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<title>13 September, 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>Effects of Chatting Styles on Sharers’ Emotions During Online Conversations</strong> -
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<div>
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Prior social sharing research suggests that cueing sharers to focus on recounting emotionally arousing details of a negative experience often increases negative affect, while cueing them to reconstrue the experience leads to emotional recovery. Extending these findings, we tested whether interpersonal encouragement of reconstrual was consistently more effective than that of recounting in improving emotions induced by different kinds of negative experiences (interpersonal conflicts vs. COVID-19 news in Study 1; regretful vs. angry conflicts in Study 2). In addition, Study 2 compared effects of two different forms of reconstrual (stimulus-reappraisal and perspective-taking) in online settings. Results showed that reconstrual generally had more beneficial effects than recounting and that the benefits of different forms of reconstrual depended on the kind of emotional experiences sharers had. Specifically, perspective-taking was especially effective in regulating anger whereas stimulus-reappraisal appeared to be more suited for improving feelings about regretful events.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/exbnz/" target="_blank">Effects of Chatting Styles on Sharers’ Emotions During Online Conversations</a>
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</div></li>
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<li><strong>Validation of Real-World Case Definitions for COVID-19 Diagnosis and Severe COVID-19 Illness Among Patients Infected with SARS-CoV-2: Translation of Clinical Trial Definitions to Real-World Settings</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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Purpose: This study assessed the performance of International Classification of Diseases 10th Revision, Clinical Modification (ICD-10-CM) coronavirus disease 2019 (COVID-19) diagnostic code U07.1 against polymerase chain reaction (PCR) test results (Objective 1), and electronic medical record (EMR)-based codified algorithm for severe COVID-19 illness based on endpoints used in the Pfizer-BioNTech COVID-19 vaccine trial against chart review (Objective 2). Methods: This retrospective, longitudinal cohort study used EMR data from the Mass General Brigham COVID-19 Data Mart (3/1/2020-11/19/2020) for adult patients with ≥1 PCR test, antigen test, or code U07.1 (Objective 1) and adult patients with a positive PCR test hospitalized with COVID-19 (Objective 2). Results: Among 354,124 patients in Objective 1, 96% had ≥1 PCR test (including 6% with ≥1 positive PCR test; 11% with ≥1 code U07.1). Code U07.1 had low sensitivity (54%) and positive predictive value (PPV; 63%) but high specificity (97%) against the PCR test. Among 300 patients hospitalized for COVID-19 randomly sampled for chart review in Objective 2, the EMR-based case definition for severe COVID-19 illness had high PPV (>95%), showing better performance than severe/critical COVID-19 endpoints defined by the World Health Organization (PPV: 79%). Conclusions: COVID-19 diagnosis based on ICD-10-CM code U07.1 had inadequate sensitivity and requires confirmation by PCR testing. The EMR-based case definition showed high PPV and can be used to identify cases of severe COVID-19 illness in real-world datasets. These findings highlight the importance of validating outcomes in real-world data, and can guide researchers analyzing COVID-19 data when PCR tests are not readily available.
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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/10.1101/2023.09.12.23295441v1" target="_blank">Validation of Real-World Case Definitions for COVID-19 Diagnosis and Severe COVID-19 Illness Among Patients Infected with SARS-CoV-2: Translation of Clinical Trial Definitions to Real-World Settings</a>
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</div></li>
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<li><strong>Determinants of de novo B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections</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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Vaccine-induced immunity may impact subsequent de novo responses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1 variants. Regardless of variant, we observed greater Spike-specific and neutralizing antibody responses in post-vaccination infections than in those who were infected without prior vaccination. Through analysis of variant-specific memory B cells as markers of de novo responses, we observed that Delta and Omicron BA.1 infections led to a marked shift in immunodominance in which some drifted epitopes elicited minimal responses, even in primary infections. Prior immunity through vaccination had a small negative impact on these de novo responses, but this did not correlate with cross-reactive memory B cells, arguing against competitive inhibition of naive B cells. We conclude that dampened de novo B cell responses against drifted epitopes are mostly a function of altered immunodominance hierarchies that are apparent even in primary infections, with a more modest contribution from pre-existing immunity, perhaps due to accelerated antigen clearance.
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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/10.1101/2023.09.12.23295384v1" target="_blank">Determinants of de novo B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections</a>
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</div></li>
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<li><strong>Prevalence of Long COVID-associated symptoms in adults with and without SARS-CoV-2 infection in Germany: Results of the population-based study: Corona Monitoring Nationwide 2021/22 (RKI-SOEP-2)</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background Controlled population-based studies on long-term health sequelae of SARS-CoV-2 can help to identify clinical signs specific to Long COVID and to evaluate this emerging public health challenge. Aim To examine prevalence differences of Long COVID-associated symptoms among adults with and without SARS-CoV-2 infection in Germany. Methods This population-based, retrospective study (11/2021-2/2022) included 7,683 working aged adults (18-65 years), a subset of the Corona Monitoring Nationwide study in Germany. Prior SARS-CoV-2 infection was defined based on self-reported PCR-confirmed infections and IgG-antibody dried blood spot testing. Participants answered a questionnaire including 19 common symptoms of Long COVID experienced in the six months preceding the survey. We estimated population-weighted prevalence of (1) individual symptoms, and (2) ≥1 symptom, with and without impact on work ability, by infection status within strata of sex, age group, income and comorbidity. We calculated model-adjusted prevalence differences and the probability that symptoms among infected are attributable to infection. Results 12 of 19 symptoms showed a significantly higher prevalence in infected than non-infected participants, including fatigue (27.5% versus 18.3%; p<0.001), concentration problems (22.2% vs. 13.1%; p<0.001), shortness of breath (15.6% vs. 7.5%; p<0.001), and smell and taste disorder (10% vs. 1.2%; p<0.001). ≥1 symptom with impact on work ability was more prevalent following infection (16.0% vs. 12.2%; p=0.06) with a model-adjusted prevalence difference of 3.8% (95%-CI -0.5-8.0). Conclusion We observed a rather small excess prevalence attributable to SARS-CoV-2 infection. However, the absolute number of persons places great demands on the health care system and may affect economic productivity.
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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/10.1101/2023.09.12.23295426v1" target="_blank">Prevalence of Long COVID-associated symptoms in adults with and without SARS-CoV-2 infection in Germany: Results of the population-based study: Corona Monitoring Nationwide 2021/22 (RKI-SOEP-2)</a>
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</div></li>
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<li><strong>Digital holo-tomographic 3D maps of COVID-19 microclots in blood to assess disease severity</strong> -
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<div>
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The coronavirus disease 2019 (COVID-19) has impacted health globally. Cumulative evidence points to long-term effects of COVID-19 such as cardiovascular and cognitive disorders diagnosed in patients even after the recovery period. In particular, micrometer-sized blood clots and hyperactivated platelets have been identified as potential indicators of long COVID. Here we resolve individual microclot structures in platelet-rich plasma of donors with different subphenotypes of COVID-19 in a label-free manner, using 3D digital holo-tomographic microscopy (DHTM). Based on 3D refractive index (RI) tomograms, the size, dry mass, and prevalence of microclot composites were quantified and then parametrically differentiated from fibrin-rich microclots and platelet aggregates in the plasma of COVID-19 donors. Importantly, fewer microclots and platelet aggregates were detected in the plasma of healthy controls when compared to COVID-19 donors. Our work highlights the utility of integrating DHTM in clinical settings that may allow the detection of individuals at risk of developing microvascular thrombotic disorders and for monitoring the efficiency of prescribed treatments by screening plasma samples.
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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/10.1101/2023.09.12.557318v1" target="_blank">Digital holo-tomographic 3D maps of COVID-19 microclots in blood to assess disease severity</a>
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</div></li>
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<li><strong>Compartmentalized SARS-CoV-2 replication in upper versus lower respiratory tract after intranasal inoculation or aerosol exposure</strong> -
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<div>
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Non-human primate models are essential for the development of vaccines and antivirals against infectious diseases. Rhesus macaques are a widely utilized infection model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We compared cellular tropism and virus replication in rhesus macaques inoculated with SARS-CoV-2 via the intranasal route, or via exposure to aerosols. Intranasal inoculation results in replication in the upper respiratory tract and limited lower respiratory tract involvement, whereas exposure to aerosols results in infection throughout the respiratory tract. In comparison to multi-route inoculation, the intranasal and aerosol inoculation routes result in reduced SARS-CoV-2 replication in the respiratory tract.
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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/10.1101/2023.09.11.557190v1" target="_blank">Compartmentalized SARS-CoV-2 replication in upper versus lower respiratory tract after intranasal inoculation or aerosol exposure</a>
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</div></li>
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<li><strong>Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 Omicron BA.2.86 and FLip Variants</strong> -
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<div>
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Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and the XBB-lineage variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose vaccinated and bivalent vaccinated healthcare workers, XBB.1.5-wave infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant Spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had relatively high fusogenicity and infectivity in CaLu-3 cells but low fusion and infectivity in 293T-ACE2 cells compared to some XBB variants, suggesting a potentially differences conformational stability of BA.2.86 Spike. Overall, our study underscores the importance of SARS-CoV-2 variant surveillance and the need for updated COVID-19 vaccines.
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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/10.1101/2023.09.11.557206v1" target="_blank">Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 Omicron BA.2.86 and FLip Variants</a>
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</div></li>
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<li><strong>Dual inhibition of coronavirus Mpro and PLpro enzymes by phenothiazines and their antiviral activity</strong> -
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<div>
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Coronavirus (CoV) replication requires efficient cleavage of viral polyproteins into an array of non-structural proteins involved in viral replication, organelle formation, viral RNA synthesis, and host shutoff. Human CoVs (HCoVs) encode two viral cysteine proteases, main protease (Mpro) and papain-like protease (PLpro), that mediate polyprotein cleavage. Using a structure-guided approach, a phenothiazine urea derivative that inhibits both SARS-CoV-2 Mpro and PLpro protease activity in vitro was identified. In silico docking studies also predicted binding of the phenothiazine to the active sites of Mpro and PLpro from distantly related alphacoronavirus, HCoV-229E (229E) and the betacoronavirus, HCoV-OC43 (OC43). The lead phenothiazine urea derivative displayed broad antiviral activity against all three HCoVs tested in cell culture infection models. It was further demonstrated that the compound inhibited 229E and OC43 at an early stage of viral replication, with diminished formation of viral replication organelles and the RNAs that are made within them, as expected following viral protease inhibition. These observations suggest that the phenothiazine urea derivative inhibits viral replication and may broadly inhibit proteases of diverse coronaviruses.
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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/10.1101/2023.09.11.557219v1" target="_blank">Dual inhibition of coronavirus Mpro and PLpro enzymes by phenothiazines and their antiviral activity</a>
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</div></li>
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<li><strong>WELPCR: Low-cost polymerase chain reaction (PCR) thermal cycler for nucleic acid amplification and sensing</strong> -
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<div>
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The COVID-19 pandemic highlighted the need for sensitive and cost-effective diagnostics. The gold standard test to diagnose infectious diseases such as COVID-19 is quantitative polymerase chain reaction (qPCR). Although there have been multiple advances in nucleic acid testing, PCR thermocyclers are expensive and typically not affordable for offering hands-on training to PCR in instructional laboratory courses in undergraduate colleges. We introduce a low-cost, portable, and automated real-time PCR device designed at the Wadhwani Electronics Lab (WEL) at IIT Bombay, christened WELPCR. WELPCR is an open-source design, and capable of reverse transcription PCR (RT-PCR) for complementary DNA synthesis, as well as end-point PCR of small amount of DNA in a test sample. The WELPCR design enables ramp rate up to 2{degrees}C/s, weighs less than 2kg, and is easy to assemble. The built-in LED display and keypad provides an intuitive and seamless user interface to configure and set up WELPCR. With bill of materials (BOM) cost less than INR Rs. 10,000, WELPCR is an attractive solution for bringing PCR technology to instructional and research laboratories in a cost-effective manner.
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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/10.1101/2023.09.11.557292v1" target="_blank">WELPCR: Low-cost polymerase chain reaction (PCR) thermal cycler for nucleic acid amplification and sensing</a>
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</div></li>
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<li><strong>Comparative Analysis of Association Networks Using Single-Cell RNA Sequencing Data Reveals Perturbation-Relevant Gene Signatures</strong> -
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<div>
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Single-cell RNA sequencing (scRNA-seq) data has elevated our understanding of systemic perturbations to organismal physiology at the individual cell level. However, despite the rich information content of scRNA-seq data, the relevance of genes to a perturbation is still commonly assessed through differential expression analysis. This approach provides a one-dimensional perspective of the transcriptomic landscape, risking the oversight of tightly controlled genes characterized by modest changes in expression but with profound downstream effects. We present GENIX (Gene Expression Network Importance eXamination), a novel platform for constructing gene association networks, equipped with an innovative network-based comparative model to uncover condition-relevant genes. To demonstrate the effectiveness of GENIX, we analyze influenza vaccine-induced immune responses in peripheral blood mononuclear cells (PBMCs) collected from recovered COVID-19 patients, shedding light on the mechanistic underpinnings of gender differences. Our methodology offers a promising avenue to identify genes relevant to perturbation responses in biological systems, expanding the scope of response signature discovery beyond differential gene expression analysis.
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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/10.1101/2023.09.11.556872v1" target="_blank">Comparative Analysis of Association Networks Using Single-Cell RNA Sequencing Data Reveals Perturbation-Relevant Gene Signatures</a>
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</div></li>
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<li><strong>Expression Level Analysis of ACE2 Receptor Gene in African-American and Non-African-American COVID-19 Patients</strong> -
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<div>
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Background: The COVID-19 pandemic caused by SARS-CoV-2 has spread rapidly across the continents. While the incidence of COVID-19 has been reported to be higher among African-American individuals, the rate of mortality has been lower compared to that of non-African-Americans. ACE2 is involved in COVID-19 as SARS-CoV-2 uses the ACE2 enzyme to enter host cells. Although the difference in COVID-19 incidence can be explained by many factors such as low accessibility of health insurance among the African-American community, little is known about ACE2 expression in African-American COVID-19 patients compared to non-African-American COVID-19 patients. The variable expression of genes can contribute to this observed phenomenon. Methodology: In this study, transcriptomes from African-American and non-African-American COVID-19 patients were retrieved from the sequence read archive and analyzed for ACE2 gene expression. HISAT2 was used to align the reads to the human reference genome, and HTseq-count was used to get raw gene counts. EdgeR was utilized for differential gene expression analysis, and enrichR was employed for gene enrichment analysis. Results: The datasets included 14 and 33 transcriptome sequences from COVID-19 patients of African-American and non-African-American descent, respectively. There were 24,092 differentially expressed genes, with 7,718 upregulated (log fold change > 1 and FDR 0.05) and 16,374 downregulated (log fold change -1 and FDR 0.05). The ACE2 mRNA level was found to be considerably downregulated in the African-American cohort (p-value = 0.0242, p-adjusted value = 0.038). Conclusion: The downregulation of ACE2 in the African-American cohort could indicate a correlation to the low COVID-19 severity observed among the African-American community.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.11.557129v1" target="_blank">Expression Level Analysis of ACE2 Receptor Gene in African-American and Non-African-American COVID-19 Patients</a>
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</div></li>
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<li><strong>Deep mutational scans of XBB.1.5 and BQ.1.1 reveal ongoing epistatic drift during SARS-CoV-2 evolution</strong> -
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<div>
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Substitutions that fix between SARS-CoV-2 variants can transform the mutational landscape of future evolution via epistasis. For example, large epistatic shifts in mutational effects caused by N501Y underlied the original emergence of Omicron variants, but whether such large epistatic saltations continue to define ongoing SARS-CoV-2 evolution remains unclear. We conducted deep mutational scans to measure the impacts of all single amino acid mutations and single-codon deletions in the spike receptor-binding domain (RBD) on ACE2-binding affinity and protein expression in the recent Omicron BQ.1.1 and XBB.1.5 variants, and we compared mutational patterns to earlier viral strains that we have previously profiled. As with previous RBD deep mutational scans, we find many mutations that are tolerated or even enhance binding to ACE2 receptor. The tolerance of sites to single-codon deletion largely conforms with tolerance to amino acid mutation. Though deletions in the RBD have not yet been seen in dominant lineages, we observe many tolerated deletions including at positions that exhibit indel variation across broader sarbecovirus evolution and in emerging SARS-CoV-2 variants of interest, most notably the well-tolerated {Delta}483 deletion in BA.2.86. The substitutions that distinguish recent viral variants have not induced as dramatic of epistatic perturbations as N501Y, but we identify ongoing epistatic drift in SARS-CoV-2 variants, including interaction between R493Q reversions and mutations at positions 453, 455, and 456, including mutations like F456L that define the newly emerging EG.5 lineage. Our results highlight ongoing drift in the effects of mutations due to epistasis, which may continue to direct SARS-CoV-2 evolution into new regions of sequence space.
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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/10.1101/2023.09.11.557279v1" target="_blank">Deep mutational scans of XBB.1.5 and BQ.1.1 reveal ongoing epistatic drift during SARS-CoV-2 evolution</a>
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<li><strong>Concurrent administration of COVID-19 and influenza vaccines enhances Spike-specific antibody responses</strong> -
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The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent versus separate administration of these vaccines remains unclear. Here, we analyzed antibody responses in healthcare workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or different days. IgG1 responses to SARS-CoV-2 Spike were higher at peak immunogenicity and 6 months following concurrent administration compared with separate administration of the COVID-19 and influenza vaccines. These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 antibody responses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.12.557347v1" target="_blank">Concurrent administration of COVID-19 and influenza vaccines enhances Spike-specific antibody responses</a>
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<li><strong>Impact of vaccinations, boosters and lockdowns on COVID-19 waves in French Polynesia</strong> -
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Estimation of the impact of vaccination and non-pharmaceutical interventions (NPIs) on COVID-19 incidence is complicated by several factors, including the successive emergence of SARS-CoV-2 variants of concern and changing population immunity resulting from vaccination and previous infection. We developed an age-structured multi-strain COVID-19 transmission model and inference framework that could estimate the impact of vaccination and NPIs while accounting for these factors. We applied this framework to French Polynesia, which experienced multiple large COVID-19 waves from multiple variants over the course of the pandemic, interspersed with periods of elimination. We estimated that the vaccination programme averted 49.6% (95% credible interval (CI) 48.7-50.5%) of the 5830 hospitalisations and 64.2% (95% CI 63.1-65.3%) of the 1540 hospital deaths that would have occurred in a baseline scenario without any vaccination up to May 2022. Vaccination also averted an estimated 34.8% (95% CI 34.5-35.2%) of 223,000 symptomatic cases in the baseline scenario. We estimated the booster campaign contributed 4.5%, 1.9% and 0.4% to overall reductions in cases, hospitalisations and hospital deaths respectively. Our results suggested that removing, or altering the timings of, the lockdowns during the first two waves had non-linear effects on overall incidence owing to the resulting effect on accumulation of population immunity. Our estimates of vaccination and booster impact differ from those for other countries due to differences in age structure, previous exposure levels and timing of variant introduction relative to vaccination, emphasising the importance of detailed analysis that accounts for these factors.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.29.23287906v2" target="_blank">Impact of vaccinations, boosters and lockdowns on COVID-19 waves in French Polynesia</a>
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<li><strong>Childhood maltreatment and subsequent risk of hospitalization or death due to COVID-19: a cohort study in the UK Biobank</strong> -
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Childhood maltreatment has been associated with some infection-related outcomes, yet its potential role in severe COVID-19 outcomes has not been addressed. Therefore, leveraging longitudinal data from the population-based UK Biobank (N=151,427), our study aimed to explore the association between childhood maltreatment and severe COVID-19 outcomes (i.e., hospitalization or death due to COVID-19) and its underlying mechanisms. Our results suggest that childhood maltreatment, particularly physical neglect, is associated with a 54.0% increased risk of severe COVID-19 outcomes (i.e., hospitalization or death due to COVID-19), which was not modified by genetic predisposition to severe COVID-19 outcomes. We found that 50.9% of this association was mediated by suboptimal socioeconomic status, lifestyle and prepandemic somatic diseases or psychiatric disorders. These findings highlight the role of early life adversities in severe health consequences across the lifespan and call for increased clinical surveillance of people exposed to childhood maltreatment in COVID-19 outbreaks and future pandemics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.12.23295354v1" target="_blank">Childhood maltreatment and subsequent risk of hospitalization or death due to COVID-19: a cohort study in the UK Biobank</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 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: hAd5-S-Fusion+N-ETSD; Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>: ImmunityBio, Inc.<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>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>: Immunosuppression; COVID-19<br/><b>Intervention</b>: Biological: NVX-CoV2372<br/><b>Sponsors</b>: University of Wisconsin, Madison; Novavax<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>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>: Influenza; COVID-19; Influenza Immunogencity; COVID-19 Immunogenicity<br/><b>Interventions</b>: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster); Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster); Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>: Duke University; Centers for Disease Control and Prevention; Arizona State University; University Hospitals Cleveland Medical Center; University of Pittsburgh; Washington University School of Medicine; Valleywise Health; VA Northeast Ohio Health Care; Senders Pediatrics<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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>: Bronchoalveolar Lavage<br/><b>Intervention</b>: Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>: Mohamed Abd Elmoniem Mohamed; Marwa Salah Abdelrazek Ghanem; Mohammad Khairy El-Badrawy; Tamer Ali Elhadidy; Dalia Abdellateif Abdelghany<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>A Phase 1 Study to Assess the Safety, Reactogenicity, and Immunogenicity of a SARS-CoV-2 Booster Vaccine (LEM-mR203) in Healthy Adults</strong> - <b>Conditions</b>: COVID-19 Infection; COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>: Biological: LEM-mR203; Biological: Placebo<br/><b>Sponsor</b>: Lemonex<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>Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); Johns Hopkins Bloomberg School of Public Health; National Institutes of Health (NIH)<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Determine the Tolerability of Intranasal LMN-301</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: LMN-301<br/><b>Sponsor</b>: Lumen Bioscience, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effectiveness of Natural Resources for Reducing Stress</strong> - <b>Conditions</b>: Distress, Emotional; COVID-19<br/><b>Interventions</b>: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure<br/><b>Sponsors</b>: Klaipėda University; Research Council of Lithuania<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>Long COVID Immune Profiling</strong> - <b>Conditions</b>: Long COVID; POTS - Postural Orthostatic Tachycardia Syndrome; Autonomic Dysfunction<br/><b>Interventions</b>: Diagnostic Test: IL-6; Diagnostic Test: cytokines (IL-17, and IFN-ɣ); Behavioral: Compass 31<br/><b>Sponsors</b>: Vanderbilt University Medical Center; American Heart Association<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 Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>: Critical Illness; COVID-19; PICS; Cognitive Impairment; Mental Health Impairment; Weakness, Muscle; Dysbiosis<br/><b>Intervention</b>: Behavioral: Fermented Food Diet<br/><b>Sponsor</b>: Mayo Clinic<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MICROVASCULAR ENDOTHELIAL ACTIVATION/DYSFUNCTION AND DYSREGULATION OF THE ANGIOPOIETIN-TIE2 SYSTEM IN THE PATHOGENESIS OF LIFE-THREATENING INFECTIONS</strong> - Microvascular endothelial activation/dysfunction has emerged as an important mechanistic pathophysiological process in the development of morbidity and mortality in life-threatening infections. The angiopoietin-Tie2 system plays an integral role in the regulation of microvascular endothelial integrity. Angiopoietin-1 (Ang-1), produced by platelets and pericytes, is the cognate agonistic ligand for Tie2, promoting endothelial quiescence and inhibiting microvascular leak. Angiopoietin-2 (Ang-2),…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prime editor-mediated functional reshaping of <em>ACE2</em> prevents the entry of multiple human coronaviruses, including SARS-CoV-2 variants</strong> - The spike protein of SARS-CoV-2 hijacks the host angiotensin converting enzyme 2 (ACE2) to meditate its entry and is the primary target for vaccine development. Nevertheless, SARS-CoV-2 keeps evolving and the latest Omicron subvariants BQ.1 and XBB have gained exceptional immune evasion potential through mutations in their spike proteins, leading to sharply reduced efficacy of current spike-focused vaccines and therapeutics. Compared with the fast-evolving spike protein, targeting host ACE2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting host calcium channels and viroporins: a promising strategy for SARS-CoV-2 therapy</strong> - Despite passing the pandemic phase of the COVID-19, researchers are still investigating various drugs. Previous evidence suggests that blocking the calcium channels may be a suitable treatment option. Ca^(2+) is required to enhance the fusion process of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, some important inflammatory factors during SARS-CoV-2 infection are dependent on Ca^(2+) level. On the other hand, viroporins have emerged as attractive targets for antiviral…</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 new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19</strong> - Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing thrombus formation. This hyperinflammation is dependent on high levels of anti-spike IgG with aberrant Fc tail glycosylation, leading to Fcγ receptor hyperactivation. For development of immune-regulatory therapeutics, drug specificity is crucial to counteract excessive…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of the BNT162b2 Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Adults</strong> - CONCLUSIONS: BNT162b2 coadministered with SIIV elicited immune responses that were noninferior to those elicited by BNT162b2 alone and SIIV alone, and BNT162b2 had an acceptable safety profile when coadministered with SIIV. The results of this study support the coadministration of BNT162b2 and SIIV in adults.</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>Farnesoid X receptor enhances epithelial ACE2 expression and inhibits viral-induced IL-6 secretion: implications for intestinal symptoms of SARS-CoV-2</strong> - CONCLUSION: By virtue of its ability to modulate epithelial ACE2 expression and inhibit virus-mediated pro-inflammatory cytokine release, FXR represents a promising target for development of new approaches to prevent intestinal manifestations of SARS-CoV-2.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting spike glycans to inhibit SARS-CoV2 viral entry</strong> - SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety…</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>PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell- and tissue-specific manner</strong> - ADP-ribosyltransferases (ARTs) mediate the transfer of ADP-ribose from NAD^(+) to protein or nucleic acid substrates. This modification can be removed by several different types of proteins, including macrodomains. Several ARTs, also known as PARPs, are stimulated by interferon indicating ADP-ribosylation is an important aspect of the innate immune response. All coronaviruses (CoVs) encode for a highly conserved macrodomain (Mac1) that is critical for CoVs to replicate and cause disease,…</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>Efficacy and safety evaluation of Azvudine in the prospective treatment of COVID-19 based on four phase III clinical trials</strong> - Azvudine (FNC) is a synthetic nucleoside analog used to treat adult patients living with human immunodeficiency virus-1 (HIV-1) infection with high viral load. After phosphorylation, Azvudine inhibits RNA-dependent RNA polymerase, leading to the discontinuation of RNA chain synthesis in viruses. In addition, Azvudine is the first dual-target nucleoside oral drug worldwide to simultaneously target reverse transcriptase and viral infectivity factors in the treatment of HIV infection. On 9 August…</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>Altered DNA methylation underlies monocyte dysregulation and innate exhaustion memory in sepsis</strong> - Innate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression in concert with emergency hematopoiesis. Epigenetic changes, notably in the form of histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA…</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 Vivo Antiviral Efficacy of LCTG-002, a Pooled, Purified Human Milk Secretory IgA product, Against SARS-CoV-2 in a Murine Model of COVID-19</strong> - Immunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosal compartments including the respiratory tract, with the secretory form of IgA (sIgA) being dominant and uniquely stable in these environments. sIgA is naturally found in human milk, which could be considered a global resource for this biologic, justifying the development of human milk sIgA as a dedicated airway therapeutic for respiratory infections such as SARS-CoV-2. In the present study, methods were therefore developed…</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>Cationic Chitosan Derivatives for the Inactivation of HIV-1 and SARS-CoV-2 Enveloped Viruses</strong> - Cationic chitosan derivatives have been widely studied as potential antimicrobial agents. However, very little is known about their antiviral activity and mode of action against enveloped viruses. We investigated the ability of hydroxypropanoic acid-grafted chitosan (HPA-CS) and N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) to inactivate enveloped viruses like the human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The…</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>Preventive treatment of coronavirus disease-2019 virus using coronavirus disease-2019-receptor-binding domain 1C aptamer by suppress the expression of angiotensin-converting enzyme 2 receptor</strong> - The cause of the worldwide coronavirus disease-2019 (COVID-19) pandemic is the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is known to employ the same entry portal as SARS-CoV, which is the type 1 transmembrane angiotensin-converting enzyme 2 (ACE2) receptor. The receptor-binding domain (RBD) is located on the spike S-protein’s S1 subunit of the spike glycoprotein. The most important and effective therapy method is inhibiting the interaction between the ACE2 receptor and the…</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>Natural PAK1 inhibitors: potent anti-inflammatory effectors for prevention of pulmonary fibrosis in COVID-19 therapy</strong> - One of the main efforts of scientists to study drug development is the discovery of novel antiviral agents that could be beneficial in the struggle against viruses that cause diseases in humans. Natural products are complex metabolites that are designed and synthesised by different sources in an attempt to optimise nature. Recently, natural products are still a source of biologically active molecules, facilitating drug discovery. A p21-activating kinase PAK1 is a key regulator of cytoskeletal…</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>Nirmatrelvir/ritonavir-induced elevation of blood tacrolimus levels in a patient in the maintenance phase post liver transplantation</strong> - Nirmatrelvir is an orally administered anti-SARS-CoV-2 drug used in combination with ritonavir, the drug-metabolizing cytochrome P450 (CYP) 3A inhibitor, to evade metabolism and extend bioavailability. Meanwhile, the immunosuppressant tacrolimus is a CYP3A4/5 substrate, and CYP3A inhibition results in drug-drug interactions. Herein, we report the case of a coronavirus disease 19 (COVID-19) patient in the maintenance phase post liver transplantation, receiving tacrolimus treatment, with a marked…</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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