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163 lines
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<title>08 April, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Post-16 students’ experience of practical science during the COVID-19 pandemic and the impact on students’ self-efficacy in practical work</strong> -
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<div>
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This paper presents the findings from a detailed study investigating UK undergraduate students’ experience of practical science in their post-16 studies during the COVID-19 pandemic. It also examines the perceived confidence and preparedness of the students in relation to areas of practical science skills at the start of their degree courses. The study employed an exploratory sequential mixed methods design, with the findings from focus groups with students at the end of their post-16 studies used to support the development of a comprehensive skills audit and quantitative survey for incoming undergraduate students. Survey data were collected in September and October 2021 from 275 students commencing Biosciences, Chemistry, Physics and Natural Science degrees at two universities in England. The research is important because although almost all students had the opportunity to undertake practical work as part of their post-16 studies during the COVID-19 pandemic, there was considerable variation in students’ experiences. The data indicate that students’ self-efficacy in relation to practical science was impacted by the closures of post-16 education establishments, ongoing social distancing and the removal of the assessment criteria for students to have ‘routinely and consistently’ undertaken each of the practical assessment requirements. The research presents important considerations which are relevant for educators supporting students’ transition from post-16 to Higher Education.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/edarxiv/gx2jh/" target="_blank">Post-16 students’ experience of practical science during the COVID-19 pandemic and the impact on students’ self-efficacy in practical work</a>
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</div></li>
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<li><strong>Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain</strong> -
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Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg relative to a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells and CD8+ T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain.
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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/10.1101/2024.04.05.588051v1" target="_blank">Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain</a>
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</div></li>
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<li><strong>Direct genome sequencing of respiratory viruses from low viral load clinical specimens using target capture sequencing technology</strong> -
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<div>
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The use of metagenomic next-generation sequencing technology to obtain complete viral genome sequences directly from clinical samples with low viral load remains challenging–especially in the case of respiratory viruses–due to the low copy number of viral versus host genomes. To overcome this limitation, target capture sequencing for the enrichment of specific genomes has been developed and applied for direct genome sequencing of viruses. However, as the efficiency of enrichment varies depending on the probes, the type of clinical sample, etc., validation is essential before target capture sequencing can be applied to clinical diagnostics. Here we evaluated the utility of target capture sequencing with a comprehensive viral probe panel for clinical respiratory specimens collected from patients diagnosed with SARS-CoV-2 or influenza type A. We focused on clinical specimens containing low copy numbers of viral genomes. Target capture sequencing yielded approximately 180- and 2000-fold higher read counts of SARS-CoV-2 and influenza A virus, respectively, than metagenomic sequencing when the RNA extracted from specimens contained 59.3 copies/L of SARS-CoV-2 or 544 copies/L of influenza A virus, respectively. In addition, the target capture sequencing identified sequence reads in all SARS-CoV-2- or influenza type A-positive specimens with <26 RNA copies/L, some of which also yielded >70% of the full-length genomes of SARS-CoV-2 or influenza A virus. Furthermore, the target capture sequencing using comprehensive probes identified co-infections with viruses other than SARS-CoV-2, suggesting that this approach will not only detect a wide range of viruses, but also contribute to epidemiological studies.
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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/10.1101/2024.04.05.588295v1" target="_blank">Direct genome sequencing of respiratory viruses from low viral load clinical specimens using target capture sequencing technology</a>
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</div></li>
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<li><strong>Epitope-anchored contrastive transfer learning for paired CD8+ T cell receptor-antigen recognition</strong> -
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<div>
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Understanding the mechanisms of T-cell antigen recognition that underpin adaptive immune responses is critical for the development of vaccines, immunotherapies, and treatments against autoimmune diseases. Despite extensive research efforts, the accurate identification of T cell receptor (TCR)-antigen binding pairs remains a significant challenge due to the vast diversity and cross-reactivity of TCRs. Here, we propose a deep-learning framework termed Epitope-anchored Contrastive Transfer Learning (EPACT) tailored to paired human CD8+ TCRs from single-cell sequencing data. Harnessing the pre-trained representations and the contrastive co-embedding space, EPACT demonstrates state-of-the-art model generalizability in predicting TCR binding specificity for unseen epitopes and distinct TCR repertoires, offering potential values for practical outcomes in real-world scenarios. The contrastive learning paradigm achieves highly precise predictions for immunodominant epitopes and facilitates interpretable analysis of epitope-specific T cells. The TCR binding strength predicted by EPACT aligns well with the surge in spike-specific immune responses targeting SARS-CoV-2 epitopes after vaccination. We further fine-tune EPACT on TCR-epitope structural data to decipher the residue-level interactions involved in T-cell antigen recognition. EPACT not only exhibits superior capabilities in quantifying inter-chain distance matrices and identifying contact residue pairs but also corroborates the presence of molecular mimicry across multiple tumor-associated antigens. Together, EPACT can serve as a useful AI approach with significant potential in practical applications and contribute toward the development of TCR-based diagnostics and immunotherapies.
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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/10.1101/2024.04.05.588255v1" target="_blank">Epitope-anchored contrastive transfer learning for paired CD8+ T cell receptor-antigen recognition</a>
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</div></li>
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<li><strong>Adaptive and Maladaptive Pathways of COVID-19 Worry on Well-Being: A Cross-National Study</strong> -
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Objective: In a preregistered study, we examined whether worries about COVID-19 are simultaneously linked with enhanced well-being through social interaction and reduced well-being through depression symptoms. Method: In August 2020, census-matched participants from high and low prevalence regions in the United States and Italy (N = 857) completed assessments of COVID-19 worry, social interaction, depression symptoms, and well-being. Results: Worries about COVID-19 predicted both more social interaction and more depression (ps < .001). In multiple mediational analyses, an adaptive pathway of COVID-19 worry through social interaction was associated with higher well-being, whereas a maladaptive pathway through depression symptoms was associated with lower well-being. Further, a comparison of high and low COVID-19 prevalence regions replicated the mediational findings for social interaction, providing evidence against reverse causation and common method variance. Conclusion: Findings suggest that normative worries about acute stressors may both benefit and undermine well-being, depending on their impact on social behavior or depression symptoms.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/h8y4c/" target="_blank">Adaptive and Maladaptive Pathways of COVID-19 Worry on Well-Being: A Cross-National Study</a>
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<li><strong>Spatial proteomics identifies a novel CRTC-dependent viral sensing pathway that stimulates production of Interleukin-11</strong> -
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<div>
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Appropriate cellular recognition of viruses is essential for the generation of effective innate and adaptive antiviral immunity. Viral sensors and their signalling components thus provide a crucial first line of host defence. Many exhibit subcellular relocalisation upon activation, triggering expression of interferon and antiviral genes. To identify novel signalling factors we analysed protein relocalisation on a global scale during viral infection. CREB Regulated Transcription Coactivators-2 and 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation upon a diversity of viral stimuli, in diverse cell types. This movement was depended on Mitochondrial Antiviral Signalling Protein (MAVS), cyclo-oxygenase proteins and protein kinase A. We identify a key effect of transcription stimulated by CRTC2/3 translocation as production of the pro-fibrogenic cytokine interleukin-11. This may be important clinically in viral infections associated with fibrosis, including SARS-CoV-2.
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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/10.1101/2024.04.04.588067v1" target="_blank">Spatial proteomics identifies a novel CRTC-dependent viral sensing pathway that stimulates production of Interleukin-11</a>
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<li><strong>Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera</strong> -
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<div>
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Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with five to six-fold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a five-fold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.
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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/10.1101/2024.04.05.588359v1" target="_blank">Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera</a>
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<li><strong>Care-full Collectives and their Care Practices</strong> -
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In my dissertation, I examine different collectives and their practices through different applied theories of care and theorize on new organizational structures and rituals. This is a study of how people came together during the first wave of Covid-19, myself included. It studies these coming-togethers through different “do-ings” and “be–ings” and juxtaposes them with different theories of care. Theories that include Annemarie Mol’s “Logic of Care”, Ella Myers’ “Worldly things”, Jenna Grant’s “Repair as Care”, Sara Ahmed’s “Fragile Connections” and Lucy Suchman’s “Relocating Innovation”. These different theories come from places like medical anthropology, STS, queer theory, and more. I give an honest account of my journey through these collectives and these theories. I also start to propose an alternate way of organizing institutions for mutual aid through two tools - archetypes and axioms.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/ds39u/" target="_blank">Care-full Collectives and their Care Practices</a>
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<li><strong>Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals.</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.
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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/10.1101/2024.04.03.24305293v1" target="_blank">Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals.</a>
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<li><strong>The Constructive and Destructive Power of Social Norms in the Presence of Authoritative Influence</strong> -
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A randomized survey experiment (N=2,868) was conducted at the onset of the COVID-19 pandemic to examine the effects of information provision on individuals’ cooperation with social distancing measures. Employing a 2 × 2 factorial design, the study examined the influence of social comparison and a powerful messenger. Using an online sample of approximately 3,000 Japanese respondents, it was found that participants demonstrated greater cooperation with social distancing measures when they perceived that they had spent a relatively <em>long</em> time outside the home compared with prevailing social norms in the previous week. Conversely, individuals who spent a relatively <em>short</em> time outside the home, exhibited the opposite effect. However, these results were observed solely in conjunction with the influence of a powerful messenger. The study also explored heterogeneous responses based on personality traits. In conclusion, the results highlight the challenges of changing behavior through informational interventions, emphasizing the role of both the characteristics of the sender and recipient of the information.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/rsbmz/" target="_blank">The Constructive and Destructive Power of Social Norms in the Presence of Authoritative Influence</a>
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<li><strong>Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19</strong> -
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The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis. Machine learning revealed marked CCR5+CD95+ CD8+ T-cell perturbations in mild-to-moderate lung disease, but attenuated T-cell responses hallmarked by elevated CXCL13 in more severe disease. Distinct sets of cells, mediators, and autoantibodies distinguished each restrictive phenotype, and differed from those of patients without significant lung involvement. These differences were reflected in divergent T-cell-based type 1 networks according to severity of lung disease. Our findings, which provide an immunological basis for active lung injury versus advanced disease after COVID-19, might offer new targets for treatment.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.04.03.587929v1" target="_blank">Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19</a>
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<li><strong>Within-host genetic diversity of SARS-CoV-2 across animal species</strong> -
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Infectious disease transmission to different host species makes eradication very challenging and expands the diversity of evolutionary trajectories taken by the pathogen. Since the beginning of the ongoing COVID-19 pandemic, SARS-CoV-2 has been transmitted from humans to many different animal species, and viral variants of concern could potentially evolve in a non-human animal. Previously, using available whole genome consensus sequences of SARS-CoV-2 from four commonly sampled animals (mink, deer, cat, and dog) we inferred similar numbers of transmission events from humans to each animal species but a relatively high number of transmission events from mink back to humans (Naderi et al., 2023). Using a genome-wide association study (GWAS), we identified 26 single nucleotide variants (SNVs) that tend to occur in deer – more than any other animal – suggesting a high rate of viral adaptation to deer. Here we quantify intra-host SARS-CoV-2 across animal species and show that deer harbor more intra-host SNVs (iSNVs) than other animals, providing a larger pool of genetic diversity for natural selection to act upon. Within-host diversity is particularly high in deer lymph nodes compared to nasopharyngeal samples, suggesting tissue-specific differences in viral population sizes or selective pressures. Neither mixed infections involving more than one viral lineage nor large changes in the strength of selection are likely to explain the higher intra-host diversity within deer. Rather, deer are more likely to contain larger viral population sizes, to be infected for longer periods of time, or to be systematically sampled at later stages of infections. Combined with extensive deer-to-deer transmission, the high levels of within-deer viral diversity help explain the apparent rapid adaptation of SARS-CoV-2 to deer.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.04.03.587973v1" target="_blank">Within-host genetic diversity of SARS-CoV-2 across animal species</a>
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<li><strong>Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology</strong> -
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Background: Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused a global pandemic. Gastric cancer (GC) poses a great threat to people's health, which is a high-risk factor for COVID-19. Previous studies have found some associations between GC and COVID-19, whereas the underlying molecular mechanisms are not well understood. Methods: We used a bioinformatics and systems biology approach to investigate the relationship between GC and COVID-19. The gene expression profiles of COVID-19 (GSE196822) and GC (GSE179252) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the shared differentially expressed genes (DEGs) for GC and COVID-19, functional annotation, protein-protein interaction (PPI) network, hub genes, transcriptional regulatory networks and candidate drugs were analyzed. Results: A total of 209 shared DEGs were identified to explore the linkages between COVID-19 and GC. Functional analyses showed that Immune-related pathway collectively participated in the development and progression of COVID-19 and GC. In addition, there are selected 10 hub genes including CDK1, KIF20A, TPX2, UBE2C, HJURP, CENPA, PLK1, MKI67, IFI6, and IFIT2. The transcription factor/gene and miRNA/gene interaction networks identified 38 transcription factors (TFs) and 234 miRNAs. More importantly, we identified ten potential therapeutic agents, including ciclopirox, resveratrol, etoposide, methotrexate, trifluridine, enterolactone, troglitazone, calcitriol, dasatinib and deferoxamine, some of which have been reported to improve and treat GC and COVID-19. This study also provides insight into the diseases most associated with mutual DEGs, which may provide new ideas for research on the treatment of COVID-19. Conclusions: This research has the possibility to be contributed to effective therapeutic in COVID-19 and GC.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.04.03.587916v1" target="_blank">Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology</a>
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<li><strong>Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19</strong> -
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The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CLpro), and papain-like protease (PLpro) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CLpro inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CLpro from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms. Through the application of a structure-based drug design (SBDD) approach, we discovered a series of novel potent non-covalent PLpro inhibitors with remarkable in vitro potency and in vivo PK properties. The co-crystal structures of PLpro with leads revealed that the residues E164 and Q269 around the S2 site are critical for improving the inhibitor's potency. The lead compound GZNL-P36 not only inhibited SARS-CoV-2 and its variants at the cellular level with EC50 ranging from 58.2 nM to 306.2 nM, but also inhibited HCoV-NL63 and HCoV-229E with EC50 of 81.6 nM and 2.66 M, respectively. Oral administration of the compound resulted in significantly improved survival and notable reductions in lung viral loads and lesions in SARS-CoV-2 infection mouse model, consistent with RNA-seq data analysis. Our results indicate that PLpro inhibitor is a promising SARS-CoV-2 therapy.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.04.03.587743v1" target="_blank">Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19</a>
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<li><strong>Comparative analysis of serological assays and sero-surveillance for SARS-CoV-2 exposure in US cattle</strong> -
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Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to pose a significant threat to public health globally. Notably, SARS-CoV-2 demonstrates a unique capacity to infect various non-human animal species, documented in captive and free-living animals. However, experimental studies revealed low susceptibility of domestic cattle (Bos taurus) to ancestral B.1 lineage SARS-CoV-2 infection, with limited viral replication and seroconversion. Despite the emergence of viral variants with potentially altered host tropism, recent experimental findings indicate greater permissiveness of cattle to SARS-CoV-2 Delta variant infection compared to other variants, though with limited seroconversion and no clear evidence of transmission. While some studies detected SARS-CoV-2 antibodies in cattle in Italy and Germany, there is no evidence of natural SARS-CoV-2 infection in cattle from the United States or elsewhere. Since serological tests have inherent problems of false positives and negatives, we conducted a comprehensive assessment of multiple serological assays on over 600 cattle serum samples, including pre-pandemic and pandemic cattle sera. We found that SARS-CoV-2 pseudovirus neutralization assays with a luciferase reporter system can produce false positive results, and care must be taken to interpret serological diagnosis using these assays. We found no serological evidence of natural SARS-CoV-2 infection or transmission among cattle in the USA. Hence, it is critical to develop more reliable serological assays tailored to accurately detect SARS-CoV-2 antibodies in cattle populations and rigorously evaluate diagnostic tools. This study underscores the importance of robust evaluation when employing serological assays for SARS-CoV-2 detection in cattle populations.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.04.03.587933v1" target="_blank">Comparative analysis of serological assays and sero-surveillance for SARS-CoV-2 exposure in US cattle</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>Effect of Probiotic Strain Lactobacillus Paracasei PS23 on Brain Fog in People With Long COVID</strong> - <b>Conditions</b>: Long COVID; Brain Fog; Cognitive Change <br/><b>Interventions</b>: Dietary Supplement: Lactobacillus paracasei PS23; Dietary Supplement: microcrystalline cellulose <br/><b>Sponsors</b>: Taipei Veterans General Hospital, Taiwan <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>Fascial Tissue Response To Manual Therapy: Implications In Long Covid Rehabilitation</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Guidebook; Other: Guidebook and Myofascial Reorganization® (RMF). <br/><b>Sponsors</b>: University of the State of Santa Catarina; Larissa Sinhorim <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>Evaluation of the Impact of Rehabilitation Strategies and Early Discharge After Respiratory Failure</strong> - <b>Conditions</b>: Acute Respiratory Failure <br/><b>Interventions</b>: Behavioral: Standard of Care; Behavioral: Rehabilitation <br/><b>Sponsors</b>: Hospital Israelita Albert Einstein <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>Diaphragmatic Breathing Exercises for Post-COVID-19 Diaphragmatic Dysfunction (DD)</strong> - <b>Conditions</b>: Post-Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Usual care of traditional treatment; Other: Specific DB program/Diaphragmatic manipulation program <br/><b>Sponsors</b>: University of Minnesota <br/><b>Recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health</strong> - The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called “gut-lung axis”. Perturbations in gut microbiota composition, termed dysbiosis, can have…</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>SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway</strong> - CONCLUSION: These findings suggest that SARS-CoV-2 infection causes BBB dysfunction via Wnt signaling. Thus, iPSC-BMELCs are a useful in vitro model for elucidating COVID-19 neuropathology and drug development.</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>Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?</strong> - Due to the health emergency created by SARS-CoV-2, the virus that causes the COVID-19 disease, the rapid implementation of a new vaccine technology was necessary. mRNA vaccines, being one of the cutting-edge new technologies, attracted significant interest and offered a lot of hope. The potential of these vaccines in preventing admission to hospitals and serious illness in people with comorbidities has recently been called into question due to the vaccines’ rapidly waning immunity. Mounting…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of PCSK9 with evolocumab modulates lipoproteins and monocyte activation in high-risk ASCVD subjects</strong> - CONCLUSIONS: This trial is the first to demonstrate that PCSK9 mAB with evolocumab can modulate circulating immune cell properties and highlights the importance of “stress” profiling of circulating immune cells that more clearly define immune contributions to ASCVD.</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 and development of novel 10,12-disubstituted aloperine derivatives against HCoV-OC43 by targeting allosteric site of host TMPRSS2</strong> - By inducing steric activation of the 10CH bond with a 12-acyl group to form a key imine oxime intermediate, 20 novel (10S)-10,12-disubstituted aloperine derivatives were successfully synthesized and assessed for their antiviral efficacy against HCoV-OC43. Of them, compound 3i exhibited the moderate activities against HCoV-OC43, as well as against the SARS-CoV-2 variant EG.5.1 with the comparable EC(50) values of 4.7 and 4.1 μM. A mechanism study revealed that it inhibited the protease activity…</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>Protocol to identify flavonoid antagonists of the SARS-CoV-2 main protease</strong> - Flavonoids are naturally occurring metabolites of plants that can inhibit the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), which is required for viral replication. Here, we present a protocol to identify flavonoid antagonists of the SARS-CoV-2 Mpro. We describe steps for the expression and purification of Mpro and a kinetic enzymatic assay for Mpro activity using a dequenching fluorescence resonance energy transfer peptide substrate. We then detail…</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>DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients</strong> - Since the discovery of copper induces cell death(cuprotosis) in 2022, it has been one of the biggest research hotspots. cuprotosis related genes (CRGs) has been demonstrated to be a potential therapeutic target for cancer, however, the molecular mechanism of CRGs in coronavirus disease 2019 (COVID-19) infected in DLBCL patients has not been reported yet. Therefore, our research objective is first to elucidate the mechanism and role of CRGs in COVID-19. Secondly, we conducted univariate and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunoglobulin G4-related disease and B-cell malignancy due to an IKZF1 gain-of-function variant</strong> - CONCLUSION: Heterozygosity for gain-of-function IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunological data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity.</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>Toll like receptor 4 mediates the inhibitory effect of SARS-CoV-2 spike protein on proximal tubule albumin endocytosis</strong> - Tubular proteinuria is a common feature in COVID-19 patients, even in the absence of established acute kidney injury. SARS-CoV-2 spike protein (S protein) was shown to inhibit megalin-mediated albumin endocytosis in proximal tubule epithelial cells (PTECs). Angiotensin-converting enzyme type 2 (ACE2) was not directly involved. Since Toll-like receptor 4 (TLR4) mediates S protein effects in various cell types, we hypothesized that TLR4 could be participating in the inhibition of PTECs albumin…</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>Coordination chemistry suggests that independently observed benefits of metformin and Zn(2+) against COVID-19 are not independent</strong> - Independent trials indicate that either oral Zn^(2+) or metformin can separately improve COVID-19 outcomes by approximately 40%. Coordination chemistry predicts a mechanistic relationship and therapeutic synergy. Zn^(2+) deficit is a known risk factor for both COVID-19 and non-infectious inflammation. Most dietary Zn^(2+) is not absorbed. Metformin is a naked ligand that presumably increases intestinal Zn^(2+) bioavailability and active absorption by cation transporters known to transport…</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>SARS-CoV-2 and the Angiotensin-Converting Enzyme 2 Receptor: Angiotensin-Converting Enzyme Inhibitor/Angiotensin 2 Receptor Blocker Utilization and a Shift Towards the Renin-Angiotensin-Aldosterone System Classical Pathway</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, uses the surface angiotensin-converting enzyme 2 (ACE2) receptor as the site of entry into host cardiac, respiratory, intestinal, renal, and nervous system cells. Predisposing risk factors such as cardiovascular disease increase the risk of developing severe disease. Hypertension is characterized by the stimulation of the renin-angiotensin-aldosterone system…</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>Ipsilateral and contralateral coadministration of influenza and COVID-19 vaccines produce similar antibody responses</strong> - BACKGROUND: World Health Organisation (WHO) and USA Centers for Disease Control and Prevention (U.S. CDC) recommendations now allow simultaneous administration of COVID-19 and other vaccines. We compared antibody responses after coadministration of influenza and bivalent COVID-19 vaccines in the same (ipsilateral) arm vs. different (contralateral) arms.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of the RLR signaling pathway by SARS-CoV-2 ORF7b is mediated by MAVS and abrogated by ORF7b-homologous interfering peptide</strong> - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterized by dysregulated immune response. Studies have shown that the SARS-CoV-2 accessory protein ORF7b induces host cell apoptosis through the tumor necrosis factor alpha (TNF-α) pathway and blocks the production of interferon beta (IFN-β). The underlying mechanism remains to be investigated. In this study, we found that ORF7b facilitated viral infection and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency</strong> - INTRODUCTION: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition.</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>Assessment of the activity of the immune system in patients with inflammatory bowel diseases and asymptomatic COVID-19</strong> - CONCLUSIONS: The increased concentration of IL-2 may result from its regulatory role in inhibiting excessive activation of the immune system; however, considering the studies of patients with severe COVID-19, its role in the initial phase of SARS-CoV-2 infection requires further research.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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