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10 | e2p46wa8 | has social distancing had an impact on slowing the spread of COVID-19? | Comparative Impact of Individual Quarantine vs. Active Monitoring of Contacts for the Mitigation of COVID-19: a modelling study BACKGROUND: Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases, such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible, and broader mitigation measures must be implemented. METHODS: To estimate the comparative efficacy of these case-based interventions to control COVID-19, we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit to the incubation period distribution and each of two sets of the serial interval distribution: a shorter one with a mean serial interval of 4.8 days and a longer one with a mean of 7.5 days. To assess variable resource settings, we consider two feasibility settings: a high feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and low feasibility setting with 50% of contacts traced, a two-day average delay, and 50% effective isolation. FINDINGS: Our results suggest that individual quarantine in high feasibility settings where at least three-quarters of infected contacts are individually quarantined contains an outbreak of COVID-19 with a short serial interval (4.8 days) 84% of the time. However, in settings where this performance is unrealistically high and the outbreak continues to grow, so too will the burden of the number of contacts traced for active monitoring or quarantine. When resources are prioritized for scalable interventions such as social distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. INTERPRETATION: Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission in order to make data-driven policy decisions regarding the cost-benefit comparisons of individual quarantine vs. active monitoring of contacts. To the extent these interventions can be implemented they can help mitigate the spread of COVID-19. |
40 | r90ty04i | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Risk factors for the evolutionary emergence of pathogens Recent outbreaks of novel infectious diseases (e.g. SARS, influenza H1N1) have highlighted the threat of cross-species pathogen transmission. When first introduced to a population, a pathogen is often poorly adapted to its new host and must evolve in order to escape extinction. Theoretical arguments and empirical studies have suggested various factors to explain why some pathogens emerge and others do not, including host contact structure, pathogen adaptive pathways and mutation rates. Using a multi-type branching process, we model the spread of an introduced pathogen evolving through several strains. Extending previous models, we use a network-based approach to separate host contact patterns from pathogen transmissibility. We also allow for arbitrary adaptive pathways. These generalizations lead to novel predictions regarding the impact of hypothesized risk factors. Pathogen fitness depends on the host population in which it circulates, and the 'riskiest' contact distribution and adaptive pathway depend on initial transmissibility. Emergence probability is sensitive to mutation probabilities and number of adaptive steps required, with the possibility of large adaptive steps (e.g. simultaneous point mutations or recombination) having a dramatic effect. In most situations, increasing overall mutation probability increases the risk of emergence; however, notable exceptions arise when deleterious mutations are available. |
17 | yn7pu9i8 | are there any clinical trials available for the coronavirus | Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol OBJECTIVES: a. 1. Death. 2. Acute Myocardial Infarction [AMI]. 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]. 4. a. Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) or b. IMV in patients who at randomisation were receiving standard oxygen therapy. 5. IMV in patients who at randomisation were receiving non-invasive mechanical ventilation. b. Similar in terms of major bleeding risk. TRIAL DESIGN: Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study. PARTICIPANTS: Inpatients will be recruited from 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit. INCLUSION CRITERIA (ALL REQUIRED): 1. Age > 18 and < 80 years. 2. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material). 3. a. Respiratory Rate ≥25 breaths /min. b. Arterial oxygen saturation≤93% at rest on ambient air. c. PaO2/FiO2 ≤300 mmHg. 4. a. D-dimer >4 times the upper level of normal reference range. b. Sepsis-Induced Coagulopathy (SIC) score >4. 5. No need of IMV. EXCLUSION CRITERIA: 1. Age <18 and >80 years. 2. IMV. 3. Thrombocytopenia (platelet count < 80.000 mm3). 4. Coagulopathy: INR >1.5, aPTT ratio > 1.4. 5. Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min). 6. Known hypersensitivity to enoxaparin. 7. History of heparin induced thrombocytopenia. 8. Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations). 9. Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves). 10. Concomitant double antiplatelet therapy. 11. Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed. 12. Pregnancy or breastfeeding or positive pregnancy test. 13. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition). 14. Lack or withdrawal of informed consent. INTERVENTION AND COMPARATOR: Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 UI subcutaneously once day). Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table. This dose is commonly used in Italy when a bridging strategy is required for the management of surgery or invasive procedures in patients taking anti-vitamin K oral anticoagulants The treatment with Enoxaparin will be initiated soon after randomization (maximum allowed starting time 12h after randomization). The treatment will be administered every 12 hours in the intervention group and every 24 hours in the control group. Treatments will be administered in the two arms until hospital discharge or the primary outcomes detailed below occur. MAIN OUTCOMES: Primary Efficacy Endpoint: 1. Death. 2. Acute Myocardial Infarction [AMI]. 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]. 4. a. Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) or b. IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces. 5. Need for IMV, in patients who at randomisation were in Cpap or NIV. Time to the occurrence of each of these events will be recorded. Clinical worsening will be analysed as a binary outcome as well as a time-to-event one. Secondary Efficacy Endpoints: : 1. Death. 2. Acute Myocardial Infarction [AMI]. 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]. 4. a. Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) or b. IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces. 5. Need for IMV in patients who at randomisation were in Cpap or NIV. 6. o D-dimer level; o Plasma fibrinogen levels; o Mean Platelet Volume; o Lymphocyte/Neutrophil ratio; o IL-6 plasma levels. MORTALITY AT 30 DAYS: Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Primary safety endpoint: Decrease in haemoglobin of 2 g/dl or more; Transfusion of 2 or more units of packed red blood cells; Bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal]; Bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); Bleeding that necessitates surgical intervention. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Secondary safety endpoint: 1. Any bleeding compromising hemodynamic. 2. Spontaneous hematoma larger than 25 cm2, or 100 cm2 if there was a traumatic cause. 3. Intramuscular hematoma documented by ultrasonography. 4. Epistaxis or gingival bleeding requiring tamponade or other medical intervention. 5. Bleeding from venipuncture for >5 minutes. 6. Haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures. 7. Haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention. 8. Any other bleeding requiring temporary cessation of a study drug. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. RANDOMISATION: Randomisation (with a 1:1 randomisation ratio) will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (<75/≥75 years); 3) BMI (<30/≥30); 4) Comorbidities (0-1/>2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment. Blinding (masking) The study is conceived as open-label: patients and all health-care personnel involved in the study will be aware of the assigned group. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size is based on the hypothesis that LMWH administered at high doses versus low doses will significantly reduce the risk of clinical worsening. The overall sample size in this study is expected to be 300 with 150 in the Low-Dose LMWH control group and 150 in the High-Dose LMWH intervention group, recruited over 10-11 months. Assuming an alpha of 5% (two tailed) and a percentage of patients who experience clinical worsening in the control group being between 25% and 30%, the study will have 80% power to detect at least 50% relative reduction in the risk of death between low and high doses of heparin. TRIAL STATUS: Protocol version 1.2 of 11/05/2020. Recruitment start (expected): 08/06/2020 Recruitment finish (expected): 30/04/2021 Trial registration EudraCT 2020-001972-13, registered on April 17th, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. |
30 | usu6laaq | is remdesivir an effective treatment for COVID-19 | Finding equipoise: CEPI revises its equitable access policy Launched at Davos in January 2017 with funding from sovereign investors and philanthropic institutions, the Coalition for Epidemic Preparedness Innovations (CEPI) is an innovative partnership between public, private, philanthropic, and civil organisations whose mission is to stimulate, finance and co-ordinate vaccine development against diseases with epidemic potential in cases where market incentives fail. As of December 2019, CEPI has committed to investing up to $706 million in vaccine development. This includes 19 vaccine candidates against its priority pathogens (Lassa fever virus, Middle East respiratory syndrome coronavirus, Nipah virus, Chikungunya, Rift Valley fever) and three vaccine platforms to develop vaccines against Disease X, a novel or unanticipated pathogen. As an entity largely supported by public funds, ensuring equitable access to vaccines whose development it supports in low- and middle-income countries is CEPI's primary focus. CEPI developed an initial equitable access policy shortly after its formation, with key stakeholders expressing strong views about its content and prescriptive nature. The CEPI board instructed that it be revisited after a year. This paper describes the process of revising the policy, and how key issues were resolved. CEPI will continue to take an iterative, rather than prescriptive, approach to its policy—one that reflects the needs of multiple stakeholders and ensures it can meet its equitable access goals. |
40 | 9c449ygv | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Comparison five primer sets from different genome region of covid-1for detection of virus infection by conventional rt-pcr Background and Objectives: The new beta-coronavirus, which caused Severe Acute Respiratory Coronavirus-2 Syndrome (SARS-CoV-2), a major respiratory outbreak in Wuhan, China in December 2019, is now prevalent in many countries around the world Identifying PCR-based viruses is a well-known and relatively stable protocol Unfortunately, the high mutation rates may lead to widespread changes in viral nucleic acid sequences, and so using specific primers for PCR can be recom-mended In this study, we evaluated the power of a conventional RT-PCR to detect SARS-CoV-2 RNA among the five set primer sets Materials and Methods: The five genomic regions of the Coronavirus SARS-2 virus including Nucleocapsids (N), Enve-lope (E), RNA depended RNA Polymerase (RdRp), ORF1ab and Spike (S) were selected for primer designing A conventional RT-PCR was performed to compare sensitivity, specificity and other analytical characteristics of primers designed against two Real Time PCR commercial kits Results: The result of the comparative analysis showed that the ORF1ab, N and RdRp primers had a sensitivity, specificity and positive predictive value higher than other primers A significant difference in the analytical sensitivity between the studied primer sets in RT-PCR kits was observed Conclusion: In this study, the ORF1ab, Nucleocapsid and RdRp regions have the best primers for identifying the SARS-CoV-2 RNA between different genes that have been suggested |
5 | hmpmm9k8 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | COVID-19 and Liver Dysfunction: Current Insights and Emergent Therapeutic Strategies The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has attracted increasing worldwide attention. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions, such as the use of potentially hepatotoxic drugs and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Based on the current evidence from case reports and case series, this review article focuses on the demographic and clinical characteristics, potential mechanisms, and treatment options for COVID-19-related liver dysfunction. This review also describes the geographical and demographic distribution of COVID-19-related liver dysfunction, as well as possible underlying mechanisms linking COVID-19 to liver dysfunction, in order to facilitate future drug development, prevention, and control measures for COVID-19. |
45 | cvvzqn4e | How has the COVID-19 pandemic impacted mental health? | Coronavirus conspiracy beliefs, mistrust, and compliance with government guidelines in England BACKGROUND: An invisible threat has visibly altered the world. Governments and key institutions have had to implement decisive responses to the danger posed by the coronavirus pandemic. Imposed change will increase the likelihood that alternative explanations take hold. In a proportion of the general population there may be strong scepticism, fear of being misled, and false conspiracy theories. Our objectives were to estimate the prevalence of conspiracy thinking about the pandemic and test associations with reduced adherence to government guidelines. METHODS: A non-probability online survey with 2501 adults in England, quota sampled to match the population for age, gender, income, and region. RESULTS: Approximately 50% of this population showed little evidence of conspiracy thinking, 25% showed a degree of endorsement, 15% showed a consistent pattern of endorsement, and 10% had very high levels of endorsement. Higher levels of coronavirus conspiracy thinking were associated with less adherence to all government guidelines and less willingness to take diagnostic or antibody tests or to be vaccinated. Such ideas were also associated with paranoia, general vaccination conspiracy beliefs, climate change conspiracy belief, a conspiracy mentality, and distrust in institutions and professions. Holding coronavirus conspiracy beliefs was also associated with being more likely to share opinions. CONCLUSIONS: In England there is appreciable endorsement of conspiracy beliefs about coronavirus. Such ideas do not appear confined to the fringes. The conspiracy beliefs connect to other forms of mistrust and are associated with less compliance with government guidelines and greater unwillingness to take up future tests and treatment. |
30 | 0jzr5anm | is remdesivir an effective treatment for COVID-19 | SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. However, as SARS-CoV-2 is an emerging virus, we know little about it. In this review, we summarize the key events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the pathogen, the signs and symptoms of the infected patients as well as the possible transmission pathways of the virus. Furthermore, we also review the current knowledge on the origin and evolution of the SARS-CoV-2. We highlight bats as the potential natural reservoir and pangolins as the possible intermediate host of the virus, but their roles are waiting for further investigation. Finally, the advances in the development of chemotherapeutic options are also briefly summarized. |
37 | vj86lgri | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | In-silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs Recently a novel coronavirus (SARS-CoV-2) emerged from Wuhan, China and has infected more than 571000 people leading to more than 26000 deaths. Since SARS-CoV-2 genome sequences show similarity with those of SARS, we sought to analyze all the available SARS-CoV-2 genomes based on the insights obtained from SARS genome specifically focusing on non-coding RNAs. Here, results are presented from the dual approach i.e identifying host encoded miRNAs that might regulate viral pathogenesis as well as identifying viral encoded miRNAs that might regulate host cell signaling pathways and aid in viral pathogenesis. Analysis utilizing first approach resulted in the identification of 10 host encoded miRNAs that could target the genome of both the viruses (SARS-CoV-2 and SARS reference genome). Interestingly our analysis revealed that there is significantly higher number of host miRNAs that could target SARS-CoV-2 genome as compared to the SARS reference genome. Results from second approach involving SARS-CoV-2 and SARS reference genome identified a set of virus encoded miRNAs which might regulate host signaling pathways. Our analysis further identified a similar "GA" rich motif in SARS-CoV-2 genome that was shown to play a vital role in lung pathogenesis during severe SARS infections. Hence, we successfully identified human and virus encoded miRNAs that might regulate pathogenesis of both these coronaviruses and the fact that more number of host miRNAs could target SARS-CoV-2 genomes possibly reveal as to why this virus follows mild pathogenesis in healthy individuals. We identified non-coding sequences in SARS-CoV-2 genomes that were earlier reported to contribute towards SARS pathology. The study provides insights into the overlapping sequences among these viruses for their effective inhibition as well as identifying new drug targets that could be used for development of new antivirals. |
21 | 5innqoip | what are the mortality rates overall and in specific populations | A cohort study of 223 patients explores the clinical risk factors for the severity diagnosis of COVID-19 BACKGROUND: Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. The clinical symptoms of severe and non-severe patients vary, and the case-fatality rate (CFR) in severe COVID-19 patients is very high. However, the information on the risk factors associated with the severity of COVID-19 and of their prognostic potential is limited. METHODS: In this retrospective study, the clinical characteristics, laboratory findings, treatment and outcome data were collected and analyzed from 223 COVID-19 patients stratified into 125 non-severe patients and 98 severe patients. In addition, a pooled large-scale meta-analysis of 1646 cases was performed. RESULTS: We found that the age, gender and comorbidities are the common risk factors associated with the severity of COVID-19. For the diagnosis markers, we found that the levels of D-dimer, C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in severe group compared with the non-severe group on admission (D-Dimer: 87.3% vs. 35.3%, P<0.001; CRP, 65.1% vs. 13.5%, P<0.001; LDH: 83.9% vs. 22.2%, P<0.001; PCT: 35.1% vs. 2.2%, P<0.001), while the levels of aspartate aminotransferase (ASP) and creatinine kinase (CK) were only mildly increased. We also made a large scale meta-analysis of 1646 cases combined with 4 related literatures, and further confirmed the relationship between the COVID-19 severity and these risk factors. Moreover, we tracked dynamic changes during the process of COVID-19, and found CRP, D-dimer, LDH, PCT kept in high levels in severe patient. Among all these markers, D-dimer increased remarkably in severe patients and mostly related with the case-fatality rate (CFR). We found adjuvant antithrombotic treatment in some severe patients achieved good therapeutic effect in the cohort. CONCLUSIONS: The diagnosis markers CRP, D-dimer, LDH and PCT are associated with severity of COVID-19. Among these markers, D-dimer is sensitive for both severity and CFR of COVID-19. Treatment with heparin or other anticoagulants may be beneficial for COVID-19 patients. |
25 | vsc50fxx | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Brain natriuretic peptide to predict successful liberation from mechanical ventilation in critically ill patients: a systematic review and meta-analysis BACKGROUND: Predicting successful liberation from mechanical ventilation (MV) in critically ill patients is challenging. Brain natriuretic peptide (BNP) has been proposed to help guide decision-making for readiness to liberate from MV following a spontaneous breathing trial (SBT). METHODS: We performed a systematic review and meta-analysis of randomized and prospective observational studies that measured BNP levels at the time of SBT in patients receiving MV. The primary endpoint was successful liberation from MV (absence of reintubation or non-invasive ventilation at 48 h). Statistical analyses included bi-variate and Moses-Littenberg models and DerSimonian-Laird pooling of areas under ROC curve (AUROC). RESULTS: A total of 731 articles were screened. Eighteen adult and 2 pediatric studies were fulfilled pre-specified eligibility. The measure of the relative variation of BNP during SBT (ΔBNP%) after exclusion of SBT failure by clinical criteria in adults yielded a sensitivity and specificity of 0.889 [0.831–0.929] and 0.828 [0.730–0.896] for successful liberation from MV, respectively, with a pooled AUROC of 0.92 [0.88–0.97]. The pooled AUROC for any method of analysis for absolute variation of BNP (ΔBNP), pre-SBT BNP, and post-SBT BNP were 0.89 [0.83–0.95], 0.77 [0.63–0.91], and 0.85 [0.80–0.90], respectively. CONCLUSION: The relative change in BNP during a SBT has potential value as an incremental tool after successful SBT to predict successful liberation from MV in adults. There is insufficient data to support the use of BNP in children or as an alternate test to clinical indices of SBT, or the use of ΔBNP, BNP-pre, and BNP-post as an alternate or incremental test. TRIAL REGISTRATION: PROSPERO CRD42018087474 (6 February 2018) |
10 | 1uwrdwv5 | has social distancing had an impact on slowing the spread of COVID-19? | Enabling and Enforcing Social Distancing Measures using Smart City and ITS Infrastructures: A COVID-19 Use Case Internet of Things is a revolutionary domain that has the caliber to impact our lives and bring significant changes to the world. Several IoT applications have been envisioned to facilitate data driven and smart application for the user. Smart City and Intelligent Transportation System (ITS) offer a futuristic vision of smart, secure and safe experience to the end user, and at the same time efficiently manage the sparse resources and optimize the efficiency of city operations. However, outbreaks and pandemics like COVID-19 have revealed limitations of the existing deployments, therefore, architecture, applications and technology systems need to be developed for swift and timely enforcement of guidelines, rules and government orders to contain such future outbreaks. This work outlines novel architecture, potential use-cases and some future directions in developing such applications using Smart City and ITS. |
38 | 4ijxyro4 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Management of Acute Severe Ulcerative Colitis in a Pregnant Woman With COVID-19 Infection: A Case Report and Review of the Literature First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively. |
45 | jmgam6sy | How has the COVID-19 pandemic impacted mental health? | The potential impact of COVID-19 on psychosis: A rapid review of contemporary epidemic and pandemic research Abstract The COVID-19 outbreak may profoundly impact population mental health because of exposure to substantial psychosocial stress. An increase in incident cases of psychosis may be predicted. Clinical advice on the management of psychosis during the outbreak needs to be based on the best available evidence. We undertook a rapid review of the impact of epidemic and pandemics on psychosis. Fourteen papers met inclusion criteria. Included studies reported incident cases of psychosis in people infected with a virus of a range of 0.9% to 4%. Psychosis diagnosis was associated with viral exposure, treatments used to manage the infection, and psychosocial stress. Clinical management of these patients, where adherence with infection control procedures is paramount, was challenging. Increased vigilance for psychosis symptoms in patients with COVID-19 is warranted. How to support adherence to physical distancing requirements and engagement with services in patients with existing psychosis requires careful consideration. Registration details: https://osf.io/29pm4. |
8 | cpc6v40g | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Severe acute respiratory syndrome-associated coronavirus infection in Toronto children: a second look. OBJECTIVES During the severe acute respiratory syndrome outbreak of 2003, there was an impetus to provide clinical information to the medical community in a timely manner. Accordingly, a preliminary report of our experience of suspected severe acute respiratory syndrome-associated coronavirus infections in children was published without microbiological findings. This report provides an update on pediatric severe acute respiratory syndrome-associated coronavirus infections in Toronto, Ontario, Canada, that includes microbiological findings. METHODS All of the children admitted to the Hospital for Sick Children between March 14 and June 15, 2003, with suspect severe acute respiratory syndrome-associated coronavirus infection were included. A proven case was defined as one that fulfilled the clinical criteria for suspect severe acute respiratory syndrome-associated coronavirus infection and demonstrated a serologic response to severe acute respiratory syndrome-associated coronavirus. Serology results, from a neutralizing antibody assay, were considered positive if the sera inhibited the development of a severe acute respiratory syndrome-associated coronavirus-specific cytopathic effect at a dilution of > or =1:8. RESULTS Neutralizing antibody to severe acute respiratory syndrome-associated coronavirus was demonstrated in 8 of 25 children admitted with suspect severe acute respiratory syndrome-associated coronavirus infection. In 3 of these 8 children, severe acute respiratory syndrome-associated coronavirus was also detected by reverse-transcription polymerase chain reaction in the stool. All 8 had documented exposure to > or =1 severe acute respiratory syndrome-associated coronavirus-infected adults residing in the same household. Exposure that was limited to visiting a Toronto hospital at which severe acute respiratory syndrome-associated coronavirus-infected patients were admitted or travel from a country in which severe acute respiratory syndrome had been reported did not result in documented infection in any of our cases. On the basis of our clinical case definition, 6 of 8 microbiologically confirmed case had been classified as having probable severe acute respiratory syndrome-associated coronavirus infection. Clinical disease was mild, nonspecific, and self-limited and was indistinguishable from that reported with other common respiratory viruses. CONCLUSIONS The factor most strongly associated with severe acute respiratory syndrome-associated coronavirus infection in Toronto children was a history of close contact with an adult severe acute respiratory syndrome-associated coronavirus case. This serves to reinforce the importance of routinely obtaining a thorough epidemiologic travel and exposure history for all subjects with suspected infectious diseases. |
21 | edzujcsa | what are the mortality rates overall and in specific populations | Forecasting the Impact of Coronavirus Disease During Delivery Hospitalization: An Aid for Resources Utilization Abstract Background The ongoing Coronavirus disease (COVID-19) pandemic has severely impacted the United States. In cases of infectious disease outbreak, forecasting models are often developed for resources utilization. Pregnancy and delivery pose unique challenges, given the altered maternal immune system and the fact that the majority of American women choose to deliver in the hospital setting. Objectives The aim of our study is to forecast the incidence of COVID-19 in general population and to forecast the overall incidence, severe cases, critical cases and fatal COVID-19 cases during delivery hospitalization in the United States. Study design We use a phenomenological model with generalized logistic growth models to forecast the incidence of COVID-19 in the United States from 4/15/2020 – 12/31/2020. Incidence data from 3/1/2020 – 4/14/2020 were used to provide best-fit model solution. Subsequently, Monte-Carlo simulation was performed for each week from 3/1/2020 – 12/31/2020 to estimate the incidence of COVID-19 in delivery hospitalizations using the available data estimate. Results From 3/1/2020 – 12/31/2020, our model forecasted a total of 860,475 cases of COVID-19 in general population across the United States. The cumulative incidence for COVID-19 during delivery hospitalization is anticipated to be 16,601 (95% CI, 9,711 – 23,491) cases. Among those, 3,308 (95% CI, 1,755 – 4,861) cases are expected to be severe, 681 (95% CI, 1324 – 1,038) critical and 52 (95% CI, 23 – 81) maternal mortality. Assuming similar baseline maternal mortality rate as the year of 2018, we projected an increase in maternal mortality rate in the US to at least 18.7 (95% CI, 18.0 – 19.5) deaths per 100,000 live birth as a direct result of COVID-19. Conclusions COVID-19 infection in pregnant women is expected to severely impact obstetrical care. From 3/1/2020 – 12/31/2020, we project 3,308 severe and 681 critical cases, with about 52 COVID-19 related maternal mortalities during delivery hospitalization in the United States. These data might be helpful for counseling and resource allocation. |
19 | 7mts2lk4 | what type of hand sanitizer is needed to destroy Covid-19? | COVID-19 and forced alcohol abstinence in India: The dilemmas around ethics and rights In response to the COVID-19 pandemic, as with other countries across the world, the Central and State Governments of India initiated several measures to slow down the spread of the virus and to 'flatten the curve'. One such measure was a 'total lockdown' for several weeks across the country. A complex and unexpected outcome of the lockdown which has medical, ethical, economic, and social dimensions is related to alcohol consumption. The lockdown and consequent acute non-availability of alcohol resulted in people with alcohol dependence going into withdrawals, black marketing of alcohol, and in extreme cases suicide resulting from the alleged frustration of not having access to alcohol. The health dilemmas around this situation are biological (e.g. pushing people into risky situations-potentially fatal alcohol withdrawal, consumption of illicit or other non-consumable alcohol) and psychosocial (e.g. isolation increasing the risk of relapses, loss of control over the decision to abstain which can be detrimental to recovery, restriction of access to services for alcohol problems). The legal and rights-related dilemmas are centred around whether States have the right to impinge on individual autonomy on the grounds of public health, the capacity of the health systems to provide appropriate services to cope with those who will struggle with the unavailability of alcohol, the constitutionality of the Central government's impinging on jurisdiction of states under the guise of a health emergency caused by the pandemic, and the ability of the State to make unbiased decisions about this issue when it is highly dependent on the revenue from the sale of alcohol and associated industries. The way forward could be a pragmatic and utilitarian approach involving continued access to alcohol, while observing all physical distancing norms necessary during the pandemic, for those who want to continue drinking; and implementing innovative measures such as tele-counselling for those who wish not to return back to drinking. |
47 | e7tkfgyg | what are the health outcomes for children who contract COVID-19? | G6PD Deficiency Overrepresented Among Pediatric COVID-19 Cases in One Saudi Children Hospital Fluorescent spot test for glucose-6-phosphate dehydrogenase (G6PD) deficiency was performed in 5 boys and 14 girls who had confirmed COVID-19. Out of those, 4 (80%) boys and 5 (36%) girls were found to be G6PD deficient. |
32 | s5fz81vp | Does SARS-CoV-2 have any subtypes, and if so what are they? | Emerging and reemerging respiratory viral infections up to Covid-19 Infectious diseases remain as the significant causes of human and animal morbidity and mortality, leading to extensive outbreaks and epidemics. Acute respiratory viral diseases claim over 4 million deaths and cause millions of hospitalizations in developing countries every year. Emerging viruses, especially the RNA viruses, are more pathogenic since most people have no herd immunity. The RNA viruses can adapt to the rapidly changing global and local environment due to the high error rate of their polymerases that replicate their genomes. Currently, coronavirus disease 2019 (COVID-19) is determined as an u28a9 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in 2019 in u28ac. Herein we discuss emerging and reemerging respiratory viral infections till to SARS-CoV-2. |
2 | nux8g0cm | how does the coronavirus respond to changes in the weather | Novel Coronavirus and Related Public Health Interventions Are Negatively Impacting Mental Health Services |
45 | unhdfzpc | How has the COVID-19 pandemic impacted mental health? | Decreased utilization of mental health emergency service during the COVID-19 pandemic During the rapid rise of the COVID-19 pandemic, a reduction of the numbers of patients presenting to emergency departments has been observed. We present an early study from a German psychiatric hospital to assess the dynamics of mental health emergency service utilization rates during the COVID-19 pandemic. Our results show that the numbers of emergency presentations decreased, and a positive correlation between these numbers and mobility of the general public suggests an impact of extended measures of social distancing. This finding underscores the necessity of raising and sustaining awareness regarding the threat to mental health in the context of the pandemic. |
38 | vsb17qt2 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment The COVID-19 pandemia is affecting people worldwide. Most of the patients suffered of a respiratory disease that will progress to an acute respiratory distress syndrome (ARDS). SARS-CoV-2 pneumonia severely ill patients, develop a systemic inflammatory response with a Cytokine Release Syndrome (CRS), that is characterized by a sudden increase in several pro-inflammatory cytokines, mainly IL-1, IL-6 and TNF-alfa by activated macrophages (M1 phenotype). Blocking IL-6 with tocilizumab and using respirator equipment seems to be a very important issue in this (SARS-CoV-2) pneumonia, but not all patients are referred to such treatments. Low dose radiotherapy (0,5 Gy), is an evidence-based anti-inflammatory treatment, that could modify the immune landscape in the lung affected of SARS-CoV-2 pneumonia, through macrophages polarization to alternatively activated Macrophages (M2 phenotype). Radiation-induced cancer risk could be assumed due to the very low dose used, the advanced age of the patients and the life-threatening condition of SARS-Cov2 pneumonia. LDRT is a cost-effective non-toxic treatment already available in most general hospitals. This fact allows that it would be used for the large number of patients that will suffer this disease, and that would not receive specific anti-IL-6 treatments in ICUs in low and middle income countries. |
5 | 4s57ls6y | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Identification of natural compounds with antiviral activities against SARS-associated coronavirus Abstract More than 200 Chinese medicinal herb extracts were screened for antiviral activities against Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay for virus-induced cytopathic effect (CPE). Four of these extracts showed moderate to potent antiviral activities against SARS-CoV with 50% effective concentration (EC50) ranging from 2.4±0.2 to 88.2±7.7μg/ml. Out of the four, Lycoris radiata was most potent. To identify the active component, L. radiata extract was subjected to further fractionation, purification, and CPE/MTS assays. This process led to the identification of a single substance lycorine as an anti-SARS-CoV component with an EC50 value of 15.7±1.2nM. This compound has a CC50 value of 14980.0±912.0nM in cytotoxicity assay and a selective index (SI) greater than 900. The results suggested that four herbal extracts and the compound lycorine are candidates for the development of new anti-SARS-CoV drugs in the treatment of SARS. |
37 | 82x7gq5z | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Molecular tracing of SARS-CoV-2 in Italy in the first three months of the epidemic The aim of this study is the characterization and genomic tracing by phylogenetic analyses of 59 new SARS-CoV-2 Italian isolates obtained from patients attending clinical centres in North and Central Italy until the end of April 2020. All but one of the newly characterized genomes belonged to the lineage B.1, the most frequently identified in European countries, including Italy. Only a single sequence was found to belong to lineage B. A mean of 6 nucleotide substitutions per viral genome was observed, without significant differences between synonymous and non-synonymous mutations, indicating genetic drift as a major source for virus evolution. tMRCA estimation confirmed the probable origin of the epidemic between the end of January and the beginning of February with a rapid increase in the number of infections between the end of February and mid-March. Since early February, an effective reproduction number (Re) greater than 1 was estimated, which then increased reaching the peak of 2.3 in early March, confirming the circulation of the virus before the first COVID-19 cases were documented. Continuous use of state-of-the-art methods for molecular surveillance is warranted to trace virus circulation and evolution and inform effective prevention and containment of future SARS-CoV-2 outbreaks. |
7 | bkp5pvir | are there serological tests that detect antibodies to coronavirus? | Use of viral lysate antigen combined with recombinant protein in Western immunoblot assay as confirmatory test for serodiagnosis of severe acute respiratory syndrome. A Western immunoblot assay for confirmatory serodiagnosis of severe acute respiratory syndrome (SARS) was developed utilizing viral lysate antigens combined with a recombinant nucleocapsid protein, GST-N (glutathione S-transferase-nucleocapsid) of the SARS coronavirus (SARS-CoV). The viral lysate antigens were separated by electrophoresis and transblotted onto nitrocellulose membranes. The resultant membrane was subsequently added with the GST-N recombinant protein at a specific location. The positions of bands corresponding to some of the structural proteins immobilized on the membrane were then located and verified with mouse or rabbit antisera specific to the respective proteins. The Western immunoblot assay was able to detect antibodies to SARS-CoV in all 40 serum specimens from SARS patients and differentiate the SARS-positive samples from those of the healthy donor or non-SARS patient controls (150 samples) when set criteria were followed. In addition, when the immunoblot was used to test samples considered falsely positive by an in-house-developed SARS-specific enzyme-linked immunosorbent assay, band patterns different from those with samples from SARS patients were obtained. |
1 | lxakf79k | what is the origin of COVID-19 | Forecasting the dynamics of COVID-19 Pandemic in Top 15 countries in April 2020: ARIMA Model with Machine Learning Approach We here predicted some trajectories of COVID-19 in the coming days (until April 30, 2020) using the most advanced Auto-Regressive Integrated Moving Average Model (ARIMA). Our analysis predicted very frightening outcomes, which defines to worsen the conditions in Iran, entire Europe, especially Italy, Spain, and France. While South Korea, after the initial blast, has come to stability, the same goes for the COVID-19 origin country China with more positive recovery cases and confirm to remain stable. The United States of America (USA) will come as a surprise and going to become the epicenter for new cases during the mid-April 2020. Based on our predictions, public health officials should tailor aggressive interventions to grasp the power exponential growth, and rapid infection control measures at hospital levels are urgently needed to curtail the COVID-19 pandemic. |
12 | qt2ddseg | what are best practices in hospitals and at home in maintaining quarantine? | Effective strategies to prevent coronavirus disease-2019 (COVID-19) outbreak in hospital |
41 | rndu5ake | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Using rapid online surveys to assess perceptions during infectious disease outbreaks: a cross-sectional survey on Covid-19 among the general public in the United States and United Kingdom Background: Given the extensive time needed to conduct a nationally representative household survey and the commonly low response rate in phone surveys, rapid online surveys may be a promising method to assess and track knowledge and perceptions among the general public during fast-moving infectious disease outbreaks. Objective: To apply rapid online surveying to determine knowledge and perceptions of coronavirus disease 2019 (Covid-19) among the general public in the United States (US) and the United Kingdom (UK). Methods: An online questionnaire was administered to 3,000 adults residing in the US and 3,000 adults residing in the UK who had registered with Prolific Academic to participate in online research. Strata by age (18 - 27, 28 - 37, 38 - 47, 48 - 57, or >=58 years), sex (male or female), and ethnicity (White, Black or African American, Asian or Asian Indian, Mixed, or "Other"), and all permutations of these strata, were established. The number of participants who could enrol in each of these strata was calculated to reflect the distribution in the US and UK general population. Enrolment into the survey within the strata was on a first-come, first-served basis. Participants completed the questionnaire between February 23 and March 2 2020. Results: 2,986 and 2,988 adults residing in the US and the UK, respectively, completed the questionnaire. 64.4% (1,924/2,986) of US and 51.5% (1,540/2,988) of UK participants had a tertiary education degree. 67.5% (2,015/2,986) of US participants had a total household income between $20,000 and $99,999, and 74.4% (2,223/2,988) of UK participants had a total household income between GBP15,000 and GBP74,999. US and UK participants' median estimate for the probability of a fatal disease course among those infected with SARS-CoV-2 was 5.0% (IQR: 2.0% - 15.0%) and 3.0% (IQR: 2.0% - 10.0%), respectively. Participants generally had good knowledge of the main mode of disease transmission and common symptoms of Covid-19. However, a substantial proportion of participants had misconceptions about how to prevent an infection and the recommended care-seeking behavior. For instance, 37.8% (95% CI: 36.1% - 39.6%) of US and 29.7% (95% CI: 28.1% - 31.4%) of UK participants thought that wearing a common surgical mask was 'highly effective' in protecting them from acquiring Covid-19. 25.6% (95% CI: 24.1% - 27.2%) of US and 29.6% (95% CI: 28.0% - 31.3%) of UK participants thought it prudent to refrain from eating at Chinese restaurants. Around half (53.8% [95% CI: 52.1% - 55.6%] of US and 39.1% [95% CI: 37.4% - 40.9%] of UK participants) thought that children were at an especially high risk of death when infected with SARS-CoV-2. Conclusions: The distribution of participants by total household income and education followed approximately that of the general population. The findings from this online survey could guide information campaigns by public health authorities, clinicians, and the media. More broadly, rapid online surveys could be an important tool in tracking the public's knowledge and misperceptions during rapidly moving infectious disease outbreaks. |
17 | uohbxoeb | are there any clinical trials available for the coronavirus | Remdesivir for the Treatment of Covid-19 — Preliminary Report BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.) |
38 | z4hkw17g | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Why is SARS-CoV-2 infection more severe in obese men? The gut lymphatics - lung axis hypothesis Consistent observations report increased severity of SARS-CoV-2 infection in overweight men with cardiovascular factors. As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. SARS-CoV2 presents the ability to infect epithelial cells of the respiratory tract as well as the intestinal tract. Several factors may increase intestinal permeability including, direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2- associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPS (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). The pro-inflammatory cytokines produced by the mesentery fat mediates systemic inflammation and aggravate acute respiratory distress syndrome (ARDS) through the mesenteric lymph drainage. |
30 | j3b964oz | is remdesivir an effective treatment for COVID-19 | An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog β-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N(4)-hydroxycytidine-5′-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses. |
3 | d3oyf7j0 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Immunization with Live Human Rhinovirus (HRV) 16 Induces Protection in Cotton Rats against HRV14 Infection Human rhinoviruses (HRVs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against HRVs are available to prevent or mitigate HRV infection. There are more than 150 antigenically heterogeneous HRV serotypes, with ∼90 HRVs belonging to major group species A and B. Development of small animal models that are susceptible to infection with major group HRVs would be beneficial for vaccine research. Previously, we showed that the cotton rat (Sigmodon hispidus) is semi-permissive to HRV16 (major group, species HRV-A virus) infection, replicating in the upper and lower respiratory tracts with measurable pathology, mucus production, and expression of inflammatory mediators. Herein, we report that intranasal infection of cotton rats with HRV14 (major group, species HRV-B virus) results in isolation of infectious virus from the nose and lung. Similar to HRV16, intramuscular immunization with live HRV14 induces homologous protection that correlated with high levels of serum neutralizing antibodies. Vaccination and challenge experiments with HRV14 and HRV16 to evaluate the development of cross-protective immunity demonstrate that intramuscular immunization with live HRV16 significantly protects animals against HRV14 challenge. Determination of the immunological mechanisms involved in heterologous protection and further characterization of infection with other major HRV serotypes in the cotton rat could enhance the robustness of the model to define heterotypic relationships between this diverse group of viruses and thereby increase its potential for development of a multi-serotype HRV vaccine. |
7 | zzljrkbf | are there serological tests that detect antibodies to coronavirus? | The diagnostic value of joint detection of serum IgMand IgG antibodies to 2019-nCoV in 2019-nCoV infection/ 中华检验医学杂志 Objective@#To investigate the diagnostic value of immunoglobulin M (IgM) and immunoglobulin G(IgG) antibodies to 2019 Novel Coronavirus (2019-nCoV) in 2019-nCoV infection.@*Method@#This is a retrospective study. Serum samples were collected from 284 patients including outpatients and inpatients in the Renmin Hospital of Wuhan University from January 20, 2020 to February 17, 2020. Among them 205 cases were 2019-nCoV infected patients, including 186 cases confirmed with nucleic acid test and 19 cases diagnosed by clinical symptoms and CT characteristics according to "the New Coronavirus Pneumonia Control Protocol (5th edition)" . A total of 79 subjects with other diseases but negative to 2019-nCoV infection were recruited as control group. Serum IgM and IgG antibodies to 2019-nCoV were measured with fully automated immunoassay technology for all subjects. Statistical significance between 2019-nCoV antibodies test and 2019-nCoV nucleic acid test was determined using the χ2 tests.@*Result@#The sensitivity of serum IgM and IgG antibodies to 2019-nCoV were 70.24%(144/205) and 96.10%(197/205) respectively and the specificity were 96.20%(76/79) and 92.41%(73/79) respectively. The positive and negative predictive values of 2019-nCoV antibodies were 95.63%(197/206) and 91.03% (71/78) respectively, and the positive and negative predictive values of 2019-nCoV nucleic acid test were 100%(186/186) and 80.61%(79/98) respectively. The total coincidence rate of diagnosing 2019-nCoV infection between antibody tests and nucleic acid test for 2019-nCoV were 88.03%(250/284).@*Conclusion@#Joint detection of serum IgM and IgG antibodies to 2019-nCoV is an effective screening and diagnostic indicators for 2019-nCoV infection, and an effective complement to the false negative results to nucleic acid test. |
50 | xemxtssg | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | N6-methyladenosine regulates PEDV replication and host gene expression Methylation of the N6 position of adenosine (m(6)A) is a widespread RNA modification that is critical for various physiological and pathological processes. Although this modification was also found in the RNA of several viruses almost 40 years ago, its biological functions during viral infection have been elucidated recently. Here, we investigated the effects of viral and host RNA methylation during porcine epidemic diarrhea virus (PEDV) infection. The results demonstrated that the m(6)A modification was abundant in the PEDV genome and the host methyltransferases METTL3 and METTL14 and demethylase FTO were involved in the regulation of viral replication. The knockdown of the methyltransferases increased PEDV replication while silencing the demethylase decreased PEDV output. Moreover, the proteins of the YTHDF family regulated the PEDV replication by affecting the stability of m(6)A-modified viral RNA. In particular, PEDV infection could trigger an increasement of m(6)A in host RNA and decrease the expression of FTO. The m(6)A modification sites in mRNAs and target genes were also altered during PEDV infection. Additionally, part of the host responses to PEDV infection was controlled by m(6)A modification, which could be reversed by the expression of FTO. Taken together, our results identified the role of m(6)A modification in PEDV replication and interactions with the host. |
9 | py6qu4tl | how has COVID-19 affected Canada | Teicoplanin potently blocks the cell entry of 2019-nCoV Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection. |
4 | olior5vk | what causes death from Covid-19? | Community pharmacists and communication in the time of COVID-19: Applying the health belief model Abstract The emergence of the novel coronavirus disease (COVID-19) pandemic presents an unprecedented health communications challenge. Healthcare providers should reinforce behaviors that limit the spread of the pandemic, including social distancing and remaining in the home whenever possible. Formal communications toolkits may not be prepared in a timely fashion. Community pharmacists can reinforce mitigation behaviors by applying the health belief model (HBM). This commentary provides an overview of the HBM and offers suggestions on how community pharmacists can use it as a guide to patient communication in these uncertain contexts. |
10 | rbku9x39 | has social distancing had an impact on slowing the spread of COVID-19? | Society of Cardiovascular Computed Tomography guidance for use of cardiac computed tomography amidst the COVID-19 pandemic Endorsed by the American College of Cardiology The world is currently suffering through a pandemic outbreak of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) known as Coronavirus Disease 2019 (COVID-19). The United States (US) Centers for Disease Control and Prevention (CDC) currently advises medical facilities to "reschedule non-urgent outpatient visits as necessary". The European Centre for Disease Prevention and Control, the United Kingdom National Health Service and several other international agencies covering Asia, North America and most regions of the world have recommended similar "social distancing" measures. The Society of Cardiovascular Computed Tomography (SCCT) offers guidance for cardiac CT (CCT) practitioners to help implement these international recommendations in order to decrease the risk of COVID-19 transmission in their facilities while deciding on the timing of outpatient and inpatient CCT exams. This document also emphasizes SCCT's commitment to the health and well-being of CCT technologists, imagers, trainees, and research community, as well as the patients served by CCT. |
7 | w6ei0g42 | are there serological tests that detect antibodies to coronavirus? | 3D printed circuit splitter and flow restriction devices for multiple patient lung ventilation using one anaesthesia workstation or ventilator. The ongoing pandemic of SARS-CoV-2 virus and its associated disease COVID-19 has resulted in widespread ventilator shortages and rationing of care. Massive global supply chain disruption and quarantine measures prevent equipment movement and medical device production. |
41 | ncfo2v89 | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | The association of race and COVID-19 mortality BACKGROUND: COVID-19 mortality disproportionately affects the Black population in the United States (US). To explore this association a cohort study was undertaken. METHODS: We assembled a cohort of 505,992 patients receiving ambulatory care at Bronx Montefiore Health System (BMHS) between 1/1/18 and 1/1/20 to evaluate the relative risk of hospitalization and death in two time-periods, the pre-COVID time-period (1/1/20–2/15/20) and COVID time-period (3/1/20–4/15/20). COVID testing, hospitalization and mortality were determined with the Black and Hispanic patient population compared separately to the White population using logistic modeling. Evaluation of the interaction of pre-COVID and COVID time periods and race, with respect to mortality was completed. FINDINGS: A total of 9,286/505,992 (1.8%) patients were hospitalized during either or both pre-COVID or COVID periods. Compared to Whites the relative risk of hospitalization of Black patients did not increase in the COVID period (p for interaction=0.12). In the pre- COVID period, compared to Whites, the odds of death for Blacks and Hispanics adjusted for comorbidity was statistically equivalent. In the COVID period compared to Whites the adjusted odds of death for Blacks was 1.6 (95% CI 1.2–2.0, p = 0.001). There was a significant increase in Black mortality risk from pre-COVID to COVID periods (p for interaction=0.02). Adjustment for relevant clinical and social indices attenuated but did not fully explain the observed difference in Black mortality. INTERPRETATION: The BMHS COVID experience demonstrates that Blacks do have a higher mortality with COVID incompletely explained by age, multiple reported comorbidities and available metrics of sociodemographic disparity. FUNDING: N/A |
24 | c2jm0g88 | what kinds of complications related to COVID-19 are associated with diabetes | Association of Diabetes Mellitus with Disease Severity and Prognosis in COVID-19: A Retrospective Cohort Study Abstract The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China, and was characterized as a pandemic by the World Health Organization. Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19. |
34 | aei1zpim | What are the longer-term complications of those who recover from COVID-19? | Assessing the Impact of COVID-19 on the Objective and Analysis of Oncology Clinical Trials -- Application of the Estimand Framework COVID-19 outbreak has rapidly evolved into a global pandemic. The impact of COVID-19 on patient journeys in oncology represents a new risk to interpretation of trial results and its broad applicability for future clinical practice. We identify key intercurrent events that may occur due to COVID-19 in oncology clinical trials with a focus on time-to-event endpoints and discuss considerations pertaining to the other estimand attributes introduced in the ICH E9 addendum. We propose strategies to handle COVID-19 related intercurrent events, depending on their relationship with malignancy and treatment and the interpretability of data after them. We argue that the clinical trial objective from a world without COVID-19 pandemic remains valid. The estimand framework provides a common language to discuss the impact of COVID-19 in a structured and transparent manner. This demonstrates that the applicability of the framework may even go beyond what it was initially intended for. |
23 | n6pov9c6 | what kinds of complications related to COVID-19 are associated with hypertension? | Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens Aims: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). Methods and Results: All adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days. ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection. The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD). The youngest deceased person aged 44 years. Among hypertensive subjects (n=543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively. At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50-1.49). Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40-2.23), diabetes (AOR: 1.52; 1.05-2.18), CVD (AOR: 1.88; 1.32-2.70) and COPD (1.88; 1.11-3.20). Only gender, age and diabetes also predicted very severe/lethal disease. Conclusion: No association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians. |
24 | 3mpqtfej | what kinds of complications related to COVID-19 are associated with diabetes | Voice from China: nomenclature of the novel coronavirus and related diseases |
8 | 0e5l9o64 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Symptoms, Stress, and HIV-Related Care Among Older People Living with HIV During the COVID-19 Pandemic, Miami, Florida |
12 | 329r3m0r | what are best practices in hospitals and at home in maintaining quarantine? | Active case finding with case management: the key to tackling the COVID-19 pandemic COVID-19 was declared a pandemic by WHO on March 11, 2020, the first non-influenza pandemic, affecting more than 200 countries and areas, with more than 5·9 million cases by May 31, 2020. Countries have developed strategies to deal with the COVID-19 pandemic that fit their epidemiological situations, capacities, and values. We describe China's strategies for prevention and control of COVID-19 (containment and suppression) and their application, from the perspective of the COVID-19 experience to date in China. Although China has contained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and nearly stopped indigenous transmission, a strong suppression effort must continue to prevent re-establishment of community transmission from importation-related cases. We believe that case finding and management, with identification and quarantine of close contacts, are vitally important containment measures and are essential in China's pathway forward. We describe the next steps planned in China that follow the containment effort. We believe that sharing countries' experiences will help the global community manage the COVID-19 pandemic by identifying what works in the struggle against SARS-CoV-2. |
26 | 0ubbqima | what are the initial symptoms of Covid-19? | Sequential symptomatic analysis in probable severe acute respiratory syndrome cases() STUDY OBJECTIVE: Previous reports on severe acute respiratory syndrome (SARS) described mainly its symptoms. However, the time sequence of symptom development was rarely discussed. The objective of this study is to chronologically document the time sequence of symptom development in probable SARS cases and compare that of the febrile non-SARS cases, thus providing valuable information for early recognition of the disease. METHODS: This prospective, descriptive, cohort study was conducted in an academic university hospital in Taipei, Taiwan, from March 14 through May 12, 2003. Patients presenting to the emergency department (ED) with a temperature of at least 38.0°C (≥100.3°F) and exposure history were evaluated with a structured protocol. Detailed time sequences of individual symptoms were recorded, and chest radiography and laboratory test results were obtained. Probable SARS cases were determined by the Center of Disease Control Taiwan. Children younger than 15 years and suspected SARS patients with negative polymerase chain reaction results were excluded from final analysis. RESULTS: Seventy-nine SARS and 220 non-SARS cases were analyzed. The major clinical symptoms of SARS patients on ED presentation were myalgia, loose stool or diarrhea, nonproductive cough or dyspnea, headache, and chills. Upper airway symptoms, including rhinorrhea and sore throat, were rarely seen in the SARS patients but were common in the non-SARS group. Characteristic symptom sequence, consisting of initial fever accompanied by diarrhea and myalgia and then progressive respiratory symptoms, was identified in 55 SARS patients (69.6%; 95% confidence interval [CI] 0.60 to 0.80) but only 7 (3.2%; 95% CI 0.008 to 0.05) non-SARS patients. Chest radiographic abnormality may precede lower respiratory tract symptoms in some SARS patients. CONCLUSION: During an outbreak period, recognition of possible SARS cases depends on the heightened awareness of its clinical presentation. Aside from travel and contact history, the time sequence of the accompanying symptoms of SARS should help first-line physicians screen SARS patients at an early stage. |
45 | xqzac814 | How has the COVID-19 pandemic impacted mental health? | Caution when linking COVID-19 to mental health consequences |
1 | yh1d2g75 | what is the origin of COVID-19 | Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats Abstract Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV). However, a recent study found that one-third of FIPV isolates have an intact 3c and suggested that it is not solely involved in FIP but is essential for intestinal replication. In order to confirm these assumptions, 27 fecal and 32 FIP coronavirus isolates were obtained from resident or adopted cats from a large metropolitan shelter during 2008–2009 and their 3a–c, E, and M genes sequenced. Forty percent of coronavirus isolates from FIP tissues had an intact 3c gene, while 60% had mutations that truncated the gene product. The 3c genes of fecal isolates from healthy cats were always intact. Coronavirus from FIP diseased tissues consistently induced FIP when given either oronasally or intraperitoneally (i.p.), regardless of the functional status of their 3c genes, thus confirming them to be FIPVs. In contrast, fecal isolates from healthy cats were infectious following oronasal infection and shed at high levels in feces without causing disease, as expected for FECVs. Only one in three cats shed FECV in the feces following i.p. infection, indicating that FECVs can replicate systemically, but with difficulty. FIPVs having a mutated 3c were not shed in the feces following either oronasal or i.p. inoculation, while FIPVs with intact 3c genes were shed in the feces following oronasal but not i.p. inoculation. Therefore, an intact 3c appears to be essential for intestinal replication. Although FIPVs with an intact 3c were shed in the feces following oronasal inoculation, fecal virus from these cats was not infectious for other cats. Attempts to identify potential FIP mutations in the 3a, 3b, E, and M were negative. However, the 3c gene of FIPVs, even though appearing intact, contained many more non-synonymous amino acid changes in the 3′ one-third of the 3c protein than FECVs. An attempt to trace FIPV isolates back to enteric strains existing in the shelter was only partially successful due to the large region over which shelter cats and kittens originated, housing conditions prior to acquisition, and rapid movement through the shelter. No evidence could be found to support a recent theory that FIPVs and FECVs are genetically distinct. |
23 | hsxwz798 | what kinds of complications related to COVID-19 are associated with hypertension? | Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up Summary Objective To investigate the characteristics and prognostic factors in the elderly patients with COVID-19. Methods Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included. The primary outcomes were death and survival till March 5. Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes. Cox regression was performed for prognostic factors. Results 339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases. Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%). Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%). Lymphocytopenia was a common laboratory finding (63.2%). Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%). Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead. Shorter length of stay was found for the dead compared with the survivors (5 (3–8) vs. 28 (26–29), P < 0.001). Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death. And a high level of lymphocytes was predictive of better outcome (HR 0.10, P < 0.001). Conclusions High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients. Rapid disease progress was noted in the dead with a median survival time of 5 days after admission. Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome. Close monitoring and timely treatment should be performed for the elderly patients at high risk. |
43 | 2py5mg3f | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Love at the time of the Covid-19 pandemic: preliminary results of an online survey conducted during the quarantine in Italy |
13 | izxqtril | what are the transmission routes of coronavirus? | Relative contributions of transmission routes for COVID-19 among healthcare personnel providing patient care. The routes of COVID-19 transmission to healthcare personnel from infected patients is the subject of debate, but is critical to the selection of personal protective equipment. The objective of this paper was to explore the contributions of three transmission routes-contact, droplet, and inhalation-to the risk of occupationally acquired COVID-19 infection among healthcare personnel (HCP). The method was quantitative microbial risk assessment, and an exposure model, where possible model parameters were based on data specific to the SARS-CoV-2 virus when available. The key finding was that droplet and inhalation transmission routes predominate over the contact route, contributing 35%, 57%, and 8.2% of the probability of infection, on average, without use of personal protective equipment. On average, 80% of inhalation exposure occurs when HCP are near patients. The relative contribution of droplet and inhalation depends upon the emission of SARS-CoV-2 in respirable particles (<10 µm) through exhaled breath, and inhalation becomes predominant, on average, when emission exceeds five gene copies per min. The predicted concentration of SARS-CoV-2 in the air of the patient room is low (< 1 gene copy per m3 on average), and likely below the limit of quantification for many air sampling methods. The findings demonstrate the value of respiratory protection for HCP, and that field sampling may not be sensitive enough to verify the contribution of SARS-CoV-2 inhalation to the risk of occupationally acquired COVID-19 infection among healthcare personnel. The emission and infectivity of SARS-CoV-2 in respiratory droplets of different sizes is a critical knowledge gap for understanding and controlling COVID-19 transmission. |
16 | s714f5r6 | how long does coronavirus remain stable on surfaces? | Vimentin Modulates Infectious Internalization of Human Papillomavirus 16 Pseudovirions Human papillomavirus (HPV) infection is the most common viral infection of the reproductive tract, with virtually all cases of cervical cancer being attributable to infection by oncogenic HPVs. However, the exact mechanism and receptors used by HPV to infect epithelial cells are controversial. The current entry model suggests that HPV initially attaches to heparan sulfate proteoglycans (HSPGs) at the cell surface, followed by conformational changes, cleavage by furin convertase, and subsequent transfer of the virus to an as-yet-unidentified high-affinity receptor. In line with this model, we established an in vitro infection system using the HSPG-deficient cell line pgsD677 together with HPV16 pseudovirions (HPV16-PsVs). While pgsD677 cells were nonpermissive for untreated HPV16-PsVs, furin cleavage of the particles led to a substantial increase in infection. Biochemical pulldown assays followed by mass spectrometry analysis showed that furin-precleaved HPV16-PsVs specifically interacted with surface-expressed vimentin on pgsD677 cells. We further demonstrated that both furin-precleaved and uncleaved HPV16-PsVs colocalized with surface-expressed vimentin on pgsD677, HeLa, HaCaT, and NIKS cells, while binding of incoming viral particles to soluble vimentin protein before infection led to a substantial decrease in viral uptake. Interestingly, decreasing cell surface vimentin by small interfering RNA (siRNA) knockdown in HeLa and NIKS cells significantly increased HPV16-PsV infectious internalization, while overexpression of vimentin had the opposite effect. The identification of vimentin as an HPV restriction factor enhances our understanding of the initial steps of HPV-host interaction and may lay the basis for the design of novel antiviral drugs preventing HPV internalization into epithelial cells. IMPORTANCE Despite HPV being a highly prevalent sexually transmitted virus causing significant disease burden worldwide, particularly cancer of the cervix, cell surface events preceding oncogenic HPV internalization are poorly understood. We herein describe the identification of surface-expressed vimentin as a novel molecule not previously implicated in the infectious internalization of HPV16. Contrary to our expectations, vimentin was found to act not as a receptor but rather as a restriction factor dampening the initial steps of HPV16 infection. These results importantly contribute to our current understanding of the molecular events during the infectious internalization of HPV16 and open a new direction in the development of alternative drugs to prevent HPV infection. |
32 | p0kv1pht | Does SARS-CoV-2 have any subtypes, and if so what are they? | Phylogenetic perspectives on the epidemiology and origins of SARS and SARS-like coronaviruses Abstract Severe Acute Respiratory Syndrome (SARS) is a respiratory disease caused by a zoonotic coronavirus (CoV) named SARS-CoV (SCoV), which rapidly swept the globe after its emergence in rural China during late 2002. The origins of SCoV have been mysterious and controversial, until the recent discovery of SARS-like CoV (SLCoV) in bats and the proposal of bats as the natural reservior of the Coronaviridae family. In this article, we focused on discussing how phylogenetics contributed to our understanding towards the emergence and transmission of SCoV. We first reviewed the epidemiology of SCoV from a phylogenetic perspective and discussed the controversies over its phylogenetic origins. Then, we summarized the phylogenetic findings in relation to its zoonotic origins and the proposed inter-species viral transmission events. Finally, we also discussed how the discoveries of SCoV and SLCoV expanded our knowledge on the evolution of the Coronaviridae family as well as its implications on the possible future re-emergence of SCoV. |
46 | 32x48xxy | what evidence is there for dexamethasone as a treatment for COVID-19? | Psychological intervention on COVID-19: A protocol for systematic review and meta-analysis INTRODUCTION: COVID-19 is novel coronavirus infection in 2019. Many reports suggested that psychological intervention is playing a positive role in COVID-19 treatment, but there is no high-quality evidence to prove its effects. This paper reports the protocol of a systematic review and meta-analysis to clarify effectiveness of psychological intervention during the treatment of COVID-19. METHODS AND ANALYSIS: The following electronic databases will be used by 2 independent reviewers: Web of Science, Embase, Cochrane Library, PubMed, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, Wan fang Database, ClinicalTrials, WHO Trials, and Chinese Clinical Trial Registry. The randomised controlled trials of psychological intervention on COVID-19 will be searched in the databases by 2 researchers independently. Clinical recovery time and effective rate will be assessed as the primary outcomes. Changes of patients physical condition (1. Time until COVID-19 RT-PCR negative in upper respiratory tract specimen; 2. Time until cough reported as mild or absent; 3. Time until dyspnea reported as mild or absent; 4. Frequency of requiring supplemental oxygen or non-invasive ventilation; 5. Frequency of requiring respiratory; 6. Incidence of severe cases; 7. Proportion of re-hospitalization or admission to ICU; 8. All-cause mortality; 9. Frequency of seriously adverse events) and changes of psychological condition (such as: SRQ-20, PHQ-9, GAD-7, Hamilton Depression Scale, Hamilton Anxiety Scale) will be assessed as the secondary outcomes. For dichotomous outcomes, such as effective rate, data will be expressed as risk ratio (RR) with 95% confidence intervals (CIs). For continuous outcomes, weighted mean differences (WMD) or standardized mean differences (SMD) will be calculated. Fixed effect model will be used for evaluating efficiency. Considering clinical heterogeneity, random effect model will be used for continuous outcomes. RESULTS: Relevant studies will be used to evaluate whether psychological intervention is effective for COVID-19. CONCLUSION: This study will provide reliable evidence for psychological intervention on COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020178699 |
9 | 2folsh35 | how has COVID-19 affected Canada | THE ROLE OF RESPIRATORY VIRUSES IN ACUTE AND CHRONIC ASTHMA Respiratory tract infections caused by viruses, 24, 70 chlamydia, 18, 19, 43, 55, 116 and mycoplasma(61) have been implicated in the pathogenesis of asthma. Viruses have been demonstrated to be associated with asthma epidemiologically in at least two ways (Fig. 1). First, during infancy, certain viruses have been implicated as potentially being responsible for the inception of the asthmatic phenotype. Second, in patients, particularly children, with established asthma, viral upper respiratory tract infections play a significant role in producing acute exacerbations of airway obstruction that may result in frequent outpatient visits or hospitalizations. 24, 55, 56, 57 This article reviews these two areas by focusing first on mechanisms by which virus infections may lead to the development of asthma in infants and children and, second, on mechanisms by which virus infections may produce acute asthmatic symptoms in patients who already have established disease. |
10 | 0o79m08j | has social distancing had an impact on slowing the spread of COVID-19? | A simplified model for expected development of the SARS-CoV-2 (Corona) spread in Germany and US after social distancing Widespread opinions and discussion exist regarding the efficiency of social distancing after crucial spread of the SARS-CoV-2 virus during the actual Covid-19 pandemic. While Germany has released a federal law that prohibits any type of direct contact for more than 2 people other countries including the US released curfews. People are now wondering whether these measures are helpful to stop or hamper the Covid-19 pandemic and to limit the spread of the new corona virus. A quantitative statement on this question depends on many parameters that are difficult to grasp mathematically and cannot therefore be made conclusively (they include consistent adherence to the measures decided, the estimated number of unreported cases, the possible limitation by test capacities, possible mutations of the virus, etc ...). However, it turns out that a reduction in the actual daily new infection rate (actual daily growth rate of reported cases, in short: infection rate) from the current value of 30-35% in the US to 10% would be extremely effective in stopping the spread of the virus. The severe restrictions in Germany which closed any public events, schools and universities a week ago might already have contributed to a reduction of the growth rate of reported cases below 30%. |
3 | 1tl71xqw | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response BACKGROUND AND AIM: As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. METHOD: We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. RESULTS: We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. CONCLUSION: In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease. |
26 | wdgy83hn | what are the initial symptoms of Covid-19? | Olfactory and Gustatory Dysfunction in a COVID-19 Patient with Ankylosing Spondylitis Treated with Etanercept: Case Report The neurologic manifestations concerning coronavirus disease 2019 (COVID-19) are highly penetrated. Anosmia and ageusia are one of the common acute neurologic symptoms, which develop in the early stage of COVID-19. However, it is not reported that how immunosuppressive agents affect these symptoms. We report olfactory and gustatory dysfunctions in a patient with ankylosing spondylitis (AS) treated with etanercept during COVID-19. A 53-year-old female showing AS controlled with tumor necrosis factor-α inhibitor, etanercept, had been diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, presenting cough and rhinorrhea. One month after diagnosis, she complained about hyposmia and hypogeusia two days before the seronegative conversion of SARS-CoV-2, which were confirmed by a neurological examination. We speculate that the etanercept may have delayed the development of olfactory and gustatory dysfunction in the patient. |
12 | gdsh8wmv | what are best practices in hospitals and at home in maintaining quarantine? | The effectiveness of quarantine and isolation determine the trend of the COVID-19 epidemics in the final phase of the current outbreak in China Abstract Objectives Since January 23rd 2020, stringent measures for controlling the novel coronavirus epidemics have been gradually enforced and strengthened in mainland China. The detection and diagnosis have been improved as well. However, the daily reported cases staying in a high level make the epidemics trend prediction difficult. Methods Since the traditional SEIR model does not evaluate the effectiveness of control strategies, a novel model in line with the current epidemics process and control measures was proposed, utilizing multisource datasets including cumulative number of reported, death, quarantined and suspected cases. Results Results show that the trend of the epidemics mainly depends on quarantined and suspected cases. The predicted cumulative numbers of quarantined and suspected cases nearly reached static states and their inflection points have already been achieved, with the epidemics peak coming soon. The estimated effective reproduction numbers using model-free and model-based methods are decreasing, as well as new infections, while new reported cases are increasing. Most infected cases have been quarantined or put in suspected class, which has been ignored in existing models. Conclusions The uncertainty analyses reveal that the epidemics is still uncertain and it is important to continue enhancing the quarantine and isolation strategy and improving the detection rate in mainland China. |
24 | xhf8yg6o | what kinds of complications related to COVID-19 are associated with diabetes | Advances in the Relationship Between Coronavirus Infection and Cardiovascular Diseases The outbreak of coronavirus disease 2019 (COVID-19) has once again aroused people's concern about coronavirus. Seven human coronaviruses (HCoVs) have been discovered so far, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU115, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2. Existing studies show that the cardiovascular disease increased the incidence and severity of coronavirus infection. At the same time, myocardial injury caused by coronavirus infection is one of the main factors contributing to poor prognosis. In this review, the recent clinical findings about the relationship between coronaviruses and cardiovascular diseases and the underlying pathophysiological mechanisms are discussed. This review aimed to provide assistance for the prevention and treatment of COVID-19. |
17 | 6q90bayx | are there any clinical trials available for the coronavirus | A rate equation approach to model the denaturation or replication behavior of the SARS coronavirus As a newly emerging virus, little is known about the SARS coronavirus, whose outbreak has brought away several hundred people's lives over the world in the year of 2003 and is seriously imperiling the human health. Revealing the denaturation and replication mechanisms of SARS coronavirus has great importance for successfully fighting SARS. However, experiments related to SARS coronavirus are extremely dangerous and therefore restricted only to certain specific labs with high safety standard. Clearly, predicting the behaviors of SARS coronavirus in a wide variety of environmental conditions, which are not easily accessible, are thus critically necessary. In this study, we proposed to quantify the survival time of SARS coronavirus either in vitro or in vivo, through introducing thermal rate process models established from the well-known Arrhenius law. The complex physical and chemical behaviors of the SARS coronavirus can then be attributed to its activation energy, frequency factor, damage function as well as the surrounding environmental conditions. Based on the first data on stability and resistance of SARS coronavirus measured by members of WHO laboratory network, the rate coefficients involved in the above equations were estimated for the first time. Predictions on the survival time of SARS coronavirus in different temperature scale were then performed. It was found theoretically that, such survival time falls in an extremely wide range, say from several seconds in high temperature to an almost infinitely long time in a low temperature environment, which has already or is being supported by the currently available tests data. Applications of the present theory to interpret several existing phenomena were presented and their implementations in developing new technical ways for SARS prevention and clinical therapy were discussed. Uncertainties involved in the theoretical models were also analyzed and predicted. Parametric studies were performed to test the effects of the rate coefficients to the survival time of SARS coronavirus. Some important factors, which can significantly vary the denaturation or replication process of SARS coronavirus were pointed out. Through regulating the parameters involved in the equation, certain potential therapies either through drug delivery or engineering approach to treat the SARS disease can possibly be established. Extension of the present model for further studies was also suggested. This study opens a new theoretical way for probing into the complex behaviors of SARS coronavirus. Modellierung der Denaturierung oder Repliziryng von SARS-Korona-Viren Zusammenfassung Der Kenntnisstand über die Eigenschaften des in 2003 neu aufgetretenen SARS Korona Virus, der einige Hundert Menschenleben gekostet hat, ist relativ gering. Die Ermittlung des Denaturierungs- und Replizierungsmechanismuses des SARS Virus ist für seine Bekämpfung von hoher Bedeutung. Experimentelle Untersuchungen an diesem extrem gefährlichen Virus dürfen nur durch Laboratorien mit einem hohen Sicherheitsstandard erfolgen. Die Vorhersage des Verhaltens des SARS Virus in unterschiedlichen Umgebungsbedingungen ist dabei erforderlich. In der vorliegenden Studie wird die überlebensdauer des Virus unter Labor- und realen Bedingungen durch Anwendung der bekannten Arrhenius-Beziehung für temperaturabhängige Vorgänge ermittelt. Das physikalische und chemische Verhalten des SARS Virus wird anhand der zugrundeliegenden Modell- Parameter beschrieben. Basierend auf den ersten Messungen von Mitgliedern des WHO-laboratory-network über die Stabilität und Widerstandsfähigkeit des Virus wurden erstmalig die Geschwindigkeitskoeffizienten des Berechnungsmodells bestimmt. Vorhersagen der Überlebensdauer des SARS-Virus unter unterschiedlichen Temperaturbedingungen wurden ausgeführt. Das sich hieraus ergebende, sehr unterschiedliche Ausmaß der Überlebensfähigkeit in Abhängigkeit der Umgebungstemperatur ist durch den Vergleich mit verfügbaren experimentellen Ergebnissen bestätigt worden. Die Anwendung der vorgestellten Modellierung zur Interpretation realer Phänomene und zur Entwicklung technischer Maßnahmen zur Vorbeugung und klinischen Therapierung von SARS wird diskutiert. Der Einfluß von Unsicherheiten des Modells wird analysiert und abgeschätzt. Parametrische Studien sind durchgeführt worden, um den Einfluß der Geschwindigkeitskoeffizienten auf die Überlebensdauer des SARS Virus darzustellen. Einige wichtige Einflußgrößen auf die Denaturierung und Replikationsfähigkeit des SARS Virus werden aufgezeigt. Durch eine Variation der Modellparameter kann die potentielle Wirksamkeit medikamentöser oder physikalischer Therapien abgeschätzt werden. Erweiterungsmöglichkeiten des vorgestellten Modells werden vorgeschlagen. Die vorliegende Studie ermöglicht neue, theoretische Vorgehensweisen zur Untersuchung des komplexen Verhaltensmusters des SARS Virus. |
25 | 0n5apnle | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Biomarkers in Pediatric ARDS: Future Directions Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children. |
18 | 9b6cepf4 | what are the best masks for preventing infection by Covid-19? | Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US. State policies mandating public or community use of face masks or covers in mitigating novel coronavirus disease (COVID-19) spread are hotly contested. This study provides evidence from a natural experiment on effects of state government mandates in the US for face mask use in public issued by 15 states plus DC between April 8 and May 15. The research design is an event study examining changes in the daily county-level COVID-19 growth rates between March 31, 2020 and May 22, 2020. Mandating face mask use in public is associated with a decline in the daily COVID-19 growth rate by 0.9, 1.1, 1.4, 1.7, and 2.0 percentage-points in 1-5, 6-10, 11-15, 16-20, and 21+ days after signing, respectively. Estimates suggest as many as 230,000-450,000 COVID-19 cases possibly averted By May 22, 2020 by these mandates. The findings suggest that requiring face mask use in public might help in mitigating COVID-19 spread. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.]. |
25 | 3iijt5im | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection? |
6 | gcrbcoj5 | what types of rapid testing for Covid-19 have been developed? | Use of Throat Swab or Saliva Specimens for Detection of Respiratory Viruses in Children Background. Nasopharyngeal (NP) specimens are commonly used for the detection of respiratory viruses, but throat and saliva specimens are easier to obtain. The objective of this study was to compare the viral yield of direct fluorescent antigen detection of NP specimens and nucleic acid amplification tests (NAT) of direct fluorescent antigen-negative NP specimens with the viral yield of NAT of throat swab and saliva specimens. Methods. NP, throat swab, and saliva specimens were obtained from children and adolescents aged ⩽17 years. Direct fluorescent antigen testing of the NP specimen for respiratory syncytial virus, influenza A and B viruses, and parainfluenza virus was performed. If no virus was detected, NAT was performed for these 4 viruses, adenovirus, and human metapneumovirus. If a virus was detected by either method, NAT for the same virus was performed for the corresponding throat swab and saliva specimens. Results. A virus was detected in 105 of the 137 NP specimens. The same virus was detectable by NAT in 87 (83%) of 105 throat swab specimens and 77 (74%) of 104 saliva specimens. The likelihood of viral detection among throat swab and saliva swab specimens was higher when the NP specimen tested positive by direct fluorescent antigen testing, compared with NAT alone, and when the specimens were obtained within 3 days after symptom onset, compared with later in the illness. Conclusions. Throat swab and saliva specimens are inferior to NP specimens for the detection of respiratory viruses but might be acceptable for screening in a setting where it is impractical to obtain an NP specimen. |
2 | j4b2534p | how does the coronavirus respond to changes in the weather | Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biological treatment and renal transplanted recipients in maintenance immunosuppressive treatment |
31 | ys5njiw0 | How does the coronavirus differ from seasonal flu? | Burden, seasonal pattern and symptomatology of acute respiratory illnesses with different viral aetiologies in children presenting at outpatient clinics in Hong Kong Abstract Respiratory viruses cause acute respiratory diseases with a broad and overlapping spectrum of symptoms. We examined the clinical symptoms and explored the patterns of various respiratory viral infections in children in Hong Kong. Among 2090 specimens collected from outpatient care (2007–2010), 1343 (64.3%) were positive for any virus by the xTAG assay, and 81 (3.9%) were positive for co-infection. The most frequently detected viruses among children aged 6–15 years were enterovirus/rhinovirus and influenza virus A, whereas most non-influenza viruses were more frequently detected in younger children. Higher body temperature was more common for illnesses associated with influenza viruses than for those associated with non-influenza viruses, but other symptoms were largely similar across all infections. The seasonality pattern varied among different viruses, with influenza virus A being the predominant virus detected in winter, and enterovirus/rhinovirus being more commonly detected than influenza virus A in the other three seasons, except for 2009. |
37 | 2hyiped2 | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Comparative analysis of primer-probe sets for the laboratory confirmation of SARS-CoV-2 Coronavirus disease 2019 (COVID-19) is newly emerging human infectious diseases, which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV). Within two months of the outbreak, more than 80,000 cases of COVID-19 have been confirmed worldwide. Since the human to human transmission occurred easily and the human infection is rapidly increasing, the sensitive and early diagnosis is essential to prevent the global outbreak. Recently, World Health Organization (WHO) announced various primer and probe sets for SARS-CoV-2 previously developed in China, Germany, Hong Kong, Japan, Thailand, and USA. In this study, we compared the ability to detect SARS-CoV-2 RNA among the seven primer-probe sets for N gene and the three primer-probe sets for Orf1 gene. The result of the comparative analysis represented that the '2019-nCoV_N2, N3' of USA and the 'ORF1ab' of China are the most sensitive primer-probe sets for N and Orf1 genes, respectively. Therefore, the appropriate combination from ORF1ab (China), 2019-nCoV_N2, N3 (USA), and NIID_2019-nCOV_N (Japan) sets should be selected for the sensitive and reliable laboratory confirmation of SARS-CoV-2. |
47 | dmrtsxik | what are the health outcomes for children who contract COVID-19? | Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Summary Background Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. Methods We retrospectively retrieved data for paediatric patients (aged 0–16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. Findings From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5–38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir–ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Interpretation Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Funding Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou. |
36 | ah8uyfe7 | What is the protein structure of the SARS-CoV-2 spike? | SARS‐CoV‐2 spike protein favors ACE2 from Bovidae and Cricetidae Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes the recent COVID‐19 public health crisis. Bat is the widely believed original host of SARS‐CoV‐2. However, its intermediate host before transmitting to humans is not clear. Some studies proposed pangolin, snake, or turtle as the intermediate hosts. Angiotensin‐converting enzyme 2 (ACE2) is the receptor for SARS‐CoV‐2, which determines the potential host range for SARS‐CoV‐2. On the basis of structural information of the complex of human ACE2 and SARS‐CoV‐2 receptor‐binding domain (RBD), we analyzed the affinity to S protein of the 20 key residues in ACE2 from mammal, bird, turtle, and snake. Several ACE2 proteins from Primates, Bovidae, Cricetidae, and Cetacea maintained the majority of key residues in ACE2 for associating with SARS‐CoV‐2 RBD. The simulated structures indicated that ACE2 proteins from Bovidae and Cricetidae were able to associate with SARS‐CoV‐2 RBD. We found that nearly half of the key residues in turtle, snake, and bird were changed. The simulated structures showed several key contacts with SARS‐CoV‐2 RBD in turtle and snake ACE2 were abolished. This study demonstrated that neither snake nor turtle was the intermediate hosts for SARS‐CoV‐2, which further reinforced the concept that the reptiles are resistant against infection of coronavirus. This study suggested that Bovidae and Cricetidae should be included in the screening of intermediate hosts for SARS‐CoV‐2. |
41 | 534936lf | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | The Collision of COVID-19 and the U.S. Health System In this article, leaders from the American College of Physicians (ACP) discuss key recommendations from ACP's vision for U.S. health care that can advise how we can act now during the COVID-19 pandemic and in the future in service to patients, our peers, and the profession. |
22 | owhx6k4t | are cardiac complications likely in patients with COVID-19? | Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer Abstract There is currently a lack of pathologic data on the novel coronavirus (severe acute respiratory syndrome coronavirus 2) pneumonia, or coronavirus disease 2019 (COVID-19), from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of the operation. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Because both patients did not exhibit symptoms of pneumonia at the time of operation, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia. |
38 | x99jcr14 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Immune dysfunction leads to mortality and organ injury in patients with COVID-19 in China: insights from ERS-COVID-19 study |
21 | e7ntocgf | what are the mortality rates overall and in specific populations | A Comparison of Mortality-related Risk Factors of COVID-19, SARS, and MERS: A Systematic Review and Meta-analysis Objective: Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment. Methods: We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI). Results: 845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients. Conclusions: COVID-19's mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes. |
26 | ysa8vb9x | what are the initial symptoms of Covid-19? | The Pace and Pulse of the Fight against Coronavirus across the US, A Google Trends Approach The coronavirus pandemic is impacting our lives at unprecedented speed and scale - including how we eat and work, what we worry about, how much we move, and our ability to earn. Google Trends can be used as a proxy for what people are thinking, needing, and planning. We use it to provide both insights into, and potential indicators of, important changes in information-seeking patterns during pandemics like COVID-19. Key questions we address are: (1) What is the relationship between the coronavirus outbreak and internet searches related to healthcare seeking, government support programs, media sources of different ideologies, planning around social activities, travel, and food, and new coronavirus-specific behaviors and concerns?; (2) How does the popularity of search terms differ across states and regions and can we explain these differences?; (3) Can we find distinct, tangible search patterns across states suggestive of policy gaps to inform pandemic response? (4) Does Google Trends data correlate with and potentially precede real-life events? We suggest strategic shifts for policy makers to improve the precision and effectiveness of non-pharmaceutical interventions (NPIs) and recommend the development of a real-time dashboard as a decision-making tool. Methods used include trend analysis of US search data; geographic analyses of the differences in search popularity across US states during March 1st to April 15th, 2020; and Principal Component Analyses (PCA) to extract search patterns across states. |
38 | q1yz9y8k | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy - achieving global consensus and visibility for cellular host-directed therapies Abstract As of May 11th 2020, the coronavirus disease 2019 (COVID-19) pandemic, caused by the novel, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused 274,361 deaths out of 3,917,366 (7% case fatality rate). As with the two other novel coronavirus zoonotic diseases of humans, SARS and MERS, no specific treatments for reducing mortality or morbidity are yet available. Deaths from COVID-19 will continue to rise globally until effective and appropriate treatments and vaccines are found. With no specific treatments being available for treating COVID-19 patients, the global medical, scientific, pharma and funding communities have rapidly initiated over 500 COVID-19 clinical on a range of antiviral drug regimens, biologics, repurposed drugs in various combinations. We focus this editorial specifically on the background to, and the rationale for, the use and evaluation of mesenchymal stromal (Stem) cells (MSCs) in treatment trials of patients with severe COVID-19 disease. This is an area which has been eclipsed by the current emphasis the huge number of trials evaluating new anti-viral drugs, repurposed drugs and combinations thereof. MSCs should also be trialed for treatment of severe cases of MERS where mortality rates are upto 34% and MERS-CoV remains a WHO priority Blueprint pathogen. It's about time funding agencies now invest more into development MSCs per se and other host-directed therapies in combination with other therapeutic interventions. MSC therapy could turn out to be an important contribution to bringing an end to the high COVID-19 and MERS death rates. |
33 | ri91u0f1 | What vaccine candidates are being tested for Covid-19? | Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19. |
49 | dqs21e0q | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Trained immunity: a tool for reducing susceptibility and severity of SARS-CoV-2 infection Abstract SARS-CoV-2 infection is mild in the majority of individuals, but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed 'trained immunity', by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections, through epigenetic, transcriptional and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole microorganism vaccines may represent an important tool for reducing susceptibility and severity to SARS-CoV-2. |
41 | 7kevqevo | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Racial and Ethnic Disparities in Population Level Covid-19 Mortality Background: Current reporting of Covid-19 mortality data by race and ethnicity across the United States could bias our understanding of population-mortality disparities. Moreover, stark differences in age distribution by race and ethnicity groups are seldom accounted for in analyses. Methods: To address these gaps, we conducted a cross-sectional study using publicly-reported Covid-19 mortality data to assess the quality of race and ethnicity data (Black, Latinx, white), and estimated age-adjusted disparities using a random effects meta-analytic approach. Results: We found only 28 states, and NYC, reported race and ethnicity-stratified Covid-19 mortality along with large variation in the percent of missing race and ethnicity data by state. Aggregated relative risk of death estimates for Black compared to the white population was 3.57 (95% CI: 2.84-4.48). Similarly, Latinx population displayed 1.88 (95% CI: 1.61-2.19) times higher risk of death than white patients. Discussion: In states providing race and ethnicity data, we identified significant population-level Covid-19 mortality disparities. We demonstrated the importance of adjusting for age differences across population groups to prevent underestimating disparities in younger population groups. The availability of high-quality and comprehensive race and ethnicity data is necessary to address factors contributing to inequity in Covid-19 mortality. |
2 | vvx0t16l | how does the coronavirus respond to changes in the weather | Detection of human coronavirus strain HKU1 in a 2 years old girl with asthma exacerbation caused by acute pharyngitis Respiratory viral infections can trigger asthma attack which may lead to sever morbidity. In this report, using molecular methods, we show the chronological association between human coronavirus - HKU1 infection and asthma exacerbation in a two years and seven months old asthmatic girl who was not under treatment and was otherwise healthy. |
17 | js8kx3yc | are there any clinical trials available for the coronavirus | Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial OBJECTIVES: The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below. TRIAL DESIGN: REALIST COVID 19 is a randomised, placebo-controlled, triple blinded trial. PARTICIPANTS: The study will be conducted in Intensive Care Units in hospitals across the United Kingdom. Patients with moderate to severe ARDS as defined by the Berlin definition, receiving invasive mechanical ventilation and with a diagnosis of COVID-19 based on clinical diagnosis or PCR test will be eligible. Patients will be excluded for the following reasons: more than 72 hours from the onset of ARDS; age < 16 years; patient known to be pregnant; major trauma in previous 5 days; presence of any active malignancy (other than non-melanoma skin cancer); WHO Class III or IV pulmonary hypertension; venous thromboembolism currently receiving anti-coagulation or within the past 3 months; patient receiving extracorporeal life support; severe chronic liver disease (Child-Pugh > 12); Do Not Attempt Resuscitation order in place; treatment withdrawal imminent within 24 hours; prisoners; declined consent; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; previously enrolled in the REALIST trial. INTERVENTION AND COMPARATOR: Intervention: Allogeneic donor CD362 enriched human umbilical cord derived mesenchymal stromal cells (REALIST ORBCEL-C) supplied as sterile, single-use cryopreserved cell suspension of a fixed dose of 400 x106 cells in 40ml volume, to be diluted in Plasma-Lyte 148 to a total volume of 200mls for administration. Comparator (placebo): Plasma-Lyte 148 Solution for Infusion (200mls). The cellular product (REALIST ORBCEL-C) was developed and patented by Orbsen Therapeutics. MAIN OUTCOMES: The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is Oxygenation Index (OI) at day 7. Secondary outcomes include: OI at days 4 and 14; respiratory compliance, driving pressure and PaO2/FiO2 ratio (PF ratio) at days 4, 7 and 14; Sequential Organ Failure Assessment (SOFA) score at days 4, 7 and 14; extubation and reintubation; ventilation free days at day 28; duration of mechanical ventilation; length of ICU and hospital stay; 28-day and 90-day mortality. RANDOMISATION: After obtaining informed consent, patients will be randomised via a centralised automated 24-hour telephone or web-based randomisation system (CHaRT, Centre for Healthcare Randomised Trials, University of Aberdeen). Randomisation will be stratified by recruitment centre and by vasopressor use and patients will be allocated to REALIST ORBCEL-C or placebo control in a 1:1 ratio. BLINDING (MASKING): The investigator, treating physician, other members of the site research team and participants will be blinded. The cell therapy facility and clinical trials pharmacist will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A sample size of 60 patients with 30 patients randomised to the intervention and 30 to the control group. If possible, recruitment will continue beyond 60 patients to provide more accurate and definitive trial results. The total number of patients recruited will depend on the pandemic and be guided by the data monitoring and ethics committee (DMEC). TRIAL STATUS: REALIST Phase 1 completed in January 2020 prior to the COVID-19 pandemic. This was an open label dose escalation study of REALIST ORBCEL-C in patients with ARDS. The COVID-19 pandemic emerged as REALIST Phase 2 was planned to commence and the investigator team decided to repurpose the Phase 2 trial as a COVID-19 specific trial. This decision was discussed and approved by the Trial Steering Committee (TSC) and DMEC. Submissions were made to the Research Ethics Committee (REC) and MHRA to amend the protocol to a COVID-19 specific patient population and the protocol amendment was accepted by the REC on 27th March 2020 and MHRA on 30th March 2020 respectively. Other protocol changes in this amendment included an increase in the time of onset of ARDS from 48 to 72 hours, inclusion of clinical outcomes as secondary outcomes, the provision of an option for telephone consent, an indicative sample size and provision to continue recruitment beyond this indicative sample size. The current protocol in use is version 4.0 23.03.2020 (Additional file 1). Urgent Public Health status was awarded by the NIHR on 2 April 2020 and the trial opened to recruitment and recruited the first participant the same day. At the time of publication the trial was open to recruitment at 5 sites across the UK (Belfast Health and Social Care Trust, King's College London, Guys and St Thomas' Hospital London, Birmingham Heartlands Hospital and the Queen Elizabeth Hospital Birmingham) and 12 patients have been recruited across these sites. Additional sites are planned to open and appropriate approvals for these are being obtained. It is estimated recruitment will continue for 6 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT03042143 (Registered 3 Feb 2017). EudraCT 2017-000585-33 (Registered 28 Nov 2017). FULL PROTOCOL: The full protocol (version 4.0 23.03.2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). |
14 | bojhhrvb | what evidence is there related to COVID-19 super spreaders | Novel Coronavirus 2019 (Covid-19) epidemic scale estimation: topological network-based infection dynamic model Backgrounds: An ongoing outbreak of novel coronavirus pneumonia (Covid-19) hit Wuhan and hundreds of cities, 29 territories globally. We present a method for scale estimation in dynamic while most of the researchers used static parameters. Methods: We use historical data and the SEIR model for important parameters assumption. And according to the timeline, we use dynamic parameters for infection topology network building. Also, the migration data is used for the Non-Wuhan area estimation which can be cross-validated for the Wuhan model. All data are from the public. Results: The estimated number of infections is 61,596 (95%CI: 58,344.02-64,847.98) by 25 Jan in Wuhan. And the estimation number of the imported cases from Wuhan of Guangzhou was 170 (95%CI: 161.27-179.26), infection scale in Guangzhou is 315 (95%CI: 109.20-520.79), while the imported cases are 168 and the scale of the infection is 339 published by the authority. Conclusions: Using dynamic network models and dynamic parameters for different time periods is an effective way of infection scale modeling. |
10 | 3dx6deei | has social distancing had an impact on slowing the spread of COVID-19? | Analysis and Prediction of the COVID-19 outbreak in Pakistan In this study, we estimate the severity of the COVID-19 outbreak in Pakistan prior to and after lockdown restrictions were eased. We also project the epidemic curve considering realistic quarantine, social distancing, and possible medication scenarios. We use a deterministic epidemic model that includes asymptomatic, quarantined, isolated, and medicated population compartments for our analysis. We calculate the basic reproduction number R0 for the pre and post lockdown periods, noting that during this time, no medication was available. The pre-lock down the value of R0 is estimated to be 1.07, and the post lockdown value is estimated to be 1.86. We use this analysis to project the epidemic curve for a variety of lockdown, social distancing, and medication scenarios. We note that if no substantial efforts are made to contain the epidemic, it will peak in mid of September, with the maximum projected active cases being close to 700,000. In a realistic, best-case scenario, we project that the epidemic peaks in early to mid-July with the maximum active cases being around 120000.We note that social distancing measures and medication, if available, will help flatten the curve, however without the reintroduction of further lockdown, it would be very difficult to bring R0 below 1. Our study strongly supports the recent WHO recommendation of reintroducing lockdowns to control the epidemic. |
7 | 0oak9ggm | are there serological tests that detect antibodies to coronavirus? | Diagnostic techniques for COVID-19 and new developments COVID-19 pandemic is a serious global health issue today due to the rapid human to human transmission of SARS-CoV-2, a new type of coronavirus that causes fatal pneumonia. SARS -CoV-2 has a faster rate of transmission than other coronaviruses such as SARS and MERS and until now there are no approved specific drugs or vaccines for treatment. Thus, early diagnosis is crucial to prevent the extensive spread of the disease. The reverse transcription-polymerase chain reaction (RT-PCR) is the most routinely used method until now to detect SARS-CoV-2 infections. However, several other faster and accurate assays are being developed for the diagnosis of COVID-19 aiming to control the spread of infection through the identification of patients and immediate isolation. In this review, we will discuss the various detection methods of the SARS-CoV-2 virus including the recent developments in immunological assays, amplification techniques as well as biosensors. |
14 | 971d0sir | what evidence is there related to COVID-19 super spreaders | The SARS-CoV-2 outbreak from a one health perspective Abstract The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. The virus shares a high level of identity with some bat coronaviruses and is recognised as a potentially zoonotic virus. We are utilizing the One Health concept to understand the emergence of the virus, as well as to point to some possible control strategies that might reduce the spread of the virus across the globe; thus, containment of such virus would be possible. |
39 | 860780z9 | What is the mechanism of cytokine storm syndrome on the COVID-19? | The ACE2‐deficient mouse: A model for a cytokine storm‐driven inflammation Angiotensin converting enzyme 2 (ACE2) plays an important role in inflammation, which is attributable at least, in part, to the conversion of the pro‐inflammatory angiotensin (Ang) II peptide into angiotensin 1‐7 (Ang 1‐7), a peptide which opposes the actions of AngII. ACE2 and AngII are present in many tissues but information on the cornea is lacking. We observed that mice deficient in the Ace2 gene (Ace2(−/−)), developed a cloudy cornea phenotype as they aged. Haze occupied the central cornea, accompanied by corneal edema and neovascularization. In severe cases with marked chronic inflammation, a cell‐fate switch from a transparent corneal epithelium to a keratinized, stratified squamous, psoriasiform‐like epidermis was observed. The stroma contained a large number of CD11c, CD68, and CD3 positive cells. Corneal epithelial debridement experiments in young ACE2‐deficient mice showed normal appearing corneas, devoid of haze. We hypothesized, however, that these mice are "primed" for a corneal inflammatory response, which once initiated, would persist. In vitro studies reveal that interleukins (IL‐1a, IL‐1b), chemokines (CCL2, CXCL8), and TNF‐α, are all significantly elevated, resulting in a cytokine storm‐like phenotype. This phenotype could be partially rescued by treatment with the AngII type 1 receptor (AT1R) antagonist, losartan, suggesting that the observed effect was mediated by AngII acting on its main receptor. Since the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) utilizes human ACE2 as the receptor for entry with subsequent downregulation of ACE2, corneal inflammation in Ace2(−/−) mice may have a similar mechanism with that in COVID‐19 patients. Thus the Ace2(−/−) cornea, because of easy accessibility, may provide an attractive model to explore the molecular mechanisms, immunological changes, and treatment modalities in patients with COVID‐19. |
3 | buwz6lu3 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2 Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9-17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy. |
23 | 3mpqtfej | what kinds of complications related to COVID-19 are associated with hypertension? | Voice from China: nomenclature of the novel coronavirus and related diseases |
2 | 33fngv0t | how does the coronavirus respond to changes in the weather | Mitigating the air pollution effect? The remarkable decline in the pollution-mortality relationship in Hong Kong Abstract Using transboundary pollution from mainland China as an instrument, we show that air pollution leads to higher cardio-respiratory mortality in Hong Kong. However, the air pollution effect has dramatically decreased over the past two decades: before 2003, a 10-unit increase in the Air Pollution Index could lead to a 3.1% increase in monthly cardio-respiratory mortality, but this effect has declined to 0.5% using recent data and is no longer statistically significant. Exploratory analyses suggest that a well-functioning medical system and immediate access to emergency services can help mitigate the contemporaneous effects of pollution on mortality. |
23 | xcv8ri21 | what kinds of complications related to COVID-19 are associated with hypertension? | Colchicina: una herramienta terapéutica potencial frente a COVID-19. Experiencia en 5 pacientes Resumen COVID-19 es una enfermedad de aparición reciente, que se ha convertido en un reto global de salud pública. Debido a la falta de conocimiento acerca del virus, se ha propuesto un número significativo de objetivos potenciales para utilizar un fármaco en particular. Presentamos aquí cinco casos con historia clínica de biopolímeros en la región glútea, que desarrollaron alogenosis iatrogénica (AI). A los 5 casos se les administró tratamiento de colchicina debido a crisis de AI, no teniendo síntomas específicos (cefalea, tos sin disnea, y artralgias), con resultado positivo en el test de SARS-CoV-2. Sus contactos cercanos tenían síntomas de leves a graves, y tres de ellos fallecieron. En la infección por SARS-CoV-2 se alteran diferentes rutas inflamatorias, en las que la colchicina reduce los niveles de citocinas y la activación de macrófagos, neutrófilos e inflamasoma. Revisamos también en este artículo los posibles mecanismos que puede utilizar colchicina para prevenir el síndrome de distrés respiratorio agudo (SDRA) en pacientes con COVID-19. Abstract COVID-19 is a newly emerged disease that has become a global public health challenge. Due to a lack of knowledge about the virus, a significant number of potential targets for using a particular drug have been proposed. Five cases with a clinical history of biopolymers in the gluteal region that developed iatrogenic allogenosis (IA) are presented here. The 5 cases were put under colchicine treatment for IA crisis and had non-specific symptoms (headache, cough without dyspnoea, and arthralgias) with a positive SARS-CoV-2 test. Their close contacts had mild to severe symptoms and three of them died. In the SARS-CoV-2 infection different inflammatory pathways are altered where colchicine reduces cytokine levels as well as the activation of macrophages, neutrophils, and the inflammasome. The possible mechanisms that colchicine may use to prevent acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection are also reviewed in this article. |
9 | memywn0w | how has COVID-19 affected Canada | Guidance for management of cancer surgery during the COVID-19 pandemic Summary: During the coronavirus disease 2019 (COVID-19) pandemic, delaying lifesaving cancer surgeries must be done with extreme caution and thoughtfulness. Modelling indicates that delays in high-risk cancer surgeries beyond 6 weeks could affect long-term outcomes for thousands of Canadians. Consequently, it is possible that postponing cancer surgery without consideration of its implications could cost more lives than can be saved by diverting all surgical resources to COVID-19. This article provides general guidance on supporting curative surgical treatment where appropriate and with available resources. |
28 | 39mu0tdr | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Screening for Active COVID-19 Infection and Immunization Status Prior to Biologic Therapy in IBD Patients at the Time of the Pandemic Outbreak Abstract Coronavirus disease 2019 has been recently classified as pandemic infection by the World Health Organization. Patients with inflammatory bowel disease (IBD) are invited to follow the national recommendations as any other person. It is unclear whether a more aggressive clinical course might develop in asymptomatic COVID-19 infected subjects during biological therapy and current evidence does not support treatment suspension. However, during pandemic, the start of treatment with immunosuppressive drugs and biologics should be postponed whenever possible and based on an individual risk assessment. When clinical conditions and the disease activity do not allow a treatment delay, before starting a biological therapy, screening of IBD patients for COVID-19 active infection by RT-PCR should be advisable, even in absence of clinical suspicion. Serum antibody testing, when available, could provide evidence of infection as well as identify patients already immune to the disease. |
42 | wwuqxx1r | Does Vitamin D impact COVID-19 prevention and treatment? | Protection of chickens against infectious bronchitis virus with a multivalent DNA vaccine and boosting with an inactivated vaccine The protective efficacy of DNA plasmids encoding avian infectious bronchitis virus (IBV) S1, N, or M protein was investigated in chickens. Chickens were inoculated monovalently (with plasmid pVAX1-16S1, pVAX1-16M, or pVAX1-16N alone) or multivalently (combination of the three different plasmids, pVAX1-16S1/M/N). A prime-boost immunization protocol against IBV was developed. Chickens were immunized with the multivalent DNA vaccine twice and then boosted with an inactivated vaccine once. Antibody titers of the chickens immunized with pVAX1-16S1/M/N were much higher than those of the monovalent groups (p < 0.01). A protective rate up to 90% was observed in the pVAX1-16S1/M/N group. The serum antibody titers in the prime-boost birds were significantly higher than those of the multivalent DNA vaccine group (p < 0.01) but not significantly different compared to the inactivated vaccine group at 49 days of age. Additionally, the prime-boost group also showed the highest level of IBV-specific cellular proliferation compared to the monovalent groups (p < 0.01) but no significant difference was found compared to the multivalent DNA vaccine group, and the prime-boost group completely protected from followed viral challenge. |
6 | j6yqbesv | what types of rapid testing for Covid-19 have been developed? | Impact of lay health worker programmes on the health outcomes of mother-child pairs of HIV exposed children in Africa: A scoping review. BACKGROUND Increased demand for healthcare services in countries experiencing high HIV disease burden and often coupled with a shortage of health workers, has necessitated task shifting from professional health workers to Lay Health Workers (LHWs) in order to improve healthcare delivery. Maternal and Child Health (MCH) services particularly benefit from task-shifting to LHWs or similar cadres. However, evidence on the roles and usefulness of LHWs in MCH service delivery in Sub-Saharan Africa (SSA) is not fully known. OBJECTIVES To examine evidence of the roles and impact of lay health worker programmes focusing on Women Living with HIV (WLH) and their HIV-exposed infants (HEIs). METHODS A scoping review approach based on Arksey and O'Malley's guiding principles was used to retrieve, review and analyse existing literature. We searched for articles published between January 2008 and July 2018 in seven (7) databases, including: MEDLINE, Embase, PsycINFO, Joanna Briggs, The Cochrane Library, EBM reviews and Web of Science. The critical constructs used for the literature search were "lay health worker", "community health worker", "peer mentor", "mentor mother," "Maternal and Child health worker", "HIV positive mothers", "HIV exposed infants" and PMTCT. RESULTS Thirty-three (33) full-text articles meeting the eligibility criteria were identified and included in the final analysis. Most (n = 13, 39.4%) of the included studies were conducted in South Africa and used a cluster RCT design (n = 13, 39.4%). The most commonly performed roles of LHWs in HIV specific MCH programmes included: community engagement and sensitisation, psychosocial support, linkage to care, encouraging women to bring their infants back for HIV testing and supporting default tracing. Community awareness on Mother to Child Transmission of HIV (MTCT), proper and consistent use of condoms, clinic attendance and timely HIV testing of HEIs, as well as retention in care for infected persons, have all improved because of LHW programmes. CONCLUSION LHWs play significant roles in the management of WLH and their HEIs, improving MCH outcomes in the process. LHW interventions are beneficial in increasing access to PMTCT services and reducing MTCT of HIV, though their impact on improving adherence to ART remains scanty. Further research is needed to evaluate ART adherence in LHW interventions targeted at WLH. LHW programmes can be enhanced by increasing supportive supervision and remuneration of LHWs. |
17 | f3lv7o4d | are there any clinical trials available for the coronavirus | Traditional Chinese medicine in the treatment of acute respiratory tract infections Summary Aims To review the evidence from Cochrane systematic reviews for the effectiveness of traditional Chinese medicinal (TCM) herbs for treating acute respiratory tract infections (ARTIs) and to discuss the limitations of current clinical trials of TCM. Findings Evidence from six Cochrane systematic reviews was weak owing to the lack of high-quality TCM trials. Limitations were usually due to biases that influenced the validity of results. Conclusions TCM is widely used for treating ARTIs. However, none of the identified studies has been well designed or conducted. In this overview, we suggest that clinical trials of TCM for ARTIs need to be re-run in accordance with internationally recognized standards. |
50 | 1242ggxm | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | [SARS-CoV-2 infection (COVID-19): what can we expect?] - Case numbers in China are clearly declining, case numbers in many European regions are no longer increasing exponentially.- Data on mortality from SARS-CoV-2 infection are contradictory; mortality is certainly lower than for SARS and MERS, but probably higher than for most seasonal flu outbreaks in recent years- The main complication of SARS-CoV-2 infection is pneumonia with development of acute respiratory distress syndrome (ARDS)- Asymptomatic and oligosymptomatic courses with virus shedding are not uncommon; they may be more frequent in children than in adults. Virus excretion in asymptomatic people and in the pre-symptomatic phase of an infection is relevant for transmission- An effective antiviral therapy has not yet been established. Steroids for anti-inflammatory therapy are not recommended- It is very important to prepare all actors in the health care system for a longer-term burden of inpatients and complications and to create the necessary capacities. Low-threshold diagnostic testing and rapid detection of infection chains remain essential for better control of the pandemic. An effective vaccine is urgent. |
21 | oxhe0dhx | what are the mortality rates overall and in specific populations | Analysis on 54 Mortality Cases of Coronavirus Disease 2019 in the Republic of Korea from January 19 to March 10, 2020 Since the identification of the first case of coronavirus disease 2019 (COVID-19), the global number of confirmed cases as of March 15, 2020, is 156,400, with total death in 5,833 (3.7%) worldwide. Here, we summarize the morality data from February 19 when the first mortality occurred to 0 am, March 10, 2020, in Korea with comparison to other countries. The overall case fatality rate of COVID-19 in Korea was 0.7% as of 0 am, March 10, 2020. |
46 | iau9kjg2 | what evidence is there for dexamethasone as a treatment for COVID-19? | COVID-19 and RAS: Unravelling an Unclear Relationship The renin-angiotensin system (RAS) plays a main role in regulating blood pressure and electrolyte and liquid balance. Previous evidence suggests that RAS may represent an important target for the treatment of lung pathologies, especially for acute respiratory distress syndrome and chronic fibrotic disease. The scientific community has recently focused its attention on angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor 1 (AT1R) inhibitors and their possible benefit/harms for patients infected by Coronavirus disease (COVID-19) who experience pneumonia, but there are still some doubts about the effects of these drugs in this setting. |
8 | isswwnzn | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Clinical Testing For Covid-19 Abstract As the novel coronavirus SARS-CoV-2 caused COVID-19 cases in the United States the initial test was developed and performed at the Center for Disease Control (CDC). As the number of cases increased the demand for tests multiplied, leading the CDC to utilize the Emergency Utilization Authorization to allow clinical and commercial laboratories to develop tests to detect the presence of the virus. Many nucleic acid tests based on reverse transcriptase-polymerase chain reaction (RT-PCR) were developed, each with different techniques, specifications and turnaround time. As the illnesses turned into a pandemic, testing became more crucial. The test supply became inadequate to meet the need that it had to be prioritized according to guidance. For surveillance, the need for serologic tests emerged. Here we review the timeline of test development, the turn-around times, the various approved tests and compare them as regards the genes they detect. We concentrate on the point-of-care tests and discuss the basis for new serologic tests. We discuss the testing guidance for prioritization and their application in a hospital setting. As SARS-CoV-2 virus arrived in the USA causing the COVID-19 illness, one of the most talked about issues in the management of the disease and the resulting pandemic has been clinical testing. A unique situation arose of a communicable and highly contagious disease necessitating the rapid diagnosis of patients and the identification of non-symptomatic infected persons. Unfortunately, the USA did not have a Food and Drug Administration (FDA) approved laboratory test for the illness. The FDA ultimately utilized its Emergency Use Authorizations (EUA) on February 4, 2020 to allow for more rapid and widespread development and implementation of in-vitro testing.1 Indeed, companies and organizations utilized the EUA to file applications for new tests based on different methodologies, amounting to 48 applications in the span of 3 months from the beginning of February to the end of April 2020. In addition, multiple other tests were put in place under a separate authorization by a Presidential memorandum in early March allowing laboratories that carry Clinical Laboratory Improvement Amendment (CLIA) certification to put tests in place without an EUA from the FDA. This created an unprecedented situation where the medical community and the public may not be familiar with the various new tests for COVID-19 that are offered to patients and hospitals. The purpose of this review is to provide information, up-to-date as of the date of submission of the manuscript to the journal, on the various tests that have been developed, their scientific basis and their interpretation. We give a real-world example demonstrating the time lag in the return of test results and review testing prioritization guidance since the supply of tests remains below the perceived need. |
4 | pim4d3ke | what causes death from Covid-19? | Complement pathway amplifies caspase-11–dependent cell death and endotoxin-induced sepsis severity Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11–dependent cell death contributes to pathology and decreases in survival time in sepsis models. Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation. Using a CRISPR-Cas9–mediated genome-wide screen, we identified novel mediators of caspase-11–dependent cell death. We found a complement-related peptidase, carboxypeptidase B1 (Cpb1), to be required for caspase-11 gene expression and subsequent caspase-11–dependent cell death. Cpb1 modifies a cleavage product of C3, which binds to and activates C3aR, and then modulates innate immune signaling. We find the Cpb1–C3–C3aR pathway induces caspase-11 expression through amplification of MAPK activity downstream of TLR4 and Ifnar activation, and mediates severity of LPS-induced sepsis (endotoxemia) and disease outcome in mice. We show C3aR is required for up-regulation of caspase-11 orthologues, caspase-4 and -5, in primary human macrophages during inflammation and that c3aR1 and caspase-5 transcripts are highly expressed in patients with severe sepsis; thus, suggesting that these pathways are important in human sepsis. Our results highlight a novel role for complement and the Cpb1–C3–C3aR pathway in proinflammatory signaling, caspase-11 cell death, and sepsis severity. |
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