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188 lines
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<title>02 June, 2023</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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<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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Suspensions of prominent accounts minimally impact platform engagement</strong> -
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<div>
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Health-related misinformation online poses threats to individual well-being and undermines public health efforts. In response, many social media platforms have temporarily or permanently suspended accounts that spread misinformation, at the risk of losing traffic vital to platform revenue. Here we examine the impact on platform engagement following removal of six prominent accounts during the COVID-19 pandemic. Focused on those who engaged with the removed accounts, we find that suspension did not meaningfully reduce activity on the platform. Moreover, we find that removal of the prominent accounts minimally impacted the diversity of information sources consumed.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/x4jau/" target="_blank">Suspensions of prominent accounts minimally impact platform engagement</a>
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</div></li>
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<li><strong>Complex Adaptive Systems and Human Resource Management: Fostering a Thriving Workforce in the Post-Pandemic Era</strong> -
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<div>
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The outbreak of COVID-19 has presented unparalleled difficulties for both companies and their staff, resulting in a state of emergency that jeopardizes the welfare of employees and the prosperity of organizations. The present article delves into the prospects of human resource management (HRM) in promoting a workforce that is sustainable and thrives in diverse situations or paradigms through the lens of complex adaptive systems. An examination of the current body of literature indicates deficiencies in comprehending the function of HRM in fostering employee thriving, particularly within the framework of broader and more remote organizational contexts. The article utilizes the framework of complex adaptive systems to suggest various human resource strategies, policies, practices, systems, and processes that can enhance the thriving of the workforce. These strategies include initiatives aimed at promoting employee well-being, flexible working arrangements, and leadership that fosters inclusivity. The significance of HR executives in steering organizations through periods of crisis and recuperation is underscored, along with the imperative to reevaluate the definition of thriving in the context of the pandemic and its enduring ramifications. The article’s final remarks entail the identification of potential avenues for future research and practice in the field of HRM. The significance of HRM in fostering a workforce that is capable of thriving sustainably, both during and post-pandemic, is underscored.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/74pg5/" target="_blank">Complex Adaptive Systems and Human Resource Management: Fostering a Thriving Workforce in the Post-Pandemic Era</a>
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</div></li>
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<li><strong>Combinatorial Regimens Augment Drug Monotherapy for SARS-CoV-2 Clearance in Mice</strong> -
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<div>
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Direct acting antivirals (DAAs) represent critical tools for combating SARS-CoV-2 variants of concern (VOCs) that evolve to escape spike-based immunity and future coronaviruses with pandemic potential. Here, we used bioluminescence imaging to evaluate therapeutic efficacy of DAAs that target SARS-CoV-2 RNA-dependent RNA polymerase (favipiravir, molnupiravir) or Main protease (nirmatrelvir) against Delta or Omicron VOCs in K18-hACE2 mice. Nirmatrelvir displayed the best efficacy followed by molnupiravir and favipiravir in suppressing viral loads in the lung. Unlike neutralizing antibody treatment, DAA monotherapy did not eliminate SARS-CoV-2 in mice. However, targeting two viral enzymes by combining molnupiravir with nirmatrelvir resulted in superior efficacy and virus clearance. Furthermore, combining molnupiravir with Caspase-1/4 inhibitor mitigated inflammation and lung pathology whereas combining molnupiravir with COVID-19 convalescent plasma yielded rapid virus clearance and 100% survival. Thus, our study provides insights into treatment efficacies of DAAs and other effective combinations to bolster COVID-19 therapeutic arsenal.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.31.543159v1" target="_blank">Combinatorial Regimens Augment Drug Monotherapy for SARS-CoV-2 Clearance in Mice</a>
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</div></li>
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<li><strong>The HLA-II immunopeptidome of SARS-CoV-2</strong> -
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<div>
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Targeted synthetic vaccines have the potential to transform our response to viral outbreaks; yet the design of these vaccines requires a comprehensive knowledge of viral immunogens, including T-cell epitopes. Having previously mapped the SARS-CoV-2 HLA-I landscape, here we report viral peptides that are naturally processed and loaded onto HLA-II complexes in infected cells. We identified over 500 unique viral peptides from canonical proteins, as well as from overlapping internal open reading frames (ORFs), revealing, for the first time, the contribution of internal ORFs to the HLA-II peptide repertoire. Most HLA-II peptides co-localized with the known CD4+ T cell epitopes in COVID-19 patients. We also observed that two reported immunodominant regions in the SARS-CoV-2 membrane protein are formed at the level of HLA-II presentation. Overall, our analyses show that HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for most of the HLA-II peptidome and non-structural and non-canonical proteins accounting for the majority of the HLA-I peptidome. These findings highlight the need for a vaccine design that incorporates multiple viral elements harboring CD4+ and CD8+ T cell epitopes to maximize the vaccine effectiveness.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.26.542482v1" target="_blank">The HLA-II immunopeptidome of SARS-CoV-2</a>
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</div></li>
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<li><strong>Single-cell multi-omic topic embedding reveals cell-type-specific and COVID-19 severity-related immune signatures</strong> -
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<div>
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The advent of single-cell multi-omics sequencing technology makes it possible for researchers to leverage multiple modalities for individual cells and explore cell heterogeneity. However, the high dimensional, discrete, and sparse nature of the data make the downstream analysis particularly challenging. Most of the existing computational methods for single-cell data analysis are either limited to single modality or lack flexibility and interpretability. In this study, we propose an interpretable deep learning method called multi-omic embedded topic model (moETM) to effectively perform integrative analysis of high-dimensional single-cell multimodal data. moETM integrates multiple omics data via a product-of-experts in the encoder for efficient variational inference and then employs multiple linear decoders to learn the multi-omic signatures of the gene regulatory programs. Through comprehensive experiments on public single-cell transcriptome and chromatin accessibility data (i.e., scRNA+scATAC), as well as scRNA and proteomic data (i.e., CITE-seq), moETM demonstrates superior performance compared with six state-of-the-art single-cell data analysis methods on seven publicly available datasets. By applying moETM to the scRNA+scATAC data in human bone marrow mononuclear cells (BMMCs), we identified sequence motifs corresponding to the transcription factors that regulate immune gene signatures. Applying moETM analysis to CITE-seq data from the COVID-19 patients revealed not only known immune cell-type-specific signatures but also composite multi-omic biomarkers of critical conditions due to COVID-19, thus providing insights from both biological and clinical perspectives.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.31.526312v2" target="_blank">Single-cell multi-omic topic embedding reveals cell-type-specific and COVID-19 severity-related immune signatures</a>
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</div></li>
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<li><strong>Geospatially-resolved public-health surveillance via wastewater sequencing</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Wastewater, which contains everything from pathogens to pollutants, is a geospatially- and temporally-linked microbial fingerprint of a given population. As a result, it can be leveraged for monitoring multiple dimensions of public health across locales and time. Here, we integrate targeted and bulk RNA sequencing (n=1,419 samples) to track the viral, bacterial, and functional content over geospatially distinct areas within Miami Dade County from 2020-2022. First, we used targeted amplicon sequencing (n=966) to track diverse SARS-CoV-2 variants across space and time, and we found a tight correspondence with clinical caseloads from University students (N = 1,503) and Miami-Dade County hospital patients (N = 3,939 patients), as well as an 8-day earlier detection of the Delta variant in wastewater vs. in patients. Additionally, in 453 metatranscriptomic samples, we demonstrate that different wastewater sampling locations have clinically and public-health-relevant microbiota that vary as a function of the size of the human population they represent. Through assembly, alignment-based, and phylogenetic approaches, we also detect multiple clinically important viruses (e.g., norovirus) and describe geospatial and temporal variation in microbial functional genes that indicate the presence of pollutants. Moreover, we found distinct profiles of antimicrobial resistance (AMR) genes and virulence factors across campus buildings, dorms, and hospitals, with hospital wastewater containing a significant increase in AMR abundance. Overall, this effort lays the groundwork for systematic characterization of wastewater to improve public health decision making and a broad platform to detect emerging pathogens.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.31.23290781v1" target="_blank">Geospatially-resolved public-health surveillance via wastewater sequencing</a>
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<li><strong>An explanation for SARS-CoV-2 rebound after Paxlovid treatment</strong> -
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In a fraction of SARS-CoV-2 infected individuals treated with the oral antiviral Paxlovid, the virus rebounds following treatment. The mechanism driving rebound is not understood. Here, we show that viral dynamic models based on the hypothesis that Paxlovid treatment near the time of symptom onset halts the depletion of target cells, but may not fully eliminate the virus, which can lead to viral rebound. We also show that the occurrence of viral rebound is sensitive to model parameters, and the time treatment is initiated, which may explain why only a fraction of individuals develop viral rebound. Finally, the models are used to test the therapeutic effects of two alternative treatment schemes. These findings also provide a possible explanation for rebounds following other antiviral treatments for SARS-CoV-2.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.30.23290747v1" target="_blank">An explanation for SARS-CoV-2 rebound after Paxlovid treatment</a>
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<li><strong>ECHOCARDIOGRAPHIC MANIFESTATIONS OF COVID 19 ILLNESS AND DEVELOPMENT OF PERSISTENT RV DYSFUNCTION AND PULMANARY HYPERTENSION AS A LONG TERM SEQUELAE OF COVID 19 ILLNESS: A STUDY AMONG PATIENTS OF SOUTH EAST ASIAN REGION</strong> -
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Abstract Objectives- To study the Echocardiographic manifestations of covid 19 illness among patients admitted in our facility, Correlate MAPSE, TAPSE, PASP, CRP levels and CTSI among covid 19 patients with their 28 day outcome as survivors and non survivors and to look for evidence of residual RV dysfunction and Pulmonary hypertension using TTE after 1 year of follow-up. Study design- Prospective observational study at various medical wards and ICUs in SMS medical college and associated hospitals. Methods- 258 patients with a Covid-19 RT-PCR positive report from a throat or a nasal swab within 72 hours of admission were included in the study. Each patient underwent a complete clinical assessment and routine blood investigations including CRP levels were done. A complete transthoracic echocardiogram was done within 48 hours of admission. Patients also underwent a HRCT chest and CTSI scores were estimated. All patients were followed for a period of 28 days. The MAPSE, TAPSE, PASP, CTSI and CRP levels were then correlated with the outcome of the patient. The survivors again underwent a TTE at 1 year after their recovery from covid-19 illness to look for residual RV dysfunction by TAPSE and the development of pulmonary hypertension as measured by PASP using Bernoulli?s equation. Results-Amongst patient of covid 19 illness the MAPSE, TAPSE, PASP, CTSI and CRP levels all correlated well with outcome of patients. While most covid-19 survivors recovered from their illness yet some patients showed evidence of persistent RV dysfunction and pulmonary hypertension even after 1 year of follow up.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.26.23290622v1" target="_blank">ECHOCARDIOGRAPHIC MANIFESTATIONS OF COVID 19 ILLNESS AND DEVELOPMENT OF PERSISTENT RV DYSFUNCTION AND PULMANARY HYPERTENSION AS A LONG TERM SEQUELAE OF COVID 19 ILLNESS: A STUDY AMONG PATIENTS OF SOUTH EAST ASIAN REGION</a>
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</div></li>
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<li><strong>SARS-CoV-2 viral replication persists in the human lung for several weeks after symptom onset in mechanically ventilated patients with severe COVID-19: a prospective tissue-sampling study</strong> -
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Background. The immunopathogenesis of severe COVID-19 is incompletely understood. Remdesivir is not recommended in mechanically ventilated (MV) patients. In the upper respiratory tract (URT) replicating (culturable) SARS-CoV-2 is recoverable for ~ 4 to 8 days after symptom onset, however, there is paucity of data about the frequency or duration of replicating virus in the lower respiratory tract (i.e. the human lung). Methods. We undertook lung tissue sampling (needle biopsy), shortly after death, in 42 mechanically ventilated (MV) decedents during the Beta and Delta waves. An independent group of 18 ambulatory patents served as a comparative control. Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, immunohistochemistry and cell-based flow cytometry of deconstructed tissue. Findings. 38% (16/42) of MV decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 weeks) after symptom onset compared to < ~5 days in the URT of ambulatory patients. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (p<0.05). NP culture was negative in 23.1% (6/26) of decedents despite lung culture positivity. This, hitherto, undescribed bio-phenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary pro-inflammatory response but concurrent with viral culture positivity. Interpretation. In a sizable subset of patients with acute COVID-19, concurrent, rather than sequential active viral replication continues to drive a heightened pro-inflammatory response in the human lung beyond the second week of illness (despite lack of viral replication in the URT) and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe COVID-19 disease.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.06.23286834v2" target="_blank">SARS-CoV-2 viral replication persists in the human lung for several weeks after symptom onset in mechanically ventilated patients with severe COVID-19: a prospective tissue-sampling study</a>
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<li><strong>Potential for bias in (sero)prevalence estimates</strong> -
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Objectives: The COVID-19 has led to many studies of seroprevalence. A number of methods exist in the statistical literature to correctly estimate disease prevalence in the presence of diagnostic test misclassification, but these methods seem to be less known and not routinely used in the public health literature. We aimed to show how widespread the problem is in recent publications, and to quantify the magnitude of bias introduced when correct methods are not used. Methods: We examined a sample of recent literature to determine how often public health researcher did not account for test performance in estimates of seroprevalence. Using straightforward calculations, we estimated the amount of bias introduced when reporting the proportion of positive test results instead of using sensitivity and specificity to estimate disease prevalence. Results: Of the seroprevalence studies sampled, 87% failed to account for sensitivity and specificity. Expected bias is often more than is desired in practice, ranging from 1% to 10%. Conclusions: Researchers conducting studies of prevalence should correctly account for test sensitivity and specificity in their statistical analysis.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.24.22282720v5" target="_blank">Potential for bias in (sero)prevalence estimates</a>
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<li><strong>Metagenomic sequencing detects human respiratory and enteric viruses in air samples collected from congregate settings.</strong> -
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Innovative methods for evaluating viral risk and spread, independent of test-seeking behavior, are needed to improve routine public health surveillance, outbreak response, and pandemic preparedness. Throughout the COVID-19 pandemic, environmental surveillance strategies, including wastewater and air sampling, have been utilized alongside widespread individual-based SARS-CoV-2 testing programs to provide population-wide data. To date, environmental surveillance strategies have mainly relied on pathogen-specific detection methods to monitor viruses through space and time. However, this provides a limited picture of the virome present in a sample, leaving us blind to most circulating viruses. In this study, we explore whether virus-agnostic deep sequencing can improve the utility of air sampling to detect human viruses captured in air samples. We show that sequence-independent single-primer amplification sequencing of nucleic acids from air samples can detect common and unexpected human respiratory and enteric viruses, including influenza virus type A and C, respiratory syncytial virus, human coronaviruses, rhinovirus, SARS-CoV-2, rotavirus, mamastrovirus, and astrovirus.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.28.23290648v1" target="_blank">Metagenomic sequencing detects human respiratory and enteric viruses in air samples collected from congregate settings.</a>
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<li><strong>Colocalization of expression transcripts with COVID-19 outcomes is rare across cell states, cell types and organs.</strong> -
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Identifying causal genes at GWAS loci can help pinpoint targets for therapeutic interventions. Expression studies can disentangle such loci but signals from expression quantitative trait loci (eQTLs) often fail to colocalize-which means that the genetic control of measured expression is not shared with the genetic control of disease risk. This may be because gene expression is measured in the wrong cell type, physiological state, or organ. We tested whether Mendelian randomization (MR) could identify genes at loci influencing COVID-19 outcomes and whether the colocalization of genetic control of expression and COVID-19 outcomes was influenced by cell type, cell stimulation, and organ. We conducted MR of cis-eQTLs from single cell (scRNA-seq) and bulk RNA sequencing. We then tested variables that could influence colocalization, including cell type, cell stimulation, RNA sequencing modality, organ, symptoms of COVID-19, and SARS-CoV-2 status among individuals with symptoms of COVID-19. The outcomes used to test colocalization were COVID-19 severity and susceptibility as assessed in the Host Genetics Initiative release 7. Most transcripts identified using MR did not colocalize when tested across cell types, cell state and in different organs. Most that did colocalize likely represented false positives due to linkage disequilibrium. In general, colocalization was highly variable and at times inconsistent for the same transcript across cell type, cell stimulation and organ. While we identified factors that influenced colocalization for select transcripts, identifying 33 that mediate COVID-19 outcomes, our study suggests that colocalization of expression with COVID-19 outcomes is partially due to noisy signals even after following quality control and sensitivity testing. These findings illustrate the present difficulty of linking expression transcripts to disease outcomes and the need for skepticism when observing eQTL MR results, even accounting for cell types, stimulation state and different organs.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.29.23290694v1" target="_blank">Colocalization of expression transcripts with COVID-19 outcomes is rare across cell states, cell types and organs.</a>
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<li><strong>Prevalence of coronary artery disease among COVID-19 patients: a systematic review and meta-analysis</strong> -
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Background Throughout the surge of the COVID-19 pandemic high rate of chronic diseases have been reported, including respiratory diseases and cardiovascular diseases. The prevalence of coronary artery disease has remained high throughout the COVID-19 pandemic, which also draws great concern towards it. This study seeks to provide a pooled estimate of the burden of coronary artery disease in COVID-19. Objective To estimate the overall prevalence of coronary artery disease among COVID-19 patients. Data Sources In this systematic review and meta-analysis, an extensive literature search was conducted in PubMed, Scopus, Embase, EBSCO ,Web of Science, Cochrane,Proquest and preprint servers (medRxiv, arXiv, bioRxiv, BioRN, ChiRxiv, ChiRN, and SSRN). References fo eligible articles, forward citation tracking, and expert opinion were used to identify other relevant articles. All published articles until 13 April 2023 were assessed as per the PROSPERO registration protocol (CRD42022367501). Study Selection, Data Extraction, and Synthesis Primary studies that reported coronary artery disease among COVID-19 patients were included. The characteristics of the study and information on the number of cases of coronary artery disease were extracted from the included studies. Individual study estimates were pooled using the random intercept logistic regression model. The heterogeneity between the selected studies was assessed using the I2 statistic, tau, tau-squared, Cochran’s Q. Prediction interval was used to identify the range into which future studies are expected to fall. Subgroup analysis based on geography (continent) was done to reduce heterogeneity. Publication bias was analyzed using doi plot and LFK index. The risk of bias in the studies was assessed as per the tools proposed by the National Institute of Health. Main outcomes The primary outcome was the pooled prevalence of coronary artery disease among COVID-19 patients within the examined population. Results 510 records were initially retrieved from electronic databases in addition to other sources like reference screening. 33 studies with 40,064 COVID-19 patients were included for quantitative synthesis. The prevalence of coronary artery disease among COVID-19 patients was 15.24% (95% CI: 11.41% - 20.06%). The prediction interval ranged from 2.49% to 55.90%. The studies were highly heterogeneous (tau-sqaured of 0.89), and subgroup analysis significantly reduced it (test of moderators: Q = 14.77, df=2, P=.002). Europe reported the highest prevalence [21.70% (14.80% - 30.65%)], and Asia has the least prevalence [10.07% (6.55% - 15.19%)]. Meta-regression for sample size was not significant (P=.11). A symmetric doi plot and an LFK index of 0.57 revealed no evidence of publication bias or small-study effects. Conclusion The burden of coronary artery disease has been considerable, varying with geography. and further research in this area is needed. Routine cardiac screening and assessment of COVID-19 patients can help uncover undiagnosed cases, and better optimise the management of all COVID-19 patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.01.23290768v1" target="_blank">Prevalence of coronary artery disease among COVID-19 patients: a systematic review and meta-analysis</a>
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<li><strong>Omicron’s Intrinsic Gene-Gene Interactions Jumped Away from Earlier SARS-CoV-2 Variants and Gene Homologs between Humans and Animals</strong> -
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Omicron and its subvariants have become the predominant SARS-CoV-2 variants worldwide. The Omicron’s basic reproduction number (R0) has been close to 20 or higher. However, it is not known what caused such an extremely high R0. This work aims to find an explanation for such high R0 Omicron infection. We found that Omicron’s intrinsic gene-gene interactions jumped away from earlier SARS-CoV-2 variants which can be fully described by a miniature set of genes reported in our earlier work. We found that the gene PTAFR (Platelet Activating Factor Receptor) is highly correlated with Omicron variants, and so is the gene CCNI (Cyclin I), which is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog. The combination of PTAFR and CCNI can lead to a 100% accuracy of differentiating Omicron COVID-19 infection and COVID-19 negative. We hypothesize that Omicron variants were potentially jumped from COVID-19-infected animals back to humans. In addition, there are also several other two-gene interactions that lead to 100% accuracy. Such observations can explain Omicron’s fast-spread reproduction capability as either of those two-gene interactions can lead to COVID-19 infection, i.e., multiplication of R0s leads to a much higher R0. At the genomic level, PTAFR, CCNI, and several other genes identified in this work rise to Omicron druggable targets and antiviral drugs besides the existing antiviral drugs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.01.526736v2" target="_blank">Omicron’s Intrinsic Gene-Gene Interactions Jumped Away from Earlier SARS-CoV-2 Variants and Gene Homologs between Humans and Animals</a>
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<li><strong>CD4+ T-cell immunity of SARS-CoV-2 patients determine pneumonia development</strong> -
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Most humans infected with SARS-CoV-2 will recover without developing pneumonia. A few SARS-CoV-2 infected patients, however, develop pneumonia, and occasionally develop cytokine storms. In such cases, it is assumed that there is an inadequate immune response to eliminate viral infected cells and an excessive inappropriate immune response causing organ damage, but little is known about this mechanism. In this study, we used single cell RNA sequencing and mass cytometry to analyze peripheral blood T cells from patients hospitalized with proven COVID-19 infection in order to clarify the differences in host immune status among COVID-19 pneumonia cases, non-pneumonia cases, and healthy controls. The results showed that a specific CD4+ T cell cluster with chemokine receptor expression patterns, CXCR3+CCR4-CCR6+ (Th1/17), was less abundant in COVID-19 pneumonia patients. Interestingly, these CD4+ T-cell clusters were identical to those we have reported to correlate with antitumor immunity and predict programmed cell death (PD)-1 blockade treatment response in lung cancer. The Th1/17 cell percentages had biomarker performance in diagnosing pneumonia cases. In addition, CTLA-4 expression of type17 helper T cells (Th17) and regulatory T cells (Treg) was found to be significantly lower. This indicates that functional suppression of Th17 was less effective and Treg function was impaired in pneumonia cases. These results suggest that imbalance of CD4+ T-cell immunity generates excessive immunity that does not lead to viral eradication. This might be a potential therapeutic target mechanism to prevent severe viral infections.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.31.543129v1" target="_blank">CD4+ T-cell immunity of SARS-CoV-2 patients determine pneumonia development</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</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>Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Extracorporeal photopheresis<br/><b>Sponsor</b>: Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases<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>Investigation of the Effect on Cognitive Skills of COVID-19 Survivors</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: green walking and intelligence gam<br/><b>Sponsors</b>: Bayburt University; Karadeniz Technical University<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>Evaluation of Safety, Tolerability, Reactogenicity, Immunogenicity of Baiya SARS-CoV-2 Vax 2 as a Booster for COVID-19</strong> - <b>Conditions</b>: COVID-19 Vaccine; COVID-19<br/><b>Interventions</b>: Biological: 50 μg Baiya SARS-CoV-2 Vax 2; Other: Placebo<br/><b>Sponsor</b>: Baiya Phytopharm 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>The Effect of Special Discharge Training in the COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: COVID-19 Discharge Education<br/><b>Sponsor</b>: Kilis 7 Aralik University<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>Physiotherapy in Mutated COVID-19 Patients</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Physiotherapy<br/><b>Sponsor</b>: Giresun University<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>To Explore the Regulatory Effect of Combined Capsule FMT on the Levels of Inflammatory Factors in Peripheral Blood of Patients With COVID-19 During Treatment.</strong> - <b>Conditions</b>: Fecal Microbiota Transplantation; COVID-19 Infection<br/><b>Intervention</b>: Procedure: Fecal microbiota transplantation<br/><b>Sponsor</b>: Shanghai 10th People’s 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>Telerehabilitation Program and Detraining in Patients With Post-COVID-19 Sequelae</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program<br/><b>Sponsor</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona<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>Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2373; Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant<br/><b>Sponsor</b>: Novavax<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>COVID-19 Vaccine Uptake Amongst Underserved Populations in East London</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccination Refusal<br/><b>Intervention</b>: Device: Patient Engagement tool<br/><b>Sponsors</b>: Queen Mary University of London; Social Action for Health<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 to Learn About How Loss of Liver Function Affects the Blood Levels of the Study Medicine Called PF-07817883.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: PF-07817883<br/><b>Sponsor</b>: Pfizer<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>Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19)</strong> - <b>Conditions</b>: Long COVID; Post-Acute Sequela of COVID-19; Post-Acute COVID-19<br/><b>Interventions</b>: Drug: AER002; Other: Placebo<br/><b>Sponsors</b>: Michael Peluso, MD; Aerium Therapeutics<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>Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: AZD3152; Other: Placebo<br/><b>Sponsor</b>: AstraZeneca<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>COVID Frequent Antigen Testing</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Diagnostic Test: SARS CoV-2 antigen tests<br/><b>Sponsors</b>: IDX20 Inc; National Institute on Minority Health and Health Disparities (NIMHD)<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>Study to Assess Safety, Reactogenicity and Immunogenicity of the repRNA(QTP104) Vaccine Against SARS-CoV-2(COVID-19)</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Biological: QTP104 1ug; Biological: QTP104 5ug; Biological: QTP104 25ug<br/><b>Sponsor</b>: Quratis Inc.<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>Effects of Individual Tailored Physical Exercise in Patients With POTS After COVID-19 - a Randomized Controlled Study</strong> - <b>Conditions</b>: Postural Orthostatic Tachycardia Syndrome; COVID-19; Post COVID-19 Condition; Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Other: Individual tailored exercise<br/><b>Sponsors</b>: Karolinska Institutet; Karolinska University Hospital<br/><b>Enrolling by invitation</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>PACT inhibits the replication of SARS-CoV-2 through the blockage of GSK-3β-N-nsp3 cascade</strong> - The protein activator of protein kinase R (PKR) (PACT) has been shown to play a crucial role in stimulating the host antiviral response through the activation of PKR, retinoic acid-inducible gene I, and melanoma differentiation-associated protein 5. Whether PACT can inhibit viral replication independent of known mechanisms is still unrevealed. In this study, we show that, like many viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks GSK-3β to facilitate its replication….</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>Evaluation of SARS-CoV-2 isolation in cell culture from nasal/nasopharyngeal swabs or saliva specimens of patients with COVID-19</strong> - It has been revealed that SARS-CoV-2 can be efficiently isolated from clinical specimens such as nasal/nasopharyngeal swabs or saliva in cultured cells. In this study, we examined the efficiency of viral isolation including SARS-CoV-2 mutant strains between nasal/nasopharyngeal swab or saliva specimens. Furthermore, we also examined the comparison of viral isolation rates by sample species using simulated specimens for COVID-19. As a result, it was found that the isolation efficiency 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>A Facile Strategy to Construct Anti-Swelling, Antibacterial and Antifogging Coatings for Protection of Medical Goggles</strong> - During the COVID-19 pandemic, traditional medical goggles are not only easy to attach bacteria and viruses in long-term exposure, but also easy to fogged up, which increases the risk of infection and affects productivity. Bacterial adhesion and fog can be significantly inhibited through the hydrogel coatings, owing to their super hydrophilic properties. But on the one hand, hydrophilic hydrogel coatings are easy to absorb water and swell in wet environment, resulting in reduced mechanical…</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>Secreted ORF8 induces monocytic pro-inflammatory cytokines through NLRP3 pathways in patients with severe COVID-19</strong> - Despite extensive research, the specific factor associated with SARS-CoV-2 infection that mediates the life-threatening inflammatory cytokine response in patients with severe COVID-19 remains unidentified. Herein we demonstrate that the virus-encoded Open Reading Frame 8 (ORF8) protein is abundantly secreted as a glycoprotein in vitro and in symptomatic patients with COVID-19. ORF8 specifically binds to the NOD-like receptor family pyrin domain-containing 3 (NLRP3) in CD14^(+) monocytes to…</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>Nsp14 of SARS-CoV-2 inhibits mRNA processing and nuclear export by targeting the nuclear cap-binding complex</strong> - To facilitate selfish replication, viruses halt host gene expression in various ways. The nuclear export of mRNA is one such process targeted by many viruses. SARS-CoV-2, the etiological agent of severe acute respiratory syndrome, also prevents mRNA nuclear export. In this study, Nsp14, a bifunctional viral replicase subunit, was identified as a novel inhibitor of mRNA nuclear export. Nsp14 induces poly(A)+ RNA nuclear accumulation and the dissolution/coalescence of nuclear speckles. Genome-wide…</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>In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19</strong> - Recently the E protein of SARS-CoV-2 has become a very important target in the potential treatment of COVID-19 since it is known to regulate different stages of the viral cycle. There is biochemical evidence that E protein exists in two forms, as monomer and homopentamer. An in silico screening analysis was carried out employing 5852 ligands (from Zinc databases), and performing an ADMET analysis, remaining a set of 2155 compounds. Furthermore, docking analysis was performed on specific sites…</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>Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir</strong> - Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithelial cells in the mucosa or skin, resulting in a vesicular rash. Licensed antivirals inhibit virus replication, but do not affect latency. On reactivation, VZV causes herpes zoster, also known as…</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>Discovery of Polyphenolic Natural Products as SARS-CoV-2 M<sup>pro</sup> Inhibitors for COVID-19</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chemical phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a…</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>Neutralizing antibody levels and epidemiological information of patients with breakthrough COVID-19 infection in Toyama, Japan</strong> - Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has exploded owing to the emergence of various SARS-CoV-2 variants and has become a major problem at present. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Analysis of 44 specimens diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or…</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>Circulating ACE2 level and zinc/albumin ratio as potential biomarkers for a precision medicine approach to COVID-19</strong> - Highly mutable influenza is successfully countered based on individual susceptibility and similar precision-like medicine approach should be effective against SARS-COV-2. Among predictive markers to bring precision medicine to COVID-19, circulating ACE2 has potential features being upregulated in both severe COVID-19 and predisposing comorbidities. Spike SARS-CoVs were shown to induce ADAM17-mediated shedding of enzymatic active ACE2, thus accounting for its increased activity that has also been…</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>Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 M<sup>pro</sup>)</strong> - The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a great threat to public health while various vaccines are available worldwide. Main protease (M^(pro)) has been validated as an effective anti-COVID-19 drug target. Using medicinal chemistry and rational drug design strategies, we identified a quinazolin-4-one series of nonpeptidic, noncovalent SARS-CoV-2 M^(pro) inhibitors based on baicalein, 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one. In particular, compound C7 exhibits superior…</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>Aurones: A Promising Scaffold to Inhibit SARS-CoV-2 Replication</strong> - Aurones are a small subgroup of flavonoids in which the basic C(6)-C(3)-C(6) skeleton is arranged as (Z)-2-benzylidenebenzofuran-3(2H)-one. These compounds are structural isomers of flavones and flavonols, natural products reported as potent inhibitors of SARS-CoV-2 replication. Herein, we report the design, synthesis, and anti-SARS-CoV-2 activity of a series of 25 aurones bearing different oxygenated groups (OH, OCH(3), OCH(2)OCH(3), OCH(2)O, OCF(2)H, and OCH(2)C(6)H(4)R) at the A- and/or…</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>Phytochemicals and micronutrients in suppressing infectivity caused by SARS-CoV-2 virions and seasonal coronavirus HCoV-229E in vivo</strong> - SARS-CoV-2 infection still poses health threats especially to older and immunocompromised individuals. New emerging variants of SARS-CoV-2, including Omicron and Arcturus, have been challenging the effectiveness of humoral immunity resulting from repeated vaccination and infection. With recent study implying a wave of new mutants in vaccinated people making them more susceptible to the newest variants and fueling a rapid viral evolution, there is a need for alternative or adjunct approaches…</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>Impact of disposable mask microplastics pollution on the aquatic environment and microalgae growth</strong> - The COVID-19 pandemic has mandated people to use medical masks to protect the public. However the improper management of disposable mask waste has led to the increase of marine pollution, in terms of water quality, and the decline in aquatic microorganisms. The aim of this research was to investigate the impact of disposable mask waste on fresh water and microalgae biomass quality. Disposable masks (untreated or treated with Enterococcus faecalis) were placed in 10-L glass reactors containing…</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>Olmesartan alleviates SARS-CoV-2 envelope protein induced renal fibrosis by regulating HMGB1 release and autophagic degradation of TGF-β1</strong> - Background and aims: Renal damage in severe coronavirus disease 2019 (COVID-19) is highly associated with mortality. Finding relevant therapeutic candidates that can alleviate it is crucial. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) have been shown to be harmless to COVID-19 patients, but it remains elusive whether ACEIs/ARBs have protective benefits to them. We wished to determine if ACEIs/ARBs had a protective effect on the renal damage…</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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