207 lines
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207 lines
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants</strong> -
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The SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 RT-PCR-confirmed COVID-19 individuals with detailed demographics and followed up to seven months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization were associated with COVID-19 severity. A subgroup of high responders maintained high neutralizing responses over time, representing ideal convalescent plasma therapy donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal plasma donors and vaccine monitoring and design.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.19.20248567v2" target="_blank">SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants</a>
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<li><strong>How closely is COVID-19 related to HCoV, SARS, and MERS? : Clinical comparison of coronavirus infections and identification of risk factors influencing the COVID-19 severity using common data model (CDM)</strong> -
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<b>Background</b> South Korea was one of the epicenters for both the 2015 Middle East Respiratory Syndrome and 2019 COVID-19 outbreaks. However, there has been a lack of published literature, especially using the Electronic Medical Records (EMR), that provides a comparative summary of the prognostic factors present in the coronavirus-derived diseases. Therefore, in this study, we aimed to evaluate the distinct clinical traits between the infected patients of different coronaviruses to observe the extent of resemblance within the clinical features and to identify unique factors by disease severity that may influence the prognosis of COVID-19 patients. <b>Methods</b> We utilized the common data model (CDM), which is the database that houses the standardized EMR. We set COVID-19 as a reference group in comparative analyses. For statistical methods, we used Levene9s test, one-way ANOVA test, Scheffe post hoc test, and Games-howell post hoc test, and Student9s t-test for continuous variables, and chi-squared test and Fisher9s exact test for categorical variables. With the variables that reflected similarity in more than two comparisons between the disease groups yet significantly different between the COVID-19 severity groups, we performed univariate logistic regression to identify which common manifestations in coronaviruses are risk factors for severe COVID-19 outcomes. <b>Findings</b> We collected the records of 2840 COVID-19 patients, 67 MERS patients (several suspected cases included), 43 SARS suspected patients, and 87 HCoV patients. We found that a significantly higher number of COVID-19 patients had been diagnosed with comorbidities compared to the MERS and HCoV groups (48.5% vs. 10.4 %, p < 0.001 and 48.5% vs. 35.6%, p < 0.05) and also that the non-mild COVID-19 patients reported more comorbidities than the mild group (55.7% vs. 47.8%, p < 0.05). There were overall increases in the levels of fibrinogen in both sets of disease and severity groups. The univariate logistic regression showed that the male sex (OR: 1.66; CI: 1.29-2.13, p < 0.001), blood type A (OR: 1.80; CI: 1.40-2.31, p < 0.001), renal disease (OR: 3.27; CI: 2.34-4.55, p < 0.001), decreased creatinine level (OR: 2.05; CI: 1.45-2.88, p < 0.001), and elevated fibrinogen level (OR: 1.59, CI: 1.21-2.09, p < 0.001) are associated with the severe COVID-19 prognosis, whereas the patients reporting gastrointestinal symptoms (OR: 0.42; CI: 0.23-0.72, p < 0.01) and increased alkaline phosphatase (OR: 0.73; CI: 0.56-0.94, p < 0.05) are more less likely to experience complications and other severe outcomes from the SARS-CoV-2 infection. <b>Interpretation</b> The present study observed the highest resemblance between the COVID-19 and SARS groups as clinical manifestations that were present in SARS group were linked to the severity of COVID-19. In particular, male individuals with blood type A and previous diagnosis of kidney failure were shown to be more susceptible to developing the poorer outcomes during COVID-19 infection, with a presentation of an elevated level of fibrinogen.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.23.20237487v4" target="_blank">How closely is COVID-19 related to HCoV, SARS, and MERS? : Clinical comparison of coronavirus infections and identification of risk factors influencing the COVID-19 severity using common data model (CDM)</a>
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<li><strong>The King's College London Coronavirus Health and Experiences of Colleagues at King's Study: SARS-CoV-2 antibody response in an occupational sample</strong> -
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We report test results for SARS-CoV-2 antibodies in an occupational group of postgraduate research students and current members of staff at Kings College London. Between June and July 2020, antibody testing kits were sent to n=2296 participants; n=2004 (86.3%) responded, of whom n=1882 (93.9%) returned valid test results. Of those that returned valid results, n=124 (6.6%) tested positive for SARS-CoV-2 antibodies, with initial comparisons showing variation by age group and clinical exposure.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.09.10.20191841v3" target="_blank">The King's College London Coronavirus Health and Experiences of Colleagues at King's Study: SARS-CoV-2 antibody response in an occupational sample</a>
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<li><strong>THE TIME TO OFFER TREATMENT FOR COVID-19</strong> -
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BACKGROUND As of January 1, 2021, there have been 81,947,503 confirmed cases of COVID-19, resulting in 1,808,041 deaths worldwide. Several vaccines are now available for emergency use, but it will take many months to immunize the world population. There is a pressing need for outpatient treatment now. We reviewed the possible options. METHODS We reviewed up-to-date information from several sources to identify potential treatments to be utilized now for COVID-19. We searched for all ongoing, completed and published trial results with subject numbers of 100 or more, and used a targeted search to find announcements of unpublished trial results. RESULTS As of December 27, 2020, we identified 750 trials currently in recruitment phase. Of these, 122 were directed at prevention in healthy individuals, 100 were classified as treatment of outpatients with documented infection, and 390 were for treatment of hospitalized inpatients. There were 9 trials focusing on the post discharge Tail phase. Among the trials, there were 60 vaccine trials, 120 trials of hydroxychloroquine, 33 trials of alternative therapy, 12 trials of colchicine, 38 trials of anticoagulants, 22 trials of the RNA polymerase inhibitor favipiravir (FVP), 19 trials of interferons, 18 trials of glucocorticoid, and 58 trials of plasma based products. Closure of enrollment was projected by the end of the year for 153 trials. We found 83 publications reporting findings in human studies on 14 classes of agents, and on 7 vaccines. There were 45 randomized or active controlled studies, the rest retrospective observational analyses. Most publications dealt with hospitalized patients, only 18 publications in outpatients. Remdesivir, convalescent plasma, and synthetic anti-spike protein antibodies have been granted emergency use authorization in the United States. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. There is data supporting the use of several antiviral medications, some of which are in use in other countries. CONCLUSION. Vaccines and antibodies are highly antigen specific. There is a need for antiviral agents in addition to mass immunization. It will be necessary for public health authorities to make hard decisions, with limited data, to prevent the continued spread of the disease and deaths.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.05.27.20115238v9" target="_blank">THE TIME TO OFFER TREATMENT FOR COVID-19</a>
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<li><strong>Redeployment and training of healthcare professionals to Intensive Care during COVID-19: a systematic review</strong> -
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Background: A rapid influx of patients to intensive care and infection control measures during the COVID-19 pandemic required the rapid development of innovative redeployment and training strategies. Methods: We conducted a systematic search of 9 databases including key terms related to intensive care AND training AND redeployment AND healthcare workers. Analysis consisted of a narrative synthesis of quantitative study outputs, and a framework-based thematic analysis of qualitative study outputs and grey literature. These results were then combined applying an interpretative synthesis. Results: Twenty papers were analysed. These took place primarily in the UK (N=8, 40%) and USA (N=5, 25%). Themes included in the results are Redeployment: Implementation strategies and learnings; Redeployed staff experience and strategies to address their needs; Redeployed staff learning needs; Training formats offered and training evaluations; and Future redeployment and training concerns. Some of the redeployment implementation and training strategies documented in this review are: Skills-based redeployment, buddy support systems, and agreeing on locally-specific principles, rather than strict procedures. Conclusion: The COVID-19 pandemic presented unique challenges to deliver training promptly while following infection control recommendations and develop flexible redeployment strategies. This study synthesises original approaches to tackle these challenges which are relevant to inform the development of targeted and adaptative training and redeployment plans.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.01.21.21250230v2" target="_blank">Redeployment and training of healthcare professionals to Intensive Care during COVID-19: a systematic review</a>
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<li><strong>The National COVID Cohort Collaborative: Clinical Characterization and Early Severity Prediction</strong> -
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Background: The majority of U.S. reports of COVID-19 clinical characteristics, disease course, and treatments are from single health systems or focused on one domain. Here we report the creation of the National COVID Cohort Collaborative (N3C), a centralized, harmonized, high-granularity electronic health record repository that is the largest, most representative U.S. cohort of COVID-19 cases and controls to date. This multi-center dataset supports robust evidence-based development of predictive and diagnostic tools and informs critical care and policy. Methods and Findings: In a retrospective cohort study of 1,926,526 patients from 34 medical centers nationwide, we stratified patients using a World Health Organization COVID-19 severity scale and demographics; we then evaluated differences between groups over time using multivariable logistic regression. We established vital signs and laboratory values among COVID-19 patients with different severities, providing the foundation for predictive analytics. The cohort included 174,568 adults with severe acute respiratory syndrome associated with SARS-CoV-2 (PCR >99% or antigen <1%) as well as 1,133,848 adult patients that served as lab-negative controls. Among 32,472 hospitalized patients, mortality was 11.6% overall and decreased from 16.4% in March/April 2020 to 8.6% in September/October 2020 (p = 0.002 monthly trend). In a multivariable logistic regression model, age, male sex, liver disease, dementia, African-American and Asian race, and obesity were independently associated with higher clinical severity. To demonstrate the utility of the N3C cohort for analytics, we used machine learning (ML) to predict clinical severity and risk factors over time. Using 64 inputs available on the first hospital day, we predicted a severe clinical course (death, discharge to hospice, invasive ventilation, or extracorporeal membrane oxygenation) using random forest and XGBoost models (AUROC 0.86 and 0.87 respectively) that were stable over time. The most powerful predictors in these models are patient age and widely available vital sign and laboratory values. The established expected trajectories for many vital signs and laboratory values among patients with different clinical severities validates observations from smaller studies, and provides comprehensive insight into COVID-19 characterization in U.S. patients. Conclusions: This is the first description of an ongoing longitudinal observational study of patients seen in diverse clinical settings and geographical regions and is the largest COVID-19 cohort in the United States. Such data are the foundation for ML models that can be the basis for generalizable clinical decision support tools. The N3C Data Enclave is unique in providing transparent, reproducible, easily shared, versioned, and fully auditable data and analytic provenance for national-scale patient-level EHR data. The N3C is built for intensive ML analyses by academic, industry, and citizen scientists internationally. Many observational correlations can inform trial designs and care guidelines for this new disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.01.12.21249511v3" target="_blank">The National COVID Cohort Collaborative: Clinical Characterization and Early Severity Prediction</a>
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<li><strong>Agent-Based Simulation for Evaluation of Contact-Tracing Policies Against the Spread of SARS-CoV-2</strong> -
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The decline of active COVID-19 cases in many countries in the world has proved that lockdown policies are indeed a very effective measure to stop the exponential spread of the virus. Still, the danger of a second wave of infections is omnipresent and it is clear, that every policy of the lockdown has to be carefully evaluated and possibly replaced by a different, less restrictive policy, before it can be lifted. Tracing of contacts and consequential tracing and breaking of infection-chains is a promising and comparably straightforward strategy to help containing the disease, although its precise impact on the epidemic is unknown. In order to quantify the benefits of tracing and similar policies we developed an agent-based model that not only validly depicts the spread of the disease, but allows for exploratory analysis of containment policies. We will describe our model and perform case studies in which we use the model to quantify impact of contact tracing in different characteristics and draw valuable conclusions about contact tracing policies in general.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.05.12.20098970v4" target="_blank">Agent-Based Simulation for Evaluation of Contact-Tracing Policies Against the Spread of SARS-CoV-2</a>
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<li><strong>Hospital load and increased COVID-19 related mortality - a nationwide study in Israel</strong> -
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The spread of Coronavirus disease 19 (COVID-19) has led to many healthcare systems being overwhelmed by the rapid emergence of new cases within a short period of time. We explore the ramifications of hospital load due to COVID-19 morbidity on COVID-19 in-hospital patient mortality. We address this question with a nationwide study based on the records of all 22,636 COVID-19 patients hospitalized in Israel from mid-July 2020 to mid-January 2021. We show that even under moderately heavy patient load (>500 countrywide hospitalized severely-ill patients; the Israeli Ministry of Health defined 800 severely-ill patients as the maximum capacity allowing adequate treatment), in-hospital mortality rate of patients with COVID-19 significantly increased compared to periods of lower patient load (250-500 severely-ill patients): 14-day mortality rates were 22.1% (Standard Error 3.1%) higher (mid-September to mid-October) and 27.2% (Standard Error 3.3%) higher (mid-December to mid-January). We further show this higher mortality rate cannot be attributed to changes in the patient population during periods of heavier load.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.01.11.21249526v3" target="_blank">Hospital load and increased COVID-19 related mortality - a nationwide study in Israel</a>
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<li><strong>A STUDY ON SOME STRUCTURAL FEATURES RESPONSIBLE FOR SARS-COV-2 INFECTION FATALITY</strong> -
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In this article Covid19 is structurally analysed to establish the pathogenic attack through its spike protein ( 1 ) The most of the bio -macromolecules starting from globular proteins to viruses with a high molecular weight average showing polymeric nature as to induce their biological activities. The tremendous infectivity mainly depends on one most important hydrodynamic properties like Zigzag nature of viral walk ( 2 ) for a specific molecular weight ( M ). Hydrodynamic s nature of mRNA –viruses like SARS-COV-2 is analysed to compute the random– zigzag motion ( 2,3) of the virus known as Radius of Gyration( Rg ) value of virus . For computation of Rg a standard curve( 4 )of Rg – M is statistically analysed with best fit regression analysis like Morgan – Morgan – Finney ( MMF ) ( 5 ) model . This zigzag – random walk ( 2 ) of SARS-COV-2 molecule computed from Rg value may be considered as fatality rate of infection ( 6 ).
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🖺 Full Text HTML: <a href="https://osf.io/m62ba/" target="_blank">A STUDY ON SOME STRUCTURAL FEATURES RESPONSIBLE FOR SARS-COV-2 INFECTION FATALITY</a>
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<li><strong>The Burden of Being Certain: National Identity Certainty Predicts Support for COVID-Related Draconian Measures and Outgroup Conspiracy Beliefs</strong> -
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The COVID-19 pandemic has introduced various controversies. Some people debate about the usage of “draconian” measures of social distancing (e.g., lockdown). Others concern the origin of the pandemic with some buying conspiracy theories that attribute the cause of COVID-19 to the plot of some powerful outgroups. The current research examined national identity certainty (i.e., the certainty people placed in national identity) as predictor of these beliefs and attitudes. Two studies (total N = 625), one longitudinal and one cross-sectional, revealed that individual differences in national identity certainty predicted increased support of draconian measures and increased outgroup conspiracy beliefs. Moreover, realistic (but not symbolic) threat accounted for the increased support for draconian measures. Symbolic (but not realistic) threat accounted for the increased outgroup conspiracy beliefs. Our findings highlight how national identity certainty constrains individuals’ beliefs and attitudes towards issues related to the pandemic.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/zgs52/" target="_blank">The Burden of Being Certain: National Identity Certainty Predicts Support for COVID-Related Draconian Measures and Outgroup Conspiracy Beliefs</a>
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<li><strong>Societal Change and Wisdom: Insights from the World after Covid Project</strong> -
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How will the world change as a result of the Covid-19 pandemic? What can people do to best adapt to the societal changes ahead? To answer these questions, over the course of the summer-fall 2020 we launched the World After COVID Project, interviewing more than 50 of the world’s leading scholars in the behavioral and social sciences, including fellows of national academies and presidents of major scientific societies. Experts independently shared their thoughts on what effects the COVID-19 pandemic will have on our societies and provided advice for successful response to new challenges and opportunities. Using mixed-method and natural language processing analyses, we distilled and analyzed these predictions and suggestions, observing a diversity of scenarios. Results also show that half of the experts approach their post-Covid predictions dialectically, highlighting both positive and negative features of the same prediction. Moreover, prosocial goals and meta-cognition—two chief tenants of the Common Wisdom model—were evident in their recommendations for how to cope with possible changes. The project provides a time capsule of experts’ predictions during major societal changes. We discuss implications for strengthening focus on prediction (vs. mere explanation) in psychological science as well as the value of uncertainty and dialecticism in forecasting.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/yma8f/" target="_blank">Societal Change and Wisdom: Insights from the World after Covid Project</a>
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<li><strong>Potential Pfizer-BioNTech SARS CoV-2 mRNA Faulty Vaccine Design: Could it Reason for the Post Vaccination Sudden Death Reports?</strong> -
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The public has a moral and legal right to know the potential hazards of COVID-19 newly approved vaccines to freely decide whether to receive any, after an informed personalized risk benefit ratio is provided. Since most of the serious adverse effects and fatalities are reported with the Pfizer-BioNTech SARS CoV-2 mRNA vaccine and a faulty design has been suggested by another researcher, we suggest that there is a high likelihood for a short-term potential hazard that might be a company specific, to be also compared it to its Moderna’s counterpart. We discuss the potential autoimmune risk that is associated with mRNA-based vaccines liking it with some of the newly reported post vaccination reports of serious adverse effects including sudden death. Importantly, we recommend CDC to change its neutral recommendation and to advice against administration of nucleic acid-based vaccines to persons complaining from autoimmune diseases and to suspend the emergency approval granted to Pfizer-BioNTech SARS CoV-2 mRNA vaccine until full investigations are performed and discussed.
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🖺 Full Text HTML: <a href="https://osf.io/4gzd3/" target="_blank">Potential Pfizer-BioNTech SARS CoV-2 mRNA Faulty Vaccine Design: Could it Reason for the Post Vaccination Sudden Death Reports?</a>
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<li><strong>Exploring the natural origins of SARS-CoV-2</strong> -
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The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2 and the distance (~1500 km) from Wuhan to Yunnan province, where the closest evolutionary related coronaviruses circulating in horseshoe bats have been identified, is fueling speculation on the natural origins of SARS-CoV-2. Here we analyse SARS-CoV-2's related horseshoe bat and pangolin Sarbecoviruses and confirm Rhinolophus affinis continues to be the likely reservoir species as its host range extends across Central and Southern China. This would explain the bat Sarbecovirus recombinants in the West and East China, trafficked pangolin infections and bat Sarbecovirus recombinants linked to Southern China. Recent ecological disturbances as a result of changes in meat consumption could then explain SARS-CoV-2 transmission to humans through direct or indirect contact with the reservoir wildlife, and subsequent emergence towards Hubei in Central China. The only way, however, of finding the animal progenitor of SARS-CoV-2 as well as the whereabouts of its close relatives, very likely capable of posing a similar threat of emergence in the human population and other animals, will be by increasing the intensity of our sampling.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.22.427830v1" target="_blank">Exploring the natural origins of SARS-CoV-2</a>
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<li><strong>CCR1 regulatory variants linked to pulmonary macrophage recruitment in severe COVID-19</strong> -
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Genome-wide association studies have identified 3p21.31 as the main risk locus for severe symptoms and hospitalization in COVID-19 patients. To elucidate the mechanistic basis of this genetic association, we performed a comprehensive epigenomic dissection of the 3p21.31 locus. Our analyses pinpoint activating variants in regulatory regions of the chemokine receptor-encoding CCR1 gene as potentially pathogenic by enhancing infiltration of monocytes and macrophages into the lungs of patients with severe COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.22.427813v1" target="_blank">CCR1 regulatory variants linked to pulmonary macrophage recruitment in severe COVID-19</a>
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<li><strong>Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies</strong> -
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SARS-CoV-2 Spike-specific antibodies contribute the majority of the neutralizing activity in most convalescent human sera. Two SARS-CoV-2 variants, N501Y.V1 (also known as B.1.1.7 lineage or VOC-202012/01) and N501Y.V2 (B.1.351 lineage), reported from the United Kingdom and South Africa, contain several mutations in the receptor binding domain of Spike and are of particular concern. To address the infectivity and neutralization escape phenotypes potentially caused by these mutations, we used SARS-CoV-2 pseudovirus system to compare the viral infectivity, as well as the neutralization activities of convalescent sera and monoclonal antibodies (mAbs) against SARS-CoV-2 variants. Our results showed that N501Y Variant 1 and Variant 2 increase viral infectivity compared to the reference strain (wild-type, WT) in vitro. At 8 months after symptom onset, 17 serum samples of 20 participants (85%) retaining titers of ID50 >40 against WT pseudovirus, whereas the NAb titers of 8 samples (40%) and 18 samples (90%) decreased below the threshold against N501Y.V1 and N501Y.V2, respectively. In addition, both N501Y Variant 1 and Variant 2 reduced neutralization sensitivity to most (6/8) mAbs tested, while N501Y.V2 even abrogated neutralizing activity of two mAbs. Taken together the results suggest that N501Y.V1 and N501Y.V2 reduce neutralization sensitivity to some convalescent sera and mAbs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.22.427749v1" target="_blank">Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dexamethasone for COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: Dexamethasone<br/><b>Sponsor</b>: University of Oklahoma<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fluvoxamine Administration in Moderate SARS-CoV-2 (COVID-19) Infected Patients</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Placebo; Drug: Fluvoxamine<br/><b>Sponsor</b>: SigmaDrugs Research Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin 0.6mg/kg/day; Drug: Ivermectin 1.0mg/kg/day; Drug: Placebo; Drug: Hydroxychloroquine<br/><b>Sponsor</b>: Corpometria Institute<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>APT™ T3X on the COVID-19 Contamination Rate</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Tetracycline hydrochloride 3%; Drug: Placebo<br/><b>Sponsors</b>: University of Nove de Julho; Santa Casa de Misericórdia de Porto Alegre<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of ORTD-1 in Patients Hospitalized With COVID-19 Related Pneumonia</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ORTD-1 low dose; Drug: ORTD-1 mid dose; Drug: ORTD-1 high dose; Other: Vehicle control<br/><b>Sponsor</b>: Oryn Therapeutics, LLC<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rapid Diagnosis of COVID-19 by Chemical Analysis of Exhaled Air</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Diagnostic Test: Performance evaluation (sensitivity and specificity) for COVID-19 diagnosis of the Vocus PTR-TOF process<br/><b>Sponsor</b>: Hospices Civils de Lyon<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Immunologic Antiviral Therapy With Omalizumab</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: Omalizumab; Other: Placebo<br/><b>Sponsor</b>: McGill University Health Centre/Research Institute of the McGill University Health Centre<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IMUNOR® Preparation in the Prevention of COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: IMUNOR<br/><b>Sponsor</b>: University Hospital Ostrava<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Experimentation With Tenofovir Disoproxyl Fumarate and Emtricitabine for COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Vitamin C 500 MG Oral Tablet; Drug: Tenofovir disoproxyl fumarate 300 MG Oral Tablet; Drug: Tenofovir disoproxyl fumarate 300 MG plus emtricitabine 200 MG Oral Tablet<br/><b>Sponsors</b>: Universidade Federal do Ceara; Conselho Nacional de Desenvolvimento Científico e Tecnológico; São José Hospital for Infectious Diseases - HSJ; Central Laboratory of Public Health of Ceará - Lacen-CE<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Doxycycline Tablets; Drug: Rivaroxaban 15Mg Tab; Combination Product: Hydroxychloroquine and Azithromycin<br/><b>Sponsor</b>: Yaounde Central Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase Ⅱb Clinical Trial of Recombinant Corona Virus Disease-19 (COVID-19) Vaccine (Sf9 Cells)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant COVID-19 vaccine (Sf9 cells); Biological: Placebo<br/><b>Sponsors</b>: Jiangsu Province Centers for Disease Control and Prevention; West China Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Participants ≥ 60 Years of Age and Hospitalized With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: BGE-175; Other: Placebo<br/><b>Sponsor</b>: BioAge Labs, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiseptic Mouth Rinses to Reduce Salivary Viral Load in COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Betadine© bucal 100 mg/ml; Drug: Oximen® 3%; Drug: Clorhexidine Dental PHB©; Drug: Vitis Xtra Forte©; Drug: Distilled Water<br/><b>Sponsors</b>: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana; Hospital Universitario Fundación Jiménez Díaz; Hospital Universitario General de Villalba; Hospital Universitario Infanta Elena; Hospital Universitario Virgen de la Arrixaca; Hospital Clínico Universitario de Valencia; Dentaid SL<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pilot Study of Cefditoren Pivoxil in COVID-19 Patients With Mild to Moderate Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Drug: Cefditoren pivoxil 400mg<br/><b>Sponsor</b>: Meiji Pharma Spain S.A.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Early Use of Hyperimmune Plasma in COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: hyperimmune plasma<br/><b>Sponsors</b>: Catherine Klersy; Policlinico San Matteo Pavia Fondazione IRCCS<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior</strong> - The fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Feasibility of using alternative swabs and storage solutions for paired SARS-CoV-2 detection and microbiome analysis in the hospital environment</strong> - CONCLUSIONS: Compared to using a clinical-grade synthetic swab, detection of SARS-CoV-2 from environmental samples collected from ICU rooms of patients with COVID was similar using consumer-grade swabs, stored in 95% ethanol. The yield was best from the swab head rather than the eluent and the low level of RNase activity and lack of antibiotics in these samples makes it possible to perform concomitant microbiome analyses. Video abstract.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody persistence in the first six months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study</strong> - CONCLUSION: Neutralizing antibodies persisted at six months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and targeted treatment of autoimmune and inflammatory diseases</strong> - The interleukin (IL)-1 family member IL-1α is a ubiquitous and pivotal pro-inflammatory cytokine. The IL-1α precursor is constitutively present in nearly all cell types in health, but is released upon necrotic cell death as a bioactive mediator. IL-1α is also expressed by infiltrating myeloid cells within injured tissues. The cytokine binds the IL-1 receptor 1 (IL-1R1), as does IL-1β, and induces the same pro-inflammatory effects. Being a bioactive precursor released upon tissue damage and...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice</strong> - SARS-CoV-2 is a single stranded RNA (ssRNA) virus and contains GU-rich sequences distributed abundantly in the genome. In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. A serum protein called serum amyloid P (SAP) has a calming effect on the innate immune system and shows efficacy as a therapeutic for fibrosis...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Host cell glutamine metabolism as a potential antiviral target</strong> - A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Experimental data using candesartan and captopril indicate no double-edged sword effect in COVID-19</strong> - The key link between renin-angiotensin system (RAS) and COVID-19 is ACE2 (angiotensin converting enzyme-2), which acts as a double-edged sword, because ACE2 increases the tissue anti-inflammatory response but it is also the entry receptor for the virus. There is an important controversy on several drugs that regulate RAS activity and possibly ACE2, and are widely used, particularly by patients most vulnerable to severe COVID-19. In the lung of healthy rats, we observed that candesartan (an...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19</strong> - SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein</strong> - The multifunctional nucleocapsid (N) protein in SARS-CoV-2 binds the ~30 kb viral RNA genome to aid its packaging into the 80-90 nm membrane-enveloped virion. The N protein is composed of N-terminal RNA-binding and C-terminal dimerization domains that are flanked by three intrinsically disordered regions. Here we demonstrate that the N protein's central disordered domain drives phase separation with RNA, and that phosphorylation of an adjacent serine/arginine rich region modulates the physical...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta-CoV that recently emerged as a human pathogen and is the causative agent of the COVID-19 pandemic. A molecular framework of how the virus manipulates host cellular machinery to facilitate infection remains unclear. Here, we focus on SARS-CoV-2 NSP1, which is proposed to be a virulence factor that inhibits protein synthesis by directly binding the human ribosome. We demonstrate biochemically that NSP1 inhibits translation of...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Quinacrine, an Antimalarial Drug with Strong Activity Inhibiting SARS-CoV-2 Viral Replication In Vitro</strong> - Quinacrine (Qx), a molecule used as an antimalarial, has shown anticancer, antiprion, and antiviral activity. The most relevant antiviral activities of Qx are related to its ability to raise pH in acidic organelles, diminishing viral enzymatic activity for viral cell entry, and its ability to bind to viral DNA and RNA. Moreover, Qx has been used as an immunomodulator in cutaneous lupus erythematosus and various rheumatological diseases, by inhibiting phospholipase A2 modulating the Th1/Th2...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cholesterol 25-hydroxylase suppresses porcine deltacoronavirus infection by inhibiting viral entry</strong> - Cholesterol 25-hydroxylase (CH25 H) is a key enzyme regulating cholesterol metabolism and also acts as a broad antiviral host restriction factor. Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus that can cause vomiting, diarrhea, dehydration and even death in newborn piglets. In this study, we found that PDCoV infection significantly upregulated the expression of CH25H in IPI-FX cells, a cell line of porcine ileum epithelium. Overexpression of CH25H inhibited...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of drug-metabolizing enzymes by Qingfei Paidu decoction: implication of herb-drug interactions in COVID-19 pharmacotherapy</strong> - Corona Virus Disease 2019 (COVID-19) has spread all over the world and brings significantly negative effects on human health. To fight against COVID-19 in a more efficient way, drug-drug or drug-herb combinations are frequently used in clinical settings. The concomitant use of multiple medications may trigger clinically relevant drug/herb-drug interactions. This study aims to assay the inhibitory potentials of Qingfei Paidu decoction (QPD, a Chinese medicine compound formula recommended for...</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting SARS-CoV-2 Viral Proteases as a Therapeutic Strategy to Treat COVID-19</strong> - The 21^(st) century has witnessed three outbreaks of coronavirus (CoVs) infections caused by severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV and SARS-CoV-2. Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, spreads rapidly and since the discovery of the first COVID-19 infection in December 2019, has caused 1.2 million deaths worldwide and 226,777 deaths in the United States alone. The high amino acid similarity between SARS-CoV-1 and SARS-CoV-2...</p></li>
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||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19, Angiotensin-Converting Enzyme 2 and Renin-Angiotensin System Inhibition: Implications for Practice</strong> - CONCLUSIONS: Further randomized trials are needed to answer definitely the question of whether RAS inhibitors are harmful or beneficial to patients with COVID-19.</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<ul>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU314054415">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313300659">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Covid 19 - Chewing Gum</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313269181">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19</strong> - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN313339294">link</a></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fahrzeuglüftungssystem und Verfahren zum Betreiben eines solchen Fahrzeuglüftungssystems</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Die Erfindung betrifft ein Fahrzeuglüftungssystem (1) zum Belüften einer Fahrgastzelle (2) eines Fahrzeugs (3), mit einem Umluftpfad (5). Die Erfindung ist gekennzeichnet durch eine wenigstens abschnittsweise in einen Umluftansaugbereich (4) des Umluftpads (5) hineinreichende Sterilisationseinrichtung (6), wobei die Sterilisationseinrichtung (6) dazu eingerichtet ist von einem aus der Fahrgastzelle (2) entnommenen Luftstrom getragene Schadstoffe zu inaktivieren und/oder abzutöten.</p></li>
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</ul>
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<img alt="embedded image" id="EMI-D00000"/>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE313868337">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251184">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251182">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>"AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2."</strong> - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN312324209">link</a></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mund-Nasen-Bedeckung</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Mund-Nasen-Bedeckung (1), wobei die Mund-Nasen-Bedeckung (1) mindestens an einem Ohr eines Trägers magnetisch befestigbar ist.</p></li>
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</ul>
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<img alt="embedded image" id="EMI-D00000"/>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE313866760">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Haptens, hapten conjugates, compositions thereof and method for their preparation and use</strong> - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU311608060">link</a></p></li>
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</ul>
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