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7 | a9f6hh7t | are there serological tests that detect antibodies to coronavirus? | Multiplex Evaluation of Influenza Neutralizing Antibodies with Potential Applicability to In-Field Serological Studies The increased number of outbreaks of H5 and H7 LPAI and HPAI viruses in poultry has major public and animal health implications. The continuous rapid evolution of these subtypes and the emergence of new variants influence the ability to undertake effective surveillance. Retroviral pseudotypes bearing influenza haemagglutinin (HA) and neuraminidase (NA) envelope glycoproteins represent a flexible platform for sensitive, readily standardized influenza serological assays. We describe a multiplex assay for the study of neutralizing antibodies that are directed against both influenza H5 and H7 HA. This assay permits the measurement of neutralizing antibody responses against two antigenically distinct HAs in the same serum/plasma sample thus increasing the amount and quality of serological data that can be acquired from valuable sera. Sera obtained from chickens vaccinated with a monovalent H5N2 vaccine, chickens vaccinated with a bivalent H7N1/H5N9 vaccine, or turkeys naturally infected with an H7N3 virus were evaluated in this assay and the results correlated strongly with data obtained by HI assay. We show that pseudotypes are highly stable under basic cold-chain storage conditions and following multiple rounds of freeze-thaw. We propose that this robust assay may have practical utility for in-field serosurveillance and vaccine studies in resource-limited regions worldwide. |
12 | iqr419fp | what are best practices in hospitals and at home in maintaining quarantine? | Prediction of Epidemic Spread of the 2019 Novel Coronavirus Driven by Spring Festival Transportation in China: A Population-Based Study After the 2019 novel coronavirus (2019-nCoV) outbreak, we estimated the distribution and scale of more than 5 million migrants residing in Wuhan after they returned to their hometown communities in Hubei Province or other provinces at the end of 2019 by using the data from the 2013–2018 China Migrants Dynamic Survey (CMDS). We found that the distribution of Wuhan's migrants is centred in Hubei Province (approximately 75%) at a provincial level, gradually decreasing in the surrounding provinces in layers, with obvious spatial characteristics of circle layers and echelons. The scale of Wuhan's migrants, whose origins in Hubei Province give rise to a gradient reduction from east to west within the province, and account for 66% of Wuhan's total migrants, are from the surrounding prefectural-level cities of Wuhan. The distribution comprises 94 districts and counties in Hubei Province, and the cumulative percentage of the top 30 districts and counties exceeds 80%. Wuhan's migrants have a large proportion of middle-aged and high-risk individuals. Their social characteristics include nuclear family migration (84%), migration with families of 3–4 members (71%), a rural household registration (85%), and working or doing business (84%) as the main reason for migration. Using a quasi-experimental analysis framework, we found that the size of Wuhan's migrants was highly correlated with the daily number of confirmed cases. Furthermore, we compared the epidemic situation in different regions and found that the number of confirmed cases in some provinces and cities in Hubei Province may be underestimated, while the epidemic situation in some regions has increased rapidly. The results are conducive to monitoring the epidemic prevention and control in various regions. |
26 | y1d2y9c0 | what are the initial symptoms of Covid-19? | Coronavirus disease 2019 (COVID-19) in pregnant women: A report based on 116 cases Abstract Background The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health emergency. Data on the effect of COVID-19 in pregnancy are limited to small case series. Objectives To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of SARS-CoV-2 infection. Study Desigh Clinical records were retrospectively reviewed for 116 pregnant women with COVID-19 pneumonia from 25 hospitals in China between January 20 and March 24, 2020. Evidence of vertical transmission was assessed by testing for SARS-CoV-2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. Results The median gestational age on admission was 38+0 (IQR 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. There were eight cases (6.9%, 8/116) of severe pneumonia but no maternal deaths. One of eight patients (1/8) that presented in the first- and early-second-trimester had a missed spontaneous abortion. Twenty-one of 99 patients (21.2%, 21/99) that had delivered had preterm birth, including six with preterm premature ruptured of membranes. The rate of spontaneous preterm birth before 37 weeks was 6.1% (6/99). There was one case of severe neonatal asphyxia that resulted in neonatal death. Eighty-six of the 100 neonates that had testing for SARS-CoV-2 had negative results, of these ten neonates had paired amniotic fluid and cord blood samples that were tested negative for SARS-CoV-2. Conclusions SARS-CoV-2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of SARS-CoV-2 infection when the infection manifests during the third-trimester of pregnancy. |
2 | 4bbpytn5 | how does the coronavirus respond to changes in the weather | Multiplexed Component Analysis to Identify Genes Contributing to the Immune Response during Acute SIV Infection Immune response genes play an important role during acute HIV and SIV infection. Using an SIV macaque model of AIDS and CNS disease, our overall goal was to assess how the expression of genes associated with immune and inflammatory responses are longitudinally changed in different organs or cells during SIV infection. To compare RNA expression of a panel of 88 immune-related genes across time points and among three tissues – spleen, mesenteric lymph nodes (MLN) and peripheral blood mononuclear cells (PBMC) – we designed a set of Nanostring probes. To identify significant genes during acute SIV infection and to investigate whether these genes are tissue-specific or have global roles, we introduce a novel multiplexed component analysis (MCA) method. This combines multivariate analysis methods with multiple preprocessing methods to create a set of 12 "judges"; each judge emphasizes particular types of change in gene expression to which cells could respond, for example, the absolute or relative size of expression change from baseline. Compared to bivariate analysis methods, our MCA method improved classification rates. This analysis allows us to identify three categories of genes: (a) consensus genes likely to contribute highly to the immune response; (b) genes that would contribute highly to the immune response only if certain assumptions are met – e.g. that the cell responds to relative expression change rather than absolute expression change; and (c) genes whose contribution to immune response appears to be modest. We then compared the results across the three tissues of interest; some genes are consistently highly-contributing in all tissues, while others are specific for certain tissues. Our analysis identified CCL8, CXCL10, CXCL11, MxA, OAS2, and OAS1 as top contributing genes, all of which are stimulated by type I interferon. This suggests that the cytokine storm during acute SIV infection is a systemic innate immune response against viral replication. Furthermore, these genes have approximately equal contributions to all tissues, making them possible candidates to be used as non-invasive biomarkers in studying PBMCs instead of MLN and spleen during acute SIV infection experiments. We identified clusters of genes that co-vary together and studied their correlation with regard to other gene clusters. We also developed novel methods to faithfully visualize multi-gene correlations on two-dimensional polar plots, and to visualize tissue specificity of gene expression responses. |
11 | 2u379fh3 | what are the guidelines for triaging patients infected with coronavirus? | Clinical and surgical consequences of the COVID-19 pandemic for patients with pediatric urological problems Statement of the EAU guidelines panel for paediatric urology, March 30 2020 Summary The COVID-19-pandemic forces hospitals to reorganize into a dual patient flow system. Healthcare professionals are forced to make decisions in patient prioritization throughout specialties. Most pediatric urology pathologies do not require immediate or urgent care, however, delay may compromise future renal function or fertility. Contact with patients and parents, either physical in safe conditions or by (video)telephone must continue. The Paediatric-Urology-Guidelines-panel of the EAU proposes recommendations on prioritization of care. Pediatric-Urology program directors must ensure education, safety and attention for mental health of staff. Upon resumption of care, adequate prioritization must ensure minimal impact on outcome. |
3 | 7dw32xby | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins COVID 19 is disease caused by novel corona virus, SARS-CoV2 originated in China most probably of Bat origin. Till date, no specific vaccine or drug has been discovered to tackle the infections caused by SARS-CoV2. In response to this pandemic, we utilized bioinformatics knowledge to develop efficient vaccine candidate against SARS-CoV2. Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes were antigenic in nature non-toxic and probably non-allergen. Modelled and refined tertiary structure was predicted as valid for further use. Protein-Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. Designed multiepitope vaccine has induced cell mediated and humoral immunity along with increased interferon gamma response. Macrophages and dendritic cells were also found increased over the vaccine exposure. In silico codon optimization and cloning in expression vector indicates that vaccine can be efficiently expressed in E. coli. In conclusion, predicted vaccine is a good antigen, probable no allergen and has potential to induce cellular and humoral immunity. |
9 | ys7yphlv | how has COVID-19 affected Canada | More effective strategies are required to strengthen public awareness of COVID-19: Evidence from Google Trends Background: The outbreak of coronavirus disease 2019 (COVID-19) has posed stress on the health and well-being of both Chinese people and the public worldwide. Global public interest in this new issue largely reflects people's attention to COVID-19 and their willingness to take precautionary actions. This study aimed to examine global public awareness of COVID-19 using Google Trends. Methods: Using Google Trends, we retrieved public query data for terms of "2019-nCoV + SARS-CoV-2 + novel coronavirus + new coronavirus + COVID-19 + Corona Virus Disease 2019" between the 31st December 2019 and the 24th February 2020 in six major English-speaking countries, including the USA, the UK, Canada, Ireland, Australia, and New Zealand. Dynamic series analysis demonstrates the overall change trend of relative search volume (RSV) for the topic on COVID-19. We compared the top-ranking related queries and sub-regions distribution of RSV about COVID-19 across different countries. The correlation between daily search volumes on the topic related to COVID-19 and the daily number of people infected with SARS-CoV-2 was analyzed. Results: The overall search trend of RSV regarding COVID-19 increased during the early period of observing time and reached the first apex on 31st January 2020. A shorter response time and a longer duration of public attention to COVID-19 was observed in public from the USA, the UK, Australia, and Canada, than that in Ireland and New Zealand. A slightly positive correlation between daily RSV about COVID-19 and the daily number of confirmed cases was observed (P < 0.05). People across countries presented a various interest to the RSV on COVID-19, and public awareness of COVID-19 was different in various sub-regions within countries. Conclusions: The results suggest that public response time to COVID-19 was different across countries, and the overall duration of public attention was short. The current study reminds us that governments should strengthen the publicity of COVID-19 nationally, strengthen the public's vigilance and sensitivity to COVID-19, inform public the importance of protecting themselves with enough precautionary measures, and finally control the spread of COVID-19 globally. |
25 | ys51rshu | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Human Coronaviruses: A Review of Virus–Host Interactions Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs. |
18 | 7lnqml8r | what are the best masks for preventing infection by Covid-19? | Terugblik aidstijdperk 1981-1996 |
35 | djuomhww | What new public datasets are available related to COVID-19? | Risks of Novel Coronavirus Disease (COVID-19) in Pregnancy; a Narrative Review INTRODUCTION: The outbreak of the new Coronavirus in China in December 2019 and subsequently in various countries around the world has raised concerns about the possibility of vertical transmission of the virus from mother to fetus. The present study aimed to review published literature in this regard. METHODS: In this narrative review, were searched for all articles published in various databases including PubMed, Scopus, Embase, Science Direct, and Web of Science using MeSH-compliant keywords including COVID-19, Pregnancy, Vertical transmission, Coronavirus 2019, SARS-CoV-2 and 2019-nCoV from December 2019 to March 18, 2020 and reviewed them. All type of articles published about COVID-19 and vertical transmission in pregnancy were included. RESULTS: A review of 13 final articles published in this area revealed that COVID-19 can cause fetal distress, miscarriage, respiratory distress and preterm delivery in pregnant women but does not infect newborns. There has been no report of vertical transmission in pregnancy, and it has been found that clinical symptoms of COVID-19 in pregnant women are not different from those of non-pregnant women. CONCLUSION: Overall, due to lack of appropriate data about the effect of COVID-19 on pregnancy, it is necessary to monitor suspected pregnant women before and after delivery. For confirmed cases both the mother and the newborn child should be followed up comprehensively. |
18 | moldq0u9 | what are the best masks for preventing infection by Covid-19? | Reusability Comparison of Melt-Blown vs Nanofiber Face Mask Filters for Use in the Coronavirus Pandemic [Image: see text] Shortage of face masks is a current critical concern since the emergence of coronavirus-2 or SARS-CoV-2 (COVID-19). In this work, we compared the melt-blown (MB) filter, which is commonly used for the N95 face mask, with nanofiber (NF) filter, which is gradually used as an effective mask filter, to evaluate their reusability. Extensive characterizations were performed repeatedly to evaluate some performance parameters, which include filtration efficiency, airflow rate, and surface and morphological properties, after two types of cleaning treatments. In the first cleaning type, samples were dipped in 75% ethanol for a predetermined duration. In the second cleaning type, 75% ethanol was sprayed on samples. It was found that filtration efficiency of MB filter was significantly dropped after treatment with ethanol, while the NF filter exhibited consistent high filtration efficiency regardless of cleaning types. In addition, the NF filter showed better cytocompatibility than the MB filter, demonstrating its harmlessness on the human body. Regardless of ethanol treatments, surfaces of both filter types maintained hydrophobicity, which can sufficiently prevent wetting by moisture and saliva splash to prohibit not only pathogen transmission but also bacterial growth inside. On the basis of these comparative evaluations, the wider use of the NF filter for face mask applications is highly recommended, and it can be reused multiple times with robust filtration efficiency. It would be greatly helpful to solve the current shortage issue of face masks and significantly improve safety for front line fighters against coronavirus disease. |
11 | covnpc8z | what are the guidelines for triaging patients infected with coronavirus? | A novel coronavirus capable of lethal human infections: an emerging picture SUMMARY: In September 2012, a novel coronavirus was isolated from a patient in Saudi Arabia who had died of an acute respiratory illness and renal failure. The clinical presentation was reminiscent of the outbreak caused by the SARS-coronavirus (SARS-CoV) exactly ten years ago that resulted in over 8000 cases. Sequence analysis of the new virus revealed that it was indeed a member of the same genus as SARS-CoV. By mid-February 2013, 12 laboratory-confirmed cases had been reported with 6 fatalities. The first 9 cases were in individuals resident in the Middle East, while the most recent 3 cases were in family members resident in the UK. The index case in the UK family cluster had travel history to Pakistan and Saudi Arabia. Although the current evidence suggests that this virus is not highly transmissible among humans, there is a real danger that it may spread to other parts of the world. Here, a brief review of the events is provided to summarize the rapidly emerging picture of this new virus. |
38 | xuczplaf | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak Abstract Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease. |
48 | t7p2j504 | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | A Modelling Analysis of Strategies for Relaxing COVID-19 Social Distancing Abstract Background: The ability of countries to contain and control COVID-19 virus transmission via social distancing is critical in the absence of a vaccine. Early activation of robust measures has been shown to control the daily infection rate, and consequential pressure on the health care system. As countries begin to control COVID-19 spread an understanding of how to ease social distancing measures to prevent a rebound in cases and deaths is required. Methods: Using COVID-19 transmission data from the outbreak source in Hubei Province, China prior to activation of containment measures, we adapted an established individual-based simulation model of the city of Newcastle, Australia. Simulation of virus transmission in this model, with and without, social distancing measures activated permitted us to quantify social distancing effectiveness. Optimal strategies for relaxing social distancing were determined under two settings: with high numbers of daily cases, as in New York; and where early social distancing activation resulted in limited ongoing transmission, as in Perth, Australia. Findings: In countries where strong social distancing measures were activated after the COVID-19 virus had spread widely, our study found these measures are required to be maintained for significant periods before being eased, to return to a situation where daily case numbers become low. In countries where early responses to the COVID-19 pandemic have been highly successful, as in Australia, we show that a staged relaxation of social distancing prevents a rebound in cases. Interpretation: Modelling studies and direct observation have shown that robust and timely social distancing have the most effect in containing the spread of the COVID-19 virus. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society and economic activity. This study demonstrates the necessity of holding robust social distancing in place until COVID-19 virus transmission has significantly decreased, and how they may then be safely eased. |
33 | 0faqel02 | What vaccine candidates are being tested for Covid-19? | Genus Avipoxvirus Poxviruses identified in skin lesions of domestic, pet or wild birds are assigned largely by default to the Avipoxvirus genus within the subfamily Chordopoxvirinae of the family Poxviridae. Avipoxviruses have been identified as the causative agent of disease in at least 232 species in 23 orders of birds. Vaccines based upon attenuated avipoxvirus strains provide good disease control in production poultry, although with the large and intensive production systems there are suggestions and real risks of emergence of strains against which current vaccines might be ineffective. Sequence analysis of the whole genome has revealed overall genome structure and function resemblance to the Chordopoxvirinae; however, avipoxvirus genomes exhibit large-scale genomic rearrangements with more extensive gene families and novel host range gene in comparison with the other Chordopoxvirinae. Phylogenetic analysis places the avipoxviruses externally to the Chorodopoxvirinae to such an extent that in the future it might be appropriate to consider the Avipoxviruses as a separate subfamily within the Poxviridae. A unique relationship exists between Fowlpox virus (FWPV) and reticuloendothelosis viruses. All FWPV strains carry a remnant long terminal repeat, while field strains carry a near full-length provirus integrated at the same location in the FWPV genome. With the development of techniques to construct poxviruses expressing foreign vaccine antigens, the avipoxviruses have gone from neglected obscurity to important vaccine vectors in the past 20 years. The seminal observation of their utility for delivery of vaccine antigens to non-avian species has driven much of the interest in this group of viruses. In the veterinary area, several recombinant avipoxviruses are commercially licensed vaccines. The most successful have been those expressing glycoprotein antigens of enveloped viruses, e.g. avian influenza, Newcastle diseases and West Nile viruses. Several recombinants have undergone extensive human clinical trials as experimental vaccines against HIV/AIDS and malaria or as treatment regimens in cancer patients. The safety profile of avipoxvirus recombinants for use as veterinary and human vaccines or therapeutics is now well established. |
15 | 4x5tciau | how long can the coronavirus live outside the body | The Mighty World of Microbes: An Overview The world of microbes on our planet is vast and diverse. This includes the normal bacterial flora present on the skin and mucous membranes of humans. The human microbiome project (HMP) was launched by NIH in 2007 as a part of a road map for medical research. The HMP serves as a template for researchers who are studying more than 1,000 microbial genomes with a focus on their role in health and disease. The study samples have been derived from five human body regions that are known to be inhabited by microbial flora. These include the gastrointestinal tract, female urogenital tract, mouth, nose, and skin. The techniques being used include finger printing, sequencing, dynamic range, and comparison of multiple samples. It is now well accepted that there are more microbial cells than human cells in the human body. Just the gastrointestinal tract harbors more than tenfold microbial cells than the number of human cells in the entire body. The understanding of the relationship between microbes and humans is at best rudimentary at this point in time. Similarly, the relationship between humans and microbes in the environment and environmental surfaces is poorly understood except for a few pathogenic microbes. |
42 | 2pwwolwy | Does Vitamin D impact COVID-19 prevention and treatment? | 74th Congress of the Italian Society of Pediatrics: Rome, Italy. 12-16 June 2018 |
22 | nnlzwaf1 | are cardiac complications likely in patients with COVID-19? | Neuroinvasive and Neurotropic Human Respiratory Coronaviruses: Potential Neurovirulent Agents in Humans In humans, viral infections of the respiratory tract are a leading cause of morbidity and mortality worldwide. Several recognized respiratory viral agents have a neuroinvasive capacity since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Among the various respiratory viruses, coronaviruses are important pathogens of humans and animals. Human Coronaviruses (HCoV) usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly, and immune-compromised individuals, they can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, respiratory distress syndrome, or even severe acute respiratory syndrome (SARS). The respiratory involvement of HCoV has been clearly established since the 1960s. In addition, for almost three decades now, the scientific literature has also demonstrated that HCoV are neuroinvasive and neurotropic and could induce an overactivation of the immune system, in part by participating in the activation of autoreactive immune cells that could be associated with autoimmunity in susceptible individuals. Furthermore, it was shown that in the murine CNS, neurons are the main target of infection, which causes these essential cells to undergo degeneration and eventually die by some form of programmed cell death after virus infection. Moreover, it appears that the viral surface glycoprotein (S) represents an important factor in the neurodegenerative process. Given all these properties, it has been suggested that these recognized human respiratory pathogens could be associated with the triggering or the exacerbation of neurological diseases for which the etiology remains unknown or poorly understood. |
28 | 1dqdwn74 | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Association Between US Administration Endorsement of Hydroxychloroquine for COVID-19 and Outpatient Prescribing |
25 | 1c47w4q5 | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19) The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions. |
17 | rh6luded | are there any clinical trials available for the coronavirus | Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial BACKGROUND: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19. METHODS: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. FINDINGS: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4·37 [95% CI 1·86-10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study. INTERPRETATION: Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. FUNDING: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine. |
13 | faojb5hb | what are the transmission routes of coronavirus? | Cluster analysis of epidemiological characteristic features of confirmed cases with the novel coronavirus (COVID-19) outside China: a descriptive study Background: Novel coronavirus COVID-19 has caused significant global outbreaks outside China. Many countries have closed their borders with China and performed obligate protective procedures, however, this disease was still rising worldwide. In this report, we aim to identify transmission patterns from China to other countries, along with describing the disease control situation of countries. Methods: We retrospectively collected information about infected cases with COVID-19 from WHO situation reports, official notification websites of health ministries and reliable local newspapers from each country. Descriptive and cluster analysis was performed to describe the transmission characteristics while the logistic regression test was used to estimate the risk factors for the occurrence of an infected individual with an unknown source. Results: A total of 446 infected cases were recorded from 24 countries outside China until 12 February 2020, with the number of reported infected cases were doubled every 3.08 days (range from 2.6 to 3.9). Besides the spread from China, the transmission was originated from sub-endemic countries (Japan, Thailand, Singapore, Malaysia, France, German). Out of 6 countries got occurrence of an infected individual with unknown source and possible potential factors contributed to this occurrence was a time of epidemic circulating, number of patients and number of clusters when the occurrence still has not happened, and notably, the unreported situation of Chinese tourists information. Conclusions: The situational reports of each country about COVID-19 should be more detailed mentioning the transmissions routes with keeping contact tracing of the unknown cases to increase the control of this disease. |
26 | 0u0u348d | what are the initial symptoms of Covid-19? | Nucleocapsid Protein as Early Diagnostic Marker for SARS Serum samples from 317 patients with patients with severe acute respiratory syndrome (SARS) were tested for the nucleocapsid (N) protein of SARS-associated coronavirus, with sensitivities of 94% and 78% for the first 5 days and 6–10 days after onset, respectively. The specificity was 99.9%. N protein can be used as an early diagnostic maker for SARS. |
15 | h4r0jpy5 | how long can the coronavirus live outside the body | Unexplained Deaths and Critical Illnesses of Suspected Infectious Cause, Taiwan, 2000–2005 We report 5 years' surveillance data from the Taiwan Centers for Disease Control on unexplained deaths and critical illnesses suspected of being caused by infection. A total of 130 cases were reported; the incidence rate was 0.12 per 100,000 person-years; and infectious causes were identified for 81 cases (62%). |
18 | dt2pew66 | what are the best masks for preventing infection by Covid-19? | Brief research report: Bidirectional impact of imperfect mask use on reproduction number of COVID-19: A next generation matrix approach() The use of masks as a means of reducing transmission of COVID-19 outside healthcare settings has proved controversial. Masks are thought to have two modes of effect: they prevent infection with COVID-19 in wearers; and prevent transmission by individuals with subclinical infection. We used a simple next-generation matrix approach to estimate the conditions under which masks would reduce the reproduction number of COVID-19 under a threshold of 1. Our model takes into account the possibility of assortative mixing, where mask users interact preferentially with other mask users. We make 3 key observations: 1. Masks, even with suboptimal efficacy in both prevention of acquisition and transmission of infection, could substantially decrease the reproduction number for COVID-19 if widely used. 2. Widespread masking may be sufficient to suppress epidemics where R has been brought close to 1 via other measures (e.g., distancing). 3. "Assortment" within populations (the tendency for interactions between masked individuals to be more likely than interactions between masked and unmasked individuals) would rapidly erode the impact of masks. As such, mask uptake needs to be fairly universal to have an effect. This simple model suggests that widespread uptake of masking could be determinative in suppressing COVID-19 epidemics in regions with R(t) at or near 1. |
23 | n32iscmr | what kinds of complications related to COVID-19 are associated with hypertension? | Nifedipine and Amlodipine Are Associated With Improved Mortality and Decreased Risk for Intubation and Mechanical Ventilation in Elderly Patients Hospitalized for COVID-19 Dihydropyridine calcium channel blockers (CCB) are typically used agents in the clinical management of hypertension. Yet, they have also been utilized in the treatment of various pulmonary disorders with vasoconstriction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been implicated in the development of vasoconstrictive, proinflammatory, and pro-oxidative effects. A retrospective review was conducted on CCB use in hospitalized patients in search of any difference in outcomes related to specific endpoints: survival to discharge and progression of disease leading to intubation and mechanical ventilation. The electronic medical records for all patients that tested positive for SARS-CoV-2 that were at or above the age of 65 and that expired or survived to discharge from a community hospital in Brooklyn, NY, between the start of the public health crisis due to the viral disease up until April 13, 2020, were included. Of the 77 patients that were identified, 18 survived until discharge and 59 expired. Seven patients from the expired group were excluded since they died within one day of presentation to the hospital. Five patients were excluded from the expired group since their age was above that of the eldest patient in the survival group (89 years old). With 65 patients left, 24 were found to have been administered either amlodipine or nifedipine (CCB group) and 41 were not (No-CCB group). Patients treated with a CCB were significantly more likely to survive than those not treated with a CCB: 12 (50%) survived and 12 expired in the CCB group vs. six (14.6%) that survived and 35 (85.4%) that expired in the No-CCB treatment group (P<.01; p=0.0036). CCB patients were also significantly less likely to undergo intubation and mechanical ventilation. Only one patient (4.2%) was intubated in the CCB group whereas 16 (39.0%) were intubated in the No-CCB treatment group (P<.01; p=0.0026). Nifedipine and amlodipine were found to be associated with significantly improved mortality and a decreased risk for intubation and mechanical ventilation in elderly patients hospitalized with COVID-19. Further clinical studies are warranted. Including either nifedipine or amlodipine in medication regimens for elderly patients with hypertension hospitalized for COVID-19 may be considered. |
21 | t5xkz9aj | what are the mortality rates overall and in specific populations | SARS case-fatality rates. |
3 | qdamvwxl | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic The ongoing novel coronavirus disease (COVID-19) pandemic has rapidly spread in early 2020, causing tens of thousands of deaths, over a million cases and widespread socioeconomic disruption. With no vaccine available and numerous national healthcare systems reaching or exceeding capacity, interventions to limit transmission are urgently needed. While there is broad agreement that travel restrictions and closure of non-essential businesses and schools are beneficial in limiting local and regional spread, recommendations around the use of face masks for the general population are less consistent internationally. In this study, we examined the role of face masks in mitigating the spread of COVID-19 in the general population, using epidemic models to estimate the total reduction of infections and deaths under various scenarios. In particular, we examined the optimal deployment of face masks when resources are limited, and explored a range of supply and demand dynamics. We found that face masks, even with a limited protective effect, can reduce infections and deaths, and can delay the peak time of the epidemic. We consistently found that a random distribution of masks in the population was a suboptimal strategy when resources were limited. Prioritizing coverage among the elderly was more beneficial, while allocating a proportion of available resources for diagnosed infected cases provided further mitigation under a range of scenarios. In summary, face mask use, particularly for a pathogen with relatively common asymptomatic carriage, can effectively provide some mitigation of transmission, while balancing provision between vulnerable healthy persons and symptomatic persons can optimize mitigation efforts when resources are limited. |
2 | yl5kox73 | how does the coronavirus respond to changes in the weather | Short-term exposure to ambient air quality of the most polluted Indian cities due to lockdown amid SARS-CoV-2 Air pollution has happened to be one of the mounting alarms to be concerned with in many Indian cities. COVID-19 epidemic endow with a unique opportunity to report the degree of air quality improvement due to the nationwide lockdown in 10 most polluted cities across the country. National Air Quality Index (NAQI) based on continuous monitoring records of seven criteria pollutants (i.e. common air pollutants with known health impacts e.g. PM(10), PM(2.5), CO, NO(2), SO(2), NH(3) and O(3)) for a total of 59 stations across the cities, satellite image derived Aerosol Optical Depth (AOD) and few statistical tools are employed to derive the outcomes. NAQI results convey that 8 cities out of the 10 air quality restored to good to satisfactory category during the lockdown period. Within week+1 of the lockdown period, PM(10) and PM(2.5) concentrations have suppressed below the permissible limit in all cities. CO and NO(2) have reduced to about -30% and -57% respectively during the lockdown period. Diurnal concentrations of PM(10) and PM(2.5) have dropped drastically on the very 4(th) day of lockdown and become consistent with minor hourly vacillation. In April 2020 the AOD amount was reduced to about 36% and 18% in contrast to April 2018 and April 2019 respectively. This add-on reporting of the possible recovery extent in air quality may help to guide alternative policy intervention in form of short term lockdown so as to testify whether this type of unconventional policy decisions may be put forward to attain a green environment.. Because, despite numerous restoration plans, air pollution levels have risen unabated in these cities. However, detailed inventory needs to be focused on identifying the localized pollution hotspots (i.e. source contribution). |
41 | 1lw5vbu9 | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Are Clinicians Contributing to Excess African American COVID-19 Deaths? Unbeknownst to Them, They May Be African Americans are overrepresented among reported coronavirus disease 2019 (COVID-19) cases and deaths. There are a multitude of factors that may explain the African American disparity in COVID-19 outcomes, including higher rates of comorbidities. While individual-level factors predictably contribute to disparate COVID-19 outcomes, systematic and structural factors have not yet been reported. It stands to reason that implicit biases may fuel the racial disparity in COVID-19 outcomes. To address this racial disparity, we must apply a health equity lens and disaggregate data explicitly for African Americans, as well as other populations at risk for biased treatment in the health-care system. |
16 | r5vkki7q | how long does coronavirus remain stable on surfaces? | Kitchen Spectroscopy: Shining a (UV) Light on Everyday Objects Fluorescent objects often lead to a sense of joy and intrigue. While the current COVID-19 pandemic limits the synthesis of "glowy things" like quantum dots, many household objects fluoresce, providing an opportunity to brighten your day while learning fundamental chemistry. |
1 | bsnibsuf | what is the origin of COVID-19 | Two-port totally extraperitoneal inguinal hernia repair: a 10-year experience. PURPOSE To evaluate the feasibility, safety, and long-term outcomes of laparoscopic two-port totally extraperitoneal (TEP) inguinal hernia repair. METHODS A 10-year retrospective analysis from 2004 to 2013 of patients undergoing two-port TEP performed by a single surgeon at three surgical centers. RESULTS 336 consecutive patients underwent two-port TEP repairing 478 hernias. 315 (93.8 %) patients were male and 21 (6.2 %) were female. Mean age ± SD was 47 ± 14 years and mean body mass index ± SD was 28.0 ± 4.7 kg/m(2). Indications for surgery included primary repair 303 (90.2 %), recurrence from open repair 28 (8.3 %), and incarcerated inguinal hernia 5 (1.5 %). 194 (57.7 %) cases were unilateral and 142 (42.3 %) were bilateral. Operative time ± SD was 38.7 ± 14.9 min for unilateral repair and 43.4 ± 17.6 min for bilateral repair. Two-port TEP was successful in 316 (94.0 %). 20 (6.0 %) cases required the addition of a third port. 2 (0.6 %) cases were converted to open repair. Mean follow-up time ± SD was 5.4 ± 2.7 years. Postoperative complications included urinary retention 5 (1.5 %), seroma 7 (2.1 %), hematoma 1 (0.3 %), surgical site infection 4 (1.2 %), and chronic inguinal pain 3 (0.9 %). 11 (2.3 %) hernias recurred. CONCLUSION Two-port TEP appears to be a feasible, safe, and effective method for laparoscopic inguinal hernia repair and should be considered a viable, less invasive alternative to conventional three-port techniques. |
34 | xyw6nqmp | What are the longer-term complications of those who recover from COVID-19? | COPD exacerbations: defining their cause and prevention Summary Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality. COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation. They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations. Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations. Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials. The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. |
22 | lqmc7yy4 | are cardiac complications likely in patients with COVID-19? | COVID-19: Zoonotic aspects |
25 | ftp67lkq | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Syndromic Surveillance |
26 | utigp2vi | what are the initial symptoms of Covid-19? | RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions. |
11 | epek8w0a | what are the guidelines for triaging patients infected with coronavirus? | Absence of Evidence of Transmission of Coronavirus Disease 2019 from a Young Child to Mother Despite Prolonged Contact |
38 | 2c7p56s1 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Activated macrophages are the main inflammatory cell in COVID-19 interstitial pneumonia infiltrates. Is it possible to show their metabolic activity and thus the grade of inflammatory burden with (18)F-Fluorocholine PET/CT? The recent outbreak of Covid-19 has represented a major challenge for the countries affected by the disease, not only in terms of loss of human life, economic downturn, and constraint on individual freedom, but also for the great pressure on the national health systems and hospitals. The 380 kDa virus has been a perfect storm, especially for those national health systems used to working with limited resources and high intensity rhythms, such as Italy. For the first time in the new century, a virtually unknown fast-spreading disease has caused a public health emergency thus forcing most countries to deal with an insurmountable logistic gap. Hence, every branch of Medicine, even though not directly involved in the treatment, has been called upon to provide its contribution to resolve the crisis. It is now becoming more apparent that Covid-19 is not solely a lung disease, but a complex systemic disease involving several organs and systems. This is due to an abnormal inflammatory response which eventually leads to multisystemic coagulopathy which mainly, but not uniquely, targets the lungs. Although the pathophysiology of this syndrome is still not fully understood, macrophages and their immune complex system seem to play a key role. It is not yet clear why some patients develop the violent immune response which results in pneumonitis while others do not. There are clues indicating that the systemic hyper-inflammation defined as macrophage activation syndrome (MAS), or cytokine storm, requires an increase in choline consumption to synthesize phosphatidylcholine and stimulate phagocytosis, organelle biogenesis, secretory functions, and endocytosis. (18)F-Fluorocholine is a synthetic analog of the naturally occurring choline normally used for PET/CT imaging of prostate cancer patients. (18)F-Fluorocholine could image and quantify the macrophage activity in pulmonary interstitial infiltrates of Covid-19 pneumonia. If the hypothesis is confirmed experimentally, (18)F-Fluorocholine PET/CT could be used to in vivo image and quantify the degree of lung inflammation and potentially stratify the gravity of this disease. |
40 | 6f1y5hhv | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | SARS-CoV-2 mutations altering regulatory properties: deciphering host's and virus's perspectives Since the first recorded case of the SARS-CoV-2, it has acquired several mutations in its genome while spreading throughout the globe. However, apart from some changes in protein coding, functional importance of these mutations in disease pathophysiology are still largely unknown. In this study, we investigated the significance of these mutations both from the host's and virus's perspective by analyzing the host miRNA binding and virus's internal ribosome entry site (IRES), respectively. Strikingly, we observed that due to the acquired mutations, host miRNAs bind differently compared to the reference; where few of the miRNAs lost and few gained the binding affinity for targeting the viral genome. Moreover, functional enrichment analysis suggests that targets of both of these gained and lost miRNAs might be involved in various host immune signaling pathways. Also, we sought to shed some insights on the impacts of mutations on the IRES structure of SARS-CoV-2. Remarkably, we detected that three particular mutations in the IRES can disrupt its secondary structure which can further make the virus less functional. These results could be valuable in exploring the functional importance of the mutations of SARS-CoV-2 and could provide novel insights into the differences observed different parts of the world. |
11 | 5r0ubg5g | what are the guidelines for triaging patients infected with coronavirus? | Characterization and Clinical Course of 1000 Patients with COVID-19 in New York: retrospective case series Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient floors, and intensive care units (ICUs). Design: Retrospective manual medical record review. Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19. Methods: We identified patients with a positive RT-SARS-CoV-2 PCR receiving care at NYP/CUIMC from March 1 through April 15. Patient data was manually abstracted from the electronic medical record. Main outcome measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, outcomes, and disposition. Results: Among the first 1000 patients with confirmed COVID-19, 151 patients were discharged from or died in the ED, 618 were admitted to the floor, and 231 were admitted or transferred to the ICU; 195 remained hospitalized and 172 had died in the hospital. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (62.9%). Compared to Chinese and Italian cohorts, hospitalized patients and ICU patients in particular had more baseline comorbidities including hypertension, diabetes, and obesity and higher rates of acute kidney injury (AKI) and dialysis. ICU patients were older and predominantly male (67.5%); 75.3% developed AKI and 31.2% required dialysis. Notably, of patients who required mechanical ventilation, only 5.9% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset. Patients in this large sample have more baseline comorbidities and more complications than previous Italian and Chinese cohorts. |
18 | ybouh0cw | what are the best masks for preventing infection by Covid-19? | Fighting Against COVID‐19 through Government Initiatives and Collaborative Governance: Taiwan Experience Taiwan is situated less than 200 km from the first Covid‐19 outbreak state, China, and has millions of international visitors yearly. Taiwan's collective efforts to block and eliminate the invisible enemy (Covid‐19) from the island, have resulted in relatively low infection and death numbers, and were hailed as a successful anomaly amid the global pandemic. In this review, I pinpoint some background on the systems and organizations that helped Taiwan streamline a task force (Command Center) in a timely manner to launch related initiatives, mobilize the public, and engage private resources to implement the strategies and policies which were further enhanced by collaborative behaviors and volunteers. Also, even subject to similar threatening conditions such as cruise ship stopover and numerous foreign immigrant workers, there were no outbreaks of community infection in Taiwan similar to Singapore, Japan, etc. Taiwan's successful measures offer good example for future comparative studies. This article is protected by copyright. All rights reserved. |
48 | 8dg8neq5 | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | Analyzing Covid-19 Data using SIRD Models The goal of this analysis is to estimate the effects of the diverse government intervention measures implemented to mitigate the spread of the Covid-19 epidemic. We use a process model based on a compartmental epidemiological framework Susceptible-Infected-Recovered-Dead (SIRD). Analysis of case data with such a mechanism-based model has advantages over purely phenomenological approaches because the parameters of the SIRD model can be calibrated using prior knowledge. This approach can be used to investigate how governmental interventions have affected the Covid-19-related transmission and mortality rate during the epidemic. |
11 | ore3r4m3 | what are the guidelines for triaging patients infected with coronavirus? | Replication of a bovine coronavirus in organ cultures of foetal trachea Abstract A strain of bovine coronavirus (BC) adapted to tissue culture, was inoculated into organ cultures of bovine foetal trachea. Haemagglutinin in the fluid from infected organ cultures reached titres of 32 and characteristic coronavirus particles were observed electron microscopically. BC virus antigen was detected in frozen sections of the organ cultures by staining with fluorescent antibody. These data were evidence that BC virus replicated in organ cultures of respiratory tissue. The use of this technique for primary isolation of bovine coronaviruses from field material is discussed. |
40 | ywhu66o7 | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Structural Considerations in the Fitness Landscape of a Virus Viral fitness is determined by replication within hosts and transmission between them. We examine how pleiotropic mutations that have antagonistic effects (i.e., antibody evasion vs. receptor binding) on viral replication within hosts can impact viral immune escape in the host population. When the host population is vaccinated, the virus escapes from passive immunity by mutations in the antibody-binding region on the surface of the target protein. However, the reduced ability of the antibody to bind the virus is often accompanied by a reduced ability of the virus to bind the cell receptor because the antibody-binding region overlaps with the receptor-binding domain (RBD). The types of permitted mutations are limited. To investigate the causal relation between a mutation in a viral genome and adaptive evolution of a viral population, we developed a mathematical model that describes the population dynamics of viruses, antibodies, and normal/infected cells within a host. The coefficients describe the binding affinity between the virus and the induced antibody and that between the virus and its receptor. Our knowledge-based index enables us to estimate the effect of a mutation in a binding region on the binding affinity. Using population genetic theory, we evaluated the probability that a mutant is fixed in a host population. The mutations that can be fixed with high probabilities may determine how long a vaccine remains effective. We simulate the adaptive evolution of coronavirus, the etiological agent of severe acute respiratory syndrome, and show that some of mutations in the RBD may have high fixation probabilities in the vaccinated host population. |
30 | iqi2pozm | is remdesivir an effective treatment for COVID-19 | Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial Around the world, several dose regimens of hydroxychloroquine have been used for COVID-19 infection treatment, with the objective of identifying a short-term course. Hydroxychloroquine was found to decrease the viral replication in a concentration-dependent manner in vitro and to be more active when added prior to the viral challenge. A loading dose is used to rapidly attain a target drug concentration, which is usually considered as approximately the steady-state concentration. With a loading dose, the minimum effective concentration is reached much more rapidly than when using only the maintenance dose from the start. Thus, we propose a hydroxychloroquine sulphate dose regimen of 400 mg twice daily at Day 1 then 400 mg once daily from Day 2 to Day 10. We aim to evaluate this in the C-20-15 DisCoVeRy trial. |
14 | vbg06yyw | what evidence is there related to COVID-19 super spreaders | Asymptomatic carriers of COVID-19 as a concern for disease prevention and control: more testing, more follow-up. Following a containment phase of two months, China has transitioned to the mitigation phase. However, China still faces the risk of COVID-19 spreading due to not only to sporadic new cases and imported cases but also asymptomatic carriers. According to daily reports from the National Health Commission of the People's Republic of China from March 31, 2020 to April 7, 2020, the number of new asymptomatic cases reported daily greatly exceeded that of new imported cases. As of 24:00 on April 7, there were a total of 1,095 asymptomatic cases with COVID-19 under medical observation on the Chinese mainland, including 358 imported cases. A growing number of studies have indicated that asymptomatic carriers are infectious to an extent and can potentially transmit COVID-19. At present, China's measures for managing asymptomatic carriers are 14 days of centralized quarantine and observation; in principle, people with two consecutive negative nucleic acid tests (at an interval of at least 24 hours) can be released from quarantine. However, asymptomatic carriers will not be included in confirmed cases unless they develop clinical manifestations while in quarantine. As "silent spreaders", asymptomatic carriers warrant attention as part of disease prevention and control. The testing and follow-up of asymptomatic carriers should be expanded to include people in close contact with patients with confirmed COVID-19 and asymptomatic cases, clusters of outbreaks, and key areas and populations with a high risk of infection. |
36 | ul53w55f | What is the protein structure of the SARS-CoV-2 spike? | Pathophysiological Characteristics and Therapeutic Approaches for Pulmonary Injury and Cardiovascular Complications of Coronavirus Disease 2019 Abstract The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major health crisis, with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) having infected over a million people around the world within a few months of its identification as a human pathogen. Initially, SARS-CoV-2 infects cells in the respiratory system and causes inflammation and cell death. Subsequently, the virus spreads out and damages other vital organs and tissues, triggering a complicated spectrum of pathophysiological changes and symptoms, including cardiovascular complications. Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function. Diverse clinical manifestations and laboratory abnormalities occur in patients with cardiovascular injury in COVID-19, characterizing the development of this complication, as well as providing clues to diagnosis and treatment. This review provides a summary of the rapidly appearing laboratory and clinical evidence for the pathophysiology and therapeutic approaches to COVID-19 pulmonary and cardiovascular complications. |
40 | c84licip | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Dissecting mammalian immunity through mutation. Although mutation and natural selection have given rise to our immune system, a well-placed mutation can also cripple it, and within an expanding population we are recognizing more and more cases of single-gene mutations that compromise immunity. These mutations are an ideal tool for understanding human immunology, and there are more ways than ever to measure their physiological effects. There are also more ways to create mutations in the laboratory, and to use these resources to systematically define the function of every gene in our genome. This review focuses on the discovery and creation of mutations in the context of mammalian immunity, with an emphasis on the use of genome-wide chemical and CRISPR/Cas9 mutagenesis to reveal gene function. |
35 | a9fi9ssg | What new public datasets are available related to COVID-19? | Time Series Prediction of COVID-19 by Mutation Rate Analysis using Recurrent Neural Network-based LSTM Model SARS-CoV-2, a novel coronavirus mostly known as COVID-19 has created a global pandemic. The world is now immobilized by this infectious RNA virus. As of May 18, already more than 4.8 million people have been infected and 316k people died. This RNA virus has the ability to do the mutation in the human body. Accurate determination of mutation rates is essential to comprehend the evolution of this virus and to determine the risk of emergent infectious disease. This study explores the mutation rate of the whole genomic sequence gathered from the patient's dataset of different countries. The collected dataset is processed to determine the nucleotide mutation and codon mutation separately. Furthermore, based on the size of the dataset, the determined mutation rate is categorized for four different regions: China, Australia, The United States, and the rest of the World. It has been found that a huge amount of Thymine (T) and Adenine (A) are mutated to other nucleotides for all regions, but codons are not frequently mutating like nucleotides. A recurrent neural network-based Long Short Term Memory (LSTM) model has been applied to predict the future mutation rate of this virus. The LSTM model gives Root Mean Square Error (RMSE) of 0.06 in testing and 0.04 in training, which is an optimized value. Using this train and testing process, the nucleotide mutation rate of 400(th) patient in future time has been predicted. About 0.1% increment in mutation rate is found for mutating of nucleotides from T to C and G, C to G and G to T. While a decrement of 0.1% is seen for mutating of T to A, and A to C. It is found that this model can be used to predict day basis mutation rates if more patient data is available in updated time. |
21 | oyw5737c | what are the mortality rates overall and in specific populations | The global burden of premature mortality due to the Middle East respiratory syndrome (MERS) using standard expected years of life lost, 2012 to 2019 BACKGROUND: It has been 8 years since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was reported in Saudi Arabia and the disease is still being reported in 27 countries; however, there is no international study to estimate the overall burden related of this emerging infectious disease. The present study was conducted to assess the burden of premature mortality due to Middle East respiratory syndrome (MERS) worldwide. METHODS: In this retrospective analysis, we have utilized publicly available data from the WHO website related to 1789 MERS patients reported between September 23, 2012 and May 17, 2019. To calculate the standard expected years of life lost (SEYLL), life expectancy at birth was set according to the 2000 global burden of disease study on levels 25 and 26 of West model life tables from Coale-Demeny at 82.5 and 80 years for females and males, respectively. RESULTS: Overall, the total SEYLL in males and females was 10,702 and 3817.5 years, respectively. The MERS patients within the age range of 30–59 year-olds had the highest SEYLL (8305.5 years) in comparison to the patients within the age groups 0–29 (SEYLL = 3744.5 years) and ≥ 60 years (SEYLL = 2466.5 years). The total SEYLL in all age groups in 2012, 2013, 2014, 2015, 2016, 2017, 2018, and 2019 were 71.5, 2006.5, 3162, 4425.5, 1809.5, 878, 1257.5 and 909 years, respectively. The most SEYLL related to MERS-CoV infection was in the early four years of the onset of the pandemic (2012 to 2015) and in the last four years of the MERS-CoV pandemic (216 to 2019), a significant reduction was observed in the SEYLL related to MERS-CoV infection in the MERS patients. CONCLUSION: We believe that the findings of this study will shed light about the burden of premature mortality due to MERS infection in the world and the results may provide necessary information for policy-makers to prevent, control, and make a quick response to the outbreak of MERS-CoV disease. |
41 | vwjxcnrb | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Law, Structural Racism, and the COVID-19 Pandemic Racial and ethnic minorities have always been the most impacted by pandemics because of: disparities in exposure to the virus; disparities in susceptibility to contracting the virus; and disparities in treatment. This article explains how structural racism, the ways in which laws are used to advantage the majority and disadvantage racial and ethnic minorities, has caused these disparities. Specifically, this article focuses on how employment, housing, health care, and COVID-19 relief laws have been manipulated to disadvantage racial and ethnic minorities, making minorities more susceptible to COVID-19 infection and death. This article uses Blumenshine's 2008 framework to outline how structural racism causes racial and ethnic minorities' disparities in exposure to viruses, in susceptibility to contracting viruses, in treatment of viruses, and in infection and death rates. This article discusses how historical and current practices of structural racism in existing employment, housing, and health care laws and the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) cause disparities in COVID-19 infections and deaths. This article suggests legal solutions to address structural racism as well as public health solutions to help mitigate the racialized effects of the disease. |
7 | yq4dtf8n | are there serological tests that detect antibodies to coronavirus? | Severe acute respiratory syndrome and dentistry A retrospective view ABSTRACT Background Severe acute respiratory syndrome, or SARS, which has created panic in Asia and in some parts of North America, is the first epidemic of the new century. Although it has been well-contained, sporadic cases continue to emerge. Objectives The authors trace the emergence of the SARS outbreak from southern China and its spread worldwide, discuss the viral etiology of the infection and its clinical features, and review the infection control guidelines issued during the outbreak by the health authorities in Hong Kong, the Centers for Disease Control and Prevention, the World Health Organization and the American Dental Association. They also review the prospects for a new outbreak and preventive measures. Overview The disease, which is caused by a novel coronavirus termed the "SARS coronavirus," or SARS-CoV, essentially spreads through droplet infection and affects people of any age. It has a mortality rate ranging from 10 to 15 percent. A major hallmark of this disease has been the rate at which it has affected health care workers through nosocomial transmission; in some countries, up to one-fourth to one-third of those infected were in this category. However, no dental health care worker has been affected by SARS in a nosocomial or dental setting. Conclusions and Clinical Implications Researchers believe that a combination of factors, including the universal infection control measures that the dental community has implemented and/or the low degree of viral shedding in the prodromal phase of SARS, may have obviated the spread of the disease in dental settings. The dental community should reflect on this outbreak to reinforce the currently applied infection control measures. |
12 | qbl4yaiq | what are best practices in hospitals and at home in maintaining quarantine? | Bat-Related Zoonoses The many emerging infectious diseases associated with Chiropteran species can have major impacts on both ecosystem and public health. As such, the scope of this chapter is to provide an overview of those potential bat-related zoonoses and their clinical relevance to people. With increased disease surveillance and a trend toward more human contact with bat populations, it is likely that additional zoonotic diseases will continue to be identified. Bat infection dynamics are driven by a complex interplay of ecological, immunological, behavioral, and anthropogenic factors. Interdisciplinary work will be needed in the future to better understand the drivers of disease emergence in bat populations and ultimately mitigate the threats that face both people and bats themselves. |
8 | igqevibd | how has lack of testing availability led to underreporting of true incidence of Covid-19? | An urgent call to address the nutritional status of women and children in Nepal during COVID-19 crises Due to the ongoing nationwide lockdown in Nepal, women and children face a greater risk of malnutrition and eventually leading to mortality and morbidity. To harness the progress made so far in improving the nutritional status of women and children, a focus on nutrition should be a part of the COVID-19 response plan. |
24 | eqewn6j4 | what kinds of complications related to COVID-19 are associated with diabetes | Use Stones from Another Mountain to Polish One's Jade: Learn from MERS Studies toexplore potential mechanisms underlying the effect of diabetes mellitus on COVID-19/ 中华内分泌代谢杂志 Epidemiology studies suggest that comorbid diabetes may have negative impact on the progression and severity of the coronavirus disease 2019 (COVID-19), which first occurred in Wuhan. However, the exact mechanism remains unclear. A recent study on another type of coronavirus infection, Middle East Respiratory Syndrome (MERS), investigated its relationship with diabetes. This essay aims to give a brief introduction to this report and related studies, and to propose suggestions on what we can learn from these investigations to conduct further studies on the potential mechanisms underlying the effect of diabetes mellitus on COVID-19. |
9 | deas7kr0 | how has COVID-19 affected Canada | Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020. Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources. |
23 | 409pz4lw | what kinds of complications related to COVID-19 are associated with hypertension? | Targeting the Vasoprotective Axis of the Renin-Angiotensin System: A Novel Strategic Approach to Pulmonary Hypertensive Therapy A decade has passed since the discovery of angiotensin-converting enzyme 2 (ACE2), a component of the ACE2–angiotensin (Ang)-(1-7)–Mas counterregulatory axis of the renin angiotensin system (RAS). ACE2 is considered an endogenous regulator of the vasoconstrictive, proliferative, fibrotic, and proinflammatory effects of the ACE–Ang II–angiotensin II type 1 receptor (AT(1)R) axis. Both animal and clinical studies have emerged to define a role for ACE2 in pulmonary arterial hypertension (PAH). There is scientific evidence supporting the concept that ACE2 maintains the RAS balance and plays a protective role in PAH. The activation of pulmonary ACE2 could influence the pathogenesis of PAH and serve as a novel therapeutic target in PAH. Current therapeutic strategies and interventions have limited success, and PAH remains a fatal disease. Thus, more research that establishes the novel therapeutic potential and defines the mechanism of the ACE2–Ang-(1-7)–Mas counterregulatory axis in PAH is needed. |
8 | jubl3vmq | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Estimation in emerging epidemics: biases and remedies When analysing new emerging infectious disease outbreaks, one typically has observational data over a limited period of time and several parameters to estimate, such as growth rate, the basic reproduction number R(0), the case fatality rate and distributions of serial intervals, generation times, latency and incubation times and times between onset of symptoms, notification, death and recovery/discharge. These parameters form the basis for predicting a future outbreak, planning preventive measures and monitoring the progress of the disease outbreak. We study inference problems during the emerging phase of an outbreak, and point out potential sources of bias, with emphasis on: contact tracing backwards in time, replacing generation times by serial intervals, multiple potential infectors and censoring effects amplified by exponential growth. These biases directly affect the estimation of, for example, the generation time distribution and the case fatality rate, but can then propagate to other estimates such as R(0) and growth rate. We propose methods to remove or at least reduce bias using statistical modelling. We illustrate the theory by numerical examples and simulations. |
4 | 4ntgq7su | what causes death from Covid-19? | Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review BACKGROUND: Increasing research reports neurological manifestations of COVID-19 patients. SARS-CoV-2 shares homology with other human coronaviruses that have also had nervous system involvement. OBJECTIVE: To review the neurological aspects of SARS-cov2 and other coronavirus, including transmission pathways, mechanisms of invasion into the nervous system, and mechanisms of neurological disease. METHODS: We conducted a systematic review of articles in PubMed, SCOPUS and EMBASE data bases. Reviewed evidence is presented in sections of this manuscript which includes pathogenesis, neuro-invasion, encephalitis, Guillain-Barré, ADEM, multiple sclerosis, polyneuropathy, and cerebrovascular disease. RESULTS: A total 67 studies were included in the final analysis of experimental studies, case reports, series of cases, cohort studies, and systematic reviews related to neurological manifestations of SARS- CoV-2 and other human coronavirus infections. The SARS-CoV-2 receptor is expressed in the nervous system. Common reported symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. Infection through the cribriform plate and olfactory bulb and dissemination through trans-synaptic transfer are some of the mechanisms proposed. Invasion of the medullary cardiorespiratory center by SARS-CoV-2 may contribute to the refractory respiratory failure observed in critically-ill COVID-19 patients. CONCLUSION: An increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that SARS-CoV-2 is a new neuropathogen. How it may cause acute and chronic neurologic disorders needs to be clarified in future research. |
14 | vish6v8e | what evidence is there related to COVID-19 super spreaders | ICU management of severe acute respiratory syndrome BACKGROUND: Severe acute respiratory syndrome (SARS) is a contagious viral illness first recognized in late 2002. It has now been documented in 26 countries worldwide, with significant outbreaks in China, Hong Kong, Singapore, and Toronto. Research into identifying the etiological agent, evaluating modes of disease transmission, and treatment options is currently ongoing. DISCUSSION: The disease can produce a severe bilateral pneumonia, with progressive hypoxemia. Up to 20% of patients require mechanical ventilatory support, with a fatal outcome occurring in about 5% of cases. CONCLUSIONS: We review the current knowledge about this disease, with particular emphasis on ICU management and infection control precautions to prevent disease transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available if you access this article at http://dx.doi.org/10.1007/s00134-003-1821-0. On that page (frame on the left side) a link takes you directly to the supplementary material. |
35 | ftu4850y | What new public datasets are available related to COVID-19? | COVID-19: Putting the General Data Protection Regulation to the Test The coronavirus disease (COVID-19) pandemic is very much a global health issue and requires collaborative, international health research efforts to address it. A valuable source of information for researchers is the large amount of digital health data that are continuously collected by electronic health record systems at health care organizations. The European Union's General Data Protection Regulation (GDPR) will be the key legal framework with regard to using and sharing European digital health data for research purposes. However, concerns persist that the GDPR has made many organizations very risk-averse in terms of data sharing, even if the regulation permits such sharing. Health care organizations focusing on individual risk minimization threaten to undermine COVID-19 research efforts. In our opinion, there is an ethical obligation to use the research exemption clause of the GDPR during the COVID-19 pandemic to support global collaborative health research efforts. Solidarity is a European value, and here is a chance to exemplify it by using the GDPR regulatory framework in a way that does not hinder but actually fosters solidarity during the COVID-19 pandemic. |
32 | 8vl0okiv | Does SARS-CoV-2 have any subtypes, and if so what are they? | A snapshot of SARS-CoV-2 genome availability up to 30th March, 2020 and its implications The SARS-CoV-2 pandemic has been growing exponentially, affecting nearly 900 thousand people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies in countries with the highest toll of confirmed cases. Although number of-available full-genomes is growing daily, and the full dataset contains sufficient phylogenetic information that would allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 datasets still present severe limitations. Studies assessing within country spread or transmission clusters should be considered preliminary at best, or hypothesis generating. Hence the need for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic. Significance Statement Although genome sequences of SARS-CoV-2 are growing daily and contain sufficient phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution. |
36 | f4c9aorn | What is the protein structure of the SARS-CoV-2 spike? | SARS-CoV-2 infection and stem cells: interaction and intervention The emergence of the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread have created a global health emergency. The resemblance with SARS-CoV in spike protein suggests that SARS-CoV-2 employs spike–driven entry into angiotensin-converting enzyme 2 (ACE2)-expressing cells. From a stem cell perspective, this review focuses on the possible involvement of ACE2(+) stem/progenitor cells from both the upper and lower respiratory tracts in coronavirus infection. Viral infection-associated acute respiratory distress syndrome and acute lung injury occur because of dysregulation of the immune response. Mesenchymal stem cells appear to be a promising cell therapy given that they favorably modulate the immune response to reduce lung injury. The use of exogenous stem cells may lead to lung repair. Therefore, intervention by transplantation of exogenous stem cells may be required to replace, repair, remodel, and regenerate lung tissue in survivors infected with coronavirus. Ultimately, vaccines, natural killer cells and induced-pluripotent stem cell-derived virus-specific cytotoxic T lymphocytes may offer off-the-shelf therapeutics for preventing coronavirus reemergence. |
49 | 68dryuux | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Strategies to Prevent SARS-CoV-2-Mediated Eosinophilic Disease in Association with COVID-19 Vaccination and Infection A vaccine to protect against COVID-19 is urgently needed. Such a vaccine should efficiently induce high-affinity neutralizing antibodies which neutralize SARS-CoV-2, the cause of COVID-19. However, there is a concern regarding both vaccine-induced eosinophilic lung disease and eosinophil-associated Th2 immunopotentiation following infection after vaccination. Here, we review the anticipated characteristics of a COVID-19 vaccine to avoid vaccine-associated eosinophil immunopathology. |
5 | car394ou | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | SARS-CoV-2 infection protects against rechallenge in rhesus macaques An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates. |
19 | g0vyzsga | what type of hand sanitizer is needed to destroy Covid-19? | Radiographic Findings and other Predictors in Adults with Covid-19 As of March 20, 2020, there were 234,073 confirmed cases of coronavirus disease 2019 (Covid-19) and 9,840 deaths worldwide. Older age and elevated d-dimer are reported risk factors for Covid-19. However, whether early radiographic change is a predictor of fatality remains unknown. We retrospectively reviewed records of all laboratory-confirmed patients admitted to a quarantine unit at Tongji Hospital, a large regional hospital in Wuhan, China, between January 31 and March 5, 2020. The Tongji Hospital ethics committee approved this study. A total of 128 patients were admitted. 102 patients were confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using RNA detection. As of March 20, 82 confirmed patients were discharged, 15 died, and 5 remained hospitalized. The median age was 57 years (range, 27 - 85), 59 (58%) were male, and 44 (43%) patients had a comorbidity. The most common symptoms were fever, cough, and dyspnea. When compared with survivors, non-survivors were older and more likely to have lymphopenia, elevated lactate dehydrogenase (LDH), elevated d-dimer, and increased hypersensitive troponin I. In a multivariate regression model that included these predictors, older age and elevated LDH were independent risk factors for fatality. Twenty-one survivors and 11 non-survivors had CT scans within the first week. We used severity score to quantify the extent of lung opacification as described in the Supplementary Appendix. The total severity score and number of involved lung lobes within the first week were significantly greater in non-survivors compared to survivors . Using univariate logistic regression analysis, higher total severity score ([≥]15) (odds ratio 53, 95% CI 3-369; p = 0.003), and more involved lung lobes (5 involved lobes) (9, 2-53; p = 0.016) in CT images within the first week were significantly associated with fatality. Moreover, in this subset of patients with CT data within the first week, higher total severity score was the only independent risk factor in a multivariate analysis incorporated the predictors discussed above (older age, lymphocytopenia, elevated LDH, elevated d-dimer, and increased troponin I). For survivors with serial CT scans performed over four weeks, total severity score peaked in the second week. This report suggests that the extent of lung lesions in early CT images is a potential predictor of poor outcome of Covid-19. This will help clinicians to identify the patients with poor prognosis at early stage. |
39 | muzqgk95 | What is the mechanism of cytokine storm syndrome on the COVID-19? | COVID-19: a new virus, but an old cytokine release syndrome Understanding the cell entry mechanism of pandemic coronavirus SARS-CoV-2 is crucial for treating the disease Zhou et al (Nature) and Hoffmann et al (Cell) identify ACE2 as a SARS-CoV-2 receptor, and the latter show its entry mechanism depends on cellular serine protease TMPRSS2 These results suggest several possible therapeutic targets, including the IL-6-STAT3 axis previously associated with cytokine release syndromes |
22 | mol4s3iz | are cardiac complications likely in patients with COVID-19? | Approach to Acute Cardiovascular Complications in COVID-19 Infection. The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to more than 187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, myocarditis) and secondary (myocardial injury/biomarker elevation, heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a "Heart-Lung" team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock. |
13 | yq4dtf8n | what are the transmission routes of coronavirus? | Severe acute respiratory syndrome and dentistry A retrospective view ABSTRACT Background Severe acute respiratory syndrome, or SARS, which has created panic in Asia and in some parts of North America, is the first epidemic of the new century. Although it has been well-contained, sporadic cases continue to emerge. Objectives The authors trace the emergence of the SARS outbreak from southern China and its spread worldwide, discuss the viral etiology of the infection and its clinical features, and review the infection control guidelines issued during the outbreak by the health authorities in Hong Kong, the Centers for Disease Control and Prevention, the World Health Organization and the American Dental Association. They also review the prospects for a new outbreak and preventive measures. Overview The disease, which is caused by a novel coronavirus termed the "SARS coronavirus," or SARS-CoV, essentially spreads through droplet infection and affects people of any age. It has a mortality rate ranging from 10 to 15 percent. A major hallmark of this disease has been the rate at which it has affected health care workers through nosocomial transmission; in some countries, up to one-fourth to one-third of those infected were in this category. However, no dental health care worker has been affected by SARS in a nosocomial or dental setting. Conclusions and Clinical Implications Researchers believe that a combination of factors, including the universal infection control measures that the dental community has implemented and/or the low degree of viral shedding in the prodromal phase of SARS, may have obviated the spread of the disease in dental settings. The dental community should reflect on this outbreak to reinforce the currently applied infection control measures. |
15 | p883xjq5 | how long can the coronavirus live outside the body | Introducing Ebola (EVD): An Unnecessary Surprise Chapter 4 tackles the Ebola (Ebola Virus Disease, EVD) pandemic of 2014/2015. It notes that coming in the wake of the ongoing HIV pandemic, the rights of those infected with Ebola to be identified and treated were largely uncontested. The questions of who would be treated, by whom, with what, remained however extremely contentious. The international response to the pandemic also saw, for the first time, not only non-state actors involved in mediating and mitigating a health crisis, but also military intervention. This chapter lays out both the uses and the dilemmas of military response. It explores the impact of these interventions in this Ebola pandemic, with a view towards possible future military deployments against health threats, and offers an initial analysis of the consequences thereof on the relationship between individual and state rights and responsibilities. |
34 | ter67nri | What are the longer-term complications of those who recover from COVID-19? | Myocardial injury and COVID-19: Possible mechanisms Abstract Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia. |
11 | gjm9dml1 | what are the guidelines for triaging patients infected with coronavirus? | Identification of a novel protein encoded by the latency-related gene of bovine herpesvirus 1 The latency-related (LR) RNA encoded by bovine herpesvirus 1 (BHV-1) is abundantly expressed and alternatively spliced in trigeminal ganglia. A mutant BHV-1 strain that contains three stop codons at the beginning of LR open reading frame (ORF)-2 (LR mutant virus) does not express ORF-2 or an adjacent reading frame that lacks an initiating ATG (RF-C). Calves latently infected with wild-type (wt) BHV-1, but not with the LR mutant virus, reactivate from latency, indicating that proteins encoded by the LR gene regulate the latency-reactivation cycle. The LR gene also contains another large ORF (ORF-1) that is approximately 200 bp downstream of stop codons inserted at the N-terminus of ORF-2. To test whether the LR mutant virus can expresses ORF-1, the authors developed antiserum directed against ORF-1. The ORF-1 antiserum recognizes specific proteins in bovine cells productively infected with wt BHV-1. ORF-1 protein expression is reduced, but not blocked, when bovine cells are infected with the LR mutant virus. Confocal microscopy demonstrated ORF-1 is present in the cytoplasm and nucleus of productively infected cells, whereas RF-C or a fusion protein containing RF-C localizes to the cytoplasm. Trigeminal ganglia from calves latently infected with wt BHV-1 contain neurons specifically stained with the ORF-1 antiserum. These studies suggest ORF-1 expression may be important for the BHV-1 latency-reactivation cycle. |
8 | 662pfa61 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against coronavirus disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the treatment of this disease, and several approved drugs such as lopinavir have been evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication of SARS-CoV-2. The effective concentrations for 50% and 90% inhibition (EC50 and EC90) of nelfinavir were 1.13 µM and 1.76 µM respectively, the lowest of the nine HIV-1 protease inhibitors including lopinavir. The trough and peak serum concentrations of nelfinavir were three to six times higher than EC50 of this drug. These results suggest that nelfinavir is a potential candidate drug for the treatment of COVID-19 and should be assessed in patients with COVID-19. |
44 | ugkxxaeb | How much impact do masks have on preventing the spread of the COVID-19? | Masking the general population might attenuate COVID-19 outbreaks The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed"one-mask protection") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to>50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects. |
14 | xbsvofir | what evidence is there related to COVID-19 super spreaders | The threat of climate change to non-dengue-endemic countries: increasing risk of dengue transmission potential using climate and non-climate datasets BACKGROUND: Dengue is a major public health problem in the tropics and sub-tropics, but the disease is less known to non-dengue-endemic countries including in Northeast Asia. However, an unexpected dengue outbreak occurred in 2014 in Japan. Given that autochthonous (domestic) dengue cases had not been reported for the past 70 years in Japan, this outbreak was highly unusual and suggests that several environmental factors might have changed in a way that favors vector mosquitoes in the Northeast Asian region. METHODS: A Climate Risk Factor (CRF) index, as validated in previous work, was constructed using climate and non-climate factors. This CRF index was compared to the number of reported dengue cases in Tokyo, Japan where the outbreak was observed in 2014. In order to identify high-risk areas, the CRF index was further estimated at the 5 km by 5 km resolution and mapped for Japan and South Korea. RESULTS: The high-risk areas determined by the CRF index corresponded well to the provinces where a high number of autochthonous cases were reported during the outbreak in Japan. At the provincial-level, high-risk areas for dengue fever were the Eastern part of Tokyo and Kanakawa, the South-Eastern part of Saitama, and the North-Western part of Chiba. While a relatively small number of high-risk areas were identified in South Korea compared with Japan, the high-risk areas in South Korea include popular tourist destinations where international visitors have been increasing. CONCLUSION: The recent dengue outbreak in Japan may signal that the two adjacent non-dengue-endemic countries are also exposed to the risk of temporal and sporadic behavior of dengue fever. It is critical to understand potential high-risk areas for future outbreaks and to set up appropriate prevention activities at the governmental-level. |
34 | dvnb90dz | What are the longer-term complications of those who recover from COVID-19? | Modeling and prediction of COVID-19 pandemic using Gaussian mixture model COVID-19 is caused by a novel coronavirus and has played havoc on many countries across the globe. A majority of the world population is now living in a restricted environment for more than a month with minimal economic activities, to prevent exposure to this highly infectious disease. Medical professionals are going through a stressful period while trying to save the larger population. In this paper, we develop two different models to capture the trend of a number of cases and also predict the cases in the days to come, so that appropriate preparations can be made to fight this disease. The first one is a mathematical model accounting for various parameters relating to the spread of the virus, while the second one is a non-parametric model based on the Fourier decomposition method (FDM), fitted on the available data. The study is performed for various countries, but detailed results are provided for the India, Italy, and United States of America (USA). The turnaround dates for the trend of infected cases are estimated. The end-dates are also predicted and are found to agree well with a very popular study based on the classic susceptible-infected-recovered (SIR) model. Worldwide, the total number of expected cases and deaths are 12.7 × 10(6) and 5.27 × 10(5), respectively, predicted with data as of 06-06-2020 and 95% confidence intervals. The proposed study produces promising results with the potential to serve as a good complement to existing methods for continuous predictive monitoring of the COVID-19 pandemic. |
27 | 7lwh917j | what is known about those infected with Covid-19 but are asymptomatic? | Phylogenetic Analysis of Feline Coronavirus Strains in an Epizootic Outbreak of Feline Infectious Peritonitis BACKGROUND: Feline coronavirus (FCoV) infection is common. In a small percentage of cats, FCoV infection is associated with the fatal disease feline infectious peritonitis (FIP). Genetically distinct virulent and avirulent strains of FCoV might coexist within a cat population. OBJECTIVES: To determine whether the strains of FCoV in FIP‐affected cats are closely related or genetically distinct from the fecally derived strains of FCoV in contemporary‐asymptomatic cats during an epizootic outbreak of FIP. ANIMALS: Four cats euthanized because of FIP and 16 asymptomatic cats. METHODS: This prospective outbreak investigation was initiated during an outbreak of FIP in cats within or rehomed from a rescue/rehoming center. Postmortem samples were collected from cats with FIP and contemporaneous fecal samples from asymptomatic cats. RNA was purified from tissue and fecal samples, FCoV gene fragments were reverse transcribed, PCR‐amplified using novel primers, and sequenced. Sequences were aligned with ClustalW and compared with published FCoV sequences. RESULTS: FCoV RNA was detected in all 4 FIP cat postmortem samples and in 9 of the 16 fecal samples from contemporary‐asymptomatic cats. Novel primers successfully amplified fragments from 4 regions of the genome for all FCoV‐positive samples. Phylogenetic analysis showed that the FIP‐associated strains of FCoV from the outbreak were very closely related to the fecally derived strains of FCoV from contemporary‐asymptomatic cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Sequence analysis provided no evidence that genetically distinct virulent and avirulent strains of FCoV were present during this FIP outbreak. |
27 | 4vgbzcx8 | what is known about those infected with Covid-19 but are asymptomatic? | Estimation of Infection Rate and Prediction of Initial Infected Individuals of COVID-19 We consider the pandemic spreading of COVID-19 for some selected countries after the outbreak of the coronavirus in Wuhan City, China. We estimated the infection rate and the initial infected individuals of COVID-19 by using the officially reported data at the early stage of the epidemic for the susceptible (S), infectable (I), quarantined (Q), and the cofirmed recovered (Rk) population model, so called SIQRk model. In the reported data we know the quarantined cases and the recovered cases. We can not know the recovered cases from the asymptomatic cases. In the SIQRk model we can estimated the model parameters and the initial infecting cases (confirmed ans asymtomatic cases) from the data fits. We obtained the infection rate in the range between 0.233 and 0.462, the basic reproduction number Ro in the range between 1.8 and 3.5, and the initial number of infected individuals in the range betwee 10 and 8409 for some selected countries. By using fitting parameters we estimated the maximum time of the infection for Germany when the government are performing the quarantine policy. The disease is undergoing to the calm state about six months after first patients were identified. |
28 | gwm36n75 | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Docking study of Chloroquine and Hydroxychloroquine interaction with SARS-CoV-2 spike glycoprotein-An in silico insight into the comparative efficacy of repurposing antiviral drugs. Recent outbreak of novel Coronavirus disease (Covid-19) pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and there are ample evidences that its Spike protein (S-protein) is mainly associated with pathogenesis as it is surface-exposed and mediates entry into host cells by binding to angiotensin-converting enzyme-2 (ACE-2) receptor. Therefore, it is the main target of neutralizing antibodies upon infection and there is always a quest to inhibit the S-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for Covid-19 is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the S-protein of SARS-CoV-2. With the help of various computational methods, we have re-explored the potential role of both of these antiviral drugs for the treatment of Covid-19 patients by comparing the efficacy of both of the drugs to bind to S-protein at its host receptor region. In our research Hydroxychloroquine exhibited potential inhibitory effectsof S-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with Covid-19. Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching Covid-19 to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with Covid-19. We further hypothesize that the comparative S-protein-drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine. |
18 | 3u1jxgyv | what are the best masks for preventing infection by Covid-19? | SARS preventive and risk behaviours of Hong Kong air travellers. This study aims to investigate Severe Acute Respiratory Syndrome (SARS)-related behaviours of travellers returning to Hong Kong by air. A total of 820 travellers returning to Hong Kong by air were interviewed about their SARS-related behaviours in April 2003. Three quarters of the respondents wore a mask most/all of the time on board, 15% did so in public places at the travel destination. Perceived susceptibility to SARS at the destination predicted mask-wearing in public places and avoidance of crowded places, and perceived efficacy was a predictor for mask-wearing during flight. Approximately 16% of the respondents stated that they would delay their medical consultation for flu-like symptoms until returning to Hong Kong. Nearly 18.2% stated that they would not wear a mask in public places at the destination if they had flu-like symptoms. Education programmes, special services and effective thermal screening are required to minimize the chance of the spread of SARS by air travellers. |
14 | c48gl27o | what evidence is there related to COVID-19 super spreaders | Severe acute respiratory syndrome--Singapore, 2003. The Singapore Ministry of Health (MOH), with assistance from the World Health Organization (WHO), has been investigating an outbreak of severe acute respiratory syndrome (SARS). This is a novel condition caused by the SARS-associated coronavirus (SARS-CoV) and is characterized by both an atypical pneumonia and efficient nosocomial transmission. This report summarizes epidemiologic features of this outbreak in Singapore, including the influence of super spreaders and the national prevention and control strategy. |
34 | 68g6guvs | What are the longer-term complications of those who recover from COVID-19? | Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective |
6 | xwzichc3 | what types of rapid testing for Covid-19 have been developed? | Short-Term Covid-19 Forecast for Latecomers The number of Covid-19 cases is increasing dramatically worldwide. Therefore, the availability of reliable forecasts for the number of cases in the coming days is of fundamental importance. We propose a simple statistical method for short-term real-time forecasting of the number of Covid-19 cases and fatalities in countries that are latecomers -- i.e., countries where cases of the disease started to appear some time after others. In particular, we propose a penalized (LASSO) regression with an error correction mechanism to construct a model of a latecomer in terms of the other countries that were at a similar stage of the pandemic some days before. By tracking the number of cases and deaths in those countries, we forecast through an adaptive rolling-window scheme the number of cases and deaths in the latecomer. We apply this methodology to Brazil, and show that (so far) it has been performing very well. These forecasts aim to foster a better short-run management of the health system capacity. |
5 | 1cph1uij | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia. |
19 | m97gtz6i | what type of hand sanitizer is needed to destroy Covid-19? | Alcohol use in times of the COVID 19: Implications for monitoring and policy Based on a literature search undertaken to determine the impacts of past public health crises, and a systematic review of the effects of past economic crises on alcohol consumption, two main scenarios—with opposite predictions regarding the impact of the current COVID‐19 pandemic on the level and patterns of alcohol consumption—are introduced. The first scenario predicts an increase in consumption for some populations, particularly men, due to distress experienced as a result of the pandemic. A second scenario predicts the opposite outcome, a lowered level of consumption, based on the decreased physical and financial availability of alcohol. With the current restrictions on alcohol availability, it is postulated that, for the immediate future, the predominant scenario will likely be the second, while the distress experienced in the first may become more relevant in the medium‐ and longer‐term future. Monitoring consumption levels both during and after the COVID‐19 pandemic will be necessary to better understand the effects of COVID‐19 on different groups, as well as to distinguish them from those arising from existing alcohol control policies. |
25 | 7vhs9rg1 | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Etiological agents of lower respiratory tract infections in Japanese children. To investigate the etiology of pediatric community-acquired pneumonia and bronchitis, we conducted a prospective, population-based study covering the total population < 15 years of age in 16 municipalities in Hokkaido, Japan, during the period of April 2000 to March 2001. Chest radiographs were available for all cases (n = 921; 398 as pneumonia and 523 as bronchitis) and paired sera for serologic assays were available for more than half of the cases. The following specimens were also collected: nasopharyngeal swabs for viral, bacteriological, mycoplasmal and chlamydial studies, blood for serology and blood culture. The children were then followed-up on days 3, 7 and 14. Specific infecting organisms were identified in a total of 853 (92.6%) out of 921 patients (398 cases of pneumonia and 523 cases of bronchitis) including 205 with mixed infection as follows: Mycoplasma pneumoniae, 252 (274%) patients; respiratory syncytial (RS) virus, 188 (20.4%); influenza A virus, 110 (11.9%); Streptococcus pneumoniae, 95 (10.3%); Haemophilus influenzae, 90 (9.8%); Haemophilus parainfluenzae, 35 (3.8%); Staphylococcus aureus, 29 (3.1%); adenovirus, 27 (2.9%); Moraxella catarrhalis, 12 (1.3%); Pseudomonas aeruginosa , 7 (0.8%); Chlamydia pneumoniae, 6 (0.7%); and other agents, 2 (0.2%). Mycoplasma infections were seen even in patients less than 5 years and RS and influenza A virus infections in patients more than 5 years of age. The importance of M. pneumoniae and RS virus in the etiology of lower respiratory infections in Japanese children was confirmed. |
31 | d63noia4 | How does the coronavirus differ from seasonal flu? | Viral pathogens among elderly people with acute respiratory infections in Shanghai, China: Preliminary results from a laboratory‐based surveillance, 2012‐2015 Acute respiratory infections (ARIs), with viral pathogens as the major contributors, are the most common illnesses worldwide, and increase the morbidity and mortality among the elderly population. The clinical and pathological features of elderly people with ARIs need to be identified for disease intervention. From January 1, 2012 through December 31, 2015, respiratory specimens from patients above 60 years old with ARIs were collected from the outpatient and inpatient settings of six sentinel hospitals in Pudong New Area. Each specimen was tested via multiplex polymerase chain reaction (PCR) for eight target viral etiologies including influenza, human rhinovirus (HRV), human para‐influenza virus (PIV), adenovirus (ADV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human coronavirus (hCoVs), and human bocavirus (hBoV). A total of 967 elderly patients with ARIs were enrolled, including 589 (60.91%) males, and the median age was 73 years old. 306 (31.64%) patients were tested positive for any one of the eight viruses, including 276 single infections and 30 co‐infections. Influenza was the predominant virus (14.17%, 137/967), detected from 21.35% (76/356) of the outpatients and 9.98% (61/611) of the inpatients. Influenza infections presented two annual seasonal peaks during winter and summer. Compared with non‐influenza patients, those with influenza were more likely to have fever, cough, sore throat, and fatigue. This study identified influenza as the leading viral pathogen among elderly with ARIs, and two seasonal epidemic peaks were observed in Shanghai. An influenza vaccination strategy needs to be advocated for the elderly population. |
38 | c51eyqpi | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Targeting innate immunity by blocking CD14: Novel approach to control inflammation and organ dysfunction in COVID-19 illness The SARS-CoV-2 pandemic has produced an unprecedented rush to develop new therapies, ranging from immunizations and antivirals to host-directed therapies to dampen potentially deleterious host inflammatory responses. With a sense of urgency, many groups have proposed repurposing approved drugs for other indications that might be deployed rapidly to control the viral infection or improve host responses. However, many of these therapies are based on drug availability rather than on a rational understanding of important steps in pathogenesis, particularly in the lungs, that lead to critical illness and life-threatening acute respiratory failure. Here we propose that the viral infection initially triggers a profound activation of innate immunity in the lungs that generates a self-perpetuating cytokine storm affecting the entire body. Inhibiting key proximal points in innate immunity pathways is feasible and offers a science-based approach to improving outcomes in moderate to severe COVID-19 illness. |
20 | 5y8cc5eb | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Anti-RAS drugs and SARS-CoV-2 infection • There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation. • The level of ACE2 expression is not completely related with the risk of COVID-19 infection. • There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials. • It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs. |
46 | y9wuszu5 | what evidence is there for dexamethasone as a treatment for COVID-19? | Rapid systematic review on clinical evidence of chloroquine and hydroxychloroquine in COVID-19: critical assessment and recommendation for future clinical trials Purpose: This study aims to critically assess the published studies of Chloroquine (CQ) and hydroxychloroquine (HCQ) for the treatment of COVID-19 and provide recommendations for future clinical trials for the COVID-19 pandemic. Method: A rapid systematic review was conducted by searching the PubMed, Embase, and China National Knowledge Infrastructure databases on April 13, 2020. Three clinical trial registry platforms, including ClinicalTrials.gov, the EU Clinical Trials Register, and the Chinese Clinical Trial Register were also complementarily searched. Results: A total of 10 clinical studies were identified, including 3 randomized controlled trials (RCTs), 1 comparative nonrandomized trial, 5 single-arm trials, and 1 interim analysis. The heterogeneity among studies of the baseline disease severity and reported endpoints made a pooled analysis impossible. CQ and HCQ (with or without azithromycin) showed significant therapeutic benefit in terms of virologic clearance rate, improvement in symptoms and imaging findings, time to clinical recovery, and length of hospital stay in 1 RCT, 4 single-arm trials, and the interim analysis, whereas no treatment benefit of CQ or HCQ was observed in the remaining 4 studies. Limitations of the included studies ranged from small sample size, to insufficient information concerning baseline patient characteristics, to potential for selection bias without detailing the rationale for exclusion, and presence of confounding factors. Conclusion: Based on the studies evaluated, there still lacked solid evidence supporting the efficacy and safety of HCQ and CQ as a treatment for COVID-19 with or without azithromycin. This emphasized the importance of robust RCTs investing HCQ/CQ to address the evidence uncertainties. Keywords: COVID-19, Systematic review, Clinical trial, Chloroquine, Hydroxychloroquine |
49 | eisfz30c | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1 COVID-19 pandemic is a global crisis that threatens our way of life. As of April 29, 2020, COVID-19 has claimed more than 200,000 lives, with a global mortality rate of ~7% and recovery rate of ~30%. Understanding the interaction of cellular targets to the SARS-CoV2 infection is crucial for therapeutic development. Therefore, the aim of this study was to perform a comparative analysis of transcriptomic signatures of infection of COVID-19 compared to different respiratory viruses (Ebola, H1N1, MERS-CoV, and SARS-CoV), to determine unique anti-COVID1-19 gene signature. We identified for the first time molecular pathways for Heparin-binding, RAGE, miRNA, and PLA2 inhibitors, to be associated with SARS-CoV2 infection. The NRCAM and SAA2 that are involved in severe inflammatory response, and FGF1 and FOXO1 genes, which are associated with immune regulation, were found to be associated with a cellular gene response to COVID-19 infection. Moreover, several cytokines, most significantly the IL-8, IL-6, demonstrated key associations with COVID-19 infection. Interestingly, the only response gene that was shared between the five viral infections was SERPINB1. The PPI study sheds light on genes with high interaction activity that COVID-19 shares with other viral infections. The findings showed that the genetic pathways associated with Rheumatoid arthritis, AGE-RAGE signaling system, Malaria, Hepatitis B, and Influenza A were of high significance. We found that the virogenomic transcriptome of infection, gene modulation of host antiviral responses, and GO terms of both COVID-19 and Ebola are more similar compared to SARS, H1N1, and MERS. This work compares the virogenomic signatures of highly pathogenic viruses and provides valid targets for potential therapy against COVID-19. |
28 | moor7dfc | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Feline Vaccination Guidelines The 1998 Report of the American Association of Feline Practitioners and Academy of Feline Medicine Advisory Panel on Feline Vaccines was developed to help veterinary practitioners formulate vaccination protocols for cats. The current panel report updates information, addresses questions, and speaks to concerns raised by the 1998 report. In addition it reviews vaccine licensing, labeling, and liability issues and suggests ways to successfully incorporate vaccination protocol changes into a private practice setting. |
21 | hj4wd5lc | what are the mortality rates overall and in specific populations | Prevalence and risk factors for mortality related to COVID-19 in a severely affected area of Madrid, Spain BACKGROUND: The coronavius disease 2019 (COVID-9) caused by the severe acute respiratory syndrome coronavirus 2 reached Spain by 31 January 2020, in April 2020, the Comunidad de Madrid suffered one of the world's highest crude mortality rate ratios. This study aimed to detect risk factors for mortality in patients with COVID-19. METHODS: Our cohort were all consecutive adult patients with laboratory-confirmed COVID-19 at a secondary hospital in Madrid, March 3-16, 2020. Clinical and laboratory data came from electronic clinical records and were compared between survivors and non-survivors, with outcomes followed up until April 4. Univariable and multivariable logistic regression methods allowed us to explore risk factors associated with in-hospital death. FINDINGS: The cohort comprised 562 patients with COVID-19. Clinical records were available for evaluation for 392 patients attended at the emergency department of our hospital, of whom 199 were discharged, 85 remained hospitalized and 108 died during hospitalization. Among 311 of the hospitalized patients, 34.7% died. Of the 392 patients with records, the median age was 71.5 years (50.6-80.7); 52.6% were men. 252 (64.3%) patients had a comorbidity, hypertension being the most common: 175 (44.6%), followed by other cardiovascular disease: 102 (26.0%) and diabetes: 97 (24.7%). Multivariable regression showed increasing odds of in-hospital death associated with age over 65 (odds ratio 8.32, 95% CI 3.01-22.96; p<0.001), coronary heart disease (2.76, 1.44-5.30; 0.002), and both lower lymphocyte count (0.34, 0.17-0.68; 0.002) and higher LDH (1.25, 1.05-1.50; 0.012) per 1-unit increase and per 100 units respectively. INTERPRETATION: COVID-19 was associated in our hospital at the peak of the pandemic with a crude mortality ratio of 19.2% and a mortality ratio of 34.7% in admitted patients, considerably above most of the ratios described in the Chinese series. These results leave open the question as to which factors, epidemiological or intrinsically viral, apart from age and comorbidities, can explain this difference in excess mortality. FUNDING: None. |
20 | 7vcf54ns | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Coronavirus and diabetes: an update |
40 | zmqaigqf | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Prediction of amino acid pairs sensitive to mutations in the spike protein from SARS related coronavirus In this study, we analyzed the amino acid pairs affected by mutations in two spike proteins from human coronavirus strains 229E and OC43 by means of random analysis in order to gain some insight into the possible mutations in the spike protein from SARS-CoV. The results demonstrate that the randomly unpredictable amino acid pairs are more sensitive to the mutations. The larger is the difference between actual and predicted frequencies, the higher is the chance of mutation occurring. The effect induced by mutations is to reduce the difference between actual and predicted frequencies. The amino acid pairs whose actual frequencies are larger than their predicted frequencies are more likely to be targeted by mutations, whereas the amino acid pairs whose actual frequencies are smaller than their predicted frequencies are more likely to be formed after mutations. These findings are identical to our several recent studies, i.e. the mutations represent a process of degeneration inducing human diseases. |
50 | 5w194etz | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Human and novel coronavirus infections in children: a review. Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. ABBREVIATIONS 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Guérin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization. |
29 | 5f95gve3 | which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information? | Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs COVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 μM < IC50 < 10 μM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19. |
15 | xi9c7d1t | how long can the coronavirus live outside the body | Reducing mortality from 2019-nCoV: host-directed therapies should be an option |
1 | m40kwgcg | what is the origin of COVID-19 | Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China. |
47 | xhyqg5u2 | what are the health outcomes for children who contract COVID-19? | The impact of school reopening on the spread of COVID-19 in England Background: In the UK, cases of COVID-19 have been declining since mid-April and there is good evidence to suggest that the effective reproduction number has dropped below 1, leading to a multi-phase relaxation plan for the country to emerge from lockdown. As part of this staggered process, primary schools are scheduled to partially reopen on 1st June. Evidence from a range of sources suggests that children are, in general, only mildly affected by the disease and have low mortality rates, though there is less certainty regarding children's role in transmission. Therefore, there is wide discussion on the impact of reopening schools. Methods: We compare eight strategies for reopening primary and secondary schools in England from 1st June, focusing on the return of particular year groups and the associated epidemic consequences. This is assessed through model simulation, modifying a previously developed dynamic transmission model for SARS-CoV-2. We quantify how the process of reopening schools affected contact patterns and anticipated secondary infections, the relative change in R according to the extent of school reopening, and determine the public health impact via estimated change in clinical cases and its sensitivity to decreases in adherence post strict lockdown. Findings: Whilst reopening schools, in any form, results in more mixing between children, an increase in R and hence transmission of the disease, the magnitude of that increase can be low dependent upon the age-groups that return to school and the behaviour of the remaining population. We predict that reopening schools in a way that allows half class sizes or that is focused on younger children is unlikely to push R above one, although there is noticeable variation between the regions of the country. Given that older children have a greater number of social contacts and hence a greater potential for transmission, our findings suggest reopening secondary schools results in larger increases in case burden than only reopening primary schools; reopening both generates the largest increase and could push R above one in some regions. The impact of less social-distancing in the rest of the population, generally has far larger effects than reopening schools and exacerbates the impacts of reopening. Discussion: Our work indicates that any reopening of schools will result in increased mixing and infection amongst children and the wider population, although the opening of schools alone is unlikely to push the value of R above one. However, impacts of other recent relaxations of lockdown measures are yet to be quantified, suggesting some regions may be closer to the critical threshold that would lead to a growth in cases. Given the uncertainties, in part due to limited data on COVID-19 in children, school reopening should be carefully monitored. Ultimately, the decision about reopening classrooms is a difficult trade-off between increased epidemiological consequences and the emotional, educational and developmental needs of children. |
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