for use in the initial detection and management of patients under investigation for 2019-nCoV. After initial assessment for symptoms and epidemiological risk factors, including travel to affected areas and exposure to confirmed 2019-nCoV patients within 14 days, patients are classified in a risk-stratified system. Upon confirmation of a suspected 2019-nCoV case, affected persons must immediately be placed in airborne infection isolation and the appropriate public health agencies notified. This modified 3I Tool will assist emergency and primary care clinicians, as well as out-of-hospital providers, in effectively managing persons with suspected or confirmed 2019-nCoV.

negative: Identification and characterization of Jingmen tick virus in rodents from Xinjiang, China Jingmen tick virus (JMTV) is a recently identified virus which provides an unexpected connection between segmented and unsegmented RNA viruses. Recent investigations reveal that JMTV including JMTV-like virus (Alongshan virus) could be associated with human disease, suggesting the significance of JMTV in public health. To better understand the genetic diversity and host range of JMTV, a total of 164 rodents representing 8 species were collected in Qapqal Xibe county of Xinjiang Uygur Autonomous Region, China, and were screened for JMTVs using RT- PCR. Consequently, JMTV was identified in 42 rodents including 23 Microtus arvalis voles (24.5%), 9 Apodemus uralensis mice (29.0%), 5 Mus musculus mice, 1 Rhombomys opimus gerbil, 1 Meriones tamariscinus gerbil, 1 Meriones libycus gerbil, 1 Cricetulus migratorius hamster and 1 Microtus gregalis vole. Interestingly, nearly complete genome sequences were successfully recovered from 7 JMTV positive samples. Although the newly identified rodent JMTVs were closely related to those previously identified in ticks from China, based on the phylogenetic analysis of the S1, S2 and S3 segments, the newly identified rodent viruses clustered into two genetic groups. One group comprised of viruses only found in M. arvalis, while another group included viruses from A. uralensis, C. migratorius and M. gregalis. However, all rodent viruses clustered together in the S4 tree. Considering rodents live in close proximity to humans, more efforts are needed to investigate the role of rodents in the evolution and transmission of JMTV in nature.

negative: Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak

negative: Astrovirus evolution and emergence Abstract Astroviruses are small, non-enveloped, positive-sense, single-stranded RNA viruses that belong to the Astroviridae family. Astroviruses infect diverse hosts and are typically associated with gastrointestinal illness; although disease can range from asymptomatic to encephalitis depending on the host and viral genotype. Astroviruses have high genetic variability due to an error prone polymerase and frequent recombination events between strains. Once thought to be species specific, recent evidence suggests astroviruses can spread between different host species, although the frequency with which this occurs and the restrictions that regulate the process are unknown. Recombination events can lead to drastic evolutionary changes and contribute to cross-species transmission events. This work reviews the current state of research on astrovirus evolution and emergence, especially as it relates to cross-species transmission and recombination of astroviruses.

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: The role of triage in the prevention and control of COVID-19 OBJECTIVE: To prevent and control public health emergencies, we set up a prescreening and triage workflow and analyzed the effects on coronavirus disease 2019 (COVID-19). METHODS: In accordance with the requirements of the level 1 emergency response of public health emergencies in Shaanxi Province, China, a triage process for COVID-19 was established to guide patients through a 4-level triage process during their hospital visits. The diagnosis of COVID-19 was based on positive COVID-19 nucleic acid testing according to the unified triage standards of the Guidelines for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (Trial version 4),(4) issued by the National Health Commission of the People’s Republic of China. RESULTS: The screened rate of suspected COVID-19 was 1.63% (4 of 246) in the general fever outpatient clinic and 8.28% (13 of 157) in the COVID-19 outpatient clinic, and they showed a significant difference (P = .00). CONCLUSIONS: The triage procedure effectively screened the patients and identified the high-risk population.

negative: A cascade of causes that led to the COVID-19 tragedy in Italy and in other European Union countries

negative: CORD-19: The COVID-19 Open Research Dataset The COVID-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on COVID-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 200K times and has served as the basis of many COVID-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and describe several shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for COVID-19.

negative: CoroNet: A Deep Neural Network for Detection and Diagnosis of COVID-19 from Chest X-ray Images BACKGROUND AND OBJECTIVE: The novel Coronavirus also called COVID-19 originated in Wuhan, China in December 2019 and has now spread across the world. It has so far infected around 1.8 million people and claimed approximately 114698 lives overall. As the number of cases are rapidly increasing, most of the countries are facing shortage of testing kits and resources. The limited quantity of testing kits and increasing number of daily cases encouraged us to come up with a Deep Learning model that can aid radiologists and clinicians in detecting COVID-19 cases using chest X-rays. METHODS: In this study, we propose CoroNet, a Deep Convolutional Neural Network model to automatically detect COVID-19 infection from chest X-ray images. The proposed model is based on Xception architecture pre-trained on ImageNet dataset and trained end-to-end on a dataset prepared by collecting COVID-19 and other chest pneumonia X-ray images from two different publically available databases. RESULTS: CoroNet has been trained and tested on the prepared dataset and the experimental results show that our proposed model achieved an overall accuracy of 89.6%, and more importantly the precision and recall rate for COVID-19 cases are 93% and 98.2% for 4-class cases (COVID vs Pneumonia bacterial vs pneumonia viral vs normal). For 3-class classification (COVID vs Pneumonia vs normal), the proposed model produced a classification accuracy of 95%. The preliminary results of this study look promising which can be further improved as more training data becomes available. CONCLUSION: CoroNet achieved promising results on a small prepared dataset which indicates that given more data, the proposed model can achieve better results with minimum pre-processing of data. Overall, the proposed model substantially advances the current radiology based methodology and during COVID-19 pandemic, it can be very helpful tool for clinical practitioners and radiologists to aid them in diagnosis, quantification and follow-up of COVID-19 cases.

negative: A Diallel of the Mouse Collaborative Cross Founders Reveals Strong Strain-Specific Maternal Effects on Litter Size Reproductive success in the eight founder strains of the Collaborative Cross (CC) was measured using a diallel-mating scheme. Over a 48-month period we generated 4,448 litters, and provided 24,782 weaned pups for use in 16 different published experiments. We identified factors that affect the average litter size in a cross by estimating the overall contribution of parent-of-origin, heterosis, inbred, and epistatic effects using a Bayesian zero-truncated overdispersed Poisson mixed model. The phenotypic variance of litter size has a substantial contribution (82%) from unexplained and environmental sources, but no detectable effect of seasonality. Most of the explained variance was due to additive effects (9.2%) and parental sex (maternal vs. paternal strain; 5.8%), with epistasis accounting for 3.4%. Within the parental effects, the effect of the dam’s strain explained more than the sire’s strain (13.2% vs. 1.8%), and the dam’s strain effects account for 74.2% of total variation explained. Dams from strains C57BL/6J and NOD/ShiLtJ increased the expected litter size by a mean of 1.66 and 1.79 pups, whereas dams from strains WSB/EiJ, PWK/PhJ, and CAST/EiJ reduced expected litter size by a mean of 1.51, 0.81, and 0.90 pups. Finally, there was no strong evidence for strain-specific effects on sex ratio distortion. Overall, these results demonstrate that strains vary substantially in their reproductive ability depending on their genetic background, and that litter size is largely determined by dam’s strain rather than sire’s strain effects, as expected. This analysis adds to our understanding of factors that influence litter size in mammals, and also helps to explain breeding successes and failures in the extinct lines and surviving CC strains.

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

negative: Systematic literature review on novel corona virus SARS-CoV-2: a threat to human era Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh-generation coronavirus family causing viral pandemic coronavirus disease (COVID-19) across globe affecting millions of people. The objectives of this study are to (1) identify the major research themes in COVID-19 literature, (2) determine the origin, symptoms and modes of transmission of COVID, (3) recommend the intervention and mitigation strategies adopted by the Governments globally against the spread of COVID-19 and the traumatization among the public? and (4) study the possible drugs/treatment plans against COVID-19. A systematic literature review and comprehensive analysis of 38 research articles on COVID-19 are conducted. An integrated Research focus parallel-ship network and keyword co-occurrence analysis are carried out to visualize the three research concepts in COVID-19 literature. Some of our observations include: (1) as SARS-CoV-2’s RNA matches ~ 96% to SARS-CoV, it is assumed to be transmitted from the bats. (2) The common symptoms are high fever, dry cough, fatigue, sputum production, shortness of breath, diarrhoea etc. (3) A lockdown across 180 affected counties for more than a month with social-distancing and the precautions taken in SARS and MERS are recommended by the Governments. (4) Researchers’ claim that nutrition and immunity enhancers and treatment plans such as arbidol, lopinavir/ritonavir, convalescent plasma and mesenchymal stem cells and drugs including remdesivir, hydroxychloroquine, azithromycin and favipiravir are effective against COVID-19. This complied report serves as guide to help the administrators, researchers and the medical officers to adopt recommended intervention strategies and the optimal treatment/drug against COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13337-020-00604-z) contains supplementary material, which is available to authorized users.

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

negative: Predicting COVID-19 malignant progression with AI techniques Background: The coronavirus disease 2019 (COVID-19) has become a worldwide pandemic since mid-December 2019, which greatly challenge public medical systems. With limited medical resources, it is a natural strategy, while adopted, to access the severity of patients then determine the treatment priority. However, our work observes the fact that the condition of many mild outpatients quickly worsens in a short time, i.e. deteriorate into severe/critical cases. Hence, it has been crucial to early identify those cases and give timely treatment for optimizing treatment strategy and reducing mortality. This study aims to establish an AI model to predict mild patients with potential malignant progression. Methods: A total of 133 consecutively mild COVID-19 patients at admission who was hospitalized in Wuhan Pulmonary Hospital from January 3 to February 13, 2020, were selected in this retrospective IRB-approved study. All mild patients at admission were categorized into groups with or without malignant progression. The clinical and laboratory data at admission, the first CT, and the follow-up CT at severe/critical stage of the two groups were compared with Chi-square test, Fisher's exact test, and t test. Both traditional logistic regression and deep learning-based methods were used to build the prediction models. The area under ROC curve (AUC) was used to evaluate the models. Results: The deep learning-based method significantly outperformed logistic regression (AUC 0.954 vs. 0.893). The deep learning-based method achieved a prediction AUC of 0.938 by combining the clinical data and the CT data, significantly outperforming its counterpart trained with clinical data only by 0.141. By further considering the temporal information of the CT sequence, our model achieved the best AUC of 0.954. The proposed model can be effectively used for finding out the mild patients who are easy to deteriorate into severe/critical cases, so that such patients get timely treatments while alleviating the limitations of medical resources.

negative: 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.

negative: Bayesian Inference of COVID-19 Spreading Rates in South Africa The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for the development of prompt mitigating responses under conditions of high uncertainty. Fundamental to the design of rapid state reactions is the ability to perform epidemiological model parameter inference for localised trajectory predictions. In this work, we perform Bayesian parameter inference using Markov Chain Monte Carlo (MCMC) methods on the Susceptible-Infected-Recovered (SIR) and Susceptible-Exposed-Infected-Recovered (SEIR) epidemiological models with time-varying spreading rates for South Africa. The results find two change points in the spreading rate of COVID-19 in South Africa as inferred from the confirmed cases. The first change point coincides with state enactment of a travel ban and the resultant containment of imported infections. The second change point coincides with the start of a state-led mass screening and testing programme which has highlighted community-level disease spread that was not well represented in the initial largely traveller based and private laboratory dominated testing data. The results further suggest that due to the likely effect of the national lockdown, community level transmissions are slower than the original imported case driven spread of the disease.

negative: Covid-19: UK budget gives £94 a week statutory sick pay to self-isolators and their carers

negative: Prisoners of war — host adaptation and its constraints on virus evolution Recent discoveries of contemporary genotypes of hepatitis B virus and parvovirus B19 in ancient human remains demonstrate that little genetic change has occurred in these viruses over 4,500–6,000 years. Endogenous viral elements in host genomes provide separate evidence that viruses similar to many major contemporary groups circulated 100 million years ago or earlier. In this Opinion article, we argue that the extraordinary conservation of virus genome sequences is best explained by a niche-filling model in which fitness optimization is rapidly achieved in their specific hosts. Whereas short-term substitution rates reflect the accumulation of tolerated sequence changes within adapted genomes, longer-term rates increasingly resemble those of their hosts as the evolving niche moulds and effectively imprisons the virus in co-adapted virus–host relationships. Contrastingly, viruses that jump hosts undergo strong and stringent adaptive selection as they maximize their fit to their new niche. This adaptive capability may paradoxically create evolutionary stasis in long-term host relationships. While viruses can evolve and adapt rapidly, their hosts may ultimately shape their longer-term evolution.

negative: Papa Giovanni XXIII Bergamo Hospital at the time of the COVID-19 outbreak: Letter from the warfront

negative: Mental health groups providing support, education in wake of COVID‐19 As news and updates continue to spread regarding the new coronavirus (COVID‐19), the deadly virus that causes respiratory illness and pneumonia, mental health groups and organizations have issued information to consumers, providers and the mental health community at large about ways of addressing the virus and seeking information from public health sources.

negative: Media's effect on shaping knowledge, awareness risk perceptions and communication practices of pandemic COVID-19 among pharmacists Abstract Background Coronavirus disease (COVID-19), an infection of the zoonotic coronavirus, is presenting a healthcare challenge around the globe. This study aims to assess the levels of disease knowledge and risk perception among pharmacists. We also recognize predictors of risk perception and perceived media roles. Methods This is a questionnaire-base cross-sectional study. The questionnaire was developed on a web-based platform and invitations were sent to pharmacists nationwide to participate in the study using social media applications. Results A total of 486 pharmacists participated in this study, where females were dominant (78.6%, n = 382). Most (40.4%, n = 198) pharmacists scored 4 out of 5 in basic disease knowledge, and more than half were able to recognize common methods of spread. Risk was highly perceived among participants, and was predicted by gender, living area, and having children (p < 0,05). Frequency of watching the media and sources of information also influenced both risk perception and perceived media roles. Conclusion Disease awareness among pharmacists, as well as risk perception must be considered for effective risk communication planning. The role of media in shaping perceptions should also be carefully studied to encourage compliance with government containment measures and engagement in preventive behaviors.

negative: A multiplex RT-PCR test for the differential identification of turkey astrovirus type 1, turkey astrovirus type 2, chicken astrovirus, avian nephritis virus, and avian rotavirus. Recent studies have revealed the presence ofastroviruses and rotavirus in numerous poorly performing and healthy chicken and turkey flocks in the United States. The phylogenetic analysis of the sequence data produced during these studies has identified four groups of avian astroviruses circulating in the United States: turkey astrovirus types 1 and 2 (TAstV-1 and TAstV-2), avian nephritis virus (ANV), and a chicken-origin astrovirus (CAstV). As the molecular epidemiology of poultry enteric disease is poorly understood, the development of updated diagnostic assays is crucial to the continued surveillance and management of enteric disease in affected as well as healthy flocks. This report details the development of a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay specific for astroviruses and avian rotavirus in turkey-origin and chicken-origin samples. The assay consists of two multiplex tests, one for turkey-origin samples and one for chicken-origin samples. The turkey sample test differentially identifies TAstV-1, TAstV-2, ANV, and avian rotavirus. The test for chicken-origin samples differentially identifies CAstV, ANV, and avian rotavirus. Assay sensitivity varied by target sequence between approximately 10 copies for avian rotavirus alone and approximately 2 x 10(6) copies for TAstV-2 in the presence of a heterologous competitor RNA sequence. Each test was shown to be specific for the intended target by testing for cross-reaction with other common avian enteric viruses. The specificity was further shown by testing 109 chicken specimens and 32 turkey specimens from commercial flocks with the appropriate test and sequencing the RT-PCR amplicons to confirm amplification of the correct target.

negative: The COVID‐19 epidemic of manuscripts In the midst of the novel coronavirus pandemic—referred to as COVID‐19—there has been much uncertainty. We remain uncertain about its precise origin, its structure and composition, how best to test for it, or for resulting immunity, whether or not exposure leads to immunity, whether or not disposable surgical masks are effective, why men and some ethnic minorities are more susceptible and just exactly what the death rate as a result of this virus is. However, one thing is absolutely clear, there has been an epidemic of manuscripts on the subject of COVID‐19 to nursing journals and, amongst these new manuscripts the rejection rate is, unfortunately, very high.

negative: Modelling input-output flows of severe acute respiratory syndrome in mainland China BACKGROUND: Severe acute respiratory syndrome (SARS) originated in China in 2002, and it spread to 26 provinces in mainland China and 32 countries across five continents in a matter of months. This outbreak resulted in 774 deaths. However, the spatial features and potential determinants of SARS input-output flows remain unclear. METHODS: We used an adjusted spatial interaction model to examine the spatial effects and potential factors associated with SARS input-output flows. RESULTS: The presence of origin-based spatial dependence positively affected SARS input-output flows from the neighbours of the origin regions. Two components of the input-output flows, migrant and hospitalization flows, exhibited distinctive features. The origin-based and destination-based spatial dependence positively affected migrant flows (i.e., due to those seeking jobs) from the neighbours of origin and destination locations. Similarly, the destination-based spatial dependence also positively affected hospitalization flows (i.e., due to those seeking treatment) from the neighbours of destination regions. However, the origin-to-destination based spatial dependence negatively affected hospitalisation flows from the neighbours of origin-to-destination regions. The direct effects accounted for 78 % of the SARS input-output flows, which was 3.56-fold greater than the indirect effects. Differences in regional income drove the SARS input-output flows. Therefore, urban income had a positive effect, whereas rural income had a negative effect. Total interregional flows increased by 3.54 % with a 1 % increase in urban income, and intraregional flows increased by 8.35 %. In contrast, the total interregional flows decreased by 3.38 % with a 1 % increase in rural income, and intraregional flows declined by 2.29 %. Railway capacity, per person gross domestic product (PGDP), urban rate and the law of distance decay also affected the input-output flows. CONCLUSIONS: Our results confirm that the SARS input-output flows presented significant geographic spatial heterogeneity and spatial effects. Income differences were the major cause of the flows between pairs of regions. Railway capacity, PGDP, and urban rate also played important roles. These findings provide valuable information for the Chinese government to control the future spread of nationwide epidemics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-2867-6) contains supplementary material, which is available to authorized users.

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: Impact of Alignment between Social Media and Business Processes on SMEs’ Business Process Performance: A Conceptual Model Abstract The development of information technology highly affects various business sectors including Small and Medium Enterprises (SMEs). Social media implementation, as one of the most widely used IT application, is expected to support SMEs’ performances. Many types of research in social media have focused on the impact of its implementation on the performance of an organization at a macro level. Research that investigates the linkage between social media and how the company performs its business process is lacking in the literature to date. This study aims to fill this gap by conducting a literature review on social media implementation particularly in SMEs. The result of this study is a conceptual model that follows the proposition of Task-Technology Fit in exploring the impact of social media on SMEs business process performances. As a technology, social media functionality must fit the tasks that SMEs must perform. The model proposed social media alignment with business process domain based on the Process Classification Framework (PCF). The performances are measured at a business process level using four indicators i.e. cost, time, quality and flexibility of the business process.

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: COVID-19-related prejudice toward Asian medical students: A consequence of SARS-CoV-2 fears in Poland The coronavirus disease 2019 (COVID-19) outbreak caused by SARS-CoV-2 has triggered global panic. We have conducted an anonymous online survey of Asian medical students in Poland to assess whether they experience any form of prejudice related to the ongoing pandemic. As demonstrated, the COVID-19 outbreak had triggered xenophobic reactions toward students of Asian-origin (n=85) before the first SARS-CoV-2 case was confirmed in Poland. Facing prejudice, including discrimination related to COVID-19, may add to feelings of isolation of students of Asian origin who study abroad, and affect career development, especially for students. We recommend that universities should proactively develop policies that support students, faculty, and staff affected by discriminatory behavior both during the current outbreak and in the future. However, preventing such behaviors should also be enforced by national authorities.

negative: The inflection point about COVID-19 may have passed

negative: Discovery, diversity and evolution of novel coronaviruses sampled from rodents in China Abstract Although rodents are important reservoirs for RNA viruses, to date only one species of rodent coronavirus (CoV) has been identified. Herein, we describe a new CoV, denoted Lucheng Rn rat coronavirus (LRNV), and novel variants of two Betacoronavirus species termed Longquan Aa mouse coronavirus (LAMV) and Longquan Rl rat coronavirus (LRLV), that were identified in a survey of 1465 rodents sampled in China during 2011–2013. Phylogenetic analysis revealed that LAMV and LRLV fell into lineage A of the genus Betacoronavirus, which included CoVs discovered in humans and domestic and wild animals. In contrast, LRNV harbored by Rattus norvegicus formed a distinct lineage within the genus Alphacoronavirus in the 3CLpro, RdRp, and Hel gene trees, but formed a more divergent lineage in the N and S gene trees, indicative of a recombinant origin. Additional recombination events were identified in LRLV. Together, these data suggest that rodents may carry additional unrecognized CoVs.

negative: Deciphering the bat virome catalog to better understand the ecological diversity of bat viruses and the bat origin of emerging infectious diseases Studies have demonstrated that ~60%–80% of emerging infectious diseases (EIDs) in humans originated from wild life. Bats are natural reservoirs of a large variety of viruses, including many important zoonotic viruses that cause severe diseases in humans and domestic animals. However, the understanding of the viral population and the ecological diversity residing in bat populations is unclear, which complicates the determination of the origins of certain EIDs. Here, using bats as a typical wildlife reservoir model, virome analysis was conducted based on pharyngeal and anal swab samples of 4440 bat individuals of 40 major bat species throughout China. The purpose of this study was to survey the ecological and biological diversities of viruses residing in these bat species, to investigate the presence of potential bat-borne zoonotic viruses and to evaluate the impacts of these viruses on public health. The data obtained in this study revealed an overview of the viral community present in these bat samples. Many novel bat viruses were reported for the first time and some bat viruses closely related to known human or animal pathogens were identified. This genetic evidence provides new clues in the search for the origin or evolution pattern of certain viruses, such as coronaviruses and noroviruses. These data offer meaningful ecological information for predicting and tracing wildlife-originated EIDs.

negative: Making sense of perceptions of risk of diseases and vaccinations: a qualitative study combining models of health beliefs, decision-making and risk perception BACKGROUND: Maintaining high levels of childhood vaccinations is important for public health. Success requires better understanding of parents' perceptions of diseases and consequent decisions about vaccinations, however few studies have considered this from the theoretical perspectives of risk perception and decision-making under uncertainty. The aim of this study was to examine the utility of subjective risk perception and decision-making theories to provide a better understanding of the differences between immunisers' and non-immunisers' health beliefs and behaviours. METHODS: In a qualitative study we conducted semi-structured in-depth interviews with 45 Australian parents exploring their experiences and perceptions of disease severity and susceptibility. Using scenarios about 'a new strain of flu' we explored how risk information was interpreted. RESULTS: We found that concepts of dread, unfamiliarity, and uncontrollability from the subjective perception of risk and ambiguity, optimistic control and omission bias from explanatory theories of decision-making under uncertainty were useful in understanding why immunisers, incomplete immunisers and non-immunisers interpreted severity and susceptibility to diseases and vaccine risk differently. Immunisers dreaded unfamiliar diseases whilst non-immunisers dreaded unknown, long term side effects of vaccines. Participants believed that the risks of diseases and complications from diseases are not equally spread throughout the community, therefore, when listening to reports of epidemics, it is not the number of people who are affected but the familiarity or unfamiliarity of the disease and the characteristics of those who have had the disease that prompts them to take preventive action. Almost all believed they themselves would not be at serious risk of the 'new strain of flu' but were less willing to take risks with their children's health. CONCLUSION: This study has found that health messages about the risks of disease which are communicated as though there is equality of risk in the population may be unproductive as these messages are perceived as unbelievable or irrelevant. The findings from this study have implications beyond the issue of childhood vaccinations as we grapple with communicating risks of new epidemics, and indeed may usefully contribute to the current debate especially in the UK of how these theories of risk and decision-making can be used to 'nudge' other health behaviours.

negative: Role of Nonstructural Proteins in the Pathogenesis of SARS‐CoV‐2 We read with great interest the study authored by Angeletti et al. regarding the role of nonstructural proteins nsp2 and nsp3 in the pathogenesis of COVID‐19(1). COVID‐19 emerged in December 2019 in Wuhan City, Hubei Province, China and is caused by a novel viral variant belonging to the viral variant belonging to the Severe acute respiratory syndrome‐related coronavirus (SARS‐rCoV) species of subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae and named SARS‐CoV‐2(2). This article is protected by copyright. All rights reserved.

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

negative: 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: A recombinant infectious bronchitis virus from a chicken with a spike gene closely related to that of a turkey coronavirus Using viral metagenomics, the complete genome sequence of an infectious bronchitis virus (IBV) strain (named ahysx-1) from a fecal sample from a healthy chicken in Anhui province, China, was determined. The genome sequence of ahysx-1 was found to be very similar to that of IBV strain ck/CH/LLN/131040 (KX252787), except for the spike gene region, which is similar to that of a turkey coronavirus strain (EU022526), suggesting that ahysx-1 is a recombinant. Recombination analysis and phylogenetic analysis based on the genomic sequences of ahysx-1 and other related strains confirmed that ahysx-1 appears to be a recombinant resulting from a recombination event that occurred between a chicken coronavirus and a turkey coronavirus. Further studies need to be performed to determine whether this recombinant IBV strain is pathogenic and whether it is transmitted between chickens and turkeys. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04488-3) contains supplementary material, which is available to authorized users.

negative: Human and novel coronavirus infections in children: a review. Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. ABBREVIATIONS 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Guérin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization.

negative: Evaluation of NxTAG Respiratory Pathogen Panel and Comparison with xTAG Respiratory Viral Panel Fast v2 and Film Array Respiratory Panel for Detecting Respiratory Pathogens in Nasopharyngeal Aspirates and Swine/Avian-Origin Influenza A Subtypes in Culture Isolates This study evaluated a new multiplex kit, Luminex NxTAG Respiratory Pathogen Panel, for respiratory pathogens and compared it with xTAG RVP Fast v2 and FilmArray Respiratory Panel using nasopharyngeal aspirate specimens and culture isolates of different swine/avian-origin influenza A subtypes (H2N2, H5N1, H7N9, H5N6, and H9N2). NxTAG RPP gave sensitivity of 95.2%, specificity of 99.6%, PPV of 93.5%, and NPV of 99.7%. NxTAG RPP, xTAG RVP, and FilmArray RP had highly concordant performance among each other for the detection of respiratory pathogens. The mean analytic sensitivity (TCID50/ml) of NxTAG RPP, xTAG RVP, and FilmArray RP for detection of swine/avian-origin influenza A subtype isolates was 0.7, 41.8, and 0.8, respectively. All three multiplex assays correctly typed and genotyped the influenza viruses, except for NxTAG RRP that could not distinguish H3N2 from H3N2v. Further investigation should be performed if H3N2v is suspected to be the cause of disease. Sensitive and specific laboratory diagnosis of all influenza A viruses subtypes is especially essential in certain epidemic regions, such as Southeast Asia. The results of this study should help clinical laboratory professionals to be aware of the different performances of commercially available molecular multiplex RT-PCR assays that are commonly adopted in many clinical diagnostic laboratories.

negative: Correction to: COVID-19 and importance of environmental sustainability The original version of this article unfortunately contains a mistake

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: Imaging of Coronavirus Disease 2019: A Chinese Expert Consensus Statement Abstract Coronavirus disease 2019 (COVID-19) is highly contagious, mainly causing inflammatory lesions in the lungs, and can also cause damage to the intestine and liver. The rapid spread of the virus that causes coronavirus disease 2019 (COVID-19) pneumonia has posed complex challenges to global public health. Early detection, isolation, diagnosis, and treatment are the most effective means of prevention and control. At present, the epidemic situation of new coronavirus infection has tended to be controlled in China, and it is still in a period of rapid rise in much of the world. The current gold standard for the diagnosis of COVID-19 is the detection of coronavirus nucleic acids, but imaging has an important role in the detection of lung lesions, stratification, evaluation of treatment strategies, and differentiation of mixed infections. This Chinese expert consensus statement summarizes the imaging features of COVID-19 pneumonia and may help radiologists across the world to understand this disease better.

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

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

negative: Risk Factors of Healthcare Workers with Corona Virus Disease 2019: A Retrospective Cohort Study in a Designated Hospital of Wuhan in China Corona Virus Disease 2019 (COVID-19) originated in Wuhan, China has caused many healthcare workers (HCWs) infected. Seventy-two HCWs manifested with acute respiratory illness were retrospectively enrolled to analyze the risk factors. The high-risk department, longer duty hours, and suboptimal hand hygiene after contacting with patients were linked to COVID-19.

negative: Overview on SARS in Asia and the World Severe Acute Respiratory Syndrome (SARS) is the first major novel infectious disease to hit the international community in the 21st century. It originated in southern China in November 2002, reached Hong Kong in February 2003 and spread rapidly thereafter to 29 countries/regions on five continents. At the end of the epidemic, the global cumulative total was 8098 with 774 deaths. Seven Asian countries/regions were among the top ten on the list. Mainland China and Hong Kong, SAR, accounted for 87% of all cases and 84% of all deaths. Severe acute respiratory syndrome is caused by a novel coronavirus. It has alarmed the world with its infectivity and significant morbidity and mortality, its lack of a rapid, reliable diagnostic test and lack of effective specific treatment and vaccination. The adverse impact on travel and business around the world, particularly in Asia, has been enormous. Some lessons learnt from this epidemic included: (1) any outbreak of infectious disease can rapidly spread around the world by air travel; (2) early reporting of the outbreak to neighbouring countries/regions and the World Health Organization is essential to prevent international spread; and (3) infection control, tracing and quarantine of contacts are essential to control the epidemic. Many questions remain unanswered, including the origin and pathogenesis of the novel coronavirus, the natural history and the best specific treatment of the disease. The SARS‐CoV has probably jumped from an animal host to humans. There is an urgent need to evaluate the human–animal habitat in southern China and to remove animal reservoirs if found.

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

negative: SARS-CoV-2: origen, estructura, replicación y patogénesis La enfermedad por coronavirus 2019, es una enfermedad respiratoria aguda con una amplia gama de manifestaciones: desde un simple resfriado, pasando por una neumonía leve, moderada o grave, hasta sepsis, shock séptico o la muerte Inició presuntamente en un mercado de animales vivos en la ciudad de Wuhan, provincia de Hubei, China, en diciembre de 2019 Su agente etiológico es el coronavirus 2 del síndrome respiratorio agudo grave, cuyo origen específico aún no se ha determinado Estudios filogenéticos orientan a, pero no confirman, que el virus pudo haberse originado en murciélagos En lo que va del siglo XXI, esta es la tercera enfermedad en el ser humano provocada por un coronavirus altamente patógeno Las primeras dos fueron el Síndrome Respiratorio Agudo Grave y el Síndrome Respiratorio del Medio Oriente Este artículo describe el conocimiento actual del origen, la estructura y la patogénesis del coronavirus 2 del síndrome respiratorio agudo grave, así como el daño tisular que provoca en los pacientes infectados (AU)Coronavirus disease 2019 is an acute respiratory illness with multiple clinical manifestations, ranging from a simple cold to mild, moderate or severe pneumonia, or even sepsis, septic shock and death It allegedly started in a live animal market in Wuhan City, Hubei Province, China, in December 2019 Its etiological agent is the severe acute respiratory syndrome coronavirus 2, its specific origin has not yet been determined Phylogenetic studies guide, but do not confirm, that the virus may have originated in bats This is the third disease in humans caused by a highly pathogenic coronavirus during the 21st century The first two were Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome This essay describes current knowledge about the origin, structure and pathogenesis of severe acute respiratory syndrome coronavirus 2, as well as the tissue damage it causes in infected patients (AU)

negative: Prise en charge des cancers du sein pendant la pandémie de COVID 19 : le CNGOF se mobilise

negative: Detection and full genome characterization of two beta CoV viruses related to Middle East respiratory syndrome from bats in Italy BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV), which belongs to beta group of coronavirus, can infect multiple host species and causes severe diseases in humans. Multiple surveillance and phylogenetic studies suggest a bat origin. In this study, we describe the detection and full genome characterization of two CoVs closely related to MERS-CoV from two Italian bats, Pipistrellus kuhlii and Hypsugo savii. METHODS: Pool of viscera were tested by a pan-coronavirus RT-PCR. Virus isolation was attempted by inoculation in different cell lines. Full genome sequencing was performed using the Ion Torrent platform and phylogenetic trees were performed using IQtree software. Similarity plots of CoV clade c genomes were generated by using SSE v1.2. The three dimensional macromolecular structure (3DMMS) of the receptor binding domain (RBD) in the S protein was predicted by sequence-homology method using the protein data bank (PDB). RESULTS: Both samples resulted positive to the pan-coronavirus RT-PCR (IT-batCoVs) and their genome organization showed identical pattern of MERS CoV. Phylogenetic analysis showed a monophyletic group placed in the Beta2c clade formed by MERS-CoV sequences originating from humans and camels and bat-related sequences from Africa, Italy and China. The comparison of the secondary and 3DMMS of the RBD of IT-batCoVs with MERS, HKU4 and HKU5 bat sequences showed two aa deletions located in a region corresponding to the external subdomain of MERS-RBD in IT-batCoV and HKU5 RBDs. CONCLUSIONS: This study reported two beta CoVs closely related to MERS that were obtained from two bats belonging to two commonly recorded species in Italy (P. kuhlii and H. savii). The analysis of the RBD showed similar structure in IT-batCoVs and HKU5 respect to HKU4 sequences. Since the RBD domain of HKU4 but not HKU5 can bind to the human DPP4 receptor for MERS-CoV, it is possible to suggest also for IT-batCoVs the absence of DPP4-binding potential. More surveillance studies are needed to better investigate the potential intermediate hosts that may play a role in the interspecies transmission of known and currently unknown coronaviruses with particular attention to the S protein and the receptor specificity and binding affinity.

negative: A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias BACKGROUND: A novel coronavirus (2019-nCoV) has raised world concern since it emerged in Wuhan Hubei China in December, 2019. The infection may result into severe pneumonia with clusters illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen 2019-nCoV pneumonia (NCOVID-19) and fifteen other pneumonia patients (NON-NCOVID-19) in out of Hubei places were involved in this study. Both NCOVID-19 and NON-NCOVID-19 patients were confirmed to be infected in throat swabs or/and sputa with or without 2019-nCoV by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the difference between NCOVID-19 and NON-NCOVID-19. RESULTS: All patients had a history of exposure to confirmed case of 2019-nCoV or travel to Hubei before illness. The median duration, respectively, was 8 (IQR:6~11) and 5 (IQR:4~11) days from exposure to onset in NCOVID-19 and NON-NCOVID-19. The clinical symptoms were similar between NCOVID-19 and NON-NCOVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) NCOVID-19 but 4 (26.67%) NON-NCOVID-19 patients had bilateral involvement while 17 (89.47%) NCOVID-19 but 1 (6.67%) NON-NCOVID-19 patients had multiple mottling and ground-glass opacity of chest CT images. Compared to NON-NCOVID-19, NCOVID-19 present remarkably more abnormal laboratory tests including AST, ALT, γ-GT, LDH and α-HBDH. CONCLUSION: The 2019-nCoV infection caused similar onsets to other pneumonias. CT scan may be a reliable test for screening NCOVID-19 cases. Liver function damage is more frequent in NCOVID-19 than NON-NCOVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of NCOVID-19.

negative: Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia BACKGROUND: A novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients. METHODS: We developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested. RESULTS: Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10(−4)-2000 TCID(50)/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests. CONCLUSIONS: The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.

negative: A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019 Coronavirus disease 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 has become an important public health issue in the world. More than 118 000 cases were confirmed around the world. The main clinical manifestations were respiratory symptoms and occasional gastrointestinal symptoms. However, there is no unified standard for the diagnosis and treatment of COVID‐19. In the retrospective analysis, we report nine cases of COVID‐19, describe the history of contact, clinical manifestations, the course of diagnosis and clinical treatment before, during and after treatment.

negative: State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans Background: Between September 2012 and 22 October 2013, 144 laboratory-confirmed and 17 probable MERS-CoV cases from nine countries were notified to WHO. Methods: We summarize what is known about the epidemiology, virology, phylogeny and emergence of MERS-CoV to inform public health policies. Results: The median age of patients (n=161) was 50 years (range 14 months to 94 years), 64.5% were male and 63.4% experienced severe respiratory disease. 76.0% of patients were reported to have ≥1 underlying medical condition and fatal cases, compared to recovered or asymptomatic cases were more likely to have an underlying condition (86.8% vs. 42.4%, p<0.001). Analysis of genetic sequence data suggests multiple independent introductions into human populations and modelled estimates using epidemiologic and genetic data suggest R0 is <1, though the upper range of estimates may exceed 1. Index/sporadic cases (cases with no epidemiologic-link to other cases) were more likely to be older (median 59.0 years vs. 43.0 years, p<0.001) compared to secondary cases, although these proportions have declined over time. 80.9% vs. 67.2% of index/sporadic and secondary cases, respectively, reported ≥1 underlying condition. Clinical presentation ranges from asymptomatic to severe pneumonia with acute respiratory distress syndrome and multi-organ failure. Nearly all symptomatic patients presented with respiratory symptoms and 1/3 of patients also had gastrointestinal symptoms. Conclusions: Sustained human-to-human transmission of MERS-CoV has not been observed. Outbreaks have been extinguished without overly aggressive isolation and quarantine suggesting that transmission of virus may be stopped with implementation of appropriate infection control measures.

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: Covid-19 pandemic and the unprecedented mobilisation of scholarly efforts prompted by a health crisis: Scientometric comparisons across SARS, MERS and 2019-nCov literature During the current century, each major coronavirus outbreak has triggered a quick surge of academic publications on this topic. The spike in research publications following the 2019 Novel Coronavirus (Covid-19), however, has been like no other. The global crisis caused by the Covid-19 pandemic has mobilised scientific efforts in an unprecedented way. In less than five months, more than 12,000 research items have been indexed while the number increasing every day. With the crisis affecting all aspects of life, research on Covid-19 seems to have become a focal point of interest across many academic disciplines. Here, scientometric aspects of the Covid-19 literature are analysed and contrasted with those of the two previous major Coronavirus diseases, i.e. SARS and MERS. The focus is on the co-occurrence of key-terms, bibliographic coupling and citation relations of journals and collaborations between countries. Certain recurring patterns across all three literatures were discovered. All three outbreaks have commonly generated three distinct and major cohort of studies: (i) studies linked to the public health response and epidemic control, (ii) studies associated with the chemical constitution of the virus and (iii) studies related to treatment, vaccine and clinical care. While studies affiliated with the category (i) seem to have been the first to emerge, they overall received least numbers of citations compared to those of the two other categories. Covid-19 studies seem to have been distributed across a broader variety of journals and subject areas. Clear links are observed between the geographical origins of each outbreak or the local geographical severity of each outbreak and the magnitude of research originated from regions. Covid-19 studies also display the involvement of authors from a broader variety of countries compared to SARS and MRS.

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: A Preliminary Study of the Virome of the South American Free-Tailed Bats (Tadarida brasiliensis) and Identification of Two Novel Mammalian Viruses Bats provide important ecosystem services as pollinators, seed dispersers, and/or insect controllers, but they have also been found harboring different viruses with zoonotic potential. Virome studies in bats distributed in Asia, Africa, Europe, and North America have increased dramatically over the past decade, whereas information on viruses infecting South American species is scarce. We explored the virome of Tadarida brasiliensis, an insectivorous New World bat species inhabiting a maternity colony in Rosario (Argentina), by a metagenomic approach. The analysis of five pooled oral/anal swab samples indicated the presence of 43 different taxonomic viral families infecting a wide range of hosts. By conventional nucleic acid detection techniques and/or bioinformatics approaches, the genomes of two novel viruses were completely covered clustering into the Papillomaviridae (Tadarida brasiliensis papillomavirus type 1, TbraPV1) and Genomoviridae (Tadarida brasiliensis gemykibivirus 1, TbGkyV1) families. TbraPV1 is the first papillomavirus type identified in this host and the prototype of a novel genus. TbGkyV1 is the first genomovirus reported in New World bats and constitutes a new species within the genus Gemykibivirus. Our findings extend the knowledge about oral/anal viromes of a South American bat species and contribute to understand the evolution and genetic diversity of the novel characterized viruses.

negative: Clinical and virological data of the first cases of COVID-19 in Europe: a case series BACKGROUND: On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020. METHODS: In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done. FINDINGS: The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log(10) copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020. INTERPRETATION: We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies. FUNDING: REACTing (Research & Action Emerging Infectious Diseases).

negative: Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge.

negative: Covid-19 pandemic and the skin - What should dermatologists know? Abstract The World has changed dramatically since the COVID-19 pandemic began. Together with our social, occupational, and personal life, the new corona virus poses novel challenges for all physicians, including dermatologists. Despite the virus not being dermatotropic, several skin conditions have emerged, mainly as a result of prolonged contact to personal protective equipment and excessive personal hygiene. Pressure injury, contact dermatitis, itch, pressure urticaria, and exacerbation of pre-existing skin diseases, including seborrheic dermatitis and acne, have been described. We have focused on the dermatologic aspects of COVID-19 infection, so that dermatologist may be aware of the skin complications and the preventive measures to be taken in the COVID-19 pandemic.

negative: Ecosystem approaches to the risk for schizophrenia

negative: Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients Abstract The SARS-CoV-2 (Covid-19) coronavirus pandemic is evolving very quickly and means a special risk for both immunosuppressed and comorbid patients. Knowledge about this growing infection is also increasing although many uncertainties remain, especially in the kidney transplant population. This manuscript presents a proposal for action with general and specific recommendations to protect and prevent infection in this vulnerable population such as kidney transplant recipients.

negative: No evidence of SARS-CoV-2 in semen of males recovering from COVID-19 Abstract Objective To describe detection of SARS-CoV-2 in seminal fluid of patients recovering from COVID-19 and describe the expression profile of ACE2 and TMPRSS2 within the testicle. Design observational, cross-sectional study Setting Tertiary referral center Patients Thirty-four adult Chinese males diagnosed with COVID-19 through confirmatory quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) from pharyngeal swab samples Intervention None Main Outcome Measures Identification of SARS-CoV-2 on qRT-PCR of single ejaculated semen samples. Semen quality was not assessed. Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets. Results Six patients (19%) demonstrated scrotal discomfort concerning for viral orchitis around the time of COVID-19 confirmation. SARS-CoV-2 was not detected in semen after a median of 31 days (IQR: 29-36 days) from COVID-19 diagnosis. Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression. Conclusions SARS-CoV-2 was not detected in the semen of patients recovering from COVID-19 one month after COVID-19 diagnosis. ACE2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression. The long-term effects of SARS-CoV-2 on male reproductive function remain unknown.

negative: Artificial intelligence for rapid identification of the coronavirus disease 2019 (COVID-19) The coronavirus disease 2019 (COVID-19) outbreak that originated in Wuhan, China has rapidly propagated due to widespread person-to-person transmission and has resulted in over 1,133,758 cases in 197 countries with a total of 62,784 deaths as of April 5, 2020. Laboratory confirmation of SARS-CoV-2 is performed with a virus-specific reverse transcriptase polymerase chain reaction (RT-PCR) test. This test can take up to two days to complete, and, due to the possibility of false negatives, serial testing may be required to reliably exclude infection. A current supply shortage of RT-PCR test kits compounds the shortcomings of entrusting diagnosis to the PCR test alone and underscores the urgent need to provide alternative methods for the rapid and accurate diagnosis of SARS-CoV-2 patients. Chest computed tomography (CT) is a valuable component in the evaluation of patients with suspected SARS-CoV-2 infection. Nevertheless, CT alone may have limited negative predictive value to fully exclude infection, because of the normal radiologic findings in some early disease patients. In this study, we use artificial intelligence (AI) algorithms to integrate chest CT findings with clinical symptoms, exposure history, and/or laboratory testing to more accurately and rapidly diagnose SARS-CoV-2 (+) patients. We included 905 RT-PCR confirmed patients. 419 (46.2%) tested positive for SARS-CoV-2 by laboratory-confirmed real-time RT-PCR assay and next-generation sequencing, while 486 patients (53.8%) tested negative (confirmed by at least two additional negative RT-PCR tests and clinical observation). The proposed AI system achieved an AUC of 0.92 and performed equally well in sensitivity compared to a senior thoracic radiologist on a testing set of 279 cases. The AI system also improved the detection of RT-PCR positive SARS-CoV-2 patients who presented with normal CTs, correctly identifying 17/25 (68%) patients, whereas all 25 RT-PCR SARS-CoV-2-positive CT-normal patients were classified as SARS-CoV-2 negative by radiologists.

negative: Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.

negative: COVID-19 update: Covid-19-associated coagulopathy

negative: PMA leading a multilateral fight against COVID-19

negative: Data Mining and Content Analysis of the Chinese Social Media Platform Weibo During the Early COVID-19 Outbreak: Retrospective Observational Infoveillance Study BACKGROUND: The coronavirus disease (COVID-19) pandemic, which began in Wuhan, China in December 2019, is rapidly spreading worldwide with over 1.9 million cases as of mid-April 2020. Infoveillance approaches using social media can help characterize disease distribution and public knowledge, attitudes, and behaviors critical to the early stages of an outbreak. OBJECTIVE: The aim of this study is to conduct a quantitative and qualitative assessment of Chinese social media posts originating in Wuhan City on the Chinese microblogging platform Weibo during the early stages of the COVID-19 outbreak. METHODS: Chinese-language messages from Wuhan were collected for 39 days between December 23, 2019, and January 30, 2020, on Weibo. For quantitative analysis, the total daily cases of COVID-19 in Wuhan were obtained from the Chinese National Health Commission, and a linear regression model was used to determine if Weibo COVID-19 posts were predictive of the number of cases reported. Qualitative content analysis and an inductive manual coding approach were used to identify parent classifications of news and user-generated COVID-19 topics. RESULTS: A total of 115,299 Weibo posts were collected during the study time frame consisting of an average of 2956 posts per day (minimum 0, maximum 13,587). Quantitative analysis found a positive correlation between the number of Weibo posts and the number of reported cases from Wuhan, with approximately 10 more COVID-19 cases per 40 social media posts (P<.001). This effect size was also larger than what was observed for the rest of China excluding Hubei Province (where Wuhan is the capital city) and held when comparing the number of Weibo posts to the incidence proportion of cases in Hubei Province. Qualitative analysis of 11,893 posts during the first 21 days of the study period with COVID-19-related posts uncovered four parent classifications including Weibo discussions about the causative agent of the disease, changing epidemiological characteristics of the outbreak, public reaction to outbreak control and response measures, and other topics. Generally, these themes also exhibited public uncertainty and changing knowledge and attitudes about COVID-19, including posts exhibiting both protective and higher-risk behaviors. CONCLUSIONS: The results of this study provide initial insight into the origins of the COVID-19 outbreak based on quantitative and qualitative analysis of Chinese social media data at the initial epicenter in Wuhan City. Future studies should continue to explore the utility of social media data to predict COVID-19 disease severity, measure public reaction and behavior, and evaluate effectiveness of outbreak communication.

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: What we do when a COVID-19 patient needs an operation: operating room preparation and guidance

negative: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020 A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 [1] On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from some clustered cases [2] Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 (COVID-19) As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization (WHO) European Region [3-5] Here we describe the epidemiology of the first cases of COVID-19 in this region, excluding cases reported in the United Kingdom (UK), as at 21 February 2020 The study includes a comparison between cases detected among travellers from China and cases whose infection was acquired due to subsequent local transmission %R doi:https://doi org/10 2807/1560-7917 ES 2020 25 9 2000178

negative: Evidence for gastrointestinal infection of SARS-CoV-2 The new coronavirus (SARS-CoV-2) outbreak originating from Wuhan, China, poses a threat to global health. While it's evident that the virus invades respiratory tract and transmits from human to human through airway, other viral tropisms and transmission routes remain unknown. We tested viral RNA in stool from 73 SARS-CoV-2-infected hospitalized patients using rRT-PCR. 53.42% of the patients tested positive in stool. 23.29% of the patients remained positive in feces even after the viral RNA decreased to undetectable level in respiratory tract. The viral RNA was also detected in gastrointestinal tissues. Furthermore, gastric, duodenal and rectal epithelia showed positive immunofluorescent staining of viral host receptor ACE2 and viral nucleocapsid protein in a case of SARS-CoV-2 infection. Our results provide evidence for gastrointestinal infection of SARS-CoV-2, highlighting its potential fecal-oral transmission route.

negative: Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data BACKGROUND: The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common nonhuman primate animal models, are limited. METHODS: We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. RESULTS: For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely ‘missing’ from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. CONCLUSIONS: For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies.

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

negative: Analysis of the infection status of the health care workers in Wuhan during the COVID-19 outbreak: A cross-sectional study BACKGROUND: Health care workers at the frontline are facing a substantial risk of infection during the coronavirus disease 2019 (COVID-19) outbreak. METHODS: We acquired information and data on the general information, infection and death status of health care workers in Wuhan during the COVID-19 outbreak and completed statistical analyses. RESULTS: We have obtained the data on 2,457 infected cases among health care workers in Wuhan, China. More than half of the infected individuals were nurses (52.06%), while 33.62% of infected cases were doctors and 14.33% of cases were medical staff. In particular, the case infection rate of nurses (2.22%) was remarkably higher than that of doctors (1.92%). Most infected cases among health care workers were female (72.28%). A majority of the infected health care workers (89.26%) came from general hospitals, followed by specialized hospitals (5.70%) and community hospitals (5.05%). The case infection rate of health care workers (2.10%) was dramatically higher than that of non-health care workers (0.43%). The case fatality rate of health care workers (0.69%) was significantly lower than that of non-health care workers (5.30%). CONCLUSIONS: The infection risk of HCWs is clearly higher than that of non-HCWs. HCWs play an essential role in fighting the pandemic. The analysis of the infection status of HCWs is essential to attract enough attention from the public, provide effective suggestions for government agencies and improve protective measures for HCWs.

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

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

negative: The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently gained popularity in discussions about the biosafety risks of gain-of-function (GOF) influenza virus research, as an argument for why this research should not be performed. There is now a moratorium in the United States on funding GOF research while the benefits and risks, including the potential for accident, are analyzed. Given the importance of this historical epidemic to ongoing policy debates, we revisit the evidence that the 1977 epidemic was not natural and examine three potential origins: a laboratory accident, a live-vaccine trial escape, or deliberate release as a biological weapon. Based on available evidence, the 1977 strain was indeed too closely matched to decades-old strains to likely be a natural occurrence. While the origin of the outbreak cannot be conclusively determined without additional evidence, there are very plausible alternatives to the laboratory accident hypothesis, diminishing the relevance of the 1977 experience to the modern GOF debate.

negative: Phylogenetic and epidemic modeling of rapidly evolving infectious diseases Abstract Epidemic modeling of infectious diseases has a long history in both theoretical and empirical research. However the recent explosion of genetic data has revealed the rapid rate of evolution that many populations of infectious agents undergo and has underscored the need to consider both evolutionary and ecological processes on the same time scale. Mathematical epidemiology has applied dynamical models to study infectious epidemics, but these models have tended not to exploit – or take into account – evolutionary changes and their effect on the ecological processes and population dynamics of the infectious agent. On the other hand, statistical phylogenetics has increasingly been applied to the study of infectious agents. This approach is based on phylogenetics, molecular clocks, genealogy-based population genetics and phylogeography. Bayesian Markov chain Monte Carlo and related computational tools have been the primary source of advances in these statistical phylogenetic approaches. Recently the first tentative steps have been taken to reconcile these two theoretical approaches. We survey the Bayesian phylogenetic approach to epidemic modeling of infection diseases and describe the contrasts it provides to mathematical epidemiology as well as emphasize the significance of the future unification of these two fields.

negative: 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.

negative: The Fecal Virome of Children with Hand, Foot, and Mouth Disease that Tested PCR Negative for Pathogenic Enteroviruses Hand, foot, and mouth disease (HFMD) affects infant and young children. A viral metagenomic approach was used to identify the eukaryotic viruses in fecal samples from 29 Thai children with clinical diagnosis of HFMD collected during the 2012 outbreak. These children had previously tested negative by PCR for enterovirus 71 and coxsackievirus A16 and A6. Deep sequencing revealed nine virus families: Picornaviridae, Astroviridae, Parvoviridae, Caliciviridae, Paramyxoviridae, Adenoviridae, Reoviridae, Picobirnaviridae, and Polyomaviridae. The highest number of viral sequences belonged to human rhinovirus C, astrovirus-MLB2, and coxsackievirus A21. Our study provides an overview of virus community and highlights a broad diversity of viruses found in feces from children with HFMD.

negative: Experience and suggestion of medical practices for burns during the outbreak of COVID-19 COVID-19 is spreading almost all over the world at present, which is infected by 2019 novel coronavirus (2019-nCoV). It was epidemic firstly in Hubei province of China. The Chinese government has formally set COVID-19 in the statutory notification and control system for infectious diseases according to the Law of the People’s Republic of China on the Prevention and Treatment of Infectious Diseases. China currently is still struggling to defend COVID-19 though great achievements and progresses are being got. Burn Department is one of sections in clinics with the highest infectious risk of COVID-19. Based on our own experiences and the guidelines on the diagnosis and treatment of COVID-19 (7th Version) with other regulations and literatures, we put forward this experience and suggestion of medical practices for burns during the outbreak of COVID-19. We hope these experiences and suggestions could benefit for our international colleagues during the pandemic of the COVID-19.

negative: Prise en charge des cancers du sein pendant la pandémie de COVID 19: le CNGOF se mobilise

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

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

negative: The substantial awareness role of web-based and social media platforms in developing countries during a pandemic scenario: the example of COVID-19 BACKGROUND: During the outbreak of coronavirus COVID-19, social media platforms have shown effectiveness in information dissemination. Delivering evidence-based medical knowledge and trustworthy recommendations is a difficult mission for classical entities, especially in a war-torn country with a fragile health system. In this context, the role of non-governmental scientific organizations was proven, filling the gap between original scientific sources and a non-English speaking population. METHODS: We reviewed an example of an organization named Syrian Researchers, which publishes based-on-reliable-sources of scientific content and has massive reachability across Middle East and beyond. RESULTS: We strongly believe that this model is a simple and suitable approach that may be helpful for other low-income or war-torn countries in the context of health-related disasters. CONCLUSIONS: This subject is of high importance and we believe that this approach may ameliorate public health knowledge, thus, participate in defying the COVID-19 consequences.

negative: Structural Factors of the Middle East Respiratory Syndrome Coronavirus Outbreak as a Public Health Crisis in Korea and Future Response Strategies The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak has originated from a failure in the national quarantine system in the Republic of Korea as most basic role of protecting the safety and lives of its citizens. Furthermore, a number of the Korean healthcare system’s weaknesses seem to have been completely exposed. The MERS-CoV outbreak can be considered a typical public health crisis in that the public was not only greatly terrorized by the actual fear of the disease, but also experienced a great impact to their daily lives, all in a short period of time. Preparedness for and an appropriate response to a public health crisis require comprehensive systematic public healthcare measures to address risks comprehensively with an all-hazards approach. Consequently, discussion regarding establishment of post-MERS-CoV improvement measures must focus on the total reform of the national quarantine system and strengthening of the public health infrastructure. In addition, the Korea Centers for Disease Control and Prevention must implement specific strategies of action including taking on the role of “control tower” in a public health emergency, training of Field Epidemic Intelligence Service officers, establishment of collaborative governance between central and local governments for infection prevention and control, strengthening the roles and capabilities of community-based public hospitals, and development of nationwide crisis communication methods.

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

negative: Grand Challenges in Migration Biology Billions of animals migrate each year. To successfully reach their destination, migrants must have evolved an appropriate genetic program and suitable developmental, morphological, physiological, biomechanical, behavioral, and life-history traits. Moreover, they must interact successfully with biotic and abiotic factors in their environment. Migration therefore provides an excellent model system in which to address several of the “grand challenges” in organismal biology. Previous research on migration, however, has often focused on a single aspect of the phenomenon, largely due to methodological, geographical, or financial constraints. Integrative migration biology asks ‘big questions’ such as how, when, where, and why animals migrate, which can be answered by examining the process from multiple ecological and evolutionary perspectives, incorporating multifaceted knowledge from various other scientific disciplines, and using new technologies and modeling approaches, all within the context of an annual cycle. Adopting an integrative research strategy will provide a better understanding of the interactions between biological levels of organization, of what role migrants play in disease transmission, and of how to conserve migrants and the habitats upon which they depend.

negative: COVID-19: What Can We Learn From Stories From the Trenches?

negative: Detection of SARS-COV-2 in Placental and Fetal Membrane Samples Introduction Since the first reports of the emergence of the novel coronavirus SARS-CoV-2 and its associated disease (COVID-19), concerns remain about whether the virus is transmissible in pregnant women from the mother to the fetus during either the antepartum period or the process of labor and delivery. One recent review reported that in a small number of cases, two PCR swabs of the placenta were sent in additional to neonatal and cord blood testing, and both placental PCR swabs were negative.1 Other studies have demonstrated the finding of SARS-CoV2 IgM in neonates born to mothers diagnosed with COVID-19 during pregnancy,2,3 findings that may indicate vertical transmission of the virus in utero. We report our experience with placental/membrane SARS-CoV2 RNA PCR swab results after delivery to a series of symptomatic mothers with confirmed COVID-19 infection in pregnancy. Methods IRB approval was obtained. All pregnant patients diagnosed with COVID-19 who gave birth between March 1, 2020 and April 20, 2020 at NYU Langone Health were identified by a search of the electronic medical record. Charts were reviewed for documentation of SARS-CoV-2 RNA RT-PCR testing sent from either the placenta or membranes within 30 minutes following delivery. PCR testing for SARS-COV-2 was performed using the cobas SARS-CoV-2 assay (Roche) or the Cepheid Xpert Xpress assay. Placental swabs were obtained from the amniotic surface after clearing the surface of maternal blood (placental PCR). Membrane swabs were obtained from between the amnion and chorion after manual separation of the membranes (membrane PCR). Maternal COVID-19 illness was categorized as mild, severe, or critical.4 The time interval from maternal diagnosis of COVID-19 to delivery was calculated in days. Infants were tested with nasopharyngeal swabs for SARS-CoV-2 PCR between days of life 1 and 5 while hospitalized. Hospitalized infants were also assessed for clinical signs and symptoms, including fever, cough, and nasal congestion. Results Of 32 COVID-19 positive pregnant patients who gave birth in this timeframe, placental or membrane swabs were sent from 11 patients (Table). Three of 11 swabs were positive. None of the infants tested positive for SARS-CoV2 on days of life 1 through 5, and none demonstrated symptoms of COVID-19 infection. Discussion Of 11 placental or membrane swabs sent following delivery, 3 swabs were positive for SARS-CoV-2, all in women with moderate to severe COVID-19 illness at time of delivery. This is the first study to demonstrate the presence of SARS-CoV-2 RNA in placental or membrane samples. While there were no clinical signs of vertical transmission, our findings raise the possibility of intrapartum viral exposure. Given the mixing of maternal and fetal fluid and tissue at time of delivery, the origin of the detected SARS-CoV-2 RNA in our series is unclear. It may represent contamination from maternal blood, amniotic fluid, or COVID-19 infection of the membranes and amniotic sac. For those infants who were delivered vaginally, contamination with vaginal secretions is also a possible source, although prior studies on vaginal secretions have failed to demonstrate the presence of COVID-19.5,6 Although all of our neonates tested negative in the first 5 days of life, many were born via cesarean deliveries with decreased length of exposure to these tissues, which may be associated with a decreased likelihood of vertical transmission. Additionally, nasopharyngeal testing immediately after delivery may not be the ideal approach to evaluate vertical transmission if exposure occurs at the time of delivery, as the virus may require a longer incubation period before these swabs convert to positive. In summary, the presence of viral RNA by RT-PCR in placenta/membranes at the time of delivery suggests the need for further research into the possibility of vertical transmission.

negative: As descobertas genômicas do SARS-CoV-2 e suas implicações na pandemia de COVID-19 Objetivo: Auxiliar no entendimento da COVID-19 em relação à origem do SARS-CoV-2, suas descobertas genômicas, patogenia, possíveis hospedeiros primários e intermediários, além da comparação com outros coronavírus Metodos: foram utilizadas as bases de dados Scientific Eletronic Library Online e PubMed, com artigos de revisão e originais, em língua portuguesa e inglesa, pesquisados no período de 05 de março a 10 de abril de 2020, adotando os seguintes descritores: SARS-CoV, COVID-19, coronavirus, Wuhan, genome, structure, origin, transmission, evolution, zoonotic Os artigos originais identificados foram incluídos nesta revisão, juntamente com artigos de suporte referenciados por estes Resultados: As características genômicas descritas até o momento podem explicar, em parte, a infectividade e a transmissibilidade do SARS-CoV-2 em humanos Devido aos notáveis recursos de SARS-CoV-2, incluindo o local otimizado do domínio de ligação ao receptor (RBD) e de clivagem polibásica, é pouco provável um cenário laboratorial para a origem do SARS-CoV-2 Conclusão: Para o presente, é de extrema importância obter mais dados genéticos e funcionais sobre o SARS-CoV-2, incluindo estudos em animais, sequenciamento do vírus em casos muito precoces e identificação dos parentes virais mais próximos do SARS-CoV-2 que circulam em animais (AU)Objective: To assist in the understanding of COVID-19 in relation to the origin of SARS-CoV-2, its genomic discoveries, pathogenesis, possible primary and intermediate hosts, in addition to comparison with other coronaviruses Methods: the Scientific Electronic Library Online and PubMed databases were used, with review articles and originals, in Portuguese and English, researched from March 5 to April 10, 2020, adopting the following descriptors: SARS-CoV , COVID-19, coronavirus, Wuhan, genome, structure, origin, transmission, evolution, zoonotic The original articles identified were included in this review, along with supporting articles referenced by them Results: The genomic characteristics described so far may partly explain the infectivity and transmissibility of SARS-CoV-2 in humans Due to the remarkable resources of SARS-CoV-2, including the optimized site of the receptor binding domain (RBD) and polybasic cleavage, a laboratory scenario for the origin of SARS-CoV-2 is unlikely Conclusion: For the present, it is extremely important to obtain more genetic and functional data on SARS-CoV-2, including studies on animals, sequencing of the virus in very early cases and identification of the closest viral relatives of SARS-CoV-2 that circulate in animals (AU)

negative: Investigation of Animal Reservoir(s) of SARS-CoV Severe acute respiratory syndrome (SARS) is a novel infectious disease in the new millennium. It has been ascertained that a new coronavirus, SARS-CoV, is the etiological agent of SARS. While the extraordinarily rapid isolation and full genome sequencing of SARS-CoV constituted a remarkable scientific achievement, identification of the actual animal reservoir(s) of SARS-CoV is more difficult. Initial evidences indicated that the masked palm civet (Paguma larvata) was the primary suspect of the animal origin of SARS (Guan et al., 2003; Song et al., 2005). Recent studies suggested that horseshoe bat is one of the real reservoirs (Lau et al., 2005; Li et al., 2005) and masked palm civet may have only served as an intermediate amplification host for SARS-CoV and fulfilled efficient interspecies transmission (Lau et al., 2005). This chapter will summarize the studies on the animal reservoir(s) of SARS-CoV.

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

negative: Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.

negative: A novel coronavirus (SARS-CoV-2) and COVID-19. By the end of 2019 the first cases of severe pneumonia of unknown origin were reported in Wuhan, China. The causative agent was identified as a novel b-coronavirus SARS-CoV-2 and the disease was named COVID-19. Since the beginning of 2020, the infection has spread worldwide, which led the WHO to declare COVID-19 a public health emergency of international concern and to characterize the current situation as a pandemic. The transmission occurs mainly via respiratory droplets and the incubation period ranges from 2 to 14 days. Most cases are mild, but some patients develop severe pneumonia with acute respiratory distress, septic shock and multi-organ failure. The most common symptoms include fever, dry cough, myalgia and shortness of breath. Characteristic laboratory findings are normal white blood cell count or mild leukopenia, marked lymphopenia, in severe cases elevated CRP, procalcitonin, LDH, and D-dimer are commonly found. Typical imaging findings include multifocal peripherally distributed ground-glass opacities or consolidations, interlobular septal thickening, crazy paving appearance and cystic changes. The overall case fatality rate is estimated to range from 1 to 3 %, however, it is dependent on age and underlying medical comorbidities. Current potential treatment options include hydroxychloroquine, remdesivir, lopinavir/ritonavir and convalescent plasma.

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: Discovery of a novel coronavirus, China Rattus coronavirus HKU24, from Norway rats supports the murine origin of Betacoronavirus 1 and has implications for the ancestor of Betacoronavirus lineage A. UNLABELLED We discovered a novel Betacoronavirus lineage A coronavirus, China Rattus coronavirus (ChRCoV) HKU24, from Norway rats in China. ChRCoV HKU24 occupied a deep branch at the root of members of Betacoronavirus 1, being distinct from murine coronavirus and human coronavirus HKU1. Its unique putative cleavage sites between nonstructural proteins 1 and 2 and in the spike (S) protein and low sequence identities to other lineage A betacoronaviruses (βCoVs) in conserved replicase domains support ChRCoV HKU24 as a separate species. ChRCoV HKU24 possessed genome features that resemble those of both Betacoronavirus 1 and murine coronavirus, being closer to Betacoronavirus 1 in most predicted proteins but closer to murine coronavirus by G+C content, the presence of a single nonstructural protein (NS4), and an absent transcription regulatory sequence for the envelope (E) protein. Its N-terminal domain (NTD) demonstrated higher sequence identity to the bovine coronavirus (BCoV) NTD than to the mouse hepatitis virus (MHV) NTD, with 3 of 4 critical sugar-binding residues in BCoV and 2 of 14 contact residues at the MHV NTD/murine CEACAM1a interface being conserved. Molecular clock analysis dated the time of the most recent common ancestor of ChRCoV HKU24, Betacoronavirus 1, and rabbit coronavirus HKU14 to about the year 1400. Cross-reactivities between other lineage A and B βCoVs and ChRCoV HKU24 nucleocapsid but not spike polypeptide were demonstrated. Using the spike polypeptide-based Western blot assay, we showed that only Norway rats and two oriental house rats from Guangzhou, China, were infected by ChRCoV HKU24. Other rats, including Norway rats from Hong Kong, possessed antibodies only against N protein and not against the spike polypeptide, suggesting infection by βCoVs different from ChRCoV HKU24. ChRCoV HKU24 may represent the murine origin of Betacoronavirus 1, and rodents are likely an important reservoir for ancestors of lineage A βCoVs. IMPORTANCE While bats and birds are hosts for ancestors of most coronaviruses (CoVs), lineage A βCoVs have never been found in these animals and the origin of Betacoronavirus lineage A remains obscure. We discovered a novel lineage A βCoV, China Rattus coronavirus HKU24 (ChRCoV HKU24), from Norway rats in China with a high seroprevalence. The unique genome features and phylogenetic analysis supported the suggestion that ChRCoV HKU24 represents a novel CoV species, occupying a deep branch at the root of members of Betacoronavirus 1 and being distinct from murine coronavirus. Nevertheless, ChRCoV HKU24 possessed genome characteristics that resemble those of both Betacoronavirus 1 and murine coronavirus. Our data suggest that ChRCoV HKU24 represents the murine origin of Betacoronavirus 1, with interspecies transmission from rodents to other mammals having occurred centuries ago, before the emergence of human coronavirus (HCoV) OC43 in the late 1800s. Rodents are likely an important reservoir for ancestors of lineage A βCoVs.

negative: SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart Coronavirus disease (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptoms of the disease range from asymptomatic to mild respiratory symptoms and even potentially life-threatening cardiovascular and pulmonary complications. Cardiac complications include acute myocardial injury, arrhythmias, cardiogenic shock and even sudden death. Furthermore, drug interactions with COVID-19 therapies may place the patient at risk for arrhythmias, cardiomyopathy and sudden death. In this review, we summarise the cardiac manifestations of COVID-19 infection and propose a simplified algorithm for patient management during the COVID-19 pandemic.

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

negative: COVID-19 and importance of environmental sustainability

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

negative: Zoonoses in the Emergence of Human Viral Diseases Viral zoonoses have represented a significant public health problem throughout history, affecting all continents. Furthermore, many viral zoonoses have emerged or reemerged in recent years, highlighting the importance of such diseases. Emerging viral zoonoses encompass a vast number of different viruses and many different transmission modes. There are many factors influencing the epidemiology of the various zoonoses, such as ecological changes, changes in agriculture and food production, the movement of pathogens, including via travel and trade, human behavior and demographical factors, and microbial changes and adaptation. Cost-effective prevention and control of emerging viral zoonoses necessitates an interdisciplinary and holistic approach and international cooperation. Surveillance, laboratory capability, research, training and education, and last but not least, information and communication are key elements.

negative: CovidSens: A Vision on Reliable Social Sensing for COVID-19 With the spiraling pandemic of the Coronavirus Disease 2019 (COVID-19), it has becoming inherently important to disseminate accurate and timely information about the disease. Due to the ubiquity of Internet connectivity and smart devices, social sensing is emerging as a dynamic AI-driven sensing paradigm to extract real-time observations from online users. In this paper, we propose CovidSens, a vision of social sensing based risk alert systems to spontaneously obtain and analyze social data to infer COVID-19 propagation. CovidSens can actively help to keep the general public informed about the COVID-19 spread and identify risk-prone areas. The CovidSens concept is motivated by three observations: 1) people actively share their experience of COVID-19 via online social media, 2) official warning channels and news agencies are relatively slower than people reporting on social media, and 3) online users are frequently equipped with powerful mobile devices that can perform data processing and analytics. We envision unprecedented opportunities to leverage posts generated by ordinary people to build real-time sensing and analytic system for gathering and circulating COVID-19 propagation data. Specifically, the vision of CovidSens attempts to answer the questions: How to distill reliable information on COVID-19 with prevailing rumors and misinformation? How to inform the general public about the state of the spread timely and effectively? How to leverage the computational power on edge devices to construct fully integrated edge-based social sensing platforms? In this vision paper, we discuss the roles of CovidSens and identify potential challenges in developing reliable social sensing based risk alert systems. We envision that approaches originating from multiple disciplines can be effective in addressing the challenges. Finally, we outline a few research directions for future work in CovidSens.

negative: Application of a Risk Analysis Tool to Middle East Respiratory Syndrome Coronavirus (MERS‐CoV) Outbreak in Saudi Arabia The Grunow–Finke assessment tool (GFT) is an accepted scoring system for determining likelihood of an outbreak being unnatural in origin. Considering its high specificity but low sensitivity, a modified Grunow–Finke tool (mGFT) has been developed with improved sensitivity. The mGFT has been validated against some past disease outbreaks, but it has not been applied to ongoing outbreaks. This study is aimed to score the outbreak of Middle East respiratory syndrome coronavirus (MERS‐CoV) in Saudi Arabia using both the original GFT and mGFT. The publicly available data on human cases of MERS‐CoV infections reported in Saudi Arabia (2012–2018) were sourced from the FluTrackers, World Health Organization, Saudi Ministry of Health, and published literature associated with MERS outbreaks investigations. The risk assessment of MERS‐CoV in Saudi Arabia was analyzed using the original GFT and mGFT criteria, algorithms, and thresholds. The scoring points for each criterion were determined by three researchers to minimize the subjectivity. The results showed 40 points of total possible 54 points using the original GFT (likelihood: 74%), and 40 points of a total possible 60 points (likelihood: 67%) using the mGFT, both tools indicating a high likelihood that human MERS‐CoV in Saudi Arabia is unnatural in origin. The findings simply flag unusual patterns in this outbreak, but do not prove unnatural etiology. Proof of bioattacks can only be obtained by law enforcement and intelligence agencies. This study demonstrated the value and flexibility of the mGFT in assessing and predicting the risk for an ongoing outbreak with simple criteria.

negative: 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.

negative: The SARS-CoV-2 outbreak: What we know 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: Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses Abstract Recent international epidemics of coronavirus-associated illnesses underscore the urgent medical and public health need for vaccine development and regulatory body approved therapies. In particular, the current coronavirus disease 2019 (COVID-19) pandemic has quickly intensified interest in developing treatment options to mitigate impact on human life. Remdesivir (GS-5734™) is a broad-spectrum antiviral drug that is now being tested as a potential treatment for COVID-19 in international, multi-site clinical trials. Currently available evidence about the antiviral effects of remdesivir against coronaviruses is primarily based on in vitro and in vivo studies (including some on a chemically related compound, GS-441524™), which have demonstrated largely favorable findings. As the pandemic progresses, information from human compassionate use cases will continue to accumulate before the clinical trials are concluded. It is imperative for public health practitioners and the One Health community to stay up to date on the most promising potential therapeutic options that are under investigation. Thus, the purpose of this review is to synthesize the knowledge to date about remdesivir as a therapeutic option for coronaviruses, with a special focus on information relevant to the One Health community.

negative: Anesthesia and COVID-19: What We Should Know and What We Should Do Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, Hubei, China, and has spread to more than 200 other countries around the world. COVID-19 is a highly contagious disease with continuous human-to-human transmission. The origin of the virus is unknown. Airway manipulations and intubations, which are common during anesthesia procedures may increasingly expose anesthesia providers and intensive care unit team members to SARS-CoV-2. Through a comprehensive review of existing studies on COVID-19, this article presents the epidemiological and clinical characteristics of COVID-19, reviews current medical management, and suggests ways to improve the safety of anesthetic procedures. Owing to the highly contagious nature of the virus and the lack of therapeutic drugs or vaccines, precautions should be taken to prevent medical staff from COVID-19.

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

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

negative: BOOK REVIEWS Book reviewed in this article: Bradley W. G. Disorders of peripheral nerves Eliasson S. G., Prensky A. L. & Hardin W. B. Jr (eds) Neurological Pathophysiology Schenk E. Neurologische Untersuchungsmethoden

negative: Commercial exchanges instead of air pollution as possible origin of COVID-19 initial diffusion phase in Italy: More efforts are necessary to address interdisciplinary research This communication aims to advocate a more coordinate activity mainly between medical and environmental scientists to clarify some confusing information related to airborne diffusion mechanisms of COVID-19. In this frame it is suggested that parameters other than environmental pollution (accounting for pollution-to-human transmission mechanisms), as for example parameters involving commercial exchanges (accounting for human-to-human transmission mechanisms), should be considered to better justify the difference in the initial diffusion of virus in Italy.

negative: COVID-19 infection and recovery in various countries: Modeling the dynamics and evaluating the non-pharmaceutical mitigation scenarios The coronavirus disease 2019 (COVID-19) pandemic radically impacts our lives, while the transmission/infection and recovery dynamics of COVID-19 remain obscure. A time-dependent Susceptible, Exposed, Infectious, and Recovered (SEIR) model was proposed and applied to fit and then predict the time series of COVID-19 evolution observed in the last three months (till 3/22/2020) in various provinces and metropolises in China. The model results revealed the space dependent transmission/infection rate and the significant spatiotemporal variation in the recovery rate, likely due to the continuous improvement of screening techniques and public hospital systems, as well as full city lockdowns in China. The validated SEIR model was then applied to predict COVID-19 evolution in United States, Italy, Japan, and South Korea which have responded differently to monitoring and mitigating COVID-19 so far, although these predictions contain high uncertainty due to the intrinsic change of the maximum infected population and the infection/recovery rates within the different countries. In addition, a stochastic model based on the random walk particle tracking scheme, analogous to a mixing-limited bimolecular reaction model, was developed to evaluate non-pharmaceutical strategies to mitigate COVID-19 spread. Preliminary tests using the stochastic model showed that self-quarantine may not be as efficient as strict social distancing in slowing COVID-19 spread, if not all of the infected people can be promptly diagnosed and quarantined.

negative: Multivariate Analyses of Codon Usage of SARS-CoV-2 and other betacoronaviruses Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus which also includes severe acute respiratory syndrome related coronavirus (SARSr-CoV) and Middle East respiratory syndrome related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses can help identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, global correspondence analysis (CA), within-group correspondence analysis (WCA) and between-group correspondence analysis (BCA) were performed among different genes in coronavirus viral sequences. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.

negative: A first look at COVID-19 information and misinformation sharing on Twitter Since December 2019, COVID-19 has been spreading rapidly across the world. Not surprisingly, conversation about COVID-19 is also increasing. This article is a first look at the amount of conversation taking place on social media, specifically Twitter, with respect to COVID-19, the themes of discussion, where the discussion is emerging from, myths shared about the virus, and how much of it is connected to other high and low quality information on the Internet through shared URL links. Our preliminary findings suggest that a meaningful spatio-temporal relationship exists between information flow and new cases of COVID-19, and while discussions about myths and links to poor quality information exist, their presence is less dominant than other crisis specific themes. This research is a first step toward understanding social media conversation about COVID-19.

negative: COVID-19 outcomes in patients with hematologic disease

negative: Safety Guidelines for Sterility of Face Shields During COVID 19 Pandemic Face shields are personal protective equipment devices that are to be used by many health care workers during COVID 19 pandemic for protection of the facial area and associated mucous membranes (eyes, nose, mouth) from droplet spread of infection. Face shields are generally not used alone, but in conjunction with other protective equipment like cap, mask, goggle, and are therefore classified as adjunctive personal protective equipment. In the wake of scarcity of face shields during the COVID 19 Pandemic, consideration of innovating newer methods of manufacturing must be considered to overcome the present day scarcity without jeopardising the safety of front line Heath care workers. All initial fast innovations comes with advantages and disadvantages, hence we thought of putting down simple guidelines for new emerged face shield use.

negative: Analysis and Prediction of False Negative Results for SARS-CoV-2 Detection with Pharyngeal Swab Specimen in COVID-19 Patients: A Retrospective Study Background: False negative results of SARS-CoV-2 nucleic acid detection pose threats to COVID-19 patients and medical workers alike. Objective: To develop multivariate models to determine clinical characteristics that contribute to false negative results of SARS-CoV-2 nucleic acid detection, and use them to predict false negative results as well as time windows for testing positive. Design: Retrospective Cohort Study (Ethics number of Tongji Hospital: No. IRBID: TJ-20200320) Setting: A database of outpatients in Tongji Hospital (University Hospital) from 15 January 2020 to 19 February 2020. Patients: 1,324 outpatients with COVID-19 Measurements: Clinical information on CT imaging reports, blood routine tests, and clinic symptoms were collected. A multivariate logistic regression was used to explain and predict false negative testing results of SARS-CoV-2 detection. A multivariate accelerated failure model was used to analyze and predict delayed time windows for testing positive. Results: Of the 1,324 outpatients who diagnosed of COVID-19, 633 patients tested positive in their first SARS-CoV-2 nucleic acid test (47.8%), with a mean age of 51 years (SD=14.9); the rest, which had a mean age of 47 years (SD=15.4), tested negative in the first test. Ground glass opacity in a CT imaging report was associated with a lower chance of false negatives (aOR, 0.56), and reduced the length of time window for testing positive by 26%. Consolidation was associated with a higher chance of false negatives (aOR, 1.57), and extended the length of time window for testing positive by 44%. In blood routine tests, basophils (aOR, 1.28) and eosinophils (aOR, 1.29) were associated with a higher chance of false negatives, and were found to extend the time window for testing positive by 23% and 41%, respectively. Age and gender also affected the significantly. Limitation: Data were generated in a large single-center study. Conclusion: Testing outcome and positive window of SARS-CoV-2 detection for COVID-19 patients were associated with CT imaging results, blood routine tests, and clinical symptoms. Taking into account relevant information in CT imaging reports, blood routine tests, and clinical symptoms helped reduce a false negative testing outcome. The predictive AFT model, what we believe to be one of the first statistical models for predicting time window of SARS-CoV-2 detection, could help clinicians improve the accuracy and efficiency of the diagnosis, and hence, optimizes the timing of nucleic acid detection and alleviates the shortage of nucleic acid detection kits around the world. Primary Funding Source: None.

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: Next weeks of SARS-CoV-2: Projection model to predict time evolution scenarios of accumulated cases in Spain Background and objectives: SARS-CoV-2 is a new type of coronavirus that can affect people and causes respiratory disease, COVID-19. It is affecting the entire planet and we focus in Spain, where the first case was detected at the end of January 2020 and in recent weeks it has increased in many cases. We need predictive models in order to be efficient and take actions. The general goal of this work is present a new model of SARS-CoV-2 to predict different scenarios of accumulated cases in Spain. Material and methods: In this short report is used a model proposed previously, based on a parametric model Weibull and in a the library BDSbiost3 developed in R to infer and predict different scenarios of the evolution of SARS-CoV-2 for the accumulated cases in Spain after the spread that affects Spain detected at the end of January of this year. Results: In the analyses presented, projective curves have been generated for the evolution of accumulated cases in which they reach about 4,000 cases or about 15,000 cases, for which the lines of the day in which the value for 90 will be reached can be seen vertically 90, 95 and 99% of the asymptote (maximum number of cases, from that day they will begin to descend or remain the same), that is why the vertical lines would indicate the brake of the disease. For the worst-case scenario, it takes 118, 126 or 142 days to reach the maximum number of cases (n = 15,000) to reach 90, 95 and 99% of the asymptote (maximum number of cases), respectively. This means translated in a time scale that in the worst case the virus will not stop its progress, in Spain, until summer 2020, hopefully before. Comments and conclusions: This model could be used to plan the resources and see if the policies or means dedicated to the virus are slowing the progress of the virus or it is necessary to implement others that are more effective, and can also validate a method for future outbreaks of diseases such as these.

negative: Co-infection with Influenza A and COVID-19 COVID-19, also called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), originated in Wuhan, China. It has caused significant morbidity and mortality worldwide and has been declared a global pandemic by the WHO. Influenza occurs mainly during the winter, with the burden of disease determined by several factors, including the effectiveness of the vaccine that season, the characteristics of the circulating viruses, and how long the season lasts. We describe the case of a 66-year-old woman who was diagnosed with influenza A and COVID-19 co-infection. LEARNING POINTS: COVID-19 can co-occur with other viral infections. Some of these co-infections have active treatments, while supportive treatment is the mainstay of treatment for others.

negative: Transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at low and intermediate risk: systematic review and meta-analysis. OBJECTIVE To examine the effect of transcatheter aortic valve implantation (TAVI) versus surgical replacement of an aortic valve (SAVR) in patients with severe aortic stenosis at low and intermediate risk of perioperative death. DESIGN Systematic review and meta-analysis DATA SOURCES: Medline, Embase, and Cochrane CENTRAL. STUDY SELECTION Randomized trials of TAVI compared with SAVR in patients with a mean perioperative risk of death <8%. REVIEW METHODS Two reviewers independently extracted data and assessed risk of bias for outcomes important to patients that were selected a priori by a parallel guideline committee, including patient advisors. We used the GRADE system was used to quantify absolute effects and quality of evidence. RESULTS 4 trials with 3179 patients and a median follow-up of two years were included. Compared with SAVR, transfemoral TAVI was associated with reduced mortality (risk difference per 1000 patients: -30, 95% confidence interval -49 to -8, moderate certainty), stroke (-20, -37 to 1, moderate certainty), life threatening bleeding (-252, -293 to -190, high certainty), atrial fibrillation (-178, -150 to -203, moderate certainty), and acute kidney injury (-53, -39 to -62, high certainty) but increased short term aortic valve reintervention (7, 1 to 21, moderate certainty), permanent pacemaker insertion (134, 16 to 382, moderate certainty), and moderate or severe symptoms of heart failure (18, 5 to 34, moderate certainty). Compared with SAVR, transapical TAVI was associated higher mortality (57, -16 to 153, moderate certainty, P=0.015 for interaction between transfemoral versus transapical TAVI) and stroke (45, -2 to 125, moderate certainty, interaction P=0.012). No study reported long term follow-up, which is particularly important for structural valve deterioration. CONCLUSIONS Many patients, particularly those who have a shorter life expectancy or place a lower value on the risk of long term valve degeneration, are likely to perceive net benefit with transfemoral TAVI versus SAVR. SAVR, however, performs better than transapical TAVI, which is of interest to patients who are not candidates for transfemoral TAVI. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016042879.

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

negative: Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, in 2019, is responsible for the COVID-19 pandemic. It is now accepted that the wild fauna, probably bats, constitute the initial reservoir of the virus, but little is known about the role pets can play in the spread of the disease in human communities, knowing the ability of SARS-CoV-2 to infect some domestic animals. We tested 21 domestic pets (9 cats and 12 dogs) living in close contact with their owners (belonging to a veterinary community of 20 students) in which two students tested positive for COVID-19 and several others (n = 11/18) consecutively showed clinical signs (fever, cough, anosmia, etc.) compatible with COVID-19 infection. Although a few pets presented many clinical signs indicative for a coronavirus infection, no animal tested positive for SARS-CoV-2 by RT-PCR and no antibodies against SARS-CoV-2 were detectable in their blood using an immunoprecipitation assay. These original data can serve a better evaluation of the host range of SARS-CoV-2 in natural environment exposure conditions.

negative: MHC class I allele diversity in cynomolgus macaques of Vietnamese origin Cynomolgus macaques (Macaca fascicularis, Mafa) have been used as important experimental animal models for carrying out biomedical researches. The results of biomedical experiments strongly depend on the immunogenetic background of animals, especially on the diversity of major histocompatibility complex (MHC) alleles. However, there is much less information available on the polymorphism of MHC class I genes in cynomolgus macaques, than is currently available for humans. In this study, we have identified 40 Mafa-A and 60 Mafa-B exons 2 and 3 sequences from 30 unrelated cynomolgus macaques of Vietnamese origin. Among these alleles, 28 are novel. As for the remaining 72 known alleles, 15 alleles are shared with other cynomolgus macaque populations and 32 are identical to alleles previously reported in other macaque species. A potential recombination event was observed between Mafa-A1*091:02 and Mafa-A1*057:01. In addition, the Mafa-A1 genes were found to be more diverse than human HLA-A and the functional residues for peptide binding sites (PBS) or TCR binding sites (TBS) in Mafa-A1 have greater variability than that for non-PBS or non-TBS regions. Overall, this study provides important information on the diversity of Mafa-A and Mafa-B alleles from Vietnamese origin, which may help researchers to choose the most appropriate animals for their studies.

negative: Development of antiviral therapy for severe acute respiratory syndrome Abstract A new disease, the severe acute respiratory distress syndrome (SARS), caused by the SARS coronavirus (SARS-CoV), emerged at the beginning of 2003 and rapidly spread throughout the world. Although the disease had disappeared in June 2003 its re-emergence cannot be excluded. The development of vaccines against SARS-CoV may take years. Therefore, the availability of effective antiviral drugs against SARS-CoV may be crucial for the control of future SARS outbreaks. In this review, experimental and clinical data about potential anti-SARS drugs is summarised and discussed. Animal model studies will be needed to help to determine which interventions warrant controlled clinical testing.

negative: Scientific Publications During the COVID-19 Pandemic • COVID-19 pandemics has shocked our world in a few months, not only by attacking individual health, but also public health and economic systems, the way people relate to each other, but has also changed scientific and editorial practices.

negative: Symmetrical polyneuropathy in Coronavirus Disease 2019 (COVID-19) The outbreak of the novel coronavirus that began in late December 2019 was announced as a pandemic by the World Health Organization as the number of cases is increasing exponentially throughout the globe. We present a patient with confirmed SARS-CoV-2 pneumonia developing symmetric polyneuropathy. To our knowledge, extrapulmonary clinical presentations of 2019 novel coronavirus disease (COVID-19) have rarely been reported. This case highlights the possible association between SARS-CoV-2 infection and nervous system involvement.

negative: Estimation of time-varying reproduction numbers underlying epidemiological processes: a new statistical tool for the COVID-19 pandemic The coronavirus pandemic has rapidly evolved into an unprecedented crisis. The susceptible-infectious-removed (SIR) model and its variants have been used for modeling the pandemic. However, time-independent parameters in the classical models may not capture the dynamic transmission and removal processes, governed by virus containment strategies taken at various phases of the epidemic. Moreover, very few models account for possible inaccuracies of the reported cases. We propose a Poisson model with time-dependent transmission and removal rates to account for possible random errors in reporting and estimate a time-dependent disease reproduction number, which may be used to assess the effectiveness of virus control strategies. We apply our method to study the pandemic in several severely impacted countries, and analyze and forecast the evolving spread of the coronavirus. We have developed an interactive web application to facilitate readers' use of our method.

negative: Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2 A newly identified novel coronavirus (SARS-CoV-2) is causing pneumonia-associated respiratory syndrome across the world. Epidemiology, genomics, and pathogenesis of the SARS-CoV-2 show high homology with that of SARS-CoV. Current efforts are focusing on development of specific antiviral drugs. Therapeutic neutralizing antibodies (NAbs) against SARS-CoV-2 will be greatly important therapeutic agents for the treatment of coronavirus disease 2019 (COVID-19). Herein, the host immune responses against SARS-CoV discussed in this review provide implications for developing NAbs and understanding clinical interventions against SARS-CoV-2. Further, we describe the benefits, challenges and considerations of NAbs against SARS-CoV-2. Although many challenges exist, NAbs still offer a therapeutic option to control the current pandemic and the possible re-emergence of the virus in the future, and their development therefore remains a high priority.

negative: A Comparative Analysis of Factors Influencing Two Outbreaks of Middle Eastern Respiratory Syndrome (MERS) in Saudi Arabia and South Korea In 2012, an emerging viral infection was identified in Saudi Arabia that subsequently spread to 27 additional countries globally, though cases may have occurred elsewhere. The virus was ultimately named Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), and has been endemic in Saudi Arabia since 2012. As of September 2019, 2468 laboratory-confirmed cases with 851 associated deaths have occurred with a case fatality rate of 34.4%, according to the World Health Organization. An imported case of MERS occurred in South Korea in 2015, stimulating a multi-month outbreak. Several distinguishing factors emerge upon epidemiological and sociological analysis of the two outbreaks including public awareness of the MERS outbreak, and transmission and synchronization of governing healthcare bodies. South Korea implemented a stringent healthcare model that protected patients and healthcare workers alike through prevention and high levels of public information. In addition, many details about MERS-CoV virology, transmission, pathological progression, and even the reservoir, remain unknown. This paper aims to delineate the key differences between the two regional outbreaks from both a healthcare and personal perspective including differing hospital practices, information and public knowledge, cultural practices, and reservoirs, among others. Further details about differing emergency outbreak responses, public information, and guidelines put in place to protect hospitals and citizens could improve the outcome of future MERS outbreaks.

negative: Clinically Significant Fear and Anxiety of COVID-19: A Psychometric Examination of the Coronavirus Anxiety Scale The present study examined the psychometric properties of the Coronavirus Anxiety Scale (CAS) using an online survey of 398 adult Amazon MTurk workers in the U.S. Confirmatory factor analyses demonstrated that the CAS measures a reliable (α = .92), unidimensional construct with a structure that was shown to be invariant across gender, race, and age. Construct validity was demonstrated with correlations between CAS scores and demographics, coronavirus diagnosis, history of anxiety, coronavirus fear, functional impairment, alcohol/drug coping, religious coping, hopelessness, suicidal ideation, as well as social attitudes (e.g., satisfaction with President Trump). The CAS also demonstrated solid discrimination ability for functional impairment (AUC =.88), while the original cut score of ≥ 9 (76% sensitivity and 90% specificity) showed the strongest diagnostic effectiveness among scores. Overall, these findings are largely consistent with the results of the first CAS investigation and support the validity of this mental health screener for COVID-19 related research and practice.

negative: COVID-19, una emergencia de salud pública mundial Resumen Un nuevo brote de coronavirus surgió el pasado 31 de diciembre de 2019 en Wuhan, China, causando conmoción entre la comunidad médica y el resto del mundo. Esta nueva especie de coronavirus fue denominada como 2019-nCoV, causante de un gran número de casos y fallecimientos en China y en cantidad creciente fuera de ella, convirtiéndose en una emergencia de salud pública a nivel mundial. 2019-nCoV es un virus con alta homología con otros coronavirus patogénicos, como los originados por zoonosis con murciélagos (SARS-CoV) causantes de aproximadamente 646 muertes en China a principios de la década. Su tasa de mortalidad no es tan elevada (aproximadamente del 2-3%), pero su rápida propagación ha propiciado la activación de protocolos para detener su diseminación. Este patógeno tiene el potencial para convertirse en pandemia, por lo que es vital seguir las recomendaciones de cuidado personal dictadas por la Organización Mundial de la Salud. Abstract A new coronavirus outbreak emerged on the 31st of December 2019 in Wuhan, China, causing commotion among the medical community and the rest of the world. This new species of coronavirus has been termed 2019-nCoV and has caused a considerable number of cases of infection and deaths in China and, to a growing degree, beyond China, becoming a worldwide public health emergency. 2019-nCoV has high homology to other pathogenic coronaviruses, such as those originating from bat-related zoonosis (SARS-CoV), which caused approximately 646 deaths in China at the start of the decade. The mortality rate for 2019-nCoV is not as high (approximately 2-3%), but its rapid propagation has resulted in the activation of protocols to stop its spread. This pathogen has the potential to become a pandemic. It is therefore vital to follow the personal care recommendations issued by the World Health Organisation.

negative: The journey of remdesivir: from Ebola to COVID-19 Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.

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: Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury INTRODUCTION: The production of antimicrobial peptides by airway epithelial cells is an important component of the innate immune response to pulmonary infection and inflammation. Hepcidin is a β-defensin-like antimicrobial peptide and acts as a principal iron regulatory hormone. Hepcidin is mostly produced by hepatocytes, but is also expressed by other cells, such as airway epithelial cells. However, nothing is known about its function in lung infections and inflammatory diseases. We therefore sought to investigate the role of airway epithelial cell-derived hepcidin in sepsis-induced acute lung injury. METHODS: Acute lung injury was induced by polymicrobial sepsis via cecal ligation and puncture (CLP) surgery. Adenovirus-mediated short hairpin RNA specific for the mouse hepcidin gene hepc1 and control adenovirus were intratracheally injected into mice. The adenovirus-mediated knockdown of hepcidin in airway epithelial cells was evaluated in vivo. Lung injury and the seven-day survival rate were assessed. The levels of hepcidin-related iron export protein ferroportin were measured, and the iron content and function of alveolar macrophages were evaluated. RESULTS: The hepcidin level in airway epithelial cells was upregulated during polymicrobial sepsis. The knockdown of airway epithelial cell-derived hepcidin aggravated the polymicrobial sepsis-induced lung injury and pulmonary bacterial infection and increased mortality (53.33% in Ad-shHepc1-treated mice versus 12.5% in Ad-shNeg-treated mice, P <0.05). The knockdown of hepcidin in airway epithelial cells also led to reduced ferroportin degradation and a low intracellular iron content in alveolar macrophages. Moreover, alveolar macrophages form the airway epithelial cell-derived hepcidin knockdown mice showed impaired phagocytic ability than those from the control mice. CONCLUSIONS: Airway epithelial cell-derived hepcidin plays an important role in CLP-induced acute lung injury. The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages.

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: Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species Continued reports of Middle East respiratory syndrome coronavirus (MERS-CoV) infecting humans have occurred since the identification of this virus in 2012. MERS-CoV is prone to cause endemic disease in the Middle East, with several dozen spillover infections to other continents. It is hypothesized that MERS-CoV originated from bat coronaviruses and that dromedary camels are its natural reservoir. Although gene segments identical to MERS-CoV were sequenced from certain species of bats and one species experimentally shed the virus, it is still unknown whether other bats can transmit the virus. Here, at the molecular level, we found that all purified bat CD26s (bCD26s) from a diverse range of species interact with the receptor binding domain (RBD) of MERS-CoV, with equilibrium dissociation constant values ranging from several to hundreds at the micromolar level. Moreover, all bCD26s expressed in this study mediated the entry of pseudotyped MERS-CoV to receptor-expressing cells, indicating the broad potential engagement of bCD26s as MERS-CoV receptors. Further structural analysis indicated that in the bat receptor, compared to the human receptor, substitutions of key residues and their adjacent amino acids leads to decreased binding affinity to the MERS-RBD. These results add more evidence to the existing belief that bats are the original source of MERS-CoV and suggest that bCD26s in many species can mediate the entry of the virus, which has significant implications for the surveillance and control of MERS-CoV infection. IMPORTANCE In this study, we found that bat CD26s (bCD26s) from different species exhibit large diversities, especially in the region responsible for binding to the receptor binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV). However, they maintain the interaction with MERS-RBD at varied affinities and support the entry of pseudotyped MERS-CoV. These bat receptors polymorphisms seem to confer evolutionary pressure for the adaptation of CD26-binding virus, such as the ancestor of MERS-CoV, and led to the generation of diversified CD26-engaging CoV strains. Thus, our data add more evidence to support that bats are the reservoir of MERS-CoV and similar viruses, as well as further emphasize the necessity to survey MERS-CoV and other CoVs among bats.

negative: Clinical and Paraclinical Characteristics of COVID-19 patients: A systematic review and meta-analysis Introduction: Recently, a new strain of coronaviruses, which originated from Wuhan City, Hubei Province, China has been identified. According to the high prevalence of new coronavirus, further investigation on the clinical and paraclinical features of this disease seems essential. Hence, we carried out this systematic review and meta-analysis to figure out the unknown features. Methods: This study was performed using databases of Web of Science, Scopus and PubMed. We considered English cross-sectional and case-series papers which reported clinical, radiological, and laboratory characteristics of patients with COVID-19. We used STATA v.11 and random effect model for data analysis. Results: In the present meta-analysis, 32 papers including 49504 COVID-19 patients were studied. The most common clinical symptoms were fever (84%), cough (65%) and fatigue (42%), respectively. The most common radiological and paraclinical features were bilateral pneumonia (61%), ground-glass opacity (50%), thrombocytopenia (36%) and lymphocytopenia (34%). The study also showed that the frequency of comorbidities and early symptoms was higher in critically severe patients. Moreover, we found the overall mortality rate of three percent. Conclusion: According to that there are many cases without Computed Tomography Scan findings or clear clinical symptoms, it is recommended to use other confirming methods such RNA sequencing in order to identification of suspicious undiagnosed patients. Moreover, while there is no access to clinical and paraclinical facilities in in public places such as airports and border crossings, it is recommended to consider factors such as fever, cough, sputum and fatigue.

negative: Pay attention to situation of SARS-CoV-2 and TCM advantages in treatment of novel coronavirus infection Since the outbreak of the new coronavirus epidemic, novel coronavirus has infected nearly 100,000 people in more than 110 countries. How to face this new coronavirus epidemic outbreak is an important issue. Basic reproduction number (R0) is an important parameter in epidemiology; The basic reproduction number of an infection can be thought of as the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection. Epidemiology dynamics is a mathematical model based on a susceptibility-infection-recovery epidemic model. Researchers analyzed the epidemiological benefits of different transmission rates for the establishment of effective strategy in prevention and control strategies for epidemic infectious diseases. In this review, the early use of TCM for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have wide application in treating infectious and non-infectious diseases. The TCM theoretical system of treating epidemic diseases with TCM and the treatment scheme of integrated Chinese and Western medicine have proved their effectiveness in clinical practice. TCM can cure COVID-19 pneumonia, and also shows that the role of TCM in blocking the progress of COVID-19 pneumonia.

negative: Keeping the Country Positive during the COVID 19 Pandemic: Evidence from India

negative: COVID-19 and Dialysis Units: What Do We Know Now and What Should We Do?

negative: Coronavirus threat to Indian population: risk factors, transmission dynamics and preparedness to prevent the spread of the virus Recent novel coronavirus outbreak in Wuhan City of Hubei province in China infected nearly 70,000 individuals and killed more than 1700 people within a short span of time leading to global pandemic. The disease is now spread to 26 countries in Asia, North America, Europe and Australasia. The virus is spreading rapidly to Asia-pacific and Southeast Asian countries. The disease is posing a serious threat to human population and has devastating impact on public health and economy. So far 3 Indians are infected and India is at risk of rapid spread of the disease because of its geographical location and other favorable conditions. With a poorer global health security index compared to China (India-57 and China-51), any such situation will have worse outcome. In near future there are also possibilities of similar kind of disease outbreak caused by new strains of coronaviruses due to factors like species jump of new viruses, high population density and inadequate medical facilities. In this short review we have highlighted the risk factors and transmission dynamics of coronaviruses that may pose a serious threat to India. We have also discussed about the possible preventive measure our country should take to control any such outbreak situation.

negative: Demonstration of CD13/Aminopeptidase N on Synovial Fluid T Cells from Patients with Different Forms of Joint Effusions Cytofluorometric analysis was performed to characterize the immunophenotype of lymphocytes of the synovial fluid (SF) and the peripheral blood (PB) from patients suffering from juvenile chronic arthritis (JCA) or rheumatoid arthritis (RA). The most obvious difference could be found in expression of the surface protease aminopeptidase N (AP N/CD13). Whereas monoclonal antibodies specific to CD13 failed to reveal surface expression on lymphocytes of the PB; 63 ± 15% of SF T cells gave positive staining for CD 13 using Leu-M7. No correlation between CD13 expression and joint disease could be found in patients who had different types of inflammatory joint effusions. CD13 expression of T cells was also found in synovial tissue and inflammatory serous cavity effusions. Fixation of T cells revealed the presence of intracellular CD13 antigen already located in the PB T cells of healthy individuals. Induction of CD13 expression on PB T cells could be demonstrated after incubation with Con A/IL-2 or SF from patients with RA. Our findings suggest a role for AP N as a new activation-associated molecule of T lymphocytes.

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: New journal selection for quantitative survey of infectious disease research: application for Asian trend analysis BACKGROUND: Quantitative survey of research articles, as an application of bibliometrics, is an effective tool for grasping overall trends in various medical research fields. This type of survey has been also applied to infectious disease research; however, previous studies were insufficient as they underestimated articles published in non-English or regional journals. METHODS: Using a combination of Scopus™ and PubMed, the databases of scientific literature, and English and non-English keywords directly linked to infectious disease control, we identified international and regional infectious disease journals. In order to ascertain whether the newly selected journals were appropriate to survey a wide range of research articles, we compared the number of original articles and reviews registered in the selected journals to those in the 'Infectious Disease Category' of the Science Citation Index Expanded™ (SCI Infectious Disease Category) during 1998-2006. Subsequently, we applied the newly selected journals to survey the number of original articles and reviews originating from 11 Asian countries during the same period. RESULTS: One hundred journals, written in English or 7 non-English languages, were newly selected as infectious disease journals. The journals published 14,156 original articles and reviews of Asian origin and 118,158 throughout the world, more than those registered in the SCI Infectious Disease Category (4,621 of Asian origin and 66,518 of the world in the category). In Asian trend analysis of the 100 journals, Japan had the highest percentage of original articles and reviews in the area, and no noticeable increase in articles was revealed during the study period. China, India and Taiwan had relatively large numbers and a high increase rate of original articles among Asian countries. When adjusting the publication of original articles according to the country population and the gross domestic product (GDP), Singapore and Taiwan were the most productive. CONCLUSION: A survey of 100 selected journals is more sensitive than the SCI Infectious Disease Category from the viewpoint of avoiding underestimating the number of infectious disease research articles of Asian origin. The survey method is applicable to grasp global trends in disease research, although the method may require further development.

negative: Stochastic dynamics of an epidemics with recurrent spillovers from an endemic reservoir Most emerging human infectious diseases have an animal origin. Yet, while zoonotic diseases originate from a primary reservoir, most theoretical studies have principally focused on single-host processes, either exclusively humans or exclusively animals, without considering the importance of animal to human transmission for understanding the dynamics of emerging infectious diseases. Here we aim to investigate the importance of spillover transmission for explaining the number and the size of outbreaks. We propose a simple stochastic Susceptible-Infected-Recovered model with a recurrent infection of an incidental host from a reservoir (e.g. humans by a zoonotic species), considering two modes of transmission, (1) animal-to-human and (2) human-to-human. The model assumes that (i) epidemiological processes are faster than other processes such as demographics or pathogen evolution and (ii) that an epidemic occurs until there are no susceptible individuals left. The results show that during an epidemic, even when the pathogens are barely contagious, multiple outbreaks are observed due to spillover transmission. Overall, the findings demonstrate that the only consideration of direct transmission between individuals is not sufficient to explain the dynamics of zoonotic pathogens in an incidental host.

negative: Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor [Image: see text] Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously called 2019-nCoV). Based on the rapid increase in the rate of human infection, the World Health Organization (WHO) has classified the COVID-19 outbreak as a pandemic. Because no specific drugs or vaccines for COVID-19 are yet available, early diagnosis and management are crucial for containing the outbreak. Here, we report a field-effect transistor (FET)-based biosensing device for detecting SARS-CoV-2 in clinical samples. The sensor was produced by coating graphene sheets of the FET with a specific antibody against SARS-CoV-2 spike protein. The performance of the sensor was determined using antigen protein, cultured virus, and nasopharyngeal swab specimens from COVID-19 patients. Our FET device could detect the SARS-CoV-2 spike protein at concentrations of 1 fg/mL in phosphate-buffered saline and 100 fg/mL clinical transport medium. In addition, the FET sensor successfully detected SARS-CoV-2 in culture medium (limit of detection [LOD]: 1.6 × 10(1) pfu/mL) and clinical samples (LOD: 2.42 × 10(2) copies/mL). Thus, we have successfully fabricated a promising FET biosensor for SARS-CoV-2; our device is a highly sensitive immunological diagnostic method for COVID-19 that requires no sample pretreatment or labeling.

negative: 2019 novel coronavirus disease in hemodialysis (HD) patients: Report from one HD center in Wuhan, China The outbreak of COVID-19 originated in Wuhan has become a global epidemic of contagious diseases, which poses a serious threat to human life and health, especially for those with underlined diseases. However, Impacts of COVID-19 epidemic on HD center and HD patients are still unknown. In this report, we reviewed the whole course of the epidemic emerged in the HD center of Renmin Hospital, Wuhan University from January 14, 2020, the day the first case was confirmed, to February 17, 2020, the day the epidemic extinction. There are totally 37 cases among 230 HD patients and 4 cases among 33 staff being diagnosed with COVID-19. The epidemiology, clinical presentation and immune profile of dialysis patients contracted COVID-19 were further studied. We found that the two key measures we took in response to the epidemic, one was upgrading level of prevention and protection on January 21 and the other one starting universal screening, isolating, and distributing the infected cases on February 4, were effective in the epidemic control. No new COVID-19 case had been diagnosed since February 13. During the epidemic, 7 HD patients died, including 6 with COVID-19 and 1 without COVID-19. The presumed causes of death were not directly related to pneumonia, but due to cardiovascular and cerebrovascular diseases, hyperkalemia, etc. Most of the leukocytes in the peripheral blood of the HD patients infected with COVID-19 decreased, and the CT images of the chest mostly showed the ground glass like changes on the right side. The symptoms of most of the patients were mild, and there were no cases admitted to ICU. The frequency of lymphocytes in PBMCs and the serum level of inflammatory cytokines were assessed in HD patients contracted COVID-19 or not, non-HD COVID-19 patients, as well as healthy volunteers. The results showed that lymphocytes of T cell, Th cells, killer T cells, as well as NK cells in PBMCs of HD patients decreased significantly than other groups. HD patients with COVID-19 also displayed remarkable lower serum level of inflammatory cytokines than other COVID-19 patients. Our study indicates that HD patients are the highly susceptible population and HD centers are high risk area in the outbreak of COVID-19 epidemic. Measures of prevention, protection, screening, isolation, and distribution are essential in the epidemic management and should be taken in the early stage. HD Patients with COVID-19 are mostly clinical mild and unlikely progress to severe pneumonia due to the impaired cellular immune function and incapability of mounting cytokines storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of COVID-19 epidemic on HD patients.

negative: COVID-19 outbreak: an elusive enemy Abstract A novel coronavirus, officially termed as severe acute respiratory syndrome (SARS)-CoV-2, emerged in Wuhan, China, toward the end of 2019. Just four months later, more than 100,000 people were diagnosed with COVID-19, the resulting disease. The genetic analysis of SARS-CoV-2 revealed that this virus is a new Betacoronavirus, closely related to bat-derived SARS-like coronaviruses. Clinical data from hospitals in China have revealed that approximately 10% of the infected patients have severe disease requiring intensive care. Since containment of the outbreak may have partially failed due to asymptomatic transmission, it is imperative to accelerate the development of rapid point-of-care diagnostic tests, vaccines, and therapeutics for the COVID-19 epidemic. A novel coronavirus — officially named as severe acute respiratory syndrome (SARS)-CoV-2 by the authorities — emerged in Wuhan, China, toward the end of 2019 [1, 2]. Just four months later, more than 100,000 cases have been diagnosed with the resulting disease, COVID-19, in more than 100 countries at the time of writing this paper [3]. Not only does mainland China have the most number of reported cases (94.4%), but its case-fatality rate is also relatively higher than that of other countries as of February 28, 2020 (China: 3.5%, 2,791 deaths among 78,961 confirmed cases; other countries: 1.4%, 67 deaths among 4,691 confirmed cases) [4]. In an attempt to restrict the outbreak, China quickly implemented an unprecedented measure of quarantining 35 million people in Wuhan and several other cities, but its impact on slowing the global spread of the virus now seems inadequate. In fact, the number of cases in local human-to-human transmission kept soaring in several countries as of March 25, 2020: Italy 63,927 cases, United States of America 42,164 cases, and Spain 33,089 cases [3]. In Japan, 1,128 cases were confirmed based on positive viral nucleic acid test results, and the overall case-fatality rate was 3.7% (i.e., 42 deaths) [3].

negative: Estimating the Case Fatality Risk of COVID-19 using Cases from Outside China There is large uncertainty around the case fatality risk (CFR) for COVID-19 in China. Therefore, we considered symptomatic cases outside of China (countries/settings with 20+ cases) and the proportion who are in intensive care units (4.0%, 14/349 on 13 February 2020). Given what is known about CFRs for ICU patients with severe respiratory conditions from a meta-analysis, we estimated a CFR of 1.37% (95%CI: 0.57% to 3.22%) for COVID-19 cases outside of China.

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: Covid-19: balancing personal risk and professional duty

negative: Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.

negative: Dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a Coronavirus Disease 2019 patient Abstract We report the dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a COVID-19 patient: from successive negative results to successive single positive nucleocapsid gene, to two positive target genes (orf1ab and nucleocapsid) by RT-PCR testing of SARS-Cov-2, and describe the diagnosis, clinical course, and management of the case. In this case, negative results of RT-PCR testing was not excluded to diagnose a suspected COVID-19 patient, clinical signs and symptoms, other laboratory findings, and chest CT images should be taken into account for the absence of enough positive evidence. This case highlights the importance of successive sampling and testing SARS-Cov-2 by RT-PCR as well as the increased value of single positive target gene from pending to positive in two specimens to diagnose laboratory-confirmed COVID-19.

negative: What Should Gastroenterologists and Patients Know About COVID-19?

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

negative: Conséquences anormales des accidents médicaux non fautifs : Jurisprudence du Conseil d’État Résumé L’indemnisation des accidents médicaux sans faute des professionnels ou des établissements est prévue par l’article L.1142-1 du code de la santé publique créé par la loi du 4 mars 2002 relative aux droits des malades et à la qualité du système de santé. Il indique les conditions d’imputabilité, de critères cliniques et de gravité. Parmi les critères cliniques « un accident médical (…) ouvre droit à la réparation des préjudices (…) au titre de la solidarité nationale, lorsqu’ils (…) qu’ils ont eu pour le patient des conséquences anormales au regard de son état de santé comme de l’évolution prévisible de celui-ci (…) ». Les ordres juridictionnels ont eu à caractériser cette « anormalité des conséquences ». Selon la jurisprudence du Conseil d’État du 12 décembre 2014 la condition d’anormalité est toujours « remplie lorsque l'acte médical a entraîné des conséquences notablement plus graves que celles auxquelles le patient était exposé de manière suffisamment probable en l’absence de traitement » et si tel n’est pas le cas, « elles ne peuvent être regardées comme anormales sauf si, dans les conditions où l’acte a été accompli, la survenance du dommage présentait une probabilité faible ; qu’ainsi, elles ne peuvent être regardées comme anormales au regard de l’état du patient lorsque la gravité de cet état a conduit à pratiquer un acte comportant des risques élevés dont la réalisation est à l’origine du dommage ». Le Conseil d’Etat a précisé, en 2019 qu’une probabilité de survenance de 3 % était une probabilité faible. Summary Compensation for no-fault medical accidents to professionals or establishments is provided for by article L.1142-1 of the public health code, created by the law of March 4, 2002 relating to the rights of patients and the quality of the health system. It indicates the conditions of accountability, clinical criteria and severity. Among the clinical criteria "a medical accident (...) gives the right to compensation for damages (...) in the name of national solidarity, when (...) they have had abnormal consequences for the patient in view of his condition as well as the foreseeable evolution of it (…)”. The jurisdictional orders have had to characterize this "abnormality of the consequences". According to the jurisprudence of the Conseil d’Etat of December 12, 2014 the condition of abnormality is always "satisfied when the medical act entailed consequences significantly more serious than those to which the patient was exposed in a sufficiently probable way in the absence of treatment ". And if this is not the case," they cannot be regarded as abnormal unless, under the conditions in which the act was performed, the occurrence of damage presented a low probability; that thus, they cannot be regarded as abnormal with regard to the state of the patient when the gravity of this state led to practicing an act involving high risks whose realization is at the origin of the damage ". The Conseil d’Etat specified in 2019 that a probability of occurrence of 3% was a low probability.

negative: COVID-2019: update on epidemiology, disease spread and management. With each passing day, more cases of Coronavirus disease (COVID-2019) are being detected and unfortunately the fear of novel corona virus 2019 (2019-nCoV) becoming a pandemic disease has come true. Constant efforts at individual, national, and international level are being made in order to understand the genomics, hosts, modes of transmission and epidemiological link of nCoV-2019. As of now, whole genome sequence of the newly discovered coronavirus has already been decoded. Genomic characterization nCoV-2019 have shown close homology with bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Structural analysis of the receptor binding site has confirmed that 2019-nCoV binds with the same ACE 2 receptor protein as human SARS virus. Compared to the previous coronavirus outbreaks, the overall mortality rate is relatively low for COVID-2019 (2-3%). Suspected cases must be quarantined till their test comes positive or they clear infection. At present, treatment of COVID-2019 is mostly based on the knowledge gained from the SARS and MERS outbreaks. Remdesivir, originally develop as a treatment for Ebola virus disease and Marburg virus infections, is being studied for it effectiveness against 2019-nCoV infection. Many other antiviral agents and vaccines are being tested but most of them are in phase I or II and hence unlikely to be of any benefit immediately with regards to current outbreak. Hence, the standard infection control techniques and preventive steps for healthy individuals and supportive care for the confirmed cases is the best available strategy to deal with current viral outbreak. .

negative: The modelling of COVID19 pathways sheds light on mechanisms, opportunities and on controversial interpretations of medical treatments. v2 The new coronavirus (2019-nCoV or SARS-CoV2), inducing the current pandemic disease (COVID-19) and causing pneumoniae in humans, is dramatically increasing in epidemic scale since its first appearance in Wuhan, China, in December 2019. The first infection from epidemic coronaviruses in 2003 fostered the spread of an overwhelming amount of related scientific efforts. The manifold aspects that have been raised, as well as their redundancy offer precious information that has been underexploited and needs to be critically re-evaluated, appropriately used and offered to the whole community, from scientists, to medical doctors, stakeholders and common people. These efforts will favour a holistic view on the comprehension, prevention and development of strategies (pharmacological, clinical etc) as well as common intervention against the new coronavirus spreading. Here we describe a model that emerged from our analysis that was focused on the Renin Angiotensin System (RAS) and the possible routes linking it to the viral infection. because the infection is mediated by the viral receptor on human cell membranes Angiotensin Converting Enzyme (ACE2), which is a key component in RAS signalling. The model depicts the main pathways determining the disease and the molecular framework for its establishment, and can help to shed light on mechanisms involved in the infection. It promptly gives an answer to some of the controversial, and still open, issues concerning predisposing conditions and medical treatments that protect from or favour the severity of the disease (such as the use of ACE inhibitors or ARBs/sartans), or to the sex related biases in the affected population. The model highlights novel opportunities for further investigations, diagnosis and appropriate intervention to understand and fight COVID19.

negative: A novel group of avian astroviruses from Neotropical passerine birds broaden the diversity and host range of Astroviridae Metagenomics is helping to expand the known diversity of viruses, especially of those with poorly studied hosts in remote areas. The Neotropical region harbors a considerable diversity of avian species that may play a role as both host and short-distance vectors of unknown viruses. Viral metagenomics of cloacal swabs from 50 Neotropical birds collected in French Guiana revealed the presence of four complete astrovirus genomes. They constitute an early diverging novel monophyletic clade within the Avastrovirus phylogeny, representing a putative new astrovirus species (provisionally designated as Avastrovirus 5) according to the International Committee on Taxonomy of Viruses (ICTV) classification criteria. Their genomic organization shares some characteristics with Avastrovirus but also with Mamastrovirus. The pan-astrovirus RT-PCR analysis of the cloacal samples of 406 wild Neotropical birds showed a community-level prevalence of 4.9% (5.1% in passerines, the highest described so far in this order of birds). By screening birds of a remote region, we expanded the known host range of astroviruses to the avian families Cardinalidae, Conopophagidae, Furnariidae, Thamnophilidae, Turdidae and Tyrannidae. Our results provide important first insights into the unexplored viral communities, the ecology, epidemiology and features of host-pathogen interactions that shape the evolution of avastroviruses in a remote Neotropical rainforest.

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

negative: Dynamic causal modelling of COVID-19 This technical report describes a dynamic causal model of the spread of coronavirus through a population. The model is based upon ensemble or population dynamics that generate outcomes, like new cases and deaths over time. The purpose of this model is to quantify the uncertainty that attends predictions of relevant outcomes. By assuming suitable conditional dependencies, one can model the effects of interventions (e.g., social distancing) and differences among populations (e.g., herd immunity) to predict what might happen in different circumstances. Technically, this model leverages state-of-the-art variational (Bayesian) model inversion and comparison procedures, originally developed to characterise the responses of neuronal ensembles to perturbations. Here, this modelling is applied to epidemiological populations to illustrate the kind of inferences that are supported and how the model per se can be optimised given timeseries data. Although the purpose of this paper is to describe a modelling protocol, the results illustrate some interesting perspectives on the current pandemic; for example, the nonlinear effects of herd immunity that speak to a self-organised mitigation process.

negative: Chapter Three The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing Abstract Coronaviruses are animal and human pathogens that can cause lethal zoonotic infections like SARS and MERS. They have polycistronic plus-stranded RNA genomes and belong to the order Nidovirales, a diverse group of viruses for which common ancestry was inferred from the common principles underlying their genome organization and expression, and from the conservation of an array of core replicase domains, including key RNA-synthesizing enzymes. Coronavirus genomes (~26–32 kilobases) are the largest RNA genomes known to date and their expansion was likely enabled by acquiring enzyme functions that counter the commonly high error frequency of viral RNA polymerases. The primary functions that direct coronavirus RNA synthesis and processing reside in nonstructural protein (nsp) 7 to nsp16, which are cleavage products of two large replicase polyproteins translated from the coronavirus genome. Significant progress has now been made regarding their structural and functional characterization, stimulated by technical advances like improved methods for bioinformatics and structural biology, in vitro enzyme characterization, and site-directed mutagenesis of coronavirus genomes. Coronavirus replicase functions include more or less universal activities of plus-stranded RNA viruses, like an RNA polymerase (nsp12) and helicase (nsp13), but also a number of rare or even unique domains involved in mRNA capping (nsp14, nsp16) and fidelity control (nsp14). Several smaller subunits (nsp7–nsp10) act as crucial cofactors of these enzymes and contribute to the emerging “nsp interactome.” Understanding the structure, function, and interactions of the RNA-synthesizing machinery of coronaviruses will be key to rationalizing their evolutionary success and the development of improved control strategies.

negative: 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.

negative: COVID-19 from veterinary medicine and one health perspectives: What animal coronaviruses have taught us

negative: Two-port totally extraperitoneal inguinal hernia repair: a 10-year experience. PURPOSE To evaluate the feasibility, safety, and long-term outcomes of laparoscopic two-port totally extraperitoneal (TEP) inguinal hernia repair. METHODS A 10-year retrospective analysis from 2004 to 2013 of patients undergoing two-port TEP performed by a single surgeon at three surgical centers. RESULTS 336 consecutive patients underwent two-port TEP repairing 478 hernias. 315 (93.8 %) patients were male and 21 (6.2 %) were female. Mean age ± SD was 47 ± 14 years and mean body mass index ± SD was 28.0 ± 4.7 kg/m(2). Indications for surgery included primary repair 303 (90.2 %), recurrence from open repair 28 (8.3 %), and incarcerated inguinal hernia 5 (1.5 %). 194 (57.7 %) cases were unilateral and 142 (42.3 %) were bilateral. Operative time ± SD was 38.7 ± 14.9 min for unilateral repair and 43.4 ± 17.6 min for bilateral repair. Two-port TEP was successful in 316 (94.0 %). 20 (6.0 %) cases required the addition of a third port. 2 (0.6 %) cases were converted to open repair. Mean follow-up time ± SD was 5.4 ± 2.7 years. Postoperative complications included urinary retention 5 (1.5 %), seroma 7 (2.1 %), hematoma 1 (0.3 %), surgical site infection 4 (1.2 %), and chronic inguinal pain 3 (0.9 %). 11 (2.3 %) hernias recurred. CONCLUSION Two-port TEP appears to be a feasible, safe, and effective method for laparoscopic inguinal hernia repair and should be considered a viable, less invasive alternative to conventional three-port techniques.

negative: Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2): A global pandemic and treatments strategies The emergence and rapid spread of novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a potentially fatal disease is swiftly evolving public health crises worldwide. The origin of SARS-CoV-2 infection was first reported in people exposed to wet animal market in Wuhan City, China in December 2019. It was suggested that the infection is likely to be of zoonotic origin and transmitted to human through yet unknown intermediary. As of (22/05/2020), there are around 4,995,996 confirmed cases reported by WHO with 327,821 deaths. SARS-CoV-2 infection is transmitted via inhalation or direct contact of infected people's droplets. It has an incubation period ranging from 2 to 14 days or more. The rate of spread of SARS-CoV-2 is more than partially resembled coronavirus (SARS-CoV and MERS). The symptoms are similar to influenza like, breathlessness, sore throat and fatigue therefore, infected person is isolated and administrated with effective treatments. Infection is mild in most but in elderly (>50 years) and those with cardiac and respiratory disorder, it may progress to pneumonia, acute respiratory distress syndrome, and multi organ failure. People with strong immunity or those developed herd immunity are asymptomatic. Fatality rate ranges to 3-4% on case basis. Diagnosis of SARS-CoV-2 is recommended in respiratory secretions by special molecular tests like PCR, chest scan and common laboratory diagnosis. Currently, the existing treatment is essentially supportive and role of antiviral agents is yet to be established as there is no vaccination or therapy available. This review focuses on epidemiology, symptoms, transmission, pathogenesis, ongoing available treatments and future perspectives of SARS-CoV-2.

negative: Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the lack of biologically relevant pre-clinical experimental models of SARS-CoV-2 infection as a complement of classic cell lines represents a major barrier for scientific and medical progress. Here, we advantageously used human reconstituted airway epithelial models of nasal or bronchial origin to characterize viral infection kinetics, tissue-level remodeling of the cellular ultrastructure and transcriptional immune signatures induced by SARS-CoV-2. Our results underline the relevance of this model for the preclinical evaluation of antiviral candidates. Foremost, we provide evidence on the antiviral efficacy of remdesivir and the therapeutic potential of the remdesivir-diltiazem combination as a rapidly available option to respond to the current unmet medical need imposed by COVID-19. One Sentence Summary New insights on SARS-CoV-2 biology and drug combination therapies against COVID-19.

negative: LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES Objective: To determine the long-term clinical problems in adult survivors of coronavirus (CoV) infection [Coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)] after hospitalisation or Intensive Care Unit (ICU) admission. Design: Systematic review and meta-analysis of the literature. Data sources: Ovid MEDLINE, EMBASE, CINAHL Plus and PsycINFO were searched using the strategy: (Coronavirus OR Coronavirus Infections OR COVID OR SARS virus OR Severe acute respiratory syndrome OR MERS OR Middle east respiratory syndrome) AND (Follow-up OR Follow-up studies OR Prevalence). Original studies reporting the clinical outcomes of adult survivors of coronavirus outbreaks two months after discharge or three months after admission were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 Level of Evidence Tool. Meta-analysis was conducted to derive pooled estimates of prevalence and severity for different outcomes at time points up to 6 months follow-up and beyond 6 months follow-up. Results: The search yielded 1169 studies of which 28 were included in this review. There were 15 Level 1b, 8 Level 2b, 2 Level 3b and 3 Level 4 studies by OCEBM grading. Pooled analysis of studies revealed that complications commonly observed were impaired diffusing capacity for carbon monoxide (DLCO) [prevalence of 27.26%, 95% CI 14.87 to 44.57] and reduced exercise capacity [(6-minute walking distance (6MWD) mean 461m, 95% CI 449.66 to 472.71] at 6 months with limited improvement beyond 6 months. Coronavirus survivors had considerable prevalence of psychological disorders such as post-traumatic stress disorder (PTSD) [38.80%, CI 30.93 to 47.31], depression [33.20%, CI 19.80 to 50.02] and anxiety [30.04%, CI 10.44 to 61.26) beyond 6 months. These complications were accompanied by low Short Form 36 (SF-36) scores at 6 months and beyond indicating reduced quality of life which is present long-term. Conclusions: The long term clinical problems in survivors of CoV infections (SARS and MERS) after hospitalisation or Intensive Care Unit (ICU) admission include respiratory dysfunction, reduced exercise capacity, psychological problems such as PTSD, depression and anxiety, and reduced quality of life. Critical care, rehabilitation and mental health services should anticipate a high prevalence of these problems following COVID-19 and ensure their adequate and timely management with the aim of restoring premorbid quality of life.

negative: Early risk factors for the duration of SARS-CoV-2 viral positivity in COVID-19 patients BACKGROUND: Pneumonia COVID-19 has became a pandemic. However, information on early risk factors for the duration of SARS-CoV-2 viral positivity is unavailable yet. METHODS: In this prospective study, a cohort of 137 patients with confirmed SARS-CoV-2 infection were enrolled. Clinical information and laboratory data were retrieved from electronic medical records. Viral positivity duration was calculated by an interval from the day SARS-CoV-2 positive confirmed to the day SARS-CoV-2 returned to negative in these 137 COVID-19 patients. Early risk factors for the duration of SARS-CoV-2 viral positivity were evaluated. FINDINGS: The median SARS-CoV-2 viral positivity duration is 12 days (range: 4 days ~ 45 days) for this cohort. Cox regression results showed a significantly shorter viral positivity duration was related to younger [hazard ratio (HR) = 0.658, p = 0.017], not severe patient (HR = 0.653, p = 0.076), higher count of lymphocytes (HR = 1.464, p = 0.033), eosinophils (HR = 1.514, p = 0.020) and CD8+ T cells (HR=1.745, p=0.033), and lower IL-6 (HR = 0.664, p = 0.036) and IL-10 (HR = 0.631, p = 0.021). Multivariate analysis with covariables adjusted results showed that the count of CD8+ T cells (HR=2.376, p=0.114) was a predominant risk factor for the SARS-CoV-2 viral positivity duration. INTERPRETATION: Our findings firstly provided early laboratory parameters such as count of CD8+ T cells, as risk factors for the duration of SARS-CoV-2 viral positivity, which have significance in control and prevention of the disease.

negative: Epidemiological, clinical, and virological characteristics of 465 hospitalized cases of coronavirus disease 2019 (COVID‐19) from Zhejiang province in China BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the associated coronavirus disease (COVID‐19) have spread throughout China. Previous studies predominantly focused on its place of origin, Wuhan, causing over estimation of the disease severity due to selection bias. We analyzed 465 confirmed cases in Zhejiang province to determine the epidemiological, clinical, and virological characteristics of COVID‐19. METHODS: Epidemiological, demographic, clinical, laboratory, and management data from qRT‐PCR confirmed COVID‐19 patients from January 17, 2020, to January 31, 2020, were collected, followed by multivariate logistic regression analysis for independent predictors of severe/critical‐type COVID‐19 and bioinformatic analysis for features of SARS‐CoV‐2 from Zhejiang province. RESULTS: Among 465 COVID‐19 patients, median age was 45 years, while hypertension, diabetes, and chronic liver disease were the most common comorbidities. History of exposure to the epidemic area was present in 170 (36.56%) and 185 (39.78%) patients were clustered in 77 families. Severe/critical‐type of COVID‐19 developed in 49 (10.54%) patients. Fever and cough were the most common symptoms, while diarrhea/vomiting was reported in 58 (12.47%) patients. Multivariate analysis revealed eight risk factors for severe/critical COVID‐19. Glucocorticoids and antibiotics were administered to 60 (12.90%) and 218(46.88%) patients, respectively. Bioinformatics showed four single amino acid mutations and one amino acid position loss in SARS‐CoV‐2 from Zhejiang province, with more similarity to humans than to viruses. CONCLUSIONS: SARS‐CoV‐2 showed virological mutations and more human transmission in Zhejiang province, indicating considerable epidemiological and clinical changes. Caution in glucocorticoid and antibiotics use is advisable.

negative: Infectious disease and economics: The case for considering multi-sectoral impacts Beyond the public health impacts of regional or global emerging and endemic infectious disease events lay wider socioeconomic consequences that are often not considered in risk or impact assessments. With rapid and extensive international travel and trade, such events can elicit economic shock waves far beyond the realm of traditional health sectors and original geographical range of a pathogen. While private sector organizations are impacted indirectly by these disease events, they are under-recognized yet effective stakeholders that can provide critical information, resources, and key partnerships to public and private health systems in response to and in preparation for potential infectious disease events and their socioeconomic consequences.

negative: Novel Viruses, Zoonotic Infections, and Travel Health Novel viruses and zoonotic infections pose global health risks.

negative: Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective Currently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, formerly known as 2019-nCoV, the causative pathogen of Coronavirus Disease 2019 (COVID-19)) has rapidly spread across China and around the world, causing an outbreak of acute infectious pneumonia. No specific anti-virus drugs or vaccines are available for the treatment of this sudden and lethal disease. The supportive care and non-specific treatment to ameliorate the symptoms of the patient are the only options currently. At the top of these conventional therapies, greater than 85% of SARS-CoV-2 infected patients in China are receiving Traditional Chinese Medicine (TCM) treatment. In this article, relevant published literatures are thoroughly reviewed and current applications of TCM in the treatment of COVID-19 patients are analyzed. Due to the homology in epidemiology, genomics, and pathogenesis of the SARS-CoV-2 and SARS-CoV, and the widely use of TCM in the treatment of SARS-CoV, the clinical evidence showing the beneficial effect of TCM in the treatment of patients with SARS coronaviral infections are discussed. Current experiment studies that provide an insight into the mechanism underlying the therapeutic effect of TCM, and those studies identified novel naturally occurring compounds with anti-coronaviral activity are also introduced.

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

negative: COVID-19-related prejudice towards Asian medical students: A consequence of SARS-CoV-2 fears in Poland Abstract The coronavirus disease 2019 (COVID-19) outbreak caused by SARS-CoV-2 has triggered global panic. We have conducted an anonymous online survey of Asian medical students in Poland to assess whether they experience any form of prejudice related to the ongoing pandemic. As demonstrated, the COVID-19 outbreak had triggered xenophobic reactions towards students of Asian-origin (n=85) before the first SARS-CoV-2 case was confirmed in Poland. Facing prejudice, including discrimination related to COVID-19, may add to feelings of isolation of students of Asian origin who study abroad, and affect career development, especially for students. We recommend that universities should proactively develop policies that support students, faculty, and staff affected by discriminatory behavior both during the current outbreak and in the future. However, preventing such behaviors should also be enforced by national authorities

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

negative: Beyond the Virus: A First Look at Coronavirus-themed Mobile Malware As the COVID-19 pandemic emerges in early 2020, a number of campaigns have started capitalizing the topic. Although a few media reports mentioned the existence of coronavirus-themed mobile malware, the research community lacks the understanding of the landscape of the coronavirus-themed mobile malware, and there is no publicly accessible dataset that could be utilized to boost the related research. In this paper, we present the first systematic study of coronavirus-themed mobile malware. We first make efforts to create a daily growing COVID-19 themed mobile app dataset, which contains $2,016$ COVID-19 themed apps and $277$ malware samples by the time of May 26, 2020. We then present an analysis of these apps from multiple perspectives including popularity and trends, installation methods, malicious behaviors and malicious campaigns. We observe that the growth of the number of COVID-19 themed apps is highly related to the number of confirmed cases of COVID-19 in the world. Most of them were released through distribution channels beyond app markets. A majority of the malicious apps (over 53%) are camouflaged as official apps using the same app identifiers and some of them use confusing similar app icons with the official ones to mislead users. Their main purposes are either stealing users' private information or making profit by using the tricks like phishing and extortion. Furthermore, we find that only 40\% of the COVID-19 malware creators are habitual developers who are active for a long time, while 60\% of them are new emerging ones in this pandemic and only released COVID-19 themed malware. The malicious developers are mainly located in US, mostly targeting countries including English countries, Arabic countries, Europe and China. To facilitate future research, we have publicly released all the well-labelled COVID-19 themed apps (and malware) to the research community.

negative: Is Africa prepared for tackling the COVID-19 (SARS-CoV-2) epidemic. Lessons from past outbreaks, ongoing pan-African public health efforts, and implications for the future

negative: A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

negative: Direct diagnosis of human respiratory coronaviruses 229E and OC43 by the polymerase chain reaction Abstract An RT-PCR-hybridization was developed that amplified genetic material from the M protein gene of HCoV-229E and HCoV-OC43. The analytic sensitivity of these original primers were compared with primers defined in the N gene and described previously. The results show that 0.05 TCID50 of HCoV-229E and 0.01 TCID50 of HCoV-OC43 can be detected by this molecular method using the original method. Detection of HCoV-229E and HCoV-OC43 in clinical specimens is possible using this method: 348 respiratory specimens (202 sputum and 146 nasal aspirates) were tested with this RT-PCR-hybridization and 12 human coronavirus are detected (3%). The method could provide a useful tool for demonstrating the role of human coronavirus in infections of the respiratory tract.

negative: The fifth anniversary of Regional Studies in Marine Science

negative: Managing neonates with respiratory failure due to SARS-CoV-2 – Authors' reply

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

negative: Machine learning using intrinsic genomic signatures for rapid classification of novel pathogens: COVID-19 case study As of February 20, 2020, the 2019 novel coronavirus (renamed to COVID-19) spread to 30 countries with 2130 deaths and more than 75500 confirmed cases. COVID-19 is being compared to the infamous SARS coronavirus, which resulted, between November 2002 and July 2003, in 8098 confirmed cases worldwide with a 9.6% death rate and 774 deaths. Though COVID-19 has a death rate of 2.8% as of 20 February, the 75752 confirmed cases in a few weeks (December 8, 2019 to February 20, 2020) are alarming, with cases likely being under-reported given the comparatively longer incubation period. Such outbreaks demand elucidation of taxonomic classification and origin of the virus genomic sequence, for strategic planning, containment, and treatment. This paper identifies an intrinsic COVID-19 genomic signature and uses it together with a machine learning-based alignment-free approach for an ultra-fast, scalable, and highly accurate classification of whole COVID-19 genomes. The proposed method combines supervised machine learning with digital signal processing for genome analyses, augmented by a decision tree approach to the machine learning component, and a Spearman’s rank correlation coefficient analysis for result validation. These tools are used to analyze a large dataset of over 5000 unique viral genomic sequences, totalling 61.8 million bp. Our results support a hypothesis of a bat origin and classify COVID-19 as Sarbecovirus, within Betacoronavirus. Our method achieves high levels of classification accuracy and discovers the most relevant relationships among over 5,000 viral genomes within a few minutes, ab initio, using raw DNA sequence data alone, and without any specialized biological knowledge, training, gene or genome annotations. This suggests that, for novel viral and pathogen genome sequences, this alignment-free whole-genome machine-learning approach can provide a reliable real-time option for taxonomic classification.

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

negative: 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: Epidemic analysis of COVID-19 in China by dynamical modeling The outbreak of novel coronavirus-caused pneumonia (COVID-19) in Wuhan has attracted worldwide attention. Here, we propose a generalized SEIR model to analyze this epidemic. Based on the public data of National Health Commission of China from Jan. 20th to Feb. 9th, 2020, we reliably estimate key epidemic parameters and make predictions on the inflection point and possible ending time for 5 different regions. According to optimistic estimation, the epidemics in Beijing and Shanghai will end soon within two weeks, while for most part of China, including the majority of cities in Hubei province, the success of anti-epidemic will be no later than the middle of March. The situation in Wuhan is still very severe, at least based on public data until Feb. 15th. We expect it will end up at the beginning of April. Moreover, by inverse inference, we find the outbreak of COVID-19 in Mainland, Hubei province and Wuhan all can be dated back to the end of December 2019, and the doubling time is around two days at the early stage.

negative: A Bibliometric Analysis of COVID-19 Research Activity: A Call for Increased Output Background: The novel coronavirus disease 2019 (COVID-19) has impacted many countries across all inhabited continents, and is now considered a global pandemic, due to its high rate of infectivity. Research related to this disease is pivotal for assessing pathogenic characteristics and formulating therapeutic strategies. The aim of this paper is to explore the activity and trends of COVID-19 research since its outbreak in December 2019. Methods: We explored the PubMed database and the World Health Organization (WHO) database for publications pertaining to COVID-19 since December 2019 up until March 18, 2020. Only relevant observational and interventional studies were included in our study. Data on COVID-19 incidence were extracted from the WHO situation reports. Research output was assessed with respect to gross domestic product (GDP) and population of each country. Results: Only 564 publications met our inclusion criteria. These articles came from 39 different countries, constituting 24% of all affected countries. China produced the greatest number of publications with 377 publications (67%). With respect to continental research activity, Asian countries had the highest research activity with 434 original publications (77%). In terms of publications per million persons (PPMPs), Singapore had the highest number of publications with 1.069 PPMPs. In terms of publications per billion-dollar GDP, Mauritius ranked first with 0.075. Conclusion: COVID-19 is a major disease that has impacted international public health on a global level. Observational studies and therapeutic trials pertaining to COVID-19 are essential for assessing pathogenic characteristics and developing novel treatment options.

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: Novel coronavirus COVID-19: an overview for emergency clinicians Prior to the global outbreak of SARS-CoV in 2003, HCoV-229E and HCoV-OC43 were the only coronaviruses known to infect humans. Following the SARS outbreak, 5 additional coronaviruses have been discovered in humans, most recently the novel coronavirus COVID-19, believed to have originated in Wuhan, Hubei Province, China. SARS-CoV and MERSCoV are particularly pathogenic in humans and are associated with high mortality. In this review, the epidemiology, pathophysiology, and management of the recently discovered COVID-19 are reviewed, with a focus on best practices and the public health implications.

negative: Large-Scale Phylogenetic Analysis of Emerging Infectious Diseases Microorganisms that cause infectious diseases present critical issues of national security, public health, and economic welfare. For example, in recent years, highly pathogenic strains of avian influenza have emerged in Asia, spread through Eastern Europe, and threaten to become pandemic. As demonstrated by the coordinated response to Severe Acute Respiratory Syndrome (SARS) and influenza, agents of infectious disease are being addressed via large-scale genomic sequencing. The goal of genomic sequencing projects are to rapidly put large amounts of data in the public domain to accelerate research on disease surveillance, treatment, and prevention. However, our ability to derive information from large comparative genomic datasets lags far behind acquisition. Here we review the computational challenges of comparative genomic analyses, specifically sequence alignment and reconstruction of phylogenetic trees. We present novel analytical results on two important infectious diseases, Severe Acute Respiratory Syndrome (SARS) and influenza. SARS and influenza have similarities and important differences both as biological and comparative genomic analysis problems. Influenza viruses (Orthymxyoviridae) are RNA based. Current evidence indicates that influenza viruses originate in aquatic birds from wild populations. Influenza has been studied for decades via well-coordinated international efforts. These efforts center on surveillance via antibody characterization of the hemagglutinin (HA) and neuraminidase (N) proteins of the circulating strains to inform vaccine design. However, we still do not have a clear understanding of (1) various transmission pathways such as the role of intermediate hosts like swine and domestic birds and (2) the key mutation and genomic recombination events that underlie periodic pandemics of influenza. In the past 30 years, sequence data from HA and N loci has become an important data type. In the past year, full genomic data has become prominent. These data present exciting opportunities to address unanswered questions in influenza pandemics. SARS is caused by a previously unrecognized lineage of coronavirus, SARS-CoV, which like influenza has an RNA based genome. Although SARS-CoV is widely believed to have originated in animals, there remains disagreement over the candidate animal source that lead to the original outbreak of SARS. In contrast to the long history of the study of influenza, SARS was only recognized in late 2002 and the virus that causes SARS has been documented primarily by genomic sequencing. In the past, most studies of influenza were performed on a limited number of isolates and genes suited to a particular problem. Major goals in science today are to understand emerging diseases in broad geographic, environmental, societal, biological, and genomic contexts. Synthesizing diverse information brought together by various researchers is important to find out what can be done to prevent future outbreaks [JON03]. Thus comprehensive means to organize and analyze large amounts of diverse information are critical. For example, the relationships of isolates and patterns of genomic change observed in large datasets might not be consistent with hypotheses formed on partial data. Moreover when researchers rely on partial datasets, they restrict the range of possible discoveries. Phylogenetics is well suited to the complex task of understanding emerging infectious disease. Phylogenetic analyses can test many hypotheses by comparing diverse isolates collected from various hosts, environments, and points in time and organizing these data into various evolutionary scenarios. The products of a phylogenetic analysis are a graphical tree of ancestor–descendent relationships and an inferred summary of mutations, recombination events, host shifts, geographic, and temporal spread of the viruses. However, this synthesis comes at a price. The cost of computation of phylogenetic analysis expands combinatorially as the number of isolates considered increases. Thus, large datasets like those currently produced are commonly considered intractable. We address this problem with synergistic development of heuristics tree search strategies and parallel computing.

negative: Moral Obligation, Public Leadership, and Collective Action for Epidemic Prevention and Control: Evidence from the Corona Virus Disease 2019 (COVID-19) Emergency To investigate the effect of villagers’ moral obligation and village cadres’ public leadership on villagers’ collective action for epidemic prevention and control, against the background of the corona virus disease 2019 (COVID-19) emergency in China, we constructed models based on the institutional analysis and development (IAD) framework and employed principal component analysis (PCA) and ordered probit regression, drawing on survey data from 533 villagers in Henan province adjacent to the COVID-19 origin province, Hubei, China. The results indicate that: (1) generally, both moral obligation and public leadership as well as their constituent indicators contributed positively to collective action for COVID-19 prevention and control; (2) moreover, moral obligation and public leadership can strengthen each other’s positive role in collective action for COVID-19 prevention and control. Based on the above findings, this paper suggests that villagers’ moral obligation can be perfected through internalizing epidemic prevention and control norms into the villagers’ moral norms by the way of villagers mastering the rural public health governance scheme. In addition, public leadership can be improved through professional training of village cadres and by motivating village elites to run for village cadres. With improved villagers’ moral obligation and village cadres’ public leadership, collective action for epidemic prevention and control could be more likely to be realized.

negative: Origin of Long-Term Storage Stability and Nitric Oxide Release Behavior of CarboSil Polymer Doped with S-Nitroso-N-acetyl-d-penicillamine [Image: see text] The prolonged and localized delivery of nitric oxide (NO), a potent antithrombotic and antimicrobial agent, has many potential biomedical applications. In this work, the origin of the long-term storage stability and sustained NO release mechanism of S-nitroso-N-acetyl-d-penicillamine (SNAP)-doped CarboSil 20 80A polymer, a biomedical thermoplastic silicone-polycarbonate-urethane, is explored. Long-term (22 days) localized NO release is achieved by utilizing a cross-linked silicone rubber as topcoats, which can greatly reduce the amount of SNAP, NAP, and NAP disulfide leaching from the SNAP-doped CarboSil films, as measured by LC–MS. Raman spectroscopy and powder X-ray diffraction characterization of SNAP-doped CarboSil films demonstrate that a polymer–crystal composite is formed during the solvent evaporation process when SNAP exceeds its solubility in CarboSil (ca. 3.4–4.0 wt %). Further, when exceeding this solubility threshold, SNAP exists in an orthorhombic crystal form within the bulk of the polymer. The proposed mechanism of sustained NO release in SNAP-doped CarboSil is that the solubilized SNAP in the polymer matrix decomposes and releases NO, primarily in the water-rich regions near the polymer/solution interface, and the dissolved SNAP in the bulk polymeric phase becomes unsaturated, resulting in the dissolution of crystalline SNAP within the bulk of the polymer. This is a very slow process that ultimately leads to NO release at the physiological flux levels for >3 weeks. The increased stability of SNAP within CarboSil is attributed to the intermolecular hydrogen bonds between the SNAP molecules that crystallize. This crystallization also plays a key role in maintaining RSNO stability within the CarboSil polymer for >8 months at 37 °C (88.5% remains). Further, intravascular catheters fabricated with this new material are demonstrated to significantly decrease the formation of Staphylococcus aureus biofilm (a leading cause of nosocomial bloodstream infections) (in vitro) over a 7 day period, with 5 log units reduction of viable cell count on catheter surfaces. It is also shown that the NO release catheters can greatly reduce thrombus formation on the catheter surfaces during 7 h implantation in rabbit veins, when compared to the control catheters fabricated without SNAP. These results suggest that the SNAP-doped CarboSil system is a very attractive new composite material for creating long-term NO release medical devices with increased stability and biocompatibility.

negative: Saudi Arabia`s measures to curb the COVID-19 outbreak: temporary suspension of the Umrah pilgrimage

negative: The role of high cholesterol in age-related COVID19 lethality Coronavirus disease 2019 (COVID19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originating in Wuhan China in 2019. The disease is notably severe in elderly and those with underlying chronic conditions. A molecular mechanism that explains why the elderly are vulnerable and why children are resistant is largely unknown. Understanding these differences is critical for safeguarding the vulnerable and guiding effective policy and treatments. Here we show loading cells with cholesterol from blood serum using the cholesterol transport protein apolipoprotein E (apoE) enhances the endocytic entry of pseudotyped SARS-CoV-2. Super resolution imaging of the SARS-CoV-2 entry point with high cholesterol showed almost twice the total number of viral entry points. The cholesterol concomitantly traffics angiotensinogen converting enzyme (ACE2) to the viral entry site where SARS-CoV-2 docks to properly exploit entry into the cell. Cholesterol also increased binding of SARS-CoV-2 receptor binding domains. In mouse lung we found age and high fat diet induced cholesterol loading into lung tissue by up to 40%. Based on these findings, we propose a cholesterol dependent model for COVID19 lethality in elderly and the chronically ill. As cholesterol increases with age and inflammation (e.g. obesity, smoking, and diabetes), the cell surface is coated with viral entry points, optimally assembled viral entry proteins, and optimal furin priming. Importantly our model suggests problems arise when cholesterol levels are high in the tissue, not the blood. In fact, rapidly dropping cholesterol in the blood may indicate severe loading of cholesterol in peripheral tissue and a dangerous situation for escalated SARS-CoV-2 infectivity. Molecules that remove cholesterol from tissue or disrupt ACE2 localization with viral entry points or furin localization for priming in the producer cells, likely reduce the severity of COVID19 in critically ill patients.

negative: Information about the new coronavirus disease (COVID-19)

negative: Human Genomic Loci Important in Common Infectious Diseases: Role of High-Throughput Sequencing and Genome-Wide Association Studies HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs). High-throughput sequencing (HTS) has transformed both the management of infectious diseases and continues to enable large-scale functional characterization of host resistance/susceptibility alleles and loci; a paradigm shift from single candidate gene studies. Application of genome sequencing technologies and genomics has enabled us to interrogate the host-pathogen interface for improving human health. Human populations are constantly locked in evolutionary arms races with pathogens; therefore, identification of common infectious disease-associated genomic variants/markers is important in therapeutic, vaccine development, and screening susceptible individuals in a population. This review describes a range of host-pathogen genomic loci that have been associated with disease susceptibility and resistant patterns in the era of HTS. We further highlight potential opportunities for these genetic markers.

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

negative: Pathogenesis of severe acute respiratory syndrome Severe acute respiratory syndrome (SARS) is a zoonotic infectious disease caused by a novel coronavirus (CoV). The tissue tropism of SARS-CoV includes not only the lung, but also the gastrointestinal tract, kidney and liver. Angiotensin-converting enzyme 2 (ACE2), the C-type lectin CD209L (also known L-SIGN), and DC-SIGN bind SARS-CoV, but ACE2 appears to be the key functional receptor for the virus. There is a prominent innate immune response to SARS-CoV infection, including acute-phase proteins, chemokines, inflammatory cytokines and C-type lectins such as mannose-binding lectin, which plays a protective role against SARS. By contrast there may be a lack of type 1 interferon response. Moreover, lymphopenia with decreased numbers of CD4+ and CD8+ T cells is common during the acute phase. Convalescent patients have IgG-class neutralizing antibodies that recognize amino acids 441–700 of the spike protein (S protein) as the major epitope.

negative: Papa Giovanni XXIII Bergamo Hospital at the time of the COVID-19 outbreak: letter from the warfront. In early December 2019, the 2019 novel coronavirus (COVID-19) was identified as the agent responsible for the first pneumonia cases of unknown origin in Wuhan, the capital of the Hubei region in China. The virus has been identified as a novel enveloped RNA betacoronavirus2 , that has been promptly named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The World Health Organization (WHO), on January 12, 2020 declared the COVID-19 a public health emergency of international concern. On March 11, the WHO made the assessment that COVID-19 can be characterized as a pandemic.

negative: Lessons learned from the 2019-nCoV epidemic on prevention of future infectious diseases Abstract Only a month after the outbreak of pneumonia caused by 2019-nCoV, more than forty-thousand people were infected. This put enormous pressure on the Chinese government, medical healthcare provider, and the general public, but also made the international community deeply nervous. On the 25th day after the outbreak, the Chinese government implemented strict traffic restrictions on the area where the 2019-nCoV had originated—Hubei province, whose capital city is Wuhan. Ten days later, the rate of increase of cases in Hubei showed a significant difference (p = 0.0001) compared with the total rate of increase in other provinces of China. These preliminary data suggest the effectiveness of a traffic restriction policy for this pandemic thus far. At the same time, solid financial support and improved research ability, along with network communication technology, also greatly facilitated the application of epidemic prevention measures. These measures were motivated by the need to provide effective treatment of patients, and involved consultation with three major groups in policy formulation—public health experts, the government, and the general public. It was also aided by media and information technology, as well as international cooperation. This experience will provide China and other countries with valuable lessons for quickly coordinating and coping with future public health emergencies.

negative: Bat origin of human coronaviruses Bats have been recognized as the natural reservoirs of a large variety of viruses. Special attention has been paid to bat coronaviruses as the two emerging coronaviruses which have caused unexpected human disease outbreaks in the 21st century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), are suggested to be originated from bats. Various species of horseshoe bats in China have been found to harbor genetically diverse SARS-like coronaviruses. Some strains are highly similar to SARS-CoV even in the spike protein and are able to use the same receptor as SARS-CoV for cell entry. On the other hand, diverse coronaviruses phylogenetically related to MERS-CoV have been discovered worldwide in a wide range of bat species, some of which can be classified to the same coronavirus species as MERS-CoV. Coronaviruses genetically related to human coronavirus 229E and NL63 have been detected in bats as well. Moreover, intermediate hosts are believed to play an important role in the transmission and emergence of these coronaviruses from bats to humans. Understanding the bat origin of human coronaviruses is helpful for the prediction and prevention of another pandemic emergence in the future.

negative: The effect of COVID-19 on global population and its fatality rate: Retrospective study by online database OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a current new virulent disease rising its transmission and fatality with each passing day in the worldwide population. COVID-19 is emerged as a respiratory infection and a suspicious origin of animals and transmission to human in Wuhan, China on December 2019. Later this, the virus was transmitted from person to person through droplets and contacts. The World Health Organization, Centers for Disease Control and Prevention, and the National Health Commission of the People’s Republic of China have taken immediate action to reduce transmission and fatality associated with COVID-19 as minimum as possible. However, action has failed to stop transmission of COVID-19 from China to other countries. Since there was no chain break of the virus, the chances are more to increase the case number and fatality. Hence, the study has been designed to perceive the current effect of COVID-19 on the global population and its fatality. The study also focused on review related to treatment for COVID-19. MATERIAL AND METHODS: Online database of epidemic disease COVID-19 cases number was collected from www.channelnewsasia.com on 7(th) April 2020. This data was used to observe the past and present circumstances in the global population and its fatality. The effect of treatment on COVID-19 was reviewed from the few databases of clinical trials (antiviral and antibacterial drugs). RESULTS: The online data are used to observe a significant increase ratio of COVID-19 cases and its fatality rate in worldwide as well as country wise. The COVID-19 cases are high in the United States (27.5%), whereas the fatality rate is high in Italy (12.47%). The prevalence of COVID-19 is expected to be reaching 4 million by the end of April 2020 and the fatality rate also might be reached high. CONCLUSION: We have come to the conclusion that the effect of COVID-19 on the global population is significantly increased and the fatality rate also elevated (2.48% to 5.52%). The hydroxychloroquine-azithromycin combination treatment has shown significant improvement in patients with COVID-19 compared to treat with other drugs.

negative: The need to manage the risk of thromboembolism in COVID-19 patients COVID-19 first presented in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20(th), 2020, there have been more than 2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. It is uncertain what the total incidences of thrombotic events in COVID-19 patients is currently at. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center.

negative: 12 Advances in Cancer Chemotherapeutic Drug Research in China In this chapter, the history of cancer chemotherapy discipline in China is briefly reviewed. Some effective antitumor drugs discovered in China are introduced such as Gengshengmeisu (actinomycin K), hydroxycamptothecin, homoharringtonine, methoxysarcolysin, N-formyl sarcolysin, nitrocaphane, glyciphosphoramide, bimolane, sobuzoxane, Sb-71 (antimony ammonia triacetic acid), and so on. New inhibitors of topoisomerases I and II such as chimmitecan and salvicine are described in detail regarding to their chemistry, antitumor activity, mechanism of action, and clinical trial. A number of effective anticancer compounds including angiogenesis inhibitor pseudolaric acid B, EGFR inhibitor quinonazoline derivative BB, and others are presented. New results obtained in our institute on several series of derivatives of N-substituted-thiourea; 3,5-substituted indolin-2-one compounds; 3-nitroquinolines; and quercetin-3-O-amino acid-esters and triaminotriazine analogs related to their design, synthesis, and antitumor evaluation are also provided. Keywords cancer, chemotherapeutic, drug research, advances in China

negative: Evaluating features of scientific conferences: A call for improvements Scientific conferences provide valuable opportunities for researchers across career stages and disciplines to present their latest work and to network with their peers. The advent of the internet has opened new possibilities for interaction, collaboration and networking, yet the uptake of tools enabling remote participation at scientific meetings has been slow. Academic conferences have become more international with high proliferation in the number of meetings and attendees, but the format and quality of their organization lags behind what is possible. As a result, the experience of attending conferences in many disciplines today is not appreciably different in many respects. A few conferences in some disciplines have recently implemented valuable changes for the community and have become more receptive to attendees with families. Many meetings could still be improved significantly in terms of diversity, inclusivity, promoting early career researcher (ECR) networking and career development, venue accessibility, and more importantly, reducing the meetings’ carbon footprint. These issues are openly visible and to some extent discussed among researchers on social media. It is important to accelerate and mandate these efforts so that researchers in all disciplines, in particular ECRs, consistently benefit from scientific gatherings, for years to come. We examined the current state of over 260 national and international academic meetings in various disciplines for features of inclusivity and sustainability and propose solutions to make conferences more modern, effective, equitable and intellectually productive for the research community and environmentally sustainable for our planet. “They always say time changes things, but you actually have to change them yourself.” — Andy Warhol

negative: Fighting against the common enemy of COVID-19: a practice of building a community with a shared future for mankind The outbreak of coronavirus disease 2019 (COVID-19) has caused more than 80 813 confirmed cases in all provinces of China, and 21 110 cases reported in 93 countries of six continents as of 7 March 2020 since middle December 2019. Due to biological nature of the novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with faster spreading and unknown transmission pattern, it makes us in a difficulty position to contain the disease transmission globally. To date, we have found it is one of the greatest challenges to human beings in fighting against COVID-19 in the history, because SARS-CoV-2 is different from SARS-CoV and MERS-CoV in terms of biological features and transmissibility, and also found the containment strategies including the non-pharmaceutical public health measures implemented in China are effective and successful. In order to prevent a potential pandemic-level outbreak of COVID-19, we, as a community of shared future for mankind, recommend for all international leaders to support preparedness in low and middle income countries especially, take strong global interventions by using old approaches or new tools, mobilize global resources to equip hospital facilities and supplies to protect noisome infections and to provide personal protective tools such as facemask to general population, and quickly initiate research projects on drug and vaccine development. We also recommend for the international community to develop better coordination, cooperation, and strong solidarity in the joint efforts of fighting against COVID-19 spreading recommended by the joint mission report of the WHO-China experts, against violating the International Health Regulation (WHO, 2005), and against stigmatization, in order to eventually win the battle against our common enemy — COVID-19.

negative: Novel coronavirus SARS-CoV-2 and COVID-19. Practice recommendations for obstetric anaesthesia: what we have learned thus far • Pregnancy does not seem to be associated with more severe COVID-19 infections. • Risk of antenatal vertical transmission of COVID-19 is low. • Epidural analgesia should be considered, provided platelet counts are not low. • Droplet precautions are indicated for all women with suspected COVID-19. • Airborne precautions recommended for general anaesthesia or higher risk thereof.

negative: Risks of Novel Coronavirus Disease (COVID-19) in Pregnancy; a Narrative Review INTRODUCTION: The outbreak of the new Coronavirus in China in December 2019 and subsequently in various countries around the world has raised concerns about the possibility of vertical transmission of the virus from mother to fetus. The present study aimed to review published literature in this regard. METHODS: In this narrative review, were searched for all articles published in various databases including PubMed, Scopus, Embase, Science Direct, and Web of Science using MeSH-compliant keywords including COVID-19, Pregnancy, Vertical transmission, Coronavirus 2019, SARS-CoV-2 and 2019-nCoV from December 2019 to March 18, 2020 and reviewed them. All type of articles published about COVID-19 and vertical transmission in pregnancy were included. RESULTS: A review of 13 final articles published in this area revealed that COVID-19 can cause fetal distress, miscarriage, respiratory distress and preterm delivery in pregnant women but does not infect newborns. There has been no report of vertical transmission in pregnancy, and it has been found that clinical symptoms of COVID-19 in pregnant women are not different from those of non-pregnant women. CONCLUSION: Overall, due to lack of appropriate data about the effect of COVID-19 on pregnancy, it is necessary to monitor suspected pregnant women before and after delivery. For confirmed cases both the mother and the newborn child should be followed up comprehensively.

negative: Policies on the use of respiratory protection for hospital health workers to protect from coronavirus disease (COVID-19)

negative: Influenza, respiratory syncytial virus and SARS Abstract Acute lower respiratory tract infections (LRTIs) are a major worldwide health problem, particularly in childhood. About 30–50% of acute LRTIs are viral in origin; of these, influenza and respiratory syncytial virus are associated with the greatest disease burden in humans. Many different influenza A viruses occur naturally in animal reservoirs, and present a constant threat of zoonotic infections and global pandemics. The pandemic (H1N1) influenza virus that emerged in humans in 2009 contained a unique combination of genes originating in swine and the global human population was highly susceptible to the novel strain. The emergence of the severe acute respiratory syndrome coronavirus in 2003, and the ensuing worldwide epidemic, highlights the fact that respiratory viral infections in humans may originate in animals. Preventative measures for influenza include annual vaccination and treatment with antiviral drugs such as the neuraminidase inhibitors oseltamivir and zanamivir. Subtype-dependent resistance to antivirals can develop and should be closely monitored.

negative: Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19, which was first reported in Wuhan, China in December, 2019. Despite the tremendous efforts to control the disease, COVID-19 has now spread to over 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are completely unknown. Here, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2. We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but ferrets and cats are permissive to infection. We found experimentally that cats are susceptible to airborne infection. Our study provides important insights into the animal models for SARS-CoV-2 and animal management for COVID-19 control.

negative: Viral Etiology of Acute Exacerbations of COPD in Hong Kong Introduction Viral respiratory infections may precipitate acute exacerbations of COPD (AECOPD). However, little is known about viral etiology related to AECOPD in Asia. We aimed to study the viral etiology of AECOPD in Hong Kong. Methods Patients admitted to an acute hospital in Hong Kong with AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005. Nasopharyngeal aspirate was collected and assessed by polymerase chain reaction (PCR) and viral culture. Spirometry was performed in the stable phase at 2 to 3 months after hospital discharge. Results There were 262 episodes of AECOPD among 196 patients (mean age, 75.7 ± 7.7 years [± SD]; 160 men). Mean FEV1 was 39.6 ± 18.9% of predicted normal, and FEV1/FVC ratio was 58.0 ± 15.2%. Fifty-eight episodes (22.1%) yielded positive viral PCR results. The viruses identified were influenza A (7.3%), coronavirus OC43 (4.6%), rhinovirus (3.1%), influenza B (2.7%), and respiratory syncytial virus (2.3%). The diagnostic yield of viral identification by PCR was 2.7 times higher than that based on conventional viral culture. The rates of identifying a positive viral etiology by PCR were similar among the subjects with FEV1 ≥ 50%, ≥ 30 to 50%, and < 30% of predicted normal. Viral infection appeared to have no effect on subsequent readmissions or mortality rate over a study period of 1 year Conclusion Influenza A and two less-attended viruses, coronavirus OC43 and rhinovirus, were the common etiologic agents in patients hospitalized with AECOPD in Hong Kong. These should be considered in developing diagnostic and intervening strategies pertaining to AECOPD.

negative: Studies on the relationship between coronaviruses from the intestinal and respiratory tracts of calves An immunofluorescence test on smears of nasal epithelial cells was used to detect coronavirus infection in the respiratory tract of calves. Thirteen gnotobiotic calves were infected with coronavirus isolates derived from faeces or respiratory material: virus was detected in faeces and nasal swabs from all animals. In 115 calves from a field survey, there was a significant association between coronavirus excretion from both respiratory and enteric routes in calves with diarrhoea. In a further 12 calves, at necropsy, the predilection sites for coronavirus growth were the distal small intestine, large intestine and the epithelia of the nasal cavity and trachea. Antigen was not found in lung tissue by immunofluoresence or immunoperoxidase staining. Infection with enteric coronavirus induced immunity to reinfection and to heterologous challenge with two coronavirus isolates derived from the respiratory tract. Nine coronaviruses were cultivated, cloned and antisera to three were prepared in pigs. There was complete virus neutralisation in tests with homologous sera and significant cross reactions with the eight other isolates which were of intestinal and respiratory origin. Thus, these bovine coronavirus isolates belonged to the same serotype despite the source of virus.

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

negative: Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2 Coronavirus disease 2019 (COVID-19) is a new emerging human infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV), originated in Wuhan seafood and animal market, China. Since December 2019, more than 69,000 cases of COVID-19 have been confirmed in China and quickly spreads to other counties. Currently, researchers put their best efforts to identify effective drugs for COVID-19. The neutralizing antibody, which binds to viral capsid in a manner that inhibits cellular entry of virus and uncoating of the genome, is the specific defense against viral invaders. In this study, we investigate to identify neutralizing antibodies that can bind to SARS-CoV-2 Sipke (S) protein and interfere with the interaction between viral S protein and a host receptor by bioinformatic methods. The sequence analysis of S protein showed two major differences in the RBD region of the SARS-CoV-2 S protein compared to SARS-CoV and SARS-CoV related bat viruses (btSARS-CoV). The insertion regions were close to interacting residues with the human ACE2 receptor. Epitope analysis of neutralizing antibodies revealed that SARS-CoV neutralizing antibodies used conformational epitopes, whereas MERS-CoV neutralizing antibodies used a common linear epitope region, which contributes to form the β-sheet structure in MERS-CoV S protein and deleted in SARS-CoV-2 S protein. To identify effective neutralizing antibodies for SARS-CoV-2, the binding affinities of neutralizing antibodies with SARS-CoV-2 S protein were predicted and compared by antibody-antigen docking simulation. The result showed that CR3022 neutralizing antibody from human may have higher binding affinity with SARS-CoV-2 S protein than SARS-CoV S protein. We also found that F26G19 and D12 mouse antibodies could bind to SARS-CoV S protein with high affinity. Our findings provide crucial clues towards the development of antigen diagnosis, therapeutic antibody, and the vaccine against SARS-CoV-2.

negative: Successes and challenges of the One Health approach in Kenya over the last decade More than 75% of emerging infectious diseases are zoonotic in origin and a transdisciplinary, multi-sectoral One Health approach is a key strategy for their effective prevention and control. In 2004, US Centers for Disease Control and Prevention office in Kenya (CDC Kenya) established the Global Disease Detection Division of which one core component was to support, with other partners, the One Health approach to public health science. After catalytic events such as the global expansion of highly pathogenic H5N1 and the 2006 East African multi-country outbreaks of Rift Valley Fever, CDC Kenya supported key Kenya government institutions including the Ministry of Health and the Ministry of Agriculture, Livestock, and Fisheries to establish a framework for multi-sectoral collaboration at national and county level and a coordination office referred to as the Zoonotic Disease Unit (ZDU). The ZDU has provided Kenya with an institutional framework to highlight the public health importance of endemic and epidemic zoonoses including RVF, rabies, brucellosis, Middle East Respiratory Syndrome Coronavirus, anthrax and other emerging issues such as anti-microbial resistance through capacity building programs, surveillance, workforce development, research, coordinated investigation and outbreak response. This has led to improved outbreak response, and generated data (including discovery of new pathogens) that has informed disease control programs to reduce burden of and enhance preparedness for endemic and epidemic zoonotic diseases, thereby enhancing global health security. Since 2014, the Global Health Security Agenda implemented through CDC Kenya and other partners in the country has provided additional impetus to maintain this effort and Kenya’s achievement now serves as a model for other countries in the region. Significant gaps remain in implementation of the One Health approach at subnational administrative levels; there are sustainability concerns, competing priorities and funding deficiencies.

negative: A Massachusetts prototype like coronavirus isolated from wild peafowls is pathogenic to chickens Abstract Coronavirus infection was investigated in apparently healthy wild peafowls in Guangdong province of China in 2003, while severe acute respiratory syndrome (SARS) broke out there. No SARS-like coronavirus had been isolated but a novel avian coronavirus strain, Peafowl/GD/KQ6/2003 (KQ6), was identified. Sequence analysis revealed that KQ6 was an avian coronavirus infectious bronchitis virus (IBV), a member of coronavirus in group 3. The genome sequence of KQ6 had extremely high degree of identity with that of a Massachusetts prototype IBV M41. KQ6 was pathogenic to chickens but non-pathogenic to peafowls under experimental conditions. Seventeen out of fifty-four (31.48%) peafowl serum samples were tested positive for specific antibodies against IBV. Present results indicate that the peafowl isolate KQ6 is a Massachusetts prototype like coronavirus strain which undergoes few genetic changes and peafowl might have acted as a natural reservoir of IBV for very long time.

negative: [COVID-19, THE KIDNEY AND HYPERTENSION]. INTRODUCTION COVID-19, is a new corona virus of the Beta Coronavirus genus which originated in bats. The virus first emerged in China in December 2019 and has rapidly spread since to other areas worldwide. The World Health Organization (WHO) has therefore recently declared it as the source of a pandemic. The disease caused by the virus manifests in most cases as a lower respiratory tract infection leading to fever, cough and dyspnea, while more severe cases can led to respiratory failure and/or multi organ failure. COVID-19 enters the human cell using the ACE2, an enzyme abundant in renal tubular epithelial cells. Theoretically, this may be significant in several ways: acute kidney injury (AKI) as well as proteinuria and/or microhematuria could be associated with the penetration of COVID-19 into the cells. Moreover, medications based on RAAS inhibition, such and ACE inhibitors and ARBs, upregulate the enzyme ACE2 and could therefore hypothetically explain the high prevalence of hypertension and diabetes reported as previous diagnoses in severe cases. In the setting of chronic kidney disease, the risk of infection with COVID-19 is not clear at this time. However, hemodialysis patients represent a unique group of patients, mostly elderly and immunocompromised, for whom dialysis is a life-saving treatment which cannot be stopped. Hence, the COVID-19 pandemic has presented a complex medical and logistic challenge for the medical staff in hospital and community based dialysis units.

negative: 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.

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

negative: Comparative Impact of Individual Quarantine vs. Active Monitoring of Contacts for the Mitigation of COVID-19: a modelling study BACKGROUND: Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases, such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible, and broader mitigation measures must be implemented. METHODS: To estimate the comparative efficacy of these case-based interventions to control COVID-19, we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit to the incubation period distribution and each of two sets of the serial interval distribution: a shorter one with a mean serial interval of 4.8 days and a longer one with a mean of 7.5 days. To assess variable resource settings, we consider two feasibility settings: a high feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and low feasibility setting with 50% of contacts traced, a two-day average delay, and 50% effective isolation. FINDINGS: Our results suggest that individual quarantine in high feasibility settings where at least three-quarters of infected contacts are individually quarantined contains an outbreak of COVID-19 with a short serial interval (4.8 days) 84% of the time. However, in settings where this performance is unrealistically high and the outbreak continues to grow, so too will the burden of the number of contacts traced for active monitoring or quarantine. When resources are prioritized for scalable interventions such as social distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. INTERPRETATION: Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission in order to make data-driven policy decisions regarding the cost-benefit comparisons of individual quarantine vs. active monitoring of contacts. To the extent these interventions can be implemented they can help mitigate the spread of COVID-19.

negative: Veno-venous Extracorporeal Membrane Oxygenation Support in COVID-19 Respiratory Distress Syndrome: Initial Experience SARS-CoV-2 may cause severe respiratory failure due to massive alveolar damage. Currently, no adequate curative therapy for Coronavirus Disease 2019 (COVID-19) disease exists. By considering overall impact of COVID-19 pandemic outbreak, an increased need of extracorporeal membrane oxygenation (ECMO) support becomes evident. We report on our preliminary institutional experience with COVID-19 patients receiving venovenous ECMO support.

negative: The COVID‐19 epidemic The current outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; previously 2019-nCoV), epi-centered in Hubei Province of the People's Republic of China, has spread to many other countries. On January 30, 2020, the WHO Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations. The case detection rate is changing hourly and daily and can be tracked in almost real time on website provided by Johns Hopkins University [1] and other websites. As of early February 2020, China bears the large burden of morbidity and mortality, whereas the incidence in other Asian countries, in Europe and North America remains low so far.

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: Dietary therapy and herbal medicine for COVID-19 prevention: A review and perspective A novel coronavirus disease (COVID-19), transmitted from humans to humans, has rapidly become the pandemic responsible for the current global health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is said to be of zoonotic origin. This review describes the etiology and signs and symptoms as well as the current allopathic therapy for COVID-19. Additionally, findings of previous studies on the immunomodulatory effects and antiviral activities of particular foods and herbs on influenza virus and coronaviruses have been collated, with the aim of promoting the use of dietary therapy and herbal medicine as COVID-19 preventive therapies, while specific drugs and vaccines are yet to be discovered or are still under development. The volume of existing reports is irrefutable evidence that foods and herbs possess a potential antiviral ability against SARS-CoV-2 and can prevent COVID-19. Foods and herbs could be used as dietary or complementary therapy to prevent infection and strengthen immunity, as antiviral agents for masks, as disinfectants to curb aerosol transmission, or as sanitizing agents to disinfect surfaces. However, these hypotheses need to be experimentally verified for SARS-CoV-2 and COVID-19 patients.

negative: SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain Virus genome sequence variants that appear over the course of an outbreak can be exploited to map the trajectory of the virus from one susceptible host to another. While such variants are usually of no functional significance, in some cases they may allow the virus to transmit faster, change disease severity, or confer resistance to antiviral therapies. Since the discovery of SARS-CoV-2 as the cause of COVID-19, the virus has spread around the globe, and thousands of SARS-CoV-2 genomes have been sequenced. The rate of sequence variation among SARS-CoV-2 isolates is modest for an RNA virus but the enormous number of human-to-human transmission events has provided abundant opportunity for selection of sequence variants. Among these, the SARS-CoV-2 Spike protein variant, D614G, was not present in the presumptive common ancestor of this zoonotic virus but was first detected in late January in Germany and China. The D614G variant steadily increased in frequency and now constitutes >97% of isolates world-wide, raising the question whether D614G confers a replication advantage to SARS-CoV-2. Structural models predict that D614G would disrupt contacts between the S1 and S2 domains of the Spike protein and cause significant shifts in conformation. Using single-cycle vectors we showed that D614G is three to nine-fold more infectious than the ancestral form on human lung and colon cell lines, as well as on other human cell lines rendered permissive by ectopic expression of human ACE2 and TMPRSS2, or by ACE2 orthologues from pangolin, pig, dog, or cat. Nonetheless, monoclonal antibodies targeting the receptor binding domain of the SARS-CoV-2 Spike protein retain full neutralization potency. These results suggest that D614G was selected for increased human-to-human transmission, that it contributed to the rapidity of SARS-CoV-2 spread around the world, and that it does not confer resistance to antiviral therapies targeting the receptor binding domain.

negative: 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.

negative: Substrate specificity profiling of SARS-CoV-2 main protease enables design of activity-based probes for patient-sample imaging In December 2019, the first cases of infection with a novel coronavirus, SARS-CoV-2, were diagnosed in Wuhan, China. Due to international travel and human-to-human transmission, the virus spread rapidly inside and outside of China. Currently, there is no effective antiviral treatment for coronavirus disease 2019 (COVID-19); therefore, research efforts are focused on the rapid development of vaccines and antiviral drugs. The SARS-CoV-2 main protease constitutes one of the most attractive antiviral drug targets. To address this emerging problem, we have synthesized a combinatorial library of fluorogenic substrates with glutamine in the P1 position. We used it to determine the substrate preferences of the SARS-CoV and SARS-CoV-2 main proteases, using natural and a large panel of unnatural amino acids. On the basis of these findings, we designed and synthesized an inhibitor and two activity-based probes, for one of which we determined the crystal structure of its complex with the SARS-CoV-2 Mpro. Using this approach we visualized SARS-CoV-2 active Mpro within nasopharyngeal epithelial cells of a patient with active COVID-19 infection. The results of our work provide a structural framework for the design of inhibitors as antiviral agents or diagnostic tests.

negative: Pneumonia Caused by Emerging Viral Agents Emerging viruses that cause pneumonia in humans are agents which normally circulate in the animal population but can move to human hosts under certain circumstances, which determines the occurrence of a new type of disease. The Middle East respiratory syndrome (MERS) is caused by a coronavirus. The disease has a wide symptomatic spectrum that can range from asymptomatic infections to fulminant respiratory failure. Diagnostic confirmation is achieved through viral isolation. Severe acute respiratory syndrome (SARS), also produced by a coronavirus, is capable of producing a serious pulmonary disease outbreak with no reappearance. The clinical presentation includes fever, malaise, cough, and headache followed by diarrhea. Other coronaviruses (HCoV-NL63 and HCoV-HKU1) can cause serious lower respiratory infections in small children, the elderly, and immunosuppressed patients. Influenza virus is widespread in nature, and avian virus may spread to humans, as has been reported with H7N9, H5N1, H10N8, and H6N1. Cardiopulmonary hantavirus syndrome, a feverish disease characterized by respiratory insufficiency and shock, is produced by Andes virus. Other emerging viruses are enterovirus D68 and polyomavirus.

negative: COVID-19 pneumonia: what has CT taught us?

negative: Studies of Novel Coronavirus Disease 19 (COVID-19) Pandemic: A Global Analysis of Literature An exponential growth of literature about novel coronavirus disease 19 (COVID-19) has been observed in the last few months. This textual analysis of 5,780 publications extracted from the Web of Science, Medline, and Scopus databases was performed to explore the current research focuses and propose further research agenda. The Latent Dirichlet allocation was used for topic modeling. Regression analysis was conducted to examine country variations in the research focuses. Results indicated that publications were mainly contributed by the United States, China, and European countries. Guidelines for emergency care and surgical, viral pathogenesis, and global responses in the COVID-19 pandemic were the most common topics. There was variation in the research approaches to mitigate COVID-19 problems in countries with different income and transmission levels. Findings highlighted the need for global research collaboration among high- and low/middle-income countries in the different stages of prevention and control the pandemic.

negative: Scientists ‘strongly condemn’ rumors and conspiracy theories about origin of coronavirus outbreak ;Science ;AAAS A group of 27 prominent public health scientists from outside China is pushing back against a steady stream of stories and even a scientific paper suggesting a laboratory in Wuhan, China, may be the origin of the outbreak of COVID-19 “The rapid, open, and transparent sharing of data on this outbreak is now being threatened by rumours and misinformation around its origins,” the scientists, from nine countries, write in a statement published online by The Lancet yesterday

negative: Commercial exchanges instead of air pollution as possible origin of COVID-19 initial diffusion phase in Italy: more efforts are necessary to address interdisciplinary research This communication aims to advocate a more coordinate activity mainly between medical and environmental scientists to clarify some confusing information related to airborne diffusion mechanisms of COVID-19. In this frame it is suggested that parameters other than environmental pollution (accounting for pollution-to human transmission mechanisms), as for example parameters involving commercial exchanges (accounting for human-to human transmission mechanisms), should be considered to better justify the difference in the initial diffusion of virus in Italy.

negative: COVID-19 excess deaths in the United States during April 2020 Background: Some have claimed that the number of COVID-19 deaths is not much greater than would be experienced in the usual course of events. We sought to estimate the number of deaths due to COVID-19 in the United States during April 2020 and compare that to the number of expected deaths in the same time period. Methods: The Institute for Health Metrics and Evaluation (IHME) predicts that 67,212 COVID-19 deaths will occur during April 2020. To obtain the number of excess COVID-19 deaths, we multiplied published infection fatality rates by age by population numbers to obtain assumed infection rates. We then subtracted the expected number of deaths calculated using life table mortality rates. Results: During April 2020 there may be 61,690 to 62,526 excess deaths. Population infection rates of 3.6% to 4.3% by mid-April 2020 would generate the number of COVID-19 deaths predicted by IHME. Conclusions: During April 2020 over 90% of the COVID-19 deaths can be classified as excess deaths. These deaths would normally occur over 11.2 to 13.3 months instead of being concentrated in 1 month.

negative: COVID‐19 and rationally layered social distancing I would like to thank Dr. Thomson for the very pertinent and relevant points that he raised in his thoughtful letter Where are we now with COVID-19? [1]. As my response will illustrate, and in what probably will become a defining feature of conversations surrounding COVID-19 for quite some time, attempts to answer will only make room for more questions. As COVID-19 is unfolding, every day is marked by novel developments. Since the editorial went to press [2], the outbreak has expanded considerably. Over 128,000 individuals were infected worldwide as of March 13, 2020, leading to 4720 deaths [3]. In early March, while the outbreak in China appeared to start to subside [4], it started to amplify in Europe and the United States. The first fatality in the United States occurred on February 29, 2020 in a suburb of Seattle. On March 4m the first death was reported outside WA state, in CA, and was the 11th death in the United States. On March 6, the first two fatalities were reported in Florida. On March 11, 2020, the World Health Organization declared the outbreak a pandemic [5].

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: Guide to Understanding the 2019 Novel Coronavirus

negative: Patient-Centred Coordinated Care in Times of Emerging Diseases and Epidemics. Contribution of the IMIA Working Group on Patient Safety. OBJECTIVES In this paper the researchers describe how existing health information technologies (HIT) can be repurposed and new technologies can be innovated to provide patient-centered care to individuals affected by new and emerging diseases. METHODS The researchers conducted a focused review of the published literature describing how HIT can be used to support safe, patient-centred, coordinated care to patients who are affected by Ebola (an emerging disease). RESULTS New and emerging diseases present opportunities for repurposing existing technologies and for stimulating the development of new HIT innovation. Innovative technologies may be developed such as new software used for tracking patients during new or emerging disease outbreaks or by repurposing and extending existing technologies so they can be used to support patients, families and health professionals who may have been exposed to a disease. The paper describes the development of new technologies and the repurposing and extension of existing ones (such as electronic health records) using the most recent outbreak of Ebola as an example.

negative: Novel Coronavirus Disease 2019 (COVID-19): An Emerging Infectious Disease in the 21st Century Background: At the beginning of the New Year 2020, China alerted the world health organization (WHO) to a cluster of unusual pneumonia cases in Wuhan After extensive speculation, eventually a new species of coronavirus introduced as the causative pathogen of the disease Coronavirus disease 2019 (COVID-19) is a name for the disease, and the virus that causes it is known SARS-CoV-2 The very rapid spread of the COVID-19 in China and in many other countries has caused fear among people across the world The novel coronavirus outbreak declared a Public Health Emergency of International Concern on 30 January 2020 Materials and Methods: Several databases such as PubMed, Scopus, Google scholar, and BioRxiv were searched for publications reporting on the novel coronavirus up to 29 February 2020 Literature searches were performed using keywords including “Coronavirus 2019”, “2019-nCoV”, “COVID-19”, and “SARS-CoV-2” Moreover, websites such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) were searched to retrieve updated data and statistics regarding the novel coronavirus We extracted data on the epidemiology, pathogenesis, virology, clinical manifestations, transmission routes, diagnosis, treatment, and prevention measures Results: From the 1416 articles identified in the initial search, 53 were remained after title and abstract screening After full-text review, 37 articles were eligible to include in our study Incubation period for COVID-19 is between 2-10 days, according to the World Health Organization (WHO) The case fatality rate in patients infected with SARC-CoV-2 is 4 3%, and the results indicate that the mortality is higher in elderly individuals and patients with chronic conditions including patients with coronary artery disease, diabetes, chronic pulmonary disease, and hypertension The mortality rate in healthy subjects is less than 1% Conclusion: The outbreak caused by the novel coronavirus is larger than the previous human coronaviruses, showing that the SARS-CoV-2 is an extremely contagious virus However, the mortality rate of COVID-19 is lower than that of other coronaviruses diseases such as SARS or MERS and other viruses like HIV and Ebola Currently, due to the lack of an effective treatment and vaccine, the best way to deal with the COVID-19 disease is to prevent transmission and spread of the virus and to execute personal protective measures

negative: COVID‐19 under spotlight: A close look at the origin, transmission, diagnosis, and treatment of the 2019‐nCoV disease Months after the outbreak of a new flu‐like disease in China, the entire world is now in a state of caution. The subsequent less‐anticipated propagation of the novel coronavirus disease, formally known as COVID‐19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS‐CoV‐2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID‐19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.

negative: Novel coronavirus takes flight from bats? Two recent studies provide initial insights into a novel coronavirus that is associated with an outbreak of human respiratory disease.

negative: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future Abstract At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.

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

negative: What the cruise-ship outbreaks reveal about COVID-19.

negative: Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a large respiratory outbreak in Wuhan, China in December 2019, is currently spreading across many countries globally. Here, we show that a TMPRSS2-expressing VeroE6 cell line is highly susceptible to SARS-CoV-2 infection, making it useful for isolating and propagating SARS-CoV-2. Our results reveal that, in common with SARS- and Middle East respiratory syndrome-CoV, SARS-CoV-2 infection is enhanced by TMPRSS2.

negative: Identification of a Novel Betacoronavirus (Merbecovirus) in Amur Hedgehogs from China While dromedaries are the immediate animal source of Middle East Respiratory Syndrome (MERS) epidemic, viruses related to MERS coronavirus (MERS-CoV) have also been found in bats as well as hedgehogs. To elucidate the evolution of MERS-CoV-related viruses and their interspecies transmission pathway, samples were collected from different mammals in China. A novel coronavirus related to MERS-CoV, Erinaceus amurensis hedgehog coronavirus HKU31 (Ea-HedCoV HKU31), was identified from two Amur hedgehogs. Genome analysis supported that Ea-HedCoV HKU31 represents a novel species under Merbecovirus, being most closely related to Erinaceus CoV from European hedgehogs in Germany, with 79.6% genome sequence identity. Compared to other members of Merbecovirus, Ea-HedCoV HKU31 possessed unique non-structural proteins and putative cleavage sites at ORF1ab. Phylogenetic analysis showed that Ea-HedCoV HKU31 and BetaCoV Erinaceus/VMC/DEU/2012 were closely related to NeoCoV and BatCoV PREDICT from African bats in the spike region, suggesting that the latter bat viruses have arisen from recombination between CoVs from hedgehogs and bats. The predicted HKU31 receptor-binding domain (RBD) possessed only one out of 12 critical amino acid residues for binding to human dipeptidyl peptidase 4 (hDPP4), the MERS-CoV receptor. The structural modeling of the HKU31-RBD-hDPP4 binding interphase compared to that of MERS-CoV and Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) suggested that HKU31-RBD is unlikely to bind to hDPP4. Our findings support that hedgehogs are an important reservoir of Merbecovirus, with evidence of recombination with viruses from bats. Further investigations in bats, hedgehogs and related animals are warranted to understand the evolution of MERS-CoV-related viruses.

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

negative: Dangerous infectious diseases: Bad news for Main Street, good news for Wall Street? Abstract We examine whether investor mood, driven by World Health Organization (WHO) alerts and media news on dangerous infectious diseases, is priced in pharmaceutical companies' stocks in the United States. We argue that disease-related news (DRNs) should not trigger rational trading. We find that DRNs have a positive and significant sentiment effect among investors (on Wall Street). The effect is stronger (weaker) for small (large) companies, who are less (more) likely to engage in the development of new vaccines. A potential negative investor climate (on Main Street) – induced by disease-related fear – does not alter the positive sentiment effect.

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

negative: SARS-associated Coronavirus Transmitted from Human to Pig SEVERE ACUTE RESPIRATORY SYNDROME–ASSOCIATED: coronavirus (SARS-CoV) was isolated from a pig during a survey for possible routes of viral transmission after a SARS epidemic. Sequence and epidemiology analyses suggested that the pig was infected by a SARS-CoV of human origin.

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: Infectious Disease Risk Across the Growing Human-Non Human Primate Interface: A Review of the Evidence Most of the human pandemics reported to date can be classified as zoonoses. Among these, there is a long history of infectious diseases that have spread from non-human primates (NHP) to humans. For millennia, indigenous groups that depend on wildlife for their survival were exposed to the risk of NHP pathogens' transmission through animal hunting and wild meat consumption. Usually, exposure is of no consequence or is limited to mild infections. In rare situations, it can be more severe or even become a real public health concern. Since the emergence of acquired immune deficiency syndrome (AIDS), nobody can ignore that an emerging infectious diseases (EID) might spread from NHP into the human population. In large parts of Central Africa and Asia, wildlife remains the primary source of meat and income for millions of people living in rural areas. However, in the past few decades the risk of exposure to an NHP pathogen has taken on a new dimension. Unprecedented breaking down of natural barriers between NHP and humans has increased exposure to health risks for a much larger population, including people living in urban areas. There are several reasons for this: (i) due to road development and massive destruction of ecosystems for agricultural needs, wildlife and humans come into contact more frequently; (ii) due to ecological awareness, many long distance travelers are in search of wildlife discovery, with a particular fascination for African great apes; (iii) due to the attraction for ancient temples and mystical practices, others travelers visit Asian places colonized by NHP. In each case, there is a risk of pathogen transmission through a bite or another route of infection. Beside the individual risk of contracting a pathogen, there is also the possibility of starting a new pandemic. This article reviews the known cases of NHP pathogens' transmission to humans whether they are hunters, travelers, ecotourists, veterinarians, or scientists working on NHP. Although pathogen transmission is supposed to be a rare outcome, Rabies virus, Herpes B virus, Monkeypox virus, Ebola virus, or Yellow fever virus infections are of greater concern and require quick countermeasures from public health professionals.

negative: Assessing the interactions between COVID-19 and influenza in the United States The 2019–2020 influenza sentinel surveillance data exhibits unexpected trends. Typical influenza seasons have a small herald wave, followed by a decrease due to school closure during holidays, and then a main post-holiday peak that is significantly larger than the pre-holiday wave. During the 2019–2020 influenza season, influenza-like illness data in the United States appears to have a markedly lower main epidemic peak compared to what would be expected based on the pre-holiday peak. We hypothesize that the 2019–2020 influenza season does have a lower than expected burden and that this deflation is due to a behavioral or ecological interaction with COVID-19. We apply an intervention analysis to assess if this influenza season deviates from expectations, then we compare multiple hypothesized drivers of the decrease in influenza in a spatiotemporal regression model. Lastly, we develop a mechanistic metapopulation model, incorporating transmission reduction that scales with COVID-19 risk perception. We find that the 2019–2020 ILI season is smaller and decreases earlier than expected based on prior influenza seasons, and that the increase in COVID-19 risk perception is associated with this decrease. Additionally, we find that a 5% average reduction in transmission is sufficient to reproduce the observed flu dynamics. We propose that precautionary behaviors driven by COVID-19 risk perception or increased isolation driven by undetected COVID-19 spread dampened the influenza season. We suggest that when surveillance for a novel pathogen is limited, surveillance streams of co-circulating infections may provide a signal.

negative: Chapter 3 Viral Emerging Pathogen Evolution Abstract The emergence of emerging and reemerging infectious diseases throughout history has been the product of the interaction of infectious agents, immunity, selective pressure, and environmental factors. The origin of the viral ancestors remains controversial, the debate remains whether the viruses existed before their host cells, evolved as molecular structures that adapted to the intracellular development or of the cells that infected or housed them as hosts. The nature of the viruses could propose a hypothetical evolutionary model based on the way they parasitize cells and the way they fuse with their host cells. So far there are no “universal” viral genes that have not allowed the hypotheses of the “common viral ancestor” to be conclusive. Insects have a special role in understanding viral evolution and how they became pathogens, suggesting a coevolutionary scenario of colonization that would initially allow the survival of viruses and later an ecological niche required for the cycle of virus replication. The coevolution of viruses and defense systems of hosts represents a fundamental role in the evolution of both viruses and host cells, a kind of arms race between viruses and hosts, and the deescalation of that war could explain the coexistence of viruses and hosts. Viruses are playing an important role in the understanding of cell evolution and have earned the right to be included in the tree of life. The aim of this chapter is to review the viral evolution and the insects as host.

negative: SARS-CoV-2 infection and stem cells: interaction and intervention The emergence of the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread have created a global health emergency. The resemblance with SARS-CoV in spike protein suggests that SARS-CoV-2 employs spike–driven entry into angiotensin-converting enzyme 2 (ACE2)-expressing cells. From a stem cell perspective, this review focuses on the possible involvement of ACE2(+) stem/progenitor cells from both the upper and lower respiratory tracts in coronavirus infection. Viral infection-associated acute respiratory distress syndrome and acute lung injury occur because of dysregulation of the immune response. Mesenchymal stem cells appear to be a promising cell therapy given that they favorably modulate the immune response to reduce lung injury. The use of exogenous stem cells may lead to lung repair. Therefore, intervention by transplantation of exogenous stem cells may be required to replace, repair, remodel, and regenerate lung tissue in survivors infected with coronavirus. Ultimately, vaccines, natural killer cells and induced-pluripotent stem cell-derived virus-specific cytotoxic T lymphocytes may offer off-the-shelf therapeutics for preventing coronavirus reemergence.

negative: Population movement, city closure and spatial transmission of the 2019-nCoV infection in China The outbreak of pneumonia caused by a novel coronavirus (2019-nCoV) in Wuhan City of China obtained global concern, the population outflow from Wuhan has contributed to spatial expansion in other parts of China. We examined the effects of population outflow from Wuhan on the 2019-nCoV transmission in other provinces and cities of China, as well as the impacts of the city closure in Wuhan. We observed a significantly positive association between population movement and the number of cases. Further analysis revealed that if the city closure policy was implemented two days earlier, 1420 (95% CI: 1059, 1833) cases could be prevented, and if two days later, 1462 (95% CI: 1090, 1886) more cases would be possible. Our findings suggest that population movement might be one important trigger of the 2019-nCoV infection transmission in China, and the policy of city closure is effective to prevent the epidemic.

negative: Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL (pro)) using the crystal structure of the highly similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are of the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart. With the 3CL (pro) molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the new coronavirus with minimal side effects, commonly fatigue and headache. The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.

negative: Virus hazards from food, water and other contaminated environments Numerous viruses of human or animal origin can spread in the environment and infect people via water and food, mostly through ingestion and occasionally through skin contact. These viruses are released into the environment by various routes including water run-offs and aerosols. Furthermore, zoonotic viruses may infect humans exposed to contaminated surface waters. Foodstuffs of animal origin can be contaminated, and their consumption may cause human infection if the viruses are not inactivated during food processing. Molecular epidemiology and surveillance of environmental samples are necessary to elucidate the public health hazards associated with exposure to environmental viruses. Whereas monitoring of viral nucleic acids by PCR methods is relatively straightforward and well documented, detection of infectious virus particles is technically more demanding and not always possible (e.g. human norovirus or hepatitis E virus). The human pathogenic viruses that are most relevant in this context are nonenveloped and belong to the families of the Caliciviridae, Adenoviridae, Hepeviridae, Picornaviridae and Reoviridae. Sampling methods and strategies, first-choice detection methods and evaluation criteria are reviewed.

negative: Molecular evolution of novel swine-origin A/H1N1 influenza viruses among and before human We find that the novel A/H1N1 influenza viruses exhibit very low genetic divergence and suffer strong purifying selection among human population and confirm that they originated from the reassortment of previous triple-reassortant swine influenza viruses including genomic segments from both avian and human lineages with North American and Eurasian swine lineages. The longer phylogenetic branch length to their nearest genetic neighbors indicates that the origin of the novel A/H1N1 is unlikely to be a very recent event. Seventy-six new unique mutations are found to be monomorphically fixed in the novel A/H1N1 virus lineages, suggesting a role of selective sweep in the early evolution of this virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-009-0393-7) contains supplementary material, which is available to authorized users.

negative: A Tempo-geographic Analysis of Global COVID-19 Epidemic Outside of China BACKGROUND: Understanding the global epidemic trends, geographic distribution, and transmission patterns of COVID-19 contribute to providing timely information for the global response of the epidemic. This study aims to understand the global pandemic geospatial patterns and trends and identify new epicenters requiring urgent attention. METHODS: Data on COVID-19 between 31(st) Dec. 2019 and 14(th) Mar. 2020 was included. The epidemic trend was analyzed using joinpoint regressions; the growth of affected countries was by descriptive analysis; and the global distribution and transmission trend by spatial analysis. FINDINGS: The number of new cases in the regions outside of China slowly increased before 24(th) Feb. and rapidly accelerated after 24(th) Feb. Compared to China, other affected countries experienced a longer duration of a slow increase at the early stage and rapid growth at the latter stages. The first apparent increase in the number of affected countries occurred from 23(rd) Jan to 1(st) Feb, and the second apparent increase started from 25(th) Feb. The fist COVID-19 cases reported by countries from 28(th) Feb. were mainly imported from Europe. The geographic distribution changed from single-center (13(th) Jan. - 20(th) Feb.) to multi-centers pattern (20(th) Feb. – 14(th) Mar.). More countries were affected with COVID-19 and developed local transmission. INTERPRETATION: The joinpoint regression and geospatial analysis indicated a multi-center pandemic of COVID-19. Strategies to prevent the new multiple centers as well as prevent ongoing transmission are needed. FUNDING: NIH.

negative: Comment on “Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade”

negative: Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing.

negative: Clinical characteristics of 82 death cases with COVID-19 Background A recently developing pneumonia caused by SARS-CoV-2 was originated in Wuhan, China, and has quickly spread across the world. We reported the clinical characteristics of 82 death cases with COVID-19 in a single center. Methods Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital′s electronic medical records according to previously designed standardized data collection forms. Findings All patients were local residents of Wuhan, and the great proportion of them were diagnosed as severe illness when admitted. Most of the death cases were male (65.9%). More than half of dead patients were older than 60 years (80.5%) and the median age was 72.5 years. The bulk of death cases had comorbidity (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), following by sepsis syndrome/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhage, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On the admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), increased C-reactive protein level (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%). A high level of IL-6 (>10 pg/ml) was observed in all detected patients. Median time from initial symptom to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p=0.002), alanine aminotransferase (p=0.037) and time from initial symptom to death were interestingly observed. Conclusion Older males with comorbidities are more likely to develop severe disease, even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but either virus itself or cytokine release storm mediated damage to other organ including cardiac, renal, hepatic, and hemorrhage should be taken seriously as well.

negative: Detection of SARS-COV-2 in Placental and Fetal Membrane Samples Introduction: Since the first reports of the emergence of the novel coronavirus SARS-CoV-2 and its associated disease (COVID-19), concerns remain about whether the virus is transmissible in pregnant women from the mother to the fetus during either the antepartum period or the process of labor and delivery. One recent review reported that in a small number of cases, two PCR swabs of the placenta were sent in additional to neonatal and cord blood testing, and both placental PCR swabs were negative.1 Other studies have demonstrated the finding of SARS-CoV2 IgM in neonates born to mothers diagnosed with COVID-19 during pregnancy,2,3 findings that may indicate vertical transmission of the virus in utero. We report our experience with placental/membrane SARS-CoV2 RNA PCR swab results after delivery to a series of symptomatic mothers with confirmed COVID-19 infection in pregnancy. Methods: IRB approval was obtained. All pregnant patients diagnosed with COVID-19 who gave birth between March 1, 2020 and April 20, 2020 at NYU Langone Health were identified by a search of the electronic medical record. Charts were reviewed for documentation of SARS-CoV-2 RNA RT-PCR testing sent from either the placenta or membranes within 30 minutes following delivery. PCR testing for SARS-COV-2 was performed using the cobas SARS-CoV-2 assay (Roche) or the Cepheid Xpert Xpress assay. Placental swabs were obtained from the amniotic surface after clearing the surface of maternal blood (placental PCR). Membrane swabs were obtained from between the amnion and chorion after manual separation of the membranes (membrane PCR). Maternal COVID-19 illness was categorized as mild, severe, or critical.4 The time interval from maternal diagnosis of COVID-19 to delivery was calculated in days. Infants were tested with nasopharyngeal swabs for SARS-CoV-2 PCR between days of life 1 and 5 while hospitalized. Hospitalized infants were also assessed for clinical signs and symptoms, including fever, cough, and nasal congestion. Results: Of 32 COVID-19 positive pregnant patients who gave birth in this timeframe, placental or membrane swabs were sent from 11 patients (Table). Three of 11 swabs were positive. None of the infants tested positive for SARS-CoV2 on days of life 1 through 5, and none demonstrated symptoms of COVID-19 infection. Discussion: Of 11 placental or membrane swabs sent following delivery, 3 swabs were positive for SARS-CoV-2, all in women with moderate to severe COVID-19 illness at time of delivery. This is the first study to demonstrate the presence of SARS-CoV-2 RNA in placental or membrane samples. While there were no clinical signs of vertical transmission, our findings raise the possibility of intrapartum viral exposure. Given the mixing of maternal and fetal fluid and tissue at time of delivery, the origin of the detected SARS-CoV-2 RNA in our series is unclear. It may represent contamination from maternal blood, amniotic fluid, or COVID-19 infection of the membranes and amniotic sac. For those infants who were delivered vaginally, contamination with vaginal secretions is also a possible source, although prior studies on vaginal secretions have failed to demonstrate the presence of COVID-19.5,6Although all of our neonates tested negative in the first 5 days of life, many were born via cesarean deliveries with decreased length of exposure to these tissues, which may be associated with a decreased likelihood of vertical transmission. Additionally, nasopharyngeal testing immediately after delivery may not be the ideal approach to evaluate vertical transmission if exposure occurs at the time of delivery, as the virus may require a longer incubation period before these swabs convert to positive. In summary, the presence of viral RNA by RT-PCR in placenta/membranes at the time of delivery suggests the need for further research into the possibility of vertical transmission.

negative: Infection of a calf with the enteric coronavirus strain Paris A tissue-culture-grown enteric coronavirus infected the whole of the gastrointestinal tract and caused enteritis and diarrhoea in a 10-day-old gnotobiotic Friesian calf. Diarrhoea occurred 2 days after inoculation and excretion of virus in faeces and rectal swabs increased until necropsy at 3 days. Virus growth, as detected by indirect immunofluorescence, virus isolation, and thin section electron microscopy, was most extensive in the epithelium of the colon and rectum at 3 days after inoculation. No virus was detected in other organs or in the pleural, peritoneal and oropharyngeal cavities. The origin and host specificity of this coronavirus is discussed.

negative: Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19. OBJECTIVE The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, has caused a pandemic which has swiftly involved the entire world and raised great public health concerns. The scientific community is actively exploring treatments that would potentially be effective in combating COVID-19. Hydroxychloroquine has been demonstrated to limit the replication of SARS-CoV-2 virus in vitro. In malarial pandemic countries, chloroquine is widely used to treat malaria. In malarial non-pandemic nations, chloroquine is not widely used. Chloroquine and hydroxychloroquine share similar chemical structures and mechanisms of action. The aim of this study was to indirectly investigate the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 by determining the prevalence of COVID-19 in malaria pandemic and non-pandemic nations. We sought evidence to support or refute the hypothesis that these drugs could show efficacy in the treatment of COVID-19. MATERIALS AND METHODS We reviewed in vitro studies, in vivo studies, original studies, clinical trials, and consensus reports, that were conducted to evaluate the antiviral activities of chloroquine and hydroxychloroquine. The studies on "COVID-19 and its allied treatment were found from World Health Organization (WHO), ISI-Web of Science, PubMed, EMBASE, Scopus, Google Scholar, and clinical trial registries. The search was based on keywords: antiviral drugs, chloroquine, hydroxychloroquine, COVID-19, COVID-19 treatment modalities, and coronavirus. In addition, we analyzed the prevalence of COVID-19 in malaria pandemic and non-pandemic countries. The review and analyses were performed on March 28, 2020. RESULTS For this study, we identified a total of 09 published articles: 03 clinical trials with sample size 150; 03 in vitro studies and 03 expert consensus reports. These studies were all suggestive that chloroquine and hydroxychloroquine can successfully treat COVID-19 infections. We found that COVID-19 infections are highly pandemic in countries where malaria is least pandemic and are least pandemic in nations where malaria is highly pandemic. CONCLUSIONS Chloroquine and hydroxychloroquine have antiviral characteristics in vitro. The findings support the hypothesis that these drugs have efficacy in the treatment of COVID-19. People are currently using these drugs for malaria. It is reasonable, given the hypothetical benefit of these two drugs, that they are now being tested in clinical trials to assess their effectiveness to combat this global health crisis.

negative: Emerging viral infections in a rapidly changing world Abstract Emerging viral infections in both humans and animals have been reported with increased frequency in recent years. Recent advances have been made in our knowledge of some of these, including severe acute respiratory syndrome-associated coronavirus, influenza A virus, human metapneumovirus, West Nile virus and Ebola virus. Research efforts to mitigate their effects have concentrated on improved surveillance and diagnostic capabilities, as well as on the development of vaccines and antiviral agents. More attention needs to be given to the identification of the underlying causes for the emergence of infectious diseases, which are often related to anthropogenic social and environmental changes. Addressing these factors might help to decrease the rate of emergence of infectious diseases and allow the transition to a more sustainable society.

negative: SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain in the host population. In turn, the virus can never completely eliminate the host population, because evolutionarily such an event is a dead end for the virus as an obligate intracellular parasite. A certain existential balance exists in the virus-host relationship. Against this backdrop, viral epidemics and pandemics only become manifest and egregious to human beings when tens and hundreds of thousands of people die and the question emerges what caused the high mortality peaks on the death chart. The answer seems clear; the emerging strain of the virus is new to the host population, and new mutations of the virus and natural selection will lead to a survival of only genetically resistant individuals in a host population. The dangers inherent to a novel virus are due to new features generally inthe molecular structure of proteins, which enable the virus to infect the cells of the host organism more intensively, dramatically challenging host immunity, and thus be transmitted more readily in the host population. In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In fact, only two scenarios will occur simultaneously in the very near future: people who are genetically resistant to the virus will get sick, recover, and develop immunity, while people who are sensitive to the virus will need drugs and vaccines, which will have to be researched and developed if they are to recover. If the pandemic does not stop, in a few decades it is anticipated that SARS-CoV-2 will become as safe as the four non-severe acute respiratory syndrome human coronaviruses (HCoV-NL63, HCoV-HKU1, HCoV-OC43, and HCoV-229E) currently circulating but causing low mortality in the human population.

negative: The aetiology, origins, and diagnosis of severe acute respiratory syndrome Summary Severe acute respiratory syndrome (SARS) is a new infectious disease that first emerged in Guangdong province, China, in November, 2002. A novel coronavirus was later identified in patients with SARS. The detection of the virus in these patients, its absence in healthy controls or other patients with atypical pneumonia, and the reproduction of a similar disease in a relevant animal model fulfilled Koch's postulates for implicating this coronavirus as the causal agent of SARS. The full genome sequence was determined within weeks of the virus's identification. The rapid progress in the aetiology, the development of laboratory diagnostic tests, and the defining of routes of viral transmission were facilitated through a unique WHO-coordinated virtual network of laboratories, which shared information on a real-time basis through daily teleconferences. Subsequent studies have indicated that the SARS coronavirus is of animal origin, that its precursor is still present in animal populations within the region, and that live-animal markets in southern China may have provided the animal-human interphase that allowed this precursor virus to adapt to human-human transmission. These findings underscore the potential for the re-emergence of SARS and the need for laboratory tests for early diagnosis. However, the low viral load in the respiratory tract makes early diagnosis of SARS a diagnostic challenge, although improvements in the sensitivity of molecular diagnostic methods continue to be made.

negative: Evidence of bat origin for Menangle virus, a zoonotic paramyxovirus first isolated from diseased pigs. Menangle virus (MenPV) is a zoonotic paramyxovirus capable of causing disease in pigs and humans. It was first isolated in 1997 from stillborn piglets at a commercial piggery in New South Wales, Australia, where an outbreak of reproductive disease occurred. Neutralizing antibodies to MenPV were detected in various pteropid bat species in Australia and fruit bats were suspected to be the source of the virus responsible for the outbreak in pigs. However, previous attempts to isolate MenPV from various fruit bat species proved fruitless. Here, we report the isolation of MenPV from urine samples of the black flying fox, Pteropus alecto, using a combination of improved procedures and newly established bat cell lines. The nucleotide sequence of the bat isolate is 94 % identical to the pig isolate. This finding provides strong evidence supporting the hypothesis that the MenPV outbreak in pigs originated from viruses in bats roosting near the piggery.

negative: Cytokine Storm Induced by SARS-CoV-2 A novel coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading globally, causing severe pneumonia and acute lung injury in many patients. Even worse, severe respiratory may develop into acute respiratory distress syndrome and multiple organ dysfunction syndrome in COVID-19. The cytokine storm caused by immune over-activation due to virus infection may be an important cause of death in the late period of progress, but the pathogenesis of cytokine storm is still unclear. This article reviews the mechanisms of SARS-CoV-2-induced cytokine storm in detail based on the current discovered researches, and put forward some valuable medication ideas for the targeted cytokines drug researches and treatment. The goal of this work will be helpful for reducing excessive immune response.

negative: 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.

negative: Power-law distribution in the number of confirmed COVID-19 cases COVID-19 is an emerging respiratory infectious disease caused by the coronavirus SARS-CoV-2. It was first reported on in early December 2019 in Wuhan, China and within three month spread as a pandemic around the whole globe. Here, we study macro-epidemiological patterns along the time course of the pandemic. We compute the distribution of confirmed COVID-19 cases and deaths for countries worldwide and for counties in the US, and show that both distributions follow a truncated power-law over five orders of magnitude. We are able to explain the origin of this scaling behavior as a dual-scale process: the large-scale spread of the virus between countries and the small-scale accumulation of case numbers within each country. Assuming exponential growth on both scales, the critical exponent of the power-law is determined by the ratio of large-scale to small-scale growth rates. We confirm this theory in numerical simulations in a simple meta-population model, describing the epidemic spread in a network of interconnected countries. Our theory gives a mechanistic explanation why most COVID-19 cases occurred within a few epicenters, at least in the initial phase of the outbreak. Assessing how well a simple dual-scale model predicts the early spread of epidemics, despite the huge contrasts between countries, could help identify critical temporal and spatial scales of response in which to mitigate future epidemic threats.

negative: Predictions for the binding domain and potential new drug targets of 2019-nCoV An outbreak of new SARS-like viral in Wuhan, China has been named 2019-nCoV. The current state of the epidemic is increasingly serious, and there has been the urgent necessity to develop an effective new drug. In previous studies, it was found that the conformation change in CTD1 was the region where SARS-CoV bound to human ACE2. Although there are mutations of the 2019-nCoV, the binding energy of ACE2 remains high. The surface glycoprotein of 2019-nCoV was coincident with the CTD1 region of the S-protein by comparing the I-TASSER prediction model with the actual SARS model, which suggests that 2019-nCoV may bind to the ACE2 receptor through conformational changes. Furthermore, site prediction on the surface glycoprotein of 2019-nCoV suggests some core amino acid area may be a novel drug target against 2019-nCoV.

negative: Powerful Sequence Similarity Search Methods and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently “Orphan” Viral Proteins The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as “genus specific” by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virions.

negative: HIV-1 did not contribute to the 2019-nCoV genome

negative: Diagnosing COVID-19: Did We Miss Anything? In late 2019, a mass of patients showing symptoms of a pneumonia-like disease of unknown origin emerged in Wuhan, China. Little did the world know it was the prelude of what would be a devastating pandemic. Samples were collected from these patients and the use of unbiased sequencing, and subsequent isolation of the pathogen using human airway epithelial cells led to the discovery of a novel coronavirus, named 2019-nCoV by the World Health Organization (WHO) and Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. The disease caused by this virus is officially called the coronavirus disease 2019 (COVID-19).

negative: Afectación clínica y sintomatológica en pacientes mayores de 65 años por COVID-19

negative: Coronavirus latest: global infections pass 100,000.

negative: Machine Learning Approach for Confirmation of COVID-19 Cases: Positive, Negative, Death and Release In recent days, Covid-19 coronavirus has been an immense impact on social, economic fields in the world. The objective of this study determines if it is feasible to use machine learning method to evaluate how much prediction results are close to original data related to Confirmed-Negative-Released-Death cases of Covid-19. For this purpose, a verification method is proposed in this paper that uses the concept of Deep-learning Neural Network. In this framework, Long short-term memory (LSTM) and Gated Recurrent Unit (GRU) are also assimilated finally for training the dataset and the prediction results are tally with the results predicted by clinical doctors. The prediction results are validated against the original data based on some predefined metric. The experimental results showcase that the proposed approach is useful in generating suitable results based on the critical disease outbreak. It also helps doctors to recheck further verification of virus by the proposed method. The outbreak of Coronavirus has the nature of exponential growth and so it is difficult to control with limited clinical persons for handling a huge number of patients with in a reasonable time. So it is necessary to build an automated model, based on machine learning approach, for corrective measure after the decision of clinical doctors. It could be a promising supplementary confirmation method for frontline clinical doctors. The proposed method has a high prediction rate and works fast for probable accurate identification of the disease. The performance analysis shows that a high rate of accuracy is obtained by the proposed method.

negative: Diversity of Middle East respiratory syndrome coronaviruses in 109 dromedary camels based on full-genome sequencing, Abu Dhabi, United Arab Emirates Middle East respiratory syndrome coronavirus (MERS-CoV) was identified on the Arabian Peninsula in 2012 and is still causing cases and outbreaks in the Middle East. When MERS-CoV was first identified, the closest related virus was in bats; however, it has since been recognized that dromedary camels serve as a virus reservoir and potential source for human infections. A total of 376 camels were screened for MERS-Cov at a live animal market in the Eastern Region of the Emirate of Abu Dhabi, UAE. In all, 109 MERS-CoV-positive camels were detected in week 1, and a subset of positive camels were sampled again weeks 3 through 6. A total of 126 full and 3 nearly full genomes were obtained from 139 samples. Spike gene sequences were obtained from 5 of the 10 remaining samples. The camel MERS-CoV genomes from this study represent 3 known and 2 potentially new lineages within clade B. Within lineages, diversity of camel and human MERS-CoV sequences are intermixed. We identified sequences from market camels nearly identical to the previously reported 2015 German case who visited the market during his incubation period. We described 10 recombination events in the camel samples. The most frequent recombination breakpoint was the junctions between ORF1b and S. Evidence suggests MERS-CoV infection in humans results from continued introductions of distinct MERS-CoV lineages from camels. This hypothesis is supported by the camel MERS-CoV genomes sequenced in this study. Our study expands the known repertoire of camel MERS-CoVs circulating on the Arabian Peninsula.

negative: A predictive decision-aid methodology for dynamic mitigation of influenza pandemics In a recent report, the Institute of Medicine has stressed the need for dynamic mitigation strategies for pandemic influenza. In response to the need, we have developed a simulation-based optimization methodology for generating dynamic predictive mitigation strategies for pandemic outbreaks affecting several regions. Our methodology can accommodate varying virus and population dynamics. It progressively allocates a limited budget to procure vaccines and antivirals, capacities for their administration, and resources required to enforce social distancing. The methodology uses measures of morbidity, mortality, and social distancing, which are translated into the costs of lost productivity and medical services. The simulation model was calibrated using historic pandemic data. We illustrate the use of our methodology on a mock outbreak involving over four million people residing in four major population centers in Florida, USA. A sensitivity analysis is presented to estimate the impact of changes in the budget availability and variability of some of the critical parameters of mitigation strategies. The methodology is intended to assist public health policy makers.

negative: Novel coronaviruses and astroviruses in bats Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronaviruses and astroviruses, which can be found from a wide range of mammals, were recently detected in bats. Strikingly, these bat viruses are genetically highly diverse and these interesting findings might help to better understand the evolution and ecology of these viruses. The discoveries of these novel bats viruses not only suggested that bats are important hosts for these virus families, but also reiterated the role of bats as a reservoir of viruses that might pose a zoonotic threat to human health.

negative: CT manifestations of the coronavirus disease 2019 of imported infection versus second-generation infection in patients outside the original district (Wuhan, China) of this disease: An observational study To explore the discrepancy in computed tomography (CT) manifestations of the coronavirus disease 2019 (COVID-19) in patients outside the original district (Wuhan, China) between cases with imported infection and second-generation infection, 22 patients with COVID-19 from 2 hospitals in Nanchong, China, 938 km away from the original district (Wuhan, China) of this disease were enrolled. All patients underwent initial and follow-up CT after admission during the treatment, and were divided into 2 groups. Group A and B were composed of 15 patients with a history of exposure to the original district (Wuhan, China) in short-term (i.e., imported infection), and 7 with a close contact with the patients with confirmed COVID-19 or with the healthy individuals from the original district (i.e., second-generation infection), respectively. Initial CT features including extent score and density score between groups were statistically compared. We found that all patients in group A and 3 of 7 patients in group B had abnormal CT findings while 4 of 7 patients in group B had not. Patients with abnormal CT findings were more frequent in group A than in group B (P < .05). On initial CT, pure ground glass opacity (GGO), and GGO with consolidation and/or other abnormalities were found in 20% (3/15) and 80% (12/15) patients in group A, respectively, while 1 (14.3%), 2 (28.6%), and 4 (57.1%) had pure GGOs, GGO with focal consolidation, and normal CT appearances in Group B, respectively. Patients with extent and density scores of ≥5 were more frequent in group A than in group B (all P-values < .01). Additionally, 3 of 4 (75%) patients with normal initial CT findings had focal pure GGO lesions on follow-up. In conclusion, COVID-19 in patients with a history of exposure to the original district can be severer than with the second-generation infection on CT.

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

negative: In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection BACKGROUND: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood. FINDINGS: A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature. In-situ histological staining of the respective cellular receptors for MERS- and SARS-Coronavirus showed highly similar staining patterns with a focus of a receptor-specific signal in kidney epithelial cells. Comparative infection experiments with SARS- and MERS-CoV in primary human kidney cells versus primary human bronchial epithelial cells showed cytopathogenic infection only in kidney cells, and only if infected with MERS-CoV. Kidney epithelial cells produced almost 1000-fold more infectious MERS-CoV progeny than bronchial epithelial cells, while only a small difference was seen between cell types when infected with SARS-CoV. CONCLUSION: Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment.

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: Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.

negative: Children are unlikely to have been the primary source of household SARS-CoV-2 infections BACKGROUND: Since its identification on the 7th of January 2020, SARS-CoV-2 has spread to more than 180 countries worldwide, causing >11,000 deaths. At present, viral disease and transmission amongst children is incompletely understood. Specifically, there is concern that children could be an important source of SARS-CoV-2 in household transmission clusters. METHODS: We performed an observational study analysing literature published between December 2019 and March 2020 of the clinical features of SARS-CoV-2 in children and descriptions of household transmission clusters of SARS-CoV-2. In these studies the index case of each cluster defined as the individual in the household cluster who first developed symptoms. FINDINGS: Drawing on studies from China, Singapore, South Korea, Japan, and Iran a broad range of clinical symptoms were observed in children. These ranged from asymptomatic to severe disease. Of the 31 household transmission clusters that were identified, 9.7% (3/31) were identified as having a paediatric index case. This is in contrast other zoonotic infections (namely H5N1 influenza virus) where 54% (30/56) of transmission clusters identified children as the index case. INTERPRETATION: Whilst SARS-CoV-2 can cause mild disease in children, the data available to date suggests that children have not played a substantive role in the intra-household transmission of SARS-CoV-2.

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

negative: Chaos theory applied to the outbreak of Covid-19: an ancillary approach to decision-making in pandemic context Predicting the course of an epidemic is difficult, predicting the course of a pandemic from an emerging virus even more so. The validity of most predictive models relies on numerous parameters, involving biological and social characteristics often unknown or highly uncertain. COVID-19 pandemic brings additional factors such as population density and movements, behaviours, quality of the health system. Data from the COVID-19 epidemics in China, Japan and South Korea were used to build up data-driven deterministic models. Epidemics occurring in selected European countries rapidly evolved to overtake most Chinese provinces, to overtake South Korean model for France and even Hubei in the case of Italy and Spain. This approach was applied to other European countries and provides relevant information to inform disease control decision-making.

negative: A systematic review of the prophylactic role of chloroquine and hydroxychloroquine in coronavirus disease‐19 (COVID‐19) OBJECTIVE: The pandemic coronavirus disease‐19 (COVID‐19) has pushed the global healthcare system to a crisis and amounted to a huge economic burden. Different drugs for prophylaxis against COVID‐19 including chloroquine (CQ) or hydroxychloroquine (HCQ) have been tried. This study was performed to systematically review the role of CQ and HCQ in preventing the spread of COVID‐19. METHODS: PubMed, EMBASE, ClinicalTrials.gov, International Clinical Trials Registry Platform and Cochrane Library databases were searched for studies that evaluated the prophylactic role of CQ or HCQ on SARS‐CoV‐2 (pre‐clinical studies) or COVID‐19 (clinical studies) until 30 March 2020. The available literature was critically appraised. RESULTS: A total of 45 articles were screened and 5 (3 in vitro pre‐clinical studies and 2 clinical opinions) were included. The pre‐clinical studies showed the prophylactic effects of CQ and HCQ against SARS‐CoV‐2. On the other hand, the clinical opinions advocated the prophylactic use of CQ and HCQ against COVID‐19. However, no original clinical studies on the prophylactic role of CQ or HCQ on COVID‐19 were available. CONCLUSION: Although pre‐clinical results are promising, to date there is a dearth of evidence to support the efficacy of CQ or HCQ in preventing COVID‐19. Considering potential safety issues and the likelihood of imparting a false sense of security, prophylaxis with CQ or HCQ against COVID‐19 needs to be thoroughly evaluated in observational studies or high‐quality randomized controlled studies.

negative: Sympatric speciation in parasites – what is sympatry? Abstract Parasites account for a large part of known species diversity and are considered to have a high potential for sympatric speciation. However, the frequency of sympatric divergence in these organisms will depend on the definition of sympatry that one uses. Like many of our current species concepts, the typical definition of sympatry is not widely applicable to parasites. Revisiting the historically defined conditions for sympatric speciation and considering the situations in which we might regard parasites as being sympatric leads us to question the classic prediction that parasites have a greater tendency to speciate in sympatry than do free-living organisms.

negative: What further should be done to control COVID-19 outbreaks in addition to cases isolation and contact tracing measures? Historically, these interventions have been successfully applied for controlling a variety of emerging infectious disease outbreaks, such as smallpox and SARS, but only partially effective for foot-and-mouth disease, and likely not effective for influenza [2,3,4] Currently, it is not yet clear whether case isolation and contact tracing measures are sufficient to contain a new outbreak from COVID-19 Recently, Hellewell and colleagues developed a stochastic transmission model to assess the potential effectiveness of case isolation and contact tracing in controlling COVID-19 outbreak [5] They suggested that in most modeled scenarios contact tracing and case isolation alone might be insufficient to control a new outbreak of COVID-19 within 3 months, especially when longer delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increased transmission before symptoms exist It is the first study using a stochastic model to evaluate the effects of isolation and contact tracing intervention for outbreak of COVID-19 In this study, the authors simplified the outputs of their model to the effects of contact tracing and isolation on the control of outbreaks under different scenarios of transmission, and included several parameters (e g , the basic reproduction number R0, the delay from symptom onset to isolation, and the probability contacts were traced) other than merely focusing on R0 This interesting study provides a timely evaluation strategy to quantify the potential effectiveness of case isolation and contact tracing measures and may bring insights for the control the COVID-19 outbreak in China and probably other areas of the world as wellDO - 10 1186/s12916-020-01551-8

negative: End-of-life care in the emergency department for the patient imminently dying of a highly transmissible acute respiratory infection (such as COVID-19)

negative: Correcting under-reported COVID-19 case numbers: estimating the true scale of the pandemic The COVID-19 virus has spread worldwide in a matter of a few months, while healthcare systems struggle to monitor and report current cases. Testing results have struggled with the relative capabilities, testing policies and preparedness of each affected country, making their comparison a non-trivial task. Since severe cases, which more likely lead to fatal outcomes, are detected at a higher rate than mild cases, the reported virus mortality is likely inflated in most countries. Lockdowns and changes in human behavior modulate the underlying growth rate of the virus. Under-sampling of infection cases may lead to the under-estimation of total cases, resulting in systematic mortality estimation biases. For healthcare systems worldwide it is important to know the expected number of cases that will need treatment. In this manuscript, we identify a generalizable growth rate decay reflecting behavioral change. We propose a method to correct the reported COVID-19 cases and death numbers by using a benchmark country (South Korea) with near-optimal testing coverage, with considerations on population demographics. We extrapolate expected deaths and hospitalizations with respect to observations in countries that passed the exponential growth curve. By applying our correction, we predict that the number of cases is highly under-reported in most countries and a significant burden on worldwide hospital capacity.

negative: Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development Novel Coronavirus (2019-nCoV) is an emerging pathogen that was first identified in Wuhan, China in late December 2019. This virus is responsible for the ongoing outbreak that causes severe respiratory illness and pneumonia-like infection in humans. Due to the increasing number of cases in China and outside China, the WHO declared coronavirus as a global health emergency. Nearly 35,000 cases were reported and at least 24 other countries or territories have reported coronavirus cases as early on as February. Inter-human transmission was reported in a few countries, including the United States. Neither an effective anti-viral nor a vaccine is currently available to treat this infection. As the virus is a newly emerging pathogen, many questions remain unanswered regarding the virus’s reservoirs, pathogenesis, transmissibility, and much more is unknown. The collaborative efforts of researchers are needed to fill the knowledge gaps about this new virus, to develop the proper diagnostic tools, and effective treatment to combat this infection. Recent advancements in plant biotechnology proved that plants have the ability to produce vaccines or biopharmaceuticals rapidly in a short time. In this review, the outbreak of 2019-nCoV in China, the need for rapid vaccine development, and the potential of a plant system for biopharmaceutical development are discussed.

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

negative: Management and Treatment of COVID-19: The Chinese Experience Abstract With over 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. The objective of this paper is to critically review the available evidence regarding the lessons learned from the Chinese experience regarding COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hebei and the rest of the country, as well as closure of all schools and non-essential businesses. Other measures included the rapid construction of two new hospitals and the establishment of Fangcang shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin and convalescent plasma infusions. These measures appeared to provide only moderate success. While some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well-controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers and contacts, and early implementation of quarantine measures with an organized, proactive and unified strategy at a national level. Delays result in significantly higher death tolls.

negative: (13)C Chemical Shifts in Proteins: A Rich Source of Encoded Structural Information Despite the formidable progress in Nuclear Magnetic Resonance (NMR) spectroscopy, quality assessment of NMR-derived structures remains as an important problem. Thus, validation of protein structures is essential for the spectroscopists, since it could enable them to detect structural flaws and potentially guide their efforts in further refinement. Moreover, availability of accurate and efficient validation tools would help molecular biologists and computational chemists to evaluate quality of available experimental structures and to select a protein model which is the most suitable for a given scientific problem. The (13)C(α) nuclei are ubiquitous in proteins, moreover, their shieldings are easily obtainable from NMR experiments and represent a rich source of encoded structural information that makes (13)C(α) chemical shifts an attractive candidate for use in computational methods aimed at determination and validation of protein structures. In this chapter, the basis of a novel methodology of computing, at the quantum chemical level of theory, the (13)C(α) shielding for the amino acid residues in proteins is described. We also identify and examine the main factors affecting the (13)C(α)-shielding computation. Finally, we illustrate how the information encoded in the (13)C chemical shifts can be used for a number of applications, viz., from protein structure prediction of both α-helical and β-sheet conformations, to determination of the fraction of the tautomeric forms of the imidazole ring of histidine in proteins as a function of pH or to accurate detection of structural flaws, at a residue-level, in NMR-determined protein models.

negative: The COVID-19 pandemic: we are all in this together

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: Epidemic update of COVID-19 in Hubei Province compared with other regions in China Abstract Aims & Background The COVID-19 outbreak spread in China and is a threat to the world. The aims of this study to help health workers better understand the epidemic of the COVID-19 and provide different control strategies toward Hubei Province and other regions in China. Methods A comprehensive search of the Chinese Center for Disease Control and Prevention official websites and announcements was performed between 20 Jan 2019 and 29 Feb 2020. The relevant data of the distribution of the infection on each reported day were obtained. Results& findings Up to 29 Feb 2020, 79,824 confirmed cases with the COVID-19 including 66,907 in Hubei Province and 12,377 in other administrative regions were reported. The SARS-COV-2 showed faster epidemic trends compared with the 2003-SARS-CoV. A total of 2,870 deaths have been reported nationwide among 79,824 confirmed cases, with a mortality of 3.6%. The mortality of the COVID-19 was significantly higher in Hubei Province than that in other regions(4.1% versus 0.84%). Since 1 Feb 2020 the number of discharged cases exceeded the number of the dead. By 29 Feb 2020, the number of discharged patients was 41,625, which exceeded the number of hospitalized patients, and the trend has further increased. Conclusions The infection of the SARS-COV-2 is spreading and increasing nationwide, and Hubei Province is the main epidemic area, with higher mortality. The outbreak is now under initial control especially in other regions outside of Hubei Province. Due to the different epidemic characteristics between Hubei Province and other regions, we should focus on different prevention and control strategies.

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

negative: What works and what does not work in response to COVID-19 prevention and control in Africa Since the emergence of the COVID-19 pandemic in December 2019 in Wuhan, China, there have been nearly 6,663,304 confirmed cases of COVID-19, including 392,802 deaths, worldwide as of 10:00 CEST 06 June 2020. In Africa, 152,442 COVID-19 cases and 4334 deaths have been reported as of 02 June 2020. The five countries with the highest commutative number of cases in Africa are South Africa, Egypt, Nigeria, Algeria, and Ghana. Africa, and the rest of world, has had to swiftly undertake the necessary measures to protect the continent from irreversible effects of the COVID-19 pandemic that is claiming lives and destroying livelihoods. The lower number of COVID-19 cases in most African countries is attributed to inadequate health systems, low-to-absent testing capacity, poor reporting systems, and insufficient numbers of medical staff. The COVID-19 pandemic poses a great threat to most African countries, from cities to rural areas, and has created a strong demand on already scarce resources. Intense mobilization of additional resources is required to implement established emergency contingency measures. Measures to prevent the spread of COVID-19 include closure of borders and restricting movement of people within a country; this has resulted in the tourism sector being adversely affected by the loss of income. Cooperative prevention and control measures are one of the promising solutions to deplete the spread of COVID-19 on the continent.

negative: COVID-19 is a challenge for dental education-A commentary The COVID-19, which appeared to originate in China in December 2019, has spread worldwide pandemically. In this commentary, authors described this new challenge for dental education using the recent literature and experience gained in the Italian University of Catanzaro.

negative: Assessing the fear of COVID-19 among different populations: A response to Ransing et al. (2020)

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: SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays revealed that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of more than 15,000 SARS-CoV-2 sequences identified a natural variant, in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients, but also describe a possibility of the emergence of natural SARS-CoV-2 quasispecies with extended ORF3b that may exacerbate COVID-19 symptoms. Highlights ORF3b of SARS-CoV-2 and related bat and pangolin viruses is a potent IFN antagonist SARS-CoV-2 ORF3b suppresses IFN induction more efficiently than SARS-CoV ortholog The anti-IFN activity of ORF3b depends on the length of its C-terminus An ORF3b with increased IFN antagonism was isolated from two severe COVID-19 cases

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: Feline Infectious Peritonitis: An Immune-Mediated Coronaviral Vasculitis Mainly through studies inducing experimental infection of susceptible cats, significant advances have recently been made in our understanding of the pathogenesis of FIP. Much of this knowledge should not presently be directly extrapolated to field cases of FIP, because the route of infection and challenge dose and strain of virus may be significantly different. Advances in the prevention and treatment of FIP will depend greatly on clarification of the exact nature of the several coronaviruses affecting cats and the role of cell-mediated immunity in resistance to FIPV.

negative: Pandémie COVID-19 : impact sur le systeme cardiovasculaire. Données disponibles au 1er avril 2020 Résumé Le syndrome respiratoire aigu sévère coronavirus 2 (SARS-CoV-2) infecte les cellules hôtes par les récepteurs de l’angiotensine, conduisant à une pneumonie liée au COVID-19. À un niveau cardiaque, le virus a un double impact ; en effet, l’infection sera plus grave si l’hôte possède des comorbidités cardiovasculaires, et le virus peut causer des lésions cardiovasculaires pouvant engager le pronostic vital. Les thérapeutiques associées au COVID-19 peuvent avoir des effets indésirables cardiovasculaires. Une attention particulière doit être accordée à la protection cardiovasculaire pendant l’infection au COVID-19. Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.

negative: Study of combining virtual screening and antiviral treatments of the Sars-CoV-2 (Covid-19) The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 and causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. Additionally, general treatments, coronavirus-specific treatments, and antiviral treatments useful in fighting COVID-19 are addressed. This review sets out to shed light on the SARS-CoV-2 and host receptor recognition, a crucial factor for successful virus infection and taking immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein of SARS-CoV-2. A variety of improved or new approaches also have been developed. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection. Moreover, the genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three-dimensional structure of the Main protease (Mpro) is available. The reported structure of the target Mpro was described in this review to identify potential drugs for COVID-19 using virtual high throughput screening.

negative: Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health(1). Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)(2–10). Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96–98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013–2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.

negative: The Evolutionary History and Spatiotemporal Dynamics of the Fever, Thrombocytopenia and Leukocytopenia Syndrome Virus (FTLSV) in China BACKGROUND: In 2007, a novel bunyavirus was found in Henan Province, China and named fever, thrombocytopenia and leukocytopenia syndrome virus (FTLSV); since then, FTLSV has been found in ticks and animals in many Chinese provinces. Human-to-human transmission has been documented, indicating that FTLSV should be considered a potential public health threat. Determining the historical spread of FTLSV could help curtail its spread and prevent future movement of this virus. METHOD/PRINCIPAL FINDINGS: To examine the pattern of FTLSV evolution and the origin of outbreak strains, as well to examine the rate of evolution, the genome of 12 FTLSV strains were sequenced and a phylogenetic and Bayesian phylogeographic analysis of all available FTLSV sequences in China were performed. Analysis based on the FTLSV L segment suggests that the virus likely originated somewhere in Huaiyangshan circa 1790 (95% highest probability density interval: 1756–1817) and began spreading around 1806 (95% highest probability density interval: 1773–1834). Analysis also indicates that when FTLSV arrived in Jiangsu province from Huaiyangshan, Jiangsu Province became another source for the spread of the disease. Bayesian factor test analysis identified three major transmission routes: Huaiyangshan to Jiangsu, Jiangsu to Liaoning, and Jiangsu to Shandong. The speed of FTLSV movement has increased in recent decades, likely facilitated by modern human activity and ecosystem changes. In addition, evidence of RNA segment reassortment was found in FTLSV; purifying selection appears to have been the dominant force in the evolution of this virus. CONCLUSION: Results presented in the manuscript suggest that the Huaiyangshan area is likely be the origin of FTLSV in China and identified probable viral migration routes. These results provide new insights into the origin and spread of FTLSV in China, and provide a foundation for future virological surveillance and control.

negative: Conspiracy beliefs are associated with lower knowledge and higher anxiety levels regarding COVID-19 among students at the University of Jordan Background: The world has been afflicted heavily by the burden of coronavirus disease 2019 (COVID-19) that overwhelmed health care systems and caused severe economic and educational deficits, in addition to anxiety among the public. The main aim of this study was to evaluate the mutual effects of belief that the pandemic was the result of a global conspiracy on knowledge and anxiety levels among students at the University of Jordan (UJ). Methods: An electronic-based survey was conducted between March 29th 2020 and March 31st 2020. The targeted population involved all undergraduate and postgraduate students from Health, Scientific and Humanities Schools at UJ. Survey sections included 26 items on: socio-demographic information, knowledge and sources of information about the disease, attitude towards the false notion that COVID-19 stemmed from a global conspiracy and items to assess the anxiety level among students during the quarantine period. Results: The total number of participants was 1540 students. The majority of participants perceived the disease as moderately dangerous (n=1079, 70.1%), with males, Jordanians and participants with lower income being more inclined to feel that the disease is very dangerous (p<0.001, 0.020, and <0.001, respectively). Lower level of knowledge and higher level of anxiety about COVID-19 were associated with the belief that the disease is part of a global conspiracy (p<0.001 and p=0.004, respectively). Females and participants with lower income were more likely to believe that the disease is related to conspiracy (p=0.001 and p<0.001, respectively). Belief in global conspiracy regarding the origin of COVID-19 was associated with misinformation about the availability of vaccine and the therapeutic use of antibiotics for COVID-19 treatment (p=0.001 and p<0.001, respectively). Ministry of Health in Jordan was the most common source of information about COVID-19 reported by the participants (n=1018). Conclusions: The false belief that COVID-19 was the result of a global conspiracy could be the consequence of lower level of knowledge about the virus and could lead to higher level of anxiety, which should be considered in the awareness tools of various media platforms about the current pandemic.

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

negative: Influence of the containment on the epidemiology of maxillo-facial emergencies during the covid-19 pandemic. Why no more cellulites of odontogenic origin?

negative: Taking the Longer View of COVID‐19 What are the prospects for dealing with COVID‐19 more effectively in the future? This editorial addresses the question from the perspective of long‐term control of coronavirus infection.

negative: Nepal’s First Case of COVID-19 and public health response

negative: Coronavirus Disease 2019 (COVID-19): Emerging and Future Challenges for Dental and Oral Medicine The epidemic of coronavirus disease 2019 (COVID-19), originating in Wuhan, China, has become a major public health challenge for not only China but also countries around the world. The World Health Organization announced that the outbreaks of the novel coronavirus have constituted a public health emergency of international concern. As of February 26, 2020, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed cases and 2,700 deaths. Infection control measures are necessary to prevent the virus from further spreading and to help control the epidemic situation. Due to the characteristics of dental settings, the risk of cross infection can be high between patients and dental practitioners. For dental practices and hospitals in areas that are (potentially) affected with COVID-19, strict and effective infection control protocols are urgently needed. This article, based on our experience and relevant guidelines and research, introduces essential knowledge about COVID-19 and nosocomial infection in dental settings and provides recommended management protocols for dental practitioners and students in (potentially) affected areas.

negative: Differential stepwise evolution of SARS coronavirus functional proteins in different host species BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.

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

negative: Privacy and Confidentiality in Emergency Medicine: Obligations and Challenges Respect for privacy and confidentiality have been professional responsibilities of physicians throughout recorded history. This article reviews the moral, religious, and legal foundations of privacy and confidentiality and discusses the distinction between these two closely related concepts. Current federal and state laws are reviewed, including HIPAA regulations and their implications for research and care in the emergency department. In the emergency department, privacy and confidentiality often are challenged by physical design, crowding, visitors, film crews, communication, and other factors. These problems are reviewed, and advice and guidelines are offered for helping preserve patients' dignity and rights to privacy and confidentiality.

negative: Evidence of a significant secretory-IgA-dominant SARS-CoV-2 immune response in human milk following recovery from COVID-19 SARS-CoV-2, commonly termed COVID-19 for the illness it causes, has infected >3.2 million people, including >220,000 deaths. Human milk IgG originates mainly from blood, therefore a SARS-CoV-2-reactive antibody (Ab) response in milk would be expected (1). However, IgG comprises only ~2% of milk Ab, with most milk Abs originating from mucosa-associated lymphatic tissue (1). Therefore, the extent of the milk immune response to SARS-CoV-2 is unknown (2). This response is critical for infants and young children, who tend not to suffer greatly from COVID-19 pathology but are likely responsible for significant virus transmission (3-5). Perhaps even more significant is the fact that milk Abs could be purified and used as a COVID-19 therapeutic, given they would likely be of the secretory (s) class and highly resistant to proteolytic degradation in the respiratory tissue (2, 6). In this preliminary report, 15 milk samples obtained from donors previously-infected with SARS-CoV-2 as well as 10 negative control samples obtained prior to December 2019 were tested for reactivity to the Receptor Binding Domain (RBD) of the SARS-CoV-2 Spike protein by ELISAs measuring IgA, IgG, IgM, and secretory Ab. Eighty percent of samples obtained post-COVID-19 exhibited IgA reactivity, and all these samples were also positive for secretory Ab reactivity, suggesting the IgA is predominantly sIgA. COVID-19 group mean OD values of undiluted milk were significantly greater for IgA (p<0.0001), secretory-type Abs (p<0.0001), and IgG (p=0.017), but not for IgM, compared to pre-pandemic group mean values. Overall, these data indicate that there is strong sIgA-dominant SARS-CoV-2 immune response in human milk after infection in the majority of individuals, and that a comprehensive study of this response is highly warranted.

negative: Identification of novel and diverse rotaviruses in rodents and insectivores, and evidence of cross-species transmission into humans Abstract Rotaviruses are an important cause of severe diarrheal illness in children globally. We characterized rotaviruses sampled in humans, insectivores (shrews) and rodents from urban and rural regions of Zhejiang province, China. Phylogenetic analyses revealed seven genotypic constellations of human rotaviruses with six different combinations of G and P genotypes – G3P[8] (50.06%), G9P[8] (36.16%), G1P[8] (8.92%), G2P[4] (4.63%), G3P[3] (0.12%), and G3P[9] (0.12%). In rodents and shrews sampled from the same locality we identified a novel genotype constellation (G32-P[46]-I24-R18-C17-M17-A28-N17-T19-E24-H19), a novel P genotype (P[45]), and two different AU-1-like rotaviruses associated with a G3P[3] genotype combination. Of particular note was a novel rotavirus from a human patient that was closely related to viruses sampled from rodents in the same region, indicative of a local species jump. In sum, these data are suggestive of the cross-species transmission of rodent rotaviruses into humans and for reassortment among human and animal rotaviruses.

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

negative: 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: Incubation periods of acute respiratory viral infections: a systematic review Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications.

negative: First detection, clinical presentation and phylogenetic characterization of Porcine epidemic diarrhea virus in Austria BACKGROUND: Porcine epidemic diarrhea (PED) is a syndrome that is characterized by rapidly spreading watery diarrhea affecting pigs of all ages, but with major effects on suckling piglets. The disease, as well as the causative Alphacoronavirus, the Porcine epidemic diarrhea virus (PEDV), was first described in Europe in the 1970s and since then has spread over many Asian and American countries, where it recently led to devastating effects on swine health and pork industry. While the disease was seldom reported in Europe within the last few decades, a few recent reports re-emergence of PED in German pig farms. The hitherto isolated German strain seems to be closely related to a low pathogenic PEDV variant from the USA. This case report describes the first detection of PEDV in Austria. CASE PRESENTATION: Reduced feed uptake and occasional diarrhea were observed in December 2014 in a group of fattening pigs, kept on an Austrian swine farm. The concerned pigs had been recently purchased from Germany. Within a few weeks, diarrhea became apparent also in pigs of Austrian origin, which were kept in a different stable on the same farm. Gastrointestinal symptoms among fattening pigs were generally mild, quickly resolving and did not lead to death. PEDV RNA was identified by RT-qPCR in pooled feces and serum and PEDV antibodies were detectable in serum in both groups of pigs. Phylogenetic analysis of the nearly complete PEDV spike gene shows that the Austrian PEDV strain is highly similar to other strains involved in recent outbreaks in Western and Central Europe. CONCLUSION: This is the first report demonstrating the presence of PEDV in Austria. The virus was probably introduced by purchasing piglets from a German source, which underlines the significance of trans-boundary animal trade for the distribution of highly contagious diseases, such as PED. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0624-1) contains supplementary material, which is available to authorized users.

negative: Clinical meanings of rapid serological assay in patients tested for SARS-Co2 RT-PCR Background RT-PCR test for identifiction of viral nucleic acid is the current standard diagnostic method for the diagnosis of COVID-19 disease but technical reasons limit the utilization of this assay on large scale screenings. Method We verified in a consecutive series of 191 symptomatic patients the clinical information that new rapid serological colorimetric test qualitatively analyzing IgM/IgG expression can provide with respect to standard assay and with respect to clinical outcome of patients. Results Rapid serological test showed a sensitivity of 30% and a specificity of 89% with respect to the standard assay but, interestingly, these performances improve after 8 days of symptoms appearance. After 10 days of symptoms the predictive value of rapid serological test is higher than that of standard assay. When the behaviour of the two immunoglobulins was evaluated with respect to time length of symptoms appearance, no significant difference in immunoglobulins behaviour was shown. Conclusions The rapid serological test analyzed in the present study is candidate to provide information on immunoreaction of the subject to COVID-19 exposure.

negative: 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.

negative: SARS in Singapore: surveillance strategies in a globalising city Abstract Public health measures employed to fight against the spread of SARS need to be guided by biomedical knowledge as well as an understanding of the social science aspects of the disease. Using Singapore as a case study, we explore how the state constructs the disease and implements measures targeted at creating a ring of defense around the island and using surveillance to monitor and prevent its spread. While there is support, there is also resentment among some Singaporeans who complain that their right to privacy has been invaded and that over surveillance may have actually occurred. Marginalisation and discrimination have not only affected the local population but in this open economy which is striving to achieve global city status, businesses, tourism, foreign talent, foreign contract workers and foreign students studying in Singapore have also been negatively affected. While Singapore has been applauded by WHO and used as an example of quick and effective response, a holistic approach to the management of infectious disease must address the social implications of strategies that are drawn from medical knowledge alone because it impinges on the social lives of people and how people interact with each other under stressful circumstances.

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

negative: COVID‐19 breakthroughs: separating fact from fiction The newly recognised coronavirus SARS‐CoV‐2, causative agent of COVID‐19, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID‐19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS‐CoV‐2 and discuss the evidence and explications for a disproportionately stronger impact of COVID‐19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS‐CoV‐2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS‐CoV‐2.

negative: Prediction of Epidemic Spread of the 2019 Novel Coronavirus Driven by Spring Festival Transportation in China: A Population-Based Study After the 2019 novel coronavirus (2019-nCoV) outbreak, we estimated the distribution and scale of more than 5 million migrants residing in Wuhan after they returned to their hometown communities in Hubei Province or other provinces at the end of 2019 by using the data from the 2013–2018 China Migrants Dynamic Survey (CMDS). We found that the distribution of Wuhan’s migrants is centred in Hubei Province (approximately 75%) at a provincial level, gradually decreasing in the surrounding provinces in layers, with obvious spatial characteristics of circle layers and echelons. The scale of Wuhan’s migrants, whose origins in Hubei Province give rise to a gradient reduction from east to west within the province, and account for 66% of Wuhan’s total migrants, are from the surrounding prefectural-level cities of Wuhan. The distribution comprises 94 districts and counties in Hubei Province, and the cumulative percentage of the top 30 districts and counties exceeds 80%. Wuhan’s migrants have a large proportion of middle-aged and high-risk individuals. Their social characteristics include nuclear family migration (84%), migration with families of 3–4 members (71%), a rural household registration (85%), and working or doing business (84%) as the main reason for migration. Using a quasi-experimental analysis framework, we found that the size of Wuhan’s migrants was highly correlated with the daily number of confirmed cases. Furthermore, we compared the epidemic situation in different regions and found that the number of confirmed cases in some provinces and cities in Hubei Province may be underestimated, while the epidemic situation in some regions has increased rapidly. The results are conducive to monitoring the epidemic prevention and control in various regions.

negative: COVID-19 Outbreak in Oman: Model-Driven Impact Analysis and Challenges Motivated by the rapid spread of COVID-19 all across the globe, we have performed simulations of a system dynamic epidemic spread model in different possible situations. The simulation, not only captures the model dynamic of the spread of the virus, but also, takes care of population and mobility data. The model is calibrated based on epidemic data and events specifically of Sultanate of Oman, which can easily be generalized. The simulation results are quite disturbing, indicating that, during a process of stringent social distancing and testing strategies, a small perturbation can lead to quite undesirable outcomes. The simulation results, although consistent in expected outcomes across changing parameters' values, also indicate a substantial mismatch with real numbers. An analysis of what can be the reason of this mismatch is also performed. Within these contradictions, for Oman, regarding the eradication of epidemic, the future is not extremely alarming.

negative: World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Abstract An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.

negative: Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP) Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. Although nucleos(t)ide analogs inhibiting viral reverse transcriptase are clinically available as anti-HBV agents, emergence of drug-resistant viruses highlights the need for new anti-HBV agents interfering with other targets. Here we report that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes. The anti-HBV effect of CsA was independent of binding to cyclophilin and calcineurin. Rather, blockade of HBV infection correlated with the ability to inhibit the transporter activity of sodium taurocholate cotransporting polypeptide (NTCP). We also found that HBV infection-susceptible cells, differentiated HepaRG cells and primary human hepatocytes expressed NTCP, while nonsusceptible cell lines did not. A series of compounds targeting NTCP could inhibit HBV infection. CsA inhibited the binding between NTCP and large envelope protein in vitro. Evaluation of CsA analogs identified a compound with higher anti-HBV potency, having a median inhibitory concentration <0.2 μM. Conclusion: This study provides a proof of concept for the novel strategy to identify anti-HBV agents by targeting the candidate HBV receptor, NTCP, using CsA as a structural platform. (Hepatology 2014;59:1726–1737)

negative: An alternative approach to minimize the risk of coronavirus (Covid-19) and similar infections Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain that was discovered in 2019 and has not been previously identified in humans. On December 31st 2019 World Health Organization (WHO) was informed of a cluster of cases with pneumonia of unknown origin from Wuhan City, Hubei province of China. The WHO announced in February 2020 that COVID-19 is the official name of the coronavirus diseases. A total of 519,899 confirmed cases with 23,592 deaths linked to this pathogen as on March 27, 2020 have been reported. Due to increasing number of infected people across the continents and huge loss to human life, the WHO has declared the novel COVID-19 outbreak a pandemic. A pandemic is defined as the "worldwide spread" of a new disease. Currently, no COVID-19 specific treatments have been approved by the United States Food and Drug Administration (US-FDA). However, the current treatment options include hydroxychloroquine, tocilizumab, remdesivir, lopinavir-ritonavir (Kaletra®), and nitazoxanide. In recent past, some natural herbal compounds have demonstrated encouraging anti-viral properties. This article attempted to summarize available information on the reported anti-viral activity of some natural products.

negative: A large number of COVID-19 interventional clinical trials were registered soon after the pandemic onset: a descriptive analysis Abstract Background There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the Coronavirus disease 2019 (COVID-19) pandemic. The number of registered trials related to COVID-19 is increasing by the day. Objectives To describe the characteristics of the currently registered clinical trials related to COVID-19. Methods We searched the World Health Organization (WHO)’s International Clinical Trials Registry Platform (ICTRP) on May 15, 2020. We included any entry that is related to COVID-19. We abstracted then descriptively analyzed the following characteristics of the registered trials: study design, status, phase, primary endpoints, experimental interventions, and geographic location among other qualifiers. Results We identified 1,308 eligible registered trials. The majority of trials were initially registered with ClinicalTrials.gov (n= 703; 53.7%) and the Chinese Clinical Trial Registry (ChiCTR) (n= 291; 22.2%). The number of participants to be enrolled across these trials was 734,657, with a median of 110 participants per trial. The most-commonly studied intervention category was pharmacologic (n=763; 58.3%), with antiparasitic medications being the most common subcategory. While over half of trials were already recruiting, we identified published peer-reviewed results for only 8 of those trials. Conclusion There is a relatively large number of registered trials but very few results published so far. While our findings suggest an appropriate initial response by the research community, the real challenge will be to get these trials completed, published, and translated into practice and policy.

negative: Energetics based epitope screening in SARS CoV-2 (COVID 19) spike glycoprotein by Immuno-informatic analysis aiming to a suitable vaccine development The recent outbreak by SARS-CoV-2 has generated a chaos in global health and economy and claimed/infected a large number of lives. Closely resembling with SARS CoV, the present strain has manifested exceptionally higher degree of spreadability, virulence and stability possibly due to some unidentified mutations. The viral spike glycoprotein is very likely to interact with host Angiotensin-Converting Enzyme 2 (ACE2) and transmits its genetic materials and hijacks host machinery with extreme fidelity for self propagation. Few attempts have been made to develop a suitable vaccine or ACE2 blocker or virus-receptor inhibitor within this short period of time. Here, attempt was taken to develop some therapeutic and vaccination strategies with a comparison of spike glycoproteins among SARS-CoV, MERS-CoV and the SARS-CoV-2. We verified their structure quality (SWISS-MODEL, Phyre2, Pymol) topology (ProFunc), motifs (MEME Suite, GLAM2Scan), gene ontology based conserved domain (InterPro database) and screened several epitopes (SVMTrip) of SARS CoV-2 based on their energetics, IC50 and antigenicity with regard to their possible glycosylation and MHC/paratopic binding (Vaxigen v2.0, HawkDock, ZDOCK Server) effects. We screened here few pairs of spike protein epitopic regions and selected their energetic, IC50, MHC II reactivity and found some of those to be very good target for vaccination. A possible role of glycosylation on epitopic region showed profound effects on epitopic recognition. The present work might be helpful for the urgent development of a suitable vaccination regimen against SARS CoV-2.

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: 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: Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biological treatment and renal transplanted recipients in maintenance immunosuppressive treatment

negative: ArCOV-19: The First Arabic COVID-19 Twitter Dataset with Propagation Networks In this paper, we present ArCOV-19, an Arabic COVID-19 Twitter dataset that covers the period from 27th of January till 31st of March 2020. ArCOV-19 is the first publicly-available Arabic Twitter dataset covering COVID-19 pandemic that includes around 748k popular tweets (according to Twitter search criterion) alongside the propagation networks of the most-popular subset of them. The propagation networks include both retweets and conversational threads (i.e., threads of replies). ArCOV-19 is designed to enable research under several domains including natural language processing, information retrieval, and social computing, among others. Preliminary analysis shows that ArCOV-19 captures rising discussions associated with the first reported cases of the disease as they appeared in the Arab world. In addition to the source tweets and the propagation networks, we also release the search queries and the language-independent crawler used to collect the tweets to encourage the curation of similar datasets.

negative: Reconstruction and prediction of viral disease epidemics A growing number of infectious pathogens are spreading among geographic regions. Some pathogens that were previously not considered to pose a general threat to human health have emerged at regional and global scales, such as Zika and Ebola Virus Disease. Other pathogens, such as yellow fever virus, were previously thought to be under control but have recently re-emerged, causing new challenges to public health organisations. A wide array of new modelling techniques, aided by increased computing capabilities, novel diagnostic tools, and the increased speed and availability of genomic sequencing allow researchers to identify new pathogens more rapidly, assess the likelihood of geographic spread, and quantify the speed of human-to-human transmission. Despite some initial successes in predicting the spread of acute viral infections, the practicalities and sustainability of such approaches will need to be evaluated in the context of public health responses.

negative: Incidence trend of 2019 novel coronavirus diseases (COVID-19) in China/ 上海预防医学 Objective To investigate the epidemical characteristics and analyze the incidence trend of 2019 novel coronavirus diseases (COVID-19) in China. Methods The daily new confirmed cases of 2019 novel coronavirus diseases (COVID-19) in China from January 25 to February 8,2020 were collected for epidemiological descriptive analysis. Results During the period from January 25 to February 8, 2020, the number of daily new confirmed cases fell for five consecutive days, from 890 cases on February 3 to 509 cases on February 8. Conclusion The incidence of 2019 novel coronavirus diseases (COVID-19) slowed down in 30 provinces (autonomous regions and municipalities directly under the central government) except Hubei and Xinjiang production and construction corps , but the overall situation is still not optimistic. It is imperative to pay close attention to the origin and destination of migrant workers and the incidence of disease in various areas, and take targeted measures to strengthen prevention and control of the disease.

negative: Chapter Eight Hosts and Sources of Endemic Human Coronaviruses Abstract The four endemic human coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 contribute a considerable share of upper and lower respiratory tract infections in adults and children. While their clinical representation resembles that of many other agents of the common cold, their evolutionary histories, and host associations could provide important insights into the natural history of past human pandemics. For two of these viruses, we have strong evidence suggesting an origin in major livestock species while primordial associations for all four viruses may have existed with bats and rodents. HCoV-NL63 and -229E may originate from bat reservoirs as assumed for many other coronaviruses, but HCoV-OC43 and -HKU1 seem more likely to have speciated from rodent-associated viruses. HCoV-OC43 is thought to have emerged from ancestors in domestic animals such as cattle or swine. The bovine coronavirus has been suggested to be a possible ancestor, from which HCoV-OC43 may have emerged in the context of a pandemic recorded historically at the end of the 19th century. New data suggest that HCoV-229E may actually be transferred from dromedary camels similar to Middle East respiratory syndrome (MERS) coronavirus. This scenario provides important ecological parallels to the present prepandemic pattern of host associations of the MERS coronavirus.

negative: Potential T-cell and B-cell Epitopes of 2019-nCoV As of early March, 2019-nCoV has infected more than one hundred thousand people and claimed thousands of lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 and has high similarity with SARS-CoV. No approved vaccine yet exists for any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein receptor binding domain. Based on these findings, the spike protein is likely immunogenic and a potential vaccine candidate. We validated our computational pipeline with SARS-CoV experimental data. The novel coronavirus 2019-nCoV has affected more than 100 countries and continues to spread. There is an immediate need for effective vaccines that contain antigens which trigger responses from human T-cells and B-cells (known as epitopes). Here we identify potential T-cell epitopes through an analysis of human antigen presentation, as well as B-cell epitopes through an analysis of protein structure. We identify a list of top candidates, including an epitope located on 2019-nCoV spike protein that potentially triggers both T-cell and B-cell responses. Analyzing 68 samples, we observe that viral mutations are more likely to happen in regions with strong antigen presentation, a potential form of immune evasion. Our computational pipeline is validated with experimental data from SARS-CoV.

negative: Antibody-Mediated “Universal” Osteoclast Targeting Platform using Calcitonin as a Model Drug PURPOSE: To generate and characterize a specific monoclonal antibody (mAb) against recombinant human RANK receptor and to develop an antiresorptive strategy using this mAb as an osteoclast-targeting platform that selectively targets osteoclast cells whilst delivering an attached (i.e. chemically conjugated) active drug cargo. METHODS: Using hybridoma technology, we generated a specific monoclonal antibody (mAb) against recombinant human RANK receptor and characterized by SDS PAGE, ELISA, Western Blot and immunocytochemistry, then synthesized osteoclast-targeting bioconjugates of salmon calcitonin (sCT) using this antibody by generating thiol groups on mAb using 2-Iminothiolane and subsequently reacting them with sCT-PEG-MAL synthesised from sCT and NHS-PEG-MAL. To test the efficacy of the conjugate in vitro, osteoclasts were generated from precursor RAW 264.7 cells by dosing with the cytokines macrophage-colony-stimulating factor (M-CSF), and RANK Ligand (RANKL) and TRAP activity assay, Resorption Pit Assay, TRAP staining were performed. Cytotoxicity of the mAb-sCT conjugate was also evaluated in RAW 264.7 cells; sCT bioactivity and CTR binding potential were evaluated by in vitro intracellular cAMP stimulation assay in human T47D breast cancer cells. RESULTS: Generation of antibody against human RANK receptor was confirmed by SDS PAGE, ELISA and Western Blot. Immunocytochemistry confirmed the osteoclast targeting potential of the antibody. Successful conjugation of the antibody with sCT was confirmed by SDS PAGE and ELISA.Multinucleated osteoclast formation was confirmed by staining for tartrate-resistant acid phosphatase (TRAP). Conjugate functionality was confirmed by TRAP activity and Resorption Pit assay, showing the inhibitory effect on osteoclast differentiation. cAMP assay confirmed the retention of calcitonin bioactivity after conjugation. CONCLUSIONS: Our strategy offers the potential for a “universal” osteoclast-targeting platform—one that targets the RANK receptor on osteoclast cells by simply altering the conjugated cargo in order to affect the specific regulation of osteoclast cells.

negative: Treatment options for COVID-19: the reality and challenges Abstract An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2-5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.

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: Explaining and responding to the Ebola epidemic The Ebola epidemic in West Africa is not merely a biomedical problem that can be seen in isolation and dealt with only through emergency medical rescue processes. The ethical dilemmas surfaced by this epidemic are also not confined to the usual micro-ethical problems associated with medical care and medical research. The pandemic, as one of many manifestations of failed human and social development that has brought the world to dangerous ‘tipping points’, requires deep introspection and action to address upstream causal processes.

negative: The characteristics and clinical value of chest CT images of novel coronavirus pneumonia AIM To investigate the characteristics and clinical value of chest computed tomography (CT) images of novel coronavirus pneumonia (NCP). MATERIALS AND METHODS Clinical data and CT images of 80 cases of NCP were collected. The clinical manifestations and laboratory test results of the patients were analysed. The lesions in each lung segment of the patient's chest CT images were characterised. Lesions were scored according to length and diffusivity. RESULTS The main clinical manifestations were fever, dry cough, fatigue, a little white sputum, or diarrhoea. A total of 1,702 scored lesions were found in the first chest CT images of 80 patients. The lesions were located mainly in the subpleural area of the lungs (92.4%). Most of the lesions were ground-glass opacity, and subsequent fusions could increase in range and spread mainly in the subpleural area. Pulmonary consolidation accounted for 44.1% of all of the lesions. Of the 80 cases, 76 patients (95%) had bilateral lung disease, four (5%) patients had unilateral lung disease, and eight (10%) patients had cord shadow. CONCLUSION The chest CT of NCP patients is characterised by the onset of bilateral ground-glass lesions located in the subpleural area of the lung, and progressive lesions that result in consolidation with no migratory lesions. Pleural effusions and mediastinal lymphadenopathy are rare. As patients can have inflammatory changes in the lungs alongside a negative early nucleic acid test, chest CT, in combination with epidemiological and laboratory tests, is a useful examination to evaluate the disease and curative effect.

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: 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: The novel coronavirus and its possible treatment by vaccines, therapeutics and drug delivery systems: Current status and future perspectives In the mid-end of December 2019, several cases of pneumonia outbreak of unknown cause and etiology were identified in Wuhan City of Hubei province in China, a city with a population of over 11 million. Till date(April 2020) around 1,051,635 confirmed cases of coronavirus disease 2019(COVID-19) and 56,985 confirmed deaths have been reported according to COVID-19 Situation Report – 75 by WHO. On 7th January 2020, the causative agent was iden-tified and named consequently as Severe Acute Respiratory Syndrome Coron-avirus 2 (SARS-CoV-2) by the Chinese Centre for Disease Control and Prevention (CCDC) from throat swab samples. Later, on 12th January 2020, this coro-navirus was named as 2019-novel coronavirus (2019-nCoV) by World Health Organization (WHO) and in 11th February 2020,it has been declared the epidemic disease caused by SARS-CoV-2 as Corona Virus Disease 2019(COVID-19) as it is spreading rapidly from its origin in Wuhan City to the rest of the world. In this context, the current review provides a landscape of the novel Corona Virus including its origin, transmission, epidemiology, drugs and vaccines in clinical trials for better understanding to the reads and peoples the status and future perspectives of this pandemic disease.

negative: Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats The pandemic caused by SARS-CoV-2 has reached nearly every country in the world with extraordinary person-to-person transmission. The most likely original source of the virus was spillover from an animal reservoir and subsequent adaptation to humans sometime during the winter of 2019 in Wuhan Province, China. Because of its genetic similarity to SARS-CoV-1, it is likely that this novel virus has a similar host range and receptor specificity. Due to concern for human-pet transmission, we investigated the susceptibility of domestic cats and dogs to infection and potential for infected cats to transmit to naïve cats. We report that cats are highly susceptible to subclinical infection, with a prolonged period of oral and nasal viral shedding that is not accompanied by clinical signs, and are capable of direct contact transmission to other cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection, but are unlikely to develop clinical disease. Further, we document that cats develop a robust neutralizing antibody response that prevented re-infection to a second viral challenge. Conversely, we found that dogs do not shed virus following infection, but do mount an anti-viral neutralizing antibody response. There is currently no evidence that cats or dogs play a significant role in human exposure; however, reverse zoonosis is possible if infected owners expose their domestic pets during acute infection. Resistance to re-exposure holds promise that a vaccine strategy may protect cats, and by extension humans, to disease susceptibility.

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

negative: The COVID-19 Pandemic: Effects on Low- and Middle-Income Countries Coronavirus Disease 2019 (COVID-19) is spreading rapidly around the world with devastating consequences on patients, health care workers, health systems, and economies. As it reaches low- and middle-income countries, its effects could be even more dire, because it will be difficult for them to respond aggressively to the pandemic. There is a great shortage of all health care providers, who will be at risk due to a lack of personal protection equipment. Social distancing will be almost impossible. The necessary resources to treat patients will be in short supply. The end result could be a catastrophic loss of life. A global effort will be required to support faltering economies and health care systems.

negative: Epidemiology of COVID-19 It seems that coronaviruses take an important place in the 21th century history. Five of seven human coronavirus was isolated in this century. Unfortunately, last three of them entered our life with a fear of outbreak, pandemic or death. Last human coronavirus which emerged world from Wuhan China, SARS CoV-2 and its clinical expression, Coronavirus disease (COVID-19) recently taken a significant place in our daily practice. Initial reports showed that, its origin was bats. It transmitted human to human by droplet and contact routes, but some doubt about airborne, fecal or intrauterine transmission also should be removed. Its R0 value is 2.3 but it could be as high as 5.7. Its case fatality rate was 6.3, but it was different in different ages and counties, and it could be over 15%. According to early models total 1012 weeks is required to control an outbreak in the community. While different countries show different daily case numbers, total number of case, case mortality rates or R0, it seems they show a similar epidemic curve. Every day we learn new data about the current outbreak. Since the outbreak is not over yet, every detail should be evaluated carefully and the updates should be followed closely to monitor the epidemiological properties of COVID-19.

negative: Update on childhood and adult infectious tracheitis Abstract The trachea is a pivotal organ of the respiratory tract. Rather than a genuine anatomic border, it acts as a crossroad in all respiratory infectious processes. Even though not strictly limited to the trachea, infections such as laryngotracheitis and tracheobronchitis are frequently diagnosed in children, in particular during the winter season. Infectious tracheitis etiologies are diverse and the distinction between viral and bacterial origins, albeit difficult, remains relevant considering the substantial differences in terms of gravity and therapeutic management. This literature review summarizes the microbiological and clinical aspects of community-acquired and nosocomial tracheitis in adults and children, as well as the adequate diagnostic and therapeutic approaches. It also highlights the emergence of fungal tracheitis in immunocompromised patients, of ventilator-associated tracheitis in intensive care medicine, and beyond all that the potential short and long-term consequences of tracheitis.

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: Outbreak of COVID-19 in a family, Wenzhou, China Since December 2019, China has experienced a widespread outbreak of COVID-19. However, at the early stage of outbreak, investigations revealed a variety of patterns resulting in the transmission of COVID-19. Thus, it is essential to understand the transmission types and the potential for sustained human-to-human transmission. Moreover, the information regarding the characteristics of transmission helps in coordinating the current screening programme, and controlling and containing measures, and also, helps in deciding the appropriate quarantine duration. Thus, this investigation reports an outbreak of COVID-19 in a family residing in Wenzhou, Zhejiang, China during the month of January−February 2020.

negative: The Role of Non-animal Origin Feed Ingredients in Transmission of Viral Pathogens of Swine: A Review of Scientific Literature The emergence of porcine epidemic diarrhea (PED) in commercial swine in North America and growing concerns about the potential for the introduction of African swine fever (ASF) from China, the European Union, or other affected regions has put a spotlight on the possible role of contaminated feed and feed ingredients in the introduction and transmission of viral swine pathogens. This paper systematically reviews the scientific literature regarding whether non-animal origin ingredients of commercial swine feed could introduce or transmit viral pathogens of swine into or within the United States. The purpose of this review is to identify, evaluate, and summarize the relevant scientific knowledge, published through March 2018, and to identify information gaps and research needs, thereby making the available evidence more accessible to policy makers, the swine industry, and the scientific community. A total of 26 documents were selected for the final review process, which included experimental studies, case reports, epidemiological investigations, and scientific opinion, among others. The review found that the scientific literature has addressed some critical experimental questions pertaining to transmission of swine viruses via feed and feed ingredients, but the current body of scientific knowledge lacks conclusive evidence of virus contamination of non-animal origin feed ingredients of commercial swine feed, particularly for imported commodities, and further investigation into the epidemiology of virus transmission via feed to swine under field conditions through natural feeding behavior is warranted. Additional studies of how imported ingredients of commercial swine feed are sourced, processed, transported and, thus, contaminated prior to importation into the United States are needed. Moving forward, studies designed to examine the likely source(s) of contamination and subsequent virus mitigation steps in processing and post-processing may be the most fruitful focus of research.

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

negative: Partial RdRp sequences offer a robust method for Coronavirus subgenus classification The recent reclassification of the Riboviria, and the introduction of multiple new taxonomic categories including both subfamilies and subgenera for coronaviruses (family Coronaviridae, subfamily Orthocoronavirinae) represents a major shift in how official classifications are used to designate specific viral lineages. While the newly defined subgenera provide much-needed standardisation for commonly cited viruses of public health importance, no method has been proposed for the assignment of subgenus based on partial sequence data, or for sequences that are divergent from the designated holotype reference genomes. Here, we describe the genetic variation of a partial region of the coronavirus RNA-dependent RNA polymerase (RdRp), which is one of the most used partial sequence loci for both detection and classification of coronaviruses in molecular epidemiology. We infer Bayesian phylogenies from more than 7000 publicly available coronavirus sequences and examine clade groupings relative to all subgenus holotype sequences. Our phylogenetic analyses are largely coherent with genome-scale analyses based on designated holotype members for each subgenus. Distance measures between sequences form discrete clusters between taxa, offering logical threshold boundaries that can attribute subgenus or indicate sequences that are likely to belong to unclassified subgenera both accurately and robustly. We thus propose that partial RdRp sequence data of coronaviruses is sufficient for the attribution of subgenus-level taxonomic classifications and we supply the R package, “MyCoV”, which provides a method for attributing subgenus and assessing the reliability of the attribution. The analysis of polymerase chain reaction amplicons derived from biological samples is the most common modern method for detection and classification of infecting viral agents, such as Coronaviruses. Recent updates to the official standard for taxonomic classification of Coronaviruses, however, may leave researchers unsure as to whether the viral sequences they obtain by these methods can be classified into specific viral taxa due to variations in the sequences when compared to type strains. Here, we present a plausible method for defining genetic dissimilarity cut-offs that will allow researchers to state which taxon their virus belongs to and with what level of certainty. To assist in this, we also provide the R package ‘MyCoV’ which classifies user generated sequences.

negative: Fractal kinetics of COVID-19 pandemic We give an update to the original paper posted on 2/17/20 -- now (as of 3/1/20) the China deaths are rapidly decreasing, and we find an exponential decline to the power law similar to the that predicted by the network model of \citet{vazquez_polynomial_2006}. At the same time, we see non-China deaths increasing rapidly, and similar to the early behavior of the China statistics. Thus, we see three stages of the spread of the disease in terms of number of deaths: exponential growth, power-law behavior, and then exponential decline in the daily rate. (Original abstract) The novel coronavirus (COVID-19) continues to grow rapidly in China and is spreading in other parts of the world. The classic epidemiological approach in studying this growth is to quantify a reproduction number and infection time, and this is the approach followed by many studies on the epidemiology of this disease. However, this assumption leads to exponential growth, and while the growth rate is high, it is not following exponential behavior. One approach that is being used is to simply keep adjusting the reproduction number to match the dynamics. Other approaches use rate equations such as the SEIR and logistical models. Here we show that the current growth closely follows power-law kinetics, indicative of an underlying fractal or small-world network of connections between susceptible and infected individuals. Positive deviations from this growth law might indicate either a failure of the current containment efforts while negative deviations might indicate the beginnings of the end of the pandemic. We cannot predict the ultimate extent of the pandemic but can get an estimate of the growth of the disease.

negative: Radiotherapy Workflow and Protection Procedures During the Coronavirus Disease 2019 (COVID-19) Outbreak: Experience of the Hubei Cancer Hospital in Wuhan, China Abstract The epidemic of Coronavirus Disease 2019 (COVID-19) first broke out in Wuhan in December 2019, and reached its peak in Wuhan in February 2020. It became a major public health challenge for China, and evolved into a global pandemic in March 2020. For radiation oncology departments, the COVID-19 pandemic presents a unique challenge for disease protection and prevention for both patients and staff, owing to the weakened immune systems of cancer patients and the need to deliver timely and uninterrupted radiotherapy. At the Hubei Cancer Hospital, the only hospital in Wuhan that specializes in oncology, we organized an emergency infection control team to lead special efforts to combat COVID-19 during this challenging time. Under its lead, the following measures were implemented in the radiation oncology department: the radiotherapy clinic was divided into different infection control zones with varying levels of protection; special staff and patient infection control training sessions were conducted and appropriate measures deployed; daily symptom testing criteria were implemented for patients undergoing treatment; special rotating schedules and infection control methods were implemented for various staff members such as medical physicists/dosimetrists and radiation therapists; modified radiotherapy workflow and specialized treatment area cleaning and disinfection policies and procedures were designed and executed; and special medical waste disposal methods were implemented. We began treating patients using this new COVID-19 radiotherapy treatment workflow and infection control measures on January 30, 2020. During more than one and a half months of uninterrupted radiation oncology clinical operation through the worst of the Wuhan outbreak, no known COVID-19 infection occurred at our radiotherapy center to our patients or employees. This report may provide valuable information for other radiation oncology departments during this unprecedented public health crisis.

negative: A phage RNA-binding protein binds to a non-cognate structured RNA and stabilizes its core structure Abstract Recent studies suggest that some RNA-binding proteins facilitate the folding of non-cognate RNAs. Here, we report that bacteriophage MS2 coat protein (MS2 CP) bound and promoted the catalytic activity of Candida group I ribozyme. Cloning of the MS2-bound RNA segments showed that this protein primarily interacts with the P5ab–P5 structure. Ultraviolet cross-linking and the T1 footprinting assay further showed that MS2 binding stabilized tertiary interactions, including the conserved L9–P5 interaction, and led to a more compact core structure. This mechanism is similar to that of the yeast mitochondrial tyrosyl-tRNA synthetase on other group I introns, suggesting that different RNA-binding proteins may use common mechanisms to support RNA structures.

negative: Emergency tracheostomy during COVID 19 Pandemic in a head and neck surgical oncology unit • Awake, Emergency, Intervention for an Unsecured 'Unable to intubate' Critical upper airway obstruction is a surgical challenge. • Aerosolization and risk COVID 19 transmission add to the already existing difficulty of surgical restoration of critical airway obstruction. • Adequate personal protection, rapid restoration of the airway with the minimum aerosol generation, and prevention of COVID 19 dissemination are keys to the success of Emergency Tracheostomy during the Pandemic.

negative: An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens This study used real-time PCR assays to screen small sample volumes for a comprehensive range of 35 respiratory pathogens. Initial thermocycling was limited to 20 cycles to avoid competition for reagents, followed by a secondary real-time multiplex PCR. Supplementary semi-nested human metapneumovirus and picornavirus PCR assays were required to complete the acute respiratory pathogen profile. Potential pathogens were detected in 85 (70%) of pernasal aspirates collected from 121 children with acute respiratory symptoms. Multiple pathogens were detected in 29 (24%) of those samples. The tandem multiplex real-time PCR was an efficient method for the rapid detection of multiple pathogens.

negative: Epidemiology and clinical features of coronavirus disease 2019 in children Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.

negative: Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei Background: Since December 2019, a novel coronavirus pneumonia (COVID-19) rapidly spread in China, reached multiple continents currently.We aimed to reveal the infectious characteristics of COVID-19 that provide more information for the research of novel coronavirus. Methods: We performed a retrospective study on the clinical characteristics of 128 COVID-19 cases with laboratory-confirmed from Xiangyang No 1 Hospitalad during January 2020 to 16 February 2020. Results: Female patients account for 53.1%. The aged below 20 years that accounts for 1.6% of overall patients. The aged in 21~50, 51~65, over 66 years were accounts for 44.5%, 35.1%,18.8%, respectively. In the difference age spectrum, all severe groups compared with non-severe groups were difference significantly ( P < 0.01 ). Fever ( 89.8% ) and Cough ( 67.2% ) were common clinical symptoms. The rate of patients with sore throats (14.1%) was rare. The rate of chest computed tomography scan showing ground glass opacity in overall, non-severe, severe groups were 63.3%, 60.7%, 76.2%, respectively. White blood cell counts in the normal range of overall patients, but severe group patients were increased significantly ( P < 0.01). Lymphocytes of overall patients were decreased. Alanine transaminase (ALT) and aspartate transaminase (AST) in the normal range of overall patients, but its were elevated in the severe group. Creatinine (CR) and blood urea nitrogen (BUN) of overall patients in the normal range. C-reactive protein (CRP) level of all patients were increased markedly, but it in the severe group was significantly higher than that in the non-severe group ( P < 0.01 ). Conclusions: Our data provide more information that advanced age, lower lymphocytes levels at the diagnosed COVID-19 patients may be a risk factor for unfavourable prognosis. The white blood cells and C-reactive protein level elevated in severe COVID-19 patients may be accompanying bacterial infection. 2019-nCov may be carries a risk factor of impaired liver and kidney function.

negative: Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity The spike (S) glycoprotein of SARS-CoV-2 is responsible for the binding to the permissive cells. The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. In this study, we used computational saturation mutagenesis approaches, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18,354 mutations in S protein were analyzed and we discovered that most of these mutations could destabilize the entire S protein and its RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. In addition, we investigated 3,705 mutations in SARS-CoV-2 RBD and 11,324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD-ACE2 interaction. The findings comprehensively provide potential target sites in the development of drugs and vaccines against COVID-19.

negative: COVID-19 in the heart and the lungs: could we "Notch" the inflammatory storm? From January 2020, coronavirus disease (COVID-19) originated in China has spread around the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The presence of myocarditis, cardiac arrest, and acute heart failure in COVID-19 patients suggests the existence of a relationship between SARS-CoV-2 infection and cardiac disease. The Notch signalling is a major regulator of cardiovascular function and it is also implicated in several biological processes mediating viral infections. In this report we discuss the possibility to target Notch signalling to prevent SARS-CoV-2 infection and interfere with the progression of COVID-19- associated heart and lungs disease.

negative: The recent challenges of highly contagious COVID-19; causing respiratory infections: symptoms, diagnosis, transmission, possible vaccines, animal models and immunotherapy COVID-19 is highly contagious pathogenic viral infection initiated from Wuhan seafood wholesale market of China on December 2019 and spread rapidly around the whole world due to onward transmission. This recent outbreak of novel coronavirus (CoV) was believed to be originated from bats and causing respiratory infections such as common cold, dry cough, fever, headache, dyspnea, pneumonia and finally Severe Acute Respiratory Syndrome (SARS) in humans. For this widespread zoonotic virus, human-to-human transmission has resulted in nearly 83 lakh cases in 213 countries and territories with 4,50,686 deaths as on 19th June 2020. This review presents a report on the origin, transmission, symptoms, diagnosis, possible vaccines, animal models and immunotherapy for this novel virus and will provide ample references for the researchers towards the ongoing development of therapeutic agents and vaccines and also preventing the spread of this disease.

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: Detection of SARS-CoV-2 in pets living with COVID-19 owners diagnosed during the COVID-19 lockdown in Spain: A case of an asymptomatic cat with SARS-CoV-2 in Europe During April-May 2020, the presence of respiratory syndrome coronavirus 2 (SARS-CoV-2) in pets living with coronavirus disease 2019 (COVID-19) owners was analyzed. From 23 pets, a cat without clinical symptoms showed positive results for SARS-CoV-2 in oropharyngeal swab using three RT-qPCR assays (negative rectal swab). SARS-CoV-2 was not detected in the remaining pets. Our finding suggests that cats may act as asymptomatic dispersers of SARS-CoV-2, although viral transmission from animals to humans seems unlikely.

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: The demand for inpatient and ICU beds for COVID-19 in the US: lessons from Chinese cities BACKGROUND: Sustained spread of SARS-CoV-2 has happened in major US cities. Capacity needs in Chinese cities could inform the planning of local healthcare resources. METHODS: We described the intensive care unit (ICU) and inpatient bed needs for confirmed COVID-19 patients in two Chinese cities (Wuhan and Guangzhou) from January 10 to February 29, 2020, and compared the timing of disease control measures in relation to the timing of SARS-CoV-2 community spread. We estimated the peak ICU bed needs in US cities if a Wuhan-like outbreak occurs. RESULTS: In Wuhan, strict disease control measures were implemented six weeks after sustained local transmission of SARS-CoV-2. Between January 10 and February 29, COVID-19 patients accounted for an average of 637 ICU patients and 3,454 serious inpatients on each day. During the epidemic peak, 19,425 patients (24.5 per 10,000 adults) were hospitalized, 9,689 (12.2 per 10,000 adults) were considered to be in serious condition, and 2,087 patients (2.6 per 10,000 adults) needed critical care per day. In Guangzhou, strict disease control measures were implemented within one week of case importation. Between January 24 and February 29, COVID-19 accounted for an average of 9 ICU patients and 20 inpatients on each day. During the epidemic peak, 15 patients were in critical condition, and 38 were classified as serious. If a Wuhan-like outbreak were to happen in a US city, the need for healthcare resources may be higher in cities with a higher prevalence of vulnerable populations. CONCLUSION: Even after the lockdown of Wuhan on January 23, the number of seriously ill COVID-19 patients continued to rise, exceeding local hospitalization and ICU capacities for at least a month. Plans are urgently needed to mitigate the effect of COVID-19 outbreaks on the local healthcare system in US cities.

negative: Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis INTRODUCTION: An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 in China leading to a Public Health Emergency of International Concern (PHEIC). Clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews on COVID-19 have been published to date. METHODS: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies and also case reports, were included, and analyzed separately. We performed a random-effects model meta-analysis to calculate pooled prevalences and 95% confidence intervals (95%CI). RESULTS: 660 articles were retrieved for the time frame (1/1/2020-2/23/2020). After screening, 27 articles were selected for full-text assessment, 19 being finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5–92.9%), cough (57.6%, 95%CI 40.8–74.4%) and dyspnea (45.6%, 95%CI 10.9–80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0–30.6%) required intensive care unit (ICU), 32.8% presented with acute respiratory distress syndrome (ARDS) (95%CI 13.7–51.8), 6.2% (95%CI 3.1–9.3) with shock. Some 13.9% (95%CI 6.2–21.5%) of hospitalized patients had fatal outcomes (case fatality rate, CFR). CONCLUSION: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and hospitalization was associated with a CFR of >13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure and facilities to treat severe 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: The experiences of health-care providers during the COVID-19 crisis in China: a qualitative study Summary Background In the early stages of the outbreak of coronavirus disease 2019 (COVID-19) in Hubei, China, the local health-care system was overwhelmed. Physicians and nurses who had no infectious disease expertise were recruited to provide care to patients with COVID-19. To our knowledge, no studies on their experiences of combating COVID-19 have been published. We aimed to describe the experiences of these health-care providers in the early stages of the outbreak. Methods We did a qualitative study using an empirical phenomenological approach. Nurses and physicians were recruited from five COVID-19-designated hospitals in Hubei province using purposive and snowball sampling. They participated in semi-structured, in-depth interviews by telephone from Feb 10 to Feb 15, 2020. Interviews were transcribed verbatim and analysed using Haase's adaptation of Colaizzi's phenomenological method. Findings We recruited nine nurses and four physicians. Three theme categories emerged from data analysis. The first was “being fully responsible for patients' wellbeing—‘this is my duty’”. Health-care providers volunteered and tried their best to provide care for patients. Nurses had a crucial role in providing intensive care and assisting with activities of daily living. The second category was “challenges of working on COVID-19 wards”. Health-care providers were challenged by working in a totally new context, exhaustion due to heavy workloads and protective gear, the fear of becoming infected and infecting others, feeling powerless to handle patients' conditions, and managing relationships in this stressful situation. The third category was “resilience amid challenges”. Health-care providers identified many sources of social support and used self-management strategies to cope with the situation. They also achieved transcendence from this unique experience. Interpretation The intensive work drained health-care providers physically and emotionally. Health-care providers showed their resilience and the spirit of professional dedication to overcome difficulties. Comprehensive support should be provided to safeguard the wellbeing of health-care providers. Regular and intensive training for all health-care providers is necessary to promote preparedness and efficacy in crisis management. Funding National Key R&D Program of China, Project of Humanities and Social Sciences of the Ministry of Education in China.

negative: Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement [Image: see text] With the ongoing pandemic of coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), our knowledge of the pathogenesis of COVID-19 is still in its infancy. Almost every aspect of the pathogen remains largely unknown, ranging from mechanisms involved in infection transmission, interplay with the human immune system, and covert mechanisms of end-organ damage. COVID-19 has manifested itself worldwide with a syndromic appearance that is dominated by respiratory dysregulations. While clinicians are focused on correcting respiratory homeostasis, echoing the original SARS, SARS-CoV-2 is also invading other end-organs, which may not exhibit overt clinical features. Nervous system involvement was not initially considered to play a significant role in patients with COVID-19. However, since this viewpoint was initially published, multiple studies have been released regarding the possible neurovirulence of SARS-CoV-2. In our previous viewpoint, we implored our colleagues to recognize the covert tactics of SARS-CoV-2 and emphasized that symptoms like anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. The past few weeks, after the viewpoint surfaced, it was noticed that it has enabled clinicians and healthcare professionals to compute the neurovirulence associated with SARS-CoV-2 in COVID-19 patients, as evidenced by very recently reported studies.

negative: Influenza A: From highly pathogenic H5N1 to pandemic 2009 H1N1. Epidemiology and clinical features The last decade has seen the emergence of two new influenza A subtypes and they have become a cause of concern for the global community. These are the highly pathogenic H5N1 influenza A virus (H5N1) and the Pandemic 2009 influenza H1N1 virus. Since 2003 the H5N1 virus has caused widespread disease and death in poultry, mainly in south East Asia and Africa. In humans the number of cases infected with this virus is few but the mortality has been about 60%. Most patients have presented with severe pneumonia and acute respiratory distress syndrome. The second influenza virus, the pandemic H1N1 2009, emerged in Mexico in March this year. This virus acquired the ability for sustained human to human spread and within a few months spread throughout the world and infected over 4 lakh individuals. The symptoms of infection with this virus are similar to seasonal influenza but it currently affecting younger individuals more often. Fortunately the mortality has been low. Both these new influenza viruses are currently circulating and have different clinical and epidemiological characteristics.

negative: Tracking the origin of early COVID-19 cases in Canada The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country's earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world's COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada's first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.

negative: Exploring the coronavirus epidemic using the new WashU Virus Genome Browser Since its debut in mid-December, 2019, the novel coronavirus (2019-nCoV) has rapidly spread from its origin in Wuhan, China, to several countries across the globe, leading to a global health crisis. As of February 7, 2020, 44 strains of the virus have been sequenced and uploaded to NCBI’s GenBank [1], providing insight into the virus’s evolutionary history and pathogenesis. Here, we present the WashU Virus Genome Browser, a web-based portal for viewing virus genomic data. The browser is home to 16 complete 2019-nCoV genome sequences, together with hundreds of related viral sequences including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus. In addition, the browser features unique customizability, supporting user-provided upload of novel viral sequences in various formats. Sequences can be viewed in both a track-based representation as well as a phylogenetic tree-based view, allowing the user to easily compare sequence features across multiple strains. The WashU Virus Genome Browser inherited many features and track types from the WashU Epigenome Browser, and additionally incorporated a new type of SNV track to address the specific needs of viral research. Our Virus Browser portal can be accessed at https://virusgateway.wustl.edu, and documentation is available at https://virusgateway.readthedocs.io/.

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

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

negative: The response of Milan's Emergency Medical System to the COVID-19 outbreak in Italy

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: COVID-19: key concepts for the surgeon Abstract In view of the current pandemic by SARS-CoV-2 it deems essential to understand the key concepts about the infection: its epidemiological origin, presentation, clinical course, diagnosis and treatment (still experimental in many cases). The knowledge about the virus is still limited, but as the pandemic progresses and the physiopathology of the disease is understood, new evidence is being massively published. Surgical specialists are facing an unprecedented situation: they must collaborate in the ER or medical wards attending these patients, while still needing to make decisions about surgical patients with probable COVID-19. The present narrative review aims to summarize the most relevant aspects and synthetize concepts on COVID-19 for surgeons.

negative: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies The emergence and rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a potentially fatal disease, is swiftly leading to public health crises worldwide. The origin of SARS-CoV-2 infection was first reported in people exposed to a seafood market in Wuhan City, China in December 2019. It has been suggested that the infection is likely to be of zoonotic origin and transmitted to humans through a not-yet-known intermediary. As of 22 May 2020, the World Health Organization reported that there were approximately 4,995,996 confirmed cases and 327,821 deaths. SARS-CoV-2 is transmitted via inhalation or direct contact with droplets from infected people. It has an incubation period ranging from 2 to ≥14 days. The rate of spread of SARS-CoV-2 is greater than that for severe acute respiratory syndrome coronavirus and Middle East respiratory coronavirus. The symptoms are similar to influenza (i.e. breathlessness, sore throat and fatigue) and infected cases are isolated and treated. Infection is mild in most cases, but in elderly (>50 years) patients and those with cardiac and respiratory disorders, it may progress to pneumonia, acute respiratory distress syndrome and multi-organ failure. People with strong immunity or those who have developed herd immunity are asymptomatic. The fatality rate ranges from 3% to 4%. Recommended methods for diagnosis of COVID-19 are molecular tests (e.g. polymerase chain reaction) on respiratory secretions, chest scan and common laboratory diagnosis. Currently, treatment is essentially supportive, and the role of antiviral agents is yet to be established as a vaccine is not yet available. This review will focus on epidemiology, symptoms, transmission, pathogenesis, ongoing available treatments and future perspectives of SARS-CoV-2.

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: Community Health Workers and Pandemic Preparedness: Current and Prospective Roles Despite the importance of community health workers (CHWs) to health systems in resource-constrained environments, relatively little has been written about their contributions to pandemic preparedness. In this perspective piece, we draw from the response to the 2014 Ebola and 2015 Zika epidemics to review examples whereby CHWs contributed to health security and pandemic preparedness. CHWs promoted pandemic preparedness prior to the epidemics by increasing the access to health services and products within communities, communicating health concepts in a culturally appropriate fashion, and reducing the burdens felt by formal healthcare systems. During the epidemics, CHWs promoted pandemic preparedness by acting as community-level educators and mobilizers, contributing to surveillance systems, and filling health service gaps. Acknowledging the success CHWs have had in these roles and in previous interventions, we propose that the cadre may be better engaged in pandemic preparedness in the future. Some practical strategies for achieving this include training and using CHWs to communicate One Health information to at-risk communities prior to outbreaks, pooling them into a reserve health corps to be used during public health emergencies, and formalizing agreements and strategies to promote the early engagement of CHWs in response actions. Recognizing that CHWs already play a role in pandemic preparedness, we feel that expanding the roles and responsibilities of CHWs represents a practical means of improving pandemic and community-level resilience.

negative: SARS-CoV-2-specific antibody detection in healthcare workers in Germany with direct contact to COVID-19 patients BACKGROUND: The novel coronavirus SARS-CoV-2 is associated with a severe respiratory manifestation, COVID-19, and presents a challenge for healthcare systems worldwide. Healthcare workers are a vulnerable cohort for SARS-CoV-2 infection due to frequent and close contact to patients with COVID-19. STUDY DESIGN: Serum samples from 316 healthcare workers of the University Hospital Essen, Germany were tested for SARS-CoV-2-IgG antibodies. A questionnaire was used to collect demographic and clinical data. Healthcare workers were grouped depending on the frequency of contact to COVID-19 patients in high-risk-group (n = 244) with daily contact to known or suspected SARS-CoV-2 positive patients, intermediated-risk-group (n = 37) with daily contact to patients without known or suspected SARS-CoV-2 infection at admission and low-risk-group (n = 35) without patient contact. RESULTS: In 5 of 316 (1.6%) healthcare workers SARS-CoV-2-IgG antibodies could be detected. The seroprevalence was higher in the intermediate-risk-group vs. high-risk-group vs. 2/37 (5.4%) vs. (3/244 (1.2%), p = 0.13). Four of the five subject were tested negative for SARS-CoV-2 via PCR. One (20%) subject was not tested via PCR since he was asymptomatic. CONCLUSION: The overall seroprevalence of SARS-CoV-2 in healthcare workers of a tertiary hospital in Germany is low (1.6%). The data indicate that the local hygiene standard might be effective.

negative: Preprinting a pandemic: the role of preprints in the COVID-19 pandemic The world continues to face an ongoing viral pandemic that presents a serious threat to human health. The virus underlying the COVID-19 disease, SARS-CoV-2, has caused over 3.2 million confirmed cases and 220,000 deaths between January and April 2020. Although the last pandemic of respiratory disease of viral origin swept the globe only a decade ago, the way science operates and responds to current events has experienced a paradigm shift in the interim. The scientific community has responded rapidly to the COVID-19 pandemic, releasing over 16,000 COVID-19 related scientific articles within 4 months of the first confirmed case, of which at least 6,000 were hosted by preprint servers. We focused our analysis on bioRxiv and medRxiv, two growing preprint servers for biomedical research, investigating the attributes of COVID-19 preprints, their access and usage rates, characteristics of their sharing on online platforms, and the relationship between preprints and their published articles. Our data provides evidence for increased scientific and public engagement (COVID-19 preprints are accessed and distributed at least 15 times more than non-COVID-19 preprints) and changes in journalistic practice with reference to preprints. We also find evidence for changes in preprinting and publishing behaviour: COVID-19 preprints are shorter, with fewer panels and tables, and reviewed faster. Our results highlight the unprecedented role of preprints and preprint servers in the dissemination of COVID-19 science, and the likely long-term impact of the pandemic on the scientific publishing landscape.

negative: CT manifestations of the coronavirus disease 2019 of imported infection versus second-generation infection in patients outside the original district (Wuhan, China) of this disease: An observational study To explore the discrepancy in computed tomography (CT) manifestations of the coronavirus disease 2019 (COVID-19) in patients outside the original district (Wuhan, China) between cases with imported infection and second-generation infection, 22 patients with COVID-19 from 2 hospitals in Nanchong, China, 938 km away from the original district (Wuhan, China) of this disease were enrolled. All patients underwent initial and follow-up CT after admission during the treatment, and were divided into 2 groups. Group A and B were composed of 15 patients with a history of exposure to the original district (Wuhan, China) in short-term (i.e., imported infection), and 7 with a close contact with the patients with confirmed COVID-19 or with the healthy individuals from the original district (i.e., second-generation infection), respectively. Initial CT features including extent score and density score between groups were statistically compared. We found that all patients in group A and 3 of 7 patients in group B had abnormal CT findings while 4 of 7 patients in group B had not. Patients with abnormal CT findings were more frequent in group A than in group B (Pâ<â.05). On initial CT, pure ground glass opacity (GGO), and GGO with consolidation and/or other abnormalities were found in 20% (3/15) and 80% (12/15) patients in group A, respectively, while 1 (14.3%), 2 (28.6%), and 4 (57.1%) had pure GGOs, GGO with focal consolidation, and normal CT appearances in Group B, respectively. Patients with extent and density scores of ≥5 were more frequent in group A than in group B (all P-valuesâ<â.01). Additionally, 3 of 4 (75%) patients with normal initial CT findings had focal pure GGO lesions on follow-up. In conclusion, COVID-19 in patients with a history of exposure to the original district can be severer than with the second-generation infection on CT.

negative: SARS-CoV-2 Isolation and Propagation from Turkish COVID-19 patients The novel coronavirus pneumonia, which was named later as Coronavirus Disease 2019 (COVID-19), is caused by the Severe Acute Respiratory Syndrome Coronavirus 2, namely SARS-CoV-2. It is a positive-strand RNA virus that is the seventh coronavirus known to infect humans. The COVID-19 outbreak presents enormous challenges for global health behind the pandemic outbreak. The first diagnosed patient in Turkey has been reported by the Republic of Turkey Ministry of Health on March 11, 2020. Today, over ninety thousand cases in Turkey, and two million cases around the world have been declared. Due to the urgent need for vaccine and anti-viral drug, isolation of the virus is crucial. Here, we report one of the first isolation and characterization studies of SARS-CoV-2 from nasopharyngeal and oropharyngeal specimens of diagnosed patients in Turkey. This study provides an isolation and replication methodology, and cell culture tropism of the virus that will be available to the research communities. Article Summary Scientists have isolated virus from Turkish COVID-19 patients. The isolation, propagation, and plaque and immune response assays of the virus described here will serve in following drug discovery and vaccine testing.

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: Newly emerged porcine enteric alphacoronavirus in southern China: Identification, origin and evolutionary history analysis Abstract Coronaviruses have a wide host range and can cause a variety of diseases with varying severity in different animals. Several enteric coronaviruses have been identified that are associated with diarrhea in swine and that have caused substantial economic losses. In this study, a newly emerged porcine enteric alphacoronavirus (PEAV), PEAV-GD-CH/2017, was identified from suckling piglets with diarrhea in southern China, and a full-length genome sequence of PEAV was obtained for systematic analysis. The novel PEAV sequence was most identical to that of bat-HKU2, and the differences between them were comprehensively compared, especially the uniform features of the S protein, which was shown to have a close relationship with betacoronaviruses and to perhaps represent unrecognized betacoronaviruses. In addition, Bayesian analysis was conducted to address the origin of PEAV, and the divergence time between PEAV and bat-HKU2 was estimated at 1926, which indicates that PEAV is not newly emerged and may have circulated in swine herds for several decades since the interspecies transmission of this coronavirus from bat to swine. The evolutionary rate of coronaviruses was estimated to be 1.93 × 10−4 substitutions per site per year for the RdRp gene in our analysis. For the origin of PEAV, we suspect that it is the result of the interspecies transmission of bat-HKU2 from bat to swine. Our results provide valuable information about the uniform features, origin and evolution of the novel PEAV, which will facilitate further investigations of this newly emerged pathogen.

negative: The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease Abstract Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.

negative: The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance.

negative: Blood Component Recalls and Market Withdrawals: Frequency, Reasons, and Management in the United States Abstract In a previous article, we reviewed the management of blood component recalls and withdrawals (G. Ramsey. Transfusion Med Rev 2004;18:36–45). Since then, US rates of recall and biological product deviation for blood components have improved significantly, particularly with regard to reduced recalls for donor infectious disease risks or testing. However, analysis of the current data from the US Food and Drug Administration suggests that 1 (0.4%) in 250 blood components is involved in market withdrawals and quarantines, with 1 in 5800 components formally recalled. Most of these units, unfortunately, had already have been transfused. The US Food and Drug Administration has issued several recent guidances that address transfusion service actions for dealing with specific infectious disease problems. This present article updates our 2004 recommendations as to when to notify physicians about transfused nonconforming blood components.

negative: Bats are key hosts in the radiation of mammal-associated Bartonella bacteria Bats are notorious reservoirs of several zoonotic diseases and may be uniquely tolerant of infection among mammals. Broad sampling has revealed the importance of bats in the diversification and spread of viruses and eukaryotes to other animal hosts. Vector-borne bacteria of the genus Bartonella are prevalent and diverse in mammals globally and recent surveys have revealed numerous Bartonella lineages in bats. We assembled a sequence database of Bartonella strains, consisting of nine genetic loci from 209 previously characterized lineages and 121 new cultured strains from bats, and used these data to perform the most comprehensive phylogenetic analysis of Bartonella to date. This analysis included estimation of divergence dates using a molecular clock and ancestral reconstruction of host associations and geography. We estimate that Bartonella began infecting mammals 62 million years ago near the Cretaceous-Paleogene boundary. Additionally, the radiation of particular Bartonella clades correlate strongly to the timing of diversification and biogeography of mammalian hosts. Bats were inferred to be the ancestral hosts of all mammal-associated Bartonella and appear to be responsible for the early geographic expansion of the genus. We conclude that bats have had a deep influence on the evolutionary radiation of Bartonella bacteria and their spread to other mammalian orders. These results support a ‘bat seeding’ hypothesis that could explain similar evolutionary patterns in other mammalian parasite taxa. Application of such phylogenetic tools as we have used to other taxa may reveal the general importance of bats in the ancient diversification of mammalian parasites. Significance statement Discovering the evolutionary history of infectious agents in animals is important for understanding the process of host adaptation and the origins of human diseases. To clarify the evolution of the Bartonella genus, which contains important human pathogens, we performed phylogenetic analysis on a broad diversity of Bartonella strains, including novel strains from bats. Our results indicate that Bartonella clades diversified along with their mammal hosts over millions of years. Bats appear to be especially important in the early radiation and geographic dispersal of Bartonella lineages. These patterns are consistent with research indicating a chiropteran origin of important human viruses and eukaryotic parasites, suggesting that bats may play a unique role as historical sources of infections to other hosts.

negative: Metagenomics detection and characterisation of viruses in faecal samples from Australian wild birds We present an optimised metagenomics method for detection and characterisation of all virus types including single and double stranded DNA/RNA and enveloped and non-enveloped viruses. Initial evaluation included both spiked and non-spiked bird faecal samples as well as non-spiked human faecal samples. From the non-spiked bird samples (Australian Muscovy duck and Pacific black ducks) we detected 21 viruses, and we also present a summary of a few viruses detected in human faecal samples. We then present a detailed analysis of selected virus sequences in the avian samples that were somewhat similar to known viruses, and had good quality (Q20 or higher) and quantity of next-generation sequencing reads, and was of interest from a virological point of view, for example, avian coronavirus and avian paramyxovirus 6. Some of these viruses were closely related to known viruses while others were more distantly related with 70% or less identity to currently known/sequenced viruses. Besides detecting viruses, the technique also allowed the characterisation of host mitochondrial DNA present and thus identifying host species, while ribosomal RNA sequences provided insight into the “ribosomal activity microbiome”; of gut parasites; and of food eaten such as plants or insects, which we correlated to non-avian host associated viruses.

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

negative: [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: Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)(3)-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.

negative: Can we contain the COVID-19 outbreak with the same measures as for SARS? Summary The severe acute respiratory syndrome (SARS) outbreak in 2003 resulted in more than 8000 cases and 800 deaths. SARS was eventually contained by means of syndromic surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine. By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82 000 confirmed cases of COVID-19 have been reported with more than 2800 deaths. Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19. COVID-19 differs from SARS in terms of infectious period, transmissibility, clinical severity, and extent of community spread. Even if traditional public health measures are not able to fully contain the outbreak of COVID-19, they will still be effective in reducing peak incidence and global deaths. Exportations to other countries need not result in rapid large-scale outbreaks, if countries have the political will to rapidly implement countermeasures.

negative: Advance in human coronaviruses research of host interactions/ 中华实用儿科临床杂志 2019-novel coronavirus (2019-nCoV) is a highly pathogenic human CoV that first emerged in Wuhan in 2019.2019-nCoV has a zoonotic origin and poses a major threat to public health.However, little is known about the viral factors contributing to the high virulence of 2019-nCoV.Many animal viruses, including CoVs, encode proteins that interfere with host gene expression, including those involved in antiviral immune responses, and these viral proteins are often major virulence factors.Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory infection.In the past 17 years, the onset of 2019-nCoV, 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 recent study of HCoVs-host interactions has contributed extensively to our understanding of infection pathogenesis of 2019-nCoV.This review discuss various host physiopathologic mechanism, such as apoptosis, innate immunity, endoplasmic reticulum (ER) stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs and provides evidence for the intensive investigate of 2019-nCoV infection.

negative: Analysis of codon usage and evolutionary rates of the 2019-nCoV genes Severe acute respiratory syndrome coronavirus 2 (2019-nCoV), which first broke out in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a mortality ranging from 3% to 6%. To better understand the evolution of the newly emerging 2019-nCoV, in this paper, we analyze the codon usage pattern of 2019-nCoV. For this purpose, we compare the codon usage of 2019-nCoV with that of other 30 viruses belonging to the subfamily of orthocoronavirinae. We found that 2019-nCoV shows a rich composition of AT nucleotides that strongly influences its codon usage, which appears to be not optimized to human host. Then, we study the evolutionary pressures influencing the codon usage and evolutionary rates of the sequences of five conserved genes that encode the corresponding proteins (viral replicase, spike, envelope, membrane and nucleocapsid) characteristic of coronaviruses. We found different patterns of both mutational bias and nature selection that affect the codon usage of these genes at different extents. Moreover, we show that the two integral membrane proteins proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins are important targets for the development of vaccines and antiviral drugs, tend to evolve faster as compared to other ones. Taken together, our results suggest that the higher evolutionary rate observed for these two genes could represent a major barrier in the development of antiviral therapeutics 2019-nCoV.

negative: Spatial-temporal characteristics of epidemic spread in-out flow—Using SARS epidemic in Beijing as a case study For better detecting the spatial-temporal change mode of individual susceptible-infected-symptomatic-treated-recovered epidemic progress and the characteristics of information/material flow in the epidemic spread network between regions, the epidemic spread mechanism of virus input and output was explored based on individuals and spatial regions. Three typical spatial information parameters including working unit/address, onset location and reporting unit were selected and SARS epidemic spread in-out flow in Beijing was defined based on the SARS epidemiological investigation data in China from 2002 to 2003 while its epidemiological characteristics were discussed. Furthermore, by the methods of spatial-temporal statistical analysis and network characteristic analysis, spatial-temporal high-risk hotspots and network structure characteristics of Beijing outer in-out flow were explored, and spatial autocorrelation/heterogeneity, spatial-temporal evolutive rules and structure characteristics of the spread network of Beijing inner in-out flow were comprehensively analyzed. The results show that (1) The outer input flow of SARS epidemic in Beijing concentrated on Shanxi and Guangdong provinces, but the outer output flow was disperse and mainly includes several north provinces such as Guangdong and Shandong. And the control measurement should focus on the early and interim progress of SARS breakout. (2) The inner output cases had significant positive autocorrelative characteristics in the whole studied region, and the high-risk population was young and middle-aged people with ages from 20 to 60 and occupations of medicine and civilian labourer. (3) The downtown districts were main high-risk hotspots of SARS epidemic in Beijing, the northwest suburban districts/counties were secondary high-risk hotspots, and northeast suburban areas were relatively safe. (4) The district/county nodes in inner spread network showed small-world characteristics and information/material flow had notable heterogeneity. The suburban Tongzhou and Changping districts were the underlying high-risk regions, and several suburban districts such as Shunyi and Huairou were the relatively low-risk safe regions as they carried out minority information/material flow. The exploration and analysis based on epidemic spread in-out flow help better detect and discover the potential spatial-temporal evolutive rules and characteristics of SARS epidemic, and provide a more effective theoretical basis for emergency/control measurements and decision-making.

negative: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

negative: How will country-based mitigation measures influence the course of the COVID-19 epidemic?

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: COVID-19: la epidemia causada por un nuevo coronavirus./ COVID-19: The outbreak caused by a new coronavirus Before the severe acute respiratory syndrome outbreak in 2003, coronaviruses (CoVs) were not considered to be highly pathogenic to humans. However, it was this epidemic that highlighted this group of viruses and included them among the causative agents of emerging epidemic diseases. In addition, in 2012, another new CoV responsible for the Middle East respiratory syndrome was identified. Both infections were considered a threat to global health security. At present, the third epidemic caused by a CoV is being faced. This new CoV, called 2019-nCoV, was originated in the city of Wuhan, China, and has been linked to severe respiratory infections in humans. Thanks to the collaboration of experts worldwide, more information about this virus and its infection is reported each day, which allows modifying the recommendations for its prevention and treatment, without forgetting that the ultimate goal is to control this epidemic. In this review, the important aspects of this new coronavirus, 2019-nCoV, and its disease, COVID-19, have been summarized with the information available up to February 2020.

negative: A new recruit for the army of the men of death The army of the men of death, in John Bunyan's memorable phrase, has a new recruit, and fear has a new face: a face wearing a surgical mask.

negative: Genetic diversity and cross-species transmission of kobuviruses in Vietnam Cross-species transmission of viruses poses a sustained threat to public health. Due to increased contact between humans and other animal species the possibility exists for cross-species transmissions and ensuing disease outbreaks. By using conventional PCR amplification and next generation sequencing, we obtained 130 partial or full genome kobuvirus sequences from humans in a sentinel cohort in Vietnam and various mammalian hosts including bats, rodents, pigs, cats, and civets. The evolution of kobuviruses in different hosts was analysed using Bayesian phylogenetic methods. We estimated and compared time of origin of kobuviruses in different host orders; we also examined the cross-species transmission of kobuviruses within the same host order and between different host orders. Our data provide new knowledge of rodent and bat kobuviruses, which are most closely related to human kobuviruses. The novel bat kobuviruses isolated from bat roosts in Southern Vietnam were genetically distinct from previously described bat kobuviruses, but closely related to kobuviruses found in rodents. We additionally found evidence of frequent cross-species transmissions of kobuviruses within rodents. Overall, our phylogenetic analyses reveal multiple cross-species transmissions both within and among mammalian species, which increases our understanding of kobuviruses genetic diversity and the complexity of their evolutionary history.

negative: COVID-19 epidemic in Sri Lanka: A mathematical and computational modelling approach to control The ongoing COVID19 outbreak originated in the city of Wuhan, China has caused a significant damage to the world population and the global economy. It has claimed more than 50,000 lives worldwide and more than one million of people have been infected as of 04th April 2020. In Sri Lanka, the first case of COVI19 was reported late January 2020 was a Chinese national and the first local case was identified in the second week of March. Since then, the government of Sri Lanka introduced various sequential measures to improve social distancing such as closure of schools and education institutes, introducing work from home model to reduce the public gathering, introducing travel bans to international arrivals and more drastically, imposed island wide curfew expecting to minimize the burden of the disease to the Sri Lankan health system and the entire community. Currently, there are 159 cases with five fatalities and also reported that 24 patients are recovered and discharged from hospitals. In this study, we use the SEIR conceptual model and its modified version by decomposing infected patients into two classes; patients who show mild symptoms and patients who tend to face severe respiratory problems and are required to treat in intensive care units. We numerically simulate the models for about five months period considering three critical parameters of COVID transmission mainly in the Sri Lankan context; efficacy of control measures, rate of overseas imported cases and time to introduce social distancing measures by the respective authorities.

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: In Silico Prediction of SARS Protease Inhibitors by Virtual High Throughput Screening A structure‐based in silico virtual drug discovery procedure was assessed with severe acute respiratory syndrome coronavirus main protease serving as a case study. First, potential compounds were extracted from protein–ligand complexes selected from Protein Data Bank database based on structural similarity to the target protein. Later, the set of compounds was ranked by docking scores using a Electronic High‐Throughput Screening flexible docking procedure to select the most promising molecules. The set of best performing compounds was then used for similarity search over the 1 million entries in the Ligand.Info Meta‐Database. Selected molecules having close structural relationship to a 2‐methyl‐2,4‐pentanediol may provide candidate lead compounds toward the development of novel allosteric severe acute respiratory syndrome protease inhibitors.

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

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: [Diagnosis, treatment, control and prevention of SARS-CoV-2 and coronavirus disease 2019: back to the future]. The ongoing outbreak of the coronavirus disease 2019 (COVID-19) as named by the World Health Organization has millions of confirmed cases around the world and has claimed hundreds of thousands of lives. The virus was named SARS-CoV-2 in February by International Committee on Taxonomy of Viruses. COVID-19 presents as fever, dry cough, dyspnea, headache and pneumonia. In a small subset of severe cases, the disease quickly progresses to respiratory failure and even death. Since the 21st century, there have been three major outbreaks caused by human coronaviruses, including the severe acute respiratory syndrome (SARS) that broke out in 2003, the Middle East respiratory syndrome (MERS) in 2012, and the recent pandemic of COVID-19. Since 2003, significant progress has been made in the study of SARS-CoV and MERS-CoV concerning their natural origins, pathogenesis, antiviral development and vaccine design. Since SARS-CoV-2 and SARS-CoV are closely related, previous findings on SARS-CoV are highly relevant to a better understanding as well as diagnosis, treatment, prevention and control of SARS-CoV-2. In this review, we highlight recent progresses in the field; compare the biological characteristics of SARS-CoV and SARS-CoV-2; summarize the urgently-needed diagnostic, treatment, prevention and control options; and provide future perspectives for the outcome of the outbreak and research questions to be answered, including some of the difficulties in vaccine development. Hopefully, our comments and suggestions would prove useful for the control of the SARS-CoV-2 epidemic in China and the world.

negative: The coronaviruses. Coronaviruses of human origin have emerged as probable important etiologic agents of acute upper respiratory tract illnesses in adults; their role in the etiology of respiratory illnesses of childhood is less certain. The first coronavirus of human origin, B814, was described in 1965 and since that time only 31 additional strains have been recovered. Ten of these were originally recovered in human embryonic tracheal organ culturesonly, and the remainder in monolayer cell cultures. All of the latter group were antigenically related to a prototype strain designated 229e. As a result of the fastidious growth requirements of these agents, most of the knowledge concerning the clinical syndromes associated with them has come from chajlenge studies in volunteers and seroepidemiologic investigations. Coronaviruses have been shown to be associated with a substantial number of adult respiratory illnesses especially during certain periods when rhinovirus infections are infrequent. Progress in propagating coronaviruses and in detecting coronavirus infections has been achieved recently: viruses similar to 229E were successfully recovered in human embryonic intestine cell cultures from patients with upper respiratory tract illnesses; 30C strains (B814, LP and EVS) were recovered in L132 cell cultures from infectious nasal washings; OC43(and OC38) viruses which were originally recovered in OC and later adapted to grow in suckling mice were not only shown to directly hemagglutinate various erythrocytes but were also adapted to grow in MK cell cultures; OC43 virus was also found to induce hemadsorption of rat and mouse erythrocytes in certain cell cultures; and a coronavirus strain was detected by immune electron microscopy. Coronaviruses are also associated with certain diseases in animals.

negative: Analysis of Serologic Cross-Reactivity Between Common Human Coronaviruses and SARS-CoV-2 Using Coronavirus Antigen Microarray The current practice for diagnosis of SARS-CoV-2 infection relies on PCR testing of nasopharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk. This testing strategy likely underestimates the true prevalence of infection, creating the need for serologic methods to detect infections missed by the limited testing to date. Here, we describe the development of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A preliminary study of human sera collected prior to the SARS-CoV-2 pandemic demonstrates overall high IgG reactivity to common human coronaviruses and low IgG reactivity to epidemic coronaviruses including SARS-CoV-2, with some cross-reactivity of conserved antigenic domains including S2 domain of spike protein and nucleocapsid protein. This array can be used to answer outstanding questions regarding SARS-CoV-2 infection, including whether baseline serology for other coronaviruses impacts disease course, how the antibody response to infection develops over time, and what antigens would be optimal for vaccine development.

negative: Forecasting the dynamics of COVID-19 Pandemic in Top 15 countries in April 2020: ARIMA Model with Machine Learning Approach We here predicted some trajectories of COVID-19 in the coming days (until April 30, 2020) using the most advanced Auto-Regressive Integrated Moving Average Model (ARIMA). Our analysis predicted very frightening outcomes, which defines to worsen the conditions in Iran, entire Europe, especially Italy, Spain, and France. While South Korea, after the initial blast, has come to stability, the same goes for the COVID-19 origin country China with more positive recovery cases and confirm to remain stable. The United States of America (USA) will come as a surprise and going to become the epicenter for new cases during the mid-April 2020. Based on our predictions, public health officials should tailor aggressive interventions to grasp the power exponential growth, and rapid infection control measures at hospital levels are urgently needed to curtail the COVID-19 pandemic.

negative: Evolution of research in health geographics through the International Journal of Health Geographics (2002–2015) Health geographics is a fast-developing research area. Subjects broached in scientific literature are most varied, ranging from vectorial diseases to access to healthcare, with a recent revival of themes such as the implication of health in the Smart City, or a predominantly individual-centered approach. Far beyond standard meta-analyses, the present study deliberately adopts the standpoint of questioning space in its foundations, through various authors of the International Journal of Health Geographics, a highly influential journal in that field. The idea is to find space as the common denominator in this specialized literature, as well as its relation to spatial analysis, without for all that trying to tend towards exhaustive approaches. 660 articles have being published in the journal since launch, but 359 articles were selected based on the presence of the word “Space” in either the title, or the abstract or the text over 13 years of the journal’s existence. From that database, a lexical analysis (tag cloud) reveals the perception of space in literature, and shows how approaches are evolving, thus underlining that the scope of health geographics is far from narrowing.

negative: Unprecedented disruptions of lives and work: Health, distress and life satisfaction of working adults in China one month into the COVID-19 outbreak We assess the health and wellbeing of normal adults living and working after one month of confinement to contain the COVID-19 outbreak in China. On Feb 20 and 21, 2020, we surveyed 369 adults in 64 cities in China that varied in their rates of confirmed coronavirus cases on their health conditions, distress and life satisfaction. 27% of the participants worked at the office, 38% resorted to working from home, and 25% stopped working due to the outbreak. Those who stopped working reported worse mental and physical health conditions as well as distress. The severity of COVID-19 in a location predicts life satisfaction, and this relationship is contingent upon the existing chronic health issues and hours of exercise of the individuals. Our evidence supports the need to pay attention to the health of people who were not affected by the virus epidemiologically, especially for people who stopped working during the outbreak. Our results highlight that physically active people might be more susceptible to wellbeing issues during the lockdown. Policymakers who are considering introducing restrictive measures to contain COVID-19 may benefit from understanding such health and wellbeing implications.

negative: SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

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

negative: Incidence of novel coronavirus (2019-nCoV) infection among people under home quarantine in Shenzhen, China Since the outbreak of 2019-nCoV in December, Chinese government has implemented various measures including travel bans, centralized treatments, and home quarantines to slowing the transmission across the country. In this study, we aimed to estimate the incidence of 2019-nCoV infection among people under home quarantine in Shenzhen, China. Methods: We used a stratified multistage random sampling method to recruit participants and collected demographic information and laboratory results of people under home quarantine. We conducted descriptive analysis to estimate the basic characteristics and to calculate the incidence in out study population. Results: A total of 2004 people under home quarantine participated in this study, of which 1637 participants finished the questionnaire with a response rate of 81.7%. Mean age of the participants was 33.7 years, ranging from 0.3 to 80.2 years. Of people who provided clear travel history, 129 people have traveled to Wuhan city and 1,046 people have traveled to other cities in Hubei province within 14 days before the home quarantine. Few (less than 1%) participants reported contact history with confirmed or suspected cases during their trip and most of these arrived at Shenzhen between Jan 24, 2020 to Jan 27, 2020. The incidence of COVID-19 in the sample was 1.5‰ (95% CI: 0.31‰–4.37‰). Conclusion: Home quarantine has been effective in preventing the early transmission of COVID-19, but that more needs to be done to improve early detection of COVID-19 infection.

negative: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.

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: COVID-19 in the heart and the lungs: could we “Notch” the inflammatory storm? From January 2020, coronavirus disease (COVID-19) originated in China has spread around the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The presence of myocarditis, cardiac arrest, and acute heart failure in COVID-19 patients suggests the existence of a relationship between SARS-CoV-2 infection and cardiac disease. The Notch signalling is a major regulator of cardiovascular function and it is also implicated in several biological processes mediating viral infections. In this report we discuss the possibility to target Notch signalling to prevent SARS-CoV-2 infection and interfere with the progression of COVID-19- associated heart and lungs disease.

negative: La sécurité sanitaire mondiale à l’heure de Nagoya SUMMMARY The International Health Regulations are the main legal instrument to prevent the international propagation of diseases, particularly related to infectious agents. It supports the exchange of samples between countries. These exchanges have raised expectations, in many countries, about the sharing of the benefits resulting from these exchanges. About influenza viruses with pandemic potential, the 2011 pandemic influenza preparedness framework Agreement is a response to these expectations. These exchanges are also influenced by the progress made in genetics. The Nagoya Protocol, which came into force in 2014, creates a new framework concerning the use of genetic resources, including about pathogens. It will have a positive impact on public health, if it facilitates the exchanges of gene sequence data about pathogens and if it permits benefits sharing internationally. Such a result is possible, if its implementation builds upon the pandemic influenza preparedness framework Agreement.

negative: COVID-19 randomised trial protocols: rapid publication without barriers

negative: Associations between media use and health information-seeking behavior on vaccinations in South Korea BACKGROUND: Although vaccinations are critical for preventing emerging infectious diseases, scant research has been conducted on risk communication. With socio-economic characteristics, health behavior, and underlying diseases under control, we investigated associations between media use, health information-seeking behavior, health information type, and vaccination in the population. METHODS: This study relied on a national survey of Korean adults (n = 1367). Participants were adult males and females age 20 and older. Web and face-to-face surveys were conducted throughout July 2014. The main outcome was vaccination (categorized as yes or no). Independent variables were time spent on media, frequency of health information-seeking behavior, and types of health information sought. RESULTS: Controlling for co-variates, logistic regression analysis was conducted to identify factors that influence Korean adults being vaccinated. Results revealed that accessible information about emerging infectious diseases, listening to the radio, and reading the newspaper were associated with increased odds of being vaccinated. Active seeking health information as well as being female and of higher socio-economic status were positively correlated with Korean adults being vaccinated. CONCLUSION: It is critical to promote health information-seeking behavior and use diverse media channels to increase acceptance and awareness of emerging infectious diseases and vaccinations. Because there are differences in vaccination awareness depending on social class, it is critical to reduce communication inequality, strengthen accessibility to vaccinations, and devise appropriate risk communication strategies that ensure Korean adults receive vaccinations.

negative: Occupational risks for COVID-19 infection

negative: Complete Genome Sequence of a Novel Swine Acute Diarrhea Syndrome Coronavirus, CH/FJWT/2018, Isolated in Fujian, China, in 2018 The full-length genome sequence of a novel swine acute diarrhea syndrome coronavirus (SADS-CoV), CH/FJWT/2018, was determined, which was genetically most closely related to CN/GDWT/2017, recently discovered in Fujian, China. The indel sites of the spike (S) gene of CH/FJWT/2018 were most similar to those of bat-origin SADS-related coronaviruses.

negative: Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.

negative: Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing BACKGROUND: The Manila clam (Ruditapes philippinarum) is a worldwide cultured bivalve species with important commercial value. Diseases affecting this species can result in large economic losses. Because knowledge of the molecular mechanisms of the immune response in bivalves, especially clams, is scarce and fragmentary, we sequenced RNA from immune-stimulated R. philippinarum hemocytes by 454-pyrosequencing to identify genes involved in their immune defense against infectious diseases. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput deep sequencing of R. philippinarum using 454 pyrosequencing technology yielded 974,976 high-quality reads with an average read length of 250 bp. The reads were assembled into 51,265 contigs and the 44.7% of the translated nucleotide sequences into protein were annotated successfully. The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. We have found sequences from molecules never described in bivalves before, especially in the complement pathway where almost all the components are present. CONCLUSIONS: This study represents the first transcriptome analysis using 454-pyrosequencing conducted on R. philippinarum focused on its immune system. Our results will provide a rich source of data to discover and identify new genes, which will serve as a basis for microarray construction and the study of gene expression as well as for the identification of genetic markers. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum.

negative: A Review on coronavirus family persistency and considerations of novel type, covid-19 features The arrival of new types of viral diseases, namely coronavirus family, have posed a serious threat for global health A new kind of coronavirus (CoV) named intense respiratory syndrome CoV-2 (SARS-CoV-2 or COVID-19) firstly diagnosed in Huanan Seafood Wholesale, Wuhan City, China The COVID-19 origination is likely to be from an animal host like bat and followed by person-person transmission unless the other routes possibility should be taken into account The COVID-19 has been spread so fast all over the world, with more than 1,569,504 infected cases and 95,269 mortality as of April, 11th 2020, regardless of potent control and quarantine policy in more countries Moreover, the SARS-CoV2 known as a novel coronavirus as it's initial genomic was less likely to be matched with the former CoV types The human-human transmission range reported to be 2-14 days and its spread expansions would be comforted by surfaces, infected hands and droplets This review focused on the persistency of different coronaviruses, like avain H7H9, SARS-CoV, MERS-CoV, Ebola virus and COVID-19, on varied surfaces as well as considering of COVID-19 features such as transmission, preventable policies, symptoms and suggested treatment ways to combat COVID-19

negative: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.

negative: Adipose-derived stromal stem cells (ASCs) as a new regenerative immediate therapy combating coronavirus (COVID-19)-induced pneumonia

negative: A multicentre collaboration to investigate the cause of severe acute respiratory syndrome Summary Severe Acute respiratory syndrome is a new disease in human beings, first recognised in late February, 2003, in Hanoi, Vietnam. The severity of the disease, combined with its rapid spread along international air-travel routes, prompted WHO to set up a network of scientists from 11 laboratories around the world to try to identify the causal agent and develop a diagnostic test. The network unites laboratories with different methods and capacities to rapidly fulfil all postulates for establishing a virus as the cause of a disease. Results are shared in real time via a secure website, on which microscopy pictures, protocols for testing, and PCR primer sequences are also posted. Findings are discussed in daily teleconferences. Progress is further facilitated through sharing between laboratories of samples and test materials. The network has identified a new coronavirus, consistently detected in samples of SARS patients from several countries, and conclusively named it as the causative agent of SARS; the strain is unlike any other known member of the genus Coronavirus. Three diagnostic tests are now available, but all have limitations.

negative: Clinical Pathway for Early Diagnosis of COVID-19: Updates from Experience to Evidence-Based Practice The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.

negative: Estimation of SARS-CoV-2 mortality during the early stages of an epidemic: a modelling study in Hubei, China and northern Italy Background. The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Wuhan, China in late 2019 is now pandemic. Reliable estimates of death from coronavirus disease 2019 (COVID-19) are essential to guide control efforts and to plan health care system requirements. The objectives of this study are to: 1) simulate the transmission dynamics of SARS-CoV-2 using publicly available surveillance data; 2) give estimates of SARS-CoV-2 mortality adjusted for bias in the two regions with the world's highest numbers of confirmed Covid-19 deaths: Hubei province, China and northern Italy. Method and Findings. We developed an age-stratified susceptible-exposed-infected-removed (SEIR) compartmental model describing the dynamics of transmission and mortality during the SARS-CoV-2 epidemic. Our model accounts for two biases; preferential ascertainment of severe cases and delayed mortality (right-censoring). We fitted our transmission model to surveillance data from Hubei province (1 January to 11 February 2020) and northern Italy (8 February to 3 March 2020). Overall mortality among all symptomatic and asymptomatic infections was estimated to be 3.0% (95% credible interval: 2.6-3.4%) in Hubei province and 3.3% (2.0-4.7%) in northern Italy. Mortality increased with age; we estimate that among 80+ year olds, 39.0% (95%CrI: 31.1-48.9%) in Hubei province and 89.0% (95%CrI: 56.2-99.6%) in northern Italy dies or will die. Limitations are that the model requires data recorded by date of onset and that sex-disaggregated mortality was not available. Conclusions. We developed a mechanistic approach to correct the crude CFR for bias due to right-censoring and preferential ascertainment and provide adjusted estimates of mortality due to SARS-CoV-2 infection by age group. While specific to the situation in Hubei, China and northern Italy during these periods, these findings will help the mitigation efforts and planning of resources as other regions prepare for SARS-CoV-2 epidemics.

negative: SARS-CoV-2 and viral sepsis: observations and hypotheses Summary Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.

negative: The hog-badger is not an edentate: systematics and evolution of the genus Arctonyx (Mammalia: Mustelidae) Hog-badgers (mustelid carnivorans classified in the genus Arctonyx) are distributed throughout East and Southeast Asia, including much of China, the eastern Indian Subcontinent, Indochina and the large continental Asian island of Sumatra. Arctonyx is usually regarded as monotypic, comprising the single species A. collaris F. Cuvier, 1825, but taxonomic boundaries in the genus have never been revised on the basis of sizeable series from throughout this geographical range. Based on a review of most available specimens in world museums, we recognize three distinctive species within the genus, based on craniometric analyses, qualitative craniodental features, external comparisons, and geographical and ecological considerations. Arctonyx albogularis (Blyth, 1853) is a shaggy-coated, medium-sized badger widely distributed in temperate Asia, from Tibet and the Himalayan region to eastern and southern China. Arctonyx collaris F. Cuvier, 1825, is an extremely large, shorter-haired badger, distributed throughout Southeast Asia, from eastern India to Myanmar, Thailand, Vietnam, Cambodia and Laos. The world's largest extant badger, A. collaris co-occurs with A. albogularis in eastern India and probably in southern China, and fossil comparisons indicate that its geographical range may have extended into central China in the middle Pleistocene. The disjunctly distributed species Arctonyx hoevenii (Hubrecht, 1891), originally described within the order ‘Edentata’ by a remarkable misunderstanding, is the smallest and darkest member of the genus and is endemic to the Barisan mountain chain of Sumatra. Apart from A. hoevenii, no other Arctonyx occurs on the Sunda Shelf below peninsular Thailand. The natural history of each species of Arctonyx, so far as is known, is briefly reviewed. No claim to original US Government works.

negative: Coronavirus disease (COVID‐19): An updated review based on current knowledge and existing literature for dermatologists The world entered the year 2020 with reports of the emergence of a new viral illness in Wuhan city, Hubei province, China. In January 2020, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified to be the causative novel coronavirus for the cluster of patients suffering from pneumonia in China. The disease was later named as coronavirus disease (COVID‐19) and was declared a pandemic by the World Health Organization on March 11, 2020. Several studies, since then, have tried to study and explain the origin of SARS‐CoV‐2, its structure and pathogenicity, epidemiology, modes of transmission, spectrum of illness and causes of mortality and morbidity. The current management strategies focus on supportive care and prevention of complications. With no definite treatment, as of now, encouraging reports of some anti‐viral and anti‐malarial drugs in the management of COVID‐19 generate some hope. This review intends to cover the current known aspects of COVID‐19 and SARS‐CoV‐19, based on the available literature.

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

negative: Travel health risk perceptions of Chinese international students in Australia – Implications for COVID-19 Abstract Background International students frequently return to their country of origin to visit friends and relatives (VFR), and are at increased risk of travel-associated infections. Little is known of their travel health seeking behaviours. China is the biggest source of international students studying in Australia and the unprecedented epidemic of COVID-19 in China makes this an important area of research. Methods Focus groups of Chinese international students were conducted to explore travel health-related knowledge, attitudes and practices. Eligible participants were studying in Sydney, and had travelled to China and Hong Kong to visit friends and relatives in the preceding 18 months. A variety of topics were explored, using a focus group guide. Thematic analysis was undertaken on the transcripts using nVivo software. The list of codes and themes were not pre-determined but developed through content analysis. Results Two focus groups were held with a total of 28 participants. Risk perception about VFR travel was generally low among Chinese international students. Pre-travel healthcare was not sought. Students strongly relied on the Internet, social media, parents and friends in China for travel health advice. Conclusion This research provides insights into Chinese international students as VFR travellers. It confirms students could be a risk population for importations of infections such as COVID-19 because of low risk perception and lack of seeking travel health advice. This can inform health promotion strategies for students.

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

negative: The reproductive number of COVID-19 is higher compared to SARS coronavirus Teaser: Our review found the average R0 for 2019-nCoV to be 3.28, which exceeds WHO estimates of 1.4 to 2.5.

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: Impact of international travel dynamics on domestic spread of 2019-nCoV in India: origin-based risk assessment in importation of infected travelers The recent pandemic caused by the 2019 outbreak of novel coronavirus (2019-nCoV or COVID-19) has affected more than 3.0 million people resulting ~ 212,000 deaths across 215 countries/territories as on 28th April 2020. The importation of the cases owing to enormous international travels from the affected countries is the foremost reason for local cycle of transmission. For a country like India, the second most populous country in the world with ~ 1.35 billion population, the management and control of 2019-nCoV domestic spread heavily relied on effective screening and strict quarantine of passengers arriving at various international airports in India from affected countries. Here, by extracting the data from FLIRT, an online airline database for more than 800 airlines, and scanning more than 180,000 flights and 39.9 million corresponding passenger seats during 4th – 25th March, we show that India experienced the highest risk index of importing the passengers from middle eastern airports. Contrary to perception, travelers from China imposed lowest risk of importing the infected cases in India. This is clearly evident form the fact that while the number of infected cases were on the peak in China India was one of the least affected countries. The number of cases in India started exhibiting a sharp increase in the infected cases only after the European countries and USA recorded large number of infected cases. We further argue that while the number of cases in middle eastern countries may still be very low, the airports in middle eastern countries, particularly Dubai, being one of the largest transit hubs for international passengers, including arriving in India, might have posed a higher risk of getting infected with 2019-nCoV. We suggest that any future travel related disease infection screening at the airports should critically assess the passengers from major transit hubs in addition to affected country of origin.

negative: The impact of ethnicity on clinical outcomes in COVID-19: A systematic review BACKGROUND: The relationship between ethnicity and COVID-19 is uncertain. We performed a systematic review to assess whether ethnicity has been reported in patients with COVID-19 and its relation to clinical outcomes. METHODS: We searched EMBASE, MEDLINE, Cochrane Library and PROSPERO for English-language citations on ethnicity and COVID-19 (1(st) December 2019-15(th) May 2020). We also reviewed: COVID-19 articles in NEJM, Lancet, BMJ, JAMA, clinical trial protocols, grey literature, surveillance data and preprint articles on COVID-19 in MedRxiv to evaluate if the association between ethnicity and clinical outcomes were reported and what they showed. PROSPERO:180654. FINDINGS: Of 207 articles in the database search, five reported ethnicity; two reported no association between ethnicity and mortality. Of 690 articles identified from medical journals, 12 reported ethnicity; three reported no association between ethnicity and mortality. Of 209 preprints, 34 reported ethnicity – 13 found Black, Asian and Minority Ethnic (BAME) individuals had an increased risk of infection with SARS-CoV-2 and 12 reported worse clinical outcomes, including ITU admission and mortality, in BAME patients compared to White patients. Of 12 grey literature reports, seven with original data reported poorer clinical outcomes in BAME groups compared to White groups. INTERPRETATION: Data on ethnicity in patients with COVID-19 in the published medical literature remains limited. However, emerging data from the grey literature and preprint articles suggest BAME individuals are at an increased risk of acquiring SARS-CoV-2 infection compared to White individuals and also worse clinical outcomes from COVID-19. Further work on the role of ethnicity in the current pandemic is of urgent public health importance. FUNDING: NIHR

negative: Bats host diverse parvoviruses as possible origin of mammalian dependoparvoviruses and source for bat-swine interspecies transmission. Compared to the enormous species diversity of bats, relatively few parvoviruses have been reported. We detected diverse and potentially novel parvoviruses from bats in Hong Kong and mainland China. Parvoviruses belonging to Amdoparvovirus, Bocaparvovirus and Dependoparvovirus were detected in alimentary, liver and spleen samples from 16 different chiropteran species of five families by PCR. Phylogenetic analysis of partial helicase sequences showed that they potentially belonged to 25 bocaparvovirus, three dependoparvovirus and one amdoparvovirus species. Nearly complete genome sequencing confirmed the existence of at least four novel bat bocaparvovirus species (Rp-BtBoV1 and Rp-BtBoV2 from Rhinolophus pusillus, Rs-BtBoV2 from Rhinolophus sinicus and Rol-BtBoV1 from Rousettus leschenaultii) and two novel bat dependoparvovirus species (Rp-BtAAV1 from Rhinolophus pusillus and Rs-BtAAV1 from Rhinolophus sinicus). Rs-BtBoV2 was closely related to Ungulate bocaparvovirus 5 with 93, 72.1 and 78.7 % amino acid identities in the NS1, NP1 and VP1/VP2 genes, respectively. The detection of bat bocaparvoviruses, including Rs-BtBoV2, closely related to porcine bocaparvoviruses, suggests recent interspecies transmission of bocaparvoviruses between bats and swine. Moreover, Rp-BtAAV1 and Rs-BtAAV1 were most closely related to human AAV1 with 48.7 and 57.5 % amino acid identities in the rep gene. The phylogenetic relationship between BtAAVs and other mammalian AAVs suggests bats as the ancestral origin of mammalian AAVs. Furthermore, parvoviruses of the same species were detected from multiple bat species or families, supporting the ability of bat parvoviruses to cross species barriers. The results extend our knowledge on the diversity of bat parvoviruses and the role of bats in parvovirus evolution and emergence in humans and animals.

negative: Rapid detection of SARS‐CoV‐2 in saliva: can an endodontist take the lead in point‐of‐care COVID‐19 testing? Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious zoonotic virus that originated from Wuhan, China, in December 2019. The resulting disease known as COVID-19 was declared as a pandemic by WHO on March 11, 2020. As of April 25, 2020, more than 2.72 million cases have been reported across 213 countries and territories, resulting in more than 187,847 deaths (https://www.who.int/emergencies/diseases/novel-coronavirus-2019). The disease spreads through aerosol droplets and has an incubation period of 1-14 days. Research addressing crucial unknowns regarding clinical severity, the extent of transmission, and treatment options is going on all over the world since the disease inception. The primary response strategy includes limiting human-to-human transmission.

negative: SARS-CoV Attack (Severe Acute Respiratory Syndrome)

negative: Coronavirus-2019. General considerations/ Coronavirus-2019. Consideraciones Generales According to what was published by the WHO (World Health Organization), a first case of acute respiratory infection, of unknown origin, appeared in the province of HUBEI, CHINA, in the city of WUHAN, (December 2019). After having ruled out other etiological agents, the isolation of a new coronavirus (7-01-2020) was achieved, which was called new coronavirus (nCOV, COVID-19), currently named SARS-CoV-2. Coronaviruses, being important pathogens, can infect the respiratory, gastrointestinal, hepatic, and nervous systems of humans and birds, livestock, bats, mice, and other wild animals. Since the outbreaks of SARS (Severe Acute Respiratory Syndrome) in 2002 and MERS (Middle East Respiratory Syndrome) in 2012, the transmission of these viruses between humans and animals has been demonstrated.

negative: Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Coronaviruses and Ocular Implications in Humans and Animals In December 2019, a novel coronavirus (CoV) epidemic, caused by the severe acute respiratory syndrome coronavirus – 2 (SARS-CoV-2) emerged from China. This virus causes the coronavirus disease 2019 (COVID-19). Since then, there have been anecdotal reports of ocular infection. The ocular implications of human CoV infections have not been widely studied. However, CoVs have been known to cause various ocular infections in animals. Clinical entities such as conjunctivitis, anterior uveitis, retinitis, and optic neuritis have been documented in feline and murine models. In this article, the current evidence suggesting possible human CoV infection of ocular tissue is reviewed. The review article will also highlight animal CoVs and their associated ocular infections. We hope that this article will serve as a start for further research into the ocular implications of human CoV infections.

negative: Prevalence and genomic characteristics of a novel reassortment mammalian orthoreovirus type 2 in diarrhea piglets in Sichuan, China. Mammalian orthoreovirus (MRV), which can infect almost all mammals, is a zoonotic virus. In this study, six strains of type 2 MRV (MRV2) were isolated from 7 diarrhea piglets from a farm that had an outbreak of diarrhea in piglets in 2018, which tested negative for porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and porcine group A rotavirus (RAV). The MRV2 isolate infected neonatal piglets, in which it induced severe diarrhea, while the virus was detected in multiple organs of piglets. Moreover, the complete genome of an MRV2 isolate was obtained, which was a novel reassortant MRV strain of human MRV, porcine MRV, chamois MRV, bat MRV, and mink MRV based on the nucleotide identity and phylogenetic tree. The S1 gene of isolate had eight unique amino acid mutations compared with available MRV2 S1 in the GenBank. To investigate the prevalence of this MRV2, 78 samples of diarrhea feces were collected from 10 pig farms in seven regions of Sichuan province. The obtained results showed that the positive rate of samples was 14% (11/78), and positive rate of farms was 60% (6/10), while the amplified fragments shared the identical amino acid mutations with the isolated strain, thus suggesting that this MRV2 strain was already prevalent in Sichuan province. The present study was first to isolate a pig-derived type 2 MRV strain in China, obtaining the complete genome of this strain, which furthers our understanding of the MRV2 epidemic and evolution.

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: Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset Background Timely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated. Method A patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial sera of COVID-19 patients were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described. Results The seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively. Conclusions Typical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection.

negative: Intrinsic growth rules of patients infected, dead and recovered with 2019 novel coronavirus in mainland China An outbreak of a novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) was first diagnosed in Wuhan, China, in December 2019 and then spread rapidly to other regions. We collected the time series data of the cumulative number of confirmed infected, dead, and cured cases from the health commissions in 31 provinces in mainland China. A descriptive model in a logistic form was formulated to infer the intrinsic epidemic rules of COVID-19, which illustrates robustness spatially and temporally. Our model is robust (R2>0.95) to depict the intrinsic growth rule for the cumulative number of confirmed infected, dead, and cured cases in 31 provinces in mainland China. Furthermore, we compared the intrinsic epidemic rules of COVID-19 in Hubei with that of severe acute respiratory syndrome (SARS) in Beijing, which was obtained from the Ministry of Public Health of China in 2003. We found that the infected case is the earliest to be saturated and has the lowest semi-saturation period compared with deaths and cured cases for both COVID-19 and SARS. All the three types of SARS cases are later to saturate and have longer semi-saturation period than that of COVID-19. Despite the virus caused SARS (SARS-CoV) and the virus caused COVID-19 (SARS-CoV-2) are homologous, the duration of the outbreak would be shorter for COVID-19.

negative: Origin and evolution of pathogenic coronaviruses Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.

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

negative: Integrating one health in national health policies of developing countries: India’s lost opportunities BACKGROUND: Globally, the threat of infectious diseases, particularly emerging infectious diseases, originating at the human-animal-environment interface, has caught health systems off guard. With forecasts that future pathogen emergence will be centred in hotspots in Asia, Africa, and Latin America, the need to prepare policy frameworks that can combat this threat is urgent. DISCUSSION: Emergence of diseases such as avian influenza and Ebola virus disease, which threatened social disruption, have established the need for intersectoral coordination/collaboration. These events led to the initiation of establishing institutionalised collaborative frameworks in India to adopt a One Health approach to disease prevention and control. However, the gains made in influenza control could not be adapted to other infectious diseases. Intersectoral coordination was briefly carried out, more as a reactive response to threats. The systemic failure to sustain such efforts have therefore, only undermined a coordinated response. The recent draft National Health Policy, 2015, has also failed to establish the need for intersectoral coordination in disease control approaches. Neglecting the need to endorse linkages between human health, animal health and husbandry, agriculture, and environmental sectors, has led to duplicative and weak response systems. The absence of health impact assessment with respect to the development agenda in policies, has cast negative effects on the health and wellbeing of man, animal, and the environment. Lack of attention to building core capacity in these critical sectors has further raised challenges in designing and deploying mitigation strategies. With developing countries like India being home to a major portion of the world’s poorest livestock farmers, the absence of a policy discourse that endorses the One Health approach in development and health policies is a major hurdle in eliminating poverty and poverty-related diseases. CONCLUSIONS: The adoption of One Health approaches in health and related sectoral policies is a critical policy requirement for India and other developing countries. The goal should be to not just establish preparedness plans, but also to encourage a policy environment where assessment and mitigation of downstream impacts of different agenda are incorporated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0181-2) contains supplementary material, which is available to authorized users.

negative: Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study OBJECTIVE: To study the neurological manifestations of patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective case series SETTING: Three designated COVID-19 care hospitals of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. PARTICIPANTS: Two hundred fourteen hospitalized patients with laboratory confirmed diagnosis of severe acute respiratory syndrome from coronavirus 2 (SARS-CoV-2) infection. Data were collected from 16 January 2020 to 19 February 2020. MAIN OUTCOME MEASURES: Clinical data were extracted from electronic medical records and reviewed by a trained team of physicians. Neurological symptoms fall into three categories: central nervous system (CNS) symptoms or diseases (headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy), peripheral nervous system (PNS) symptoms (hypogeusia, hyposmia, hypopsia, and neuralgia), and skeletal muscular symptoms. Data of all neurological symptoms were checked by two trained neurologists. RESULTS: Of 214 patients studied, 88 (41.1%) were severe and 126 (58.9%) were non-severe patients. Compared with non-severe patients, severe patients were older (58.7 ± 15.0 years vs 48.9 ± 14.7 years), had more underlying disorders (42 [47.7%] vs 41 [32.5%]), especially hypertension (32 [36.4%] vs 19 [15.1%]), and showed less typical symptoms such as fever (40 [45.5%] vs 92 [73%]) and cough (30 [34.1%] vs 77 [61.1%]). Seventy-eight (36.4%) patients had neurologic manifestations. More severe patients were likely to have neurologic symptoms (40 [45.5%] vs 38 [30.2%]), such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]) and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). CONCLUSION: Compared with non-severe patients with COVID-19, severe patients commonly had neurologic symptoms manifested as acute cerebrovascular diseases, consciousness impairment and skeletal muscle symptoms.

negative: COVID-19: Conceptos clave para el cirujano Resumen Ante la pandemia por SARS-CoV-2 resulta fundamental conocer los aspectos claves de la infección: su origen epidemiológico, presentación, curso clínico, diagnóstico y los tratamientos empleados (aún experimentales en muchos casos). El conocimiento sobre el virus es limitado, pero a medida que progresa la pandemia y se conoce más su fisiopatología, se está publicando nueva evidencia de forma masiva. Los especialistas quirúrgicos se enfrentan a una situación sin precedentes: deben colaborar en plantas médicas o urgencias atendiendo a estos pacientes y además tomar decisiones sobre pacientes quirúrgicos con posible COVID-19. Esta revisión narrativa pretende resumir los aspectos más relevantes y sintetizar los conceptos básicos sobre COVID-19 para los cirujanos. Abstract In view of the current pandemic by SARS-CoV-2 it deems essential to understand the key concepts about the infection: its epidemiological origin, presentation, clinical course, diagnosis and treatment (still experimental in many cases). The knowledge about the virus is still limited, but as the pandemic progresses and the physiopathology of the disease is understood, new evidence is being massively published. Surgical specialists are facing an unprecedented situation: they must collaborate in the ER or medical wards attending these patients, while still needing to make decisions about surgical patients with probable COVID-19. The present narrative review aims to summarize the most relevant aspects and synthetize concepts on COVID-19 for surgeons.

negative: 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

negative: Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2 Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19 (coronavirus disease 2019), which was first reported in Wuhan, China, in December 2019. Despite extensive efforts to control the disease, COVID-19 has now spread to more than 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are unknown. In this study, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2. We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but ferrets and cats are permissive to infection. Additionally, cats are susceptible to airborne transmission. Our study provides insights into the animal models for SARS-CoV-2 and animal management for COVID-19 control.

negative: Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy Abstract The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome. A cytokine storm has been shown in patients who develop fatal complications, as observed in past coronavirus infections. The management includes ventilatory support and broad-spectrum antiviral drugs, empirically utilized, as a targeted therapy and vaccines have not been developed. Based upon our limited knowledge on the pathogenesis of CoViD-19, a potential role of some anti-rheumatic drugs may be hypothesized, acting as direct antivirals or targeting host immune response. Antimalarial drugs, commonly used in rheumatology, may alter the lysosomal proteases that mediates the viral entry into the cell and have demonstrated efficacy in improving the infection. Anti-IL-1 and anti-IL-6 may interfere with the cytokine storm in severe cases and use of tocilizumab has shown good outcomes in a small cohort. Baricitinib has both antiviral and anti-inflammatory properties. Checkpoints inhibitors such as anti-CD200 and anti-PD1 could have a role in the treatment of CoViD-19. Rheumatic disease patients taking immunosuppressive drugs should be recommended to maintain the chronic therapy, prevent infection by avoiding social contacts and pausing immunosuppressants in case of infection. National and international registries are being created to collect data on rheumatic patients with CoViD-19.

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: $\alpha$-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: COVID-19 diagnosis prediction in emergency care patients: a machine learning approach The coronavirus disease (COVID-19) pandemic has increased the necessity of immediate clinical decisions and effective usage of healthcare resources. Currently, the most validated diagnosis test for COVID-19 (RT-PCR) is in shortage in most developing countries, which may increase infection rates and delay important preventive measures. The objective of this study was to predict the risk of positive COVID-19 diagnosis with machine learning, using as predictors only results from emergency care admission exams. We collected data from a sample of 235 adult patients from the Hospital Israelita Albert Einstein in Sao Paulo, Brazil, from 17 to 30 of March, 2020, of which 102 (43%) received a positive diagnosis of COVID-19 from RT-PCR tests. Five machine learning algorithms (neural networks, random forests, gradient boosting trees, logistic regression and support vector machines) were trained on a random sample of 70% of the patients, and performance was tested on new unseen data (30%). The best predictive performance was obtained by the support vector machines algorithm (AUC: 0.85; Sensitivity: 0.68; Specificity: 0.85; Brier Score: 0.16). In conclusion, we found that targeted decisions for receiving COVID-19 tests using only routinely-collected data is a promising new area with the use of machine learning algorithms.

negative: Covid-19 in South Korea. A novel coronavirus (severe acute respiratory syndrome-CoV-2) that initially originated from Wuhan, China, in December 2019 has already caused a pandemic. While this novel coronavirus disease (covid-19) frequently induces mild diseases, it has also generated severe diseases among certain populations, including older-aged individuals with underlying diseases, such as cardiovascular disease and diabetes. As of 31 March 2020, a total of 9786 confirmed cases with covid-19 have been reported in South Korea. South Korea has the highest diagnostic rate for covid-19, which has been the major contributor in overcoming this outbreak. We are trying to reduce the reproduction number of covid-19 to less than one and eventually succeed in controlling this outbreak using methods such as contact tracing, quarantine, testing, isolation, social distancing and school closure. This report aimed to describe the current situation of covid-19 in South Korea and our response to this outbreak.

negative: Research Communications of the 25th ECVIM‐CA Congress

negative: Coronavirus Disease 2019 (COVID-19) Pneumonia in a Hemodialysis Patient Coronavirus disease 2019 (COVID-19) is a highly infective disease caused by the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2). Previous studies of the COVID-19 pneumonia outbreak were based on information from the general population. Limited data are available for hemodialysis patients with COVID-19 pneumonia. This report describes the clinical characteristics of COVID-19 in an in-center hemodialysis patient, as well as our experience in implementing steps to prevent the spread of COVID-19 pneumonia among in-center hemodialysis patients. The diagnosis, infection control, and treatment of COVID-19 in hemodialysis patients are discussed in this report, and we conclude with recommendations for how a dialysis facility can respond to COVID-19 based on our experiences.

negative: Screening and managing of suspected or confirmed novel coronavirus (COVID-19) patients: experiences from a tertiary hospital outside Hubei province Objectives: To report our experiences screening and managing patients with suspected or confirmed novel coronavirus (COVID-19) disease using a hospital-specific protocol. Design: Longitudinal cohort study. Setting: A 1,200 bed tertiary care teaching hospital in Chengdu, Sichuan, China. Participants: 802 adults presenting to hospital with concerns of having COVID-19, 1,246 inpatients and 2,531 hospital visitors. Interventions: Screening and management of patients using a hospital-specific protocol, which included fever triage, monitoring visitors and patients, emergency response, personnel training for healthcare team members, health education for patients and family, medical materials management, disinfection and wastes disposal protocols. Results: Between 23 January and 28 February 2020, 73 people were identified as having fever plus respiratory signs with/without a history of exposure and were tested for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by our hospital lab using RT PCR. Forty-five of these 73 people were subsequently excluded based on one negative RT PCR result plus positive results to quick screening tests for flu or other respiratory viruses. The remaining 28 people received a second RT PCR test 24 h later. Three people were confirmed positive for COVID-19 based on two consecutive positive RT PCR tests whilst 25 people were excluded based on two consecutive negative tests. The three COVID-19 confirmed cases received non-critical care. There were no new infections of medical staff or new infections of other hospital inpatients. Conclusions: All three cases were detected as a result of vigilant monitoring of hospital visitors. Whilst screening out-patients presenting to a fever clinic remains important, monitoring visitors must not be overlooked.

negative: Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV–IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV–IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

negative: Molecular Detection of SARS-CoV-2 in Formalin Fixed Paraffin Embedded Specimens Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of human coronavirus disease 2019 (COVID-19), emerged in Wuhan, China in December 2019. The virus rapidly spread globally, resulting in a public-health crisis including more than one million cases and tens of thousands of deaths. Here, we describe the identification and evaluation of commercially available reagents and assays for the molecular detection of SARS-CoV-2 in infected formalin fixed paraffin embedded (FFPE) cell pellets. We identified a suitable rabbit polyclonal anti-SARS-CoV spike protein antibody and a mouse monoclonal anti-SARS-CoV nucleocapsid protein (NP) antibody for cross detection of the respective SARS-CoV-2 proteins by immunohistochemistry (IHC) and immunofluorescence assay (IFA). Next, we established RNAscope in situ hybridization (ISH) to detect SARS-CoV-2 RNA. Furthermore, we established a multiplex fluorescence ISH (mFISH) to detect positive-sense SARS-CoV-2 RNA and negative-sense SARS-CoV-2 RNA (a replicative intermediate indicating viral replication). Finally, we developed a dual staining assay using IHC and ISH to detect SARS-CoV-2 antigen and RNA in the same FFPE section. These reagents and assays will accelerate COVID-19 pathogenesis studies in humans and in COVID-19 animal models.

negative: Tracking the genomic footprints of SARS-CoV-2 transmission Abstract There is considerable public and scientific interest on the origin, spread and evolution of SARS-CoV-2. A recent study by Lu et al. [1], conducted genomic sequencing and analysis of SARS-CoV-2 in Guangdong, revealing its early transmission out of Hubei and shedding light on the effectiveness of controlling local transmission chains.

negative: Covid-19 and cardiovascular disease Guideline: Diagnosis and management of cardiovascular disease during the covid-19 pandemicPublished by the European Society of Cardiology.This summary is based on the version published on 21 April 2020 (https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance).

negative: End-of-life decisions and care in the midst of a global coronavirus (COVID-19) pandemic

negative: Comorbidities and multi-organ injuries in the treatment of COVID-19

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: Geographical disparities in emergency department presentations for acute respiratory infections and risk factors for presenting: a population-based cohort study of Western Australian children INTRODUCTION: Studies examining acute respiratory infections (ARIs) in emergency department (EDs), particularly in rural and remote areas, are rare. This study aimed to examine the burden of ARIs among Aboriginal and non-Aboriginal children presenting to Western Australian (WA) EDs from 2002 to 2012. METHOD: Using a retrospective population-based cohort study linking ED records to birth and perinatal records, we examined presentation rates for metropolitan, rural and remote Aboriginal and non-Aboriginal children from 469 589 births. We used ED diagnosis information to categorise presentations into ARI groups and calculated age-specific rates. Negative binomial regression was used to investigate association between risk factors and frequency of ARI presentation. RESULTS: Overall, 26% of presentations were for ARIs. For Aboriginal children, the highest rates were for those aged <12 months in the Great Southern (1233 per 1000 child-years) and Pilbara regions (1088 per 1000 child-years). Rates for non-Aboriginal children were highest in children <12 months in the Southwest and Kimberley (400 and 375 per 1000 child-years, respectively). Presentation rates for ARI in children from rural and remote WA significantly increased over time in all age groups <5 years. Risk factors for children presenting to ED with ARI were: male, prematurity, caesarean delivery and residence in the Kimberley region and lower socio-economic areas. CONCLUSION: One in four ED presentations in WA children are for ARIs, representing a significant out-of-hospital burden with some evidence of geographical disparity. Planned linkages with hospital discharge and laboratory detection data will aid in assessing the sensitivity and specificity of ARI diagnoses in ED.

negative: Modelling the transmission dynamics of COVID-19 in six high burden countries The new coronavirus disease, officially known as COVID-19, originated in China in 2019 and has since spread around the globe. We presented a modified Susceptible-Latent-Infected-Removed (SLIR) compartmental model of COVID-19 disease transmission with nonlinear incidence during the epidemic period. We provided the model calibration to estimate parameters with day wise corona virus (COVID-19) data i.e. reported cases by worldometer from the period of 15th February to 30th March, 2020 in six high burden countries including Australia, Italy, Spain, USA, UK and Canada. We estimate transmission rates for each countries and found that the highest transmission rate country in Spain, which may be increase the new cases and deaths in Spain than the other countries. Sensitivity analysis was used to identify the most important parameters through the partial rank correlation coefficient method. We found that the transmission rate of COVID-19 had the largest influence on the prevalence. We also provides the prediction of new cases in COVID-19 until May 18, 2020 using the developed model and recommends, control strategies of COVID-19. The information that we generated from this study would be useful to the decision makers of various organizations across the world including the Ministry of Health in Australia, Italy, Spain, USA, UK and Canada to control COVID-19.

negative: Gender differences in patients with COVID-19: Focus on severity and mortality Importance: The recent outbreak of Novel Coronavirus (SARS-CoV-2) Disease (COVID-19) has put the world on alert, that is reminiscent of the SARS outbreak seventeen years ago. Objective: We aim to compare the severity and mortality between male and female patients with both COVID-19 and SARS, to explore the most useful prognostic factors for individualized assessment. Design, Setting, and Participants: We extracted the data from a case series of 43 hospitalized patients we treated, a public data set of the first 37 cases died of COVID-19 in Wuhan city and 1019 survived patients from six cities in China. We also analyzed the data of 524 patients with SARS, including 139 deaths, from Beijing city in early 2003. Main Outcomes and Measures: Severity and mortality. Results: Older age and high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. The percentages of older age (≥65 years) were much higher in the deceased group than in the survived group in patients with both COVID-19 (83.8 vs. 13.2, P<0.001) and SARS (37.4 vs. 4.9, P<0.001). In the case series, men tend to be more serious than women (P=0.035), although age was comparable between men and women. In the public data set, age was also comparable between men and women in the deceased group or the survived group in patients with COVID-19. Meanwhile, gender distribution was exactly symmetrical in the 1019 survivors of COVID-19. However, the percentage of male were higher in the deceased group than in the survived group (70.3 vs. 50.0, P=0.015). The gender role in mortality was also observed in SARS patients. Survival analysis showed that men (hazard ratio [95% CI] 1.47 [1.05-2.06, P= 0.025) had a significantly higher mortality rate than women in patients with SARS. Conclusions and Relevance: Older age and male gender are risk factors for worse outcome in patients with COVID. While men and women have the same susceptibility to both SARS-CoV-2 and SARS-CoV, men may be more prone to have higher severity and mortality independent of age and susceptibility.

negative: Estimation of COVID-2019 burden and potential for international dissemination of infection from Iran The Coronavirus Disease 2019 (COVID-19) epidemic began in Wuhan, China in late 2019 and continues to spread globally, with exported cases confirmed in 28 countries at the time of writing. During the interval between February 19 and 23, 2020, Iran reported its first 43 cases with eight deaths. Three exported cases originating in Iran were identified, suggesting a underlying burden of disease in that country than is indicated by reported cases. A large epidemic in Iran could further fuel global dissemination of COVID-19. We sought to estimate COVID-19 outbreak size in Iran based on known exported case counts and air travel links between Iran and other countries, and to anticipate where infections originating in Iran may spread to next. We assessed interconnectivity between Iran and other countries using using International Air Transport Association (IATA) data. We used the methods of Fraser et al. to estimate the size of the underlying epidemic that would result in cases being observed in the United Arab Emirates (UAE), Lebanon, and Canada. Time at risk estimates were based on a presumed 6 week epidemic age, and length of stay data for visitors to Iran derived from the United Nations World Tourism Organization (UNWTO). We evaluated the relationship between the strength of travel links with Iran, and destination country rankings on the Infectious Disease Vulnerability Index (IDVI), a validated metric that estimates the capacity of a country to respond to an infectious disease outbreak . Scores range between 0-1, with higher scores reflecting greater capacity to manage infectious outbreaks. UAE, Lebanon, and Canada ranked 3rd, 21st, and 31st, respectively, for outbound air travel volume from Iran in February 2019. We estimated that 18,300 (95% confidence interval: 3770 to 53,470) COVID-19 cases would have had to occur in Iran, assuming an outbreak duration of 1.5 months in the country, in order to observe these three internationally exported cases reported at the time of writing. Results were robust under varying assumptions about undiagnosed case numbers in Syria, Azerbaijan and Iraq. Even if it were assumed that all cases were identified in all countries with certainty, the "best case" outbreak size was substantial (1820, 95% CI: 380-5320 cases), and far higher than reported case counts. Given the low volumes of air travel to countries with identified cases of COVID-19 with origin in Iran (such as Canada), it is likely that Iran is currently experiencing a COVID-19 epidemic of significant size for such exportations to be occurring. This is concerning, both for public health in Iran itself, and because of the high likelihood for outward dissemination of the epidemic to neighbouring countries with lower capacity to respond to infectious diseases epidemics.

negative: A Social Network Model of the COVID-19 Pandemic In the COVID-19 coronavirus pandemic, currently vaccines and specific anti-viral treatment are not yet available. Thus, preventing viral transmission by case isolation, quarantine, and social distancing is essential to slowing its spread. Here we model social networks using weighted graphs, where vertices represent individuals and edges represent contact. As public health measures are implemented, connectivity in the graph decreases, resulting in lower effective reproductive numbers, and reduced viral transmission. For COVID-19, model parameters were derived from the coronavirus epidemic in China, validated by epidemic data in Italy, then applied to the United States. We calculate that, in the U.S., the public is able to contain viral transmission by limiting the average number of contacts per person to less than 7 unique individuals over each 5 day period. This increases the average social distance between individuals to 10 degrees of separation.

negative: Assessment of the risk of infectious aerosols leaking to the environment from BSL-3 laboratory HEPA air filtration systems using model bacterial aerosols Abstract To assess the risk of infectious bacterial aerosols leaking to the environment, the filtration efficiency of a biosafety level 3 (BSL-3) laboratory high-efficiency particulate (HEPA) filter was investigated using the aerosolized bacteria Serratia marcescens. The aerosol size was measured using an Andersen sampler. Eight first stage HEPA filters (numbered 1–8) were distributed in contaminated labs and exhausts from each of the first stage HEPA filters were aggregated and filtered through one second stage HEPA filter before being released to the environment. In total, 8 first-stage and 1 second-stage HEPA filters from the BSL-3 air purification system were analyzed. No S. marcescens was detected in first stage filters 1, 2, 4, 5, 7 and 8 and the second stage HEPA filter. The filtration efficiencies against aerosolized S. marcescens were >99.9999%. First stage filter numbers 3 and 6 had filtration efficiencies of 99.9825% and 99.9906%, respectively. When filter number 3 was replaced by a new filter and the bracket for filter number 6 was sealed, no aerosolized S. marcescens was detected in the filtered air. Our work suggests that the BSL-3 laboratory HEPA filter air purification system is effective against bacterial aerosols, with little to no bacterial leakage into the environment.

negative: In the pipeline Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer Let’s take inventory on the therapies that are being developed for the coronavirus epidemic Here is a very thorough list of at Biocentury, and I should note that (like Stat and several other organizations) they’re making all their Covid-19 content free to all readers during this crisis I’d like to zoom in today on the potential small-molecule therapies, since some of these have the most immediate prospects for use in the real world The ones at the front of the line are repurposed drugs that are already approved for human use, for a lot of obvious reasons The Biocentury list doesn’t cover these, but here’s an article at Nature Biotechnology that goes into detail Clinical trials are a huge time sink – they sort of have to be, in most cases, if they’re going to be any good – and if you’ve already done all that stuff it’s a huge leg up, even if the drug itself is not exactly a perfect fit for the disease So what do we have? The compound that is most advanced is probably remdesivir from Gilead, at right This has been in development for a few years as an RNA virus therapy – it was originally developed for Ebola, and has been tried out against a whole list of single-strand RNA viruses That includes the related coronaviruses SARS and MERS, so Covid-19 was an obvious fit The compound is a prodrug – that phosphoramide gets cleaved off completely, leaving the active 5-OH compound GS-44-1524 It mechanism of action is to get incorporated into viral RNA, since it’s taken up by RNA polymerase and it largely seems to evade proofreading This causes RNA termination trouble later on, since that alpha-nitrile C-nucleoside is not exactly what the virus is expecting in its genome at that point, and thus viral replication is inhibited

negative: Community pharmacists and communication in the time of COVID-19: Applying the health belief model Abstract The emergence of the novel coronavirus disease (COVID-19) pandemic presents an unprecedented health communications challenge. Healthcare providers should reinforce behaviors that limit the spread of the pandemic, including social distancing and remaining in the home whenever possible. Formal communications toolkits may not be prepared in a timely fashion. Community pharmacists can reinforce mitigation behaviors by applying the health belief model (HBM). This commentary provides an overview of the HBM and offers suggestions on how community pharmacists can use it as a guide to patient communication in these uncertain contexts.

negative: Initiation of a new infection control system for the COVID-19 outbreak

negative: Replication of a bovine coronavirus in organ cultures of foetal trachea Abstract A strain of bovine coronavirus (BC) adapted to tissue culture, was inoculated into organ cultures of bovine foetal trachea. Haemagglutinin in the fluid from infected organ cultures reached titres of 32 and characteristic coronavirus particles were observed electron microscopically. BC virus antigen was detected in frozen sections of the organ cultures by staining with fluorescent antibody. These data were evidence that BC virus replicated in organ cultures of respiratory tissue. The use of this technique for primary isolation of bovine coronaviruses from field material is discussed.

negative: Astroviruses Astroviruses are positive-sense, single-stranded RNA viruses. Their genomes contain three open reading frames, but the exact number of encoded proteins remains unknown. Astroviruses were originally identified in association with childhood diarrhea; subsequently, they have been identified as a common enteric virus infecting children under the age of 2. Infection is not restricted to humans, however, and host-specific astroviruses have been found in association with a variety of mammalian and avian species. Generally, infection causes a mild, self-limiting gastroenteritis, although infection in chickens and ducklings can result in nephritis or severe hepatitis, respectively. The immune response to astrovirus infection is only poorly characterized and may differ between mammalian and avian species. In this article, the current knowledge of astroviruses is reviewed, including their molecular virology, viral evolution, pathogenesis, and immune response.

negative: Wet markets—a continuing source of severe acute respiratory syndrome and influenza? Summary Context Live-animal markets (wet markets) provide a source of vertebrate and invertebrate animals for customers in tropical and subtropical regions of the world. Wet markets sell live poultry, fish, reptiles, and mammals of every kind. Live-poultry markets (mostly chicken, pigeon, quail, ducks, geese, and a wide range of exotic wild-caught and farm-raised fowl) are usually separated from markets selling fish or red-meat animals, but the stalls can be near each other with no physical separation. Despite the widespread availability of affordable refrigeration, many Asian people prefer live animals for fresh produce. Wet markets are widespread in Asian countries and in countries where Asian people have migrated. Live-poultry markets were the source of the H5N1 bird-influenza virus that transmitted to and killed six of 18people in Hong Kong. Starting point Yi Guan and colleagues (Science 2003; 302: 276–78) recently reported the isolation of severe acute respiratory syndrome (SARS) coronavirus (CoV) from Himalayan palm civets (Paguna larvata) in wet markets in Shenzen, southern China. These researchers also found serological evidence of infection in raccoon dogs (Nyctereutes pro-cuyoinboides). Serological evidence for SARS CoV in human beings working in these markets, taken together with the earliest cases of SARS in restaurant workers, supports the contention of a potential zoonotic origin for SARS. Where next? Will SARS reappear? This question confronts public-health officials worldwide, particularly infectious disease personnel in those regions of the world most affected by the disease and the economic burden of SARS, including China, Taiwan, and Canada. Will the virus re-emerge from wet markets or from laboratories working with SARS CoV, or are asymptomatic infections ongoing in human beings? Similar questions can be asked about a pandemic of influenza that is probably imminent. Knowledge of the ecology of influenza in wet markets can be used as an early-warning system to detect the reappearance of SARS or pandemic influenza.

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: Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5, and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV, and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P = 0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin.

negative: STUDIES ON NEW VIRUS ISOLATES RECOVERED IN TRACHEAL ORGAN CULTURE

negative: Response to COVID-19 by the surgical community

negative: Elevated expression of ACE2 in tumor-adjacent normal tissues of cancer patients The rapidly developing COVID-19 pandemic has raised a concern that cancer patients may have increased susceptibility to SARS-CoV-2 infection. This discussion has mostly focused on therapy-induced immune suppression. Here, we examined the expression patterns of ACE2, the receptor through which SARX-CoV2 enters human cells, and found that ACE2 mRNA levels are elevated in tumor-adjacent normal tissues of cancer patients, including in normal-adjacent lung tissues of lung cancer patients. These observations raise the possibility that the elevated COVID-19 risk of cancer patients may not be limited to those undergoing immune-suppressing treatment.

negative: At the Heart of the Matter: Unmasking and Addressing COVID-19's Toll on Diverse Populations

negative: 2518. The Role of Non-Influenza Viruses in the Seasonal Viral Respiratory Illness: A Epidemiologic Study From October 2016–March 2017 BACKGROUND: Influenza virus (IV) is a leading cause of morbidity and mortality worldwide; however, understanding the contribution of non-influenza viruses (NIV) to the annual burden of respiratory illnesses (RI) is evolving. Improvements in diagnostic techniques, including the increasing clinical use of respiratory viral PCR panels (vPCR), have markedly advanced our understanding of the contributions of NIV to the “influenza season.” METHODS: A retrospective analysis of all vPCR results from one hospital system, collected between October 1, 2016 and March 7, 2017, including inpatient and outpatient samples was performed. 2,047 vPCR tests were reviewed; after removing those with undetermined results and internal control samples, 1,924 were analyzed. Data points abstracted included detection and identification of virus, and date of detection. We compared the total and monthly rates of NIV with IV, throughout the study period. RESULTS: Of 1,924 vPCR results, 985 (51%) were positive for a respiratory virus. Of these, 302 (31%) were IV, and 683 (69%) were NIV. For every month studied, the ratio of NIV to IV exceeded 50%, including the height of the season. The most commonly detected viruses were Influenza A (30%), Rhino/Enterovirus (24%), RSV (19%), Coronavirus OC43 (7%) and Metapneumovirus (5%). The peak influenza incidence temporally coincided with the national peak months of January and February. The NIV incidence paralleled the trend in IV incidence, dominated by Rhino/Enterovirus and RSV, but without a specific virus driving the trend. CONCLUSION: Non-influenza respiratory viruses cause substantial viral RI during the winter months. Many viral syndromes during the height of influenza season have traditionally been attributed to IV, including influenza-like-illness (ILI); however, these can now be better characterized using patient-specific vPCR panels, leading to improved understanding of NIV epidemiology. Even during the period of highest IV incidence, NIV infections were more common than IV. Understanding the high prevalence of NIV infections may improve the judicious use of both antibiotics and antivirals. There may also be a role for refinement of ILI, including best practices for diagnosis and treatment. DISCLOSURES: All Authors: No reported disclosures.

negative: Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases PURPOSE: Infection with COVID-19 potentially can result in severe outcomes and death from “cytokine storm syndrome”, resulting in novel coronavirus pneumonia (NCP) with severe dyspnea, acute respiratory distress syndrome (ARDS), fulminant myocarditis and multiorgan dysfunction with or without disseminated intravascular coagulation. No published treatment to date has been shown to adequately control the inflammation and respiratory symptoms associated with COVID-19, apart from oxygen therapy and assisted ventilation. We evaluated the effects of using high dose oral and/or IV glutathione in the treatment of 2 patients with dyspnea secondary to COVID-19 pneumonia. METHODS: Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms. CONCLUSION: Oral and IV glutathione, glutathione precursors (N-acetyl-cysteine) and alpha lipoic acid may represent a novel treatment approach for blocking NF-κB and addressing “cytokine storm syndrome” and respiratory distress in patients with COVID-19 pneumonia.

negative: Origins of the 1918 Pandemic: Revisiting the Swine “Mixing Vessel” Hypothesis How influenza A viruses host-jump from animal reservoir species to humans, which can initiate global pandemics, is a central question in pathogen evolution. The zoonotic and spatial origins of the influenza virus associated with the “Spanish flu” pandemic of 1918 have been debated for decades. Outbreaks of respiratory disease in US swine occurred concurrently with disease in humans, raising the possibility that the 1918 virus originated in pigs. Swine also were proposed as “mixing vessel” intermediary hosts between birds and humans during the 1957 Asian and 1968 Hong Kong pandemics. Swine have presented an attractive explanation for how avian viruses overcome the substantial evolutionary barriers presented by different cellular environments in humans and birds. However, key assumptions underpinning the swine mixing-vessel model of pandemic emergence have been challenged in light of new evidence. Increased surveillance in swine has revealed that human-to-swine transmission actually occurs far more frequently than the reverse, and there is no empirical evidence that swine played a role in the emergence of human influenza in 1918, 1957, or 1968. Swine-to-human transmission occurs periodically and can trigger pandemics, as in 2009. But swine are not necessary to mediate the establishment of avian viruses in humans, which invites new perspectives on the evolutionary processes underlying pandemic emergence.

negative: Origins and pathogenesis of Middle East respiratory syndrome-associated coronavirus: recent advances Middle East respiratory syndrome-associated coronavirus (MERS-CoV) has been a significant research focus since its discovery in 2012. Since 2012, 2,040 cases and 712 deaths have been recorded (as of August 11, 2017), representing a strikingly high case fatality rate of 36%. Over the last several years, MERS-CoV research has progressed in several parallel and complementary directions. This review will focus on three particular areas: the origins and evolution of MERS-CoV, the challenges and achievements in the development of MERS-CoV animal models, and our understanding of how novel proteins unique to MERS-CoV counter the host immune response. The origins of MERS-CoV, likely in African bats, are increasingly clear, although important questions remain about the establishment of dromedary camels as a reservoir seeding human outbreaks. Likewise, there have been important advances in the development of animal models, and both non-human primate and mouse models that seem to recapitulate human disease are now available. How MERS-CoV evades and inhibits the host innate immune response remains less clear. Although several studies have identified MERS-CoV proteins as innate immune antagonists, little of this work has been conducted using live virus under conditions of actual infection, but rather with ectopically expressed proteins. Accordingly, considerable space remains for major contributions to understanding unique ways in which MERS-CoV interacts with and modulates the host response. Collectively, these areas have seen significant advances over the last several years but continue to offer exciting opportunities for discovery.

negative: Cross‐Species Transmission of Deltacoronavirus and the Origin of Porcine Deltacoronavirus Deltacoronavirus is the last identified Coronaviridae subfamily genus. Differing from other coronavirus (CoV) genera, which mainly infect birds or mammals, deltacoronaviruses (δ‐CoVs) reportedly infect both animal types. Recent studies show that a novel δ‐CoV, porcine deltacoronavirus (PDCoV), can also infect calves and chickens with the potential to infect humans, raising the possibility of cross‐species transmission of δ‐CoVs. Here, we explored the deep phylogenetic history and cross‐species transmission of δ‐CoVs. Virus–host co‐phylogenetic analyses showed that δ‐CoVs have undergone frequent host switches in birds, and sparrows may serve as the unappreciated hubs for avian to mammal transmission. Our molecular clock analyses show that PDCoV possibly originated in Southeast Asia in the 1990s, and that the PDCoV cluster shares a common ancestor with Sparrow‐CoV of around 1810. Our findings contribute valuable insights into the diversification, evolution, and interspecies transmission of δ‐CoVs and the origin of PDCoV, providing a model for exploring the relationships of δ‐CoVs in birds and mammals.

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

negative: SARS-CoV-2 detection from nasopharyngeal swab samples without RNA extraction The ongoing COVID-19 pandemic has reached more than 200 countries and territories worldwide. Given the large requirement of SARS-CoV-2 diagnosis and considering that RNA extraction kits are in short supply, we investigated whether two commercial RT-qPCR kits were compatible with direct SARS-CoV-2 detection from nasopharyngeal swab samples. We show that one of the tested kits is fully compatible with direct SARS-CoV-2 detection suggesting that omission of an RNA extraction step should be considered in SARS-CoV-2 diagnosis.

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: Estimation of Coronavirus Disease 2019 (COVID-19) Burden and Potential for International Dissemination of Infection From Iran

negative: Hypertransaminasemia in the course of infection with SARS-CoV-2: Incidence and pathogenetic hypothesis In patients infected with severe acute respiratory syndrome coronavirus 2, the respiratory symptoms, such as fever, cough and dyspnea, are the most frequent clinical manifestations. These patients may also present with less well-defined symptoms like diarrhea, nausea, vomiting and/or abdominal discomfort both at the time of diagnosis and during the clinical course. In a few cases, these symptoms may also present before the appearance of respiratory symptoms. To penetrate the body, Severe acute respiratory syndrome coronavirus 2 uses ACE2 receptors, which are present not only in respiratory epithelium but also in gastrointestinal mucosa and liver cholangiocytes. In several cases, viral RNA is detectable in the stool of patients with coronavirus disease 2019 (COVID-19). The liver damage seems to show a multifactorial origin. About 2%-11% of patients with COVID-19 have known underlying hepatic pathologies. In 14%-53% of COVID-19 cases, there is an alteration of the indices of liver cytolysis and is more frequently observed in severe forms of COVID-19, especially during hospitalization.

negative: Origin and transmission of Feline coronavirus type I in domestic cats from Northern Italy: a phylogeographic approach Feline coronavirus (FCoV) is responsible, along with an inadequate immune response of the host, for Feline infectious peritonitis (FIP), one of the most frequent and deadly infectious feline disease worldwide. This study analyzed the genetic characteristics of the spike (S) gene of 33 FCoVs circulating in Northern Italy between 2011 and 2015 in cats with or without FIP. In order to reconstruct the most probable places of origin and dispersion of FCoV among Italian cats, a phylogeographic approach was performed based on 106 FCoV S gene partial sequences from cats, including the 33 novel Italian sequences and 73 retrieved from public databases. Only FCoV type I was found in the Italian cats. The estimated mean evolutionary rate of FCoV was 2.4 × 10(-2) subs/site/year (95% HPD: 1.3-3.7 × 10(-2)), confirming the high genetic variability in the circulating strains. All the isolates clustered in a unique highly significant clade that likely originated from USA between the 1950s and the 1970s, confirming the first descriptions of the disease in American cats. Our results suggest that from USA the virus likely entered Germany and thereafter spread to other European countries. Phylogeography showed that sequences segregated mainly by geographical origin. In the 2010s Italian sequences clustered in different subclades, confirming that different strains cocirculate in Italy. Further studies on archival samples and other genetic regions of FCoV are suggested in order to confirm the present results and to reconstruct a more in-depth detailed virus dispersion pattern for the definition of possible control measures.

negative: Is the kidney a target of SARS-CoV-2? The new disease produced by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible virus, and it is associated to a broad clinical spectrum going from subclinical presentation to severe respiratory distress and multiorgan failure. Like other coronaviruses, SARS-CoV-2 recognizes human angiotensin-converting enzyme 2 as a cellular receptor that allows it to infect different host cells and likely disrupts renin-angiotensin-aldosterone system homeostasis. Particularly, a considerable incidence of many renal abnormalities associated to COVID-19 has been reported, including proteinuria, hematuria, and acute kidney injury. Moreover, it has been recently demonstrated that SARS-CoV-2 can infect podocytes and tubular epithelial cells, which could contribute to the development of the aforementioned renal abnormalities. In this review, we discuss the biological aspects of SARS-CoV-2 infection, how understanding current knowledge about SARS-CoV-2 infection may partly explain the involvement of the kidneys in the pathophysiology of COVID-19, and what questions have arisen and remain to be explored.

negative: A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV The outbreak of COVID-19 caused by SARS-CoV-2 virus has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein to 3.1 Å. CR3022 targets a highly conserved epitope, distal from the receptor-binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBD on the trimeric S protein are in the “up” conformation and slightly rotated. Overall, this study provides molecular insights into antibody recognition of SARS-CoV-2.

negative: People at Risk of Influenza Pandemics: The Evolution of Perception and Behavior Influenza pandemics can severely impact human health and society. Understanding public perception and behavior toward influenza pandemics is important for minimizing the effects of such events. Public perception and behavior are expected to change over the course of an influenza pandemic, but this idea has received little attention in previous studies. Our study aimed to understand the dynamics of public perception and behavior over the course of the 2009 H1N1 influenza pandemic. Three consecutive cross-sectional surveys were administered among Beijing residents with random-digit dialing techniques in March 2008 and August and November 2009. Effective samples of 507, 508 and 1006 respondents were interviewed in each of the three surveys, respectively. The mean scores of risk perception were low to moderate across the three surveys. The perceived risk of infection of self was significantly lower than that of the community, revealing an optimistic bias. Longitudinally, the perceived risk of contracting H1N1 increased, whereas the perceived risk of being unable to obtain medicine and medical care once influenza permeated the community first increased and then decreased. Responsive actions toward influenza varied. Most respondents took actions that required little extra effort, such as ventilating rooms; these actions did not change over time. Comparatively, a smaller number of respondents took actions for coping with influenza, such as vaccination; however, these actions were taken by an increasing number of respondents over time. The association between risk perception and behavior was unstable. Positive, insignificant, and negative associations were obtained in the three surveys. In conclusion, the evolving patterns of risk perception and responsive behavior over the course of an influenza pandemic are sensitive to how risk and behavior are defined and scoped.

negative: 2 US federal oversight of biological materials and the IBC Abstract This chapter will give a thorough overview of the laws and guidelines regulating research use of biological materials in the United States and how Institutional Biosafety Committees (IBC) came to be tasked with providing oversight for these activities. The anthrax attacks after 9/11 demonstrated that information gained from life science research can be used to threaten national security and public health. Since these attacks, the public has demanded increased oversight of research. IBC oversight falls under the National Institutes of Health Guidelines. Over the years, other federal agencies have increased the demands on the IBC by promulgating new legislation and regulations. The following agencies play a role in regulating research: National Science Advisory Board for Biosecurity, National Research Council, National Institutes of Health, Food and Drug Administration, Environmental Protection Agency, Department of Human and Health Services, U.S. Department of Agriculture, and Department of Justice.

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: COVID‐19 is a challenge for dental education—A commentary The COVID‐19, which appeared to originate in China in December 2019, has spread worldwide pandemically. In this commentary, authors described this new challenge for dental education using the recent literature and experience gained in the Italian University of Catanzaro.

negative: The Panhandle Formed by Influenza A and C Virus NS Non-Coding Regions Determines NS Segment Expression Exchange of the extremities of the NS segment of type A and C influenza viruses in reverse genetics systems was used to assess their putative role in type specificity. Restoration of each specific proximal panhandle was mandatory to allow the rescue of viruses with heterotypic extremities. Moreover, the transcription level of the modified segment seemed to be directly affected by the distal panhandle strength.

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: Novel astroviruses in insectivorous bats. Bats are increasingly recognized to harbor a wide range of viruses, and in most instances these viruses appear to establish long-term persistence in these animals. They are the reservoir of a number of human zoonotic diseases including Nipah, Ebola, and severe acute respiratory syndrome. We report the identification of novel groups of astroviruses in apparently healthy insectivorous bats found in Hong Kong, in particular, bats belonging to the genera Miniopterus and Myotis. Astroviruses are important causes of diarrhea in many animal species, including humans. Many of the bat astroviruses form distinct phylogenetic clusters in the genus Mamastrovirus within the family Astroviridae. Virus detection rates of 36% to 100% and 50% to 70% were found in Miniopterus magnater and Miniopterus pusillus bats, respectively, captured within a single bat habitat during four consecutive visits spanning 1 year. There was high genetic diversity of viruses in bats found within this single habitat. Some bat astroviruses may be phylogenetically related to human astroviruses, and further studies with a wider range of bat species in different geographic locations are warranted. These findings are likely to provide new insights into the ecology and evolution of astroviruses and reinforce the role of bats as a reservoir of viruses with potential to pose a zoonotic threat to human health.

negative: SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability The emergence of SARS-CoV-2 has resulted in more than 200,000 infections and nearly 9,000 deaths globally so far. This novel virus is thought to have originated from an animal reservoir, and acquired the ability to infect human cells using the SARS-CoV cell receptor hACE2. In the wake of a global pandemic it is essential to improve our understanding of the evolutionary dynamics surrounding the origin and spread of a novel infectious disease. One way theory predicts selection pressures should shape viral evolution is to enhance binding with host cells. We first assessed evolutionary dynamics in select betacoronavirus spike protein genes to predict where these genomic regions are under directional or purifying selection between divergent viral lineages at various scales of relatedness. With this analysis, we determine a region inside the receptor-binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein and its union with human receptor hACE2. Next, to gain further insights into factors associated with coronaviruses recognition of the human host receptor, we performed modeling studies of five different coronaviruses and their potential binding to hACE2. Modeling results indicate that interfering with the salt bridges at hot spot 353 could be an effective strategy for inhibiting binding, and hence for the prevention of coronavirus infections. We also propose that a glycine residue at the receptor binding domain of the spike glycoprotein can have a critical role in permitting bat variants of the coronaviruses to infect human cells.

negative: SARS virus: The beginning of the unraveling of a new coronavirus Severe acute respiratory syndrome (SARS) virus caused a severe outbreak in several regions of the world in 2003. The virus is a novel coronavirus, which may have an origin in wild animals such as civet cats in southern China. Its genome structure, gene expression pattern and protein profiles are similar to those of other coronaviruses. However, distinct patterns of several open reading frames in the SARS virus genome may contribute to its severe virulence. The potential mutability of the coronavirus genome may pose problems in the control of future SARS outbreaks. The mechanism of SARS pathogenesis may involve both direct viral cytocidal effects on the target cells and immune-mediated mechanisms. The life cycle of the SARS virus is largely unknown; however, based on the analogy with other coronaviruses, several potential targets for antiviral development are identified. Vaccines offer an important preventive measure for possible future recurrences of SARS, but the prospect for their development is still unknown because of the uncertainty regarding the role of immune responses in SARS virus pathogenesis. The comparative studies of other coronaviruses offer insights into the understanding of SARS virus.

negative: Does infection of 2019 novel coronavirus cause acute and/or chronic sialadenitis? 2019 novel coronavirus (2019-nCoV) is widespread in China and other countries. The target of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV) is angiotensin-converting enzyme 2 (ACE2) positive cells. ACE2 is present in the salivary gland duct epithelium, and thus it could be the target of 2019-nCoV and SARS-CoV. SARS-CoV-related animal model experiments show that it can infect the epithelial cells on the salivary gland duct in Chinese rhesus macaques by targeting ACE2. Clinical studies confirmed that 2019-nCoV and SARS-CoV could be detected in saliva of human patients. We hypothesize that the infection of 2019-nCoV and SARS-CoV will lead to inflammatory pathological lesions in patients' target organs, and possibly inflammatory lesions in salivary glands. 2019-nCoV may cause acute sialoadenitis in the acute phase of infection. After the acute phase, chronic sialoadenitis may be caused by fibrosis repairment. Although there was no direct evidence to prove this, the available indirect evidence indicates a high probability of our hypothesis.

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: Introductions and early spread of SARS-CoV-2 in the New York City area New York City (NYC) has emerged as one of the epicenters of the current SARS-CoV-2 pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus causing COVID-19 in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV2 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. Moreover, we find evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.

negative: Global trends in infectious diseases at the wildlife-livestock interface. The role and significance of wildlife-livestock interfaces in disease ecology has largely been neglected, despite recent interest in animals as origins of emerging diseases in humans. Scoping review methods were applied to objectively assess the relative interest by the scientific community in infectious diseases at interfaces between wildlife and livestock, to characterize animal species and regions involved, as well as to identify trends over time. An extensive literature search combining wildlife, livestock, disease, and geographical search terms yielded 78,861 publications, of which 15,998 were included in the analysis. Publications dated from 1912 to 2013 and showed a continuous increasing trend, including a shift from parasitic to viral diseases over time. In particular there was a significant increase in publications on the artiodactyls-cattle and bird-poultry interface after 2002 and 2003, respectively. These trends could be traced to key disease events that stimulated public interest and research funding. Among the top 10 diseases identified by this review, the majority were zoonoses. Prominent wildlife-livestock interfaces resulted largely from interaction between phylogenetically closely related and/or sympatric species. The bird-poultry interface was the most frequently cited wildlife-livestock interface worldwide with other interfaces reflecting regional circumstances. This review provides the most comprehensive overview of research on infectious diseases at the wildlife-livestock interface to date.

negative: Minimally invasive nephron-sparing surgery for unilateral Wilms tumor. Minimally invasive surgery (MIS) for nephrectomy has been described since the early 1990s. More recently, MIS has been used for nephron-sparing surgery (NSS) when treating benign conditions. However, reports of NSS using MIS for malignant conditions are sparse. In this report, we describe our retroperitoneal laparoscopic approach for NSS for a localized Wilms tumor.

negative: Search for trends of Covid-19 infection in India, China, Denmark, Brazil, France. Germany and the USA on the basis of power law scaling The corona virus (SARS-CoV-2) or Covid-19 pandemic is growing alarmingly throughout the whole world. Using the power law scaling we analyze the data of different countries and three states of India up to 1st April, 2020 and explain in terms of power law exponent. We find significant reduction in growth of infections in China and Denmark (g reduced from approximately 2.18 to 0.05 and 11.41 to 6.95, respectively). Very slow reduction is also seen in Brazil and Germany (g reduced from approximately 6 to 4 and 11 to 7, respectively). Infection in India is growing (g=9.23) though lesser in number than that in the USA (highest g of 16 approximately, studied so far), Italy and a few other countries. Among three Indian states the growth in West Bengal (g=0.64) is much slower than other states like Maharashtra and Kerala (g=3.23 and 3.32, respectively). Some future predictions, though not rigid, has also been incorporated in our analysis. The earlier lock-down and stricter measures from the Governments concerned are being thought to be the only possible solutions, in the present situation, to fight against this virus.

negative: Biosafety and biosecurity approaches to restrain/contain and counter SARS-CoV-2/COVID-19 pandemic: a rapid-review Emergence and reemergence of infectious diseases pose significant public health risks that are continuously haunting human civilization in the past several decades. Such emerging pathogens should be considered as a high threat to humans, animals, and environmental health. The year 2020 was welcomed by another significant virus from family Coronaviridae called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease 2019 (COVID-19). The disease was first reported in the city of Wuhan, Hubei province, China. Within a short time, this disease attained the status of the Public Health Emergency of International Concern. Presently, COVID-19 has spread to more than 150 countries, therefore, the World Health Organization (WHO) called it a pandemic. The Chinese government, along with WHO, other health agencies, and many nations, are monitoring the current situation closely to analyze the impact of SARS-CoV-2/COVID-19 on humans, animals, and environmental health. In the context of the current situation, biosafety and biosecurity measure that focus on One Health aspects of the disease outbreaks and the SARS-CoV-2 spread are of great importance to restrain this pathogen. Along with these efforts, standard precaution and control measures should also be taken at personal and community level to prevent the spreading of any contagion diseases, including COVID-19. Researchers are putting their very high efforts to develop suitable vaccines and therapeutics/drugs to combat COVID-19. This review aims to highlight the importance of biosafety, biosecurity, One Health approach, and focusing on recent developments and the ways forward to prevent and control COVID-19 in a useful way.

negative: Emerging diseases. New coronavirus reveals some of its secrets.

negative: Active surveillance for suspected COVID-19 cases in inpatients with information technology

negative: Research methodology and characteristics of journal articles with original data, preprint articles and registered clinical trial protocols about COVID-19 BACKGROUND: The research community reacted rapidly to the emergence of COVID-19. We aimed to assess characteristics of journal articles, preprint articles, and registered trial protocols about COVID-19 and its causal agent SARS-CoV-2. METHODS: We analyzed characteristics of journal articles with original data indexed by March 19, 2020, in World Health Organization (WHO) COVID-19 collection, articles published on preprint servers medRxiv and bioRxiv by April 3, 2010. Additionally, we assessed characteristics of clinical trials indexed in the WHO International Clinical Trials Registry Platform (WHO ICTRP) by April 7, 2020. RESULTS: Among the first 2118 articles on COVID-19 published in scholarly journals, 533 (25%) contained original data. The majority was published by authors from China (75%) and funded by Chinese sponsors (75%); a quarter was published in the Chinese language. Among 312 articles that self-reported study design, the most frequent were retrospective studies (N = 88; 28%) and case reports (N = 86; 28%), analyzing patients’ characteristics (38%). Median Journal Impact Factor of journals where articles were published was 5.099. Among 1088 analyzed preprint articles, the majority came from authors affiliated in China (51%) and were funded by sources in China (46%). Less than half reported study design; the majority were modeling studies (62%), and analyzed transmission/risk/prevalence (43%). Of the 927 analyzed registered trials, the majority were interventional (58%). Half were already recruiting participants. The location for the conduct of the trial in the majority was China (N = 522; 63%). The median number of planned participants was 140 (range: 1 to 15,000,000). Registered intervention trials used highly heterogeneous primary outcomes and tested highly heterogeneous interventions; the most frequently studied interventions were hydroxychloroquine (N = 39; 7.2%) and chloroquine (N = 16; 3%). CONCLUSIONS: Early articles on COVID-19 were predominantly retrospective case reports and modeling studies. The diversity of outcomes used in intervention trial protocols indicates the urgent need for defining a core outcome set for COVID-19 research. Chinese scholars had a head start in reporting about the new disease, but publishing articles in Chinese may limit their global reach. Mapping publications with original data can help finding gaps that will help us respond better to the new public health emergency.

negative: COVID-19 in Hemodialysis Patients: A Report of 5 Cases In December 2019, an outbreak of coronavirus disease (COVID-19) due to the novel SARS-CoV-2 virus began in China and spread rapidly worldwide. It is unknown whether hemodialysis patients represent a distinct group of patients with certain characteristics that may make them susceptible to infection or severe disease. In this Case Report, we describe the clinical and epidemiological features of COVID-19 in 201 maintenance hemodialysis patients in Zhongnan Hospital of Wuhan university, including 5 maintenance hemodialysis patients who contracted COVID-19 disease. Of the 5 patients with COVID-19, one had a definite history of contact with an infected person. The age range of the patients was 47–67 years. Diarrhea (80%), fever (60%), and fatigue (60%) were the most common symptoms. Lymphopenia occurred in all patients.Chest computerized tomography (CT) scans showed ground glass opacity in the lungs of all patients. Up to February 13, 2020, none of the patients had developed severe complications (acute respiratory distress syndrome, shock, multiple organ dysfunction) or died.

negative: Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Review Since its origin in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a pandemic and spread to 209 countries. As coronavirus disease 2019 (COVID-19) is a very rapidly emerging disease, organ-specific studies related to it have been reported. Apart from respiratory findings, some studies have highlighted inflammatory consequences in the heart, kidney, and/or liver as well. Cardiac involvement in COVID-19 seems to be a result of an inflammatory storm in response to the infection. Moreover, direct viral invasion of cardiomyocytes, as well as a myocardial injury due to oxidative stress, may account for acute cardiac injury in COVID-19. Nevertheless, the mechanism of heart injury in COVID-19 is not clear yet. However, multiple studies that highlight the clinical features, laboratory findings, and prognosis of acute myocardial injury (AMI) in COVID-19-affected individuals have been published. In this review, we have summarized the findings of all those studies as well as the clinical features and management of cardiac injury discussed by some case reports.

negative: Defining the Epidemiology of Covid-19 - Studies Needed.

negative: Influence of the intestinal microbiota on disease susceptibility in kittens with experimentally-induced carriage of atypical enteropathogenic Escherichia coli. Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection can be found in individuals with and without diarrhea. It remains unclear to what extent, under what conditions, or by what mechanisms aEPEC serves as a primary pathogen in individuals with diarrhea. It seems likely that a combination of host and bacterial factors enable aEPEC to cause disease in some individuals and not in others. The purpose of this study was to determine the impact of aEPEC on intestinal function and diarrhea in kittens following experimentally-induced carriage and the influence of a disrupted intestinal microbiota on disease susceptibility. Results of this study identify aEPEC as a potential pathogen in kittens. In the absence of disruption to the intestinal microbiota, kittens are resistant to clinical signs of aEPEC carriage but demonstrate significant occult changes in intestinal absorption and permeability. Antibiotic-induced disruption of the intestinal microbiota prior to infection increases subsequent intestinal water loss as determined by % fecal wet weight. Enrichment of the intestinal microbiota with a commensal member of the feline mucosa-associated microbiota, Enterococcus hirae, ameliorated the effects of aEPEC experimental infection on intestinal function and water loss. These observations begin to unravel the mechanisms by which aEPEC infection may be able to exploit susceptible hosts.

negative: The Effectiveness of Social Distancing in Mitigating COVID-19 Spread: a modelling analysis Background The novel coronavirus COVID19 has been classified by the World Health Organisation as a pandemic due to its worldwide spread. The ability of countries to contain and control transmission is critical in the absence of a vaccine. We evaluated a range of social distancing measures to determine which strategies are most effective in reducing the peak daily infection rate, and consequential pressure on the health care system. Methods Using COVID19 transmission data from the outbreak source in Hubei Province, China, collected prior to activation of containment measures, we adapted an established individual based simulation model of the city of Newcastle, Australia, population 272,409. Simulation of virus transmission in this community model without interventions provided a baseline from which to compare alternative social distancing strategies. The infection history of each individual was determined, as was the time infected. From this model generated data, the rate of growth in cases, the magnitude of the epidemic peak, and the outbreak duration were obtained. Findings The application of all four social distancing interventions: school closure, workplace non-attendance, increased case isolation, and community contact reduction is highly effective in flattening the epidemic curve, reducing the maximum daily case numbers, and lengthening outbreak duration. These were also found to be effective even after 10 weeks delay from index case arrivals. The most effective single intervention was found to be increasing case isolation, to 100 percent of children and 90 percent of adults. Interpretation As strong social distancing intervention strategies had the most effect in reducing the epidemic peak, this strategy may be considered when weaker strategies are first tried and found to be less effective. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society. Tradeoffs may need to be made between the effectiveness of social distancing strategies and population willingness to adhere to them.

negative: The spatiotemporal estimation of the dynamic risk and the international transmission of 2019 Novel Coronavirus (COVID-19) outbreak: A global perspective An ongoing novel coronavirus SARS-CoV-2 pneumonia infection outbreak called COVID-19 started in Wuhan, Hubei Province, China, in December 2019. It both spread rapidly to all provinces in China and started spreading around the world quickly through international human movement from January 2020. Currently, the spatiotemporal epidemic transmission patterns, prediction models, and possible risk analysis for the future are insufficient for COVID-19 but we urgently need relevant information, particularly from the global perspective. We have developed a novel two-stage simulation model to simulate the spatiotemporal changes in the number of COVID-19 cases and estimate the future worldwide risk. Based on the connectivity of countries to China and the country's medical and epidemic prevention capabilities, different scenarios are generated to analyze the possible transmission throughout the world and use this information to evaluate each country's vulnerability to and the dynamic risk of COVID-19. Countries' vulnerability to the COVID-19 outbreak from China is calculated for 63 countries around the world. Taiwan, South Korea, Hong Kong, and Japan are the most vulnerable areas. The relationship between each country's vulnerability and days before the first imported case occurred shows a very high exponential decrease. The cumulative number of cases in each country also has a linear relationship with vulnerability, which can compare and quantify the initial epidemic prevention capabilities to various countries' management strategies. In total, 1,000 simulation results of future cases around the world are generated for the spatiotemporal risk assessment. According to the simulation results of this study, if there is no specific medicine for it, it will likely form a global pandemic. This method can be used as a preliminary risk assessment of the spatiotemporal spread for a new global epidemic. * Note: This study was completed on February 15, 2020.

negative: False-Negative Results of Real-Time Reverse-Transcriptase Polymerase Chain Reaction for Severe Acute Respiratory Syndrome Coronavirus 2: Role of Deep-Learning-Based CT Diagnosis and Insights from Two Cases The epidemic of 2019 novel coronavirus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still gradually spreading worldwide. The nucleic acid test or genetic sequencing serves as the gold standard method for confirmation of infection, yet several recent studies have reported false-negative results of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Here, we report two representative false-negative cases and discuss the supplementary role of clinical data with rRT-PCR, including laboratory examination results and computed tomography features. Coinfection with SARS-COV-2 and other viruses has been discussed as well.

negative: Actualización de la situación epidemiológica de la infección por SARS-CoV-2 en España. Comentarios a las recomendaciones de manejo de la infección en pediatría

negative: Porcine epidemic diarrhea: A retrospect from Europe and matters of debate Abstract A retrospect is given on the emergence of porcine epidemic diarrhea (PED) during the early seventies in Europe. While, at first, it appeared as a disease affecting feeder pigs, fattening- and adult swine, it later also became pathogenic for neonatal and suckling pigs hereby drastically increasing its economic impact. Isolation of the causative virus revealed a new porcine coronavirus, the origin of which has never been clarified. Pathogenesis studies with the prototype strain CV777 showed severe villous atrophy in neonatal pigs and the virus-animal interactions showed many similarities with transmissible gastro-enteritis virus (TGEV), another porcine coronavirus. Disease patterns in field outbreaks showed muchvariation but, while farm related factors played a role, possible genetic variations of virus strains in Europe have not been examined and are thus unknown. CV777 in experimental pigs caused diarrheal disease and mortality rates similar to those later encountered in Asia and more recently with the “original” US strains even though genomic typing of the prototype European strain have shown that it belongs to the S-INDEL strains. In Europe, PED has become endemic during the eighties and nineties and subsequently regressed so that, after 2000, swine populations in many countries have largely become seronegative. Sporadic outbreaks have recently reappeared showing a large variety of clinical outcomes.

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

negative: Human food consumption patterns concerning COVID-19 pandemic In recent months, despite being aware of the COVID-19 pandemic, many countries faced increasing epidemic of this disease. Nearly all countries tried to decrease human-to-human contact as the principal mode of transmission of SARS-CoV-2. Other modes of transmission also need to be clarified in more depth, especially, the foodborne transmission (FBT). We assessed the effect of animal origin foods (AOF) consumption on the pandemic of COVID-19. For this purpose, we studied the relationship among 20 food supply as independent variables, and the parameter of Total Cases (TC) as dependent variable. The statistical analyses included parametric, non-parametric, frequentist, and Bayesian methods. Results showed a relationship between a group of AOF and TC. So, the role of FBT of COVID-19 should be more significant than previously thought. The possibility of Animal Origin Foodborne Transmission should be taken into more consideration. The perspective is to expand the surveillance of SARS-Cov-2 during the food production chain.

negative: The discrepant epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerged infection in humans affecting the Arabian Peninsula, Europe, and North Africa. The source and persistence of the infection in humans remains unknown. The aim of this paper was to apply a risk analysis approach to the epidemiology of MERS-CoV and to understand the source of ongoing infections. The epidemiology of MERS-CoV was reviewed and compared to SARS. Each observed feature of MERS-CoV epidemiology was summarized and fitted to either an epidemic or one of two sporadic scenarios (either animal or deliberate release). As of May 2014, MERS-CoV has infected over 681 people and killed a further 204 over 2 years. In contrast, there were 8,273 cases and 775 deaths from SARS within 8 months. MERS-CoV has a more sporadic pattern unlike the clear epidemic pattern seen with SARS, and an unusual concentration of cases in the Middle East, without epidemics in other countries to which it has spread. SARS, with a higher reproductive number (R0), was eliminated from humans within 8 months of emerging, yet MERS-CoV, with a low R0 has persisted in humans over a far more prolonged period. This is at odds with the expected behavior of a virus with a low R0, which theoretically should not persist unless there are ongoing introductions of infection into humans, and poses the question “what is the source of continuing infections in humans?” A hospital outbreak in Al Ahsa, the Kingdom of Saudi Arabia (KSA), had a classic epidemic pattern with some human-to-human transmission. However, 3 different strains were identified in that outbreak, an unexpected and unexplained finding for what appears to be a single source outbreak. Since this outbreak in April 2013, there has been a large increase in new cases, mainly in KSA in April and May 2014, with no corresponding epidemics in other countries. Yet MERS-CoV was present in KSA over several mass gatherings (which predispose to epidemics), including the Hajj pilgrimage, without an epidemic arising. Furthermore, although the virus has been identified in bats and camels, the mode of ongoing transmission to humans remains uncertain. Although some cases appear to be transmitted from human to human, and a few have animal or camel exposure, many cases have no history of contact with either animals or human cases. A high proportion of asymptomatic or otherwise undetected cases have been postulated as an explanation for the unusual epidemiology, yet active surveillance does not support this. When the observed data were fitted to different disease patterns, the features of MERS-CoV fit better with a sporadic pattern, with evidence for either deliberate release or an animal source. There are many discrepancies in the observed epidemiology of MERS-CoV, which better fits a sporadic than an epidemic pattern. Possible explanations of the unusual features of the epidemiology include human-to-human transmission with a large proportion of undetected cases; or sporadic ongoing infections from a non-human source; or a combination of both. Possible sources of ongoing sporadic infection in humans include animals (camels appear the most likely source), or deliberate release. The latter could explain 3 strains being present in a single hospital outbreak. Genetic testing should be conducted to determine whether the virus is evolving to be more transmissible. Better ascertainment of mild or asymptomatic cases is also needed. Finally, the discrepant epidemiology warrants critical analysis of all possible explanations, and involvement of all stakeholders in biosecurity, and deliberate release must be seriously considered and at least acknowledged as a possibility.

negative: Novel Middle East respiratory syndrome coronavirus

negative: COVID-19: The outbreak caused by a new coronavirus. Before the severe acute respiratory syndrome outbreak in 2003, coronaviruses (CoVs) were not considered to be highly pathogenic to humans. However, it was this epidemic that highlighted this group of viruses and included them among the causative agents of emerging epidemic diseases. In addition, in 2012, another new CoV responsible for the Middle East respiratory syndrome was identified. Both infections were considered a threat to global health security. At present, the third epidemic caused by a CoV is being faced. This new CoV, called 2019-nCoV, was originated in the city of Wuhan, China, and has been linked to severe respiratory infections in humans. Thanks to the collaboration of experts worldwide, more information about this virus and its infection is reported each day, which allows modifying the recommendations for its prevention and treatment, without forgetting that the ultimate goal is to control this epidemic. In this review, the important aspects of this new coronavirus, 2019-nCoV, and its disease, COVID-19, have been summarized with the information available up to February 2020.

negative: Emerging Viruses Emerging viruses are viruses that appear suddenly in the human population. These are viruses to which man has no history of exposure and thus no or limited immunity; they are not new evolutionary creations, but are viruses than man meets due to environmental changes, such as deforestation, entering into new habitats, or viruses that are transmitted from one species of animal to humans. Most of these viruses are terrifying, and cause hemorrhagic fever, a complete destruction of the circulation system; they include Lassa fever, Nipah virus, Ebola, HIV, Severe acute respiratory syndrome (SARS), and, recently, Middle East respiratory syndrome (MERS), which is the latest in a series of “new” respiratory viruses infecting man. It is possible that unknown emerging viruses are the cause of death, often listed as “death due to an unknown cause,” as in the retrospective cases of HIV. Emerging viruses might also include poliovirus and influenza, since their introduction into the human population is (was) often sudden and due to changes in the environment or due to contact with other animal species. For examples, polio was a result of changes in sanitation in the countries of North America and Western Europe, and influenza is constantly jumping from aquatic birds to man and other animal species where genomic reassortment occurs.

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

negative: Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review Infectious diseases attributable to unsafe water supply, sanitation and hygiene (e.g. Cholera, Leptospirosis, Giardiasis) remain an important cause of morbidity and mortality, especially in low-income countries. Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases. There have been little critical analyses of the methodological approaches. Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods. We conducted a systematic review of English-language papers published from 2000 to 2015. Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods. We found 102 full text papers that met our criteria and were included in the analysis. The most commonly used methods were grouped in two clusters: process-based models (PBM) and time series and spatial epidemiology (TS-SE). In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g. Vibrio cholerae); TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g. Campylobacter). Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections. The most common limitations comprised: non-inclusion of key factors (e.g. biological mechanism, demographic heterogeneity, human behavior), reporting bias, poor data quality, and collinearity in exposures. Furthermore, the methods often did not distinguish among the multiple sources of time-lags (e.g. patient physiology, reporting bias, healthcare access) between environmental drivers/exposures and disease detection. Key areas of future research include: disentangling the complex effects of weather/climate on each exposure-health outcome pathway (e.g. person-to-person vs environment-to-person), and linking weather data to individual cases longitudinally.

negative: Covid-19 and cardiovascular disease. Guideline: Diagnosis and management of cardiovascular disease during the covid-19 pandemicPublished by the European Society of Cardiology.This summary is based on the version published on 21 April 2020 (https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance).

negative: Multinational modeling of SARS-CoV-2 spreading dynamics: Insights on the heterogeneity of COVID-19 transmission and its potential healthcare burden Background: Modelling and projections of COVID-19 using a single set of transmission parameters can be an elaborated because the application of different levels of containment measures at different stages of the worldwide COVID-19 outbreak. Methods: We developed a piecewise fitting SEIR methodology to fit the progress of the COVID-19 that can be applied on any of the 185 countries listed in John Hopkins Coronavirus Resource Center. The contagious contact rate, the rate of removal and the initially exposed population were obtained at three different stages of the pandemic for a set of 18 countries, and globally for the total number of cases worldwide. The active number of infections and the removed populations were fitted simultaneously to validate the SEIR model against the available time series reports on the number of confirmed infections, recoveries and deaths. We evaluate the effect of a reduction of contagious contact rate on the level of burden put on local healthcare infrastructure considering different levels of intervention. As a guideline for future public health interventions, we also estimated the maximum number of future cases and its potential peak date. Findings: We project that the peak in the number of infections worldwide will take place after the third quarter of 2020 with a decline rate that might extend beyond 2020. For 12 out of the 18 countries analyzed, we observe that, following the trend at the date of this study, the number of severe infections will surpass their healthcare capacity. For a 90% reduction scenario of the contagious contact rate, four out of the 18 countries analyzed will undergo a significant delay in the peak of infection, extending the course of the epidemic further than our simulation window (365 days). Interpretation: We identify three stages for the COVID-19 transmission dynamics, which suggest that it is highly heterogeneous between countries and its contagious contact rate, is currently affected by both local responses of the public health interventions and to the population's adherence to the measures. Funding: No funding received.

negative: Evaluation of Enzyme-Linked Immunoassay and Colloidal Gold- Immunochromatographic Assay Kit for Detection of Novel Coronavirus (SARS-Cov-2) Causing an Outbreak of Pneumonia (COVID-19) Abstract BACKGROUND: In December 2019, a novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19) occurred in Wuhan, China. Travel-associated cases have also been reported in other countries. The number of cases has increased rapidly but laboratory diagnosis is limited. METHODS: We collect two groups of cases diagnosed with COVID-19 for experiments. One group collected 63 samples for Enzyme-linked immunosorbent assay (ELISA) IgG and IgM antibodies. The other group collected 91 plasma samples for colloidal gold-immunochromatographic assay (GICA). RESULTS: The sensitivity of the combined ELISA IgM and ELISA IgG detection was 55/63 ( 87.3%), The sensitivity of the combined GICA IgM and GICA IgG detection was 75/91 ( 82.4%), Both methods are negative for healthy controls, specificity of 100% .There is no significant difference between the sensitivity of between ELISA and GICA (IgM+ IgG). CONCLUSIONS: ELISA and GICA for specific IgM and IgG antibodies are conventional serological assays, they are simple, fast, and safe, the results can be used for clinical reference, and the huge clinical diagnosis and treatment pressure can be greatly relieved.

negative: COVID-19 in the Cancer Patient The novel Coronavirus Disease 2019 (COVID-19) was first reported in China in December 2019. Since then, it has spread across the world to become one of the most serious life-threatening pandemics since the influenza pandemic of 1918. This review article will focus on the specific risks and nuanced considerations of COVID-19 in the cancer patient. Important perioperative management recommendations during this outbreak are emphasized, in addition to discussion of current treatment techniques and strategies available in the battle against COVID-19.

negative: Moroccan Medicinal plants as inhibitors against SARS-CoV-2 main protease: Computational investigations The new Corona-virus, recently called the severe acute respiratory syndrome Coronavirus (SARS-CoV-2) appears for the first time in China and more precisely in Wuhan (December 2019). This disease can be fatal. Seniors, and people with other medical conditions (diabetes, heart disease…), may be more vulnerable and become seriously ill. This is why research into drugs to treat this infection remains essential in several research laboratories. Natural herbal remedies have long been the main, if not the only, remedy in the oral tradition for treating illnesses. Modern medicine has known its success thanks to traditional medicine, the effectiveness of which derives from medicinal plants. The objective of this study is to determine if the components of natural origin have an anti-viral effect and which can prevent humans from infection by this coronavirus using the most reliable method is molecular docking, which used to find the interaction between studied molecules and the protein, in our case we based on the inhibitor of Coronavirus (nCoV-2019) main protease. The results of molecular docking showed that among 67 molecules of natural origin, three molecules (Crocin, Digitoxigenin, and β-Eudesmol) are proposed as inhibitors against the coronavirus based on the energy types of interaction between these molecules and studied protein. [Image: see text] Communicated by Ramaswamy H. Sarma HIGHLIGHTS: Determine natural compounds that can have an anti-viral effect and which can prevent humans from infection by this coronavirus; Molecular docking to find interaction between the molecules studied and the receptor of COVID-19; The synthesis of these molecules and the evaluation of their in vitro activity against SARS-Cov-2 could be interesting.

negative: In silico fight against novel coronavirus by finding chromone derivatives as inhibitor of coronavirus main proteases enzyme Novel coronavirus, 2019-nCoV is a danger to the world and is spreading rapidly. Very little structural information about 2019-nCoV make this situation more difficult for drug designing. Benzylidenechromanones, naturally occurring oxygen heterocyclic compounds, having capability to inhibit various protein and receptors, have been designed here to block mutant variety of coronavirus main protease enzyme (SARC-CoV-2 M(pro)) isolated from 2019-nCoV with the assistance of molecular docking, bioinformatics and molecular electrostatic potential. (Z)-3-(4′-chlorobenzylidene)-thiochroman-4-one showed highest binding affinity to the protein. Binding of a compound to this protein actually inhibits the replication and transcription of the virus and, ultimately, stop the virus multiplication. Incorporation of any functional groups to the basic benzylidenechromanones enhances their binding ability. Chloro and bromo substitutions amplify the binding affinity. ADME studies of all these compounds indicate they are lipophilic, high gastro intestine absorbable and blood-brain barrier permeable. The outcome reveals that the investigated benzylidenechromanones can be examined in the case of 2019-nCoV as potent inhibitory drug of SARC-CoV-2 M(pro), for their strong inhibition ability, high reactivity and effective pharmacological properties. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11224-020-01537-5) contains supplementary material, which is available to authorized users.

negative: Conserved antigenic sites between MERS-CoV and Bat-coronavirus are revealed through sequence analysis BACKGROUND: MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV. RESULTS: Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein’s antigenic sites are found to be conserved with those in HKU4 and HKU5. CONCLUSION: This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13029-016-0049-7) contains supplementary material, which is available to authorized users.

negative: Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.

negative: A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses The H1 subtype of influenza A viruses (IAVs) has been circulating in swine since the 1918 human influenza pandemic. Over time, and aided by further introductions from nonswine hosts, swine H1 viruses have diversified into three genetic lineages. Due to limited global data, these H1 lineages were named based on colloquial context, leading to a proliferation of inconsistent regional naming conventions. In this study, we propose rigorous phylogenetic criteria to establish a globally consistent nomenclature of swine H1 virus hemagglutinin (HA) evolution. These criteria applied to a data set of 7,070 H1 HA sequences led to 28 distinct clades as the basis for the nomenclature. We developed and implemented a web-accessible annotation tool that can assign these biologically informative categories to new sequence data. The annotation tool assigned the combined data set of 7,070 H1 sequences to the correct clade more than 99% of the time. Our analyses indicated that 87% of the swine H1 viruses from 2010 to the present had HAs that belonged to 7 contemporary cocirculating clades. Our nomenclature and web-accessible classification tool provide an accurate method for researchers, diagnosticians, and health officials to assign clade designations to HA sequences. The tool can be updated readily to track evolving nomenclature as new clades emerge, ensuring continued relevance. A common global nomenclature facilitates comparisons of IAVs infecting humans and pigs, within and between regions, and can provide insight into the diversity of swine H1 influenza virus and its impact on vaccine strain selection, diagnostic reagents, and test performance, thereby simplifying communication of such data. IMPORTANCE A fundamental goal in the biological sciences is the definition of groups of organisms based on evolutionary history and the naming of those groups. For influenza A viruses (IAVs) in swine, understanding the hemagglutinin (HA) genetic lineage of a circulating strain aids in vaccine antigen selection and allows for inferences about vaccine efficacy. Previous reporting of H1 virus HA in swine relied on colloquial names, frequently with incriminating and stigmatizing geographic toponyms, making comparisons between studies challenging. To overcome this, we developed an adaptable nomenclature using measurable criteria for historical and contemporary evolutionary patterns of H1 global swine IAVs. We also developed a web-accessible tool that classifies viruses according to this nomenclature. This classification system will aid agricultural production and pandemic preparedness through the identification of important changes in swine IAVs and provides terminology enabling discussion of swine IAVs in a common context among animal and human health initiatives.

negative: The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future The respiratory system, which includes the trachea, airways, and distal alveoli, is a complex multi-cellular organ that intimately links with the cardiovascular system to accomplish gas exchange. In this review and as members of the NIH/NHLBI-supported Progenitor Cell Translational Consortium, we discuss key aspects of lung repair and regeneration. We focus on the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung repair and regeneration. We also provide future directions for an improved understanding of the cell biology of the respiratory system, as well as new therapeutic avenues.

negative: 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: COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy? Renin–angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known to induce an increased expression of angiotensin‐converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus‐2 (SARS‐CoV‐2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease‐19 (COVID‐19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS‐CoV‐2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID‐19 infection.

negative: Influence of COVID-19 confinement in students performance in higher education This study explores the effects of COVID-19 confinement in the students performance in higher education. Using a field experiment of 458 students from three different subjects in Universidad Autonoma de Madrid (Spain), we study the differences in assessments by dividing students into two groups. The first group (control) corresponds to academic years 2017/2018 and 2018/2019. The second group (experimental) corresponds to students from 2019/2020, which is the group of students that interrupted their face-to-face activities because of the confinement. The results show that there is a significant positive effect of the COVID-19 confinement on students performance. This effect is also significative in activities that did not change their format when performed after the confinement. We find that this effect is significative both in subjects that increased the number of assessment activities and subjects that did not change the workload of students. Additionally, an analysis of students learning strategies before confinement shows that students did not study in a continuous basis. Based on these results, we conclude that COVID-19 confinement changed students learning strategies to a more continuous habit, improving their efficiency. For these reasons, better scores in students assessment are expected due to COVID-19 confinement that can be explained by an improvement in their learning performance.

negative: The emerging novel Middle East respiratory syndrome coronavirus: The “knowns” and “unknowns” A novel lineage C betacoronavirus, originally named human coronavirus EMC/2012 (HCoV-EMC) and recently renamed Middle East respiratory syndrome coronavirus (MERS-CoV), that is phylogenetically closely related to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5, which we discovered in 2007 from bats in Hong Kong, has recently emerged in the Middle East to cause a severe acute respiratory syndrome (SARS)-like infection in humans. The first laboratory-confirmed case, which involved a 60-year-old man from Bisha, the Kingdom of Saudi Arabia (KSA), who died of rapidly progressive community-acquired pneumonia and acute renal failure, was announced by the World Health Organization (WHO) on September 23, 2012. Since then, a total of 70 cases, including 39 fatalities, have been reported in the Middle East and Europe. Recent clusters involving epidemiologically-linked household contacts and hospital contacts in the Middle East, Europe, and Africa strongly suggested possible human-to-human transmission. Clinical and laboratory research data generated in the past few months have provided new insights into the possible animal reservoirs, transmissibility, and virulence of MERS-CoV, and the optimal laboratory diagnostic options and potential antiviral targets for MERS-CoV-associated infection.

negative: Effect of cadmium on the expression levels of interleukin-1α and interleukin-10 cytokines in human lung cells Cadmium is an environmentally hazardous metal, which causes toxicity in humans. Inhalation of cigarette smoke and industrial fumes containing cadmium are sources of cadmium exposure. It is responsible for the malfunction of various organs, leading to disease particularly in the lungs, liver and kidneys. In the present study, the effect of cadmium chloride (CdCl(2)) on cell viability, and the expression levels of interleukin (IL)-1α and IL-10 cytokines at various concentrations and incubation durations were assessed in MRC-9 human normal lung and A549 human lung cancer cells to elucidate the mechanism of cadmium toxicity. Cell viability was measured using a crystal violet dye binding assay. The expression levels of the cytokines were measured by cytokine specific enzyme-linked immunosorbent assay kits. The viability assay results revealed higher sensitivity of the A549 lung cancer cells to CdCl(2) compared with the normal MRC-9 lung cells. In the normal MRC-9 lung cells, higher expression levels of the cytokines were observed at the lowest CdCl(2) concentration at a shorter exposure time compared with the lung cancer cells. Higher levels of the cytokines were observed in the A549 lung cancer cells at all other times and concentrations compared with the MRC-9 cells, indicating higher levels of inflammation. The cytokine levels were reduced at higher CdCl(2) concentrations and longer exposure durations, demonstrating the toxic effect of cadmium. The results indicated that CdCl(2) affected the expression levels of the cytokines and led to cytotoxicity in human lung cells, and suggested that compounds which reduce inflammation may prevent cadmium toxicity.

negative: A Radiation Mitigator as a Potential Treatment for COVID-19

negative: Where are we with understanding of COVID-19? Coronavirus disease 2019 caused by SARS-CoV-2 originated from China and spread across every corner of the world. The scientific interest on COVID-19 increased after WHO declared it a pandemic in the early February of 2020. In fact, this pandemic has had a worldwide impact on economy, health, and lifestyle like no other in the last 100 years. SARS-CoV-2 belongs to Coronaviridae family and causes the deadliest clinical manifestations when compared to other viruses in the family. COVID-19 is an emerging zoonotic disease that has resulted in over 383,000 deaths around the world. Scientists are scrambling for ideas to develop treatment and prevention strategies to thwart the disease condition. In this review, we have attempted to summarize the latest information on the virus, disease, prevention, and treatment strategies. The future looks promising.

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

negative: Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know Abstract In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19–infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of coronavirus syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of coronavirus syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.

negative: CHALLENGES IN THE FIGHT AGAINST THE COVID-19 PANDEMIC IN UNIVERSITY HOSPITALS

negative: Porcine Epidemic Diarrhea Virus and Discovery of a Recombinant Swine Enteric Coronavirus, Italy Porcine epidemic diarrhea virus (PEDV) has been detected sporadically in Italy since the 1990s. We report the phylogenetic relationship of swine enteric coronaviruses collected in Italy during 2007–2014 and identify a drastic shift in PEDV strain variability and a new swine enteric coronavirus generated by recombination of transmissible gastroenteritis virus and PEDV.

negative: Two resource distribution strategies for dynamic mitigation of influenza pandemics As recently pointed out by the Institute of Medicine, the existing pandemic containment and mitigation models lack the dynamic decision support capabilities. We present two simulation-based optimization models for developing dynamic predictive resource distribution strategies for cross-regional pandemic outbreaks. In both models, the underlying simulation mimics the disease and population dynamics of the affected regions. The quantity-based optimization model generates a progressive allocation of limited quantities of mitigation resources, including vaccines, antiviral, administration capacities, and social distancing enforcement resources. The budget-based optimization model strives instead allocating a total resource budget. Both models seek to minimize the impact of ongoing outbreaks and the expected impact of potential outbreaks. The models incorporate measures of morbidity, mortality, and social distancing, translated into the societal and economic costs of lost productivity and medical expenses. The models were calibrated using historic pandemic data and implemented on a sample outbreak in Florida, with over four million inhabitants. The quantity-based model was found to be inferior to the budget-based model, which was advantageous in its ability to balance the varying relative cost and effectiveness of individual resources. The models are intended to assist public health policy makers in developing effective distribution policies for mitigation of influenza pandemics.

negative: Detection of Covid-19 From Chest X-ray Images Using Artificial Intelligence: An Early Review In 2019, the entire world is facing a situation of health emergency due to a newly emerged coronavirus (COVID-19). Almost 196 countries are affected by covid-19, while USA, Italy, China, Spain, Iran, and France have the maximum active cases of COVID-19. The issues, medical and healthcare departments are facing in delay of detecting the COVID-19. Several artificial intelligence based system are designed for the automatic detection of COVID-19 using chest x-rays. In this article we will discuss the different approaches used for the detection of COVID-19 and the challenges we are facing. It is mandatory to develop an automatic detection system to prevent the transfer of the virus through contact. Several deep learning architecture are deployed for the detection of COVID-19 such as ResNet, Inception, Googlenet etc. All these approaches are detecting the subjects suffering with pneumonia while its hard to decide whether the pneumonia is caused by COVID-19 or due to any other bacterial or fungal attack.

negative: Coronavirus disease 2019 (COVID-19): What we need to know

negative: COVID-19 research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine What is new? KEY FINDINGS: Clinical decision-makers must be informed by the best, most trustworthy, highest-quality, robust evidence. This translates into how much confidence we can have in the research findings and thus be optimally informed for decision-making. The estimates of effect in clinical research depends on the underlying research methodology. COVID-19 disease is presenting global health systems, clinicians, and patients grave challenges. No treatment or prophylaxis currently exists for COVID-19. The overall body of COVID-19 research is very flawed methodologically. An examination of hydroxychloroquine-azithromycin research findings due to the recent media focus revealed very low-quality methodology underpins the research. Vast amounts of time and resources are being allocated to COVID-19 research, and being potentially squandered. WHAT THIS ADDS TO WHAT WAS KNOWN: Flawed methodology and sub-optimal reporting of research findings could lead to biased estimates of effect. This could lead to treatment decisions that are not optimal based on biased estimates which could harm the patient. This article provides specific suggestions for improving on the COVID-19 methods and reporting with a focus on the issues that researchers must consider in their methodology and reporting if we are to have confidence in the estimates of effect. Failure to consider harms in research could be detrimental to the patient. This article focuses on the potential harms when therapeutic agents such as hydroxychloroquine, are being considered. WHAT IS THE IMPLICATION AND WHAT SHOULD CHANGE NOW: Research thus far on finding an optimal therapeutic agent (s) for COVID-19 could be hampered by methodologically flawed research. COVID-19 researchers must immediately and acutely focus on improving their methodology and reporting.

negative: Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.

negative: Identification of potential vaccine candidates against SARS-CoV-2, A step forward to fight novel coronavirus 2019-nCoV: A Reverse Vaccinology Approach The recent Coronavirus Disease 2019 (COVID-19) causes an immense health crisis to global public health. The World Health Organization (WHO) declared the COVID-19 as a pandemic. The COVID-19 is the etiologic agent of a recently arose disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Presently, there is no vaccine available against this emerged viral disease. Therefore, it is indeed a need of the hour to develop an effectual and safe vaccine against this decidedly pandemic disease. In the current study, we collected SARS-CoV-2 genome from Indian geographical origin against human host, further more using reverse vaccinology and immunoinformatics tools here we claim effective vaccine candidates that can be mile stone in battle against COVID19. This novel study divulged two promising antigenic peptide GVYFASTEK and NFRVQPTESIV from surface glycoproteins (protein accession no. – QIA98583.1 and QHS34546.1) of SARS-CoV-2, which were predicated to be interacted with class I and class II MHC alleles and showed up to 90% conservancy and high value of antigenicity. Subsequently, the molecular docking studies were verified molecular interaction of these prime antigenic peptides with the residues of HLA-A*11-01 allele for MHC Class I and HLA DRB1*04-01 allele for MHC class II. After vigorous analysis, these peptides were predicted to be suitable epitopes which are capable to elicit the strong cell-mediated immune response against the SARS-CoV-2. Consequences from the present study could facilitate selecting SARS-CoV-2 epitopes for vaccine production pipelines in the immediate future. This novel research will certainly pave the way for a fast, reliable and virtuous platform to provide timely countermeasure of this dangerous pandemic disease, COVID-19.

negative: Forecasting COVID-19 impact on hospital bed-days, ICU-days, ventilator-days and deaths by US state in the next 4 months Key Points Question: Assuming social distancing measures are maintained, what are the forecasted gaps in available health service resources and number of deaths from the COVID-19 pandemic for each state in the United States? Findings: Using a statistical model, we predict excess demand will be 64,175 (95% UI 7,977 to 251,059) total beds and 17,380 (95% UI 2,432 to 57,955) ICU beds at the peak of COVID-19. Peak ventilator use is predicted to be 19,481 (95% UI 9,767 to 39,674) ventilators. Peak demand will be in the second week of April. We estimate 81,114 (95% UI 38,242 to 162,106) deaths in the United States from COVID-19 over the next 4 months. Meaning: Even with social distancing measures enacted and sustained, the peak demand for hospital services due to the COVID-19 pandemic is likely going to exceed capacity substantially. Alongside the implementation and enforcement of social distancing measures, there is an urgent need to develop and implement plans to reduce non-COVID-19 demand for and temporarily increase capacity of health facilities. Abstract Importance: This study presents the first set of estimates of predicted health service utilization and deaths due to COVID-19 by day for the next 4 months for each state in the US. Objective: To determine the extent and timing of deaths and excess demand for hospital services due to COVID-19 in the US. Design, Setting, and Participants: This study used data on confirmed COVID-19 deaths by day from WHO websites and local and national governments; data on hospital capacity and utilization for US states; and observed COVID-19 utilization data from select locations to develop a statistical model forecasting deaths and hospital utilization against capacity by state for the US over the next 4 months. Exposure(s): COVID-19. Main outcome(s) and measure(s): Deaths, bed and ICU occupancy, and ventilator use. Results: Compared to licensed capacity and average annual occupancy rates, excess demand from COVID-19 at the peak of the pandemic in the second week of April is predicted to be 64,175 (95% UI 7,977 to 251,059) total beds and 17,380 (95% UI 2,432 to 57,955) ICU beds. At the peak of the pandemic, ventilator use is predicted to be 19,481 (95% UI 9,767 to 39,674). The date of peak excess demand by state varies from the second week of April through May. We estimate that there will a total of 81,114 (95% UI 38,242 to 162,106) deaths from COVID-19 over the next 4 months in the US. Deaths from COVID-19 are estimated to drop below 10 deaths per day between May 31 and June 6. Conclusions and Relevance: In addition to a large number of deaths from COVID-19, the epidemic in the US will place a load well beyond the current capacity of hospitals to manage, especially for ICU care. These estimates can help inform the development and implementation of strategies to mitigate this gap, including reducing non-COVID-19 demand for services and temporarily increasing system capacity. These are urgently needed given that peak volumes are estimated to be only three weeks away. The estimated excess demand on hospital systems is predicated on the enactment of social distancing measures in all states that have not done so already within the next week and maintenance of these measures throughout the epidemic, emphasizing the importance of implementing, enforcing, and maintaining these measures to mitigate hospital system overload and prevent deaths.

negative: The Indirect Benefit on Respiratory Health From the World’s Effort to Reduce Transmission of SARS – CoV-2

negative: Mathematical Models of Infectious Diseases in Livestock: Concepts and Application to the Spread of Highly Pathogenic Avian Influenza Virus Strain Type H5N1 Animal health governance faces new challenges as the ecology of infectious livestock diseases is changing (Tomley and Shirley 2009). Environmental and climate changes, intensification of livestock production, modification in land-use and agricultural practices, globalization of human travel, the development of the trade of livestock and livestock products have created conditions for an increase in the emergence and re-emergence of infectious agents in the last decades (Weiss and McMichael 2004; Randolph and Rogers 2010; Jones et al. 2008; Gibbs 2005). The frequency of emergence of new highly pathogenic avian influenza viruses (HPAIV) has increased over the past 20 years, as well as the economic impact of associated outbreaks (Alexander and Brown 2009). Bluetongue virus serotypes have continuously increased their spatial distribution, specifically in a northern direction. Treatment-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), have appeared. Numerous infectious diseases such as foot-and-mouth disease (FMD) are endemic in many parts of the world, and may have a high impact on animal health and farmer livelihood. Moreover, they constrain the ability of affected countries to trade livestock and livestock-derived products. Production systems in developed countries are also vulnerable. For example, outbreaks of FMD in United Kingdom in 2001, classical swine fever in Holland in 1997/1998, and highly pathogenic avian influenza H7N7 in Holland in 2003 resulted in the loss of millions of animals, mainly as a result of culling of affected and exposed animals. Finally, infectious livestock diseases are a threat for public health: about 75% of human infectious agents that emerged in the last 25 years had an animal origin (King et al. 2006).

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: The effect of uncontrolled travelers and social distancing on the spread of novel coronavirus disease (COVID-19) in Colombia

negative: Tylosema esculentum (Marama) Tuber and Bean Extracts Are Strong Antiviral Agents against Rotavirus Infection Tylosema esculentum (marama) beans and tubers are used as food, and traditional medicine against diarrhoea in Southern Africa. Rotaviruses (RVs) are a major cause of diarrhoea among infants, young children, immunocompromised people, and domesticated animals. Our work is first to determine anti-RV activity of marama bean and tuber ethanol and water extracts; in this case on intestinal enterocyte cells of human infant (H4), adult pig (CLAB) and adult bovine (CIEB) origin. Marama cotyledon ethanolic extract (MCE) and cotyledon water extract (MCW) without RV were not cytotoxic to all cells tested, while seed coat and tuber extracts showed variable levels of cytotoxicity. Marama cotyledon ethanolic and water extracts (MCE and MCW, resp.) (≥0.1 mg/mL), seed coat extract (MSCE) and seed coat water extract (MSCW) (0.01 to 0.001 mg/mL), especially ethanolic, significantly increased cell survival and enhanced survival to cytopathic effects of RV by at least 100% after in vitro co- and pre-incubation treatments. All marama extracts used significantly enhanced nitric oxide release from H4 cells and enhanced TER (Ω/cm(2)) of enterocyte barriers after coincubation with RV. Marama cotyledon and seed coat extracts inhibited virion infectivity possibly through interference with replication due to accumulation of nitric oxide. Marama extracts are therefore promising microbicides against RV.

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: COVID-19: An Appeal for an Intersectoral Approach to Tackle With the Emergency The knowledge of disease determinants is a pre-requisite for disease prevention. Infectious diseases determinants can be classified in three ways, as: primary or secondary; intrinsic or extrinsic; and associated with host, agent, or environment. In the specific case of COVID-19 several of these determinants are currently unknown leading to difficulties in public health approach to this disease. In this paper, we attempt to address several of the current gaps on COVID-19 using a systematic analysis on recent findings and some preliminary knowledge on animal coronaviruses. A discussion on the impact of COVID-19 determinants in disease prevention and control will be based on the Environmental Change and Infectious Disease (EnVID) systemic framework to address several challenges that may affect the control of the SARS- CoV-2 pandemic spread both in industrialized and in developing Countries.

negative: Does infection of 2019 novel coronavirus cause acute and/or chronic sialadenitis? Abstract 2019 novel coronavirus (2019-nCoV) is widespread in China and other countries. The target of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV) is angiotensin-converting enzyme 2 (ACE2) positive cells. ACE2 is present in the salivary gland duct epithelium, and thus it could be the target of 2019-nCoV and SARS-CoV. SARS-CoV-related animal model experiments show that it can infect the epithelial cells on the salivary gland duct in Chinese rhesus macaques by targeting ACE2. Clinical studies confirmed that 2019-nCoV and SARS-CoV could be detected in saliva of human patients. We hypothesize that the infection of 2019-nCoV and SARS-CoV will lead to inflammatory pathological lesions in patients’ target organs, and possibly inflammatory lesions in salivary glands. 2019-nCoV may cause acute sialoadenitis in the acute phase of infection. After the acute phase, chronic sialoadenitis may be caused by fibrosis repairment. Although there was no direct evidence to prove this, the available indirect evidence indicates a high probability of our hypothesis.

negative: Pediatric SARS, H1N1, MERS, EVALI, and Now Coronavirus Disease (COVID-19) Pneumonia: What Radiologists Need to Know OBJECTIVE. The purpose of this article is to review new pediatric lung disorders-including disorders that have occurred in recent years years such as severe acute respiratory syndrome (SARS), swine-origin influenza A (H1N1), Middle East respiratory syndrome (MERS), e-cigarette or vaping product use-associated lung injury (EVALI), and coronavirus disease (COVID-19) pneumonia-to enhance understanding of the characteristic imaging findings. CONCLUSION. Although the clinical symptoms of SARS, H1N1, MERS, EVALI, and COVID-19 pneumonia in pediatric patients may be nonspecific, some characteristic imaging findings have emerged or are currently emerging. It is essential for radiologists to have a clear understanding of the characteristic imaging appearances of these lung disorders in pediatric patients to ensure optimal patient care.

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

negative: [covid-19, the Kidney and Hypertension] INTRODUCTION: COVID-19, is a new corona virus of the Beta Coronavirus genus which originated in bats. The virus first emerged in China in December 2019 and has rapidly spread since to other areas worldwide. The World Health Organization (WHO) has therefore recently declared it as the source of a pandemic. The disease caused by the virus manifests in most cases as a lower respiratory tract infection leading to fever, cough and dyspnea, while more severe cases can led to respiratory failure and/or multi organ failure. COVID-19 enters the human cell using the ACE2, an enzyme abundant in renal tubular epithelial cells. Theoretically, this may be significant in several ways: acute kidney injury (AKI) as well as proteinuria and/or microhematuria could be associated with the penetration of COVID-19 into the cells. Moreover, medications based on RAAS inhibition, such and ACE inhibitors and ARBs, upregulate the enzyme ACE2 and could therefore hypothetically explain the high prevalence of hypertension and diabetes reported as previous diagnoses in severe cases. In the setting of chronic kidney disease, the risk of infection with COVID-19 is not clear at this time. However, hemodialysis patients represent a unique group of patients, mostly elderly and immunocompromised, for whom dialysis is a life-saving treatment which cannot be stopped. Hence, the COVID-19 pandemic has presented a complex medical and logistic challenge for the medical staff in hospital and community based dialysis units.

negative: Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes SUMMARY: Genome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS) related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY: https://www.genomedetective.com/app/typingtool/cov SUPPLEMENTARY INFORMATION:

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: Covid-19 pandemic and the unprecedented mobilisation of scholarly efforts prompted by a health crisis: Scientometric comparisons across SARS, MERS and 2019-nCov literature During the current century, each major coronavirus outbreak has triggered a quick and immediate surge of academic publications on this topic. The spike in research publications following the 2019 Novel Coronavirus (Covid-19) outbreak, however, has been like no other. The global crisis caused by the Covid-19 pandemic has mobilised scientific efforts in an unprecedented way. In less than five months, more than 12,000 research items have been indexed while the number increasing every day. With the crisis affecting all aspects of life, research on Covid-19 seems to have become a focal point of interest across many academic disciplines. Here, scientometric aspects of the Covid-19 literature are analysed and contrasted with those of the two previous major Coronavirus diseases, i.e. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The focus is on the co-occurrence of key-terms, bibliographic coupling and citation relations of journals and collaborations between countries. Certain recurring patterns across all three literatures were discovered. All three outbreaks have commonly generated three distinct and major cohort of studies: (i) studies linked to the public health response and epidemic control, (ii) studies associated with the chemical constitution of the virus and (iii) studies related to treatment, vaccine and clinical care. While studies affiliated with the category (i) seem to have been the first to emerge, they overall received least numbers of citations compared to those of the two other categories. Covid-19 studies seem to have been distributed across a broader variety of journals and subject areas. Clear links are observed between the geographical origins of each outbreak or the local geographical severity of each outbreak and the magnitude of research originated from regions. Covid-19 studies also display the involvement of authors from a broader variety of countries compared to SARS and MRS.

negative: Lung Transplantation for Elderly Patients With End-Stage COVID-19 Pneumonia

negative: NSs Encoded by Groundnut Bud Necrosis Virus Is a Bifunctional Enzyme Groundnut bud necrosis virus (GBNV), a member of genus Tospovirus in the family Bunyaviridae, infects a large number of leguminosae and solanaceae plants in India. With a view to elucidate the function of nonstructural protein, NSs encoded by the small RNA genome (S RNA), the NSs protein of GBNV- tomato (Karnataka) [1] was over-expressed in E. coli and purified by Ni-NTA chromatography. The purified rNSs protein exhibited an RNA stimulated NTPase activity. Further, this activity was metal ion dependent and was inhibited by adenosine 5′ (β, γ imido) triphosphate, an ATP analog. The rNSs could also hydrolyze dATP. Interestingly, in addition to the NTPase and dATPase activities, the rNSs exhibited ATP independent 5′ RNA/DNA phosphatase activity that was completely inhibited by AMP. The 5′ α phosphate could be removed from ssDNA, ssRNA, dsDNA and dsRNA thus confirming that rNSs has a novel 5′ α phosphatase activity. K189A mutation in the Walker motif A (GxxxxGKT) resulted in complete loss of ATPase activity, but the 5′ phosphatase activity was unaffected. On the other hand, D159A mutation in the Walker motif B (DExx) resulted in partial loss of both the activities. These results demonstrate for the first time that NSs is a bifunctional enzyme, which could participate in viral movement, replication or in suppression of the host defense mechanism.

negative: Detection of 20 respiratory viruses and bacteria by influenza-like illness surveillance in Beijing, China, 2016–2018

negative: COVID-19 in South Korea A novel coronavirus (severe acute respiratory syndrome-CoV-2) that initially originated from Wuhan, China, in December 2019 has already caused a pandemic. While this novel coronavirus disease (COVID-19) frequently induces mild diseases, it has also generated severe diseases among certain populations, including older-aged individuals with underlying diseases, such as cardiovascular disease and diabetes. As of 31 March 2020, a total of 9786 confirmed cases with COVID-19 have been reported in South Korea. South Korea has the highest diagnostic rate for COVID-19, which has been the major contributor in overcoming this outbreak. We are trying to reduce the reproduction number of COVID-19 to less than one and eventually succeed in controlling this outbreak using methods such as contact tracing, quarantine, testing, isolation, social distancing and school closure. This report aimed to describe the current situation of COVID-19 in South Korea and our response to this outbreak.

negative: Tabagisme et maladie à coronavirus 2019 (COVID-19)

negative: Intra-model Variability in COVID-19 Classification Using Chest X-ray Images X-ray and computed tomography (CT) scanning technologies for COVID-19 screening have gained significant traction in AI research since the start of the coronavirus pandemic. Despite these continuous advancements for COVID-19 screening, many concerns remain about model reliability when used in a clinical setting. Much has been published, but with limited transparency in expected model performance. We set out to address this limitation through a set of experiments to quantify baseline performance metrics and variability for COVID-19 detection in chest x-ray for 12 common deep learning architectures. Specifically, we adopted an experimental paradigm controlling for train-validation-test split and model architecture where the source of prediction variability originates from model weight initialization, random data augmentation transformations, and batch shuffling. Each model architecture was trained 5 separate times on identical train-validation-test splits of a publicly available x-ray image dataset provided by Cohen et al. (2020). Results indicate that even within model architectures, model behavior varies in a meaningful way between trained models. Best performing models achieve a false negative rate of 3 out of 20 for detecting COVID-19 in a hold-out set. While these results show promise in using AI for COVID-19 screening, they further support the urgent need for diverse medical imaging datasets for model training in a way that yields consistent prediction outcomes. It is our hope that these modeling results accelerate work in building a more robust dataset and a viable screening tool for COVID-19.

negative: SARS‐CoV‐2: What can saliva tell us? An epidemic pneumonia was first reported in the city of Wuhan, China, in the end of December 2019, had its aetiological agent identified as a new coronavirus (Zhu et al., 2020). The World Health Organisation (WHO) declared on 11 March 2020 that the epidemic of the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic now called COVID-19.

negative: Inside China and COVID-19: Questions and answers

negative: Angiotensin-converting enzyme 2 autoantibodies: further evidence for a role of the renin-angiotensin system in inflammation Traditionally viewed as important in the regulation of blood pressure, the renin-angiotensin system - and specifically the angiotensin-converting enzyme (ACE)-angiotensin (Ang) II-AT(1 )receptor axis - may play a prominent role to promote inflammation and fibrosis. ACE2, a new component of the renin-angiotensin system, has emerged as a key enzyme that selectively degrades Ang II and generates Ang-(1-7), a bioactive peptide with anti-inflammatory and anti-fibrotic actions. Takahashi and colleagues demonstrate circulating titers of inhibitory autoantibodies against ACE2 in patients with systemic sclerosis. The current study reveals a potentially novel mechanism to attenuate the catalytic activity of ACE2, thereby promoting the actions of Ang II.

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: 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: 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: The more I fear about COVID-19, the more I wear medical masks: A survey on risk perception and medical masks uses The legal behaviors in using medical masks in public have been finally promulgated by the Vietnamese Government after 47 days since the WHO declared the Public Health Emergency of International Concern (PHEIC) due to the COVID-19 pandemic. From a sample of 345 Vietnamese respondents aged from 15 to 47 years, this brief note found that the risk perception of COVID-19 danger significantly increases the likelihood of wearing the medical masks. In addition, there is a weak evidence about the differences in age under the COVID-19 outbreaks. More noticeably, those who use masks before COVID-19 pandemic tend to maintain their behaviors. Our results offer the insightful into Vietnamese citizens responses in terms of using medical masks; even the uses of this method are still controversial. Our results are robust by performing Exploratory Factor Analysis for five features and further regressions.

negative: A Bayesian reanalysis of the effects of hydroxychloroquine and azithromycin on viral carriage in patients with COVID-19 Gautret and colleagues reported results of a non-randomised open-label case series which examined the effects of hydroxychloroquine and azithromycin on viral load in the upper respiratory tract of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. The authors report that hydroxychloroquine (HCQ) had significant virus reducing effects, and that dual treatment of both HCQ and azithromycin further enhanced virus reduction. This data has triggered speculation whether these drugs should be considered as candidates for the treatment of severe COVID-19. However, questions have been raised regarding the study's data integrity, statistical analyses, and experimental design. We therefore reanalysed the original data to interrogate the main claims of the paper. Here we apply Bayesian statistics to assess the robustness of the original papers claims by testing four variants of the data: 1) The original data; 2) Data including patients who deteriorated; 3) Data including patients who deteriorated with exclusion of untested patients in the comparison group; 4) Data that includes patients who deteriorated with the assumption that untested patients were negative. To ask if HCQ monotherapy is effective, we performed an A/B test for a model which assumes a positive effect, compared to a model of no effect. We find that the statistical evidence is highly sensitive to these data variants. Statistical evidence for the positive effect model ranged from strong for the original data (BF ~11), to moderate when including patients who deteriorated (BF ~4.35), to anecdotal when excluding untested patients (BF ~2), and to anecdotal negative evidence if untested patients were assumed positive (BF ~0.6). To assess whether HCQ is more effective when combined with AZ, we performed the same tests, and found only anecdotal evidence for the positive effect model for the original data (BF ~2.8), and moderate evidence for all other variants of the data (BF ~5.6). Our analyses only explore the effects of different assumptions about excluded and untested patients. These assumptions are not adequately reported, nor are they justified in the original paper, and we find that varying them causes substantive changes to the evidential support for the main claims of the original paper. This statistical uncertainty is exacerbated by the fact that the treatments were not randomised, and subject to several confounding variables including the patients' consent to treatment, different care centres, and clinical decision-making. Furthermore, while the viral load measurements were noisy, showing multiple reversals between test outcomes, there is greater certainty around other clinical outcomes such as the 4 patients who seriously deteriorated. The fact that all of these belonged to the HCQ monotherapy group should be assigned greater weight when evaluating the potential clinical efficacy of HCQ. Randomised controlled trials are currently underway, and will be critical in resolving this uncertainty as to whether HCQ and AZ are effective as a treatment for COVID-19.

negative: Efficacy of single-incision laparoscopic totally extraperitoneal repair for irreducible or incarcerated inguinal hernia. INTRODUCTION The aim of this study was to evaluate the efficacy of single-incision laparoscopic surgery for totally extraperitoneal repair (SILS-TEP) of irreducible inguinal hernias and incarcerated inguinal hernias. METHODS We performed a retrospective analysis of 194 patients, including 16 with irreducible or incarcerated hernia, who had undergone SILS-TEP from May 2016 to December 2017 at Kinki Central Hospital. The outcomes of patients with irreducible or incarcerated hernia and those with reducible hernia were compared. For irreducible or incarcerated hernia, laparoscopic exploration with hernia reduction through an intraumbilical incision was performed. If no bowel resection was needed, one-stage SILS-TEP was performed. If bowel resection was required, two-stage SILS-TEP was performed 2-3 months after the bowel resection. RESULTS Of the 16 patients, 8 had an irreducible hernia, and 8 had an incarcerated hernia. The eight patients with an incarcerated hernia underwent emergency surgery, and among these patients, two needed single-incision laparoscopic partial resection of the ileum followed by two-stage SILS-TEP. Fourteen patients, excluding the two patients who required single-incision laparoscopic partial resection of the ileum, underwent laparoscopic exploration with hernia reduction followed by one-stage SILS-TEP. Among these 14 patients, one with an irreducible hernia required conversion to Kugel patch repair. The operative outcomes were generally comparable between the two groups. However, the operative time was longer for unilateral hernia, and more seromas were seen in the irreducible or incarcerated group. No other major complications or cases of hernia recurrence were noted in this study. CONCLUSIONS SILS-TEP, which offers good cosmetic results, can be safely performed for irreducible or incarcerated inguinal hernia.

negative: Increased Viral Titers and Subtle Changes in Plaque Morphology Upon Passage of SARS-CoV in Cells from Different Species

negative: 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.

negative: Corona Epidemic in Indian context: Predictive Mathematical Modelling The novel Coronavirus pathogen Covid-19 is a cause of concern across the world as the human-to-human infection caused by it is spreading at a fast pace. The virus that first manifested in Wuhan, China has travelled across continents. The increase in number of deaths in Italy, Iran, USA, and other countries has alarmed both the developed and developing countries. Scientists are working hard to develop a vaccine against the virus, but until now no breakthrough has been achieved. India, the second most populated country in the world, is working hard in all dimensions to stop the spread of community infection. Health care facilities are being updated; medical and paramedical staffs are getting trained, and many agencies are raising awareness on the issues related to this virus and its transmission. The administration is leaving no stone unturned to prepare the country to mitigate the adverse effects. However, as the number of infected patients, and those getting cured is changing differently in different states everyday it is difficult to predict the spread of the virus and its fate in Indian context. Different states have adopted measures to stop the community spread. Considering the vast size of the country, the population size and other socio-economic conditions of the states, a single uniform policy may not work to contain the disease. In this paper, we discuss a predictive mathematical model that can give us some idea of the fate of the virus, an indicative data and future projections to understand the further course this pandemic can take. The data can be used by the health care agencies, the Government Organizations and the Planning Commission to make suitable arrangements to fight the pandemic. Though the model is preliminary, it can be used at regional level to manage the health care system in the present scenario. The recommendations can be made, and advisories prepared based on the predictive results that can be implemented at regional levels.

negative: Prior and Novel Coronaviruses, COVID-19, and Human Reproduction: What Is Known? Structured Abstract Objective To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. Design Review of English publications in PubMed and Embase to April 6, 2020. Methods Manuscripts were screened for reports including coronavirus, reproduction, including pathophysiology and pregnancy. Intervention(s) None. Main Outcome Measure(s) Reproductive outcomes; effects on gametes; pregnancy outcomes; neonatal complications. Results Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. SARS-CoV-1 may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following COVID-19 infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-CoV-2 adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or MERS, but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. COVID-19 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. Conclusion COVID-19 infection may adversely affect some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.

negative: Recent progress in understanding 2019 novel coronavirus (SARS-CoV-2) associated with human respiratory disease: detection, mechanisms and treatment ABSTRACT Viral respiratory diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) always pose a severe threat to people. First identified in late December 2019, a novel coronavirus (2019-nCoV; SARS-CoV-2) has affected many provinces in China and multiple countries worldwide. The viral outbreak has aroused panic and a public-health emergency around the world, and the number of infections continues to rise. However, the causes and consequences of the pneumonia remain unknown. To effectively implement epidemic prevention, early identification and diagnosis are critical to disease control. Here we scrutinise a series of available studies by global scientists on the clinical manifestations, detection methods and treatment options for the disease caused by SARS-CoV-2, named coronavirus disease 2019 (COVID-19), and also propose potential strategies for preventing the infection.

negative: Knowledge about pandemic influenza preparedness among vulnerable migrants in Thailand This study was designed to assess factors associated with a high level of knowledge about influenza among displaced persons and labor migrants in Thailand. We conducted a cross-sectional study of 797 documented and undocumented migrants thought to be vulnerable to influenza during the early stages of the 2009 H1N1 pandemic. Data were collected on socio-demographic factors, migration status, health information sources, barriers to accessing public healthcare services and influenza-related knowledge using a 201-item interviewer-assisted questionnaire. Among the different types of influenza, participants' awareness of avian influenza was greatest (81%), followed by H1N1 (78%), human influenza (61%) and pandemic influenza (35%). Logistic regression analyses identified 11 factors that significantly predicted a high level of knowledge about influenza. Six or more years of education completed [odds ratio (OR) 6.89 (95% confidence interval (CI) 3.58–13.24)] and recent participation in an influenza prevention activity [OR 5.27 (95% CI 2.78–9.98)] were the strongest predictors. Recommendations to aid public health efforts toward pandemic mitigation and prevention include increasing accessibility of education options for migrants and increasing frequency and accessibility of influenza prevention activities, such as community outreach and meetings. Future research should seek to identify which influenza prevention activities and education materials are most effective.

negative: Coronavirus infections of man associated with diseases other than the common cold About 14,000 paired sera, from patients with various types of acute infectious diseases with suspected viral origin, were screened by complement fixation against a wide set of viral antigens, including coronavirus OC43. A significant change in OC43 antibodies was recorded in 33 cases and a constant high titre, defined as a titre occurring in the respective age group in less than 1 % of all sera examined, was found in 45 cases. On the basis of careful retrospective analysis of hospital case records it was concluded that in 28 cases with an increase of OC43 antibody litres, and in two with titre decrease, a disease could be associated with an acute coronavirus infection. In 16 cases the disease was dominated by respiratory symptoms. Eight of these patients, four children and four adults, had pneumonia. Three of the eight pneumonia patients had, however, another concomitant infection, too. Four patients had neurological symptoms, one had severe perimyocarditis, and in five cases fever was the only symptom recorded. Among the patients with a statistically significant high titre of OC43 antibodies, there were 14 cases where a suggestive association with a disease could be envisaged on the basis of hospital records. Five of these patients had pneumonia. These results suggest that human coronaviruses, so far considered only as one group of causative agents of the common cold, may also be associated with other and more severe diseases in all age groups.

negative: COVID-19 experience: first Italian survey on healthcare staff members from a Mother-Child Research hospital using combined molecular and rapid immunoassays test The fast spread of the novel coronavirus (SARS-CoV-2) has become a global threat hitting the worldwide fragile health care system. In Italy, there is a continued COVID-19 growth of cases and deaths that requires control measures for the correct management of the epidemiological emergency. To contribute to increasing the overall knowledge of COVID-19, systematic tests in the general population are required. Here, we describe the first Italian survey performed in 727 employees belonging to a Mother-Child Research hospital tested for both viral (nasopharyngeal and oropharyngeal swabs) and antibody presence. Individuals were divided into three risk categories (high, medium and low) according to their job activity. Only one subject was positive at the swab test while 17.2% of the cohort was positive for the presence of antibodies. Results highlighted that the presence of Positive antibodies is significantly associated with high and medium risk exposure occupation (p-value=0.026) as well as cold and conjunctivitis symptoms (p-value=0.016 and 0.042 respectively). Moreover, among healthcare professionals, the category of medical doctors showed a significant association with the presence of antibodies against SARS-CoV-2 (p-value=0.0127). Finally, we detected a rapid decrease in antibody intensity between two assessments performed within a very short period (p-value=0.009). Overall, the present study increases our knowledge of the epidemiological data of COVID-19 infection in Italy, suggesting a high prevalence of immune individuals (i.e. at least among at-risk categories) and the efficacy of the combined diagnostic protocol to monitor the possible outbreak.

negative: First Reported Cases of SARS-CoV-2 Infection in Companion Animals — New York, March–April 2020 On April 22, CDC and the U.S. Department of Agriculture (USDA) reported cases of two domestic cats with confirmed infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). These are the first reported companion animals (including pets and service animals) with SARS-CoV-2 infection in the United States, and among the first findings of SARS-CoV-2 symptomatic companion animals reported worldwide. These feline cases originated from separate households and were epidemiologically linked to suspected or confirmed human COVID-19 cases in their respective households. Notification of presumptive positive animal test results triggered a One Health* investigation by state and federal partners, who determined that no further transmission events to other animals or persons had occurred. Both cats fully recovered. Although there is currently no evidence that animals play a substantial role in spreading COVID-19, CDC advises persons with suspected or confirmed COVID-19 to restrict contact with animals during their illness and to monitor any animals with confirmed SARS-CoV-2 infection and separate them from other persons and animals at home (1).

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: Functional Immune Deficiency Syndrome via Intestinal Infection in COVID-19 Using a Systems Biology approach, we integrated genomic, transcriptomic, proteomic, and molecular structure information to provide a holistic understanding of the COVID-19 pandemic. The expression data analysis of the Renin Angiotensin System indicates mild nasal, oral or throat infections are likely and that the gastrointestinal tissues are a common primary target of SARS-CoV-2. Extreme symptoms in the lower respiratory system likely result from a secondary-infection possibly by a comorbidity-driven upregulation of ACE2 in the lung. The remarkable differences in expression of other RAS elements, the elimination of macrophages and the activation of cytokines in COVID-19 bronchoalveolar samples suggest that a functional immune deficiency is a critical outcome of COVID-19. We posit that using a non-respiratory system as a major pathway of infection is likely determining the unprecedented global spread of this coronavirus. One Sentence Summary A Systems Approach Indicates Non-respiratory Pathways of Infection as Key for the COVID-19 Pandemic

negative: Molecular basis of COVID-19 relationships in different species: a one health perspective Abstract Outside the Hubei province, China, the mild form of infection and the progressive recover of the COVID-19 patients suggest the intervention of “unconventional” biological mechanisms worthy of attention. Based on the high-homology between the Spike protein epitopes of taxonomically-related coronaviruses, we hypothesized that past contact with infected dogs shield humans against the circulating SARS-CoV-2. Elseways, the recurrent virus exposure over a short time-lapse might result in the Antibody Dependent Enhancement, triggering the violent immune reaction responsible for the severe clinical outcomes observed in the Hubei province. Nevertheless, further experimental studies are desired for a confidential evaluation of the postulated hypotheses.

negative: New understanding of the damage of SARS-CoV-2 infection outside the respiratory system Abstract Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3,000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.

negative: Novel Virus Discovery and Genome Reconstruction from Field RNA Samples Reveals Highly Divergent Viruses in Dipteran Hosts We investigated whether small RNA (sRNA) sequenced from field-collected mosquitoes and chironomids (Diptera) can be used as a proxy signature of viral prevalence within a range of species and viral groups, using sRNAs sequenced from wild-caught specimens, to inform total RNA deep sequencing of samples of particular interest. Using this strategy, we sequenced from adult Anopheles maculipennis s.l. mosquitoes the apparently nearly complete genome of one previously undescribed virus related to chronic bee paralysis virus, and, from a pool of Ochlerotatus caspius and Oc. detritus mosquitoes, a nearly complete entomobirnavirus genome. We also reconstructed long sequences (1503-6557 nt) related to at least nine other viruses. Crucially, several of the sequences detected were reconstructed from host organisms highly divergent from those in which related viruses have been previously isolated or discovered. It is clear that viral transmission and maintenance cycles in nature are likely to be significantly more complex and taxonomically diverse than previously expected.

negative: Mass Spectrometric Identification of SARS-CoV-2 Proteins from Gargle Solution Samples of COVID-19 Patients Mass spectrometry (MS) can deliver valuable diagnostic data that complements genomic information and allows us to increase our current knowledge of the COVID-19 disease caused by the SARS-CoV-2 virus. We developed a simple, MS-based method to specifically detect SARS-CoV-2 proteins from gargle solution samples of COVID-19 patients. Our protocol consists of an acetone precipitation and tryptic digestion of proteins contained within the gargle solution, followed by a targeted MS analysis. Our methodology identifies unique peptides originating from SARS-CoV-2 nucleoprotein. Building on these promising initial results, faster MS protocols can now be developed as routine diagnostic tools for COVID-19 patients. Graphical Abstract Image credit (left): Gerd Altmann, Pixabay License, https://pixabay.com/illustrations/corona-coronavirus-virus-covid-19-4959447

negative: What are the factors influencing the COVID-19 outbreak in Latin America?

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

negative: Target specific mining of COVID-19 scholarly articles using one-class approach In recent years, several research articles have been published in the field of corona-virus caused diseases like severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and COVID-19. In the presence of numerous research articles, extracting best-suited articles is time-consuming and manually impractical. The objective of this paper is to extract the activity and trends of corona-virus related research articles using machine learning approaches. The COVID-19 open research dataset (CORD-19) is used for experiments, whereas several target-tasks along with explanations are defined for classification, based on domain knowledge. Clustering techniques are used to create the different clusters of available articles, and later the task assignment is performed using parallel one-class support vector machines (OCSVMs). Experiments with original and reduced features validate the performance of the approach. It is evident that the k-means clustering algorithm, followed by parallel OCSVMs, outperforms other methods for both original and reduced feature space.

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: Coronavirus Diseases (COVID-19) Current Status and Future Perspectives: A Narrative Review At the end of 2019 a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing severe acute respiratory syndrome expanded globally from Wuhan, China. In March 2020 the World Health Organization declared the SARS-Cov-2 virus a global pandemic. We performed a narrative review to describe existing literature with regard to Corona Virus Disease 2019 (COVID-19) epidemiology, pathophysiology, diagnosis, management and future perspective. MEDLINE, EMBASE and Scopus databases were searched for relevant articles. Although only when the pandemic ends it will be possible to assess the full health, social and economic impact of this global disaster, this review represents a picture of the current state of the art. In particular, we focus on public health impact, pathophysiology and clinical manifestations, diagnosis, case management, emergency response and preparedness.

negative: Selective bottlenecks shape evolutionary pathways taken during mammalian adaptation of a 1918-like avian influenza virus Avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among mammals by acquiring mutations in hemagglutinin (HA) and polymerase. Using the ferret model, we trace the evolutionary pathway by which an avian-like virus evolves the capacity for mammalian replication and airborne transmission. During initial infection, within-host HA diversity increased drastically. Then, airborne transmission fixed 2 polymerase mutations that do not confer a detectable replication advantage. In later transmissions, selection fixed advantageous HA1 variants. Transmission initially involved a “loose” bottleneck, which became strongly selective after additional HA mutations emerged. The stringency and evolutionary forces governing between-host bottlenecks may therefore change throughout host adaptation. Mutations occurred in multiple combinations in transmitted viruses, suggesting that mammalian transmissibility can evolve through multiple genetic pathways despite phenotypic constraints. Our data provide a glimpse into avian influenza virus adaptation in mammals, with broad implications for surveillance on potentially zoonotic viruses.

negative: X-Ray Structure and Inhibition of 3C-like Protease from Porcine Epidemic Diarrhea Virus Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects pigs and can have mortality rates approaching 100% in piglets, causing serious economic impact. The 3C-like protease (3CL(pro)) is essential for the coronaviral life cycle and is an appealing target for the development of therapeutics. We report the expression, purification, crystallization and 2.10 Å X-ray structure of 3CL(pro) from PEDV. Analysis of the PEDV 3CL(pro) structure and comparison to other coronaviral 3CL(pro)’s from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CL(pro)’s are conserved, with the exception of a loop that comprises the protease S(2) pocket. We found a known inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL(pro), (R)-16, to have inhibitor activity against PEDV 3CL(pro), despite that SARS-3CL(pro) and PEDV 3CL(pro) share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in (R)-16 binding to SARS-3CL(pro) are conserved in PEDV-3CL(pro); however, the sequence variation and positional difference in the loop forming the S(2) pocket may account for large observed difference in IC(50) values. This work advances our understanding of the subtle, but important, differences in coronaviral 3CL(pro) architecture and contributes to the broader structural knowledge of coronaviral 3CL(pro)’s.

negative: Unprecedented disruption of lives and work: Health, distress and life satisfaction of working adults in China one month into the COVID-19 outbreak Abstract We assess the health and wellbeing of normal adults living and working after one month of confinement to contain the COVID-19 outbreak in China. On Feb 20–21, 2020, we surveyed 369 adults in 64 cities in China that varied in their rates of confirmed coronavirus cases on their health conditions, distress and life satisfaction. 27% of the participants worked at the office, 38% resorted to working from home, and 25% stopped working due to the outbreak. Those who stopped working reported worse mental and physical health conditions as well as distress. The severity of COVID-19 in an individual's home city predicts their life satisfaction, and this relationship is contingent upon individuals’ existing chronic health issues and their hours of exercise. Our evidence supports the need to pay attention to the health of people who were not infected by the virus, especially for people who stopped working during the outbreak. Our results highlight that physically active people might be more susceptible to wellbeing issues during the lockdown. Policymakers who are considering introducing restrictive measures to contain COVID-19 may benefit from understanding such health and wellbeing implications.

negative: The epidemiology, diagnosis and treatment of COVID-19 Abstract In December 2019, the outbreak of the novel coronavirus disease (COVID-19) in China spread worldwide, becoming an emergency of major international concern. SARS-CoV-2 infection causes clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus. Human-to-human transmission via droplets, contaminated hands or surfaces has been described, with incubation times of 2-14 days. Early diagnosis, quarantine, and supportive treatments are essential to cure patients. This paper reviews the literature on all available information about the epidemiology, diagnosis, isolation and treatments of COVID-19. Treatments, including antiviral agents, chloroquine and hydroxychloroquine, corticosteroids, antibodies, convalescent plasma transfusion and vaccines, are discussed in this article. In addition, registered trials investigating treatment options for COVID-19 infection are listed.

negative: A scientometric overview of CORD-19 As the COVID-19 pandemic unfolds, researchers from all disciplines are coming together and contributing their expertise. CORD-19, a dataset of COVID-19 and coronavirus publications, has recently been published alongside calls to help mine the information it contains, and to create tools to search it more effectively. Here, we focus on the delineation of the publications included in CORD-19, and analyse this delineation from a scientometric perspective. We find that CORD-19 contains research not only on COVID-19 and coronaviruses, but on viruses in general. Publications from CORD-19 mostly focus on a few, well-defined areas, including: coronaviruses (primarily SARS, MERS, COVID-19); public health and viral epidemics; the molecular biology of viruses; influenza and other families of viruses; immunology and antivirals; methodology (testing, diagnosing, clinical trials). CORD-19 publications published in 2020, especially focused on topics of pressing relevance (spread, infection, efficacy of counter-measures), are disproportionately popular on social media. While we fully endorse the initiative that led to CORD-19, we also advise to consider its relatively broad content critically.

negative: 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.

negative: Assessment of Health Information About COVID-19 Prevention on the Internet: Infodemiological Study BACKGROUND: The internet is a large source of health information and has the capacity to influence its users. However, the information found on the internet often lacks scientific rigor, as anyone may upload content. This factor is a cause of great concern to scientific societies, governments, and users. OBJECTIVE: The objective of our study was to investigate the information about the prevention of coronavirus disease 2019 (COVID-19) on the internet. METHODS: On February 29, 2020, we performed a Google search with the terms “Prevention coronavirus,” “Prevention COVID-19,” “Prevención coronavirus,” and “Prevención COVID-19”. A univariate analysis was performed to study the association between the type of authorship, country of publication, and recommendations to avoid COVID-19 according to the World Health Organization (WHO). RESULTS: In total, 80 weblinks were reviewed. Most of them were produced in the United States and Spain (n=58, 73%) by digital media sources and official public health organizations (n=60, 75%). The most mentioned WHO preventive measure was “wash your hands frequently” (n=65, 81%). A less frequent recommendation was to “stay home if you feel unwell” (n=26, 33%). The analysis by type of author (official public health organizations versus digital media) revealed significant differences regarding the recommendation to wear a mask when you are healthy only if caring for a person with suspected COVID-19 (odds ratio [OR] 4.39). According to the country of publication (Spain versus the United States), significant differences were detected regarding some recommendations such as “wash your hands frequently” (OR 9.82), “cover your mouth and nose with your bent elbow or tissue when you cough or sneeze” (OR 4.59), or “stay home if you feel unwell” (OR 0.31). CONCLUSIONS: It is necessary to urge and promote the use of the websites of official public health organizations when seeking information on COVID-19 preventive measures on the internet. In this way, users will be able to obtain high-quality information more frequently, and such websites may improve their accessibility and positioning, given that search engines justify the positioning of links obtained in a search based on the frequency of access to them.

negative: ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

negative: COVID-19 Epidemic in the Middle Province of Northern Italy: Impact, Logistics, and Strategy in the First Line Hospital The novel coronavirus (COVID-19) began in China in early December 2019 and rapidly has spread to many countries around the globe, with the number of confirmed cases increasing every day. An epidemic has been recorded since February 20 in a middle province in Northern Italy (Lodi province, in the low Po Valley). The first line hospital had to redesign its logistical and departmental structure to respond to the influx of COVID-19-positive patients who needed hospitalization. Logistical and structural strategies were guided by the crisis unit, managing in 8 days from the beginning of the epidemic to prepare the hospital to be ready to welcome more than 200 COVID-19-positive patients with different ventilatory requirements, keeping clean emergency access lines, and restoring surgical interventions and deferred urgent, routine activity.

negative: Bird Flu, SARS and Beyond In the politically sensitive year of 1997, Hong Kong experienced an outbreak of avian flu when the deadly H5N1 virus unprecedentedly jumped the species barrier from chickens and infected human beings. Hong Kong decided to slaughter over a million chickens, and the virus was stopped in its tracks. In 2003, Hong Kong was the epicenter of the SARS pandemic, which originated in Guangdong province. The Faculty of Medicine played key roles in both instances, with its Microbiology Department successfully identifying a novel coronavirus as being responsible for SARS. Hong Kong learned from its experience and took action to combat the emergence of new infectious diseases. Such vigilance paid off in 2009, when swine flu swept the world, and in 2013, when a novel avian flu H7N9 emerged in China.

negative: Heat inactivation of serum interferes with the immunoanalysis of antibodies to SARS-CoV-2 The detection of serum antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as a new tool for the coronavirus disease-2019 (COVID-19) diagnosis. Since many coronaviruses are sensitive to heat, heating inactivation of samples at 56 ℃ prior to testing is considered a possible method to reduce the risk of transmission, but the effect of heating on the measurement of SARS-CoV-2 antibodies is still unclear. By comparing the levels of SARS-CoV-2 antibodies before and after heat inactivation of serum at 56 ℃ for 30 minutes using a quantitative fluorescence immunochromatographic assay, we shown that heat inactivation significantly interferes with the levels of antibodies to SARS-CoV-2. The IgM levels of all the 34 serum samples (100%) from COVID-19 patients decreased by an average level of 53.56%. The IgG levels were decreased in 22 of 34 samples (64.71%) by an average level of 49.54%. Similar changes can also be observed in the non-COVID-19 diseases group (n=9). Of note, 44.12% of the detected IgM levels were dropped below the cut-off value after heating, suggesting heat inactivation can lead to false-negative results of these samples. Our results indicate that heat inactivation of serum at 56 ℃ for 30 minutes interferes with the immunoanalysis of antibodies to SARS-CoV-2. Heat inactivation prior to immunoanalysis is not recommended and the possibility of false-negative results should be considered if the sample was pre-inactivated by heating.

negative: Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1 In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive. Kaposi's sarcoma-associated herpesvirus (KSHV) primarily exists in a latent state, while only 1–3% of cells support lytic infection at any specific time. KSHV reactivation from latency is an exceedingly intricate process mediated by the integration of viral and cellular factors. Previously, our lab has described early growth response-1 (Egr-1) as an essential component for the KSHV reactivation process via its ability to mediate transcription of KSHV ORF50, the gene encoding for replication and transcription activator (RTA), a viral component known to control the switch from latent to lytic infection. In here, electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) experiments revealed that Egr-1 binds KSHV ORF50 promoter (ORF50P) in at least two different GC-rich binding domains. Expression profiles of cellular egr-1 and KSHV-encoded ORF50 follow a similar pattern during de novo KSHV infection. Over-expressing Egr-1, a signaling component downstream of Raf>MEK>ERK1/2, in KSHV-infected cells activates KSHV lytic replication. Through performing more physiologically relevant experiments, we analyzed the effect of a dietary supplement containing resveratrol on KSHV-infected cells. Our results, for the first time, demonstrate resveratrol to act in lowering ERK1/2 activity and expression of Egr-1 in KSHV-infected cells, resulting in the suppression of virus reactivation from latency. Taken together, these findings will undoubtedly contribute to future studies on not only combating KSHV related disease conditions, but also on other herpesviruses-induced pathogenesis.

negative: Integrated analysis of bulk multi omic and single-cell sequencing data confirms the molecular origin of hemodynamic changes in Covid-19 infection explaining coagulopathy and higher geriatric mortality Besides severe respiratory distress, recent reports in Covid-19 patients have found a strong association between platelet counts and patient survival. Along with hemodynamic changes such as prolonged clotting time, high fibrin degradation products and D-dimers, increased levels of monocytes with disturbed morphology have also been identified. In this study, through an integrated analysis of bulk RNA-sequencing data from Covid-19 patients with data from single-cell sequencing studies on lung tissues, we found that most of the cell-types that contributed to the altered gene expression were of hematopoietic origin. We also found that differentially expressed genes in Covid-19 patients formed a significant pool of the expressing genes in phagocytic cells such as Monocytes and Platelets. Interestingly, while we observed a general enrichment for Monocytes in Covid-19 patients, we found that the signal for FCGRA3+ Monocytes was depleted. Further, we found evidence that age-associated gene expression changes in Monocytes and Platelets, associated with inflammation, mirror gene expression changes in Covid-19 patients suggesting that pro-inflammatory signalling during aging may worsen the infection in older patients. We identified more than 20 genes that change in the same direction between Covid-19 infection and aging cells that may act as potential therapeutic targets. Of particular interest were IL2RG, GNLY and GMZA expressed in Platelets, which facilitates cytokine signalling in Monocytes through an interaction with Platelets. To understand whether infection can directly manipulate the biology of Monocytes and Platelets, we hypothesize that these non-ACE2 expressing cells may be infected by the virus through the phagocytic route. We observed that phagocytic cells such as Monocytes, T-cells, and Platelets have a significantly higher expression of genes that are a part of the Covid-19 viral interactome. Hence these cell-types may have an active rather than a reactive role in viral pathogenesis to manifest clinical symptoms such as coagulopathy. Therefore, our results present molecular evidence for pursuing both anti-inflammatory and anticoagulation therapy for better patient management especially in older patients.

negative: Personal protective equipment (PPE) for vitreoretinal surgery during COVID-19

negative: COVID-19 y enfermedad cardiovascular In December 2019, in Wuhan in the province of Hubei in China, there was a report on a group of 27 patients with a pneumonia of unknown origin, linked to exposure in a market with shellfish, fish, and live animals. In January 2020, a new strain of coronavirus (SARS-CoV-2) was isolated in these patients. The disease caused by this virus has been given the name of COVID-19. During the initial stages of the pandemic, and given the scarcity of studies published about this, it was believed that this coronavirus only caused respiratory symptoms. However, as the number of patients increased, it was observed that cardiovascular disease had a fundamental role in the development and prognosis of the infection. The most important risk factors associated with mortality are age and the presence of comorbidities, particularly cardiovascular ones. The increase in the levels of troponin, natriuretic peptides, and D-dimer are of prognostic values in patients with an infection due to SARS-CoV-2. Patients with COVID-19 have an increased risk of acute myocardial infarction, myocarditis, heart failure, shock, arrhythmias, and sudden death, in relation to the systematic response to the virus and to the treatments needed in the acute phase. A review is presented in this article of the cardiovascular involvement due to SARS-CoV-2 (COVID-19).

negative: Coronavirus disease (COVID-19) in neurology and neurosurgery: A scoping review of the early literature Coronavirus disease 2019 (COVID-19) is a devastating respiratory illness that has dramatically changed the medical landscape around the world. In parallel with a rise in the number of cases globally, the COVID-19 literature has rapidly expanded with experts around the world disseminating knowledge and collaborating on best practices. To date, the literature has predominantly consisted of case reports, case series, and systemic protocols for dealing with this deadly disease from a plethora of specialties with larger observational and randomized studies only now starting to emerge. This scoping review of MEDLINE, EMBASE, SCOPUS, and the Cochrane Library aims to evaluate and summarize the current status of the COVID-19 literature at it applies to neurology and neurosurgery. Neurological symptomatology, neurological risk factors for poor prognosis, pathophysiology for neuroinvasion, and actions taken by neurological or neurosurgical services to manage the current COVID-19 crisis are reviewed.

negative: Editorial. Endonasal neurosurgery during the COVID-19 pandemic: the Singapore perspective

negative: Initial impacts of global risk mitigation measures taken during the combatting of the COVID-19 pandemic Abstract This paper presents an analysis of risk mitigation measures taken by countries around the world facing the current COVID-19 outbreak. In light of the current pandemic the authors collated and clustered (using harmonised terminology) the risk mitigation measures taken around the globe in the combat to contain, and since March 11 2020, to limit the spread of the SARS-CoV-2 virus known to cause the Coronavirus disease 2019 (COVID-19). This overview gathers lessons learnt, providing an update on the current knowledge for authorities, sectors and first responders on the effectiveness of said measures, and may allow enhanced prevention, preparedness and response for future outbreaks. Various measures such as mobility restrictions, physical distancing, hygienic measures, socio-economic restrictions, communication and international support mechanisms have been clustered and are reviewed in terms of the nature of the actions taken and their qualitative early-perceived impact. At the time of writing, it is still too premature to express the quantitative effectiveness of each risk mitigation cluster, but it seems that the best mitigation results are reported when applying a combination of voluntary and enforceable measures.

negative: Tourism crises and island destinations: Experiences in Penang, Malaysia Abstract Crisis management and tourism is attracting increasing attention as an industry practice and subject of academic enquiry, not least in South East Asia which has been affected by a number of severe crises in recent years. However, organisations are not always well prepared and response strategies can be deficient. The paper discusses issues of tourism crisis management with specific reference to the popular Malaysian destination of Penang. Findings are based on qualitative research consisting of semi-structured interviews with industry leaders from assorted sectors. Tourism in Penang emerges as vulnerable to regional and global events which act as a trigger for tourism crises, demanding a response in which various strategies are employed. The destination is also seen to recover fairly quickly from experiences of crises, but a well designed and formulated tourism crisis management plan under the stewardship of the public sector is necessary to mitigate further damage in the future.

negative: Coronavirus Disease 2019 (COVID-19): A Perspective from China In December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in Wuhan, Hubei Province, China and spread across China and beyond. On February 12, 2020, WHO officially named the disease caused by the novel coronavirus as Coronavirus Disease 2019 (COVID-19). Since most COVID-19 infected patients were diagnosed with pneumonia and characteristic CT imaging patterns, radiological examinations have become vital in early diagnosis and assessment of disease course. To date, CT findings have been recommended as major evidence for clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the etiology, epidemiology, and clinical symptoms of COVID-19, while highlighting the role of chest CT in prevention and disease control. A full translation of this article in Chinese is available in the supplement. - 请见䃼充资料阅读文章中文版∘

negative: Early dynamics of transmission and control of COVID-19: a mathematical modelling study BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 95 333 confirmed cases as of March 5, 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Combining a mathematical model of severe SARS-CoV-2 transmission with four datasets from within and outside Wuhan, we estimated how transmission in Wuhan varied between December, 2019, and February, 2020. We used these estimates to assess the potential for sustained human-to-human transmission to occur in locations outside Wuhan if cases were introduced. METHODS: We combined a stochastic transmission model with data on cases of coronavirus disease 2019 (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January, 2020, and February, 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. To estimate the early dynamics of transmission in Wuhan, we fitted a stochastic transmission dynamic model to multiple publicly available datasets on cases in Wuhan and internationally exported cases from Wuhan. The four datasets we fitted to were: daily number of new internationally exported cases (or lack thereof), by date of onset, as of Jan 26, 2020; daily number of new cases in Wuhan with no market exposure, by date of onset, between Dec 1, 2019, and Jan 1, 2020; daily number of new cases in China, by date of onset, between Dec 29, 2019, and Jan 23, 2020; and proportion of infected passengers on evacuation flights between Jan 29, 2020, and Feb 4, 2020. We used an additional two datasets for comparison with model outputs: daily number of new exported cases from Wuhan (or lack thereof) in countries with high connectivity to Wuhan (ie, top 20 most at-risk countries), by date of confirmation, as of Feb 10, 2020; and data on new confirmed cases reported in Wuhan between Jan 16, 2020, and Feb 11, 2020. FINDINGS: We estimated that the median daily reproduction number (R(t)) in Wuhan declined from 2·35 (95% CI 1·15–4·77) 1 week before travel restrictions were introduced on Jan 23, 2020, to 1·05 (0·41–2·39) 1 week after. Based on our estimates of R(t), assuming SARS-like variation, we calculated that in locations with similar transmission potential to Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. INTERPRETATION: Our results show that COVID-19 transmission probably declined in Wuhan during late January, 2020, coinciding with the introduction of travel control measures. As more cases arrive in international locations with similar transmission potential to Wuhan before these control measures, it is likely many chains of transmission will fail to establish initially, but might lead to new outbreaks eventually. FUNDING: Wellcome Trust, Health Data Research UK, Bill & Melinda Gates Foundation, and National Institute for Health Research.

negative: 2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China Abstract We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.

negative: Transmission parameters of the A/H1N1 (2009) influenza virus pandemic: a review Please cite this paper as: Boëlle P‐Y et al. (2011) Transmission parameters of the A/H1N1 (2009) influenza virus pandemic: a review. Influenza and Other Respiratory Viruses 5(5), 306–316. Background The new influenza virus A/H1N1 (2009), identified in mid‐2009, rapidly spread over the world. Estimating the transmissibility of this new virus was a public health priority. Methods We reviewed all studies presenting estimates of the serial interval or generation time and the reproduction number of the A/H1N1 (2009) virus infection. Results Thirteen studies documented the serial interval from household or close‐contact studies, with overall mean 3 days (95% CI: 2·4, 3·6); taking into account tertiary transmission reduced this estimate to 2·6 days. Model‐based estimates were more variable, from 1·9 to 6 days. Twenty‐four studies reported reproduction numbers for community‐based epidemics at the town or country level. The range was 1·2–3·1, with larger estimates reported at the beginning of the pandemic. Accounting for under‐reporting in the early period of the pandemic and limiting variation because of the choice of the generation time interval, the reproduction number was between 1·2 and 2·3 with median 1·5. Discussion The serial interval of A/H1N1 (2009) flu was typically short, with mean value similar to the seasonal flu. The estimates of the reproduction number were more variable. Compared with past influenza pandemics, the median reproduction number was similar (1968) or slightly smaller (1889, 1918, 1957).

negative: A territory-wide study of early COVID-19 outbreak in Hong Kong community: A clinical, epidemiological and phylogenomic investigation Background: Initial cases of coronavirus disease 2019 (COVID-19) reported in Hong Kong were mostly imported cases from Mainland China. However, most cases reported in February 2020 were local infections with unknown source, indicating local community transmissions. This study aimed to report the clinical, epidemiological and phylogenomic characteristics of the local cases of COVID-19 in our community. Methods: We extracted the demographic, clinical and epidemiological data from 50 COVID-19 patients, who accounted for 53.8% of the cases in Hong Kong by the end of February 2020. We used both Nanopore and Illumina platforms to perform whole-genome sequencing (WGS) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from these patients. Phylogenetic relatedness among these local cases and their placement in the global phylogeny were examined. The evolutionary rate and divergence time of transmission were also determined. Findings: Of these 50 patients, only three (6.0%) had visited Wuhan while 43 (86.0%) did not have recent travel records. The average interval from symptom onset to hospital admission was 8.5 days. The most common signs and symptoms on admission were cough (74.0%) and fever (58.0%). Radiographic abnormality was found in 46 (92.0%) patients. Three (6.0%) patients required ICU admission. Phylogenetic analysis concurred with epidemiological investigation that 42 (84.0%) cases could be grouped into six transmission clusters. Forty-four (88.0%) cases harboured a common mutation Orf3a G251V. Global phylogeny of SARS-CoV-2 revealed that most (88.0%) cases in Hong Kong were clustered in two subclades with the strains from other countries. The estimated time to the most recent common ancestor (tMRCA) of COVID-2019 outbreak in Hong Kong was December 24, 2019 with an evolutionary rate of 3.04x10-3 substitutions per site per year. The reproduction number value was 1.84 as of February 28, 2020 in Hong Kong. Interpretation: We provided a territory-wide overview of COVID-19 in Hong Kong, which has borders connecting to Mainland China. Transmission in closed settings especially during family and religious gatherings is a hallmark of the recently reported cases. The reproduction number value indicated an ongoing outbreak in the community. Social distancing and vigilant epidemiological control are crucial to the containment of COVID-19 transmission

negative: NewsCAP: Multisystem inflammatory syndrome in children appears to be related to COVID-19

negative: Antigenic Subversion: A Novel Mechanism of Host Immune Evasion by Ebola Virus In addition to its surface glycoprotein (GP(1,2)), Ebola virus (EBOV) directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. The generation of secreted antigens has been studied in several viruses and suggested as a mechanism of host immune evasion through absorption of antibodies and interference with antibody-mediated clearance. However such a role has not been conclusively determined for the Ebola virus sGP. In this study, we immunized mice with DNA constructs expressing GP(1,2) and/or sGP, and demonstrate that sGP can efficiently compete for anti-GP(12) antibodies, but only from mice that have been immunized by sGP. We term this phenomenon “antigenic subversion”, and propose a model whereby sGP redirects the host antibody response to focus on epitopes which it shares with membrane-bound GP(1,2), thereby allowing it to absorb anti-GP(1,2) antibodies. Unexpectedly, we found that sGP can also subvert a previously immunized host's anti-GP(1,2) response resulting in strong cross-reactivity with sGP. This finding is particularly relevant to EBOV vaccinology since it underscores the importance of eliciting robust immunity that is sufficient to rapidly clear an infection before antigenic subversion can occur. Antigenic subversion represents a novel virus escape strategy that likely helps EBOV evade host immunity, and may represent an important obstacle to EBOV vaccine design.

negative: Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. These genomes were from the viruses causing infections in the earliest recognized phase of the pandemic affecting Houston. Substantial viral genomic diversity was identified, which we interpret to mean that the virus was introduced into Houston many times independently by individuals who had traveled from different parts of the country and the world. The majority of viruses are apparent progeny of strains derived from Europe and Asia. We found no significant evidence of more virulent viral types, stressing the linkage between severe disease, underlying medical conditions, and perhaps host genetics. We discovered a signal of selection acting on the spike protein, the primary target of massive vaccine efforts worldwide. The data provide a critical resource for assessing virus evolution, the origin of new outbreaks, and the effect of host immune response. Significance COVID-19, the disease caused by the SARS-CoV-2 virus, is a global pandemic. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. We identified no evidence that a particular strain or its progeny causes more severe disease, underscoring the connection between severe disease, underlying health conditions, and host genetics. Some amino acid replacements in the spike protein suggest positive immune selection is at work in shaping variation in this protein. Our analysis traces the early molecular architecture of SARS-CoV-2 in Houston, and will help us to understand the origin and trajectory of future infection spikes.

negative: Signals of T(h)2 immune response from COVID-19 patients requiring intensive care

negative: Persistence of intestinal SARS-CoV-2 infection in patients with COVID-19 leads to re-admission after pneumonia resolved Abstract The current reports of COVID-19 focus on the respiratory system, but intestinal infections caused by SARS-CoV-2 are also worthy of attention. Here we report persistence of intestinal SARS-CoV-2 infection in three cases with COVID-19 leads to re-admission after pneumonia resolved.

negative: A mathematical model for simulating the transmission of Wuhan novel Coronavirus As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probable be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from a seafood market (reservoir) to people, we simplified the model as Reservoir-People transmission network model. The basic reproduction number (R0) was calculated from the RP model to assess the transmissibility of the 2019-nCoV.

negative: Discovery of retroviral homologs in bats: implications for the origin of mammalian gammaretroviruses. Gammaretroviruses infect a wide range of vertebrate species where they are associated with leukemias, neurological diseases and immunodeficiencies. However, the origin of these infectious agents is unknown. Through a phylogenetic analysis of viral gene sequences, we show that bats harbor an especially diverse set of gammaretroviruses. In particular, phylogenetic analysis places Rhinolophus ferrumequinum retrovirus (RfRV), a new gammaretrovirus identified by de novo analysis of the Rhinolophus ferrumequinum transcriptome, and six other gammaretroviruses from different bat species, as basal to other mammalian gammaretroviruses. An analysis of the similarity in the phylogenetic history between the gammaretroviruses and their bat hosts provided evidence for both host-virus codivergence and cross-species transmission. Taken together, these data provide new insights into the origin of the mammalian gammaretroviruses.

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

negative: Imaging in corona virus disease 2019 (COVID-19)—A scoping review Coronavirus Disease-2019 (COVID-19) originated in the Wuhan, Hubei Province, China in November 2019 and has since been declared a pandemic by the WHO. COVID-19 is an acute infectious disease, primarily affecting the respiratory system. Currently, real-time reverse transcription polymerase chain reaction (RT-PCR) performed on respiratory specimens is considered the reference by which to diagnose COVID-19. However, the limitations of RT-PCR, specifically, the fact that it is time-consuming and inadequate for the assessment of disease severity, have affected the process of epidemiological disease containment and has taken a toll on the healthcare management chain. As the risk of infection for other patients and personnel must be kept to a minimum, the indications for imaging have to be carefully considered. Imaging is primarily performed in patients with a negative RT-PCR, but a high clinical suspicion of COVID-19, or, in patients with diagnosed COVID-19 who are suffering from moderate to severe symptoms. In this article, we review the typical imaging findings in COVID-19, the differential diagnoses, and common complications.

negative: Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4.

negative: Norming COVID‐19: The Urgency of a Non‐Humanist Holism

negative: Laboratory diagnosis of SARS-CoV-2 - A review of current methods At present the whole world is facing pandemic of the Coronavirus disease (COVID-19); caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease has rapidly spreads across the world from its origin of Wuhan, China and affected millions people worldwide and make them to remain in their homes. The knowledge of available laboratory methods is essential for early and correct diagnosis of COVID-19 to identify new cases as well as monitoring treatment of confirmed cases. In this review we aim to provide the updated information about selection of specimens and availability of various diagnostic methods and their utility with current findings for the laboratory diagnosis of SARS-CoV-2 infection. This will guide the healthcare professionals and government organizations to make strategy for establishing diagnostic facilities for SARS-CoV-2 infections.

negative: Coronary and structural heart disease interventions during COVID-19 pandemic: A road map for clinicians and health care delivery systems BACKGROUND: Because of the COVID-19 pandemic, cath labs have had to modify their workflow for elective and urgent patients. METHODS: We surveyed 16 physicians across 3 hospitals in our healthcare system to address COVID-19 related concerns in the management of interventional and structural heart disease patients, and to formulate system wide criteria for deferring cases till after the pandemic. RESULTS: Our survey yielded common concerns centered on the need to protect patients, cath lab staff and physicians from unnecessary exposure to COVID-19; for COVID-19 testing prior to arrival to the cath lab; for clear communication between the referring physician and the interventionalist; but there was initial uncertainty among physicians regarding the optimal management of ST elevation myocardial infarction (STEMI; percutaneous coronary intervention versus thrombolytics). Patients with stable angina and hemodynamically stable acute coronary syndromes were deemed suitable for initial medical management, except when they had large ischemic burden. Most transcatheter aortic valve implantations (TAVI) were felt appropriate for postponement except in symptomatic patients with aortic valve area <0.5 cm(2) or recent hospitalization for heart failure (HF). Most percutaneous mitral valve repair (pMVR) procedures were felt appropriate for postponement except in patients with HF. All left atrial appendage closure (LAAC) and patent foramen ovale (PFO)/atrial septal defect (ASD) closure procedures were felt appropriate for postponement. CONCLUSION: Our survey of an experienced team of clinicians yielded concise guidelines to direct the management of CAD and structural heart disease patients during the initial phases of the COVID-19 pandemic.

negative: Evolution and Structural Organization of the C Proteins of Paramyxovirinae The phosphoprotein (P) gene of most Paramyxovirinae encodes several proteins in overlapping frames: P and V, which share a common N-terminus (PNT), and C, which overlaps PNT. Overlapping genes are of particular interest because they encode proteins originated de novo, some of which have unknown structural folds, challenging the notion that nature utilizes only a limited, well-mapped area of fold space. The C proteins cluster in three groups, comprising measles, Nipah, and Sendai virus. We predicted that all C proteins have a similar organization: a variable, disordered N-terminus and a conserved, α-helical C-terminus. We confirmed this predicted organization by biophysically characterizing recombinant C proteins from Tupaia paramyxovirus (measles group) and human parainfluenza virus 1 (Sendai group). We also found that the C of the measles and Nipah groups have statistically significant sequence similarity, indicating a common origin. Although the C of the Sendai group lack sequence similarity with them, we speculate that they also have a common origin, given their similar genomic location and structural organization. Since C is dispensable for viral replication, unlike PNT, we hypothesize that C may have originated de novo by overprinting PNT in the ancestor of Paramyxovirinae. Intriguingly, in measles virus and Nipah virus, PNT encodes STAT1-binding sites that overlap different regions of the C-terminus of C, indicating they have probably originated independently. This arrangement, in which the same genetic region encodes simultaneously a crucial functional motif (a STAT1-binding site) and a highly constrained region (the C-terminus of C), seems paradoxical, since it should severely reduce the ability of the virus to adapt. The fact that it originated twice suggests that it must be balanced by an evolutionary advantage, perhaps from reducing the size of the genetic region vulnerable to mutations.

negative: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study BACKGROUND: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. METHODS: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. FINDINGS: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. INTERPRETATION: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. FUNDING: National Key R&D Program of China.

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: 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: 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: Global academic response to COVID‐19: Cross‐sectional study This study explores the response to COVID‐19 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A cross‐sectional bibliometric review of COVID‐19 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submission‐to‐acceptance time and availability of original data. Publisher‐responsiveness was assessed by measuring the acceptance‐to‐publication time and the provision of open access. Three hundred and ninety‐eight of 2,835 COVID‐19 and 55 of 1,513 MERS search results were eligible. Most COVID‐19 studies were clinical reports (n = 242; 60.8%). The submission‐to‐acceptance [median: 5 days (IQR: 3–11) versus 71.5 days (38–106); P < .001] and acceptance‐to‐publication [median: 5 days (IQR: 2–8) versus 22.5 days (4–48·5‐; P < .001] times were strikingly shorter for COVID‐19. Almost all COVID‐19 (n = 396; 99.5%) and MERS (n = 55; 100%) studies were open‐access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID‐19 and 10 (18.2%) MERS studies (P = .203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only one‐in‐four were published alongside original data, which is a key target for improvement.

negative: COVID-19, A Clinical Syndrome Manifesting as Hypersensitivity Pneumonitis

negative: The “Three Italy” of the COVID-19 epidemic and the possible involvement of SARS-CoV-2 in triggering complications other than pneumonia Coronavirus disease 2019 (COVID-19), first reported in Wuhan, the capital of Hubei, China, has been associated to a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In March 2020, the World Health Organization declared the SARS-CoV-2 infection a global pandemic. Soon after, the number of cases soared dramatically, spreading across China and worldwide. Italy has had 12,462 confirmed cases according to the Italian National Institute of Health (ISS) as of March 11, and after the “lockdown” of the entire territory, by May 4, 209,254 cases of COVID-19 and 26,892 associated deaths have been reported. We performed a review to describe, in particular, the origin and the diffusion of COVID-19 in Italy, underlying how the geographical circulation has been heterogeneous and the importance of pathophysiology in the involvement of cardiovascular and neurological clinical manifestations.

negative: All eyes on Coronavirus—What do we need to know as ophthalmologists

negative: Hypolipidemia is associated with the severity of COVID-19 Abstract Background Many patients with coronavirus disease 2019 (COVID-19) suffer multiple organ dysfunctions. However, whether patients develop dyslipidemia is unknown. Objective In this study, we aimed to investigate the pathological alterations of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and total cholesterol (TC) in COVID-19 patients and their relationships with the disease severity. Methods A retrospective study was performed to examine serum levels of LDL-c, HDL-c, and TC on 597 COVID-19 patients (mild: 394; severe, 171; critical: 32) who were hospitalized in our center between February 1 and March 3, 2020. Age and gender-matched normal subjects (n=50) who had routine laboratory lipid tests between October 1 and November 1, 2019 in our center were included as the control group. Results LDL-c and TC levels were significantly lower in COVID-19 patients as compared with normal subjects (p<0.001). There were significant and gradual decreases in levels of LDL-c (median (IQR) in mg/dL, mild: 91 (76, 104); severe 86 (69, 102); critical: 69 (48, 81); p<0.02) and TC (mild: 173 (148, 203); severe 167 (138, 197); critical: 125 (95, 162); p<0.05) across all three groups. HDL-c levels only decreased significantly in critical cases as compared to levels in mild and severe cases. LDL-c and TC levels inversely correlated with C-reactive protein and IL-6, and positively correlated with the number of lymphocytes in patients. Conclusions Development of hypolipidemia starts in patients with mild symptoms. It progressively becomes worse in an association with the disease severity.

negative: COVID-19: Emergence, Spread, Possible Treatments, and Global Burden The Coronavirus (CoV) is a large family of viruses known to cause illnesses ranging from the common cold to acute respiratory tract infection. The severity of the infection may be visible as pneumonia, acute respiratory syndrome, and even death. Until the outbreak of SARS, this group of viruses was greatly overlooked. However, since the SARS and MERS outbreaks, these viruses have been studied in greater detail, propelling the vaccine research. On December 31, 2019, mysterious cases of pneumonia were detected in the city of Wuhan in China's Hubei Province. On January 7, 2020, the causative agent was identified as a new coronavirus (2019-nCoV), and the disease was later named as COVID-19 by the WHO. The virus spread extensively in the Wuhan region of China and has gained entry to over 210 countries and territories. Though experts suspected that the virus is transmitted from animals to humans, there are mixed reports on the origin of the virus. There are no treatment options available for the virus as such, limited to the use of anti-HIV drugs and/or other antivirals such as Remdesivir and Galidesivir. For the containment of the virus, it is recommended to quarantine the infected and to follow good hygiene practices. The virus has had a significant socio-economic impact globally. Economically, China is likely to experience a greater setback than other countries from the pandemic due to added trade war pressure, which have been discussed in this paper.

negative: How will this continue? Modelling interactions between the COVID-19 pandemic and policy responses Much of the uncertainty about the progression of the COVID-19 pandemic stems from questions about when and how non-pharmaceutical interventions (NPI) by governments, in particular social distancing measures, are implemented, to what extent the population complies with these measures, and how compliance changes through time. Further uncertainty comes from a lack of knowledge of the potential effects of removing interventions once the epidemic is declining. By combining an epidemiological model of COVID-19 for the United Kingdom with simple sub-models for these societal processes, this study aims to shed light on the conceivable trajectories that the pandemic might follow over the next 1.5 years. We show strong improvements in outcomes if governments review NPI more frequently whereas, in comparison, the stability of compliance has surprisingly small effects on cumulative mortality. Assuming that mortality does considerably increase once a country's hospital capacity is breached, we show that the inherent randomness of societal processes can lead to a wide range of possible outcomes, both in terms of disease dynamics and mortality, even when the principles according to which policy and population operate are identical.. Our model is easily modified to take other aspects of the socio-pandemic interaction into account.

negative: Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus This paper concerns study of the genome of the Wuhan Seafood Market isolate believed to represent the causative agent of the disease COVID-19. This is to find a short section or sections of viral protein sequence suitable for preliminary design proposal for a peptide synthetic vaccine and a peptidomimetic therapeutic, and to explore some design possibilities. The project was originally directed towards a use case for the Q-UEL language and its implementation in a knowledge management and automated inference system for medicine called the BioIngine, but focus here remains mostly on the virus itself. However, using Q-UEL systems to access relevant and emerging literature, and to interact with standard publically available bioinformatics tools on the Internet, did help quickly identify sequences of amino acids that are well conserved across many coronaviruses including 2019-nCoV. KRSFIEDLLFNKV was found to be particularly well conserved in this study and corresponds to the region around one of the known cleavage sites of the SARS virus that are believed to be required for virus activation for cell entry. This sequence motif and surrounding variations formed the basis for proposing a specific synthetic vaccine epitope and peptidomimetic agent. The work can, nonetheless, be described in traditional bioinformatics terms, and readily reproduced by others, albeit with the caveat that new data and research into 2019-nCoV is emerging and evolving at an explosive pace. Preliminary studies using molecular modeling and docking, and in that context the potential value of certain known herbal extracts, are also described.

negative: Risk Factors for COVID-19 versus non-COVID-19 related in-hospital and community deaths by Local Authority District in Great Britain Objectives: To undertake a preliminary hypothesis-generating analysis exploring putative risk factors for coronavirus diseae 2019 (COVID-19) population-adjusted deaths, compared with non-COVID-19 related deaths, at a local authority district (LAD) level in hospital, care homes and at home. Design: Ecological retrospective cohort study Setting Local authority districts (LADs) in England, Scotland and Wales (Great Britain (GB)). Participants All LAD deaths registered by week 16 of 2020. Main Outcome Measures Death registration where COVID-19 is mentioned as a contributing factor per 100,000 people in all settings, and in i) cares homes, ii) hospitals or iii) home only, in comparison to non-COVID-19 related deaths. Results Across GB by week 16 of 2020, 20,684 deaths had been registered mentioning COVID-19, equivalent to 25.6 per 100,000 people. Significant risk factors for LAD COVID-19 death in comparison to non-COVID-19 related death were air pollution and proportion of the population who were female. Significant protective factors were higher air temperature and proportion of the population who were ex-smokers. Conversely, for all COVID-19 unrelated deaths in comparison to COVID-19 deaths, higher rates of communal living, higher population rates of chronic kidney disease, chronic obstructive pulmonary disease, cerebrovascular disease deaths under 75 and dementia were predictive of death, whereas, higher rates of flight passengers was protective. Looking at individual setttings, the most notable findings in care homes was Scotland being a significant risk factor for COVID-19 related deaths compared to England. For hospital setting, the proportion of the population who were from black and Asian minority ethnic (BAME) groups significantly predicted COVID-19 related death. Conclusions This is the first study within GB to assess COVID-19 related deaths in comparison to COVID-19 unrelated deaths across hospital, care homes and home combined. As an ecological study, the results cannot be directly extrapolated to individuals. However, the analysis may be informative for public health policy and protective measures. From our hypothesis-generating analysis, we propose that air pollution is a significant risk factor and high temperature a significant protective factor for COVID-19 related deaths. These factors cannot readily be modelled at an individual level. Scottish local authorities and local authorities with a higher proportion of individuals of BAME origin are potential risk factors for COVID-19 related deaths in care homes and in hospitals, respectively. Altogether, this analysis shows the benefits of access to high quality open data for public information, public health policy and further research.

negative: Community Under Stress: Trust, Reciprocity, and Community Collective Efficacy During SARS Outbreak The study of epidemics is almost non-existent in sociological literature, even though such outbreaks can have detrimental effects on communities. The occurrence of SARS (Severe Acute Respiratory Syndrome) in 2003 provides a rare opportunity to understand the social functioning of a community during the outbreak of an epidemic. To evaluate the extensive social impact of such an outbreak, we focus on the effects of perceived collective efficacy. Specifically, we focus on how the collective efficacy of a community, measured by trust and reciprocal relations, is related to collective action in places where SARS occurred and those where SARS did not occur. The study is based on a unique data set, the 2003 Taiwan Social Image Survey, collected during the outbreak of SARS in Taiwan. Our findings show that community collective efficacy, measured by trust and reciprocity, is not associated with community collective action when an outbreak of an epidemic occurs.

negative: Trend Analysis and Forecasting of COVID-19 outbreak in India COVID-19 is spreading really fast around the world. The current study describes the situation of the outbreak of this disease in India and predicts the number of cases expected to rise in India. The study also discusses the regional analysis of Indian states and presents the preparedness level of India in combating this outbreak. The study uses exploratory data analysis to report the current situation and uses time-series forecasting methods to predict the future trends. The data has been considered from the repository of John Hopkins University and covers up the time period from 30th January 2020 when the first case occurred in India till the end of 24th March 2020 when the Prime Minister of India declared a complete lockdown in the country for 21 days starting 25th March 2020. The major findings show that number of infected cases in India is rising quickly with the average infected cases per day rising from 10 to 73 from the first case to the 300th case. The current mortality rate for India stands around 1.9. Kerala and Maharashtra are the top two infected states in India with more than 100 infected cases reported in each state, respectively. A total of 25 states have reported at least one infected case, however only 8 of them have reported deaths due to COVID-19. The ARIMA model prediction shows that the infected cases in India may reach up to 700 thousands in next 30 days in worst case scenario while most optimistic scenario may restrict the numbers up to 1000-1200. Also, the average forecast by ARIMA model in next 30 days is around 7000 patients from the current numbers of 536. Based on the forecasting model by Holts linear trends, an expected 3 million people may get infected if control measures are not taken in the near future. This study will be useful for the key stakeholders like Government Officials and Medical Practitioners in assessing the trends for India and preparing a combat plan with stringent measures. Also, this study will be helpful for data scientists, statisticians, mathematicians and analytics professionals in predicting outbreak numbers with better accuracy.

negative: Implementing a One Health approach to emerging infectious disease: reflections on the socio-political, ethical and legal dimensions BACKGROUND: ‘One Health’ represents a call for health researchers and practitioners at the human, animal and environmental interfaces to work together to mitigate the risks of emerging and re-emerging infectious diseases (EIDs). A One Health approach emphasizing inter-disciplinary co-operation is increasingly seen as necessary for effective EID control and prevention. There are, however, socio-political, ethical and legal challenges, which must be met by such a One Health approach. DISCUSSION: Based on the philosophical review and critical analysis of scholarship around the theory and practice of One Health it is clear that EID events are not simply about pathogens jumping species barriers; they are comprised of complex and contingent sets of relations that involve socioeconomic and socio-political drivers and consequences with the latter extending beyond the impact of the disease. Therefore, the effectiveness of policies based on One Health depends on their implementation and alignment with or modification of public values. SUMMARY: Despite its strong motivating rationale, implementing a One Health approach in an integrated and considered manner can be challenging, especially in the face of a perceived crisis. The effective control and prevention of EIDs therefore requires: (i) social science research to improve understanding of how EID threats and responses play out; (ii) the development of an analytic framework that catalogues case experiences with EIDs, reflects their dynamic nature and promotes inter-sectoral collaboration and knowledge synthesis; (iii) genuine public engagement processes that promote transparency, education and capture people’s preferences; (iv) a set of practical principles and values that integrate ethics into decision-making procedures, against which policies and public health responses can be assessed; (v) integration of the analytic framework and the statement of principles and values outlined above; and (vi) a focus on genuine reform rather than rhetoric.

negative: Epidemiology of COVID-19 It seems that coronaviruses take an important place in the 21th century history. Five of seven human coronavirus was isolated in this century. Unfortunately, last three of them entered our life with a fear of outbreak, pandemic or death. Last human coronavirus which emerged world from Wuhan China, SARS CoV-2 and its clinical expression, Coronavirus disease (COVID-19) recently taken a significant place in our daily practice. Initial reports showed that, its origin was bats. It transmitted human to human by droplet and contact routes, but some doubt about airborne, fecal or intrauterine transmission also should be removed. Its R0 value is 2.3 but it could be as high as 5.7. Its case fatality rate was 6.3, but it was different in different ages and counties, and it could be over 15%. According to early models total 10–12 weeks is required to control an outbreak in the community. While different countries show different daily case numbers, total number of case, case mortality rates or R0, it seems they show a similar epidemic curve. Every day we learn new data about the current outbreak. Since the outbreak is not over yet, every detail should be evaluated carefully and the updates should be followed closely to monitor the epidemiological properties of COVID-19.

negative: COVID-19 detection using deep learning models to exploit Social Mimic Optimization and structured chest X-ray images using fuzzy color and stacking approaches Abstract Coronavirus causes a wide variety of respiratory infections and it is an RNA-type virus that can infect both humans and animal species. It often causes pneumonia in humans. Artificial intelligence models have been helpful for successful analyses in the biomedical field. In this study, Coronavirus was detected using a deep learning model, which is a sub-branch of artificial intelligence. Our dataset consists of three classes namely: coronavirus, pneumonia, and normal X-ray imagery. In this study, the data classes were restructured using the Fuzzy Color technique as a preprocessing step and the images that were structured with the original images were stacked. In the next step, the stacked dataset was trained with deep learning models (MobileNetV2, SqueezeNet) and the feature sets obtained by the models were processed using the Social Mimic optimization method. Thereafter, efficient features were combined and classified using Support Vector Machines (SVM). The overall classification rate obtained with the proposed approach was 99.27%. With the proposed approach in this study, it is evident that the model can efficiently contribute to the detection of COVID-19 disease.

negative: How to handle patients with autoimmune rheumatic and inflammatory bowel diseases in the COVID-19 era: An expert opinion • A correct patient risk stratification is of paramount importance for the proper management of economic and human resources. • It's fundamental to prioritize clinical trials evaluating dosing, prophylaxis, and treatment with immunosuppressant in COVID-19 in order to avoid either an overuse and a treatment shortage. • Future controlled studies may highlight in our patients a potential preventive role of immunosuppressant therapies in the development of severe forms of Covid-19. • Despite the overall risk of infection in rheumatic and gastroenterological diseases a conclusive association between these diseases and COVID −19 remains questionable.

negative: A nomenclature for avian coronavirus isolates and the question of species status. Currently, there is no agreed naming system for isolates of infectious bronchitis virus (IBV), whose host is the domestic fowl (Gallus gallus domesticus). A uniform, informative system for naming IBV isolates would be very helpful. Furthermore, the desirability of a single naming system has become more important with the recent discoveries that coronaviruses with genome organizations and gene sequences very similar to those of IBV have been isolated from turkeys (Meleagris gallopavo) and pheasants (Phasianus colchicus). To date, no genetic features have been found that are unique to turkey isolates and to pheasant isolates that would permit unequivocal differentiation from IBVs. Should the avian coronaviruses from turkeys, pheasants and other birds each be considered as distinct coronavirus species? Or should avian coronaviruses that have gene sequences similar to those of IBV be treated as host-range variants of IBV or, more objectively, as host-range variants of a species that might be called avian coronavirus (ACoV)? Clearly, the topic of avian coronavirus species differentiation requires debate. For the moment, a naming system for avian coronavirus isolates is overdue. Increasingly, papers will include data of coronaviruses isolated from more than one species of bird. It is desirable to have a nomenclature for avian coronaviruses that indicates the host species of origin. Furthermore, it would be helpful if the name of an isolate included the country/region of origin, an isolate number and the year of isolation. The names of avian paramyxovirus (APMV) and avian influenza virus (AIV) isolates have long since contained this information; I suggest that we adopt a similar convention for isolates of avian coronaviruses. For example, the D274 isolate of IBV could be named chicken/Netherlands/D274/78. Representatives of avian coronaviruses from turkey and pheasant would include turkey/United States(Nc)/NC95/95 and pheasant/UK/750/83. Two upper case letters would be used to denote country of isolation, whereas one upper and one lower case letter would be used to indicate state or province, e.g. Nc, North Carolina. The full-length names could be abbreviated, when desired, similar to the convention used for AIV isolates, e.g. chNL78, tyUS(Nc)95 and phUK83. If the serotype of an isolate has been clearly established, this might be included in the name at end, like the serotype designation of AIVs, e.g. chicken/China/NRZ/91 (Mass.) for the Chinese isolate of the Massachusetts serotype. This suggested naming system for isolates is essentially neutral with regard to whether viruses from different bird species should be considered as different coronavirus species or simply as variants of just one avian coronavirus species. In my opinion an informative nomenclature for avian coronavirus isolates is required now, to improve communication, and need not be delayed until a decision on the definition of coronavirus species has been made.

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: The association between international and domestic air traffic and the coronavirus (COVID-19) outbreak BACKGROUND: The World Health Organization (WHO) has declared the current outbreak of the novel coronavirus (COVID-19) a global pandemic. Many countries are facing increasing numbers of COVID-19 cases, which are, in their origin mostly attributed to regular international flight connections with China. This study aims to investigate this relation by analyzing available data on air traffic volume and the spread of COVID-19 cases. METHODS: and findings: We analyzed available data on current domestic and international passenger volume and flight routes and compared these to the distribution of domestic and international COVID-19 cases. RESULTS: Our data indicate a strong linear correlation between domestic COVID-19 cases and passenger volume for regions within China (r(2) = 0.92, p = 0.19) and a significant correlation between international COVID-19 cases and passenger volume (r(2) = 0.98, p < 0.01). CONCLUSIONS: The number of flight routes as well as total passenger volume are highly relevant risk factors for the spread of current COVID-19. Multiple regions within Asia, as well as some in North America and Europe are at serious risk of constant exposure to COVID-19 from China and other highly infected countries. Risk for COVID-19 exposure remains relatively low in South America and Africa. If adequate measures are taken, including on-site disease detection and temporary passenger quarantine, limited but not terminated air traffic can be a feasible option to prevent a long-term crisis. Reasonable risk calculations and case evaluations per passenger volume are crucial aspects which must be considered when reducing international flights.

negative: Corticosteroids as Adjunctive Therapy in Severe Community-Acquired Pneumonia Mortality in community acquired pneumonia (CAP) has not decreased in the intensive care unit (ICU), despite progress in antimicrobial therapy [1, 2]. Approximately 10% of patients hospitalized with CAP are admitted to the ICU [3]. In a multicenter study by Mongardon et al. in patients with severe pneumococcal CAP admitted to the ICU, the mortality rate was 29%, with high proportions of patients in septic shock and needing mechanical ventilation [4]. Severe CAP is a progressive disease and patients may die despite early and adequate antibiotic treatment. The host local and systemic inflammatory immune response in patients with severe CAP is exacerbated and disproportionate and this is probably the main cause for the high mortality in this specific population, as it contributes to impaired alveolar gas exchange, sepsis and end-organ dysfunction [5]. In this specific population of patients with severe CAP, adjuvant treatments, such as corticosteroids, may be beneficial.

negative: The global spread of 2019-nCoV: a molecular evolutionary analysis The global spread of the 2019-nCoV is continuing and is fast moving, as indicated by the WHO raising the risk assessment to high. In this article, we provide a preliminary phylodynamic and phylogeographic analysis of this new virus. A Maximum Clade Credibility tree has been built using the 29 available whole genome sequences of 2019-nCoV and two whole genome sequences that are highly similar sequences from Bat SARS-like Coronavirus available in GeneBank. We are able to clarify the mechanism of transmission among the countries which have provided the 2019-nCoV sequence isolates from their patients. The Bayesian phylogeographic reconstruction shows that the 2019–2020 nCoV most probably originated from the Bat SARS-like Coronavirus circulating in the Rhinolophus bat family. In agreement with epidemiological observations, the most likely geographic origin of the new outbreak was the city of Wuhan, China, where 2019-nCoV time of the most recent common ancestor emerged, according to molecular clock analysis, around November 25(th), 2019. These results, together with previously recorded epidemics, suggest a recurring pattern of periodical epizootic outbreaks due to Betacoronavirus. Moreover, our study describes the same population genetic dynamic underlying the SARS 2003 epidemic, and suggests the urgent need for the development of effective molecular surveillance strategies of Betacoronavirus among animals and Rhinolophus of the bat family.

negative: COVID-19 and the anti-lessons of history

negative: Duration of quarantine in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a question needing an answer

negative: Middle East Respiratory Syndrome: What Clinicians Need to Know Abstract A severe viral illness caused by a newly discovered coronavirus was first reported in the Middle East in 2012. The virus has since been named the Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV cases have been reported in several countries around the world in travelers from the Middle East. The illness has a high mortality rate. Limited human-to-human transmission has occurred including transmission to health care workers. The source of the virus remains unclear, but camels are a possible source. Two unrelated imported cases of MERS-CoV have been reported in the United States. Neither a vaccine nor effective therapy against the virus is available. International cooperation and information sharing will be key to understanding and ending the MERS-CoV outbreak.

negative: Recombination Between High-Risk Human Papillomaviruses and Non-Human Primate Papillomaviruses: Evidence of Ancient Host Switching Among Alphapapillomaviruses We use all the currently known 405 Papillomavirus (PV) sequences, 343 curated PV sequences from both humans and animals from the PAVE data base, to analyse the recombination dynamics of these viruses at the whole genome levels. After showing some evidence of human and non-human primate PV recombination, we report a comprehensive recombination analysis of all currently known 82 Alphapapillomaviruses (Alpha-PVs). We carried out an exploratory study and found novel recombination events between High-Risk HPV Types and Macaca fascicularis PV1 (MfPV1), Macaca Fuscata PV2 (MfuPV2) and Pan Paniscus PV1 (PpPV1) Papillomaviruses. This is the first evidence of interactions between PVs from different hosts and hence postulates the likelihood of ancient host switching among Alpha-PVs. Notwithstanding these results should be interpreted with caution because the major and minor parents indicated by RDP4 program are simply the sequences in the alignment that most closely resemble the actual parents. We found statistically significant differences between the phylogenies of the PV sequences with recombination regions and PV sequences without recombination regions using the Shimodaira–Hasegawa phylogenetic incongruence testing. We show that not more than 76MYA Alpha-PVs were in the same biological niche, a pre-requisite for recombination, and as the hosts evolved and diversified, the viruses adapted to specific host niches which eventually led to coevolution with specific hosts before speciation of primate species. Thus providing evidence that in ancient times no earlier than the Cretaceous period of the Mesozoic age, Alpha-PVs recombined and switched hosts, but whether this host switching is occurring currently is unknown. However, a clearer picture of the PVs evolutionary landscape can only be achieved with the incremental discovery of PV sequences, especially from the animal kingdom. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00239-020-09946-0) contains supplementary material, which is available to authorized users.

negative: Coronavirus: Why Men are More Vulnerable to Covid-19 Than Women? Amid of coronavirus disease 2019 (Covid-19) pandemic, much emphasis was initially placed on the elderly or those who have preexisting health conditions such as obesity, hypertension, and diabetes as being at high risk of contracting and/or dying of Covid-19. But it is now becoming clear that being male is also a factor. The epidemiological findings reported across different parts of the world indicated higher morbidity and mortality in males than females. While it is still too early to determine why the gender gap is emerging, this article point to several possible factors such as higher expression of angiotensin-converting enzyme-2 (ACE 2; receptors for coronavirus) in male than female, sex-based immunological differences driven by sex hormone and X chromosome. Furthermore, a large part of this difference in number of deaths is caused by gender behavior (lifestyle), i.e., higher levels of smoking and drinking among men compared to women. Lastly, studies reported that women had more responsible attitude toward the Covid-19 pandemic than men. Irresponsible attitude among men reversibly affect their undertaking of preventive measures such as frequent handwashing, wearing of face mask, and stay at home orders.

negative: The phylogeny of SARS coronavirus Different tree-building methods consistently place the SARS corona-virus (SARS-CoV) as a basal Group 2 coronavirus rather than as an ungrouped species as concluded by others. Detailed comparisons of the SARS-CoV genomic sequence with those of six other coronaviruses failed to find evidence of recombination or genomic rearrangement using computational methods designed for that purpose.

negative: Viral Metagenomics Revealed Sendai Virus and Coronavirus Infection of Malayan Pangolins (Manis javanica) Pangolins are endangered animals in urgent need of protection. Identifying and cataloguing the viruses carried by pangolins is a logical approach to evaluate the range of potential pathogens and help with conservation. This study provides insight into viral communities of Malayan Pangolins (Manis javanica) as well as the molecular epidemiology of dominant pathogenic viruses between Malayan Pangolin and other hosts. A total of 62,508 de novo assembled contigs were constructed, and a BLAST search revealed 3600 ones (≥300 nt) were related to viral sequences, of which 68 contigs had a high level of sequence similarity to known viruses, while dominant viruses were the Sendai virus and Coronavirus. This is the first report on the viral diversity of pangolins, expanding our understanding of the virome in endangered species, and providing insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into other mammals.

negative: Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies The pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV-1) and COVID-19 coronavirus (SARS-CoV-2) have all emerged into the human population with devastating consequences. These viruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics to combat these highly pathogenic coronaviruses. Here, we describe the isolation and characterization of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs are capable of potently neutralizing MERS-CoV or SARS-CoV-1 S pseudotyped viruses. The crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs block receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S, and demonstrate that this cross-reactive VHH is capable of neutralizing SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.

negative: Bat-Origin Coronaviruses Expand Their Host Range to Pigs Infections with bat-origin coronaviruses have caused severe illness in humans by ‘host jump’. Recently, novel bat-origin coronaviruses were found in pigs. The large number of mutations on the receptor-binding domain allowed the viruses to infect the new host, posing a potential threat to both agriculture and public health.

negative: Note from the editors: novel coronavirus (2019-nCoV)

negative: Coronavirus membrane fusion mechanism offers a potential target for antiviral development The coronavirus disease 2019 (COVID-19) pandemic has focused attention on the need to develop effective therapies against the causative agent, SARS-CoV-2, and also against other pathogenic coronaviruses (CoV) that have emerged in the past or might appear in future. Researchers are therefore focusing on steps in the CoV replication cycle that may be vulnerable to inhibition by broad-spectrum or specific antiviral agents. The conserved nature of the fusion domain and mechanism across the CoV family make it a valuable target to elucidate and develop pan-CoV therapeutics. In this article, we review the role of the CoV spike protein in mediating fusion of the viral and host cell membranes, summarizing the results of research on SARS-CoV, MERS-CoV, and recent peer-reviewed studies of SARS-CoV-2, and suggest that the fusion mechanism be investigated as a potential antiviral target. We also provide a supplemental file containing background information on the biology, epidemiology, and clinical features of all human-infecting coronaviruses, along with a phylogenetic tree of these coronaviruses.

negative: Coronavirus infections reported by ProMED, February 2000–January 2020 Abstract Introduction Sources describing the global burden of emerging diseases accurately are still limited. We reviewed coronavirus infections reported by ProMED and assessed the reliability of the data retrieved compared to published reports. We evaluated the effectiveness of ProMED as a source of epidemiological data on coronavirus. Methods Using the keyword “coronavirus” in the ProMED search engine, we reviewed all the information from the reports and collected data using a structured form, including year, country, gender, occupation, the number of infected individuals, and the number of fatal cases. Results We identified 109 entries reported between February 29, 2000 and January 22, 2020. A total of 966 cases were reported, with death reported in 188 cases, suggesting an overall case fatality rate (CFR) of 19.5%. Of 70 cases for which the gender was reported, 47 (67.1%) were male. Most of the cases were reported from China, the United Arab Emirates, and Saudi Arabia, with reports from other countries, including imported cases in Europe and North America. Conclusions Internet-based reporting systems such as ProMED are useful to gather information and synthesize knowledge on emerging infections. Although certain areas need to be improved, ProMED provided useful information about coronaviruses especially during outbreaks.

negative: Multi-Cultural Project Initiative: An inclusive representation of “Coronavirus Guidelines for America”

negative: Caffeine removal using Elaeis guineensis activated carbon: adsorption and RSM studies The palm (Elaeis guineensis), known as dendê, is an important oleaginous Brazilian plant with a high performance of oil production. In this work, a 23 full experimental design was performed and the response surface method (RSM) was used to indicate the optimum parameter of caffeine adsorption on Elaeis guineensis endocarp activated carbon, since the endocarp is the main by-product from dendê oil production. It was set the adsorbent point of zero charge (pHpzc), and the material was characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The RSM results indicate removal efficiency (%) at the optimal conditions, 0.20 g of adsorbent, and caffeine initial concentration of 20 mg/L, and acidic medium was about 95%. Based on ANOVA and F test (Fcalculated > Fstandard), the mathematical/statistical model obtained fits well to the experimental data. The overall kinetic studies showed time was achieved after 5 h and caffeine adsorption followed the pseudo-second-order model suggesting chemisorption is a predominant mechanism. Redlich-Peterson and Sips models best represented the experimental data (0.967 < R2 < 0.993). Thermodynamic revealed that caffeine adsorption was spontaneous at all temperatures studied, exothermic, and probably with changes in the adsorbate-adsorbent complex during the process. The tests conducted in different water matrixes corroborate the suitability of this adsorbent to be used in caffeine removal even in a complex solution.

negative: [Spike protein in the detection and treatment of novel coronavirus]. Recently a COVID-19 pneumonia pandemic caused by a novel coronavirus 2019-nCoV has broken out over the world. In order to better control the spread of the pandemic, there's an urgent need to extensively study the virus' origin and the mechanisms for its infectivity and pathogenicity. Spike protein is a special structural protein on the surface of coronavirus. It contains important information about the evolution of the virus and plays critical roles in the processes of cellular recognition and entry. In the past decades, spike protein has always been one of the most important objects in research works on coronaviruses closely related to human life. In this review we introduce these research works related to spike proteins, hoping it will provide reasonable ideas for the control of the current pandemic, as well as for the diagnosis and treatment of COVID-19.

negative: Molecular evolution analysis and geographic investigation of severe acute respiratory syndrome coronavirus-like virus in palm civets at an animal market and on farms. Massive numbers of palm civets were culled to remove sources for the reemergence of severe acute respiratory syndrome (SARS) in Guangdong Province, China, in January 2004, following SARS coronavirus detection in market animals. The virus was identified in all 91 palm civets and 15 raccoon dogs of animal market origin sampled prior to culling, but not in 1,107 palm civets later sampled at 25 farms, spread over 12 provinces, which were claimed to be the source of traded animals. Twenty-seven novel signature variation residues (SNVs) were identified on the spike gene and were analyzed for their phylogenetic relationships, based on 17 sequences obtained from animals in our study and from other published studies. Analysis indicated that the virus in palm civets at the live-animal market had evolved to infect humans. The evolutionary starting point was a prototype group consisting of three viral sequences of animal origin. Initially, seven SNV sites caused six amino acid changes, at positions 147, 228, 240, 479, 821, and 1080 of the spike protein, to generate low-pathogenicity viruses. One of these was linked to the first SARS patient in the 2003-2004 period. A further 14 SNVs caused 11 amino acid residue changes, at positions 360, 462, 472, 480, 487, 609, 613, 665, 743, 765, and 1163. The resulting high-pathogenicity groups were responsible for infections during the so-called early-phase epidemic of 2003. Finally, the remaining six SNVs caused four amino acid changes, at positions 227, 244, 344, and 778, which resulted in the group of viruses responsible for the global epidemic.

negative: Phylogeny of SARS-CoV as inferred from complete genome comparison SARS-CoV, as the pathogeny of severe acute respiratory syndrome (SARS), is a mystery that the origin of the virus is still unknown even a few isolates of the virus were completely sequenced. To explore the genesis of SARS-CoV, the FDOD method previously developed by us was applied to comparing complete genomes from 12 SARS-CoV isolates to those from 12 previously identified coronaviruses and an unrooted phylogenetic tree was constructed. Our results show that all SARS-CoV isolates were clustered into a clique and previously identified coronaviruses formed the other clique. Meanwhile, the three groups of coronaviruses depart from each other clearly in our tree that is consistent with the results of prevenient papers. Differently, from the topology of the phylogenetic tree we found that SARS-CoV is more close to group 1 within genus coronavirus. The topology map also shows that the 12 SARS-CoV isolates may be divided into two groups determined by the association with the SARS-CoV from the Hotel M in Hong Kong that may give some information about the infectious relationship of the SARS.

negative: Comparative analysis of rodent and small mammal viromes to better understand the wildlife origin of emerging infectious diseases BACKGROUND: Rodents represent around 43% of all mammalian species, are widely distributed, and are the natural reservoirs of a diverse group of zoonotic viruses, including hantaviruses, Lassa viruses, and tick-borne encephalitis viruses. Thus, analyzing the viral diversity harbored by rodents could assist efforts to predict and reduce the risk of future emergence of zoonotic viral diseases. RESULTS: We used next-generation sequencing metagenomic analysis to survey for a range of mammalian viral families in rodents and other small animals of the orders Rodentia, Lagomorpha, and Soricomorpha in China. We sampled 3,055 small animals from 20 provinces and then outlined the spectra of mammalian viruses within these individuals and the basic ecological and genetic characteristics of novel rodent and shrew viruses among the viral spectra. Further analysis revealed that host taxonomy plays a primary role and geographical location plays a secondary role in determining viral diversity. Many viruses were reported for the first time with distinct evolutionary lineages, and viruses related to known human or animal pathogens were identified. Phylogram comparison between viruses and hosts indicated that host shifts commonly happened in many different species during viral evolutionary history. CONCLUSIONS: These results expand our understanding of the viromes of rodents and insectivores in China and suggest that there is high diversity of viruses awaiting discovery in these species in Asia. These findings, combined with our previous bat virome data, greatly increase our knowledge of the viral community in wildlife in a densely populated country in an emerging disease hotspot. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-018-0554-9) contains supplementary material, which is available to authorized users.

negative: Which preventive measures might protect health care workers from SARS? BACKGROUND: Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS) was observed among health care workers (HCWs) during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective. METHODS: A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the "case group" and the "control group", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs. RESULTS: After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases. CONCLUSION: Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.

negative: Origins of peptidases Abstract The distribution of all peptidase homologues across all phyla of organisms was analysed to determine within which kingdom each of the 271 families originated. No family was found to be ubiquitous and even peptidases thought to be essential for life, such as signal peptidase and methionyl aminopeptides are missing from some clades. There are 33 peptidase families common to archaea, bacteria and eukaryotes and are assumed to have originated in the last universal common ancestor (LUCA). These include peptidases with different catalytic types, exo- and endopeptidases, peptidases with different tertiary structures and peptidases from different families but with similar structures. This implies that the different catalytic types and structures pre-date LUCA. Other families have had their origins in the ancestors of viruses, archaea, bacteria, fungi, plants and animals, and a number of families have had their origins in the ancestors of particular phyla. The evolution of peptidases is compared to recent hypotheses about the evolution of organisms.

negative: The unsynchronized changes of CT image and nucleic acid detection in COVID-19: reports the two cases from Gansu, China The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been considered as a criterion for ending antiviral treatment. We compared the two COVID-19 cases with similar backgrounds and CT image repeated intervals under treatment. Our report highlighted the unsynchronized expression in the changes of CT image and nucleic acid detection in COVID-19, and lasting positive nucleic acid test result in patients recovered from pneumonia. It may be contributed to recognize the disease and improve prevention.

negative: First Reported Cases of SARS-CoV-2 Infection in Companion Animals - New York, March-April 2020 On April 22, CDC and the U.S. Department of Agriculture (USDA) reported cases of two domestic cats with confirmed infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). These are the first reported companion animals (including pets and service animals) with SARS-CoV-2 infection in the United States, and among the first findings of SARS-CoV-2 symptomatic companion animals reported worldwide. These feline cases originated from separate households and were epidemiologically linked to suspected or confirmed human COVID-19 cases in their respective households. Notification of presumptive positive animal test results triggered a One Health* investigation by state and federal partners, who determined that no further transmission events to other animals or persons had occurred. Both cats fully recovered. Although there is currently no evidence that animals play a substantial role in spreading COVID-19, CDC advises persons with suspected or confirmed COVID-19 to restrict contact with animals during their illness and to monitor any animals with confirmed SARS-CoV-2 infection and separate them from other persons and animals at home (1).

negative: Geographical Distance to the Epicenter of Covid-19 Predicts the Burnout of Working Population: Ripple effect or Typhoon Eye effect? Covid-19 originated in Wuhan and rippled across China. We investigate how the geographical distance of working adults to the epicenter of Wuhan predicts their burnout. Preliminary results of a survey of 308 working adults in 53 cities showed the distance to the epicenter of Wuhan had an inverted U-shaped relationship with the burnout. Such results help to identify regions where people would need more psychiatric assistance, carrying direct implications to healthcare practitioners and policymakers.

negative: Coronavirose systémique chez le furet (Mustela putorius) : intérêt de l’analyse histologique et immunohistochimique. À propos de trois cas Résumé Contexte Une nouvelle coronavirose a été décrite chez le furet, notamment en Espagne et aux États-Unis, induite par un Coronavirus du groupe 1, proche du Coronavirus responsable de l’entérite catarrhale enzootique et à l’origine de lésions histologiques similaires à celle de la péritonite infectieuse féline (PIF) dans l’espèce féline. Objectif Démontrer l’origine virale de lésions pyogranulomateuses sévères au sein de tissus lymphoïdes ou viscéraux de trois furets. Méthodes Analyse histologique et immunohistochimique de lésions reçues au laboratoire suite à des autopsies ou des laparotomies exploratrices pratiquées par des vétérinaires. Résultats L’analyse histologique révèle une inflammation pyogranulomateuse multicentrique, touchant préférentiellement les nœuds lymphatiques abdominaux et différents organes abdominaux. L’analyse immunohistochimique permet la mise en évidence d’antigènes viraux de Coronavirus en position intramacrophagique au sein de lésions pyogranulomateuses ganglionnaires. Conclusion Ces trois cas d’inflammation pyogranulomateuse multicentrique sont dus à une coronavirose qui présente de nombreux points de ressemblance avec la PIF. Summary Background A disease resembling feline infectious peritonitis (FIP) has been recognized recently in ferrets, mostly in United States and in Spain. This disease is due to a Group 1 Coronavirus, closely related to the ferret enteric Coronavirus. Objective To demonstrate the viral origin of severe pyogranulomatous lymphoid and visceral lesions in three ferrets. Methods Histopathology and immunohistochemistry of lesions received in our laboratory. Results Severe pyogranulomatous inflammation was observed in the abdominal lymph nodes and in various organs. Positive labelling of Coronavirus antigen was demonstrated in macrophages in the pyogranulomatous lesions by immunohistochemistry. Conclusion The three cases of severe pyogranulomatous disseminated inflammation were due to a Coronavirus, causing a systemic coronavirosis in ferret with a high similarity to FIP.

negative: In this issue of Occupational Medicine The recent COVID-19 outbreak in Wuhan city (Hubei Province of central China), presents significant public health challenges not only in china but across all affected countries worldwide. Koh [1] succinctly describes what coronaviruses are, and outlines six known species associated with human illnesses. The article also describes countries of origin of previous coronavirus disease outbreaks and reports number of known fatalities with associated case-fatality rates. Occupations implicated in the current COVID-19 outbreak are detailed and groups at high risk of contracting the infection e.g. healthcare workers highlighted. Social stigmatisation associated with COVID-19 is explored and suggested measures to contain the infection discussed.

negative: SARS-CoV-2 Gastrointestinal Infection Causing Hemorrhagic Colitis: Implications for Detection and Transmission of COVID-19 Disease

negative: Travel implications of emerging coronaviruses: SARS and MERS-CoV Summary The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and of the Middle East Syndrome Cornavirus (MERS-CoV) caused widespread fear and concern for their potential threat to global health security. There are similarities and differences in the epidemiology and clinical features between these two diseases. The origin of SARS-COV and MERS-CoV is thought to be an animal source with subsequent transmission to humans. The identification of both the intermediate host and the exact route of transmission of MERS-CoV is crucial for the subsequent prevention of the introduction of the virus into the human population. So far MERS-CoV had resulted in a limited travel-associated human cases with no major events related to the Hajj.

negative: COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance Abstract This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2′ spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles’ Heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding studies. The enzyme 11β-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.

negative: Epidemiological analysis of COVID‐19 and practical experience from China The rapid spread of the epidemic has aroused widespread concern in the international community. Severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) originated from Wuhan's Huanan wholesale seafood market, with bats as the likely original hosts and pangolins as potential intermediate hosts. The current source of the disease is mainly patients infected with SARS‐COV‐2. Patients in the incubation period may also become sources of infection. The virus is mainly transmitted via respiratory droplets and contact, and the population is generally susceptible. The epidemic has progressed through the local outbreak stage and community transmission stage due to exposure at Wuhan's Huanan wholesale seafood market and is now in the stage of large‐scale transmission due to the spread of the epidemic. The basic productive number (R0) at the beginning of the epidemic was 2.2, with an average incubation period of 5.2 days. The proportion of critically ill patients was 23.4%, the mortality rate was lower than those of SARS and Middle East respiratory syndrome, and 96.5% of deaths occurred in Hubei Province, where the outbreak occurred first. Among them, elderly men with underlying diseases had a higher mortality rate. Chinese medical staff have summarized a set of effective strategies and methods in the diagnosis and treatment of this disease that are worthy of reference for their international counterparts. With powerful government intervention and the efforts of Chinese medical staff, China's outbreak has gradually improved.

negative: Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report Abstract The ongoing outbreak of COVID-19 that began in Wuhan, China, has constituted a Public Health Emergency of International Concern, with cases confirmed in multiple countries. Currently, patients are the primary source of infection. We report a confirmed case of COVID-19 whose oropharyngeal swab test of SARS-CoV-2 RNA turned positive in convalescence. This case highlights the importance of active surveillance of SARS-CoV-2 RNA for infectivity assessment.

negative: A Novel Coronavirus (COVID-19) Outbreak A Call for Action

negative: Recent discovery and development of inhibitors targeting coronaviruses Human coronaviruses (CoVs) are enveloped viruses with a positive-sense single-stranded RNA genome. Currently, six human CoVs have been reported including human coronavirus 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1), severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and MiddleEast respiratory syndrome (MERS) coronavirus (MERS-CoV). They cause moderate to severe respiratory and intestinal infections in humans. In this review, we focus on recent advances in the research and development of small-molecule anti-human coronavirus therapies targeting different stages of the CoV life cycle.

negative: Potential Treatments for COVID-19; a Narrative Literature Review SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11(th). There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.

negative: 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: “The Art of War” in the Era of Coronavirus Disease 2019 (COVID-19)

negative: COVID-19 in a tertiary hospital from Romania: Epidemiology, preparedness and clinical challenges

negative: Rapid surveillance of COVID-19 in the United States using a prospective space-time scan statistic: Detecting and evaluating emerging clusters Abstract Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China in December 2019, and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is a pandemic with an estimated death rate between 1% and 5%; and an estimated R 0 between 2.2 and 6.7 according to various sources. As of March 28th, 2020, there were over 649,000 confirmed cases and 30,249 total deaths, globally. In the United States, there were over 115,500 cases and 1891 deaths and this number is likely to increase rapidly. It is critical to detect clusters of COVID-19 to better allocate resources and improve decision-making as the outbreaks continue to grow. Using daily case data at the county level provided by Johns Hopkins University, we conducted a prospective spatial-temporal analysis with SaTScan. We detect statistically significant space-time clusters of COVID-19 at the county level in the U.S. between January 22nd-March 9th, 2020, and January 22nd-March 27th, 2020. The space-time prospective scan statistic detected “active” and emerging clusters that are present at the end of our study periods – notably, 18 more clusters were detected when adding the updated case data. These timely results can inform public health officials and decision makers about where to improve the allocation of resources, testing sites; also, where to implement stricter quarantines and travel bans. As more data becomes available, the statistic can be rerun to support timely surveillance of COVID-19, demonstrated here. Our research is the first geographic study that utilizes space-time statistics to monitor COVID-19 in the U.S.

negative: Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19 OBJECTIVE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, has caused a pandemic which has swiftly involved the entire world and raised great public health concerns. The scientific community is actively exploring treatments that would potentially be effective in combating COVID-19. Hydroxychloroquine has been demonstrated to limit the replication of SARS-CoV-2 virus in vitro. In malarial pandemic countries, chloroquine is widely used to treat malaria. In malarial non-pandemic nations, chloroquine is not widely used. Chloroquine and hydroxychloroquine share similar chemical structures and mechanisms of action. The aim of this study was to indirectly investigate the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 by determining the prevalence of COVID-19 in malaria pandemic and non-pandemic nations. We sought evidence to support or refute the hypothesis that these drugs could show efficacy in the treatment of COVID-19. MATERIALS AND METHODS: We reviewed in vitro studies, in vivo studies, original studies, clinical trials, and consensus reports, that were conducted to evaluate the antiviral activities of chloroquine and hydroxychloroquine. The studies on "COVID-19 and its allied treatment were found from World Health Organization (WHO), ISI-Web of Science, PubMed, EMBASE, Scopus, Google Scholar, and clinical trial registries. The search was based on keywords: antiviral drugs, chloroquine, hydroxychloroquine, COVID-19, COVID-19 treatment modalities, and coronavirus. In addition, we analyzed the prevalence of COVID-19 in malaria pandemic and non-pandemic countries. The review and analyses were performed on March 28, 2020. RESULTS: For this study, we identified a total of 09 published articles: 03 clinical trials with sample size 150; 03 in vitro studies and 03 expert consensus reports. These studies were all suggestive that chloroquine and hydroxychloroquine can successfully treat COVID-19 infections. We found that COVID-19 infections are highly pandemic in countries where malaria is least pandemic and are least pandemic in nations where malaria is highly pandemic. CONCLUSIONS: Chloroquine and hydroxychloroquine have antiviral characteristics in vitro. The findings support the hypothesis that these drugs have efficacy in the treatment of COVID-19. People are currently using these drugs for malaria. It is reasonable, given the hypothetical benefit of these two drugs, that they are now being tested in clinical trials to assess their effectiveness to combat this global health crisis.

negative: Speculation is not evidence: antihypertensive therapy and COVID-19

negative: Predicting the angiotensin converting enzyme 2 (ACE2) utilizing capability as the receptor of SARS-CoV-2 Abstract SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia pandemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2. As a result, we predicted that SARS-CoV-2 tends to utilize ACE2s of various mammals, except murines, and some birds, such as pigeon. This prediction may help to screen the intermediate hosts of SARS-CoV-2.

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: Tourism today: Why is it a global phenomenon embracing all our lives?

negative: Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19? In December 2019, a new coronavirus, named SARS-CoV-2, has emerged from China causing pneumonia outbreaks first in the Wuhan region and have now spread worldwide because of its probable high transmission efficiency. Due to the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the best tool to find therapeutic solution. Chloroquine, remdesivir, lopinavir, ribavirin or ritonavir have shown efficacy to inhibit coronavirus in vitro. Teicoplanin, an antibiotic used to treat staphylococci infection, previously showed efficacy to inhibit the first stage of MERS-coronarivus viral cycle in human cells. This activity is conserved on the SARS-Cov-2, thus placing teicoplanin as a potential treatment for patients with this virus.

negative: Endoplasmic reticulum as a potential therapeutic target for covid-19 infection management? In December 2019, many pneumonia cases with unidentified sources appeared in Wuhan, Hubei, China, with clinical symptoms like viral pneumonia. Deep sequencing analysis of samples from lower respiratory tract revealed a novel coronavirus, called 2019 novel coronavirus (2019-nCoV). Currently there is a rapid global spread. World Health Organization declare the disease a pandemic condition. The pathologic source of this disease was a new RNA virus from Coronaviridae family, which was named COVID-19. SARS-CoV-2 entry starts with the binding of the spike glycoprotein expressed on the viral envelope to ACE2 on the alveolar surface followed by clathrin-dependent endocytosis of the SARS-CoV-2 and ACE2 complex. SARS-CoV-2 enters the cells through endocytosis process, which is possibly facilitated, via a pH dependent endosomal cysteine protease cathepsins. Once inside the cells, SARS-CoV-2 exploits the endogenous transcriptional machinery of alveolar cells to replicate and spread through the entire lung. Endosomal acidic pH for SARS-CoV-2 processing and internalization is critical. After entering the cells, it possibly activates or hijack many intracellular pathways in favor of its replication. In the current opinion article, we will explain the possible involvement of unfolded protein response as a cellular stress response to the SARS-CoV-2 infection.

negative: Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats Abstract Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV). However, a recent study found that one-third of FIPV isolates have an intact 3c and suggested that it is not solely involved in FIP but is essential for intestinal replication. In order to confirm these assumptions, 27 fecal and 32 FIP coronavirus isolates were obtained from resident or adopted cats from a large metropolitan shelter during 2008–2009 and their 3a–c, E, and M genes sequenced. Forty percent of coronavirus isolates from FIP tissues had an intact 3c gene, while 60% had mutations that truncated the gene product. The 3c genes of fecal isolates from healthy cats were always intact. Coronavirus from FIP diseased tissues consistently induced FIP when given either oronasally or intraperitoneally (i.p.), regardless of the functional status of their 3c genes, thus confirming them to be FIPVs. In contrast, fecal isolates from healthy cats were infectious following oronasal infection and shed at high levels in feces without causing disease, as expected for FECVs. Only one in three cats shed FECV in the feces following i.p. infection, indicating that FECVs can replicate systemically, but with difficulty. FIPVs having a mutated 3c were not shed in the feces following either oronasal or i.p. inoculation, while FIPVs with intact 3c genes were shed in the feces following oronasal but not i.p. inoculation. Therefore, an intact 3c appears to be essential for intestinal replication. Although FIPVs with an intact 3c were shed in the feces following oronasal inoculation, fecal virus from these cats was not infectious for other cats. Attempts to identify potential FIP mutations in the 3a, 3b, E, and M were negative. However, the 3c gene of FIPVs, even though appearing intact, contained many more non-synonymous amino acid changes in the 3′ one-third of the 3c protein than FECVs. An attempt to trace FIPV isolates back to enteric strains existing in the shelter was only partially successful due to the large region over which shelter cats and kittens originated, housing conditions prior to acquisition, and rapid movement through the shelter. No evidence could be found to support a recent theory that FIPVs and FECVs are genetically distinct.

negative: Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-α in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-α. Further study indicated that IFN-γ+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV.

negative: SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology The sudden emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019 from the Chinese province of Hubei and its subsequent pandemic spread highlight the importance of understanding the full molecular details of coronavirus infection and pathogenesis. Here, we compared a variety of replication features of SARS-CoV-2 and SARS-CoV and analysed the cytopathology caused by the two closely related viruses in the commonly used Vero E6 cell line. Compared to SARS-CoV, SARS-CoV-2 generated higher levels of intracellular viral RNA, but strikingly about 50-fold less infectious viral progeny was recovered from the culture medium. Immunofluorescence microscopy of SARS-CoV-2-infected cells established extensive cross-reactivity of antisera previously raised against a variety of nonstructural proteins, membrane and nucleocapsid protein of SARS-CoV. Electron microscopy revealed that the ultrastructural changes induced by the two SARS viruses are very similar and occur within comparable time frames after infection. Furthermore, we determined that the sensitivity of the two viruses to three established inhibitors of coronavirus replication (Remdesivir, Alisporivir and chloroquine) is very similar, but that SARS-CoV-2 infection was substantially more sensitive to pre-treatment of cells with pegylated interferon alpha. An important difference between the two viruses is the fact that - upon passaging in Vero E6 cells - SARS-CoV-2 apparently is under strong selection pressure to acquire adaptive mutations in its spike protein gene. These mutations change or delete a putative ‘furin-like cleavage site’ in the region connecting the S1 and S2 domains and result in a very prominent phenotypic change in plaque assays.

negative: The origins of cellular life All life on earth can be naturally classified into cellular life forms and virus-like selfish elements, the latter being fully dependent on the former for their reproduction. Cells are reproducers that not only replicate their genome but also reproduce the cellular organization that depends on semipermeable, energy-transforming membranes and cannot be recovered from the genome alone, under the famous dictum of Rudolf Virchow, Omnis cellula e cellula. In contrast, simple selfish elements are replicators that can complete their life cycles within the host cell starting from genomic RNA or DNA alone. The origin of the cellular organization is the central and perhaps the hardest problem of evolutionary biology. I argue that the origin of cells can be understood only in conjunction with the origin and evolution of selfish genetic elements. A scenario of precellular evolution is presented that involves cohesion of the genomes of the emerging cellular life forms from primordial pools of small genetic elements that eventually segregated into hosts and parasites. I further present a model of the coevolution of primordial membranes and membrane proteins, discuss protocellular and non-cellular models of early evolution, and examine the habitats on the primordial earth that could have been conducive to precellular evolution and the origin of cells.

negative: The case of Complement activation in COVID-19 multiorgan impact The novel coronavirus disease COVID-19 originates in the lungs, but may extend to other organs, causing, in severe cases, multiorgan damage, including cardiac injury and acute kidney injury. In severe cases, the presence of kidney injury is associated with increased risk of death, highlighting the relevance of this organ as a target of SARS-CoV-2 infection. COVID-19-associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation. The complement system represents the first response of the host immune system to SARS-CoV-2 infection, but there is growing evidence that unrestrained activation of complement induced by the virus in the lungs and other organs plays a major role in acute and chronic inflammation, endothelial cell dysfunction, thrombus formation and intravascular coagulation, and ultimately contributes to multiple organ failure and death. In this review we will discuss the relative role of the different complement activation products in the pathogenesis of COVID-19-associated tissue inflammation and thrombosis and propose the hypothesis that blockade of the terminal complement pathway may represent a potential therapeutic option for the prevention and treatment of lung and multi-organ damage.

negative: COVID‐19, chronicle of an expected pandemic What is COVID‐19? What are the causes, parameters, and effects of this disease? What are the short‐ and long‐term prospects? Philippe Sansonetti, Infectious disease specialist and Chief Editor of EMBO Molecular Medicine, explains why the fate of the epidemic is in our hands.[Image: see text]

negative: Translational Knowledge Map of COVID-19 A translational knowledge map of COVID-19, based on the analysis of scientific papers and networks citation concurrence of terms and keywords of the terms: covid- 19, 2019-ncov and sars-cov-2 in leading databases (MEDLINE, web of Science and Scopus), was constructed. Some fields of the research on covid-19 are connected together, differing in structure, content and evolution.

negative: Novel corona virus disease (COVID-19) in pregnancy: What clinical recommendations to follow?

negative: Comparison of SARS-CoV-2 spike protein binding to human, pet, farm animals, and putative intermediate hosts ACE2 and ACE2 receptors The emergence of a novel coronavirus, SARS-CoV-2, resulted in a pandemic. Here, we used recently released X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptor allows to define residues important for binding. From the 20 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S-binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites located near the S-interface. Of note, pigs and dogs which are not or not effectively infected, respectively, have only a few changes in the binding site have relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with viruses from bat and pangolin revealed that the latter contains only one substitution, whereas the bat virus exhibits five. However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-COV-2. IMPORTANCE SARS-CoV-2 is threatening people worldwide and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the species barrier might be low. However, the lower expression of ACE2 in the upper respiratory tract of some pets and livestock means more research and monitoring should be done to explore the animal source of infection and the risk of potential cross-species transmission. Finally, the analysis also showed that SARS-CoV-2 may not specifically adapted to any of its putative intermediate hosts.

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: AGA Institute Rapid Recommendations for Gastrointestinal Procedures During the COVID-19 Pandemic

negative: The Links Between Public and Ecosystem Health in Light of the Recent Ebola Outbreaks and Pandemic Emergence

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: Meta-analysis of transcriptomes of SARS-Cov2 infected human lung epithelial cells identifies transmembrane serine proteases co-expressed with ACE2 and biological processes related to viral entry, immunity, inflammation and cellular stress The COVID-19 pandemic resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December 2019 in the Chinese city of Wuhan in the province Hubei has placed immense burden on national economies and global health. At present neither vaccination nor therapies are available although several antiviral agents such as remdesivir, originally an Ebola drug, nelfinavir, an HIV-1 protease inhibitor and other drugs such as lopinavir have been evaluated. Here, we performed a meta-analysis of RNA-sequencing data from three studies employing human lung epithelial cells. Of these one focused on lung epithelial cells infected with SARS-CoV-2. We aimed at identifying genes co-expressed with angiotensin I converting enzyme 2 (ACE2) the human cell entry receptor of SARS-CoV-2, and unveiled several genes correlated or inversely correlated with high significance, among the most significant of these was the transmembrane serine protease 4 (TMPRSS4). Serine proteases are known to be involved in the infection process by priming the virus spike protein. Pathway analysis revealed papilloma virus infection amongst the most significantly correlated pathways. Gene Ontologies revealed regulation of viral life cycle, immune responses, pro-inflammatory responses-several interleukins such as IL6, IL1, IL20 and IL33, IFI16 regulating the interferon response to a virus, chemo-attraction of macrophages, last and not least cellular stress resulting from activated Reactive Oxygen Species. We believe that this dataset will aid in a better understanding of the molecular mechanism(s) underlying COVID-19.

negative: A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.

negative: Building an International Consortium for Tracking Coronavirus Health Status Information is the most potent protective weapon we have to combat a pandemic, at both the individual and global level. For individuals, information can help us make personal decisions and provide a sense of security. For the global community, information can inform policy decisions and offer critical insights into the epidemic of COVID-19 disease. Fully leveraging the power of information, however, requires large amounts of data and access to it. To achieve this, we are making steps to form an international consortium, Coronavirus Census Collective (CCC, coronaviruscensuscollective.org), that will serve as a hub for integrating information from multiple data sources that can be utilized to understand, monitor, predict, and combat global pandemics. These sources may include self-reported health status through surveys (including mobile apps), results of diagnostic laboratory tests, and other static and real-time geospatial data. This collective effort to track and share information will be invaluable in predicting hotspots of disease outbreak, identifying which factors control the rate of spreading, informing immediate policy decisions, evaluating the effectiveness of measures taken by health organizations on pandemic control, and providing critical insight on the etiology of COVID-19. It will also help individuals stay informed on this rapidly evolving situation and contribute to other global efforts to slow the spread of disease. In the past few weeks, several initiatives across the globe have surfaced to use daily self-reported symptoms as a means to track disease spread, predict outbreak locations, guide population measures and help in the allocation of healthcare resources. The aim of this paper is to put out a call to standardize these efforts and spark a collaborative effort to maximize the global gain while protecting participant privacy.

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: Global Trends in Epidemiology of Coronavirus Disease 2019 (COVID-19) In December 2019, suddenly 54 cases of viral pneumonia emerged in Wuhan, China, caused by some unknown microorganism. The virus responsible for these pneumonia infections was identified as novel coronavirus of the family Coronaviridae. The novel coronavirus was renamed as COVID-19 by WHO. Infection from the virus has since increased exponentially and has spread all over the world in more than 196 countries. The WHO has declared a Public Health Emergency of International Concern due to the outbreak of COVID-19. The virus is highly infectious and can cause human-to-human transmission. Every 24 h, cases of COVID-19 increase severalfolds. The WHO is monitoring the SARS-CoV-2 spread very closely via a global surveillance system. The current situation demands the enforcement of strict laws which would help in inhibiting the further spread of COVID-19. Social distancing, international travel restrictions to affected countries, and hygiene are three important ways to nullify SARS-CoV-2.Government and private organizations need to come forward and work together during this pandemic. Public awareness, social distancing, and sterilization must be maintained to neutralize the viral infection, especially in major hot spots.

negative: Assessing public health capabilities during emergency preparedness tabletop exercises: reliability and validity of a measurement tool. OBJECTIVES Improving the ability of local public health agencies to respond to large-scale emergencies is an ongoing challenge. Tabletop exercises can provide an opportunity for individuals and groups to practice coordination of emergency response and evaluate performance. The purpose of this study was to develop a valid and reliable self-assessment performance measurement tool for tabletop exercise participants. METHODS The study population comprised 179 public officials who attended three tabletop exercises in Massachusetts and Maine between September 2005 and November 2006. A 42-item questionnaire was developed to assess five public health functional capabilities: (1) leadership and management, (2) mass casualty care, (3) communication, (4) disease control and prevention, and (5) surveillance and epidemiology. Analyses were undertaken to examine internal consistency, associations among scales, the empirical structure of the items, and inter-rater agreement. RESULTS Thirty-seven questions were retained in the final questionnaire and grouped according to the original five domains. Alpha coefficients were 0.81 or higher for all scales. The five-factor solution from the principal components analysis accounted for 60% of the total variance, and the factor structure was consistent with the five domains of the original conceptual model. Inter-rater agreement ranged from good to excellent. CONCLUSIONS The resulting 37-item performance measurement tool was found to reliably measure public health functional capabilities in a tabletop exercise setting, with preliminary evidence of a factor structure consistent with the original conceptualization and of criterion-related validity.

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: The timing of one-shot interventions for epidemic control The apparent early success in China's large-scale intervention to control the COVID-19 epidemic has led to interest in whether other countries can replicate it as well as concerns about a resurgence of the epidemic if or when China relaxes the interventions. In this paper we look at the impact of a single short-term intervention on an epidemic. We see that if an intervention cannot be sustained long-term, it has the greatest impact if it is imposed once infection levels have become large enough that there is an appreciable number of infections present. For minimising the total number infected it should start close to the peak so that there is no rebound once the intervention is stopped, while to minimise the peak prevalence, it should start earlier, allowing two peaks of comparable size rather than one very large peak. In populations with distinct subgroups, synchronized interventions are less effective than targeting the interventions in each sub-population separately. We do not attempt to clearly determine what makes an intervention sustainable or not. We believe that is a policy question. If an intervention is sustainable, it should be kept in place. Our intent is to offer insight into how best to time an intervention whose impact on society is too great to maintain.

negative: Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted from person to person and, in 2 months, has caused more than 82 000 laboratory-confirmed cases of coronavirus disease 2019 (COVID-19) and 2800 deaths in 46 countries. The total number of cases and deaths has surpassed that of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV). Although both COVID-19 and severe acute respiratory syndrome (SARS) manifest as pneumonia, COVID-19 is associated with apparently more efficient transmission, fewer cases of diarrhoea, increased mental confusion, and a lower crude fatality rate. However, the underlying virus–host interactive characteristics conferring these observations on transmissibility and clinical manifestations of COVID-19 remain unknown. Methods We systematically investigated the cellular susceptibility, species tropism, replication kinetics, and cell damage of SARS-CoV-2 and compared findings with those for SARS-CoV. We compared SARS-CoV-2 and SARS-CoV replication in different cell lines with one-way ANOVA. For the area under the curve comparison between SARS-CoV-2 and SARS-CoV replication in Calu3 (pulmonary) and Caco2 (intestinal) cells, we used Student's t test. We analysed cell damage induced by SARS-CoV-2 and SARS-CoV with one-way ANOVA. Findings SARS-CoV-2 infected and replicated to comparable levels in human Caco2 cells and Calu3 cells over a period of 120 h (p=0·52). By contrast, SARS-CoV infected and replicated more efficiently in Caco2 cells than in Calu3 cells under the same multiplicity of infection (p=0·0098). SARS-CoV-2, but not SARS-CoV, replicated modestly in U251 (neuronal) cells (p=0·036). For animal species cell tropism, both SARS-CoV and SARS-CoV-2 replicated in non-human primate, cat, rabbit, and pig cells. SARS-CoV, but not SARS-CoV-2, infected and replicated in Rhinolophus sinicus bat kidney cells. SARS-CoV-2 consistently induced significantly delayed and milder levels of cell damage than did SARS-CoV in non-human primate cells (VeroE6, p=0·016; FRhK4, p=0·0004). Interpretation As far as we know, our study presents the first quantitative data for tropism, replication kinetics, and cell damage of SARS-CoV-2. These data provide novel insights into the lower incidence of diarrhoea, decreased disease severity, and reduced mortality in patients with COVID-19, with respect to the pathogenesis and high transmissibility of SARS-CoV-2 compared with SARS-CoV. Funding May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Richard Yu and Carol Yu, Michael Seak-Kan Tong, Respiratory Viral Research Foundation, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, The Hong Kong Hainan Commercial Association South China Microbiology Research Fund, The Jessie & George Ho Charitable Foundation, Perfect Shape Medical, The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government, The Theme-Based Research Scheme of the Research Grants Council, Sanming Project of Medicine in Shenzhen, and The High Level-Hospital Program, Health Commission of Guangdong Province, China.

negative: Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model Abstract The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1,000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.

negative: Middle East Respiratory Syndrome coronavirus (MERS CoV): Update 2013 Middle East Respiratory Syndrome coronavirus (MERS CoV) came to attention as an emerging pathogen causing severe respiratory illness in patients from the Middle East in September 2012. As of 14 June 2013, 58 human cases of MERS CoV infection have been confirmed, including 33 deaths (case fatality rate of 57%). MERS CoV is a beta-coronavirus, in the same family as SARS-CoV, and shares a probable origin from bats. No animal reservoir or intermediates have been definitely implicated in transmission. Limited human-to-human transmission has occurred within several clusters, as individuals without a recent travel history have become infected after exposure to an ill returned traveler.

negative: Novel coronavirus infection and pregnancy

negative: Time to realise the true potential of Ayurveda against COVID-19

negative: Why is chest CT important for early diagnosis of COVID-19? Prevalence matters SARS-CoV-2 viral infection is a global pandemic disease (COVID-19). Reaching a swift, reliable diagnosis of COVID-19 in the emergency departments is imperative to direct patients to proper care and to prevent disease dissemination. COVID-19 diagnosis is based on the identification of viral RNA through RT-PCR from oral-nasopharyngeal swabs, which however presents suboptimal sensitivity and may require several hours in overstressed laboratories. These drawbacks have called for an additional, complementary first line approach. CT is the gold standard method for the detection of interstitial pneumonia, a hallmark feature of COVID-19, often present in the asymptomatic stage of the disease. Here, we show that CT scan presents a sensitivity of 95.48% (std.err=0.35%), vastly outperforming RT-PCR. Additionally, as diagnostic accuracy is influenced by disease prevalence, we argue that predictive values provide a more precise measure of CT reliability in the current pandemics. We generated a model showing that CT scan is endowed with a high negative predictive value (> 90%) and positive predictive value (69 - 84%), for the range of prevalence seen in countries with rampant dissemination. We conclude that CT is an expedite and reliable diagnostic tool to support first line triage of suspect COVID-19 patients in areas where the diffusion of the virus is widespread.

negative: Pandemic Risk Modelling This chapter will explore the nature of communicable diseases, a brief history of pandemics, and will introduce the mathematical models used to evaluate the risk pandemics pose to human populations. Such modelling is used in a public health context, where modelling past and current events provides insight in how to respond most effectively to a new outbreak. It is also used in the context of risk mutualisation and transfer. As recently as 2013, a survey of 30,000 insurance executives placed global pandemic as the biggest extreme risk facing insurers (Towers Watson. 2013. Insurers Rate Global Pandemic as the Major Extreme Risk. 3 December). The chapter will introduce the principles used to model these events in the insurance industry and will conclude with a review of the way these models are applied in an unconventional risk transfer context.

negative: Food Security in an Insecure Future Food security in the Middle East is directly affected by a challenging combination of ongoing destructive conflicts, a global economic downturn, widespread poverty, high population growth, corruption, intolerance, and the potentially damaging consequences of climate change. Many Arab countries demonstrate nearly all the features of those countries classified as poor, less developed, or failing to achieve the eight Millennium Goals. Even the economies of the richer oil-exporting countries in the Region have been seriously damaged by the downturn in oil and gas prices as new sources come on stream elsewhere and demand falls as a result of renewable sources of energy becoming available.

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: Will the antimalarial drug take over to combat COVID-19? BACKGROUND: China has been fighting the epidemic of pneumonia-like diseases first detected for over a month in the city of Wuhan in December 2019. The disease epidemic is caused by a novel coronavirus, called COVID-19, which has now infected more than 700,000 people worldwide. With a death toll approaching that of China’s SARS-CoV outbreak in 2002 and 2003, 2019-nCoV has contributed to an international emergency in public health, placing all health organizations on high alert. Such large numbers of infected and deceased people require an urgent need for reliable, inexpensive, and cheap drugs to control and reduce the outbreak. OBJECTIVE: To systematically review and evaluate the pattern of COVID-19 and the treatment plans. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The articles were searched from databases like PubMed, the Cochrane Library, ScienceDirect, and the Health Research and Development Information Network (HERDIN) combining MeSH and free-text terms. RESULTS: This analysis highlights the agent of COVID-19 and the possible transmission. The current research taking place to overcome this complex disease and the urgent need to develop improved therapeutics are also discussed. CONCLUSION: Herein, we present an epidemiological overview of the currently available information on the treatment claimed to have helped to bring the situation under control.

negative: Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m(6)A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

negative: The next big threat to global health? 2019 novel coronavirus (2019-nCoV): What advice can we give to travellers? – Interim recommendations January 2020, from the Latin-American society for Travel Medicine (SLAMVI)

negative: A conceptual model for the outbreak of Coronavirus disease 2019 (COVID-19) in Wuhan, China with individual reaction and governmental action The ongoing Coronavirus Disease 2019 (COVID-19) outbreak, originated in the end of 2019 in Wuhan, China, has claimed more than 2200 lives and posed a huge threat to global public health. The Chinese government has implemented control measures including setting up special hospitals and travel restriction to mitigate the spread. We propose conceptual models for the outbreak in Wuhan with the consideration of individual behavioural reaction and governmental actions, e.g., holiday extension, travel restriction, hospitalisation and quarantine. We employed the estimates of these two key components from the 1918 influenza pandemic in London, United Kingdom, incorporated zoonotic introductions and the emigration, then computed future trends and the reporting ratio. The model is concise in structure, and it successfully captures the course of the COVID-19 outbreak, and thus sheds light on understanding the trends of the outbreak.

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: CovidNet: To Bring Data Transparency in the Era of COVID-19 Timely, creditable, and fine-granular case information is vital for local communities and individual citizens to make rational and data-driven responses to the COVID-19 pandemic. This paper presents CovidNet, a COVID-19 tracking project associated with a large scale epidemic dataset, which was initiated by 1Point3Acres. To the best of our knowledge, the project is the only platform providing real-time global case information of more than 4,124 sub-divisions from over 27 countries worldwide with multi-language supports. The platform also offers interactive visualization tools to analyze the full historical case curves in each region. Initially launched as a voluntary project to bridge the data transparency gap in North America in January 2020, this project by far has become one of the major independent sources worldwide and has been consumed by many other tracking platforms. The accuracy and freshness of the dataset is a result of the painstaking efforts from our voluntary teamwork, crowd-sourcing channels, and automated data pipelines. As of May 18, 2020, the project website has been visited more than 200 million times and the CovidNet dataset has empowered over 522 institutions and organizations worldwide in policy-making and academic researches. All datasets are openly accessible for non-commercial purposes at https://coronavirus.1point3acres.com via a formal request through our APIs.

negative: Discussing the ABCs of Health Security-Antibiotic Resistance, Biothreats, and Coronavirus. 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 interaction 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