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198 lines
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<title>19 August, 2022</title>
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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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<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>A syntenin inhibitor blocks endosomal entry of SARS-CoV-2 and a panel of RNA viruses</strong> -
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Viruses are dependent on interactions with host factors in order to efficiently establish an infection and replicate. Targeting such interactions provides an attractive strategy to develop novel antivirals. Syntenin is a protein known to regulate the architecture of cellular membranes by its involvement in protein trafficking, and has previously been shown to be important for HPV infection. Here we show that a highly potent and metabolically stable peptide inhibitor that binds to the PDZ1 domain of syntenin inhibits SARS-CoV-2 infection by blocking the endosomal entry of the virus. Furthermore, we found that the inhibitor also hampered chikungunya infection, and strongly reduced flavivirus infection, which are completely dependent on receptor mediated endocytosis for their entry. In conclusion, we have identified a novel pan-viral inhibitor that efficiently target a broad range of RNA viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.18.504268v1" target="_blank">A syntenin inhibitor blocks endosomal entry of SARS-CoV-2 and a panel of RNA viruses</a>
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<li><strong>A note on variable susceptibility, the herd-immunity threshold and modeling of infectious diseases</strong> -
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The unfolding of the COVID-19 pandemic has been very difficult to predict using mathematical models for infectious diseases. While it has been demonstrated that variations in susceptibility have a damping effect on key quantities such as the incidence peak, the herd-immunity threshold and the final size of the pandemic, this complex phenomenon is almost impossible to measure or quantify, and it remains unclear how to incorporate it for modeling and prediction. In this work we show that, from a modeling perspective, variability in susceptibility on an individual level is equivalent with a fraction theta of the population having an ``artificial99 sterilizing immunity. Given that this new parameter theta can be estimated, we also derive formulas for R0, the herd-immunity threshold and the final size of the pandemic. In the particular case of SARS-CoV-2, there is by now undoubtedly variable susceptibility due to waning immunity from both vaccines and previous infections, and our findings may be used to greatly simplify models. If such variations were also present prior to the first wave, as indicated by a number of studies, these findings can help explain why the magnitude of the initial waves of SARS-CoV-2 was relatively low, compared to what one may have expected based on standard models.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.07.08.21260175v2" target="_blank">A note on variable susceptibility, the herd-immunity threshold and modeling of infectious diseases</a>
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<li><strong>Digital Health Interventions and Quality of Home-based Primary Care for Older Adults: A Scoping Review Protocol</strong> -
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Introduction: Digital health interventions have expanded, particularly in home-based primary care (HBPC) following the increase in the older adult population and the need to respond to the higher demand of chronic conditions and health frailties of this population. There was an even greater demand with COVID-19 and subsequent isolation/social distancing measures for this group considered at risk. The objective of this study is to map and identify the uses and types of digital health interventions and their impacts on the quality of HBPC for older adults worldwide. Methods and analysis: This is a scoping review protocol which will enable a rigorous, transparent and reliable synthesis of knowledge. The review will be developed in the theoretical perspective of Arksey and O malley, with updates by Levac et al. and Peters et al. based on the Joanna Briggs Institute manual, and guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Data from white literature will be extracted from multidisciplinary health databases such as: the Virtual Health Library, LILACS, PubMed, Scopus, Web of Science, CINAHL and Embase; while Google Scholar will be used for gray literature. No date limit or language restrictions will be determined. The quantitative data will be analyzed through descriptive statistics and qualitative data through thematic analysis. The results will be submitted to stakeholder consultation for preliminary sharing of the study and will later be disseminated through publication in open access scientific journals, scientific events and academic and community journals. The full scoping review report will present the main impacts, challenges, opportunities and gaps found in publications related to the use of digital technologies in primary home care. Discussion: The organization of this protocol will increase the methodological rigor, quality, transparency and accuracy of scoping reviews, reducing the risk of bias.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.01.22273008v2" target="_blank">Digital Health Interventions and Quality of Home-based Primary Care for Older Adults: A Scoping Review Protocol</a>
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</div></li>
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<li><strong>Trends in risk factors and symptoms associated with SARS-CoV-2 and Rhinovirus test positivity in King County, Washington: A Test-Negative Design Study of the Greater Seattle Coronavirus Assessment Network</strong> -
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Importance: Few US studies have reexamined risk factors for SARS-CoV-2 positivity in the context of widespread vaccination and new variants or considered risk factors for co-circulating endemic viruses, such as rhinovirus. Objective: To understand how risk factors and symptoms associated with SARS-CoV-2 test positivity changed over the course of the pandemic and to compare these to the factors associated with rhinovirus test positivity. Design: This test-negative design study used multivariable logistic regression to assess associations between SARS-CoV-2 and rhinovirus test positivity and self-reported demographic and symptom variables over a 22-month period. Setting: King County, Washington, June 2020-April 2022 Participants: 23,278 symptomatic individuals of all ages enrolled in a cross-sectional community surveillance study. Exposures: Self-reported data for 15 demographic and health behavior variables and 16 symptoms. Main Outcome(s) and Measure(s): RT-PCR confirmed SARS-CoV-2 or rhinovirus infection. Results: Close contact with a SARS-CoV-2 case (adjusted odds ratio, aOR 4.3, 95% CI 3.7-5.0) and loss of smell/taste (aOR 3.7, 95% CI 3.0-4.5) were the variables most associated with SARS-CoV-2 test positivity, but both attenuated during the Omicron period. Contact with a vaccinated case (aOR 2.4, 95% CI 1.7-3.3) was associated with a lower odds of test positivity than contact with an unvaccinated case (aOR 4.4, 95% CI 2.7-7.3). Sore throat was associated with Omicron infection (aOR 2.3, 95% CI 1.6-3.2) but not Delta. Vaccine effectiveness for participants fully vaccinated with a booster dose was 43% (95% CI 11-63%) for Omicron and 92% (95% CI 61-100%) for Delta. Variables associated with rhinovirus test positivity included age <12 years (aOR 4.0, 95% CI 3.5-4.6) and reporting a runny or stuffy nose (aOR 4.6, 95% CI 4.1-5.2). Race, region, and household crowding were significantly associated with both SARS-CoV-2 and rhinovirus test positivity. Conclusions and Relevance: Estimated risk factors and symptoms associated with SARS-CoV-2 infection have changed over time. There was a shift in reported symptoms between the Delta and Omicron variants as well as reductions in the protection provided by vaccines. Racial and socioeconomic disparities persisted in the third year of SARS-CoV-2 circulation and were also present in rhinovirus infection, although the causal pathways remain unclear. Trends in testing behavior and availability may influence these results.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.12.22278203v1" target="_blank">Trends in risk factors and symptoms associated with SARS-CoV-2 and Rhinovirus test positivity in King County, Washington: A Test-Negative Design Study of the Greater Seattle Coronavirus Assessment Network</a>
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<li><strong>Two years of Covid-19: Excess mortality by age, region, gender, and race/ethnicity in the United States during the Covid-19 pandemic, March 1, 2020, through February 28, 2022</strong> -
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I<b>ntroduction:</b> Excess mortality does not depend on labeling the cause of death and is an accurate representation of the pandemic population-level effects. A comprehensive evaluation of all-cause excess mortality in the United States during the first two years of the Covid-19 pandemic, stratified by age, sex, region, and race/ethnicity can provide insight into the extent and variation in harm. <b>Methods:</b> With Centers for Disease Control and Prevention (CDC)/National Center for Health Statistics (NCHS) data from 2014-2022, we use seasonal autoregressive integrated moving averages (sARIMA) to estimate excess mortality during the pandemic, defined as the difference between the number of observed and expected deaths. We continuously correct the number of monthly expected deaths to reflect the decreased population owing to cumulative pandemic-associated excess deaths recorded. We calculate excess mortality for the total US population, and by age, sex, US census division, and race/ethnicity. <b>Results:</b> From March 1, 2020, through February 28, 2022, there were 1.17 million excess deaths in the United States. Overall, mortality was 20% higher than expected during the study period. Of the excess deaths, 799,477 (68%) were among residents aged 65 and older. The largest relative increase in all-cause mortality was 27% among adults ages 18-49 years. Males comprised most of the excess mortality (57%), though this predominance declined with increasing age. A higher relative increase in mortality occurred among Hispanic and non-Hispanic Black persons. Excess mortality differed by region; the highest rates were in the South, including in the population ages ≥65 years. Excess mortality rose and fell contemporaneously with Covid-19 waves. <b>Conclusion:</b> In the first two years of the pandemic, the US experienced 1.17 million excess deaths, with greater relative increases in all-cause mortality among men, in Black and Hispanic people, and in the South.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.16.22278800v1" target="_blank">Two years of Covid-19: Excess mortality by age, region, gender, and race/ethnicity in the United States during the Covid-19 pandemic, March 1, 2020, through February 28, 2022</a>
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<li><strong>A probabilistic approach for the study of epidemiological dynamics of infectious diseases: basic model and properties</strong> -
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The dynamics of epidemiological phenomena associated to infectious diseases have long been modelled with different approaches. However, recent pandemic events exposed many areas of opportunity to improve the existing models. We develop a model based on the idea that infection and also, transitions between different stages during an infection and possibly the disease that it may cause, are alike sampling processes. The resulting modelling scheme proves to be easy to implement but very robust, and easy to extend to answer questions that emerge from close examination of data trends in the COVID-19 pandemic, and other infectious diseases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.16.22278844v1" target="_blank">A probabilistic approach for the study of epidemiological dynamics of infectious diseases: basic model and properties</a>
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<li><strong>How Have Global Scientists Responded to Tackling COVID-19?</strong> -
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Since the outbreak of COVID-19, the global scientific communities across almost all countries have made urgent, intensive, and continuous effort on understanding, fighting and modeling the COVID-19 pandemic. COVID-19 research turns out to be the first overwhelming global scientific reaction to significant global crises and threats. This literature analysis report collects and summarizes the profiles, trends, quality and impact of this global scientific response. It collects and analyzes 346,267 scientific references in English, involving researchers from 189 countries and regions in 27 subject areas. The report generates a picture of how global scientists have responded to COVID-19 between Jan 2020 and Mar 2022 in terms of their publication quantity, impact, focused major problems, and research areas and methods over country/region, discipline and time and collaboratively. The report also captures broad-reaching distributions and trends of modeling COVID-19 by AI, data science, analytics, shallow and deep machine learning, epidemic modeling, applied mathematics, and social science methods, etc. We further show the correlations between publication quality and quantity and economic status and COVID-19 infections globally and in major countries and regions. The literature analysis results of this global scientific response to COVID-19 present a comprehensive global, regional and subject-specific picture of the significant cross-disciplinary, cross-country, cross-problem, and cross-technique profiles and differences of the COVID-19 publication quantity and quality. The report also discloses significant imbalances in the COVID-19 research across countries/regions, subject areas, problems, topics, methods, research collaborations, and economic statuses. We share the source and analytical data of this global literature analysis for further research on this unprecedented and future crises.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.16.22278871v1" target="_blank">How Have Global Scientists Responded to Tackling COVID-19?</a>
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<li><strong>RapiD_AI: A framework for Rapidly Deployable AI for novel disease & pandemic preparedness</strong> -
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COVID-19 is unlikely to be the last pandemic that we face. According to an analysis of a global dataset of historical pandemics from 1600 to the present, the risk of a COVID-like pandemic has been estimated as 2.63% annually or a 38% lifetime probability. This rate may double over the coming decades. While we may be unable to prevent future pandemics, we can reduce their impact by investing in preparedness. In this study, we propose RapiD_AI: a framework to guide the use of pretrained neural network models as a pandemic preparedness tool to enable healthcare system resilience and effective use of ML during future pandemics. The RapiD_AI framework allows us to build high-performing ML models using data collected in the first weeks of the pandemic and provides an approach to adapt the models to the local populations and healthcare needs. The motivation is to enable healthcare systems to overcome data limitations that prevent the development of effective ML in the context of novel diseases. We digitally recreated the first 20 weeks of the COVID-19 pandemic and experimentally demonstrated the RapiD_AI framework using domain adaptation and inductive transfer. We (i) pretrain two neural network models (Deep Neural Network and TabNet) on a large Electronic Health Records dataset representative of a general in-patient population in Oxford, UK, (ii) fine-tune using data from the first weeks of the pandemic, and (iii) simulate local deployment by testing the performance of the models on a held-out test dataset of COVID-19 patients. Our approach has demonstrated an average relative/absolute gain of 4.92/4.21% AUC compared to an XGBoost benchmark model trained on COVID-19 data only. Moreover, we show our ability to identify the most useful historical pretraining samples through clustering and to expand the task of deployed models through inductive transfer to meet the emerging needs of a healthcare system without access to large historical pretraining datasets.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.09.22278600v2" target="_blank">RapiD_AI: A framework for Rapidly Deployable AI for novel disease &amp; pandemic preparedness</a>
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<li><strong>Longitudinal lung function assessment of patients hospitalised with COVID-19 using 1H and 129Xe lung MRI</strong> -
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<b>Introduction</b>: Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pathophysiological pulmonary changes during the post-acute period in these patients remains unclear. <b>Methods</b>: Patients who were hospitalised due to COVID 19 pneumonia underwent a pulmonary <sup>1</sup>H and <sup>129</sup>Xe MRI protocol at 6, 12, 25 and 50 weeks after hospital admission. The imaging protocol included: ultra short echo time, dynamic contrast enhanced lung perfusion, <sup>129</sup>Xe lung ventilation, <sup>129</sup>Xe diffusion weighted and <sup>129</sup>Xe 3D spectroscopic imaging of gas exchange. <b>Results</b>: 9 patients were recruited and underwent MRI at 6 (n=9), 12 (n=9), 25 (n=6) and 51 (n=8) weeks after hospital admission. Patients with signs of interstitial lung damage at 3 months were excluded from this study. At 6 weeks after hospital admission, patients demonstrated impaired <sup>129</sup>Xe gas transfer (RBC:M) but normal lung microstructure (ADC, Lm<sub>D</sub>). Minor ventilation abnormalities present in four patients were largely resolved in the 6 to 25 week period. At 12 week follow up, all patients with lung perfusion data available (n=6) showed an increase in both pulmonary blood volume and flow when compared to 6 weeks, though this was not statistically significant. At 12 week follow up, significant improvements in <sup>129</sup>Xe gas transfer were observed compared to 6-week examinations, however <sup>129</sup>Xe gas transfer remained abnormally low at weeks 12, 25 and 51. Changes in <sup>129</sup>Xe gas transfer correlated significantly with changes in pulmonary blood volume and TLCO Z-score. <b>Conclusions</b>: This study demonstrates that 1H and <sup>129</sup>Xe MRI is sensitive to functional pulmonary changes in the follow up of patients who were hospitalised with COVID-19. Impairment of xenon transfer may indicate damage to the pulmonary microcirculation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.06.22272747v2" target="_blank">Longitudinal lung function assessment of patients hospitalised with COVID-19 using 1H and 129Xe lung MRI</a>
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<li><strong>Inconsistent directions of change in case severity across successive SARS-CoV-2 variant waves suggests an unpredictable future</strong> -
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Objective To determine how the severity of successively dominant SARS-CoV-2 variants changed over the course of the COVID-19 pandemic. Design Retrospective cohort analysis. Setting Community- and hospital- sequenced COVID-19 cases in the NHS Greater Glasgow and Clyde (NHS GG&C) Health Board. Participants All sequenced non-nosocomial adult COVID-19 cases in NHS GG&C infected with the relevant SARS-CoV-2 lineages during analysis periods. B.1.177/Alpha: 1st November 2020 - 30th January 2021 (n = 1640). Alpha/Delta: 1st April - 30th June 2021 (n = 5552). AY.4.2 Delta/non-AY.4.2 Delta: 1st July - 31st October 2021 (n = 9613). Non-AY.4.2 Delta/Omicron: 1st - 31st December 2021 (n = 3858). Main outcome measures Admission to hospital, ICU, or death within 28 days of positive COVID-19 test Results For B.1.177/Alpha, 300 of 807 B.1.177 cases were recorded as hospitalised or worse, compared to 232 of 833 Alpha cases. After adjustment, the cumulative odds ratio was 1.51 (95% CI: 1.08-2.11) for Alpha versus B.1.177. For Alpha/Delta, 113 of 2104 Alpha cases were recorded as hospitalised or worse, compared to 230 of 3448 Delta cases. After adjustment, the cumulative odds ratio was 2.09 (95% CI: 1.42-3.08) for Delta versus Alpha. For non-AY.4.2 Delta/AY.4.2 Delta, 845 of 8644 non-AY.4.2 Delta cases were recorded as hospitalised or worse, compared to 101 of 969 AY.4.2 Delta cases. After adjustment, the cumulative odds ratio was 0.99 (95% CI: 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta. For non-AY.4.2 Delta/Omicron, 30 of 1164 non-AY.4.2 Delta cases were recorded as hospitalised or worse, compared to 26 of 2694 Omicron cases. After adjustment, the median cumulative odds ratio was 0.49 (95% CI: 0.22-1.06) for Omicron versus non-AY.4.2 Delta. Conclusions The direction of change in disease severity between successively emerging SARS-CoV-2 variants of concern was inconsistent. This heterogeneity demonstrates that severity associated with future SARS-CoV-2 variants is unpredictable.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.24.22272915v3" target="_blank">Inconsistent directions of change in case severity across successive SARS-CoV-2 variant waves suggests an unpredictable future</a>
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<li><strong>Field assessment of BinaxNOW antigen tests as COVID-19 treatment entry point at a community testing site in San Francisco during evolving omicron surges</strong> -
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Background. COVID-19 oral treatments require initiation within 5 days of symptom onset. Although antigen tests are less sensitive than RT-PCR, rapid results could facilitate entry to treatment. As SARS-CoV-2 variants and host immunity evolve, it is important to characterize the use case for rapid antigen tests for treatment entry. Methods. We collected anterior nasal swabs for BinaxNOW and RT-PCR testing and clinical data at a walk-up, community site in San Francisco, California between January and June 2022. SARS-CoV-2 genomic sequences were generated from positive samples and classified according to subtype and variant. Monte Carlo simulations were conducted to estimate the expected proportion of SARS-CoV-2 infected persons who would have been diagnosed within 5 days of symptom onset using RT-PCR versus BinaxNOW testing. Results. Among 25,309 persons tested with BinaxNOW, 2,952 had concomitant RT-PCR. 1321/2952 (44.7%) were SARS-CoV-2 RT-PCR positive. We identified waves of predominant omicron BA.1, BA.2, BA.2.12, BA.4, and BA.5 among 720 sequenced samples. Among 1,321 RT-PCR positive samples, 938/1321 (71%) were detected by BinaxNOW; 95% (774/817) of those with Ct value <30 were detected by BinaxNOW. BinaxNOW detection was consistent over lineages. In analyses to evaluate entry to treatment, BinaxNOW detected 82.7% (410/496, 95% CI: 79-86%) of persons with COVID-19 within 5 days of symptom onset. In comparison, RT-PCR (24-hour turnaround) detected 83.1% (412/496 95% CI: 79-86%) and RT-PCR (48-hour turnaround) detected 66.3% (329/496 95% CI: 62-70%) of persons with COVID-19 within 5 days of symptom onset. Conclusions. BinaxNOW detected high viral load from anterior nasal swabs consistently across omicron sublineages emerging between January and June of 2022. Simulations support BinaxNOW as an entry point for COVID-19 treatment in a community field setting.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.17.22278913v1" target="_blank">Field assessment of BinaxNOW antigen tests as COVID-19 treatment entry point at a community testing site in San Francisco during evolving omicron surges</a>
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<li><strong>Development and use of a method based on the anti-N reactivity of longitudinal samples to better estimate SARS-CoV-2 seroprevalence in a vaccinated population</strong> -
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Background: Serosurveys have been key to public health decision-making since the beginning of the SARS-CoV-2 pandemic. However, emerging evidence suggests that vaccination decreases the sensitivity of anti-nucleocapsid (N) serologies, making them less reliable to assess recently-acquired infections. We therefore developed and tested a new approach based on the ratio of the anti-N absorbance of longitudinal samples to overcome this limitation. Methods: Previously vaccinated repeat plasma donors infected between 12/15/2021 and 03/20/2022 were included if they made at least one donation pre-infection (reference sample) and one donation post-infection (test sample). All samples were tested using an in-house anti-N ELISA, the sensitivity of which had been determined prior to the vaccination era. Instead of using the previously determined signal cut-off (conventional approach), seropositivity was determined based on the ratio between the anti-N absorbance of the test and reference samples. The approach was tested in a real-world setting during three cross-sectional serosurveys carried out among plasma donors in Québec (Canada) from 01/17/2022 to 03/18/2022. Results: Using a cut-off ratio of 1.5, this approach had a sensitivity of 95.2% among the 248 previously vaccinated and infected donors compared with 63.3% for the conventional approach. When tested in a real-world setting, the ratio-based approach yielded an adjusted seroprevalence of 27.4% (95% confidence interval [CI]=23.8%-30.9%) at the latest time point considered, compared to 15.1% (95% CI=12.2%-18.0%) for the conventional approach. Conclusions: This article describes a new and highly-sensitive approach that captures a significantly greater proportion of vaccinated individuals with a recent history of SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.15.22278798v1" target="_blank">Development and use of a method based on the anti-N reactivity of longitudinal samples to better estimate SARS-CoV-2 seroprevalence in a vaccinated population</a>
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<li><strong>Uptake of Sotrovimab for prevention of severe COVID-19 and its safety in the community in England</strong> -
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Sotrovimab is a neutralising monoclonal antibody (nMAB), currently administrated in England to treat extremely clinically vulnerable COVID-19 patients. Trials have shown it to have mild or moderate side effects, however safety in real-world settings has not been yet evaluated. We used national databases to investigate its uptake and safety in community patients across England. We used a cohort study to describe uptake and a self-controlled case series design to evaluate the risks of 49 pre-specified suspected adverse events in the 2-28 days post-treatment. Between December 11, 2021 and May 24, 2022, there were 172,860 COVID-19 patients eligible for treatment. Of the 22,815 people who received Sotrovimab, 21,487 (94.2%) had a positive SARS-CoV-2 test and 5,999 (26.3%) were not on the eligible list. Between treated and untreated eligible individuals, the mean age (54.6, SD: 16.1 vs 54.1, SD: 18.3) and sex distribution (women: 60.9% vs 58.1%; men: 38.9% vs 41.1%) were similar. There were marked variations in uptake between ethnic groups, which was higher amongst Indian (15.0%; 95%CI 13.8, 16.3), Other Asian (13.7%; 95%CI 11.9, 15.8), White (13.4%; 95%CI 13.3, 13.6), and Bangladeshi (11.4%; 95%CI 8.8, 14.6); and lower amongst Black Caribbean individuals (6.4%; 95%CI 5.4, 7.5) and Black Africans (4.7%; 95%CI 4.1, 5.4). We found no increased risk of any of the suspected adverse events in the overall period of 2-28 days post-treatment, but an increased risk of rheumatoid arthritis (IRR 3.08, 95% CI 1.44, 6.58) and of systematic lupus erythematosus (IRR 5.15, 95% CI 1.60, 16.60) in the 2-3 days post- treatment, when we narrowed the risk period.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.17.22278893v1" target="_blank">Uptake of Sotrovimab for prevention of severe COVID-19 and its safety in the community in England</a>
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<li><strong>Prevalence and Characterization of Bacteria Present in the Nasopharynx of Outpatients with and without SARS-CoV-2</strong> -
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COVID-19 has emerged as a highly contagious and debilitating disease caused by the SARS-CoV-2 virus and has claimed the lives of over 6.8 million people worldwide. Bacterial co-infections are one of many co-morbidities that have been suggested to impact the outcome of COVID-19 in patients. The primary goal of this study was to assess the prevalence of bacterial co-infections and to describe any trends observed during the height of the COVID-19 pandemic. To do this, we investigated SARS-CoV-2 and bacterial co-infections from outpatient RT-PCR testing in Texas. The results indicate <i>Staphylococcus aureus</i>, <i>Streptococcus pneumoniae</i>, <i>Klebsiella pneumoniae</i>, <i>Moraxella catarrhalis</i>, and <i>Haemophilus influenzae</i> were the most frequently detected bacterial pathogens in both SARS-CoV-2 positive and SARS-CoV-2 negative patients and that these bacterial pathogens were present in these two patient populations at similar proportions. We also detected <i>Staphylococcus aureus</i> in a significantly larger proportion of males relative to females and people under 65 years of age relative to those 65 and over. Finally, we found that Hispanics were 75% more likely to be SARS-CoV-2 positive than non-Hispanics. The results suggest that COVID-19 patients may benefit from rapid diagnostic tests for bacterial pathogens and that this information could help delineate targeted antimicrobial therapy.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.17.22278915v1" target="_blank">Prevalence and Characterization of Bacteria Present in the Nasopharynx of Outpatients with and without SARS-CoV-2</a>
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<li><strong>Impact of the COVID-19 Pandemic on Personal Networks and Neurological Outcomes of People with Multiple Sclerosis: A Case-Control Cross-sectional and Longitudinal Analysis</strong> -
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Background: The COVID–19 pandemic has negatively impacted the social fabric of people with multiple sclerosis (pwMS). Objective: To evaluate the associations between personal social network environment and neurological function in pwMS and controls during the COVID–19 pandemic and compare with the pre–pandemic baseline. Methods: We first analyzed data collected from 8 cohorts of pwMS and control participants during the COVID–19 pandemic (March–December 2020). We then leveraged data collected between 2017–2019 in 3 of the 8 cohorts for longitudinal comparison. Participants completed a questionnaire that quantified the structure and composition of their personal social network, including the health behaviors of network members. We assessed neurological disability using three interrelated patient–reported outcomes: Patient Determined Disease Steps (PDDS), Multiple Sclerosis Rating Scale–Revised (MSRS–R), and Patient Reported Outcomes Measurement Information System (PROMIS)–Physical Function. We identified the network features associated with neurologic disability using paired t–tests and covariate–adjusted regressions. Results: In the cross-sectional analysis of the pandemic data from 1130 pwMS and 1250 control participants, higher percent of network members with a perceived negative health influence was associated with greater neurological symptom burden in pwMS (MSRS-R: Beta[95% CI]=2.181[1.082, 3.279], p<.001) and worse physical function in controls (PROMIS-Physical Function: Beta[95% CI]=-5.707[-7.405, -4.010], p<.001). In the longitudinal analysis of 230 pwMS and 136 control participants, the percent of people contacted “weekly or less” (p<.001) decreased during the COVID-19 pandemic for both pwMS (30.34% to 18.78%) and controls (23.48% to 14.89%) when compared to the pre-pandemic period. PwMS further experienced a greater reduction in network size (p<.001), increase in constraint (a measure of close ties of the network, p<.001) and decrease in maximum degree (highest number of ties of a network member, p<.001) than controls during the COVID–19 pandemic. These changes in network features were not associated with worsening neurological disability during the pandemic. Conclusions: Our findings suggest that negative health influences in personal social networks are associated with worse disability in all participants, and the COVID–19 pandemic led to contraction of personal social networks to a greater extent for pwMS than controls.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.17.22278896v1" target="_blank">Impact of the COVID-19 Pandemic on Personal Networks and Neurological Outcomes of People with Multiple Sclerosis: A Case-Control Cross-sectional and Longitudinal Analysis</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>A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SIM0417; Drug: Placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<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>Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Self-management of post COVID-19 respiratory outcomes<br/><b>Sponsor</b>: University of Manitoba<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 Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Casirivimab and Imdevimab Drug Combination; Drug: Remdesivir; Drug: Favipiravir<br/><b>Sponsor</b>: Mansoura University Hospital<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>The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BCG (Bacillus Calmette-Guérin) vaccine; Other: Placebo<br/><b>Sponsors</b>: Oswaldo Cruz Foundation; University of Sao Paulo; Federal University of Juiz de Fora<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>Cognitive Rehabilitation in Post-COVID-19 Condition</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Goal Management Training (GMT)<br/><b>Sponsors</b>: Lovisenberg Diakonale Hospital; University of Oslo; Icahn School of Medicine at Mount Sinai; University of Toronto; UiT The Arctic University of Norway; Oslo University 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>Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Diagnostic Test: Nasal Swab; Diagnostic Test: Nasopharyngeal swab<br/><b>Sponsor</b>: LumiraDx UK Limited<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>Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Education; Other: Motivational<br/><b>Sponsor</b>: University of Chicago<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 Booster Immunization With COVID-19 Vaccine,Inactivated Co -Administration With Influenza Vaccine and Pneumococcal Polysaccharide Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Adult group in immunogenicity and safety study of combined immunization; Biological: Elderly group in immunogenicity and safety study of combined immunization; Biological: Adult group in safety observation study of combined immunization; Biological: Elderly group in safety observation study of combined immunization<br/><b>Sponsor</b>: Sinovac Biotech Co., Ltd<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>EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: TREATMENT GROUP (TG); Other: CONTROL GROUP (CG)<br/><b>Sponsor</b>: University Vila Velha<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>Long-term Effects of SARS-CoV-2 on the Central Nervous System and One-year Follow-up of “Long COVID-19” Patients</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Diagnostic Test: Perfusion brain scintigraphy imaging<br/><b>Sponsor</b>: Brugmann University 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>Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Biological: Allogeneic umbilical cord mesenchymal stem cells; Biological: Controlled normal saline<br/><b>Sponsor</b>: Ever Supreme Bio Technology Co., Ltd.<br/><b>Active, not 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>Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Temelimab 54mg/kg; Drug: Placebo<br/><b>Sponsor</b>: GeNeuro SA<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>Active Cycle Of Breathing Technique Verses Breathing Exercises In Post ICU COVID-19 Patients</strong> - <b>Condition</b>: Post Covid-19 Patients<br/><b>Interventions</b>: Other: Chest physiotherapy with breathing exercises and ACBT; Other: Chest physiotherapy with breathing exercises<br/><b>Sponsor</b>: Riphah International University<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 Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Vitamin D Deficiency<br/><b>Intervention</b>: Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion<br/><b>Sponsor</b>: Pauls Stradins Clinical University Hospital<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>Addressing Vaccine Hesitancy and Increasing COVID-19 Vaccine Uptake Among African American Young Adults in the South</strong> - <b>Conditions</b>: COVID-19; Vaccine Uptake<br/><b>Intervention</b>: Behavioral: Tough Talks COVID<br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; University of Alabama at Birmingham; National Institute on Minority Health and Health Disparities (NIMHD)<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</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>Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study</strong> - Aim: COVID-19 is a global health threat. Therapeutics are urgently needed to cure patients severely infected with COVID-19. Objective: to investigate potential candidates of nsp12 inhibitors by searching for druggable cavity pockets within the viral protein and drug discovery. Methods: A virtual screening of ZINC natural products on SARS-CoV-2 nsp12’s druggable cavity was performed. A lead compound with the highest affinity to nsp12 was simulated dynamically for 10 ns. Results: ZINC03977803 was…</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 feedback regulation of memory B cell development in SARS-CoV-2 mRNA vaccination</strong> - Feedback inhibition of humoral immunity by antibodies was initially documented in guinea pigs by Theobald Smith in 1909, who showed that passive administration of excess anti-Diphtheria toxin inhibited immune responses ¹ . Subsequent work documented that antibodies can enhance or inhibit immune responses depending on antibody isotype, affinity, the physical nature of the antigen, and engagement of immunoglobulin (Fc) and complement (C’) receptors ^(2, 3) . However, little is known about how…</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 Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019</strong> - Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro…</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>Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the pre-hairpin intermediate of the spike protein</strong> - Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide inhibitors which…</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>Antiviral effect of cetylpyridinium chloride in mouthwash on SARS-CoV-2</strong> - Cetylpyridinium chloride (CPC), a quaternary ammonium compound, which is present in mouthwash, is effective against bacteria, fungi, and enveloped viruses. This study was conducted to explore the antiviral effect of CPC on SARS-CoV-2. There are few reports on the effect of CPC against wild-type SARS-CoV-2 at low concentrations such as 0.001%-0.005% (10-50 µg/mL). Interestingly, we found that low concentrations of CPC suppressed the infectivity of human isolated SARS-CoV-2 strains (Wuhan, Alpha,…</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>Holistic care of patients with diabetic foot ulcers during the COVID-19 era: integration of Henderson’s Need Theory</strong> - The COVID-19 pandemic has inhibited the practice of diabetic foot ulcer care, particularly in the community. Comprehensive theory-based nursing care is needed to prevent further complications. Unfortunately, a study combining theory with nursing care in diabetic foot ulcer care has not been explored. When caring for patients with diabetic foot ulcers, who are also at increased risk of severe complications from COVID-19, it is important to take a holistic view of the patient and consider all 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>Identification of a promising inhibitor from <em>Illicium verum</em> (star anise) against the main protease of SARS-CoV-2: insights from the computational study</strong> - SARS-CoV-2, the causing agent of coronavirus disease (COVID-19), first broke out in Wuhan and rapidly spread worldwide, resulting in a global health emergency. The lack of specific drugs against the coronavirus has made its spread challenging to control. The main protease (M^(pro)) is a key enzyme of SARS-CoV-2 used as a key target in drug discovery against the coronavirus. Medicines derived from plant phytoconstituents have been widely exploited to treat various diseases. The present study has…</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>UBR5 Acts as an Antiviral Host Factor against MERS-CoV via Promoting Ubiquitination and Degradation of ORF4b</strong> - Within the past 2 decades, three highly pathogenic human coronaviruses have emerged, namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The health threats and economic burden posed by these tremendously severe coronaviruses have paved the way for research on their etiology, pathogenesis, and treatment. Compared to SARS-CoV and SARS-CoV-2, MERS-CoV genome…</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>Antimicrobial peptides: Defending the mucosal epithelial barrier</strong> - The recent epidemic caused by aerosolized SARS-CoV-2 virus illustrates the importance and vulnerability of the mucosal epithelial barrier against infection. Antimicrobial proteins and peptides (AMPs) are key to the epithelial barrier, providing immunity against microbes. In primitive life forms, AMPs protect the integument and the gut against pathogenic microbes. AMPs have also evolved in humans and other mammals to enhance newer, complex innate and adaptive immunity to favor the persistence 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>SEMgsa: topology-based pathway enrichment analysis with structural equation models</strong> - CONCLUSIONS: SEMgsa is a novel yet powerful method for identifying enrichment with regard to gene expression data. It takes into account topological information and exploits pathway perturbation statistics to reveal biological information. SEMgsa is implemented in the R package SEMgraph, easily available at https://CRAN.R-project.org/package=SEMgraph .</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 spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate that hepatocytes are susceptible to infection in different models: primary hepatocytes derived from humanized angiotensin-converting enzyme-2 mice (hACE2)…</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>Ultrabright nanoparticle-labeled lateral flow immunoassay for detection of anti-SARS-CoV-2 neutralizing antibodies in human serum</strong> - The level of anti-SARS-CoV-2 neutralizing antibodies (NAb) is an indispensable reference for evaluating the acquired protective immunity against SARS-CoV-2. Here, we established an ultrabright nanoparticles-based lateral flow immunoassay (LFIA) for one-step rapid semi-quantitative detection of anti-SARS-CoV-2 NAb in vaccinee’s serum. Once embedded in polystyrene (PS) nanoparticles, the aggregation-induced emission (AIE) luminogen, AIE(490), exhibited ultrabright fluorescence due to the rigidity…</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>Lymphatic coagulation and neutrophil extracellular traps in lung-draining lymph nodes of COVID-19 decedents</strong> - Clinical manifestations of severe COVID-19 include coagulopathies that are exacerbated by the formation of neutrophil extracellular traps (NETs). Here, we report that pulmonary lymphatic vessels, which traffic neutrophils and other immune cells to the lung-draining lymph node (LDLN), can also be blocked by fibrin clots in severe COVID-19. Immunostained tissue sections from COVID-19 decedents revealed widespread lymphatic clotting not only in the lung, but notably in the LDLN, where the extent 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>Complement C3 inhibition in severe COVID-19 using compstatin AMY-101</strong> - Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated…</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>Adding Insult to Injury - Does COVID-19 Promote ARDS by Inhibiting Surfactant?</strong> - No abstract</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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