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188 lines
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<title>05 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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<li><strong>Funding Solutions in Real Estate: The Influence of the COVID-19 Pandemic on Lending</strong> -
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<div>
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The global real estate industry has always been closely tied to economic fluctuations, and the COVID-19 pandemic has been no exception. One of the most significant aspects affected by this crisis is real estate lending. In this article, we will explore the evolving landscape of funding solutions in the real estate sector and how the pandemic has reshaped the lending environment.
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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/n6vm5/" target="_blank">Funding Solutions in Real Estate: The Influence of the COVID-19 Pandemic on Lending</a>
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</div></li>
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<li><strong>SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia</strong> -
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<div>
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Age is a major risk factor for coronavirus disease (COVID-19)-associated severe pneumonia and mortality; however, the underlying mechanism remains unclear. Herein, we investigated whether age-related deregulation of RNAi components and RNA splicing factors affects COVID-19 severity. Decreased expression of RNAi components (Dicer and XPO5) and splicing factors (SRSF3 and hnRNPA3) correlated with increased severity of COVID-19 and SARS-CoV-2 nucleocapsid (N) protein-induced pneumonia. N protein induced autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, repressing miRNA biogenesis and RNA splicing and inducing DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 were downregulated with age in mouse lung tissues. Older mice experienced more severe N protein-induced pneumonia than younger mice. However, treatment with a poly(ADP-ribose) polymerase inhibitor (PJ34) or aromatase inhibitor (anastrozole) relieved N protein-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.
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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/10.1101/2023.10.03.560426v1" target="_blank">SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia</a>
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</div></li>
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<li><strong>Comparative single-cell analysis reveals IFN-γ as a driver of respiratory sequelae post COVID-19</strong> -
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<div>
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Post-acute sequelae of SARS-CoV-2 infection (PASC) represents an urgent public health challenge, with its impact resonating in over 60 million individuals globally. While a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood studies, with few focusing on samples derived from post-COVID affected tissues. Further, clinical studies alone often provide correlative insights rather than causal relationships. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to truly understand the etiology of PASC. In this study, we have made comprehensive comparisons between bronchoalveolar lavage fluid (BAL) single-cell RNA sequencing (scRNAseq) data derived from clinical PASC samples and relevant PASC mouse models. This revealed a strong pro-fibrotic monocyte-derived macrophage response in respiratory PASC (R-PASC) in both humans and mice, and abnormal interactions between pulmonary macrophages and respiratory resident T cells. IFN-g emerged as a key node mediating the immune anomalies in R-PASC. Strikingly, neutralizing IFN-g post the resolution of acute infection reduced lung inflammation, tissue fibrosis, and improved pulmonary gas-exchange function in two mouse models of R-PASC. Our study underscores the importance of performing comparative analysis to understand the root cause of PASC for developing effective therapies.
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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/10.1101/2023.10.03.560739v1" target="_blank">Comparative single-cell analysis reveals IFN-γ as a driver of respiratory sequelae post COVID-19</a>
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</div></li>
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<li><strong>mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting</strong> -
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<div>
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To address the limitations of whole-spike COVID vaccines, we explored mRNA vaccines encoding membrane-anchored receptor-binding domain (RBD-TMs), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail (CT) fragments of the SARS-CoV-2 spike protein. In naive mice, RBD-TM mRNA vaccines against ancestral SARS-CoV-2, Beta, Delta, Delta-plus, Kappa, Omicron BA.1 or BA.5, all induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays indicated broad neutralizing activity against a range of variant RBDs. In the setting of a heterologous boost, against the background of exposure to ancestral whole spike vaccines, sVNT studies suggested that RBD-TM vaccines were able to overcome the detrimental effects of immune imprinting. Omicron BA.1 and BA.5 RBD-TM booster vaccines induced serum antibodies with 12 and 22-fold higher neutralizing activity against the target RBD than their equivalent whole spike variants. Boosting with BA.1 or BA.5 RBD-TM provided good protection against more recent variants including XBB and XBB.1.5. Each RBD-TM mRNA is 28% of the length of its whole-spike equivalent. This advantage will enable tetravalent mRNA vaccines to be developed at well-tolerated doses of formulated mRNA.
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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/10.1101/2023.10.04.560777v1" target="_blank">mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting</a>
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</div></li>
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<li><strong>Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors</strong> -
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<div>
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The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global morbidity and mortality. A crucial viral protein, the non-structural protein 14 (nsp14), catalyzes the methylation of viral RNA and plays a critical role in viral genome replication and transcription. Due to the low mutation rate in the nsp region among various SARS-CoV-2 variants, nsp14 has emerged as a promising therapeutic target. However, discovering potential inhibitors remains a challenge. In this work, we introduce a computational pipeline for the rapid and efficient identification of potential nsp14 inhibitors by leveraging virtual screening and the NCI open compound collection, which contains 250,000 freely available molecules for researchers worldwide. The introduced pipeline provides a cost-effective and efficient approach for early-stage drug discovery by allowing researchers to evaluate promising molecules without incurring synthesis expenses. Our pipeline successfully identified seven promising candidates after experimentally validating only 40 compounds. Notably, we discovered NSC620333, a compound that exhibits a strong binding affinity to nsp14 with a dissociation constant of 427 {+/-} 84 nM. In addition, we gained new insights into the structure and function of this protein through molecular dynamics simulations. We identified new conformational states of the protein and determined that residues Phe367, Tyr368, and Gln354 within the binding pocket serve as stabilizing residues for novel ligand interactions. We also found that metal coordination complexes are crucial for the overall function of the binding pocket. Lastly, we present the solved crystal structure of the nsp14-MTase complexed with SS148, a potent inhibitor of methyltransferase activity at the nanomolar level (IC50 value of 70 {+/-} 6 nM). Our computational pipeline accurately predicted the binding pose of SS148, demonstrating its effectiveness and potential in accelerating drug discovery efforts against SARS-CoV-2 and other emerging viruses.
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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/10.1101/2023.10.03.560722v1" target="_blank">Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors</a>
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</div></li>
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<li><strong>Post-acute immunological and behavioral sequelae in mice after Omicron infection</strong> -
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<div>
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Progress in understanding long COVID and developing effective therapeutics is hampered in part by the lack of suitable animal models. Here we used ACE2-transgenic mice recovered from Omicron (BA.1) infection to test for pulmonary and behavioral post-acute sequelae. Through in-depth phenotyping by CyTOF, we demonstrate that naive mice experiencing a first Omicron infection exhibit profound immune perturbations in the lung after resolving acute infection. This is not observed if mice were first vaccinated with spike-encoding mRNA. The protective effects of vaccination against post-acute sequelae were associated with a highly polyfunctional SARS-CoV-2-specific T cell response that was recalled upon BA.1 breakthrough infection but not seen with BA.1 infection alone. Without vaccination, the chemokine receptor CXCR4 was uniquely upregulated on multiple pulmonary immune subsets in the BA.1 convalescent mice, a process previously connected to severe COVID-19. Taking advantage of recent developments in machine learning and computer vision, we demonstrate that BA.1 convalescent mice exhibited spontaneous behavioral changes, emotional alterations, and cognitive-related deficits in context habituation. Collectively, our data identify immunological and behavioral post-acute sequelae after Omicron infection and uncover a protective effect of vaccination against post-acute pulmonary immune perturbations.
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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/10.1101/2023.06.05.543758v2" target="_blank">Post-acute immunological and behavioral sequelae in mice after Omicron infection</a>
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</div></li>
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<li><strong>Time warping between main epidemic time series in epidemiological surveillance</strong> -
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The most common reported epidemic time series in epidemiological surveillance are the daily or weekly incidence of new cases, the hospital admission count, the ICU admission count, and the death toll, which played such a prominent role in the struggle to monitor the Covid-19 pandemic. We show that pairs of such curves are related to each other by a generalized renewal equation depending on a smooth time varying delay and a smooth ratio generalizing the reproduction number. Such a functional relation is also explored for pairs of simultaneous curves measuring the same indicator in two neighboring countries. Given two such simultaneous time series, we develop, based on a signal processing approach, an efficient numerical method for computing their time varying delay and ratio curves, and we verify that its results are consistent. Indeed, they experimentally verify symmetry and transitivity requirements and we also show, using realistic simulated data, that the method faithfully recovers time delays and ratios. We discuss several real examples where the method seems to display interpretable time delays and ratios. The proposed method generalizes and unifies many recent related attempts to take advantage of the plurality of these health data across regions or countries and time, providing a better understanding of the relationship between them. An implementation of the method is publicly available at the EpiInvert CRAN package.
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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/10.1101/2023.02.07.23285605v2" target="_blank">Time warping between main epidemic time series in epidemiological surveillance</a>
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</div></li>
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<li><strong>Behavioural and Social Predictors of COVID-19 Vaccine Uptake among Persons with Disabilities in Kenya.</strong> -
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The uptake of the COVID-19 vaccine by persons with disabilities remains largely unknown in low-and middle-income countries. This evidence gap necessitates disability-focused research to inform improvements in access and inclusion in the last mile of COVID-19 vaccination programs and to support future programs for other vaccine-preventable diseases. We aimed to identify behavioural and social predictors of COVID-19 uptake among persons with disabilities in Kenya. This was a convergent parallel mixed method study that involved questionnaires (792), key informants interviews, and focus group discussions among persons with disabilities and key stakeholders (government actors and professional associations). Data were analysed using STATA statistical analysis software (version 14). Chi-square (X2) and Fisher’s exact tests were used to test for differences in categorical variables; multivariate regression analysis was employed to ascertain the factors that influence uptake of COVID-19 among persons with disabilities (PWDs) in Kenya. Approximately 59% of persons with disabilities reported to be fully vaccinated, with significant disparities noted among those with cognition (34.2%) and self-care (36.6%) impairments. Confidence in vaccine benefits (Adjusted odds ration [OR]; 11.3, 95% CI; 5.2-24.2), health worker recommendation (OR; 2.6, 95% CI; 1.8-3.7), employment (OR; 2.1, 95% CI; 1.4-3.1), perceived risk (OR; 2.0, 95% CI; 1.3-3.1), age and area of residence were statistically significant predictors of vaccine uptake among PWDs. The primary reasons for low uptake included perceived negative vaccine effects and lack of adequate information. No association was found between having a primary caregiver and/or assistive device, with COVID-19 vaccine uptake. Subsequent vaccination deployments should map and reach PWDs through relevant institutions of PWDs, and localized vaccination campaigns. Related communication strategies should leverage on behaviour change techniques that inspire confidence in vaccines, and on the credibility and trust in health workers to improve vaccine uptake.
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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/10.1101/2023.10.03.23296513v1" target="_blank">Behavioural and Social Predictors of COVID-19 Vaccine Uptake among Persons with Disabilities in Kenya.</a>
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</div></li>
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<li><strong>United States Marijuana Legalization and Opioid Mortality Trends Before and During the First Year of the COVID-19 Pandemic</strong> -
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To determine if marijuana legalization reduced opioid mortality, the U.S. opioid and fentanyl subset death trends during the 2010-2019 decade were compared in states and District of Columbia (D.C.) (jurisdictions) that had implemented marijuana legalization with states that had not. Acceleration of opioid mortality during 2020, first year of the COVID-19 pandemic, was also compared in recreational and medicinal-only legalizing jurisdictions. Joinpoint methodology was applied to Centers for Disease Control and Prevention WONDER data. Trends in legalizing jurisdictions were cumulative aggregates. The overall opioid and fentanyl death rates and percentage of opioid deaths due to fentanyl increased more during 2010-2019 in jurisdictions that legalized marijuana than in those that did not (pairwise comparison p=0.007, 0.05, and 0.006, respectively). By 2019, the opioid and fentanyl death rates were 44% and 50% greater in the legalizing than non-legalizing jurisdictions, respectively. When the COVID-19 pandemic hit in 2020, jurisdictions that implemented recreational marijuana legalization before 2019 had significantly greater increases in both overall opioid and fentanyl death rates than jurisdictions with medicinal-only legalization. For all opioids, the mean (95% confidence interval [CI]) 2019-to-2020 increases were 46.5% (95% CI, 36.6% to 56.3%) and 29.1% (95% CI 20.2% to 37.9%), respectively (p=0.02). For fentanyl, they were 115.6% (95% CI, 80.2% to 151.6%) and 55.4% (95% CI, 31.6% to 79.2%), respectively (p=0.01). Marijuana legalization is correlated with worsening of the U.S. opioid epidemic, and especially during the COVID-19 pandemic with recreational legalization.
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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/10.1101/2023.10.03.23296502v1" target="_blank">United States Marijuana Legalization and Opioid Mortality Trends Before and During the First Year of the COVID-19 Pandemic</a>
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</div></li>
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<li><strong>Moral Judgments Impact Perceived Risks from COVID-19 Exposure</strong> -
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<div>
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The COVID-19 pandemic has created enormously difficult decisions for individuals trying to navigate both the risks of the pandemic and the demands of everyday life. Good decision making in such scenarios can have life and death consequences. For this reason, it is important to understand what drives risk assessments during a pandemic, and, in particular, to investigate the ways that these assessments might deviate from ideal risk assessments. Two studies (N = 841) investigate risk judgments related to COVID-19. The results indicate that risk judgments are sensitive to factors unrelated to the objective risks of infection. In particular, activities that are morally justified are perceived as safer while those that might subject people to blame, or culpability, are seen as riskier.
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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://psyarxiv.com/59s2g/" target="_blank">Moral Judgments Impact Perceived Risks from COVID-19 Exposure</a>
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<li><strong>Prevalence and factors associated with fear of COVID-19 in military personnel during the second epidemic wave in Peru</strong> -
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There is few research in military members that provided protection and security during the COVID-19 crisis. We aimed to determine the prevalence and factors associated with fear of COVID-19 in military members. A cross-sectional study was conducted between November 02 and 09, 2021, during the second wave of the COVID-19 pandemic in the region of Lambayeque, Peru. The outcome was fear of COVID-19, measured with the Fear of COVID-19 Scale. The association with resilience (abbreviated CD-RISC), food insecurity (HFIAS), physical activity (IPAQ-S), eating disorder (EAT-26), and other socio-labor variables were assessed. Of 525 participants, the median age was 22, 95.8% were male, and 19.2% experienced fear of COVID-19. A higher prevalence of fear of COVID-19 was associated with age (PR=1.03; 95% CI: 1.01-1.06), religion (PP=2.05; 95% CI: 1.04-4.05), eating disorder (PR=2.95; 95% CI: 1.99-4.36), and having a relative with mental disorder (PR=2.13; 95% CI: 1.09-4.17). Overweight (PR=0.58; 95% IC: 0.37-0.90) and a high level of resilience (PR=0.63; 95% IC: 0.43-0.93) were associated with a lower prevalence of fear of COVID-19. Two out of ten military personnel were afraid of COVID-19. We recommend special attention to the factors associated with the development of suicide risk in military personnel.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296474v1" target="_blank">Prevalence and factors associated with fear of COVID-19 in military personnel during the second epidemic wave in Peru</a>
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</div></li>
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<li><strong>Mendelian Randomization Reveals the Role of HMGCR in Pulmonary Arterial Hypertension Treatment, Independent of LDL Cholesterol Concentration</strong> -
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Introduction: Specific lipid-reducing therapeutics, including statins, are known for mitigating cardiovascular diseases due to their comprehensive benefits including anti-inflammatory properties, antioxidative stress response, and enhancement of endothelial function. The objective of our study was to determine the causative impact of lipid-reducing agents (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitor) on the outcomes of pulmonary hypertension via a two-sample Mendelian randomization (MR) analysis. Methods: Two types of genetic tools were employed to estimate the exposure to lipid-lowering drugs, comprising expression quantitative trait loci of the drug9s target genes and genetic variations close to or within the target genes related to low-density lipoprotein (LDL cholesterol derived from a genome-wide association study). We utilized summary-data-based MR (SMR) and inverse-variance-weighted MR (IVWMR) methodologies for estimating effect sizes. Results: SMR analysis indicated that elevated HMGCR expression correlates with increased pulmonary hypertension risk (β=-0.964, se=0.276). Yet, no evident causative link between HMGCR-regulated LDL cholesterol and COVID-19 hospitalization was observed in the IVW-MR analysis (β = -0.21, se= 0.17). Conclusions: Our Mendelian randomization investigation unveiled a possible positive impact of lipid-lowering therapeutics on the prognosis of pulmonary hypertension. Importantly, no causal relation was established between LDL cholesterol and pulmonary hypertension.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.02.23295606v1" target="_blank">Mendelian Randomization Reveals the Role of HMGCR in Pulmonary Arterial Hypertension Treatment, Independent of LDL Cholesterol Concentration</a>
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<li><strong>Modeling spillover dynamics: understanding emerging pathogens of public health concern</strong> -
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The emergence of infectious diseases with pandemic potential is a major public health threat worldwide. According to the World Health Organization, around 60% of the reported emerging infectious diseases are zoonoses and have been triggered by spillover events. Although the dynamics of spillover events are not yet well understood, mathematical modeling has the potential to characterize the highly complex interactions among pathogens, wildlife, humans, and the environment where they coexist. In this work, motivated by discussions on the introductory phase of SARS-CoV-2 towards a pandemic scenario, we address the so far unexplored emergence of novel infectious agents. Aiming at gaining insights into the dynamics of spillover events and the final outcome of an eventual disease outbreak in a population, we propose a continuous time stochastic modeling framework to describe a cross-species disease transmission by coupling the dynamics of animal reservoirs and human hosts. A complete analysis of the system is conducted, followed by numerical experiments where we investigate different scenarios of spillover events. Applied to the emergence of SARS-CoV-2 and monkeypox viruses, our results provide insights into the emergence of new infectious diseases able to cause not only local outbreaks but eventually explosive epidemics towards a pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.02.23296428v1" target="_blank">Modeling spillover dynamics: understanding emerging pathogens of public health concern</a>
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<li><strong>Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing</strong> -
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Background: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false- negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive analytical sensitivity in the lab, the assessment of clinical accuracy with IACs is often overlooked. In some cases, the IACs were run spatially, complicating assay workflow. Therefore, the multiplex assay for pathogen and IAC is needed. Results: We developed a one-pot duplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for saliva samples, a non-invasive and simple collected specimen for POC NAATs. The ORF1ab gene of SARS-CoV-2 was used as a target and a human 18S ribosomal RNA in human saliva was employed as an IAC to ensure clinical reliability of the RT-LAMP assay. The optimized assay could detect SARS-CoV-2 viral particles down to 100 copies/μL of saliva within 30 minutes without RNA extraction. The duplex RT-LAMP for SARS-CoV-2 and IAC is successfully amplified in the same reaction without cross-reactivity. The valid results were easily visualized in triple-line lateral flow immunoassay, in which two lines (flow control and IAC lines) represent valid negative results and three lines (flow control, IAC, and test line) represent valid positive results. This duplex assay demonstrated a clinical sensitivity of 95%, specificity of 100%, and accuracy of 96% in 30 clinical saliva samples. Significance: IACs play a crucial role in ensuring user confidence with respect to the accuracy and reliability of at-home and POC molecular diagnostics. We demonstrated the multiplex capability of SARS-COV-2 and human18S ribosomal RNA RT-LAMP without complicating assay design. This generic platform can be extended in a similar manner to include human18S ribosomal RNA IACs into different clinical sample matrices.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296477v1" target="_blank">Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing</a>
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<li><strong>Some principles for using epidemiologic study results to parameterize transmission models</strong> -
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Background: Infectious disease models, including individual based models (IBMs), can be used to inform public health response. For these models to be effective, accurate estimates of key parameters describing the natural history of infection and disease are needed. However, obtaining these parameter estimates from epidemiological studies is not always straightforward. We aim to 1) outline challenges to parameter estimation that arise due to common biases found in epidemiologic studies and 2) describe the conditions under which careful consideration in the design and analysis of the study could allow us to obtain a causal estimate of the parameter of interest. In this discussion we do not focus on issues of generalizability and transportability. Methods: Using examples from the COVID-19 pandemic, we first identify different ways of parameterizing IBMs and describe ideal study designs to estimate these parameters. Given real-world limitations, we describe challenges in parameter estimation due to confounding and conditioning on a post-exposure observation. We then describe ideal study designs that can lead to unbiased parameter estimates. We finally discuss additional challenges in estimating progression probabilities and the consequences of these challenges. Results: Causal estimation can only occur if we are able to accurately measure and control for all confounding variables that create non-causal associations between the exposure and outcome of interest, which is sometimes challenging given the nature of the variables we need to measure. In the absence of perfect control, non-causal parameter estimates should still be used, as sometimes they are the best available information we have. Conclusions: Identifying which estimates from epidemiologic studies correspond to the quantities needed to parameterize disease models, and determining whether these parameters have causal interpretations, can inform future study designs and improve inferences from infectious disease models. Understanding the way in which biases can arise in parameter estimation can inform sensitivity analyses or help with interpretation of results if the magnitude and direction of the bias is understood.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.03.23296455v1" target="_blank">Some principles for using epidemiologic study results to parameterize transmission models</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>Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <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 of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile) <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <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>Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC)</strong> - <b>Conditions</b>: Long Covid19; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Dietary Supplement: Flavonoids <br/><b>Sponsors</b>: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado <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>Exercise Interventions in Post-acute Sequelae of Covid-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Exercise <br/><b>Sponsors</b>: University of Virginia <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease <br/><b>Interventions</b>: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing) <br/><b>Sponsors</b>: Sarang K. Yoon, DO, MOH; Westat; Novavax <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Motivational Interviewing for Vaccine Uptake in Latinx Adults</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Other: EHR alert; Behavioral: Motivational Interviewing; Behavioral: Warm hand off to nurse <br/><b>Sponsors</b>: Boston College; East Boston Neighborhood Health Center; Harvard School of Public Health (HSPH); Boston Children’s Hospital; National Institute of Nursing Research (NINR) <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>Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects</strong> - <b>Conditions</b>: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection <br/><b>Interventions</b>: Combination Product: RQ-001; Other: Placebo <br/><b>Sponsors</b>: Red Queen Therapeutics, Inc.; PPD <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of “Sputnik Lite” for the Prevention of COVID-19 With Altered Antigenic Composition.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: “Sputnik Lite” vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <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 Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19</strong> - <b>Conditions</b>: COVID-19, SARS-CoV-2 <br/><b>Interventions</b>: Biological: Biological: AZD3152; Biological: Biological: Placebo <br/><b>Sponsors</b>: AstraZeneca <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>Examining the Function of Cs4 on Post-COVID-19 Disorders</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Other: Chinese medicine nutritional supplement Cs4 <br/><b>Sponsors</b>: The University of Hong Kong <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>Amantadine Therapy for Cognitive Impairment in Long COVID</strong> - <b>Conditions</b>: Long COVID; Post-COVID19 Condition; Post-Acute COVID19 Syndrome <br/><b>Interventions</b>: Drug: Amantadine <br/><b>Sponsors</b>: Ohio State 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>Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia</strong> - <b>Conditions</b>: Parosmia <br/><b>Interventions</b>: Procedure: Stellate Ganglion Block; Other: Placebo <br/><b>Sponsors</b>: Lawson Health Research Institute <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>CPAP Efficacy in Post-COVID Patients With Sleep Apnea</strong> - <b>Conditions</b>: COVID-19; Sleep Apnea <br/><b>Interventions</b>: Device: Continuous positive airway pressure <br/><b>Sponsors</b>: University of Pittsburgh <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>Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2)</strong> - <b>Conditions</b>: Systemic Inflammatory Response Syndrome <br/><b>Interventions</b>: Biological: Allogeneic thyTreg 5.000.000; Biological: Allogeneic thyTreg 10.000.000 <br/><b>Sponsors</b>: Hospital General Universitario Gregorio Marañon; Instituto de Salud Carlos III <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>SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SA55 Injection; Other: Placebo for SA55 injection <br/><b>Sponsors</b>: Sinovac Life Sciences Co., Ltd. <br/><b>Recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What do we know about the function of SARS-CoV-2 proteins?</strong> - The COVID-19 pandemic has highlighted the importance in the understanding of the biology of SARS-CoV-2. After more than two years since the first report of COVID-19, it remains crucial to continue studying how SARS-CoV-2 proteins interact with the host metabolism to cause COVID-19. In this review, we summarize the findings regarding the functions of the 16 non-structural, 6 accessory and 4 structural SARS-CoV-2 proteins. We place less emphasis on the spike protein, which has been the subject of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High-affinity binding to the SARS-CoV-2 spike trimer by a nanostructured, trivalent protein-DNA synthetic antibody</strong> - Multivalency enables nanostructures to bind molecular targets with high affinity. Although antibodies can be generated against a wide range of antigens, their shape and size cannot be tuned to match a given target. DNA nanotechnology provides an attractive approach for designing customized multivalent scaffolds due to the addressability and programmability of the nanostructure shape and size. Here, we design a nanoscale synthetic antibody (“nano-synbody”) based on a three-helix bundle DNA…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bioactive metabolites identified from Aspergillus terreus derived from soil</strong> - Aspergillus terreus has been reported to produce many bioactive metabolites that possess potential activities including anti-inflammatory, cytotoxic, and antimicrobial activities. In the present study, we report the isolation and identification of A. terreus from a collected soil sample. The metabolites existing in the microbial ethyl acetate extract were tentatively identified by HPLC/MS and chemically categorized into alkaloids, terpenoids, polyketides, γ-butyrolactones, quinones, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2</strong> - The Omicron subvariants of SARS-CoV-2 have multiple mutations in the S-proteins and show high transmissibility. We previously reported that tea catechin (-)-epigallocatechin gallate (EGCG) and its derivatives including theaflavin-3,3’-di-O-digallate (TFDG) strongly inactivated the conventional SARS-CoV-2 by binding to the receptor binding domain (RBD) of the S-protein. Here we show that Omicron subvariants were effectively inactivated by green tea, Matcha, and black tea. EGCG and TFDG strongly…</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>AMPK inhibitor, compound C, inhibits coronavirus replication in vitro</strong> - The coronavirus disease (COVID-19) pandemic has resulted in more than six million deaths by October 2022. Vaccines and antivirals for severe acute respiratory syndrome coronavirus 2 are now available; however, more effective antiviral drugs are required for effective treatment. Here, we report that a potent AMP-activated protein kinase (AMPK) inhibitor, compound C/dorsomorphin, inhibits the replication of the human coronavirus OC43 strain (HCoV-OC43). We examined HCoV-OC43 replication in control…</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 First-In-Human Phase 1 Study of Simnotrelvir, a 3CL-like Protease Inhibitor for Treatment of COVID-19, in Healthy Adult Subjects</strong> - Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier:…</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>An in-vitro evaluation of antifungal, anti-lungcancer (A549), and anti-hyperglycemic activities potential of Andrographis paniculata (Burm. f.) flower extract</strong> - The medical plant research has received more attention among researchers especially after the Covid-19 pandemic. This research performed to evaluate the antifungal, anti-lung cancer (A549), and anti-hyperglycemic activities of aqueous extract of Andrographis paniculata flower. Interestingly, A. paniculata flower aqueous extract contains pharmaceutically valuable phytochemicals such as alkaloid, phenolics, terpenoids, tannins, flavonoids, and protein. It also showed fine antifungal activity…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development in biomarkers of breast cancer: a bibliometric analysis from 2011 to 2020</strong> - CONCLUSIONS: In the past decade, most research has focused on basic and clinical studies, of which microRNAs (miRNAs) and circulating tumor DNAs (ctDNAs) associated with the inhibition and attenuation of BC have become the focus of recent research.</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 loneliness on depression in young people: a multiple mediated effects model</strong> - CONCLUSIONS: The findings indicate that the inability to alleviate negative emotions through socialization and interpersonal companionship during COVID-19 contributed to increased loneliness and subsequent depression. Reduced resilience due to loneliness may lead individuals to project unfavorable interpersonal experiences onto other aspects of life and believe they are incapable of overcoming challenges, thereby deteriorating depression conditions. Enhancing an individual’s resilience may help…</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>Virus on surfaces: Chemical mechanism, influence factors, disinfection strategies, and implications for virus repelling surface design</strong> - While SARS-CoV-2 is generally under control, the question of variants and infections still persists. Fundamental information on how the virus interacts with inanimate surfaces commonly found in our daily life and when in contact with the skin will be helpful in developing strategies to inhibit the spread of the virus. Here in, a critically important review of current understanding of the interaction between virus and surface is summarized from chemistry point-of-view. The…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The role of cross-reactive immunity to emerging coronaviruses: Implications for novel universal mucosal vaccine design</strong> - Host immune response to coronaviruses and the role of cross-reactivity immunity among different coronaviruses are crucial for understanding and combating the continuing COVID-19 outbreak and potential subsequent pandemics. This review paper explores how previous exposure to common cold coronaviruses and more pathogenic coronaviruses may elicit a protective immune response against SARS-CoV-2 infection, and discusses the challenges posed by some variants of concern that may escape current…</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>Multi-structural molecular docking (MOD) combined with molecular dynamics reveal the structural requirements of designing broad-spectrum inhibitors of SARS-CoV-2 entry to host cells</strong> - New variants of SARS-CoV-2 that can escape immune response continue to emerge. Consequently, there is an urgent demand to design small molecule therapeutics inhibiting viral entry to host cells to reduce infectivity rate. Despite numerous in silico and in situ studies, the structural requirement of designing viral-entry inhibitors effective against multiple variants of SARS-CoV-2 has yet to be described. Here we systematically screened the binding of various natural products (NPs) to six…</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>Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome</strong> - Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms….</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>Antibacterial and anti-corona virus (229E) activity of Nigella sativa oil combined with photodynamic therapy based on methylene blue in wound infection: in vitro and in vivo study</strong> - Microbial skin infections, antibiotic resistance, and poor wound healing are major problems, and new treatments are needed. Our study targeted solving this problem with Nigella sativa (NS) oil and photodynamic therapy based on methylene blue (MB-PDT). Antibacterial activity and minimum inhibitory concentration (MIC) were determined via agar well diffusion assay and broth microdilution, respectively. Transmission electron microscopy (TEM) proved deformations in Staphylococcus aureus ATCC 6538….</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>N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry</strong> - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is highly pathogenic to piglets and poses a major threat to the swine industry. SADS-CoV has a wide cell tropism and pathogenic potential in younger animals. Therefore, understanding how SADS-CoV enters cells is essential for curbing its re-emergence and spread. Here, we report that tunicamycin, an N-linked glycoprotein inhibitor, inhibited the attachment of SADS-CoV to host cells, suggesting that the SADS-CoV receptor may be an N-linked…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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