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186 lines
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<title>17 March, 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>Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in Long COVID</strong> -
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Background. Critical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production of neuroactive tryptophan catabolites (TRYCATs), including kynurenine (KYN) and quinolinic acid. The TRYCAT pathway has not been studied extensively in association with the physiosomatic and affective symptoms of Long COVID. Methods. In the present study, we measured serum tryptophan (TRY), TRYCATs, insulin resistance (using the HOMA2-IR index), C-reactive protein (CRP), physiosomatic, depression and anxiety symptoms in 90 Long COVID patients, 3-10 months after remission of acute infection. Results. We were able to construct an endophenotypic class of severe Long COVID (22% of the patients) with very low TRY and oxygen saturation (SpO2, during acute infection), increased kynurenine, KYN/TRY ratio, CRP, and very high ratings on all symptom domains. One factor could be extracted from physiosomatic symptoms (including chronic fatigue-fibromyalgia), depression, and anxiety symptoms, indicating that all domains are manifestations of the common physio-affective phenome. Three Long COVID biomarkers (CRP, KYN/TRY, IR) explained around 40% of the variance in the physio-affective phenome. The latter and the KYN/TRY ratio were significantly predicted by peak body temperature (PBT) and lowered SpO2 during acute infection. One validated latent vector could be extracted from the three symptom domains and a composite based on CRP, KYN/TRY, IR (Long COVID), and PBT and SpO2 (acute COVID-19). Conclusion. The physio-affective phenome of Long COVID is a manifestation of inflammatory responses during acute and Long COVID and lowered plasma tryptophan and increased kynurenine may contribute to these effects.
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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/10.1101/2023.03.11.23287152v1" target="_blank">Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in Long COVID</a>
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</div></li>
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<li><strong>Increased Influenza Severity in Children in the Wake of SARS-CoV-2</strong> -
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The SARS-CoV-2 pandemic and subsequent interruption of influenza circulation has lowered population immunity to influenza, especially among children with few pre-pandemic exposures. We compared the incidence and severity of influenza A/H3N2 and influenza B/Victoria between 2022 and two pre-pandemic seasons and found an increased frequency of severe influenza in 2022.
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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/10.1101/2023.03.11.23286858v1" target="_blank">Increased Influenza Severity in Children in the Wake of SARS-CoV-2</a>
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</div></li>
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<li><strong>Predicting COVID-19 pandemic waves with biologically and behaviorally informed universal differential equations</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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In the early stages of the COVID-19 pandemic, it became clear that pandemic waves and population responses were locked in a mutual feedback loop. The initial lull following strict interventions in the first wave often led to a second wave, as restrictions were relaxed. We test the ability of new hybrid machine learning techniques, namely universal differential equations (UDEs) with learning biases, to make predictions in a such a dynamic behavior-disease setting. We develop a UDE model for COVID-19 and test it both with and without learning biases describing simple assumptions about disease transmission and population response. Our results show that UDEs, particularly when supplied with learning biases, are capable of learning coupled behavior-disease dynamics and predicting second waves in a variety of populations. The model predicts a second wave of infections 55% of the time across all populations, having been trained only on the first wave. The predicted second wave is larger than the first. Without learning biases, model predictions are hampered: the unbiased model predicts a second wave only 25% of the time, typically smaller than the first. The biased model consistently predicts the expected increase in the transmission rate with rising mobility, whereas the unbiased model predicts a decrease in mobility as often as a continued increase. The biased model also achieves better accuracy on its training data thanks to fewer and less severely divergent trajectories. These results indicate that biologically informed machine learning can generate qualitatively correct mid to long-term predictions of COVID-19 pandemic waves.
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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/10.1101/2023.03.11.23287141v1" target="_blank">Predicting COVID-19 pandemic waves with biologically and behaviorally informed universal differential equations</a>
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</div></li>
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<li><strong>Comparison of Capillary Blood Self-Collection using the Tasso-SST Device with Venous Phlebotomy for anti-SARS-CoV-2 Antibody Measurement</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Measuring seroprevalence over time is a valuable epidemiological tool for improving our understanding of COVID-19 immunity. Due to the large number of collections required for population surveillance as well as concerns about potential infection risk to the collectors, self-collection approaches are being increasingly pursued. To advance this methodology, we collected paired venous and capillary blood samples by routine phlebotomy and Tasso-SST device respectively from 26 participants and measured total immunoglobulin (Ig) and IgG antibodies to the SARS-CoV-2 receptor binding domain (RBD) by enzyme-linked immunosorbent assay (ELISA) on both specimens. Qualitatively, no discrepancies were noted in binary results between Tasso and venipuncture-derived plasma. Furthermore, in vaccinated participants, correlation between Tasso and venous Ig total and IgG specific antibody quantitative levels was high (Total Ig: ρ ; = 0.72, 95% CI (0.39- 0.90); IgG ρ ; = 0.85, 95% CI (0.54, 0.96)). Our results support the use of Tasso at-home collection devices for antibody testing.
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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/10.1101/2023.03.13.23286935v1" target="_blank">Comparison of Capillary Blood Self-Collection using the Tasso-SST Device with Venous Phlebotomy for anti-SARS-CoV-2 Antibody Measurement</a>
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</div></li>
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<li><strong>Pre-pandemic inequalities in the burden of disease: a Scottish Burden of Disease study</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Health inequalities in Scotland have been well documented, including the contribution of different causes to inequalities in mortality. Our aim was to estimate inequalities within a burden of disease framework, accounting for both premature mortality and the effects of morbidity, to understand the contribution of specific diseases to health inequalities prior to the COVID-19 pandemic. Methods: Disability Adjusted Life Years (DALYs) for 13 disease groupings and 70 individual causes of disease and injury were sourced from the Scottish Burden of Disease Study. Area level deprivation was measured using the Scottish Index of Multiple Deprivation. Inequalities were measured by the range, Relative Index of Inequality, Slope Index of Inequality, and attributable DALYs were estimated by using the least deprived deciles as a reference. Results: Marked inequalities were observed across several measures. The overall disease burden was double that in the most deprived areas (50,355 vs 20,955 DALYS per 100, 000), largely driven by inequalities in premature mortality. The rate in the most deprived areas was around 48% higher than the mean population rate (RII = 0.96), with 35% of DALYs attributed to differences in area-based deprivation. Many of the leading causes of disease burden in 2019 – heart disease, drug use disorders, lung cancer and COPD – were also the leading drivers of absolute and relative inequalities in the disease burden. Conclusion: This study demonstrates that even before the COVID-19 pandemic there continues to be a steep stepwise gradient in the burden of disease experienced across the Scottish population. This was evident for premature mortality and morbidity and almost every specific cause of death. Keywords: Burden of disease; DALY; Disability-adjusted life year; Inequalities; Population health; Scottish burden of disease.
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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/10.1101/2023.03.15.23286907v1" target="_blank">Pre-pandemic inequalities in the burden of disease: a Scottish Burden of Disease study</a>
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</div></li>
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<li><strong>Increased vaccine sensitivity of an emerging SARS-CoV-2 variant</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with improvements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and ≥5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of ≥4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and ≥2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses.
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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/10.1101/2023.03.11.23287148v1" target="_blank">Increased vaccine sensitivity of an emerging SARS-CoV-2 variant</a>
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</div></li>
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<li><strong>COVID-19-related changes in adolescents’ daily-life social interactions and psychopathology symptoms</strong> -
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<div>
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Early findings on the impact of the COVID-19 pandemic on adolescents, suggest that – despite being at the lowest physical health risk – both their mental health and day-to-day social lives are strongly affected. In this longitudinal study, we assessed changes in adolescent psychopathology symptoms, the quality and quantity of daily-life social interactions, and the relationship between social interactions and psychopathology symptoms before and during the pandemic. A sample of n=173 Flemish adolescents (mean age=16.0 at latest measurement; 89% girls) from the SIGMA cohort was tested between January 2018 - June 2019; and between April 27th - May 10th 2020. Subclinical psychopathology was assessed using the Brief Symptom Inventory-53; daily social interactions were assessed in six-day experience sampling periods with ten daily questionnaires. Multilevel linear and logistic regression analyses indicated lower general psychopathology and anxiety symptoms, beyond age effects; fewer face-to-face social interactions, more online social interactions; and higher-quality face-to-face interactions during the pandemic than before. Negative associations between psychopathology and the quality of face-to-face peer and family interactions were stronger during the pandemic than pre-pandemic. The observed decrease and stability in psychopathology symptoms is surprising and potentially reflects resilience. Although digital communication may buffer much of the quarantine-induced distress, the current results imply that high-quality face-to-face interactions with family and peers may have been more powerful in keeping adolescents resilient. As restrictions are lifted and adolescents’ daily lives and social worlds change, it is crucial to learn more about the longer-term effects of the experienced social deprivation.
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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/5nfp2/" target="_blank">COVID-19-related changes in adolescents’ daily-life social interactions and psychopathology symptoms</a>
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</div></li>
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<li><strong>Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of break-through infections in hemodialysis patients</strong> -
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<div>
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Background Individuals on hemodialysis are more vulnerable to SARS-CoV-2 infection than the general population due to end-stage kidney disease-induced immunosuppression. Methods 26 hemodialysis patients experiencing SARS-CoV-2 infection after 3rd vaccination were matched 1:1 to 26 out of 92 SARS-CoV-2 naives by age, sex, dialysis vintage and immunosuppressive drugs receiving a 4th vaccination with an mRNA-based vaccine. A competitive surrogate neutralization assay was used to monitor vaccination success. To determine infection neutralization titers, Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC), Omicron sub-lineage BA.1, BA.5, and BQ.1.1. 50% inhibitory concentration (IC50, serum dilution factor 1:x) was determined before, four weeks after and 6 months after the 4th vaccination. Results 52 hemodialysis patients received four COVID-19 vaccinations and were followed up for a median of 6.3 months. Patient characteristics did not differ between the matched cohorts. Patients without a SARS-CoV-2 infection had a significant reduction of real virus neutralization capacity for all Omicron sub-lineages after six months (p<0.001 each). Those patients with a virus infection did not experience a reduction of real virus neutralization capacity after six months. Compared to the other Omicron VoC the BQ.1.1 sub-lineage had the lowest virus neutralization capacity. Conclusions SARS-CoV-2-naive hemodialysis patients had significantly decreased virus neutralization capacity six months after the 4th vaccination whereas patients with a SARS-CoV-2 infection had no change in neutralization capacity. This was independent of age, sex, dialysis vintage and immunosuppression. Therefore, in infection-naive hemodialysis patients a fifth COVID-19 vaccination might be reasonable 6 months after the 4th vaccination.
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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/10.1101/2023.03.14.23287246v1" target="_blank">Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of break-through infections in hemodialysis patients</a>
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</div></li>
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<li><strong>Lapses in the person radar: ADHD symptoms predict difficulty in interpersonal distancing</strong> -
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<div>
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Objective: Across contexts, from social cognition to the COVID-19 pandemic response, individual variation in the regulation of interpersonal distance has typically been viewed as a voluntary choice. Here we examine the frequency of unintentional lapses in interpersonal distancing, and their relationship with childhood ADHD symptoms. Method: We administered a novel measure of difficulty in interpersonal distancing across 3 undergraduate samples (total N = 1,233), in addition to measures of recalled childhood ADHD symptoms, mind wandering and hyperfocus. Results: Almost all (>97%) participants reported unintentional lapses in maintaining interpersonal distance, with 16% experiencing such lapses frequently. Thirty percent of the variance in these reports was accounted for by attentional traits: Inattentive and hyperactive/impulsive ADHD symptoms jointly predicted difficulties with interpersonal distancing, with the former relationship fully mediated by hyperfocus and spontaneous mind wandering. Conclusion: Both inattentive and hyperactive/impulsive ADHD symptoms confer vulnerability to frequent unintentional lapses in interpersonal distancing.
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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/2yrfj/" target="_blank">Lapses in the person radar: ADHD symptoms predict difficulty in interpersonal distancing</a>
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</div></li>
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<li><strong>Peg-interferon Lambda Single Dose Treatment for COVID-19: A Call to Avoid another Hydroxychloroquine Fiasco.</strong> -
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<div>
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In this perspective, I counter-argue a claim that was recently made that a single dose of Peg-interferon lambda can significantly lower incidence of COVID-19 hospitalizations or emergency department visits. Some major flaws in a recently published article that suggested this benefit are discussed while asking the global authorities to learn from the prior mistakes and to be of utmost caution when considering its final decision regarding adoption of a single dose of Peg-interferon lambda to manage COVID-19. It has been declined to be published by the respective NEJM that published the fraudulent claim without any comment and it’s reasonable that many journals might be hesitant to allow a peer review. However, no matter my argument could seem harsh, the loss of millions of lives due to corrupted American journals and health care authorities that allowed failure pharmacotherapeutics to manage COVID-19 patients in return of billions of dollars profits is much harsher and I’ll not be surprised if this preprint follows numerous previous ones that I was tired and eventually gave up and stopped seeking to find a peer review opportunity.
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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/5xd6q/" target="_blank">Peg-interferon Lambda Single Dose Treatment for COVID-19: A Call to Avoid another Hydroxychloroquine Fiasco.</a>
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<li><strong>Public engagement with biomedical science: An analysis of Black, Hispanic, and General Population adults in the United States</strong> -
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<div>
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The COVID-19 pandemic has highlighted the need to better understand public engagement with biomedical science across groups - especially those that have been historically marginalized by the medical science community. However, common approaches to studying group differences in science attitudes are often limited by small sample sizes or by categorizing individuals based on demographic variables, which may obscure meaningful variability within a given population. We recruited three probability-based samples of Black (N = 963), General Population (N = 957), and Hispanic (N = 964) adults living in the U.S. (October 21 - November 5, 2021). Employing a novel application of a non-negative matrix factorization model to conduct an attitudinal-based segmentation that categorized individuals based on distinct orientations toward biomedical science, our analysis revealed 10 unique mindsets across the three surveyed populations. Overall, our work underscores the value of recruiting independent samples from underserved and marginalized communities by revealing underexplored variation in how different publics orient toward biomedical science.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.15.530692v1" target="_blank">Public engagement with biomedical science: An analysis of Black, Hispanic, and General Population adults in the United States</a>
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</div></li>
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<li><strong>Modelling the viral dynamics of the SARS-CoV-2 Delta and Omicron variants in different cell types</strong> -
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<div>
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We use viral kinetic models fitted to viral load data from in vitro studies to explain why the SARS-CoV-2 Omicron variant replicates faster than the Delta variant in nasal cells, but slower than Delta in lung cells, which could explain Omicron’s higher transmission potential and lower severity. We find that in both nasal and lung cells, viral infectivity is higher for Omicron but the virus production rate is higher for Delta. However, the differences are unequal between cell types, and ultimately leads to the basic reproduction number and growth rate being higher for Omicron in nasal cells, and higher for Delta in lung cells. In nasal cells, Omicron alone can enter via a TMPRSS2-independent pathway, but it is primarily increased efficiency of TMPRSS2-dependent entry which accounts for Omicron’s increased activity. This work paves the way for using within-host mathematical models to understand the transmission potential and severity of future variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.15.529513v1" target="_blank">Modelling the viral dynamics of the SARS-CoV-2 Delta and Omicron variants in different cell types</a>
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</div></li>
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<li><strong>Human antigen R differentially modulates the translation of SARS-CoV-2 genomic and sub-genomic RNAs</strong> -
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<div>
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Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) viral RNA associates with different RNA-binding host proteins at each stage of its life cycle, although the potential role of human antigen R (HuR) is unclear. Here, we found that HuR bound the 5’-untranslated region (5’-UTR) of SARS-CoV-2, and knockdown and knockout studies revealed the importance of such binding in viral translation. We identified 5’-UTR mutations in SARS-CoV-2 variants of concern that altered the HuR-binding affinity. Interestingly, HuR promoted non-structural protein translation through the genomic 5’-UTR and suppressed the structural protein translation from the sub-genomic 5’-UTR, which required polypyrimidine tract-binding protein binding to the 5’-UTR. HuR knockout increased the sensitivity to remdesivir treatment by decreasing its half-maximal inhibitory concentration by 10-fold. An antisense oligonucleotide (whose binding site overlapped the HuR-binding site) reduced viral RNA production and viral titers in wild-type cells but not HuR-knockout cells, further suggesting that HuR binds the SARS-CoV-2 5’-UTR and promotes replication. Our results indicate that HuR supports SARS-CoV-2 life cycle by promoting differential translational reprogramming of genomic and sub-genomic RNAs, implying that HuR can potentially be targeted for therapeutic interventions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.15.532790v1" target="_blank">Human antigen R differentially modulates the translation of SARS-CoV-2 genomic and sub-genomic RNAs</a>
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<li><strong>Tetravalent SARS-CoV-2 S1 Subunit Protein Vaccination Elicits Robust Humoral and Cellular Immune Responses in SIV-Infected Rhesus Macaque Controllers</strong> -
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<div>
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The COVID-19 pandemic has highlighted the need for safe and effective vaccines to be rapidly developed and distributed worldwide, especially considering the emergence of new SARS-CoV-2 variants. Protein subunit vaccines have emerged as a promising approach due to their proven safety record and ability to elicit robust immune responses. In this study, we evaluated the immunogenicity and efficacy of an adjuvanted tetravalent S1 subunit protein COVID-19 vaccine candidate composed of the Wuhan, B.1.1.7 variant, B.1.351 variant, and P.1 variant spike proteins in a nonhuman primate model with controlled SIVsab infection. The vaccine candidate induced both humoral and cellular immune responses, with T- and B cell responses mainly peaking post-boost immunization. The vaccine also elicited neutralizing and cross-reactive antibodies, ACE2 blocking antibodies, and T-cell responses, including spike specific CD4+ T cells. Importantly, the vaccine candidate was able to generate Omicron variant spike binding and ACE2 blocking antibodies without specifically vaccinating with Omicron, suggesting potential broad protection against emerging variants. The tetravalent composition of the vaccine candidate has significant implications for COVID-19 vaccine development and implementation, providing broad antibody responses against numerous SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.15.532808v1" target="_blank">Tetravalent SARS-CoV-2 S1 Subunit Protein Vaccination Elicits Robust Humoral and Cellular Immune Responses in SIV-Infected Rhesus Macaque Controllers</a>
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<li><strong>The highly conserved stem-loop II motif is dispensable for SARS-CoV-2</strong> -
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<div>
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The stem-loop II motif (s2m) is a RNA structural element that is found in the 3’ untranslated region (UTR) of many RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over twenty-five years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth in vitro, or growth and viral fitness in Syrian hamsters in vivo. We also compared the secondary structure of the 3’ UTR of wild type and s2m deletion viruses using SHAPE-MaP and DMS-MaPseq. These experiments demonstrate that the s2m forms an independent structure and that its deletion does not alter the overall remaining 3’UTR RNA structure. Together, these findings suggest that s2m is dispensable for SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.15.532878v1" target="_blank">The highly conserved stem-loop II motif is dispensable for SARS-CoV-2</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: CareSuperb COVID-19 Antigen Home Test Kit<br/><b>Sponsor</b>: AccessBio, 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>Use of E-health Based Exercise Intervention After COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Exercise training using an e-health tool<br/><b>Sponsors</b>: Norwegian University of Science and Technology; University of Oslo<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>Effect of Selected Types of Breathing Exercises on Different Outcome Measures in Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: breathing exercise<br/><b>Sponsor</b>: Basma Mosaad Abd-elrahman Abushady<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Calcitriol; Other: Placebo<br/><b>Sponsor</b>: Universitas Sebelas Maret<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: P1101 (Ropeginterferon alfa-2b); Procedure: SOC<br/><b>Sponsor</b>: National Taiwan University Hospital<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>Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant variant COVID-19 vaccine (Sf9 cell); Biological: Recombinant COVID-19 vaccine (CHO cell); Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Compare QLS1128 With Placebo in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu Pharmaceutical Co., Ltd.<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>Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Hormone Replacement Therapy<br/><b>Interventions</b>: Drug: Climara 0.1Mg/24Hr Transdermal System; Other: Hydrogel patch<br/><b>Sponsors</b>: Istanbul University - Cerrahpasa (IUC); Turkish Menopause and Osteoporosis Society; Karakoy Rotary Club; Rebul Pharmacy<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Other: Pursed lip breathing; Other: Cognitive Behavior Therapy; Other: Diaphragmatic breathing exercise; Other: Kinesio tape<br/><b>Sponsor</b>: Cairo 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>Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)</strong> - <b>Conditions</b>: Covid19; Hydrogen-oxygen Gas; AMS-H-03<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Device: OLO-1 Medical Molecular Sieve Oxygen Generator<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<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>Oxygen Atomizing Inhalation of EGCG in the Treatment COVID-19 Pneumonia in Cancer Patients</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Neoplasms Malignant<br/><b>Interventions</b>: Drug: EGCG; Drug: Placebo<br/><b>Sponsor</b>: Shandong Cancer Hospital and Institute<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>The Use of Photobiomodulation in the Treatment of Oral Complaints of Long COVID-19.A Randomized Controlled Trial.</strong> - <b>Conditions</b>: Xerostomia; COVID-19; Long COVID; Persistent COVID-19<br/><b>Interventions</b>: Combination Product: Institutional standard treatment for xerostomia and Long Covid; Radiation: Photobiomodulation Therapy; Radiation: Placebo Photobiomodulation Therapy<br/><b>Sponsor</b>: University of Nove de Julho<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>Balneotherapy for Patients With Post-acute Coronavirus Disease (COVID) Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: Balneotherapy and aquatic exercises<br/><b>Sponsors</b>: Parc de Salut Mar; Caldes de Montbui’s City Council; Consorcio Centro de Investigación Biomédica en Red (CIBER); European Regional Development Fund<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Assess the Efficacy of HH-120 Nasal Spray for Prevention of SARS-CoV-2 Infection in Adult Close Contacts of Individuals Infected With SARS-CoV-2</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: HH-120 nasal spray 1; Drug: HH-120 nasal spray 2; Drug: Placebo Comparator 1; Drug: Placebo Comparator 2<br/><b>Sponsor</b>: Beijing Ditan Hospital<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The enzymatic hydrolysate of fucoidan from Sargassum hemiphyllum triggers immunity in plants</strong> - Fucoidans are polysaccharides that consist predominantly of sulfated L-fucoses, from which, fucoidan oligosaccharides (FOSs) are prepared through different methods. Fucoidan has versatile physiological activities, like antiviral functions against SARS CoV-2 and bioactivitiy in enhancing immune responses. Although fucoidan or FOS has been widely used in mammals as functional foods and new drugs, its application in plants is still very limited. Moreover, whether fucoidan or its derived hydrolytic…</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 confirmed COVID-19 in a patient with newly diagnosed hypertension and preexisting type 2 diabetes mellitus: a case report</strong> - CONCLUSION: Poor blood glucose management in the case of COVID-19 may increase the pathogen’s susceptibility, the likelihood that patients will be admitted to the hospital, and the likelihood that mortality will be enhanced.</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>Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial</strong> - BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase (CK) values, and autoantibodies recognizing 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) or the signal recognition particle (SRP). There are currently no approved therapies for IMNM and many patients experience active disease despite off-label treatment with intravenous immunoglobulin, glucocorticoids, and immunosuppressants. Detection 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>Delivery of anti-microRNA-21 by lung-targeted liposomes for pulmonary fibrosis treatment</strong> - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder with a low survival rate. Pulmonary fibrosis is one of the complications of COVID-19 and has a high prevalence in COVID-19 patients. Currently, no effective therapies other than lung transplantation are available to cure IPF and post-COVID-19 pulmonary fibrosis. MicroRNAs are small non-coding RNAs that mediate the development and progression of pulmonary fibrosis, thus making them potent drug candidates for this serious disease….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Insights of different analytical approaches for estimation of budesonide as COVID-19 replication inhibitor in its novel combinations: green assessment with AGREE and GAPI approaches</strong> - Simple, direct, rapid, and sensitive HPLC and spectrophotometric methods were established for simultaneous estimation of a novel combination of budesonide and azelastine (BUD/AZL) in their laboratory-prepared mixture and dosage form according to the medicinally recommended ratio 1:4.28. Budesonide is an important inhalation corticosteroid that plays a vital role in the inhibition of COVID-19 replication and cytokine production. The first chromatographic method was created for the simultaneous…</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 multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection</strong> - COVID-19 is a systemic disease involving multiple organs. We previously established a platform to derive organoids and cells from human pluripotent stem cells to model SARS-CoV-2 infection and perform drug screens^(1,2). This provided insight into cellular tropism and the host response, yet the molecular mechanisms regulating SARS-CoV-2 infection remain poorly defined. Here we systematically examined changes in transcript profiles caused by SARS-CoV-2 infection at different multiplicities 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>Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients</strong> - CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the ‘cytokine storm’ in COVID-19.</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>Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors</strong> - The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopeptide antibiotics teicoplanin derivatives that bind to the SARS-CoV-2 spike (S) protein, interrupt its interaction with ACE2 receptor and selectively inhibit viral entry mediated by S protein….</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>Paving New Roads Using <em>Allium sativum</em> as a Repurposed Drug and Analyzing its Antiviral Action Using Artificial Intelligence Technology</strong> - CONCLUSIONS: The COVID-19 pandemic has triggered interest among researchers to conduct future research on molecular docking with clinical trials before releasing salutary remedies against the deadly malady.</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>Brevicillin, a novel lanthipeptide from the genus Brevibacillus with antimicrobial, antifungal and antiviral activity</strong> - CONCLUSION: This study provides detailed description of a novel lanthipeptide and demonstrates its effective antibacterial, antifungal and anti-SARS-CoV-2 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>Evaluation of residual humoral immune response against SARS-CoV-2 by a surrogate virus neutralization test (sVNT) 9 months after BNT162b2 primary vaccination</strong> - The humoral response to SARS-CoV-2 vaccination has shown to be temporary, although may be more prolonged in vaccinated individuals with a history of natural infection. We aimed to study the residual humoral response and the correlation between anti-Receptor Binding Domain (RBD) IgG levels and antibody neutralizing capacity in a population of health care workers (HCWs) after 9 months from COVID-19 vaccination. In this cross-sectional study, plasma samples were screened for anti-RBD IgG using 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>Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2</strong> - Gemcitabine is a nucleoside analogue of deoxycytidine and has been reported to be a broad-spectrum antiviral agent against both DNA and RNA viruses. Screening of a nucleos(t)ide analogue-focused library identified gemcitabine and its derivatives (compounds 1, 2a, and 3a) blocking influenza virus infection. To improve their antiviral selectivity by reducing cytotoxicity, 14 additional derivatives were synthesized in which the pyridine rings of 2a and 3a were chemically modified….</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 novel mAb broadly neutralizes SARS-CoV-2 VOCs in vitro and in vivo, including the Omicron variants</strong> - Novel immune escape variants have emerged as SARS-CoV-2 continues to spread worldwide. Many of the variants cause breakthrough infections in vaccinated populations, posing great challenges to current antiviral strategies targeting the immunodominance of the receptor-binding domain within the spike protein. Here, we found that a novel broadly neutralizing monoclonal antibody (mAb), G5, provided efficient protection against SARS-CoV-2 variants of concern (VOCs) in vitro and in vivo. A single dose…</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>Mucosal immunization with Ad5-based vaccines protects Syrian hamsters from challenge with omicron and delta variants of SARS-CoV-2</strong> - SARS-CoV-2 variant clades continue to circumvent antibody responses elicited by vaccination or infection. Current parenteral vaccination strategies reduce illness and hospitalization, yet do not significantly protect against infection by the more recent variants. It is thought that mucosal vaccination strategies may better protect against infection by inducing immunity at the sites of infection, blocking viral transmission more effectively, and significantly inhibiting the evolution of new…</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>2-Deoxy-D-Glucose: A Novel Pharmacological Agent for Killing Hypoxic Tumor Cells, Oxygen Dependence-Lowering in Covid-19, and Other Pharmacological Activities</strong> - The nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) has shown promising pharmacological activities, including inhibition of cancerous cell growth and N-glycosylation. It has been used as a glycolysis inhibitor and as a potential energy restriction mimetic agent, inhibiting pathogen-associated molecular patterns. Radioisotope derivatives of 2-DG have applications as tracers. Recently, 2-DG has been used as an anti-COVID-19 drug to lower the need for supplemental oxygen. In the present…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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