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<title>27 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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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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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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🖺 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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<li><strong>Homeworking and Division of Domestic Work: the Role of Gender Role Attitudes in Germany</strong> -
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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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🖺 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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<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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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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🖺 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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<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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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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🖺 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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<li><strong>Reduced Monocyte Proportions and Responsiveness in Convalescent COVID-19 Patients</strong> -
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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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🖺 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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<li><strong>Discovery of a novel inhibitor of macropinocytosis with antiviral activity</strong> -
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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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🖺 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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<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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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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<li><strong>Navigating vaccination choices: The intersecting dynamics of institutional trust, belonging and message perception among Congolese migrants in the UK (A reflexive thematic analysis)</strong> -
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Background The COVID-19 pandemic has disproportionately impacted intersectionally marginalised migrants, revealing systemic disparities in health outcomes and vaccine uptake. An in-depth understanding of the underlying social and structural factors influencing health behaviours is necessary to develop tailored interventions for migrants but has been seldom explored. Therefore, this qualitative study aimed to explore the contextual factors shaping COVID-19 vaccination decision-making among Congolese migrants in the UK. Methods A community-based participatory research study was designed and led by a community-academic partnership in London, UK (2021-2022). Peer-led, semi-structured interviews were conducted in Lingala with 32 adult Congolese migrants and explored beliefs, perceptions and lived experiences of migration, healthcare and vaccination and the COVID-19 pandemic. Reflexive thematic analysis generated two themes and a model conceptualising the vaccination decision-making process was developed. Participants and community partners were financially compensated, and the study received ethical approval from the University of London ethics committee (REC: 2021.0128). Findings Participants highlighted the incompatibility of lockdown restrictions with their communal culture, which intensified feelings of exclusion and alienation. They expressed concerns about COVID-19 vaccination safety and effectiveness, partly informed by experiences and legacies of discrimination and exploitation of Black Africans. Inequality in the pandemic response and COVID-19 outcomes heightened participants’ sense that their views and needs were being overlooked; accordingly, government sources and information were perceived as coercive and untrustworthy. Drawing on this data, our model depicts the interplay between institutional trust, belonging, and message perception which shaped participants’ vaccination decisions and led to (non-)engagement with COVID-19 vaccination. Conclusion This research enhances understanding of how social and contextual factors may influence migrants’ engagement with health interventions. It underscores the necessity of partnering with migrant communities to understand their needs in context and co-design tailored interventions and inclusive messaging strategies which foster trust and belonging. Implementing systemic changes to address structural inequalities will be crucial to create an environment that supports engagement with health-protective behaviours and enhances health outcomes among migrant communities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.25.23297575v1" target="_blank">Navigating vaccination choices: The intersecting dynamics of institutional trust, belonging and message perception among Congolese migrants in the UK (A reflexive thematic analysis)</a>
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<li><strong>Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub</strong> -
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Importance: COVID-19 continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Objective: To project COVID-19 hospitalizations and deaths from April 2023–April 2025 under two plausible assumptions about immune escape (20% per year and 50% per year) and three possible CDC recommendations for the use of annually reformulated vaccines (no vaccine recommendation, vaccination for those aged 65+, vaccination for all eligible groups). Design: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023–April 15, 2025 under six scenarios representing the intersection of considered levels of immune escape and vaccination. State and national projections from eight modeling teams were ensembled to produce projections for each scenario. Setting: The entire United States. Participants: None. Exposure: Annually reformulated vaccines assumed to be 65% effective against strains circulating on June 15 of each year and to become available on September 1. Age and state specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. Main outcomes and measures: Ensemble estimates of weekly and cumulative COVID-19 hospitalizations and deaths. Expected relative and absolute reductions in hospitalizations and deaths due to vaccination over the projection period. Results: From April 15, 2023–April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November–January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% PI: 1,438,000–4,270,000) hospitalizations and 209,000 (90% PI: 139,000–461,000) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% CI: 104,000–355,000) fewer hospitalizations and 33,000 (95% CI: 12,000–54,000) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000–598,000) fewer hospitalizations and 49,000 (95% CI: 29,000–69,000) fewer deaths. Conclusion and Relevance: COVID-19 is projected to be a significant public health threat over the coming two years. Broad vaccination has the potential to substantially reduce the burden of this disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.26.23297581v1" target="_blank">Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub</a>
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<li><strong>Assessing the causal effect of air pollution on risk of SARS-CoV-2 infection</strong> -
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Introduction Emerging evidence suggests association of air pollution exposure with risk of SARS-CoV-2 infection, but many of these findings are limited by study design, lack of individual-level covariate data or are specific to certain subpopulations. We aim to evaluate causal effects of air pollution on risk of infection, whilst overcoming these limitations. Methods Concentrations for black carbon(BC), particulate matter 10(PM<sub>10</sub>), particulate matter 2.5(PM<sub>2.5</sub>), nitrogen dioxide(NO<sub>2</sub>) and oxides of nitrogen(NO<sub>x</sub>) from the Department of Environment, Food and Rural Affairs (DEFRA) and Effect of Low-level Air Pollution: A Study in Europe (ELAPSE) were linked to postcodes of 53,683 Virus Watch study participants. The primary outcome was first SARS-CoV-2 infection, between 1st September 2020 and 30th April 2021. Regression analysis used modified Poisson with robust estimates, clustered by household, adjusting for individual (e.g., age, sex, ethnicity) and environmental covariates(e.g., population density, region) to estimate total and direct effects. Results Single pollutant analysis showed the direct effect of higher risk of SARS-CoV-2 infection with increased exposure to PM<sub>2.5</sub>(RR1.11,95%CI 1.08;1.15), PM<sub>10</sub>(RR1.06,95%CI 1.04;1.09), NO<sub>2</sub>(RR1.04,95%CI 1.04;1.05) and NO<sub>x</sub>(RR1.02,95%CI 1.02;1.02) per 1μg/m<sup>3</sup> increment with DEFRA 2015-19 data. Sensitivity analyses altering covariates, exposure window and modelled air pollution data source produced similar estimates. Higher risk of SARS-CoV-2 per 10<sup>-5</sup>m<sup>-1</sup> increment of BC (RR1.86, 95%CI 1.62;2.14) was observed using ELAPSE data. Conclusion Long term exposure to higher concentrations of air pollutions increases the risk of SARS-CoV-2 infection, highlighting that adverse health effects of air pollution is not only limited to non-communicable diseases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.26.23297598v1" target="_blank">Assessing the causal effect of air pollution on risk of SARS-CoV-2 infection</a>
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<li><strong>Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection</strong> -
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BACKGROUND: Although RNA viruses like SARS-CoV-2 are generally thought to be transient, the persistence of viral components beyond the acute phase can be driven by a variety of virologic and immunologic factors. Recent studies have suggested that SARS-CoV-2 antigens may persist following COVID-19 but were limited by a lack of comparison to a large number of true negative control samples. METHODS: Using single molecule array (Simoa) assays for SARS-CoV-2 spike, S1, and nucleocapsid antigen in plasma from 171 pandemic-era individuals in the post-acute phase of SARS-CoV-2 infection and 250 pre-pandemic control samples, we compared prevalence of antigen detection. We used logistic regression models and prevalence ratios (PRs) to assess the relationship between demographic and disease factors and antigen persistence. RESULTS: Compared to the proportion of antigen positivity in the pre-pandemic controls (2%), detection of any SARS-CoV-2 antigen was more frequent across all post-acute COVID-19 time bins (3-6 months: 12.6%, p<0.001; 6-10 months, 10.7%, p=0.0002; 10-14 months, 7.5%, p=0.017). These differences were driven by spike protein for up to 14 months and nucleocapsid in the first 6 months after infection. The co-occurrence of multiple antigens at a single timepoint was uncommon. Hospitalization for acute COVID-19 (versus not hospitalized) and worse self-reported health during acute COVID-19 among those not hospitalized (versus more benign illness) were associated with higher prevalence of post-acute antigen detection (PR 1.86, p=0.03; PR 3.5, p=0.07, respectively) in the pandemic era. CONCLUSIONS: Our findings provide strong evidence that SARS-CoV-2 antigens can persist beyond the period of acute illness. The observation that more than 10% of plasma samples for over a year following initial SARS-CoV-2 infection contain detectable viral antigen, which are potentially immunogenic, has significant implications given the sheer number of people infected with SARS-CoV-2 to date. More work will be needed to determine whether these antigens have a causal role in post-acute sequelae of SARS-CoV-2 infection (PASC).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.24.23297114v2" target="_blank">Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection</a>
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<li><strong>Scaling Behavioral Interventions in the Presence of Spillover: Implications for Randomized Controlled Trials and Evidence-Based Policy Making</strong> -
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Randomized Control Trials (RCTs) are increasingly relied upon by policymakers as part of efforts to incorporate evidence into the policymaking process, a movement known as evidence-based policymaking, or EBPM. Testing possible policy interventions via RCTs before full rollout is commonly thought to be the gold standard of evidence in the EBPM process. However, real-world policy changes do not always scale up as expected. Even large-N RCTs targeting a random sample of policy beneficiaries do not capture the influence of social networks and risk missing consequential spillover effects. We illustrate this issue by assessing the efficacy of monetary incentives to increase COVID-19 vaccination in an RCT over the entire population of a medium-sized European town (~40,000 residents). We use administrative vaccination data as our primary outcome. Since the entire population was randomized, we are able to estimate spillover effects within households. There were significant negative spillover effects on booster vaccinations that we attribute to a displacement effect, potentially driven by long lines at the vaccination events. Our results illustrate that using a population-level RCT to test whether a policy scales can help avoid costly, ineffective, or even counterproductive policy outcomes.
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🖺 Full Text HTML: <a href="https://osf.io/k5uap/" target="_blank">Scaling Behavioral Interventions in the Presence of Spillover: Implications for Randomized Controlled Trials and Evidence-Based Policy Making</a>
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<li><strong>Policy impact evaluation: A potential use case for longitudinal monitoring of viruses in wastewater at small geographic scales</strong> -
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We used wastewater monitoring data to evaluate the impact of public health policies and interventions on the spread of COVID-19 among a university population. We first evaluated the correlation between incident, reported COVID-19 cases and wastewater SARS-CoV-2 RNA concentrations and observed changes to the correlation over time. Using a difference-in-differences approach, we evaluated the association between university COVID-19 policy changes and levels of SARS-CoV-2 RNA concentrations in wastewater. Policy changes associated with a significant change in campus wastewater SARS-CoV-2 RNA concentrations included changes to face covering recommendations, indoor gathering bans, and routine surveillance testing requirements and availability. We did not observe changes in SARS-CoV-2 RNA concentrations associated with other policy changes. The work presented herein demonstrates how longitudinal wastewater monitoring of viruses may be used for causal inference such as policy impact evaluation, especially at small geographic scales.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.25.23297556v1" target="_blank">Policy impact evaluation: A potential use case for longitudinal monitoring of viruses in wastewater at small geographic scales</a>
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<li><strong>Changes in emergency department utilization in vulnerable populations after COVID-19 shelter in place orders</strong> -
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Purpose: To compare emergency department (ED) utilization and admission rates for patients with a history of mental health (MH), substance use disorder (SUD) and social determinants of health (SDOH) before and after implementing COVID-199s shelter-inplace (SIP) orders. Methods: This was a retrospective, multicenter study leveraging electronic medical record data from 20 EDs across a large Midwest integrated healthcare system from 5/2/2019 to 12/31/2019 (pre-SIP) and from 5/2/2020 to 12/31/2020 (post-SIP). Diagnoses were documented in the patient9s medical records. Poisson and logistic regression models were used to evaluate ED utilization and admission rate changes. Results: 871,020 total ED encounters from 487,028 unique patients were captured. 2,572 (0.53%) patients had a documented Z code for SDOH. Patients with previously diagnosed MH or SUDs were more likely to seek ED care after the SIP orders were implemented (RR: 1.20, 95% CI: 1.18 - 1.22, p<0.001), as were patients with SDOH (RR: 2.37, 95% CI: 2.19 - 2.55, p<0.001). Patients with both previously diagnosed MH or SUD and a documented SDOH had even higher ED utilization (RR: 3.31, 95% CI: 2.83 - 3.88, p<0.001) than those with either condition alone. Patients with MH and SUDs (OR: 0.89, 95% CI: 0.86 - 0.92, p<0.001) or SDOH (OR: 0.67, 95% CI: 0.54, 0.83, p<0.001) were less likely to be admitted post-SIP orders while patients with a history of diseases of physiologic systems were more likely to be admitted. Conclusions: Vulnerable populations with a history of MH, SUD, and SDOH experienced increased ED utilization but a lower rate of hospital admissions after the implementation of SIP orders. The findings highlight the importance of addressing these needs to mitigate the impact of public health crises on these populations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.25.23297561v1" target="_blank">Changes in emergency department utilization in vulnerable populations after COVID-19 shelter in place orders</a>
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<li><strong>Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection</strong> -
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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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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.25.23297469v1" target="_blank">Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection</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>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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<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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<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 gene expression of the adenosine 5’-monophosphate-activated protein kinase (AMPK) and its relation with the IL-6 and IL-10 plasma levels in COVID-19 patients</strong> - CONCLUSION: Increasing AMPK gene expression is likely a necessary effort of the immune system to inhibit inflammation in critical COVID-19. However, this effort seems to be inadequate, probably due to factors that induce inflammation, like erythrocyte sedimentation rate (ESR) and IL-6.</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 neurotropism-induced anxiety and depression-like behaviors require Microglia activation</strong> - The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with a wide range of “long COVID” neurological symptoms. However, the mechanisms governing SARS-CoV-2 neurotropism and its effects on long-term behavioral changes remain poorly understood. Using a highly virulent mouse-adapted SARS-CoV-2 strain, denoted as SARS2-N501Y (MA30) , we demonstrated that intranasal inoculation of SARS2-N501Y (MA30) results in…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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