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178 lines
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<title>28 October, 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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<ul>
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<li><strong>Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development</strong> -
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<div>
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Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable of evading prior immunity. The mutation and evolution of SARS-CoV-2 have created a demand for persistent efforts in vaccine development. SARS-CoV-2 Spike protein has been the primary target for COVID-19 vaccine development, but it is also the hotspot of mutations directly involved in host susceptibility and immune evasion. Our ability to predict emerging mutants and select conserved epitopes is critical for the development of a broadly neutralizing therapy or a universal vaccine. In this article, we review the general paradigm of immune responses to COVID-19 vaccines, highlighting the immunological epitopes of Spike protein that are likely associated with eliciting protective immunity resulting from vaccination. Specifically, we analyze the structural and evolutionary characteristics of the SARS-CoV-2 Spike protein related to immune activation and function via the toll-like receptors (TLRs), B cells, and T cells. We aim to provide a comprehensive analysis of immune epitopes of Spike protein, thereby contributing to the development of new strategies for broad neutralization or universal vaccination.
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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/10.1101/2023.10.26.564184v1" target="_blank">Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development</a>
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</div></li>
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<li><strong>Impact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant</strong> -
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<div>
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During the COVID-19 pandemic, hematopoietic stem cell transplant (HSCT) recipients faced an elevated mortality rate from SARS-CoV-2 infection, ranging between 10-40%. The SARS-CoV-2 mRNA vaccines are important tools in preventing severe disease, yet their efficacy in the post-transplant setting remains unclear, especially in patients subjected to myeloablative chemotherapy and immunosuppression. We evaluated the humoral and adaptive immune responses to the SARS-CoV-2 mRNA vaccination series in 42 HSCT recipients and 5 healthy controls. Peripheral blood mononuclear nuclear cells and serum were prospectively collected before and after each dose of the SARS-CoV-2 vaccine. Post-vaccination responses were assessed by measuring anti-spike IgG and nucleocapsid titers, and antigen specific T cell activity, before and after vaccination. In order to examine mechanisms behind a lack of response, pre- and post-vaccine samples were selected based on humoral and cellular responses for single-cell RNA sequencing with TCR and BCR sequencing. Our observations revealed that while all participants eventually mounted a humoral response, transplant recipients had defects in memory T cell populations that were associated with an absence of T cell response, some of which could be detected pre-vaccination.
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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/10.1101/2023.10.26.564259v1" target="_blank">Impact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant</a>
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</div></li>
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<li><strong>Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies</strong> -
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<div>
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A current challenge is the emergence of SARS-CoV-2 variants, such as BQ.1.1 and XBB.1.5, that can evade immune defenses, thereby limiting antibody drug effectiveness. Emergency-use antibody drugs, including the widely effective bebtelovimab, are losing their benefits. One potential approach to address this issue are bispecific antibodies which combine the targeting abilities of two antibodies with distinct epitopes. We engineered neutralizing bispecific antibodies in the IgG-scFv format from two initially non-neutralizing antibodies, CvMab-6 (which binds to the receptor-binding domain [RBD]) and CvMab-62 (targeting a spike protein S2 subunit epitope adjacent to the known anti-S2 antibody epitope). Furthermore, we created a bispecific antibody by incorporating the scFv of bebtelovimab with our anti-S2 antibody, demonstrating significant restoration of effectiveness against bebtelovimab-resistant BQ.1.1 variants. This study highlights the potential of neutralizing bispecific antibodies, which combine existing less effective anti-RBD antibodies with anti-S2 antibodies, to revive the effectiveness of antibody therapeutics compromised by immune-evading variants.
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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/10.1101/2023.10.26.564289v1" target="_blank">Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies</a>
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</div></li>
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<li><strong>Eviction Moratorium Litigation: What Courts Said, and What Courts Missed</strong> -
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<div>
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In 2020, federal, state, and local governments imposed eviction moratoriums to prevent mass homelessness and limit the spread of COVID-19. Landlords responded to this unprecedented action by filing lawsuits around the country. This Article analyzes the litigation. It examines the claims of landlords, defenses raised by the government, and how courts dealt with each of them. It also highlights the ways that courts misunderstand the rental market and devalue tenants. The Article shows that, before the Supreme Court intervened in mid-2021, most landlord suits failed, either because courts rejected their claims or governments ran out the clock, demonstrating that mass eviction moratoriums can protect the most vulnerable in times of crisis.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/zumw2/" target="_blank">Eviction Moratorium Litigation: What Courts Said, and What Courts Missed</a>
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</div></li>
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<li><strong>Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection</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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Background. Acute kidney injury (AKI) is common in hospitalized patients with SARS-CoV2 infection despite vaccination and leads to long-term kidney dysfunction. However, peripheral blood molecular signatures in AKI from COVID-19 and their association with long-term kidney dysfunction are yet unexplored. Methods. In patients hospitalized with SARS-CoV2, we performed bulk RNA sequencing using peripheral blood mononuclear cells (PBMCs). We applied linear models accounting for technical and biological variability on RNA-Seq data accounting for false discovery rate (FDR) and compared the functional enrichment and pathway results to a historical sepsis-AKI cohort. Finally, we evaluated the association of these signatures with long-term trends in kidney function. Results. Of 283 patients, 106 had AKI. After adjustment for sex, age, mechanical ventilation, and chronic kidney disease (CKD), we identified 2635 significant differential gene expressions at FDR<0.05. Top canonical pathways were EIF2 signaling, oxidative phosphorylation, mTOR signaling, and Th17 signaling, indicating mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Comparison with sepsis associated AKI showed considerable overlap of key pathways (48.14%). Using follow-up estimated glomerular filtration rate (eGFR) measurements from 115 patients, we found that 164/2635 (6.2%) of the significantly differentiated genes were associated with overall decrease in long-term kidney function. The strongest associations were autophagy, renal impairment via fibrosis and cardiac structure/function. Conclusions. We show that AKI in SARS-CoV2 is a multifactorial process with mitochondrial dysfunction driven by ER stress whereas long-term kidney function decline is associated with cardiac structure and function, and immune dysregulation. Functional overlap with sepsis-AKI also highlights common signatures indicating generalizability in therapeutic approaches.
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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/10.1101/2023.10.25.23297469v2" target="_blank">Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection</a>
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</div></li>
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<li><strong>Comparative Organ Disease Burden and Sequelae of Influenza and SARS-CoV-2 Infection: An Observational Study Using Real-World Data</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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Infections with SARS-CoV-2 and influenza are associated with acute and post-acute complications and sequelae of many organ systems (i.e., disease burden). It is important to understand the global disease burden that associates with and follows acute infection in order to establish preventive and therapeutic strategies and to reduce the use of health resources and improve patient health outcomes. To address these questions, we utilized the National Covid Cohort Collaborative, which is an integrated and harmonized data repository of electronic health record data in the USA. From this database, we included in analysis 346,648 eligible SARS-CoV-2-infected patients, 78,086 eligible influenza infected patients, and 146,635 uninfected controls. We describe the disease burden that extends over 2-3 months following infection, and we quantify the reduction of disease burden by treatment. We identify a burden of disease following medically attended influenza that is comparable to that of medically attended SARS-CoV-2 infection. However, in contrast to SARS-CoV-2, influenza acute infection and disease burden are not responsive to antiviral treatment and thus remain as an unmet medical need. Focusing therapeutic strategies solely on the short-term management of acute infection may also underestimate the extended health benefits of antiviral treatment.
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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/10.1101/2023.10.26.23297626v2" target="_blank">Comparative Organ Disease Burden and Sequelae of Influenza and SARS-CoV-2 Infection: An Observational Study Using Real-World Data</a>
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</div></li>
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<li><strong>Sort-Seq: immune repertoire-based scRNA-Seq systematization</strong> -
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<div>
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The functional programs chosen by B and T cell clones fundamentally determine the architecture of immune response to distinct challenges. Advances in scRNA-Seq have improved our understanding of the diversity and stability of these programs, but it has proven difficult to link this information with known lymphocyte subsets. Here, we introduce Sort-Seq, an immune repertoire-based method that allows exact positioning of phenotypically defined lymphocyte subsets within scRNA-Seq data. Sort-Seq outperformed CITE-Seq for accurate mapping of the classical CD4+ T helper (Th) cell subsets (Th1, Th1-17, Th17, Th22, Th2a, Th2, and Treg), offering a more powerful approach to the surface phenotype-based scRNA-Seq classification of adaptive lymphocyte subpopulations. Using integrated scRNA-Seq, Sort-Seq, and CITE-Seq data from 122 donors, we provide a comprehensive Th cell scRNA-Seq reference map. Exploration of this dataset revealed the low plasticity and extreme sustainability of the Th17, Th22, Th2, and Th2a cell programs over years. We also develop Cultivation-based Antigen-specific T cell identificatoR in Replicates (CultivAToRR), which identified >80 SARS-CoV-2-specific CD4+ TCR{beta} clonotypes in a single donor across a wide frequency range. We complemented these results with frequency-based capturing of COVID-19-responsive clonotypes and screening against known SARS-CoV-2-specific TCRs. Positioning within the annotated scRNA-Seq map revealed functional subtypes of Th cell clones involved in primary and secondary responses against SARS-CoV-2. The ability to capture low-frequency antigen-specific T cell clones in combination with Sort-Seq-based scRNA-Seq annotation creates an integral pipeline that links challenge-responsive clones with their exact functional subtypes, providing a solid foundation for investigating T cell roles in healthy and pathological immune responses and vaccine development.
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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/10.1101/2023.10.24.563704v1" target="_blank">Sort-Seq: immune repertoire-based scRNA-Seq systematization</a>
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</div></li>
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<li><strong>Cost-effectiveness analysis of COVID-19 booster doses and oral antivirals in the Indo-Pacific</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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Background: Decision-makers in middle-income countries need evidence on the cost-effectiveness of COVID-19 booster doses and oral antivirals to appropriately prioritise these healthcare interventions. Methods: We used a dynamic transmission model to assess the cost-effectiveness of COVID-19 booster doses and oral antivirals in Fiji, Indonesia, Papua New Guinea, and Timor-Leste. We conducted cost-effectiveness analysis from both healthcare and societal perspectives using 3% discounting for ongoing costs and health benefits. We developed an interactive R Shiny which allows the user to vary key model assumptions, such as the choice of discounting rate, and view how these assumptions affect model results. Findings: Booster doses were cost saving and therefore cost-effective in all four middle-income settings from both healthcare and societal perspectives using 3% discounting. Providing oral antivirals was cost-effective from a healthcare perspective if procured at a low generic ($25 United States Dollars) or middle-income reference price ($250 United States Dollars); however, their cost-effectiveness was strongly influenced by rates of wastage or misuse, and the ongoing costs of care for patients hospitalised with COVID-19. Interestingly, the cost or wastage of rapid antigen tests did not appear strongly influential over the cost-effectiveness of oral antivirals in any of the four study settings. Conclusions: Our results support that government funded COVID-19 booster programs continue to be cost-effective in middle-income settings. Oral antivirals demonstrate the potential to be cost-effective if procured at or below a middle-income reference price of $250 USD per schedule. Further research should quantify the rates of wastage or misuse of oral COVID-19 antivirals in middle-income settings.
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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/10.1101/2023.10.26.23297613v1" target="_blank">Cost-effectiveness analysis of COVID-19 booster doses and oral antivirals in the Indo-Pacific</a>
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</div></li>
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<li><strong>COVID-19 first lockdown as a window into language acquisition: associations between caregiver-child activities and vocabulary gains.</strong> -
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<div>
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The COVID-19 pandemic, and the resulting closure of daycare centers worldwide, led to unprecedented changes in children’s learning environments. This period of increased time at home with caregivers, with limited access to external sources (e.g., daycares) provides a unique opportunity to examine the associations between the caregiver-child activities and children’s language development. The vocabularies of 1742 children aged 8-36 months across 13 countries and 12 languages were evaluated at the beginning and end of the first lockdown period in their respective countries (from March to September 2020). Children who had less passive screen exposure and whose caregivers read more to them showed larger gains in vocabulary development during lockdown, after controlling for SES and other caregiver-child activities. Children also gained more words than expected (based on normative data) during lockdown; either caregivers were more aware of their child’s development, or vocabulary development benefited from intense caregiver-child interaction during lockdown or both. We discuss these results in the context of the extraordinary circumstances of the COVID-19 pandemic and highlight limitations of the study.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/5ejwu/" target="_blank">COVID-19 first lockdown as a window into language acquisition: associations between caregiver-child activities and vocabulary gains.</a>
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</div></li>
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<li><strong>Homeworking and Division of Domestic Work: the Role of Gender Role Attitudes in Germany</strong> -
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<div>
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Homeworking is often portrayed as a work-life balance measure. Though in theory homeworking can provide workers with more time for leisure and family, due to the boundary blurring between work and life spheres, it can exacerbate gender inequalities. Empirically, the evidence is mixed whether homeworking increases women’s time in domestic labour and men’s time in paid labour. We extend the debate by exploring how individuals’ gender role attitudes moderate the relationship between homeworking and the division of domestic work. We apply hybrid models to the German Panel Analysis of Intimate Relationships and Family Dynamics Survey. The data covers from 2008 to 2021 which includes the unique COVID-19 pandemic. Results show that gender role attitudes matter. When gaining access to homeworking egalitarian men increased their contribution to childcare, while traditional men did not. Similarly, homeworking traditional women increased their childcare contribution. During the pandemic, only traditional women did even more childcare, while men contributed more regardless of their gender role attitudes.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/85b23/" target="_blank">Homeworking and Division of Domestic Work: the Role of Gender Role Attitudes in Germany</a>
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</div></li>
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<li><strong>Reduced mobility? Urban exodus? Medium-term impacts of the COVID-19 pandemic on internal population movements in Latin American countries</strong> -
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<div>
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The COVID‐19 pandemic has impacted the national systems of population movement around the world. Existing work has focused on countries of the Global North and restricted to the immediate effects of COVID-19 data during 2020. Data have represented a major limitation to monitor change in mobility patterns in countries in the Global South. Drawing on aggregate anonymised mobile phone location data from Meta‐Facebook users, we aim to analyse the extent and persistence of changes in the levels (or intensity) and spatial patterns of internal population movement across the rural-urban continuum in Argentina, Chile and Mexico over a 26-month period from March 2020 to May 2022. We reveal an overall systematic decline in the level of short- and long-distance movement during the enactment of nonpharmaceutical interventions in 2020, with the largest reductions occurred in the most dense areas. We also show that these levels bounced back closer to pre-pandemic levels in 2022 following the relaxation of COVID-19 stringency measures. However, the intensity of these movements has remained below pre-pandemic levels in many areas in 2022. Additionally our findings lend some support to the idea of an urban exodus. They reveal a continuing negative net balances of short-distance movements in the most dense areas of capital cities in Argentina and Mexico, reflecting a pattern of suburbanisation. Chile displays limited changes in the net balance of short-distance movements but reports a net loss of long-distance movements. These losses were, however, temporary, moving to neutral and positive balances in 2021 and 2022.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/2gf6b/" target="_blank">Reduced mobility? Urban exodus? Medium-term impacts of the COVID-19 pandemic on internal population movements in Latin American countries</a>
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</div></li>
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<li><strong>A deep learning framework for predicting the neutralizing activity of COVID-19 therapeutics and vaccines against evolving SARS-CoV-2 variants</strong> -
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<div>
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Understanding how viral variants evade neutralization is crucial for improving antibody-based treatments, especially with rapidly evolving viruses like SARS-CoV-2. Yet, conventional assays are limited in the face of rapid viral evolution, relying on a narrow set of viral isolates, and falling short in capturing the full spectrum of variants. To address this, we have developed a deep learning approach to predict changes in neutralizing antibody activity of COVID-19 therapeutics and vaccines against emerging viral variants. First, we trained a variational autoencoder (VAE) using all 67,885 unique SARS-CoV-2 spike protein sequences from the NCBI virus (up to October 31, 2022) database to encode spike protein variants into a latent space. Using this VAE and a curated dataset of 7,069 in vitro assay data points from the NCATS OpenData Portal, we trained a neural network regression model to predict fold changes in neutralizing activity of 40 COVID-19 therapeutics and vaccines against spike protein sequence variants, relative to their neutralizing activity against the ancestral strain (Wuhan-Hu-1). Our model also employs Bayesian inference to quantify prediction uncertainty, providing more nuanced and informative estimates. To validate the model's predictive capacity, we assessed its performance on a test set of in vitro assay data collected up to eight months after the data included in the model training (N = 980). The model accurately predicted fold changes in neutralizing activity for this prospective dataset, with an R2 of 0.77. Expanding our methodology to include all available data from NCBI virus and NCATS OpenData Portal up to date, we assessed predicted changes in activity for current COVID-19 monoclonal antibodies and vaccines against newly identified SARS-CoV-2 lineages. Our predictions suggest that current therapeutic and vaccine-induced antibodies will have significantly reduced activity against newer XBB descendants, notably EG.5, FL.1.5.1, and XBB.1.16. Using the model, we were able to primarily attribute the observed predicted loss in activity to the F456L spike mutation found in EG.5 and FL.1.5.1 sequences. Conversely, mRNA-bivalent vaccines are predicted to be less susceptible to the recent BA.2.86 variant compared to new XBB descendants. These findings align closely with recent research, underscoring the potential of deep learning in shaping therapeutic and vaccine strategies for emerging viral variants.
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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/10.1101/2023.10.24.563847v1" target="_blank">A deep learning framework for predicting the neutralizing activity of COVID-19 therapeutics and vaccines against evolving SARS-CoV-2 variants</a>
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</div></li>
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<li><strong>Reduced Monocyte Proportions and Responsiveness in Convalescent COVID-19 Patients</strong> -
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<div>
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The clinical manifestations of acute severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and COVID-19 suggest a dysregulation of the host immune response that leads to inflammation, thrombosis, and organ dysfunction. It is less clear whether these dysregulated processes persist during the convalescent phase of disease or during long COVID. We investigated the effects of SARS-CoV-2 infection on the proportions of classical, intermediate, and non-classical monocytes, their activation status, and their functional properties in convalescent COVID-19 patients and uninfected control subjects. We found that the percentage of total monocytes was decreased in convalescent COVID-19 patients compared to uninfected controls. This was due to decreased intermediate and non-classical monocytes. Classical monocytes from convalescent COVID-19 patients demonstrated a decrease in activation markers, such as CD56, in response to stimulation with bacterial lipopolysaccharide (LPS). In addition, classical monocytes from convalescent COVID-19 patients showed decreased expression of CD142 (tissue factor), which can initiate the extrinsic coagulation cascade, in response to LPS stimulation. Finally, we found that monocytes from convalescent COVID-19 patients produced less TNF- and IL-6 in response to LPS stimulation, than those from uninfected controls. In conclusion, SARS-CoV-2 infection exhibits a clear effect on the relative proportions of monocyte subsets, the activation status of classical monocytes, and proinflammatory cytokine production that persists during the convalescent phase of disease.
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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/10.1101/2023.10.25.563806v1" target="_blank">Reduced Monocyte Proportions and Responsiveness in Convalescent COVID-19 Patients</a>
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</div></li>
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<li><strong>Discovery of a novel inhibitor of macropinocytosis with antiviral activity</strong> -
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<div>
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Several viruses hijack various forms of endocytosis in order to infect host cells. Here, we report the discovery of a new molecule with antiviral properties that we named virapinib, which limits viral entry by macropinocytosis. The identification of virapinib derives from a chemical screen using High-Throughput Microscopy, where we identified new chemical entities capable of preventing infection with a pseudotype virus expressing the spike (S) protein from SARS-CoV-2. Subsequent experiments confirmed the capacity of virapinib to inhibit infection by SARS-CoV-2, as well as by additional viruses, such as Monkeypox virus and TBEV. Mechanistic analyses revealed that the compound inhibited macropinocytosis, limiting this entry route for the viruses. Importantly, virapinib has no significant toxicity to host cells. In summary, we present a new molecule that inhibits viral entry via the endocytic route, offering a new alternative to prevent viral infection.
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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/10.1101/2023.10.25.563967v1" target="_blank">Discovery of a novel inhibitor of macropinocytosis with antiviral activity</a>
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</div></li>
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<li><strong>Early antiviral CD4 and CD8 T cell responses are associated with upper respiratory tract clearance of SARS-CoV-2</strong> -
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<div>
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T cells are involved in protective immunity against numerous viral infections. Limited data have been available regarding roles of human T cell responses controlling SARS-CoV-2 viral clearance in primary COVID-19. Here, we examined longitudinal SARS-CoV-2 upper respiratory tract viral RNA levels and early adaptive immune responses from 95 unvaccinated individuals with acute COVID-19. Acute SARS-CoV-2-specific CD4 and CD8 T cell responses were evaluated in addition to antibody responses. Most individuals with acute COVID-19 developed rapid SARS-CoV-2-specific T cell responses during infection, and both early CD4 T cell and CD8 T cell responses correlated with reduced upper respiratory tract SARS-CoV-2 viral RNA, independent of neutralizing antibody titers. Overall, our findings indicate a distinct protective role for SARS-CoV-2-specific T cells during acute COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.25.564014v1" target="_blank">Early antiviral CD4 and CD8 T cell responses are associated with upper respiratory tract clearance of SARS-CoV-2</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Concordance Between Exhaled Air Test (eBAM-CoV) and RT-PCR to Detect SARS-CoV-2</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19; Coronavirus <br/><b>Interventions</b>: Device: eBAM Cov Testing <br/><b>Sponsors</b>: Centre Hospitalier Universitaire de Nīmes; University of Nimes; brains’ laboratory sas, FRANCE <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Safety, Tolerability and Immunogenicity of EG-COVII in Healthy Adult</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: EG-COVII <br/><b>Sponsors</b>: EyeGene Inc. <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>Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers</strong> - <b>Conditions</b>: Viral Infection COVID-19 <br/><b>Interventions</b>: Drug: Aterixen <br/><b>Sponsors</b>: Valenta Pharm JSC <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>Long COVID Brain Fog: Cognitive Rehabilitation Trial</strong> - <b>Conditions</b>: Long COVID; Brain Fog; Cognitive Impairment; Cognitive Dysfunction; Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Speed of Processing Training; Behavioral: In-lab Instrumental Activities of Daily Living Training; Behavioral: In-lab Brain Health Training; Behavioral: Transfer Package; Behavioral: Follow Up Phone Calls; Behavioral: Vocational Rehabilitation; Behavioral: Peer Mentoring <br/><b>Sponsors</b>: University of Alabama at Birmingham; National Institute on Disability, Independent Living, and Rehabilitation Research <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>Paradoxical Response to Chest Wall Loading in Mechanically Ventilated Patients</strong> - <b>Conditions</b>: ARDS; COVID-19; Mechanical Ventilation Pressure High; Ventilator-Induced Lung Injury <br/><b>Interventions</b>: Diagnostic Test: Manual loading of the chest wall <br/><b>Sponsors</b>: HealthPartners Institute <br/><b>Withdrawn</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 Practical RCT of TCM in the Treatment of LCOVID and Analysis of Syndrome Types and Medication Characteristics.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Drug: Traditional Chinese medicine treatment; Drug: Western medicine treatment <br/><b>Sponsors</b>: Chinese University of Hong Kong <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>Immunogenicity of Concomitant Administration of COVID-19 Vaccines With Influenza Vaccines</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccine Reaction; Contaminant Injected <br/><b>Interventions</b>: Biological: Omicron-containing COVID-19 vaccine; Biological: influenza vaccine <br/><b>Sponsors</b>: Catholic Kwandong University; Korea University Guro Hospital <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Narrative Intervention for Long COVID-19 (NICO)</strong> - <b>Conditions</b>: Long COVID; Long Covid19 <br/><b>Interventions</b>: Behavioral: Narrative Intervention for Long COVID-19 (NICO) <br/><b>Sponsors</b>: University of Colorado, Denver <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>Home-Based Respiratory Muscle Strength Training Program for Individuals With Post-COVID-19 Persistent Dyspnea</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Dyspnea <br/><b>Interventions</b>: Device: Respiratory Muscle Strength Trainers <br/><b>Sponsors</b>: University of South Florida <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>Inspiratory Muscle Strength Training in Post-Covid Syndrome</strong> - <b>Conditions</b>: Cardiovascular Abnormalities; Post-COVID-19 Syndrome; Physical Exercise <br/><b>Interventions</b>: Other: Inspiratory muscle strength training <br/><b>Sponsors</b>: D’Or Institute for Research and Education <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>Inspiratory Muscle Training in People With Long COVID-19- A Pilot Investigation.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: PrO2 <br/><b>Sponsors</b>: University of Bath; Swansea University <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>Rural Tailored Communication to Promote SARS-CoV-2 Antibody Testing in Saliva</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Behavioral: General SARS-CoV-2 Communication; Behavioral: Rural-Targeted SARS-CoV-2 Communication <br/><b>Sponsors</b>: Michigan State University; National Cancer Institute (NCI); Johns Hopkins University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation Therapy for COVID-19</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Compensatory Cognitive Training for COVID-19; Behavioral: Holistic Cognitive Education <br/><b>Sponsors</b>: VA Office of Research and Development <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID Rehabilitation</strong> - <b>Conditions</b>: Rehabilitation; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders <br/><b>Interventions</b>: Behavioral: One day course; Behavioral: Individual follow-ups <br/><b>Sponsors</b>: University Hospital of North Norway; University of Bergen; Oslo University Hospital; Norwegian University of Science and Technology <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>Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection <br/><b>Interventions</b>: Drug: GST-HG171/ritonavir; Drug: ritonavir <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <br/><b>Active, not 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>The SARS-CoV-2 nucleocapsid protein suppresses innate immunity by remodeling stress granules to atypical foci</strong> - Viruses deploy multiple strategies to suppress the host innate immune response to facilitate viral replication and pathogenesis. Typical G3BP1^(+) stress granules (SGs) are usually formed in host cells after virus infection to restrain viral translation and to stimulate innate immunity. Thus, viruses have evolved various mechanisms to inhibit SGs or to repurpose SG components such as G3BP1. Previous studies showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection…</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>Molecular Mechanism of Labelling Functional Cysteines by Heterocyclic Thiones</strong> - Heterocyclic thiones have recently been identified as reversible covalent warheads, consistent with their mild electrophilic nature. Little is known so far about their mechanism of action in labelling nucleophilic sidechains, especially cysteines. The vast number of tractable cysteines promotes a wide range of target proteins to examine; however, our focus was put on functional cysteines. We chose the main protease of SARS-CoV-2 harboring Cys145 at the active site that is a structurally…</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>Resolving a guanine-quadruplex structure in the SARS-CoV-2 genome through circular dichroism and multiscale molecular modeling</strong> - The genome of SARS-CoV-2 coronavirus is made up of a single-stranded RNA fragment that can assume a specific secondary structure, whose stability can influence the virus’s ability to reproduce. Recent studies have identified putative guanine quadruplex sequences in SARS-CoV-2 genome fragments that are involved in coding for both structural and non-structural proteins. In this contribution, we focus on a specific G-rich sequence referred to as RG-2, which codes for the non-structural protein 10…</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>Assessing the post hoc effectiveness of tixagevimab-cilgavimab for prevention of SARS-CoV-2 infections in solid organ transplant recipients</strong> - CONCLUSION: In a large cohort of SOT recipients, we found that Tix-Cil reduced infection risk even amidst emergent Omicron subvariants. Additionally, the extent of measurable humoral response to Tix-Cil may indicate relative effectiveness. Pre-exposure monoclonal antibody therapy may represent a strategy that will continue to offer clinical benefit for immunocompromised persons who are known to derive limited protection from vaccinations.</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 cell-penetrating peptide derived from SARS-CoV-2 protein Orf9b allosterically inhibits MARK4 activity and mitigates tau toxicity</strong> - Abnormal activation of microtubule affinity-regulating kinase 4 (MARK4) and its phosphorylation of the microtubule-associated protein tau are believed to play a role in the pathogenesis of Alzheimer’s disease, and MARK4 inhibition can be a strategy to develop disease-modifying therapy. Here we report the development of a membrane-permeable peptide that inhibits MARK4 activity in an allosteric manner. The SARS-CoV-2-derived protein Orf9b inhibited MARK4-mediated tau phosphorylation in primary…</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>Integrin αvβ1 facilitates ACE2-mediated entry of SARS-CoV-2</strong> - Integrins have been suggested to be involved in SARS-CoV-2 infection, but the underlying mechanisms remain largely unclear. This study aimed to investigate how integrins facilitate the ACE2-mediated cellular entry of SARS-CoV-2. We first tested the susceptibility of a panel of human cell lines to SARS-CoV-2 infection using the spike protein pseudotyped virus assay and examined the expression levels of integrins in these cell lines by qPCR, western blot and flow cytometry. We found that integrin…</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>PGAM5 degrades PDCoV N protein and activates type I interferon to antagonize viral replication</strong> - In recent years, porcine deltacoronavirus (PDCoV) has become a new intestinal coronavirus in pigs, rapidly spreading across multiple countries and causing significant financial losses in the global pig industry. Currently, no effective commercial vaccine is available to prevent this virus’ spread. Thus, it becomes crucial to investigate the interaction between the virus and its host to acquire valuable insights into the underlying mechanisms of viral replication and develop innovative strategies…</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 molecular dynamics simulations analysis of repurposing drugs for COVID-19 using bioinformatics methods</strong> - A number of multidisciplinary methods have piqued the interest of researchers as means to accelerate and lower the cost of medication creation. The goal of this research was to find target proteins and then select a lead drug against SARS-CoV-2. The three-dimensional structure is taken from the RCSB PDB using its specific PDB ID 6lu7. Virtual screening based on pharmacophores is performed using Molecular Operating Environment software. We looked for a potent inhibitor in the FDA-approved…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Two Soluble ACE2-Fc Variants on Blood Pressure and Albuminuria in Hypertensive Mice: Research Letter</strong> - CONCLUSIONS: Soluble ACE2-Fc variant K reduces blood pressure and tends to lower albuminuria in hypertensive mice. Furthermore, soluble ACE2-Fc variant K has prolonged tissue retention, associated with increased tissue ACE2 activity. The results support further studies directed at the therapeutic potential of soluble ACE2-Fc variant K for cardiovascular and kidney protection.</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 CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections</strong> - Marburg and Ebola filoviruses are two of the deadliest infectious agents and several outbreaks have occurred in the last decades. Although several receptors and co-receptors have been reported for Ebola virus, key host factors remain to be elucidated. In this study, using a haploid cell screening platform, we identify the guanine nucleotide exchange factor CCZ1 as a key host factor in the early stage of filovirus replication. The critical role of CCZ1 for filovirus infections is validated in 3D…</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>TMPRSS2 is a functional receptor for human coronavirus HKU1</strong> - Four endemic seasonal human coronaviruses causing common colds, HKU1, 229E, NL63 and OC43 circulate worldwide¹. After binding to cellular receptors, coronavirus spike proteins are primed for fusion by transmembrane-serine protease 2 (TMPRSS2) or endosomal cathepsins^(2-9). NL63 uses angiotensin-converting enzyme 2 (ACE2) as a receptor^(10), whereas 229E uses human aminopeptidase-N^(11). HKU1 and OC43 spikes bind cells through 9-O40 acelytated sialic acid but their protein receptors remain…</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>Epidemiological profile of COVID-19 in patients with prostate cancer undergoing androgen deprivation therapy at a Brazilian Cancer Center</strong> - CONCLUSION: Androgen deprivation therapy was not associated with protective factors or potential treatments in patients with prostate cancer and COVID-19. Although the number of patients analyzed was limited, and there may have been a selection bias, this is a unique study that cannot be expanded or replicated in similar (unvaccinated) populations.</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 lectin pathway of complement activation reduces Acute Respiratory Distress Syndrome severity in a mouse model of SARS-CoV-2 infection</strong> - Most COVID-19 patients requiring ICU care develop an acute respiratory distress syndrome (ARDS), characterised by severe hypoxemia, decreased lung compliance, and high vascular permeability. Activation of the complement system is a hallmark of moderate and severe COVID-19, with abundant deposition of complement proteins reported in inflamed tissue and on the endothelium during COVID-19. Using a transgenic mouse model of SARS-CoV-2 infection we assessed the therapeutic utility of an inhibitory…</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>Computational screening of neuropilin 1 unveils novel potential anti-SARS-CoV-2 therapeutics</strong> - Neuropilin 1 (NRP-1) inhibition has shown promise in reducing the infectivity of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and preventing the virus entry into nerve tissues, thereby mitigating neurological symptoms in COVID-19 patients. In this study, we employed virtual screening, including molecular docking, Molecular Dynamics (MD) simulation, and Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations, to identify potential NRP-1 inhibitors. From a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats treated with the ACE2 inhibitor MLN-4760</strong> - CONCLUSIONS: Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H(2)S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2…</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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