title: Evaluation of the secondary transmission pattern and epidemic prediction of COVID-19 in the four metropolitan areas of China

text: Understanding the transmission dynamics of COVID-19 is crucial for evaluating its spread pattern, especially in metropolitan areas of China, as its spread can lead to secondary outbreaks outside Wuhan, the center of the new coronavirus disease outbreak. In addition, the experiences gained and lessons learned from China have the potential to provide evidence to support other metropolitan areas and large cities outside China with emerging cases. We used data reported from January 24, 2020, to February 23, 2020, to fit a model of infection, estimate the likely number of infections in four high-risk metropolitan areas based on the number of cases reported, and increase the understanding of the COVID-19 spread pattern. Considering the effect of the official quarantine regulations and travel restrictions for China, which began January 23~24, 2020, we used the daily travel intensity index from the Baidu Maps app to roughly simulate the level of restrictions and estimate the proportion of the quarantined population. A group of SEIR model statistical parameters were estimated using Markov chain Monte Carlo (MCMC) methods and fitting on the basis of reported data. As a result, we estimated that the basic reproductive number, R0, was 2.91 in Beijing, 2.78 in Shanghai, 2.02 in Guangzhou, and 1.75 in Shenzhen based on the data from January 24, 2020, to February 23, 2020. In addition, we inferred the prediction results and compared the results of different levels of parameters. For example, in Beijing, the predicted peak number of cases was approximately 466 with a peak time of February 29, 2020; however, if the city were to implement different levels (strict, mild, or weak) of travel restrictions or regulation measures, the estimation results showed that the transmission dynamics would change and that the peak number of cases would differ by between 56% and ~159%. We concluded that public health interventions would reduce the risk of the spread of COVID-19 and that more rigorous control and prevention measures would effectively contain its further spread but that the risk will increase when businesses and social activities return to normal before the end of the epidemic. Besides, the experiences gained and lessons learned from China are potential to provide evidences supporting for other metropolitan areas and big cities with emerging cases outside China.


title: Design an efficient multi-epitope peptide vaccine candidate against SARS-CoV-2: An in silico analysis

text: Background To date, no specific vaccine or drug has been proven to be effective for SARS-CoV-2 infection. Therefore, we implemented immunoinformatics approach to design an efficient multi-epitopes vaccine against SARS-CoV-2. Results The designed vaccine construct has several immunodominant epitopes from structural proteins of Spike, Nucleocapsid, Membrane and Envelope. These peptides promote cellular and humoral immunity and Interferon gamma responses. In addition, these epitopes have antigenicity ability and no allergenicity probability. To enhance the vaccine immunogenicity, we used three potent adjuvants; Flagellin, a driven peptide from high mobility group box 1 as HP-91 and human beta defensin 3 protein. The physicochemical and immunological properties of the vaccine structure were evaluated. Tertiary structure of the vaccine protein was predicted and refined by I-Tasser and galaxi refine and validated using Rampage and ERRAT. Results of Ellipro showed 242 residues from vaccine might be conformational B cell epitopes. Docking of vaccine with Toll-Like Receptors 3, 5 and 8 proved an appropriate interaction between the vaccine and receptor proteins. In silico cloning demonstrated that the vaccine can be efficiently expressed in Escherichia coli. Conclusions The designed multi epitope vaccine is potentially antigenic in nature and has the ability to induce humoral and cellular immune responses against SARS-CoV-2. This vaccine can interact appropriately with the TLR3, 5, and 8. Also, this vaccine has high quality structure and suitable characteristics such as high stability and potential for expression in Escherichia coli.


title: Dissemination and co-circulation of SARS-CoV2 subclades exhibiting enhanced transmission associated with increased mortality in Western Europe and the United States

text: Mechanisms underlying the acute respiratory distress syndrome (ARDS)-like clinical manifestations leading to deaths in patients who develop COVID-19 remain uncharacterized. While multiple factors could influence these clinical outcomes, we explored if differences in transmissibility and pathogenicity of SARS-CoV2 variants could contribute to these terminal clinical consequences of COVID-19. We analyzed 34,412 SARS-CoV2 sequences deposited in the Global Initiative for Sharing All Influenza Data (GISAID) SARS-CoV2 sequence database to determine if regional differences in circulating strain variants correlated with increased mortality in Europe, the United States, and California. We found two subclades descending from the Wuhan HU-1 strain that rapidly became dominant in Western Europe and the United States. These variants contained nonsynonymous nucleotide mutations in the Orf1ab segment encoding RNA-dependent RNA polymerase (C14408T), the spike protein gene (A23403G), and Orf1a (G25563T), which resulted in non-conservative amino acid substitutions P323L, D614G, and Q57H, respectively. In Western Europe, the A23403G-C14408T subclade dominated, while in the US, the A23403G-C14408T-G25563T mutant became the dominant strain in New York and parts of California. The high cumulative frequencies of both subclades showed inconsistent but significant association with high cumulative CFRs in some of the regions. When the frequencies of the subclades were analyzed by their 7-day moving averages across each epidemic, we found co-circulation of both subclades to temporally correlate with peak mortality periods. We postulate that in areas with high numbers of these co-circulating subclades, a person may get serially infected. The second infection may trigger a hyperinflammatory response similar to the antibody-dependent enhancement (ADE) response, which could explain the ARDS-like manifestations observed in people with co-morbidity, who may not mount sufficient levels of neutralizing antibodies against the first infection. Further studies are necessary but the implication of such a mechanism will need to be considered for all current COVID-19 vaccine designs.


title: Receptor utilization of angiotensin converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV

text: 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.


title: An Outbreak of a New Infectious Disease COVID-19: β-coronaviruses as a Threat to Global Healthcare ;Вспышка нового инфекционного заболевания COVID-19: β-коронавирусы как угроза глобальному здравоохранению

text: Coronaviruses are the largest group of known positive-strand RNA viruses Coronavirus infection can affect various animal species, as well as humans Over the past two decades, coronaviruses have caused epidemic outbreaks of two respiratory diseases: the Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome At the end of 2019, a new type of virus was detected in China The virus has been spread by humantohuman transmission and has caused a viral pneumonia outbreak The emergence of a new coronavirus proves that the diseases caused by this group of viruses pose a threat to global health due to the potential for a pandemic, and, therefore, need careful monitoring The objective of the study was to analyse the current epidemic situation for the new coronavirus infection (COVID-19) caused by SARS-CoV-2, taking into account previous outbreaks of infections caused by MERS-CoV and SARS-CoV Î²-coronaviruses which pose the greatest threat to human health The review briefly describes two epidemic outbreaks caused by SARS-CoV (2002â€“2004) and MERS-CoV (2012â€“present), summarises the current epidemic situation for the new SARS-CoV-2 coronavirus, describes the main restrictive measures undertaken to prevent the spread of infection in Russia The paper considers aspects of potential specific therapy and the development of prophylactic vaccines against the new coronavirus infection The review concludes that SARS-CoV-2 has pandemic potential and that new strains of Î²-coronaviruses are likely to cause outbreaks in the future The paper points to the need for careful monitoring of the disease and conducting preventive anti-epidemic measures to curb the spread of infection ;ÐšÐ¾Ñ€Ð¾Ð½Ð°Ð²Ð¸Ñ€ÑƒÑÑ‹ ÑÐ²Ð»ÑÑŽÑ‚ÑÑ ÑÐ°Ð¼Ð¾Ð¹ Ð±Ð¾Ð»ÑŒÑˆÐ¾Ð¹ Ð³Ñ€ÑƒÐ¿Ð¿Ð¾Ð¹ Ð¸Ð· Ð¸Ð·Ð²ÐµÑÑ‚Ð½Ñ‹Ñ… Ð ÐÐš-Ð¿Ð¾Ð»Ð¾Ð¶Ð¸Ñ‚ÐµÐ»ÑŒÐ½Ñ‹Ñ… Ð²Ð¸Ñ€ÑƒÑÐ¾Ð² ÐšÐ¾Ñ€Ð¾Ð½Ð°Ð²Ð¸Ñ€ÑƒÑÐ½Ð°Ñ Ð¸Ð½Ñ„ÐµÐºÑ†Ð¸Ñ ÑÐ¿Ð¾ÑÐ¾Ð±Ð½Ð° Ð¿Ð¾Ñ€Ð°Ð¶Ð°Ñ‚ÑŒ Ñ€Ð°Ð·Ð»Ð¸Ñ‡Ð½Ñ‹Ðµ Ð²Ð¸Ð´Ñ‹ Ð¶Ð¸Ð²Ð¾Ñ‚Ð½Ñ‹Ñ…, Ð° Ñ‚Ð°ÐºÐ¶Ðµ Ñ‡ÐµÐ»Ð¾Ð²ÐµÐºÐ° Ð—Ð° Ð¿Ð¾ÑÐ»ÐµÐ´Ð½Ð¸Ðµ Ð´Ð²Ð° Ð´ÐµÑÑÑ‚Ð¸Ð»ÐµÑ‚Ð¸Ñ ÐºÐ¾Ñ€Ð¾Ð½Ð°Ð²Ð¸Ñ€ÑƒÑÑ‹ ÑÐ²Ð¸Ð»Ð¸ÑÑŒ Ð¿Ñ€Ð¸Ñ‡Ð¸Ð½Ð¾Ð¹ ÑÐ¿Ð¸Ð´ÐµÐ¼Ð¸Ñ‡ÐµÑÐºÐ¸Ñ… Ð²ÑÐ¿Ñ‹ÑˆÐµÐº Ð´Ð²ÑƒÑ… Ñ€ÐµÑÐ¿Ð¸Ñ€Ð°Ñ‚Ð¾Ñ€Ð½Ñ‹Ñ… Ð·Ð°Ð±Ð¾Ð»ÐµÐ²Ð°Ð½Ð¸Ð¹: Ð±Ð»Ð¸Ð¶Ð½ÐµÐ²Ð¾ÑÑ‚Ð¾Ñ‡Ð½Ð¾Ð³Ð¾ Ñ€ÐµÑÐ¿Ð¸Ñ€Ð°Ñ‚Ð¾Ñ€Ð½Ð¾Ð³Ð¾ ÑÐ¸Ð½Ð´Ñ€Ð¾Ð¼Ð° Ð¸ Ñ‚ÑÐ¶ÐµÐ»Ð¾Ð³Ð¾ Ð¾ÑÑ‚Ñ€Ð¾Ð³Ð¾ Ñ€ÐµÑÐ¿Ð¸Ñ€Ð°Ñ‚Ð¾Ñ€Ð½Ð¾Ð³Ð¾ ÑÐ¸Ð½Ð´Ñ€Ð¾Ð¼Ð° Ð’ ÐºÐ¾Ð½Ñ†Ðµ 2019 Ð³ Ð² ÐšÐ¸Ñ‚Ð°Ðµ Ð±Ñ‹Ð» Ð²Ñ‹ÑÐ²Ð»ÐµÐ½ Ð½Ð¾Ð²Ñ‹Ð¹ Ð²Ð¸Ð´ Ð²Ð¸Ñ€ÑƒÑÐ°, ÑÐ¿Ð¾ÑÐ¾Ð±Ð½Ñ‹Ð¹ Ð¿ÐµÑ€ÐµÐ´Ð°Ð²Ð°Ñ‚ÑŒÑÑ Ð¾Ñ‚ Ñ‡ÐµÐ»Ð¾Ð²ÐµÐºÐ° Ðº Ñ‡ÐµÐ»Ð¾Ð²ÐµÐºÑƒ, Ð²Ñ‹Ð·Ð²Ð°Ð²ÑˆÐ¸Ð¹ Ð²ÑÐ¿Ñ‹ÑˆÐºÑƒ Ð²Ð¸Ñ€ÑƒÑÐ½Ð¾Ð¹ Ð¿Ð½ÐµÐ²Ð¼Ð¾Ð½Ð¸Ð¸ ÐŸÐ¾ÑÐ²Ð»ÐµÐ½Ð¸Ðµ Ð½Ð¾Ð²Ð¾Ð³Ð¾ ÐºÐ¾Ñ€Ð¾Ð½Ð°Ð²Ð¸Ñ€ÑƒÑÐ° Ð¿Ð¾Ð´Ñ‚Ð²ÐµÑ€Ð¶Ð´Ð°ÐµÑ‚, Ñ‡Ñ‚Ð¾ Ð·Ð°Ð±Ð¾Ð»ÐµÐ²Ð°Ð½Ð¸Ñ, Ð²Ñ‹Ð·Ñ‹Ð²Ð°ÐµÐ¼Ñ‹Ðµ Ð´Ð°Ð½Ð½Ð¾Ð¹ Ð³Ñ€ÑƒÐ¿Ð¿Ð¾Ð¹ Ð²Ð¸Ñ€ÑƒÑÐ¾Ð², ÑÐ²Ð»ÑÑŽÑ‚ÑÑ ÑƒÐ³Ñ€Ð¾Ð·Ð¾Ð¹ Ð´Ð»Ñ Ð¼Ð¸Ñ€Ð¾Ð²Ð¾Ð³Ð¾ Ð·Ð´Ñ€Ð°Ð²Ð¾Ð¾Ñ…Ñ€Ð°Ð½ÐµÐ½Ð¸Ñ Ð² ÑÐ²ÑÐ·Ð¸ Ñ Ð²Ð¾Ð·Ð¼Ð¾Ð¶Ð½Ð¾ÑÑ‚ÑŒÑŽ Ð²Ð¾Ð·Ð½Ð¸ÐºÐ½Ð¾Ð²ÐµÐ½Ð¸Ñ Ð¿Ð°Ð½Ð´ÐµÐ¼Ð¸Ð¸ Ð¸ Ð½ÑƒÐ¶Ð´Ð°ÑŽÑ‚ÑÑ Ð² Ñ‚Ñ‰Ð°Ñ‚ÐµÐ»ÑŒÐ½Ð¾Ð¼ Ð¼Ð¾Ð½Ð¸Ñ‚Ð¾Ñ€Ð¸Ð½Ð³Ðµ Ð¦ÐµÐ»ÑŒ Ñ€Ð°Ð±Ð¾Ñ‚Ñ‹ â€“ Ð¾Ð±Ð·Ð¾Ñ€ Ñ‚ÐµÐºÑƒÑ‰ÐµÐ¹ ÑÐ¿Ð¸Ð´ÐµÐ¼Ð¸Ñ‡ÐµÑÐºÐ¾Ð¹ ÑÐ¸Ñ‚ÑƒÐ°Ñ†Ð¸Ð¸ Ð¿Ð¾ Ð½Ð¾Ð²Ð¾Ð¹ ÐºÐ¾Ñ€Ð¾Ð½Ð°Ð²Ð¸Ñ€ÑƒÑÐ½Ð¾Ð¹ Ð¸Ð½Ñ„ÐµÐºÑ†Ð¸Ð¸ COVID-19, Ð²Ñ‹Ð·Ñ‹Ð²Ð°ÐµÐ¼Ð¾Ð¹ Ð²Ð¸Ñ€ÑƒÑÐ¾Ð¼ SARS-CoV-2, Ñ ÑƒÑ‡ÐµÑ‚Ð¾Ð¼ Ð¿Ñ€ÐµÐ´Ñ‹Ð´ÑƒÑ‰Ð¸Ñ… Ð²ÑÐ¿Ñ‹ÑˆÐµÐº Ð¸Ð½Ñ„ÐµÐºÑ†Ð¸Ð¹, Ð²Ñ‹Ð·Ð²Ð°Ð½Ð½Ñ‹Ñ… Î²-ÐºÐ¾Ñ€Ð¾Ð½Ð°Ð²Ð¸Ñ€ÑƒÑÐ°Ð¼Ð¸ MERS-CoV Ð¸ SARS-CoV, ÐºÐ°Ðº Ð¿Ñ€ÐµÐ´ÑÑ‚Ð°Ð²Ð»ÑÑŽÑ‰Ð¸Ñ… Ð½Ð°Ð¸Ð±Ð¾Ð»ÑŒÑˆÑƒÑŽ Ð¾Ð¿Ð°ÑÐ½Ð¾ÑÑ‚ÑŒ Ð´Ð»Ñ Ñ‡ÐµÐ»Ð¾Ð²ÐµÐºÐ° Ð’ Ð¾Ð±Ð·Ð¾Ñ€Ðµ ÐºÑ€Ð°Ñ‚ÐºÐ¾ Ð¾Ð¿Ð¸ÑÐ°Ð½Ñ‹ Ð´Ð²Ðµ ÑÐ¿Ð¸Ð´ÐµÐ¼Ð¸Ñ‡ÐµÑÐºÐ¸Ðµ Ð²ÑÐ¿Ñ‹ÑˆÐºÐ¸, Ð²Ñ‹Ð·Ð²Ð°Ð½Ð½Ñ‹Ðµ Ð²Ð¸Ñ€ÑƒÑÐ°Ð¼Ð¸ SARS-CoV (2002â€“2004 Ð³Ð³ ) Ð¸ MERS-CoV (2012 Ð³ â€“ Ð½Ð°ÑÑ‚Ð¾ÑÑ‰ÐµÐµ Ð²Ñ€ÐµÐ¼Ñ), Ð¿Ñ€ÐµÐ´ÑÑ‚Ð°Ð²Ð»ÐµÐ½Ð° Ñ‚ÐµÐºÑƒÑ‰Ð°Ñ ÑÐ¿Ð¸Ð´ÐµÐ¼Ð¸Ñ‡ÐµÑÐºÐ°Ñ ÑÐ¸Ñ‚ÑƒÐ°Ñ†Ð¸Ñ, ÑÐ²ÑÐ·Ð°Ð½Ð½Ð°Ñ Ñ Ð½Ð¾Ð²Ñ‹Ð¼ ÐºÐ¾Ñ€Ð¾Ð½Ð°Ð²Ð¸Ñ€ÑƒÑÐ¾Ð¼ SARS-CoV-2, Ð¸Ð·Ð»Ð¾Ð¶ÐµÐ½Ñ‹ Ð¾ÑÐ½Ð¾Ð²Ð½Ñ‹Ðµ Ð¾Ð³Ñ€Ð°Ð½Ð¸Ñ‡Ð¸Ñ‚ÐµÐ»ÑŒÐ½Ñ‹Ðµ Ð¼ÐµÑ€Ð¾Ð¿Ñ€Ð¸ÑÑ‚Ð¸Ñ, Ð¿Ñ€ÐµÐ´Ð¿Ñ€Ð¸Ð½Ð¸Ð¼Ð°ÐµÐ¼Ñ‹Ðµ Ð´Ð»Ñ Ð½ÐµÐ´Ð¾Ð¿ÑƒÑ‰ÐµÐ½Ð¸Ñ Ñ€Ð°ÑÐ¿Ñ€Ð¾ÑÑ‚Ñ€Ð°Ð½ÐµÐ½Ð¸Ñ Ð¸Ð½Ñ„ÐµÐ Ñ†Ð¸Ð¸ Ð² Ð Ð¾ÑÑÐ¸Ð¸ Ð Ð°ÑÑÐ¼Ð¾Ñ‚Ñ€ÐµÐ½Ñ‹ Ð°ÑÐ¿ÐµÐºÑ‚Ñ‹ Ð²Ð¾Ð·Ð¼Ð¾Ð¶Ð½Ð¾Ð¹ ÑÐ¿ÐµÑ†Ð¸Ñ„Ð¸Ñ‡ÐµÑÐºÐ¾Ð¹ Ñ‚ÐµÑ€Ð°Ð¿Ð¸Ð¸ Ð¸ Ñ€Ð°Ð·Ñ€Ð°Ð±Ð¾Ñ‚ÐºÐ¸ Ð¿Ñ€Ð¾Ñ„Ð¸Ð»Ð°ÐºÑ‚Ð¸Ñ‡ÐµÑÐºÐ¸Ñ… Ð²Ð°ÐºÑ†Ð¸Ð½Ð½Ñ‹Ñ… Ð¿Ñ€ÐµÐ¿Ð°Ñ€Ð°Ñ‚Ð¾Ð² Ð¿Ñ€Ð¾Ñ‚Ð¸Ð² Ð½Ð¾Ð²Ð¾Ð¹ ÐºÐ¾Ñ€Ð¾Ð½Ð°Ð²Ð¸Ñ€ÑƒÑÐ½Ð¾Ð¹ Ð¸Ð½Ñ„ÐµÐºÑ†Ð¸Ð¸ Ð¡Ð´ÐµÐ»Ð°Ð½ Ð²Ñ‹Ð²Ð¾Ð´ Ð¾ Ð²Ð¾Ð·Ð¼Ð¾Ð¶Ð½Ð¾Ð¼ Ð¿Ð°Ð½Ð´ÐµÐ¼Ð¸Ñ‡ÐµÑÐºÐ¾Ð¼ Ð¿Ð¾Ñ‚ÐµÐ½Ñ†Ð¸Ð°Ð»Ðµ Ð²Ð¸Ñ€ÑƒÑÐ° SARS-CoV-2 Ð¸ Ð²Ñ‹ÑÐ¾ÐºÐ¾Ð¹ Ð²ÐµÑ€Ð¾ÑÑ‚Ð½Ð¾ÑÑ‚Ð¸ Ð²Ð¾Ð·Ð½Ð¸ÐºÐ½Ð¾Ð²ÐµÐ½Ð¸Ñ Ð² Ð±ÑƒÐ´ÑƒÑ‰ÐµÐ¼ Ð²ÑÐ¿Ñ‹ÑˆÐµÐº Ð¸Ð½Ñ„ÐµÐºÑ†Ð¸Ð¹, Ð²Ñ‹Ð·Ð²Ð°Ð½Ð½Ñ‹Ñ… Ð½Ð¾Ð²Ñ‹Ð¼Ð¸ ÑˆÑ‚Ð°Ð¼Ð¼Ð°Ð¼Ð¸ Î²-ÐºÐ¾Ñ€Ð¾Ð½Ð°Ð²Ð¸Ñ€ÑƒÑÐ¾Ð² Ð£ÐºÐ°Ð·Ð°Ð½Ð¾ Ð½Ð° Ð½ÐµÐ¾Ð±Ñ…Ð¾Ð´Ð¸Ð¼Ð¾ÑÑ‚ÑŒ Ð¾ÑÑƒÑ‰ÐµÑÑ‚Ð²Ð»ÐµÐ½Ð¸Ñ Ñ‚Ñ‰Ð°Ñ‚ÐµÐ»ÑŒÐ½Ð¾Ð³Ð¾ Ð¼Ð¾Ð½Ð¸Ñ‚Ð¾Ñ€Ð¸Ð½Ð³Ð° Ð·Ð°Ð±Ð¾Ð»ÐµÐ²Ð°Ð½Ð¸Ñ Ð¸ Ð¿Ñ€Ð¾Ð²ÐµÐ´ÐµÐ½Ð¸Ñ Ð¿Ñ€ÐµÐ²ÐµÐ½Ñ‚Ð¸Ð²Ð½Ñ‹Ñ… Ð¿Ñ€Ð¾Ñ‚Ð¸Ð²Ð¾ÑÐ¿Ð¸Ð´ÐµÐ¼Ð¸Ñ‡ÐµÑÐºÐ¸Ñ… Ð¼ÐµÑ€Ð¾Ð¿Ñ€Ð¸ÑÑ‚Ð¸Ð¹ Ð´Ð»Ñ ÑÐ´ÐµÑ€Ð¶Ð¸Ð²Ð°Ð½Ð¸Ñ Ñ€Ð°ÑÐ¿Ñ€Ð¾ÑÑ‚Ñ€Ð°Ð½ÐµÐ½Ð¸Ñ Ð¸Ð½Ñ„ÐµÐºÑ†Ð¸Ð¸


New potential interaction with emergency COVID-19 medicine remdesivir


docid: fzusgbww

title: Acute mental health responses during the COVID-19 pandemic in Australia

text: The acute and long-term mental health impacts of the COVID-19 pandemic are unknown. The current study examined the acute mental health responses to the COVID-19 pandemic in 5070 adult participants in Australia, using an online survey administered during the peak of the outbreak in Australia (27th March to 7th April 2020). Self-report questionnaires examined COVID-19 fears and behavioural responses to COVID-19, as well as the severity of psychological distress (depression, anxiety and stress), health anxiety, contamination fears, alcohol use, and physical activity. 78% of respondents reported that their mental health had worsened since the outbreak, one quarter (25.9%) were very or extremely worried about contracting COVID-19, and half (52.7%) were worried about family and friends contracting COVID-19. Uncertainty, loneliness and financial worries (50%) were common. Rates of elevated psychological distress were higher than expected, with 62%, 50%, and 64% of respondents reporting elevated depression, anxiety and stress levels respectively, and one in four reporting elevated health anxiety in the past week. Participants with self-reported history of a mental health diagnosis had significantly higher distress, health anxiety, and COVID-19 fears than those without a prior mental health diagnosis. Demographic (e.g., non-binary or different gender identity; Aboriginal and Torres Strait Islander status), occupational (e.g., being a carer or stay at home parent), and psychological (e.g., perceived risk of contracting COVID-19) factors were associated with distress. Results revealed that precautionary behaviours (e.g., washing hands, using hand sanitiser, avoiding social events) were common, although in contrast to previous research, higher engagement in hygiene behaviours was associated with higher stress and anxiety levels. These results highlight the serious acute impact of COVID-19 on the mental health of respondents, and the need for proactive, accessible digital mental health services to address these mental health needs, particularly for those most vulnerable, including people with prior history of mental health problems. Longitudinal research is needed to explore long-term predictors of poor mental health from the COVID-19 pandemic.


title: Impact of mitigating interventions and temperature on the instantaneous reproduction number in the COVID-19 epidemic among 30 US metropolitan areas

text: Background: After more than three months into the coronavirus disease (COVID-19) epidemic, over 170,000 people had died worldwide. The current study aims to evaluate how mitigating interventions affected the epidemic process in the 30 largest metropolitan areas in the US and whether temperature played a role in the epidemic process. Methods: Publicly available COVID-19 cases and deaths data and weather data were analyzed at the metropolitan level. The time-varying reproductive numbers were used to explore the trends. Results: We found that virus transmissibility, measured by instantaneous reproduction number (Rt), had declined significantly since the end of March for all areas and almost all of them reached a Rt of 1 or below by April 15, 2020. Cities with warm temperature tended to have a lower peak Rt than that of cities with cold temperature. However, large geographic variations exist. Conclusions: Though the end of epidemic of COVID-19 is near, temperature may have some weak effects on the virus transmission, and the return of the coronavirus outbreak is still possible.


title: Core Outcome Set for Clinical Trials of COVID-19 based on Traditional Chinese and Western Medicine

text: Background: Development of a core outcome set (COS) for clinical trials for COVID-19 is urgent because of the pandemic wreaking havoc worldwide and the heterogeneity of outcomes in clinical trials. Methods: A preliminary list of outcomes were developed after a systematic review of protocols of clinical trials for COVID-19. Then, two rounds of the Delphi survey were conducted. Stakeholders were traditional Chinese medicine (TCM) experts, Western medicine (WM) experts, nurses and the public. Patients with confirmed COVID-19 were also invited to participate in a questionnaire written in understandable language. Frontline clinicians, as well as nurse, methodologist, evidence based-medicine researcher, and staff from the Chinese Clinical Trials Registry participated by video conference to vote. Results: Ninety-seven eligible study protocols were identified from 160 clinical trials. Seventy-six outcomes were identified from TCM clinical trials and 126 outcomes were identified from WM clinical trials. Finally, 145 outcomes were included in the first round of the Delphi survey. Then, a COS for clinical trials of TCM and WM was developed. The COS include clinical outcomes (recovery/improvement/progression/death), etiology (SARS-CoV-2 nucleic-acid tests, viral load), inflammatory factor (C-reactive protein), vital signs (temperature, respiration), blood and lymphatic-system parameters (lymphocytes, virus antibody), respiratory outcomes (Pulmonary imaging, blood oxygen saturation, PaO2/FiO2 ratio, arterial blood gas analysis, mechanical ventilation, oxygen intake, pneumonia severity index), clinical efficacy (prevalence of preventing patients with mild-to-moderate disease progressing to severe disease), symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instrument/definition were also recommended. Conclusion: A COS for COVID-19 may improve consistency of outcome reporting in clinical trials.


title: Diagnostic power of chest CT for COVID-19: to screen or not to screen

text: Background: chest CT is increasingly used for COVID-19 screening in healthcare systems with limited SARS-CoV-2 PCR capacity. Its diagnostic value was supported by studies with methodological concerns and its use is controversial. Here we investigated its potential to diagnose COVID-19 in symptomatic patients and to screen asymptomatic patients in a prospective study with minimal selection bias. Methods: From March 19, 2020 to April 20, 2020 we performed parallel SARS-CoV-2 PCR and CT with categorization of COVID-19 suspicion by CO-RADS, in 859 patients with COVID-19 symptoms and 1138 controls admitted to the hospital for COVID-19 unrelated medical urgencies. CT-CORADS was categorized on a 5-point scale from 1 (very low suspicion) to 5 (very high suspicion). AUC under ROC curve were calculated in symptomatic versus asymptomatic patients to predict positive SARS-CoV-2 positive PCR and likelihood ratios for each CO-RADS score were used for rational selection of diagnostic thresholds. Findings: CT-CORADS had significant (P<0.0001) diagnostic power in both symptomatic (AUC=0.891) and asymptomatic (AUC=0.700) patients hospitalized during SARS-CoV-2 peak prevalence. In symptomatic patients (41.7% PCR+), CO-RADS [≥] 3 detected positive PCR with high sensitivity (89.1%) and 72.5% specificity. In asymptomatic patients (5.3% PCR+), a CO-RADS score [≥] 3 detected SARS-CoV-2 infection with low sensitivity (45.0%) but high specificity (88.8%). Interpretation: CT-CORADS has meaningful diagnostic power in symptomatic patients, supporting its application for time-sensitive triage. Sensitivity in asymptomatic patients is insufficient to justify its use as screening approach. Incidental detection of CO-RADS [≥] 3 in asymptomatic patients should trigger reflex testing for respiratory pathogens.


docid: dsklkntt

title: Off-Label Real World Experience Using Tocilizumab for Patients Hospitalized with COVID-19 Disease in a Regional Community Health System: A Case-Control Study

text: Objective: To determine if Tocilizumab treatment in patients hospitalized with laboratory confirmed SARS-CoV-2 infection and subsequent COVID-19 disease provides short-term survival benefit. Design: Case-control, observational study that includes an observation period from arrival to discharge or inpatient death. Both Cox proportional hazards and average treatment effects models were used to determine survival and treatment benefits. Setting: Three Cone Health acute care hospitals including one COVID dedicated facility. Patients: Patients admitted with confirmed SARS-CoV-2 from March 16, 2020 through April 22, 2020. Exposure: Tocilizumab dosed at either 400 mg fixed dose or 8 mg/kg weight-based dose with maximum single dose of 800mg. Measurements and Main Results: Overall, 86 patients were admitted during the observation period with confirmed COVID-19 disease. Of these, 21 received Tocilizumab during the hospital stay. Both the Cox model and treatment effects models showed short-term survival benefit. There was an associated 75% reduction in the risk of inpatient death when treated (HR 0.25; 95% CI 0.07-0.90) in the Cox model. This association was confirmed in the treatment effects model where we found a 52.7% reduced risk of dying while hospitalized compared to those not treated (RR 0.472; 95% CI 0.449-0.497). In both models, we show short-term survival benefit in patients with severe COVID-19 illness.


title: Extubation and the Risks of Coughing and Laryngospasm in the Era of Coronavirus Disease-19 (COVID-19)

text: The coronavirus disease-19 (COVID-19) pandemic has prompted new interest among anesthesiologists and intensivists in controlling coughing and expectoration of potentially infectious aerosolized secretions during intubation and extubation. However, the fear of provoking laryngospasm may cause avoidance of deep or sedated extubation techniques which could reduce coughing and infection risk. This fear may be alleviated with clear understanding of the mechanisms and effective management of post-extubation airway obstruction including laryngospasm. We review the dynamic function of the larynx from the vantage point of head-and-neck surgery, highlighting two key concepts: 1. The larynx is a complex organ that may occlude reflexively at levels other than the true vocal folds; 2. The widely held belief that positive-pressure ventilation by mask can “break” laryngospasm is not supported by the otorhinolaryngology literature. We review the differential diagnosis of acute airway obstruction after extubation, discuss techniques for achieving smooth extubation with avoidance of coughing and expectoration of secretions, and recommend, on the basis of this review, a clinical pathway for optimal management of upper airway obstruction including laryngospasm to avoid adverse outcomes.


title: Assessing the burden of COVID-19 in Canada

text: Background: The burden of COVID-19 in Canada is unequally distributed geographically, with the largest number of cases and fatalities recorded in Quebec and Ontario while other provinces experienced limited outbreaks. To date, however, no study has assessed how provincial epidemics have unfolded in a comparative perspective. This is essential to calibrate projections of the future course of the epidemic and plan health care resources for the second wave of infections. Methods: Using newly released individual-level data collected by the Public Health Agency of Canada, we assess COVID-19-related morbidity and mortality across age and gender groups at the provincial level through a combination of demographic and survival analyses. Results: Quebec has the highest absolute and per capita number of COVID-19 confirmed positive cases, hospitalizations and fatalities in all age groups. In each province, a higher number of women than men test positive for the disease, especially above age 80. Yet consistently across age groups, infected men are more likely to be hospitalized and enter intensive care than women do. These gender differences in hospitalisation rates account for the higher case fatality risk due to COVID-19 among men compared to women. Interpretation: Although health care capacity across provinces has been sufficient to treat severe cases, we find that the main factor accounting for gender differences in COVID-19-related mortality is the need for hospitalization and intensive care, especially above age 80. This suggests a selection effect of severe cases requiring to be treated in a hospital setting that needs to be further investigated.


docid: omyxxwua

title: COVID-19 pandemic: Time for the anesthesiologist to be in action

text: Covid-19 pandemic has taken over the world in a storm. Starting from the Chinese city of Wuhan, it has engulfed almost every country, and every nation of the world. The rapid pace of emerging statistics has baffled the healthcare community, and hospitals have been fighting day and night to treat the known patients. The cities have been locked down and international medical academic authorities have been quick to offer updated guidelines and protocols. The electronic media has been pivotal in rapid dissemination of the new knowledge about dealing with this catastrophe. This editorial offers an overview of the development of the pandemic and the ways and means to tackle it. It mainly stresses upon the most vital role of care in intensive care units, which needs exercise of utmost dedication, and professional expertise by the anesthesiologists, the intensivists and supporting staff.


title: Quantifying Respiratory Airborne Particle Dispersion Control Through Improvised Reusable Masks

text: Objective: To determine the effectiveness of non-medical grade washable masks or face coverings in controlling airborne dispersion from exhalation (both droplet and aerosol), and to aid in establishing public health strategies on the wearing of masks to reduce COVID-19 transmission. Design: This comparative effectiveness study using an exhalation simulator to conduct 94 experiment runs with combinations of 8 different fabrics, 5 mask designs, and airflows for both talking and coughing. Setting: Non-airtight fume hood and multiple laser scattering particle sensors. Participants: No human participants. Exposure: 10% NaCl nebulized solution delivered by an exhalation simulator through various masks and fabrics with exhalation airflows representative of "coughing" and "talking or singing." Main Outcomes and Measures: The primary outcome was reduction in aerosol dispersion velocity, quantity of particles, and change in dispersion direction. Measurements used in this study included peak expiratory flow (PEF), aerosol velocity, concentration area under curve (AUC), and two novel metrics of expiratory flow dispersion factor (EDF) and filtration efficiency indicator (FEI). Results: Three-way multivariate analysis of variance establishes that factors of fabric, mask design, and exhalation breath level have a statistically significant effect on changing direction, reducing velocity or concentration (Fabric: P = < .001, Wilks' {Lambda} = .000; Mask design: P = < .001, Wilks' {Lambda} = .000; Breath level: P = < .001, Wilks' {Lambda} = .004). There were also statistically significant interaction effects between combinations of all primary factors. Conclusions and Relevance: The application of facial coverings or masks can significantly reduce the airborne dispersion of aerosolized particles from exhalation. The results show that wearing of non-medical grade washable masks or face coverings can help increase the effectiveness of non-pharmaceutical interventions (NPI) especially where infectious contaminants may exist in shared air spaces. However, the effectiveness varies greatly between the specific fabrics and mask designs used.


title: Cardiac or Infectious? Transfer Learning with Chest X-Rays for ER Patient Classification

text: One of the challenges with urgent evaluation of patients with acute respiratory distress syndrome (ARDS) in the emergency room (ER) is distinguishing between cardiac vs infectious etiologies for their pulmonary findings. We evaluated ER patient classification for cardiac and infection causes with clinical data and chest X-ray image data. We show that a deep-learning model trained with an external image data set can be used to extract image features and improve the classification accuracy of a data set that does not contain enough image data to train a deep-learning model. We also conducted clinical feature importance analysis and identified the most important clinical features for ER patient classification. This model can be upgraded to include a SARS-CoV-2 specific classification with COVID-19 patients data. The current model is publicly available with an interface at the web link: http://nbttranslationalresearch.org/.


title: Research on COVID-19 virus spreading statistics based on the examples of the cases from different counties

text: The novel coronavirus COVID-19 originally identified in December 2019, based on the data issued by March 30, 2020 daily report, the epidemic of SARS-CoV-2 so far has caused 693224 cases and resulted in 33106 deaths in more than 200 countries. Referring to the data reported, World Health Organization declared the outbreak a pandemic. We considered the chain-binomial type of the model which involves short stages of high infectivity and approximately constant incubation periods. This research paper is to study and analyze the COVID-19 Virus spreading statistics on the examples of the cases from the different counties. High correlation coefficients (91.64%) and determinants (83.98%) between the total volumes of virus spread and recovery are considered to be high and indicate the correctness of the Bailey model. Thus, as of March 30, with the results of statistical and mathematical data processing, it is difficult to predict the future spread-reduction variables of the pandemic.


To Act.......or to wait for the evidence_ Ethics in the time of covid-19!


docid: ajuzxjgx

title: Highly sensitive quantitative and rapid immunochromatographic diagnosis of the clinical samples using scanning electron microscopy - preparing for future outbreaks.

text: As pathogens such as the influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can easily cause pandemics, the development of rapid diagnostic tests is crucial for implementing efficient quarantine measures, providing effective treatments to patients, and preventing or containing a pandemic infection. Here, we developed the immunochromatography-NanoSuit method, an improved immunochromatography method combined with a conventional scanning electron microscope (SEM), which enables the observation of immunocomplexes labeled with a colloidal metal. The detection ability of our method is comparable to that of real-time reverse transcription-polymerase chain reaction with a detection time of approximately 15 min. Our new immunochromatography-NanoSuit method suppresses cellulose deformity and makes it possible to easily focus and acquire high-resolution images of gold/platinum labeled immunocomplexes of influenza A, without the need for conductive treatment as with a conventional SEM. This easy and highly sensitive quantitative analysis by immunochromatography can be utilized to diagnose various infections including SARS-CoV-2.


title: COVID-19 Datasets: A Survey and Future Challenges

text: In December 2019, a novel virus named as COVID-19 emerged in the city of Wuhan, China. In early 2020, the COVID-19 virus spread in all continents of the world except Antarctica causing widespread infections and deaths due to its contagious characteristics and no medically proven treatment. The COVID-19 pandemic has been termed as most consequential global crisis after the World Wars. The first line of defense against the COVID-19 spread are the non-pharmaceutical measures like social distancing and personal hygiene. On the other hand, the medical service providers are the first responders for infected persons with severe symptoms of COVID-19. The great pandemic affecting billions of lives economically and socially has motivated the scientific community to come up with solutions based on computer-aided digital technologies for diagnosis, prevention, and estimation of COVID-19. Some of these efforts focus on statistical and Artificial Intelligence-based analysis of the available data concerning COVID-19. All of these scientific efforts necessitate that the data brought to service for the analysis should be open-source to promote the extension, validation, and collaboration of the work in the fight against the global pandemic. Our survey is motivated by the open-source efforts that can be mainly categorized as: (a) COVID-19 diagnosis from CT scans and X-ray images, (b) COVID-19 case reporting, transmission estimation, and prognosis from epidemiological, demographic, and mobility data, (c) COVID-19 emotional and sentiment analysis from social media, and (d) knowledge-based discovery and semantic analysis from the collection of scholarly articles covering COVID-19. We review and critically analyze works in these directions that are accompanied by open-source data and code. We hope that the article will provide the scientific community with an initiative to start open-source extensible and transparent research in the collective fight against COVID-19.


Comorbidities might be a risk factor for the incidence of COVID-19: Evidence from a web-based survey of 780,961 participants


Alteration of Consciousness as Initial Presentation in COVID-19: Observation


title: Identifying and Ranking Common COVID-19 Symptoms from Arabic Twitter

text: Objective: The aim of this study is to identify the most common symptoms reported by covid-19 patients in the Arabic language and order the symptoms appearance based on the collected data. Methods: We search the Arabic content of Twitter for personal reports of covid-19 symptoms from March 1st to May 27th, 2020. We identify 463 Arabic users who tweeted testing positive for covid-19 and extract the symptoms they publicly associate with covid-19. Furthermore, we ask them directly through personal messages to opt in and rank the appearance of the first three symptoms they experienced right before (or after) diagnosed with covid-19. Finally, we track their Twitter timeline to identify additional symptoms that were mentioned within +-5 days from the day of tweeting having covid-19. In summary, a list of 270 covid-19 reports were collected and symptoms were (at least partially) ranked from early to late. Results: The collected reports contained roughly 900 symptoms originated from 74% (n=201) male and 26% (n=69) female Twitter users. The majority (82%) of the tracked users were living in Saudi Arabia (46%) and Kuwait (36%). Furthermore, 13% (n=36) of the collected reports were asymptomatic. Out of the users with symptoms (n=234), 66% (n=180) provided a chronological order of appearance for at least three symptoms. Fever 59% (n=139), Headache 43% (n=101), and Anosmia 39% (n=91) were found to be the top three symptoms mentioned by the reports. They count also for the top-3 common first symptoms in a way that 28% (n=65) said their covid journey started with a Fever, 15% (n=34) with a Headache and 12% (n=28) with Anosmia. Out of the Saudi symptomatic reported cases (n=110), the most common three symptoms were Fever 59% (n=65), Anosmia 42% (n=46), and Headache 38% (n=42).


title: Study of the lymphocyte change between COVID-19 and non-COVID-19 pneumonia cases suggesting other factors besides uncontrolled inflammation contributed to multi-organ injury

text: Background: The corona virus disease 2019 (COVID-19) shows unusually high transmission rate and unique clinical characteristics, with key pathological mechanism remaining unclear. Here, we analysed the laboratory data based on clinical samples from COVID-19 patients, in parallel comparison with non-COVID-19 pneumonia cases, in an attempt to elucidate the key pathological features of COVID-19 during its infection of the human body. Methods: We analysed biochemical indices and lymphocyte subpopulation in COVID-19 patients, and compare these data from non-COVID-19 pneumonia cases. Correlation analysis was performed between leukocyte subgroups count and biochemical indexes in COVID-19 patients. Results: The study enrolled 110 patients, comprising 88 COVID-19 patients and 22 non-COVID-19 pneumonia cases. We observed significant differences, including abnormal biochemical indices (CRP, LDH, AST, eGFR, and sodium ion concentration) and reduced lymphocyte subsets count, between the COVID-19 patients and non-COVID-19-caused pneumonia cases. Correlation analysis indicates that the count for lymphocyte subsets-but not that for neutrophils and monocytes-exhibits a significant negative correlation with biochemical indices relating to organ injury, in the COVID-19 infected patients. Conclusions: The study indicates significantly different clinical features between 2019 novel coronavirus (2019-nCoV)-caused and non-2019-nCoV-caused pneumonia, especially in terms of lymphocytopenia and organ injury. Notably, correlation analysis demonstrates that tissue damage in COVID-19 patients is attributed to virus infection itself rather than uncontrolled inflammatory responses ("cytokine storm"). These findings provide new insights for developing efficient therapeutic strategies against COVID-19 infection.


title: Structural Basis of SARS-CoV-2 Spike Protein Priming by TMPRSS2

text: Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive. TMPRSS2 is responsible for priming of the viral spike protein that entails cleavage of the spike protein at two potential sites, Arg685/Ser686 and Arg815/Ser816. The present study aims to investigate the conformational details of complex between TMPRSS2 and SARS-CoV-2 spike protein, in order to discern the finer details of the priming of viral spike and to point candidate drug targets. Briefly, full length structural model of TMPRSS2 was developed and docked against the resolved structure of SARS-CoV-2 spike protein with directional restraints of both cleavage sites. The docking simulations showed that TMPRSS2 interacts with the two different loops of SARS-CoV-2 spike protein, each containing different cleavage sites. Key functional residues of TMPRSS2 (His296, Ser441 and Ser460) were found to interact with immediate flanking residues of cleavage sites of SARS-CoV-2 spike protein. Compared to the N-terminal cleavage site (Arg685/Ser686), TMPRSS2 region that interact with C-terminal cleavage site (Arg815/Ser816) of the SARS-CoV-2 spike protein was predicted as relatively more druggable. In summary, the present study provide structural characteristics of molecular complex between human TMPRSS2 and SARS-CoV-2 spike protein and points to the candidate drug targets that could further be exploited to direct structure base drug designing.


title: The elusive test for unfair excessive pricing under EU law: revisiting United Brands in the light of Competition and Markets Authority v Flynn Pharma Ltd

text: The European Commission has historically proved relatively reluctant to intervene in the area of excessive pricing. This is probably partly because the test outlined in United Brands v Commission remains unclear in various respects. In a recent decision of the English Court of Appeal–Competition and Markets Authority v Flynn Pharma–the English court sought to revisit some of the problematic aspects of the United Brands test. While the decision places a useful light on the intrinsic problems with the test, it is argued that in certain respects the Court of Appeal's reading is questionable and that significant uncertainties remain. In particular, the questions of what qualifies a price as being “unfair in itself” and how the economic value of a product should be assessed remain problematic. Until these issues are addressed more thoroughly by the EU courts, the enforcement of unfair excessive pricing will continue to prove problematic.


title: Proteomic and Metabolomic Characterization of COVID-19 Patient Sera

text: Severe COVID-19 patients account for most of the mortality of this disease. Early detection and effective treatment of severe patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model correctly classified severe patients with an accuracy of 93.5%, and was further validated using ten independent patients, seven of which were correctly classified. We identified molecular changes in the sera of COVID-19 patients implicating dysregulation of macrophage, platelet degranulation and complement system pathways, and massive metabolic suppression. This study shows that it is possible to predict progression to severe COVID-19 disease using serum protein and metabolite biomarkers. Our data also uncovered molecular pathophysiology of COVID-19 with potential for developing anti-viral therapies.


Neighborhood Effects and Urban Inequalities: The Impact of Covid‐19 on the Periphery of Salvador, Brazil


title: Strengthening of Molecular Diagnosis of SARS-CoV-2 / COVID-19 with a Special Focus on India

text: Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), a novel coronavirus initially reported in Wuhan, China, is the causative agent of coronavirus disease (COVID-19) pandemic Symptoms of the disease comprise of fever, tiredness, dry cough, aches and pains, nasal congestion, runny nose, sore throat, diarrhoea and pneumonia at the late stage SARS-CoV-2 has severely crippled the healthcare system and has caused huge economic losses Following the outbreak, the SARS-CoV-2 was recognized timely and its genome was sequenced, leading to the development of real-time polymerase chain reaction assays for its detection in clinical samples collected from suspected cases The management of the pandemic is limited by a number of misconceptions and insufficient information about laboratory testing for SARS-CoV-2 to confirm the disease This includes a lack of awareness about procedures for the collection, transport, testing, and handling of biological samples for COVID diagnosis This article provides an overview of the current laboratory diagnostic methods with a purpose to provide information and guidance to laboratories, stakeholders, broader community and especially public health professionals involved in laboratory testing for SARS-CoV-2


title: ScRNA-seq discover cell cluster change under OAB: ACE2 expression reveal possible alternation of 2019-nCoV infectious pathway

text: Objective Previous study indicated that bladder cells which express ACE2 were a potential infection route of 2019-nCov. This study observed some differences of bladder cell cluster and their ACE2 expression between OAB mice and healthy mice, indicating the change of infectious possibility and pathway under overactive bladder (OAB) circumstance. Material and method Pubic dataset acquisition was used to get ACE2 expression in normal human bladder and mice bladder (GSE129845). We built up over OAB model and studied the impact on cell typing and ACE2 expression. By way of using single-cell RNA sequencing (scRNA-seq) technique, bladder cell clustering and ACE2 expression in various cell types were measured respectively. Result In pubic database (healthy human and mice bladder), ACE2 expression in humans and mice is concentrated in bladder epithelial cells. The disappearance of umbrella cells, a component of bladder epithelial, was found in our OAB model. In the two mouse bladder samples, ACE2 expression of epithelial cells is 34.1%, also the highest of all cell types. Conclusion The disappearance of umbrella cell may alternate the infection pathway of 2019-nCov and relate to the onset and progression of OAB.


title: Estimating the risk of 2019 Novel Coronavirus death during the course of the outbreak in China, 2020

text: Since the first case of Novel Coronavirus (2019-nCov) was identified in December 2019 in Wuhan City, China, the number of cases continues to grow across China and multiple cases have been exported to other countries. The cumulative number of reported deaths is at 637 as of February 7, 2020. Here we statistically estimated the time-delay adjusted death risk for Wuhan as well as for China excluding Wuhan to interpret the current severity of the epidemic in China. We found that the latest estimates of the death risk in Wuhan could be as high as 20% in the epicenter of the epidemic whereas we estimate it ~1% in the relatively mildly-affected areas. Because the elevated death risk estimates are likely associated with a breakdown of the medical/health system, enhanced public health interventions including social distancing and movement restrictions should be effectively implemented to bring the epidemic under control.


title: Lessons from a rapid systematic review of early SARS-CoV-2 serosurveys

text: 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.


title: Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19

text: Background: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in laboratory-confirmed COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients from a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared among severe and nonsevere patients. Immune response phenotyping based on late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratify patients with different disease severities and outcome. Laboratory parameters in patients with different immune response phenotypes and disease severities were analyzed. Findings: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those who with low IgG levels (51.8% versus 32.3%; p=0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 72.3%, 48.5%, 33.3%, and 15.6%, respectively (p<0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher proinflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p<0.05). Recovery rate for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p=0.0592). Dead cases only occurred in NLRhiIgGhi and NLRhiIgGlo phenotypes. Interpretation: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on late IgG response and NLR could act as a simple complementary tool to discriminate between severe and nonsevere COVID-19 patients, and further predict their clinical outcome.


title: SARS-CoV-2 Genome Analysis of Japanese Travelers in Nile River Cruise

text: Japan has reported 26 cases of coronavirus disease 2019 (COVID-19) linked to cruise tours on the River Nile in Egypt between March 5 and 15, 2020. Here, we characterized the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome of isolates from 10 travelers who returned from Egypt and from patients possibly associated with these travelers. We performed haplotype network analysis of SARS-CoV-2 isolates using genome-wide single-nucleotide variations. Our analysis identified two potential Egypt-related clusters from these imported cases, and these clusters were related to globally detected viruses in different countries.


title: Covid-19 clinical data analysis using Ball Mapper

text: In this note we provide a result of analysis of blood test data from patients with SARS-Cov-2 using Ball Mapper Algorithm. We observe that patients with the virus and in particularly patients who end up in Intensive Care Unit have quite narrow values of those parameters. Please note that this is a preliminary work and it need to be validated on much larger dataset which we are trying to acquire at the moment.


title: AI based Chest X-Ray (CXR) Scan Texture Analysis Algorithm for Digital Test of COVID-19 Patients

text: Chest Imaging in COVID-19 patient management is becoming an essential tool for controlling the pandemic that is gripping the international community. It is already indicated in patients with COVID-19 and worsening respiratory status. The rapid spread of the pandemic to all continents, albeit with a nonuniform community transmission, necessitates chest imaging for medical triage of patients presenting moderate-severe clinical COVID-19 features. This paper reports the development of innovative machine learning schemes for the analysis of Chest X-Ray (CXR) scan images of COVID-19 patients in almost real-time, demonstrating significantly high accuracy in identifying COVID-19 infection. The performance testing was conducted on a combined dataset comprising CXRs of positive COVID-19 patients, patients with various viral and bacterial infections, as well as persons with a clear chest. The test resulted in successfully distinguishing CXR COVID-19 infection from the other cases with an average accuracy of 94.43%, sensitivity 95% and specificity 93.86%.


title: Novel coronavirus (2019-NCoV): Disease briefings

text: Coronavirus (CoV) (2019‐nCoV) is a large, enveloped, positive‐sense, single‐stranded RNA virus. The abnormal outbreak of 2019‐nCoV in Wuhan warns of the risk of CoV (2019‐nCoV) to public health which causes viral pneumonia outbreak. In our review, we will discuss the biology of CoVs and the potential risk of the novel CoV (2019‐nCoV) and guide us to strategic objectives for controlling the virus.


title: Predictors of COVID-19 incidence, mortality, and epidemic growth rate at the country level

text: Background. The burden of the coronavirus disease 2019 (COVID-19) pandemic has been geographically disproportionate. Certain weather factors and population characteristics are thought to drive transmission, but studies examining these factors are limited. We aimed to identify weather, sociodemographic, and geographic drivers of COVID-19 at the global scale using a comprehensive collection of country/territory-level data, and to use discovered associations to estimate the timing of community transmission. Methods. We examined COVID-19 cases and deaths reported up to May 2, 2020 across 205 countries and territories in relation to weather data collected from capital cities for the eight weeks prior to and four weeks after the date of the first reported case, as well as country/territory-level population, geographic, and planetary data. We performed univariable and multivariable regression modeling and odds ratio analyses to investigate associations with COVID-19 cases, deaths, and epidemic growth rate. We also conducted maximum likelihood analysis to estimate the timing of initial community spread. Findings. Lower temperature (p<0.0001), lower humidity (p=0.006), higher altitude (p=0.0080), higher percentage of urban population (p<0.0001), increased air travelers (p=0.00019), and higher prevalence of obesity (p<0.0001) were strong independent predictors of national COVID-19 incidence, mortality, and epidemic growth rate. Temperature at 5-7 weeks before the first reported case best predicted epidemic growth, suggesting that significant community transmission was occurring on average 1-2 months prior to detection. Interpretation. The results of this ecologic analysis demonstrate that global COVID-19 burden and timing of country-level epidemic growth can be predicted by weather and population factors. In particular, we find that cool, dry, and higher altitude environments, as well as more urban and obese populations, may be conducive to more rapid epidemic spread. Funding sources: None.


title: Estimating SARS-CoV-2 seroprevalence and epidemiological parameters with uncertainty from serological surveys

text: Establishing how many people have already been infected by SARS-CoV-2 is an urgent priority for controlling the COVID-19 pandemic. Patchy virological testing has hampered interpretation of confirmed case counts, and unknown rates of asymptomatic and mild infections make it challenging to develop evidence-based public health policies. Serological tests that identify past infection can be used to estimate cumulative incidence, but the relative accuracy and robustness of various sampling strategies has been unclear. Here, we used a flexible framework that integrates uncertainty from test characteristics, sample size, and heterogeneity in seroprevalence across tested subpopulations to compare estimates from sampling schemes. Using the same framework and making the assumption that serological positivity indicates immune protection, we propagated these estimates and uncertainty through dynamical models to assess the uncertainty in the epidemiological parameters needed to evaluate public health interventions. We examined the relative accuracy of convenience samples versus structured surveys to estimate population seroprevalence, and found that sampling schemes informed by demographics and contact networks outperform uniform sampling. The framework can be adapted to optimize the design of serological surveys given particular test characteristics and capacity, population demography, sampling strategy, and modeling approach, and can be tailored to support decision-making around introducing or removing interventions.


title: Efficient Prevalence Estimation and Population Screening for SARS-CoV-2

text: The testing capacity for SARS-CoV-2 using RT-PCR analyses can be substantially increased by using pooling techniques. Here we discuss two important consequences of this. First, prevalence estimation can be done with a very limited number of RT-PCR analysis. Second, for screening purposes, the number of detected cases can largely increased.


title: Identification of immunodominant linear epitopes from SARS-CoV-2 patient plasma

text: A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) is the source of a current pandemic (COVID-19) with devastating consequences in public health and economic stability. Using a peptide array to map the antibody response of plasma from healing patients, we identified immunodominant linear epitopes corresponding to key proteolytic sites on the spike protein.


title: Emergency Use Authorization of Remdesivir: The Need for a Transparent Distribution Process

text: This Viewpoint reviews the FDA's May 2020 Emergency Use Authorization of the antiviral drug remdesivir for treatment of COVID-19 and discusses the need for a transparent distribution plan of a drug not otherwise available in the US and for which demand will likely exceed supply [ABSTRACT FROM AUTHOR] Copyright of JAMA: Journal of the American Medical Association is the property of American Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )


title: Incubation Period and Reproduction Number for novel coronavirus (COVID-19) infections in India

text: Novel coronavirus (COVID 19) rapidly spread from China to other parts of the world. Knowledge of incubation period and reproduction number is important in controlling any epidemic. The distribution of these parameters helps estimate the epidemic size and transmission potential of the disease. We estimated incubation period and reproduction number of COVID 19 for India utilizing data reported by Ministry of Health and Family Welfare (MoHFW), Government of India (GOI) and data in public domain. The mean incubation period seems to be larger at 6.93 (SD=5.87, 95% CI: 6.11, 7.75). and 95th percentile estimate for best fit normal distribution is 17.8 days. Weibull distribution, the best fit for the reproduction number estimated pre lockdown reproduction number as 2.6 (95% CI=2.34, 2.86) and post lockdown reduced to 1.57 (95% CI=1.3 , 1.84) implying effectiveness of the epidemic response strategies. The herd immunity is estimated between 36 to 61% for R0 of 1.57 and 2.6 respectively.


title: COVID-19 Pandemic: Is Chronic Inflammation a Major Cause of Death?

text: Abstract Background. Today humanity is facing another infectious threat: a newly emerging virus SARS-CoV-2 causing COVID-19. It was already described that COVID-19 mortality among elderly people and people with such underlying conditions as obesity, cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes s increased. Dysregulation of the immune responses vital for antiviral defense, which are typical for chronic inflammation, led us to a hypothesis that chronic inflammation is the main risk factor for increased susceptibility and mortality from COVID-19. Method. Based on the available information for 126 countries, statistical analysis to find out whether the difference in incidence and mortality within countries can be explained by the existing chronic inflammation among the countries population, was conducted. Results. A positive correlation between the percentage of people dying from chronic noncommunicable diseases and COVID-19 incidence (p<0.001) and mortality (p<0.001) within countries. Conclusion. The problem of COVID-19-caused high mortality rate may be a consequence of the high number of people having chronic low-grade inflammation as a precondition, and thus, one of the potential ways to reduce risk of morbidity and mortality is to focus on this widespread health problem, mainly occurring in developed countries and to take corresponding diagnostic, preventative, and treatment measures.


docid: feqwdynl

title: Focus on Mental Health During the Coronavirus (COVID-19) Pandemic: Applying Learnings from the Past Outbreaks

text: The 2019 novel coronavirus (COVID-19) has gained global attention after it originated from China at the end of 2019, and later turned into pandemic as it affected about 118,000 in 114 countries by March 11, 2020. By March 13, 2020, it was declared a national emergency in the United States as the number of COVID-19 cases, and the death toll rose exponentially. To contain the spread of the disease, the world scientist community came together. However, the unpreparedness of the nations, even with the advanced medical sciences and resources, has failed to address the mental health aspect amongst the public, as all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of COVID-19 pneumonia. Our efforts in this review are to evaluate and study similar outbreaks from the past to understand its adverse impact on mental health, implement adequate steps to tackle and provide a background to physicians and healthcare workers at the time of such outbreaks to apply psychological first aid.


Reflecting on the Current Challenges Amid a Pandemic


title: Ilaprazole and other novel prazole-based compounds that bind Tsg101 inhibit viral budding of HSV-1/2 and HIV from cells

text: In many enveloped virus families, including HIV and HSV, a crucial, yet unexploited, step in the viral life cycle is releasing particles from the infected cell membranes. This release process is mediated by host ESCRT complex proteins, which is recruited by viral structural proteins and provides the mechanical means for membrane scission and subsequent viral budding. The prazole drug, tenatoprazole, was previously shown to bind to ESCRT complex member Tsg101 and quantitatively block the release of infectious HIV-1 from cells in culture. In this report we show that tenatoprazole and a related prazole drug, ilaprazole, effectively block infectious Herpes Simplex Virus (HSV)-1/2 release from Vero cells in culture. By electron microscopy, we found that both prazole drugs block the release of HSV particles from the cell nuclear membrane resulting in their accumulation in the nucleus. Ilaprazole also quantitatively blocks the release of HIV-1 from 293T cells with an EC50 of 0.8 μM, which is more potent than tenatoprazole. Finally, we synthesized and tested multiple novel prazole-based analogs that demonstrate both binding to Tsg101 and inhibition of viral egress in the nanomolar range of HIV-1 from 293T cells. Our results indicate that prazole-based compounds may represent a class of drugs with potential to be broad-spectrum antiviral agents against multiple enveloped viruses, by interrupting cellular Tsg101 interaction with maturing virus, thus blocking the budding process that releases particles from the cell. Importance These results provide the basis for the development of drugs that target enveloped virus budding that can be used ultimately to control multiple virus infections in humans.


title: Biosynthesis of silver nanoparticles and exopolysaccharide using novel Thermophilic strain (Ts-1) of Bacillus amyloliquefaciens

text: In the developing world, Nanotechnology became an efficient method in therapeutics, antimicrobials, diagnostics, catalysis, microelectronics, and high sensitivity biomolecular detection. As well as on the other hand, Exopolysaccharides are biopolymers which are also widely used in food formulation, bio- flocculants, bio-absorbents, drug delivery agents. As the chemical methods of synthesizing nanoparticles and polymers are environmentally risky, costly, and toxic. In the present study, we focused on production, purification, and characterization of silver nanoparticles (AgNPs) and exopolysaccharide (EPS) by eco-friendly, extracellular biosynthetic methods using novel thermophilic Bacillus amyloliquefaciens strain Ts-1. This strain was isolated from soil samples by employing pour and spread plate techniques. After obtaining pure culture, the bacterium was used for the synthesis of AgNPs and EPS. Nanoparticles were synthesized from AgNO3 by using reducing agents secreted by bacteria, and Exopolysaccharide biosynthesis is carried out in three steps by the organism in the presence of a carbon source. Synthesis of colloidal AgNPs and EPS was monitored by UV-Visible spectroscopy and Visual observation, respectively. SEM, Edax and FTIR were performed for the characterization of the AgNPs and EPS such as their size, morphology and composition and we also showed the catalytic activity of AgNps in degradation of methylene blue.


Association Between Nursing Home Crowding and COVID-19 Infection and Mortality in Ontario, Canada


title: THE MUC5B PROMOTOR POLYMORPHISM ASSOCIATES WITH SEVERE COVID-19

text: Background Diversity in response to exposition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is common and may be related to the innate immune response. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorphism, rs35705950. The high expressing T-allele of rs35705950 is an accepted risk allele for a non-infectious aging lung disease called idiopathic pulmonary fibrosis (IPF). However, given the theory of trade-offs in aging lung disease and the importance of high expression for an adequate immune response, we hypothesize that the T-allele is protective against severe coronavirus disease 2019 (COVID-19). Methods We collected demographics, radiology, survival data and MUC5B rs35705950 allele status for 108 patients requiring hospitalisation for COVID-19 at St Antonius Hospital in The Netherlands. For comparison of allele frequencies and allele carriership with a white control cohort, the patient cohort was divided in a white (n=83) and non-white cohort. Results The patients had a median age of 66 years and consisted predominantly of males (74%) and 23 patients (21%) died. The T-allele frequencies of rs35705950 in white patients was 0.04 which was significantly lower than the T-allele frequency of 0.10 in white controls (p= 0.02). Moreover, comparison of the number of carriers and non-carriers of the T allele showed that only 8.4% of patients carried the T-allele versus 18% of controls (p=0.029; OR= 0.41, CI=0.19-0.94). Conclusions The MUC5B rs35705950 promoter polymorphism associates with COVID-19. The risk allele (T) for IPF is protective against the development of severe COVID-19 disease. This is a further example of a trade-off between optimal expression levels in the respiratory system which associates with aging diseases. However, these results require further investigation.


title: Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry

text: Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies. IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.


docid: ctralhne

title: CHEST DRAIN AEROSOL GENERATION IN COVID-19 AND EMISSION REDUCTION USING A SIMPLE ANTI-VIRAL FILTER

text: INTRODUCTION The COVID-19 pandemic has been characterised by significant in-hospital virus transmission and deaths among healthcare workers. Sources of in-hospital transmission are not fully understood, with special precautions currently reserved for procedures previously shown to generate aerosols (particles <5 microns). Pleural procedures are not currently considered AGPs, reflecting a lack of data in this area. METHODS An underwater seal chest drain bottle (R54500, Rocket Medical UK) was set up inside a 60-litre plastic box and connected via an airtight conduit to a medical air supply. A multichannel particle counter (TSI Aerotrak 9310 Aerosol Monitor) was placed inside the box, allowing measurement of particle count/cubic foot (pc/ft3) within six channel sizes: 0.3-0.5, 0.5-1, 1-3, 3-5, 5-10 and >10 microns. Stabilised particle counts at 1, 3 and 5 L/min were compared by Wilcoxon signed rank test; p-values were Bonferroni-adjusted. Measurements were repeated with a simple anti-viral filter, designed using repurposed materials by the study team, attached to the drain bottle. The pressure within the bottle was measured to assess any effect of the filter on bottle function. RESULTS Aerosol emissions increased with increased air flow, with the largest increase observed in smaller particles (0.3-3 microns). Concentration of the smallest particles (0.3-0.5 microns) increased from background levels by 700, 1400 and 2500 pc/ft3 at 1, 3 and 5 L/min, respectively. However, dispersion of particles of all sizes was effectively prevented by use of the viral filter at all flow rates. Use of the filter was associated with a maximum pressure rise of 0.3 cm H2O after 24 hours of flow at 5 L/min, suggesting minimal impact on drain function. CONCLUSIONS A bubbling chest drain is a source of aerosolised particles, but emission can be prevented using a simple anti-viral filter. These data should be considered when designing measures to reduce in-hospital spread of SARS-CoV-2.


title: Epidemiological and Clinical Characteristics of Children with Coronavirus Disease 2019

text: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen which mainly spreads by droplets. Most published studies focused on adult patients with coronavirus disease 2019 (COVID-19), but data concerning pediatric patients is limited. This study aimed to determine epidemiological characteristics and clinical features of pediatric patients with COVID-19. Methods: We reviewed and analyzed data on pediatric patients with laboratory-confirmed COVID-19, including basic information, epidemiological history, clinical manifestations, laboratory and radiologic findings, treatment, outcome and follow-up results. Results: From January 20th to February 27th of 2020, a total of 74 pediatric patients with COVID-19 were included in this study. Of the 68 cases whose epidemiological data were complete, 65 (65/68, 95.59%) cases were household contacts of adults whose symptoms developed earlier. Forty (59.46%) of the infected children were male, and the median age and body weight are 6 (0.10-15.08) years and 24 (4.20-87.00) kg, respectively. Except for one critically ill case, 20 (27.03%) patients did not show any symptoms of infection, 24 (32.43%) patients had acute upper respiratory tract infection and 29 (39.19%) patients were diagnosed with mild pneumonia. Cough (24/74, 32.43%) and fever (20, 27.03%) were the predominant symptoms of 44 (59.46%) symptomatic patients at onset of the illness. Abnormalities in leukocyte count were found in 23 (31.08%) children and 10 (13.51%) children presented with abnormal lymphocyte count. Of the 34 (45.95%) patients who had nucleic acid testing results for common respiratory pathogens, 19 (19 / 34, 51.35%) showed co-infection with other pathogens other than SARS-CoV-2.Ten (13.51%) children had RT-PCR analysis of SARS-CoV-2 for fecal specimens and 8 of them showed prolonged existence of SARS-CoV-2 RNA 11 (5-23) days after nasopharynx swabs turning negative. Abnormalities in chest imaging were observed in 37 (50.00%) patients and 28 (37.84%) of them only presented with nontypical changes.All children had good prognosis with a median hospitalization duration of 11 days and follow-up period of 16.5 days. During the follow-up period, all the patients remained in quarantine at designated site and home for two 14-day obervation periods and showed no clinical manifestation,but 3 of the 8 cases with prolonged fecal shedding of SARS-CoV-2 still showed positive result of feces test.


title: Multidisciplinary approach to COVID-19 risk communication: A framework and tool for individual and regional risk assessment

text: The COVID-19 pandemic has exceeded over ten million cases globallywith no vaccine available yet. Different approaches are followed to mitigate its impact and reduce its spreading in different countries, but limiting mobility and exposure have been de-facto precaution to reduce transmission. However, a full lockdown cannot be sustained for a prolonged period. Evidence-based, multidisciplinary approach on risk zoning, personal and transmission risk assessment on a near real-time, and risk communication would support the optimized decisions to minimize the impact of coronavirus on our lives. This paper presents a framework to assess the individual and regional risk of COVID-19 along with risk communication tools and mechanisms. Relative risk scores on a scale of 100 represent the integrated risk of influential factors. The personal risk model incorporates: age, exposure history, symptoms, local risk and existing health condition, whereas regional risk is computed through the actual cases of COVID-19, public health risk factors, socioeconomic condition of the region, and immigration statistics. A web application tool (www.covira.info) has been developed, where anyone can assess their risk and find the guided information links primarily for Nepal. This study provides regional risk for Nepal, but the framework is scalable across the world. However, personal risk can be assessed immediately from anywhere.


title: Forecast of the COVID-19 outbreak, collapse of medical facilities, and lockdown effects in Tokyo, Japan

text: Background: The number of patients of COVID-19 in Tokyo has been increasing gradually through the end of March, 2020. Object: Support for policymaking requires forecasting of the entire course and outcome of the outbreak including the date of collapse of medical facilities if a lockdown is not initiated. Moreover, the effects of a lockdown must be considered when choosing to initiate one. Method: Data of Tokyo patients with symptoms during January 14 − March 28, 2020 were used to formulate a susceptible−infected−recovered (SIR) model using three age classes and to estimate the basic reproduction number (R0). Based on the estimated R0, We inferred outbreak outcomes including the date of collapse of medical facilities if a lockdown were not enacted. Then we estimate the lockdown effects. Results: Results suggest R0 as 2.86, with a 95% confidence interval of [2.73, 2.97]. Collapse of medical facilities can be expected to occur on April 26 if no lockdown occurs. The total number of deaths can be expected to be half a million people. If a lockdown were enacted from April 6, and if more than 60% of trips outside the home were restricted voluntarily, then a collapse of medical facilities could be avoided. Discussion and Conclusion: The estimated R0 was similar to that found from other studies conducted in China and Japan. Results demonstrate that a lockdown with reasonable cooperation of residents can avoid a collapse of medical facilities and save 0.25 million mortality cases.


title: COVID-19 misinformation: mere harmless delusions or much more? A knowledge and attitude cross-sectional study among the general public residing in Jordan

text: Abstract Since the emergence of the recent coronavirus disease 2019 (COVID-19) and its spread as a pandemic, media was teeming with misinformation that led to psychologic, social and economic consequences among the global public. Probing knowledge and anxiety regarding this novel infectious disease is necessary to identify gaps and sources of misinformation which can help public health efforts to design and implement more focused interventional measures. The aim of this study was to evaluate the knowledge, attitude and effects of misinformation about COVID-19 on anxiety level among the general public residing in Jordan. An online survey was used that targeted people aged 18 and above and residing in Jordan. The questionnaire included items on the following: demographic characteristics of the participants, knowledge about COVID-19, anxiety level and misconceptions regarding the origin of the pandemic. The total number of participants included in final analysis was 3150. The study population was predominantly females (76.0%), with mean age of 31 years. The overall knowledge of COVID-19 was satisfactory. Older age, male gender, lower monthly income and educational levels, smoking and history of chronic disease were associated with perceiving COVID-19 as a very dangerous disease. Variables that were associated with a higher anxiety level during the pandemic included: lower monthly income and educational level, residence outside the capital (Amman) and history of smoking. Misinformation about the origin of the pandemic (being part of a conspiracy, biologic warfare and the 5G networks role) was also associated with higher anxiety and lower knowledge about the disease. Social media platforms, TV and news releases were the most common sources of information about the pandemic. The study showed the potential harmful effects of misinformation on the general public and emphasized the need to meticulously deliver timely and accurate information about the pandemic to lessen the health, social and psychological impact of the disease.


title: SARS-CoV-2: virus mutations in specific European populations

text: Abstract The SARS-CoV-2 virus is being intensively studied, particularly, its evolution in the increasingly available sequences between countries/continents with classical phylogenetic tree representation. More recently, certain protein mutations are correlated with specific functional impacts. Our clinical data from patients suggest different clinical symptoms between European countries. Among others, SARS-CoV-2 mutations could explain these disparities. Our analyses point out an association of diverse mutations, including co-evolving ones, in a few SARS-CoV-2 proteins, with specific countries. We therefore suggest combining clinical information from patients and the determination of the associated SARS-CoV-2 genome to better understand the specific symptoms.


title: Evidence of a significant secretory-IgA-dominant SARS-CoV-2 immune response in human milk following recovery from COVID-19

text: 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.


title: Survival of hospitalized COVID-19 patients in Northern Italy: a population-based cohort study by the ITA-COVID19 Network

text: Background COVID19 case fatality rate in hospitalized patients varies across countries and studies, but reliable estimates specific for age, sex, and comorbidities are needed to design trials for COVID19 interventions. Aim of this study is to provide population-based survival curves of hospitalized COVID19 patients. Methods A cohort study was conducted in Lombardy, Veneto, and Reggio Emilia using COVID19 registries linked to hospital discharge databases containing patient clinical histories. All patients with positive SARS CoV 2 RTPCR test on oral/nasopharyngeal swabs hospitalized from 21st February to 21st April 2020 were identified. Kaplan Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex and Charlson Index. Findings Overall 42,926 hospitalized COVID19 patients were identified. Patients' median age was 69 years (IQR: 57; 79), 62.6% were males, 69.4% had a Charlson Index of 0. In total, 11,205 (26.1%) patients died over a median follow-up of 24 days (IQR: 10; 35). Survival curves showed that 22.0% of patients died within 14 days and 27.6% within 30 days of hospitalization. Survival was higher in younger patients and in females. Younger patients with comorbidities had a lower survival than older ones with comorbidities. Interpretation Over 27% of hospitalized COVID19 patients died within one month in three areas of Northern Italy that were heavily affected by SARS CoV 2 infection. Such a high fatality rate suggests that trials should focus on survival and have follow-up of at least one month.


title: Subtitling speed in Media Accessibility research: some methodological considerations

text: Media Accessibility researchers who analyze existing subtitled materials or who create them in the lab for experimental purposes often report on the average subtitling speed of their samples as a measure to describe the rate at which their materials were delivered to viewers. However, they not always describe the methodology behind their calculations, which may be problematic because the literature shows no uniformity in the way that the average subtitling speed is estimated. This paper delves into the notion of average subtitling speed as used in Media Accessibility research. It first looks at the role of subtitling speed in guidelines issued by the industry and regulators. Then it moves on to explore how the average subtitling speed is approached in the scholarly literature, which shows three different methods to calculate this parameter. The comparability and interchangeability of those methods is then analyzed from a statistical standpoint. A reflection follows on the use of the average subtitling speed as a measure to inform about the speed of subtitling samples, before concluding with some methodological recommendations that may help improve the way that the average subtitling speed is reported in scholarly works.


title: Laboratory based surveillance of SARS-CoV-2 in Pakistan

text: COVID-19 cases are alarmingly increasing in Pakistan since May 2020. Laboratory based surveillance system has been in place since the start of the pandemic. The genomic surveillance of SARS-CoV-2 strains isolated locally has been conducted based on partial ORF1b. The sequences were classified to show the phylogenetic correlation and showed 100% homology with those detected in neighboring countries India and China. The rapid increase in cases has led to development of robust strategies to enhance the laboratory testing capacity. We are currently meeting the country requirement to diagnose the virus in the community. Nonetheless, factors like recent ease in lockdown measures has led to massive rise in number of cases in few weeks time.


title: Management of Acute Stroke During COVID-19 Global Pandemic

text: The COVID-19 pandemic is a serious public health emergency, which has caught the world unawares. The rapidly escalating intensity of this outbreak has overwhelmed the existent health care resources leading to major implications on the optimal management of other important medical emergencies like stroke. Timely treatment of acute stroke is imperative to prevent disability, thereby necessitating the need for guidelines so as to maintain the continuum of stroke care, while also protecting health care personnel. We have summarized the global consensus with focus on India.


title: Accounting for imperfect detection reveals role of host traits in structuring viral diversity of a wild bat community

text: Understanding how multi-scale host heterogeneity affects viral community assembly can illuminate ecological drivers of infection and host-switching. Yet, such studies are hindered by imperfect viral detection. To address this issue, we used a community occupancy model – refashioned for the hierarchical nature of molecular-detection methods – to account for failed detection when examining how individual-level host traits affect herpesvirus richness in eight species of wild bats. We then used model predictions to examine the role of host sex and species identity on viral diversity at the levels of host individual, population, and community. Results demonstrate that cPCR and viral sequencing failed to perfectly detect viral presence. Nevertheless, model estimates correcting for imperfect detection show that reproductively active bats, especially reproductively active females, have significantly higher viral richness, and host sex and species identity interact to affect viral richness. Further, host sex significantly affects viral turnover across host populations, as females host more heterogeneous viral communities than do males. Results suggest models of viral ecology benefit from integration of multi-scale host factors, with implications for bat conservation and epidemiology. Furthermore, by accounting for imperfect detection in laboratory assays, we demonstrate how statistical models developed for other purposes hold promising possibilities for molecular and epidemiological applications.


title: COVID-19 in China: Risk Factors and R0 Revisited

text: The COVID-19 epidemic had spread rapidly through China and subsequently has proliferated globally leading to a pandemic situation around the globe. Human-to-human transmissions, as well as asymptomatic transmissions of the infection, have been confirmed. As of April 3rd, public health crisis in China due to COVID-19 is potentially under control. We compiled a daily dataset of case counts, mortality, recovery, temperature, population density, and demographic information for each prefecture during the period of January 11 to April 07, 2020 (excluding Wuhan from our analysis due to missing data). Understanding the characteristics of spatiotemporal clustering of the COVID-19 epidemic and R0 is critical in effectively preventing and controlling the ongoing global pandemic. The prefectures were grouped based on several relevant features using unsupervised machine learning techniques. We performed a computational analysis utilizing the reported cases in China to estimate the revised R0 among different regions for prevention planning in an ongoing global pandemic. Finally, our results indicate that the impact of temperature and demographic (different age group percentage compared to the total population) factors on virus transmission may be characterized using a stochastic transmission model. Such predictions will help prioritize segments of a given community/ region for action and provide a visual aid in designing prevention strategies for a specific geographic region. Furthermore, revised estimation and our methodology will aid in improving the human health consequences of COVID-19 elsewhere.


title: Colon Cancer and SARS-CoV-2: Impact of ACE2 Expression in Susceptibility to COVID-19

text: Novel coronavirus disease (COVID-19) pandemic has become a global health emergency. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with angiotensin-converting enzyme 2 (ACE2) to enter the cells and infects diverse human tissues. It has been reported that a few conditions, including cancer, predispose individuals to SARS-CoV-2 infection and severe form of COVID-19. These findings led us to evaluate the susceptibility of colon adenocarcinoma (COAD) patients to SARS-CoV-2 infection by investigation of ACE2 expression in their tumor tissues. The expression analysis revealed that both mRNA and protein levels of ACE2 had increased in colon cancer samples than normal group. Next, the prognosis analysis has indicated that the upregulation of ACE2 was not correlated with patient survival outcomes. Further assessment displayed the hypomethylation of the ACE2 gene promoter in COAD patients. Surprisingly, this methylation status has a strong negative correlation with ACE2 gene expression. The functional enrichment analysis of the genes that had similar expression patterns with ACE2 in colon cancer tissues demonstrated that they mainly enriched in Vitamin digestion and absorption, Sulfur relay system, and Fat digestion and absorption pathways. Finally, we found that ACE2 gene expression had a significant association with the immune cell infiltration levels in COAD patients. In conclusion, it has plausible that COAD patients are more likely to be infected with SARS-CoV-2 and experience severe injuries. Moreover, COVID-19 would bring unfavorable survival outcomes of patients with colon cancer by the way of immune cell infiltration linked process. The present study highlights the importance of preventive actions for COAD patients during the COVID-19 pandemic.


title: Digestive Manifestations in Patients Hospitalized with COVID-19

text: Background: The prevalence and significance of digestive manifestations in COVID-19 remain uncertain. Methods: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were manually abstracted from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. Results: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least one gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were elevated to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio 0.93, 95% confidence interval 0.76-1.15) or liver test abnormalities on admission (odds ratio 1.31, 95% confidence interval 0.80-2.12) were not independently associated with mechanical ventilation or death. Conclusions: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common but the majority were mild and their presence was not associated with a more severe clinical course.


title: Neutralizing Antibodies Isolated by a site-directed Screening have Potent Protection on SARS-CoV-2 Infection

text: Neutralizing antibody is one of the most effective interventions for acute pathogenic infection. Currently, over three million people have been identified for SARS-CoV-2 infection but SARS-CoV-2-specific vaccines and neutralizing antibodies are still lacking. SARS-CoV-2 infects host cells by interacting with angiotensin converting enzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spike glycoprotein. Therefore, blocking the interaction of SARS-CoV-2-RBD and ACE2 by antibody would cause a directly neutralizing effect against virus. In the current study, we selected the ACE2 interface of SARS-CoV-2-RBD as the targeting epitope for neutralizing antibody screening. We performed site-directed screening by phage display and finally obtained one IgG antibody (4A3) and several domain antibodies. Among them, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to act as neutralizing antibodies due to their capabilities to block the interaction between SARS-CoV-2-RBD and ACE2-positive cells. The domain antibody 4A12 was predicted to have the best accessibility to all three ACE2-interfaces on the spike homotrimer. Pseudovirus and authentic SARS-CoV-2 neutralization assays showed that all four antibodies could potently protect host cells from virus infection. Overall, we isolated multiple formats of SARS-CoV-2-neutralizing antibodies via site-directed antibody screening, which could be promising candidate drugs for the prevention and treatment of COVID-19.


Paying the ultimate price


title: Identification of RT-PCR-Negative Asymptomatic COVID-19 Patients via Serological Testing

text: Asymptomatic individuals with coronavirus disease (COVID-19) have been identified via nucleic acid testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the epidemiologic characteristics and viral shedding pattern of asymptomatic patients remain largely unknown. In this study, serological testing was applied when identifying nine asymptomatic cases of COVID-19 who showed persistent negative RT-PCR test results for SARS-CoV-2 nucleic acid and no symptoms of COVID-19. Two asymptomatic cases were presumed to be index patients who had cleared the virus when their close contacts developed symptoms of COVID-19. Three of the asymptomatic cases were local individuals who spontaneously recovered before their presumed index patients developed symptoms of COVID-19. This report presents the epidemiologic and clinical characteristics of asymptomatic individuals with SARS-CoV-2 infection that were undetected on RT-PCR tests in previous epidemiologic investigations probably due to the transient viral shedding duration.