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183 lines
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<title>07 October, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Understanding SARS-CoV-2 Spike glycoprotein clusters and their impact on immunity of the population from Rio Grande do Norte, Brazil</strong> -
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<div>
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SARS-CoV-2 genome underwent mutations since it started circulating intensively within the human populations. The aim of this study was to understand the fluctuation of the spike clusters concomitant to high rate of population immunity either due to natural infection and/or vaccination in a state of Brazil that had high rate of infection and vaccination coverage. A total of 1715 SARS-CoV-2 sequences from the state of Rio Grande do Norte, Brazil, were retrieved from GISAID and subjected to cluster analysis. Immunoinformatics were used to predict T- and B-cell epitopes, followed by simulation to estimate either pro- or anti-inflammatory responses and correlate with circulating variants. From March 2020 to June 2022, Rio Grande do Norte reported 579,931 COVID-19 cases with a 1.4% fatality rate across three major waves: May-Sept 2020, Feb-Aug 2021, and Jan-Mar 2022. Cluster 0 variants (wild type strain, Zeta) were prevalent in the first wave and Delta in the latter half of 2021, featuring fewer unique epitopes. Cluster 1 (Gamma [P1]) dominated the first half of 2021. Late 2021 had Clusters 2 (Omicron) and 3 (Omicron sublineages) with the most unique epitopes, while Cluster 4 (Delta sublineages) emerged in the second half of 2021 with fewer unique epitopes. Cluster 1 epitopes showed a high pro-inflammatory propensity, while others exhibited a balanced cytokine induction. The clustering method effectively identified Spike groups that may contribute to immune evasion and clinical presentation, and explain in part the clinical outcome.
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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/10.1101/2023.10.05.561101v1" target="_blank">Understanding SARS-CoV-2 Spike glycoprotein clusters and their impact on immunity of the population from Rio Grande do Norte, Brazil</a>
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</div></li>
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<li><strong>Protection of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort</strong> -
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<b>Background</b> <br /> The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. <br /> <b>Methods</b> <br /> Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. <br /> <b>Results</b> <br /> 1,298 infections were detected among 9,560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95%CI 0.9 to 23.8) overall; 24.0% (95%CI 8.5 to 36.8) in the first two months post-vaccination, reducing to 10.3% (95%CI -11.4 to 27.8) and 1.7% (95%CI -17.0 to 17.4) at 2-4 and 4-6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95%CI 46.9 to 75.0) and 29.1% (95%CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0-6, and 6-12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. <br /> <b>Conclusions</b> <br /> Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. <br /> <b>Funding</b> <br /> UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, and others.
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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/10.1101/2023.09.29.23296330v3" target="_blank">Protection of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort</a>
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</div></li>
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<li><strong>Quantitatively assessing early detection strategies for mitigating COVID-19 and future pandemics</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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Researchers and policymakers have proposed systems to detect novel pathogens earlier than existing surveillance systems by monitoring samples from hospital patients, wastewater, and air travel, in order to mitigate future pandemics. How much benefit would such systems offer? We developed, empirically validated, and mathematically characterized a quantitative model that simulates disease spread and detection time for any given disease and detection system. We find that hospital monitoring could have detected COVID-19 in Wuhan 0.4 weeks earlier than it was actually discovered, at 2,300 cases (standard error: 76 cases) compared to 3,400 (standard error: 161 cases). Wastewater monitoring would not have accelerated COVID-19 detection in Wuhan, but provides benefit in smaller catchments and for asymptomatic or long-incubation diseases like polio or HIV/AIDS. Monitoring of air travel provides little benefit in most scenarios we evaluated. In sum, early detection systems can substantially mitigate some future pandemics, but would not have changed the course of COVID-19.
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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/10.1101/2023.06.08.23291050v2" target="_blank">Quantitatively assessing early detection strategies for mitigating COVID-19 and future pandemics</a>
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</div></li>
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<li><strong>Hill numbers at the edge of a pandemic: rapid SARS-COV2 surveillance using clinical, pooled, or wastewater sequence as a sensor for population change</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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The COVID-19 pandemic has highlighted the critical role of genomic surveillance for guiding policy and control strategies. Timeliness is key, but rapid deployment of existing surveillance is difficult because current approaches are based in sequence alignment and phylogeny. Millions of SARS-CoV-2 genomes have been assembled, the largest collection of sequence data in history. Phylogenetic methods are ill equipped to handle this sheer scale. We introduce a pan-genomic measure that examines the information diversity of a k-mer library drawn from a country9s complete set of sequenced genomes. Quantifying diversity is central to ecology. Studies that measure the diversity of various environments increasingly use the concept of Hill numbers, or the effective number of species in a sample, to provide a simple metric for comparing species diversity across environments. The more diverse the sample, the higher the Hill number. We adopt this ecological approach and consider each k-mer an individual and each genome a transect in the pan-genome of the species. Applying Hill numbers in this way allows us to summarize the temporal trajectory of pandemic variants by collapsing each day9s assemblies into genomic equivalents. We do this quickly, without alignment or trees, using modern genome sketching techniques to accommodate millions of genomes in one condensed view of pandemic dynamics. Using data from the UK, USA, and South Africa, we trace the ascendence of new variants of concern as they emerge in local populations. This history of emerging variants uses all available data as it is sequenced, intimating variant sweeps to dominance or declines to extinction at the leading edge of the COVID19 pandemic. The surveillance technique we introduce in a SARS-CoV-2 context here can operate on genomic data generated over any pandemic time course and is organism agnostic.
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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/10.1101/2022.06.23.22276807v3" target="_blank">Hill numbers at the edge of a pandemic: rapid SARS-COV2 surveillance using clinical, pooled, or wastewater sequence as a sensor for population change</a>
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</div></li>
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<li><strong>Heterologous booster with a novel formulation containing glycosylated trimeric S protein is effective againstOmicron</strong> -
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<div>
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In this study, we evaluated the efficacy of a heterologous three-dose vaccination schedule against the Omicron BA.1 SARS-CoV-2 variant infection using a mouse intranasal challenge model. The vaccination schedules tested in this study consisted of a primary series of 2 doses covered by two commercial vaccines: an mRNA-based vaccine (mRNA1273) or a non-replicative vector-based vaccine AZD1222/ChAdOx1, hereafter referred to as AZD1222). These were followed by a heterologous booster dose using one of the two vaccine candidates previously designed by us: one containing the glycosylated and trimeric spike protein (S) from the ancestral virus (SW-Vac 2 microg), and the other from the Delta variant of SARS-CoV-2 (SD-Vac 2 microg), both formulated with Alhydrogel as an adjuvant. For comparison purposes, homologous three-dose schedules of the commercial vaccines were used. The mRNA-based vaccine, whether used in heterologous or homologous schedules, demonstrated the best performance, significantly increasing both humoral and cellular immune responses. In contrast, for the schedules that included the AZD1222 vaccine as the primary series, the heterologous schemes showed superior immunological outcomes compared to the homologous 3-dose AZD1222 regimen. For these schemes no differences were observed in the immune response obtained when SW-Vac 2microg or SD-Vac 2 microg were used as a booster dose. Neutralizing antibody levels against Omicron BA.1 were low, especially for the schedules using AZD1222. However, a robust Th1 profile, known to be crucial for protection, was observed, particularly for the heterologous schemes that included AZD1222. All the tested schedules were capable of inducing populations of CD4 T effector, memory, and follicular helper T lymphocytes. It is important to highlight that all the evaluated schedules demonstrated a satisfactory safety profile and induced multiple immunological markers of protection. Although the levels of these markers were different among the tested schedules, they appear to complement each other in conferring protection against intranasal challenge with Omicron BA.1 in K18-hACE2 mice. In summary, the results highlight the potential of using the S protein (either ancestral Wuhan or Delta variant)-based vaccine formulation as heterologous boosters in the management of COVID-19, particularly for certain commercial vaccines currently in use.
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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/10.1101/2023.10.05.557343v1" target="_blank">Heterologous booster with a novel formulation containing glycosylated trimeric S protein is effective againstOmicron</a>
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</div></li>
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<li><strong>Interventions used to improve air flow in hospitals - a rapid review</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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The COVID-19 pandemic has highlighted the need for improved air flow in hospitals, to reduce the transmission of airborne infections such as COVID-19. The aim of this review was to map the existing literature on intervention used to improve air flow in hospitals, understanding challenges in implementation and the findings of any evaluations. We reviewed peer-reviewed articles identified on three databases, MEDLINE, Web of Science and the Cochrane Library with no restriction on date. 5846 articles were identified, 130 were reviewed and 18 were included: ten articles were from databases and eight articles were identified through hand searching. Results were discussed in terms of three categories: (i) concentration of aerosol particles, (ii) changes in/effect of air speed and ventilation and (iii) improvements or reduction in health conditions. Eight studies included an evaluation, the majority only had one comparator condition however three had multiple conditions. The most common device or method that was outlined by researchers was HEPA filters, which can remove particles with a size of 3 microns. Articles outline different interventions to improve air flow and some demonstrate their effectiveness in terms of improving health outcomes for patients, they also suggest either mechanical and natural ventilation are the best methods for dispersing particulate matter as well as perhaps two air cleaning units rather than one. With different methods comes different strengths and weaknesses however, the key finding is that air flow improvement measures reduce the likelihood of nosocomial infections.
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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/10.1101/2023.10.06.23296654v1" target="_blank">Interventions used to improve air flow in hospitals - a rapid review</a>
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<li><strong>A portable, easy-to-use paper-based biosensor for rapid in-field detection of fecal contamination on fresh produce farms</strong> -
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<div>
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Laboratory-based nucleic acid amplification tests (NAATs) are highly sensitive and specific, but they require the transportation of samples to centralized testing facilities and have long turnaround times. During the Coronavirus Disease 2019 (COVID-19) pandemic, substantial advancement has been achieved with the development of paper-based point-of-care (POC) NAATs, offering features such as low cost, being easy to use, and providing rapid sample-to-answer times. Although most of the POC NAATs innovations target clinical settings, we have developed a portable, paper-based loop-mediated isothermal amplification (LAMP) testing platform for on-farm applications, capable of detecting Bacteroidales as a fecal contamination biomarker. Our integrated platform includes a drop generator, a heating and imaging unit, and paper-based biosensors, providing sensitive results (limit of detection 3 copies of Bacteroidales per cm2) within an hour of sample collection. We evaluated this integrated platform on a commercial lettuce farm with a concordance of 100% when compared to lab-based tests. Our integrated paper-based LAMP testing platform holds great promise as a reliable and convenient tool for on-site NAATs. We expect that this innovation will encourage the fresh produce industry to adopt NAATs as a complementary tool for decision-making in growing and harvesting. We also hope that our work can stimulate further research in the development of on-farm diagnostic tools for other agricultural applications, leading to improved food safety and technology innovation.
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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/10.1101/2023.10.04.560915v1" target="_blank">A portable, easy-to-use paper-based biosensor for rapid in-field detection of fecal contamination on fresh produce farms</a>
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</div></li>
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<li><strong>The more symptoms the better? Covid-19 vaccine side effects and long-term neutralizing antibody response</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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Protection against SARS-CoV-2 wanes over time, and booster uptake has been low, in part because of concern about side effects. We examined the relationships between local and systemic symptoms, biometric changes, and neutralizing antibodies (nAB) after mRNA vaccination. Data were collected from adults (n = 364) who received two doses of either BNT162b2 or mRNA-1273. Serum nAB concentration was measured at 1 and 6 months post-vaccination. Daily symptom surveys were completed for six days starting on the day of each dose. Concurrently, objective biometric measurements, including skin temperature, heart rate, heart rate variability, and respiratory rate, were collected. We found that certain symptoms (chills, tiredness, feeling unwell, and headache) after the second dose were associated with increases in nAB at 1 and 6 months post-vaccination, to roughly 140-160% the level of individuals without each symptom. Each additional symptom predicted a 1.1-fold nAB increase. Greater increases in skin temperature and heart rate after the second dose predicted higher nAB levels at both time points, but skin temperature change was more predictive of durable (6 month) nAB response than of short-term (1 month) nAB response. In the context of low ongoing vaccine uptake, our convergent symptom and biometric findings suggest that public health messaging could seek to reframe systemic symptoms after vaccination as desirable.
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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/10.1101/2023.09.26.23296186v2" target="_blank">The more symptoms the better? Covid-19 vaccine side effects and long-term neutralizing antibody response</a>
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</div></li>
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<li><strong>HERV activation segregates ME/CFS from fibromyalgia and defines a novel nosological entity for patients fulfilling both clinical criteria</strong> -
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<div>
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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia (FM) are chronic diseases with poorly understood pathophysiology and diagnosis based on clinical assessment of unspecific symptoms. The recent post-COVID-19 condition, which shares similarities with ME/CFS and FM, has raised concerns about viral-induced transcriptome changes in post-viral syndromes. Viral infections, and other types of stress, are known to unleash human endogenous retroviruses (HERV) repression that if maintained could lead to symptom chronicity. This study evaluated this possibility for ME/CFS and FM on a selected cohort of female patients complying with diagnosis criteria for ME/CFS, FM, or both, and matched healthy controls (n=43). The results show specific HERV fingerprints for each disease, confirming biological differences between ME/CFS and FM. Unexpectedly, HERV profiles segregated patients that met both ME/CFS and FM clinical criteria from patients complying only with ME or FM criteria, while clearly differentiating patients from healthy subjects, supporting that the highly prevalent comorbidity condition must constitute a different nosological entity. Moreover, HERV profiles exposed significant quantitative differences within the ME/CFS group that correlated with differences in immune gene expression and patient symptomatology, supporting ME/CFS patient subtyping and confirming immunological disturbances in this disease. Pending issues include validation of HERV profiles as disease biomarkers of post-viral syndromes and understanding the role of HERV during infection and beyond.
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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/10.1101/2023.10.05.561025v1" target="_blank">HERV activation segregates ME/CFS from fibromyalgia and defines a novel nosological entity for patients fulfilling both clinical criteria</a>
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</div></li>
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<li><strong>Who Saves the Saviours During a Pandemic? Career Calling Protects Healthcare Workers from Burnout and Resigning</strong> -
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<div>
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This study investigates whether career calling protects from the detrimental effects of fear of COVID-19 and job demand on burnout and turnover intentions during the COVID-19 pandemic. Data were collected in a sample of 275 Italian healthcare workers in charge of COVID-19 patients. Direct, indirect, and conditional effects were tested using a path model. The results showed a significant sequential mediation effect: Demand partially mediates the relation between fear of COVID-19 and burnout; burnout completely mediates the impact of fear of COVID-19 on turnover intention. Career calling moderates the impact of fear of COVID-19 on demand and of burnout on turnover intentions. When calling is high, the effects of fear of COVID-19 on perceived job demand, and the effect of burnout on turnover intentions are null. This study supports the notion that career calling is a personal resource that protects people from the negative consequences of highly stressful work environments.
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🖺 Full Text HTML: <a href="https://osf.io/snguz/" target="_blank">Who Saves the Saviours During a Pandemic? Career Calling Protects Healthcare Workers from Burnout and Resigning</a>
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</div></li>
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<li><strong>Relative Deprivation, Psychological Wellbeing, and Problematic Internet Use among Young Adults During COVID-19 Lockdown: A Fuzzy-Set Qualitative Comparative Analysis (fsQCA)</strong> -
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<div>
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Individuals’ relative deprivation, psychological distress and addictive use of the internet are increasing concerns during the COVID-19 crisis. However, the related literature on these effects during the pandemic is lacking. We adopt social comparison theory as the framework to improve our understanding of the relationships between relative deprivation, psychological distress, life dissatisfaction, and problematic Internet use. In this study, young adult participants were recruited from one department of a university in China during the COVID-19 lockdown. A fuzzy-set qualitative comparative analysis (fsQCA) was employed to explore the effects of relative deprivation evoked by social comparison on individuals’ psychological distress, life dissatisfaction, and problematic Internet use. Our results—obtained by adopting fsQCA—demonstrate that relative deprivation evoked by upward comparison is a key predictor of psychological distress, life dissatisfaction, and problematic Internet use during the campus lockdown. Also, psychological distress is linked to problematic Internet use. Our results provide novel insights into the phenomenon of relative deprivation during the COVID-19 crisis. We propose measures to improve individuals’ psychological wellbeing and reduce their problem behaviors, including: conducting psychological lectures emphasizing the danger of social comparisons; balancing the needs of faculty members and students, and epidemic control; avoiding inconsistent closed-off campus rules in campus management; and developing a counseling program addressing relative deprivation, psychological wellbeing, and problematic Internet use.
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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/6u8nf/" target="_blank">Relative Deprivation, Psychological Wellbeing, and Problematic Internet Use among Young Adults During COVID-19 Lockdown: A Fuzzy-Set Qualitative Comparative Analysis (fsQCA)</a>
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</div></li>
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<li><strong>Independent regulation of Z-lines and M-lines during sarcomere assembly in cardiac myocytes revealed by the automatic image analysis software sarcApp</strong> -
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<div>
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Sarcomeres are the basic contractile units within cardiac myocytes, and the collective shortening of sarcomeres aligned along myofibrils generates the force driving the heartbeat. The alignment of the individual sarcomeres is important for proper force generation, and misaligned sarcomeres are associated with diseases including cardiomyopathies and COVID-19. The actin bundling protein, -actinin-2, localizes to the Z-Bodies of sarcomere precursors and the Z-Lines of sarcomeres, and has been used previously to assess sarcomere assembly and maintenance. Previous measurements of -actinin-2 organization have been largely accomplished manually, which is time-consuming and has hampered research progress. Here, we introduce sarcApp, an image analysis tool that quantifies several components of the cardiac sarcomere and their alignment in muscle cells and tissue. We first developed sarcApp to utilize deep learning- based segmentation and real space quantification to measure -actinin-2 structures and determine the organization of both precursors and sarcomeres/myofibrils. We then expanded sarcApp to analyze M-Lines using the localization of myomesin and a protein that connects the Z-Lines to the M-Line (titin). sarcApp produces 33 distinct measurements per cell and 24 per myofibril that allow for precise quantification of changes in sarcomeres, myofibrils, and their precursors. We validated this system with perturbations to sarcomere assembly. Surprisingly, we found perturbations that affected Z-Lines and M-Lines differently, suggesting that they may be regulated independently during sarcomere assembly.
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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/10.1101/2023.01.11.523681v3" target="_blank">Independent regulation of Z-lines and M-lines during sarcomere assembly in cardiac myocytes revealed by the automatic image analysis software sarcApp</a>
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</div></li>
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<li><strong>Fourth dose of Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Elicits Robust Long-lasting Humoral Responses in mice</strong> -
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<div>
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The COVID-19 pandemic has underscored the pressing need for safe and effective booster vaccines, particularly in considering the emergence of new SARS-CoV-2 variants and addressing vaccine distribution inequalities. Dissolving microneedle array patches (MAP) offer a promising delivery method, enhancing immunogenicity and improving accessibility through the skin’s immune potential. In this study, we evaluated a microneedle array patch-based S1 subunit protein COVID-19 vaccine candidate, which comprised a bivalent formulation targeting the Wuhan and Beta variant alongside a monovalent Delta variant spike proteins in a murine model. Notably, the second boost of homologous bivalent MAP-S1(WU+Beta) induced a 15.7-fold increase in IgG endpoint titer, while the third boost of heterologous MAP-S1RS09Delta yielded a more modest 1.6-fold increase. Importantly, this study demonstrated that the administration of four doses of the MAP vaccine induced robust and long-lasting immune responses, persisting for at least 80 weeks. These immune responses encompassed various IgG isotypes and remained statistically significant for one year. Furthermore, neutralizing antibodies against multiple SARS-CoV-2 variants were generated, with comparable responses observed against the Omicron variant. Overall, these findings emphasize the potential of MAP-based vaccines as a promising strategy to combat the evolving landscape of COVID-19 and to deliver a safe and effective booster vaccine worldwide.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.05.561047v1" target="_blank">Fourth dose of Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Elicits Robust Long-lasting Humoral Responses in mice</a>
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<li><strong>Unveiling the antiviral capabilities of targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2</strong> -
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<div>
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The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the enzymes in charge of pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated quinone-based compounds, discovering potent HsDHODH inhibition (low nanomolar IC50) and promising in vitro anti-SARS-CoV-2 activity (low micromolar EC50). These compounds exhibited low toxicity, indicating potential for further development. Additionally, we employed computational tools like molecular docking and QSAR models to analyse protein-ligand interactions. These findings represent a significant step forward in the search for effective antiviral treatments and have great potential to impact the development of new broad-spectrum antiviral drugs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.04.560875v1" target="_blank">Unveiling the antiviral capabilities of targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2</a>
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<li><strong>The Trajectory of Depression and Anxiety Among Children and Adolescents over Two Years of the COVID-19 Pandemic</strong> -
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Longitudinal research examining childrens mental health (MH) over the course of the COVID-19 pandemic is scarce. We examined trajectories of depression and anxiety over two pandemic years among children with and without MH disorders. Parents and children 2 to 18 years completed surveys at seven timepoints (April 2020 to June 2022). Parents completed validated measures of depression and anxiety for children 8to 18 years, and validated measures of emotional/behavioural symptoms for children 2 to 7 years old. Children 10 years and older completed validated measures of depression and anxiety. Latent growth curve analysis determined depression and anxiety trajectories, accounting for demographics, child and parent MH. Data were available on 1315 unique children (1259 parent-reports, 550 child-reports). Trajectories were stable across the study period, however individual variation in trajectories was statistically significant. Of included covariates, only initial symptom level predicted symptom trajectories. Among participants with pre-COVID data, a significant increase in depression symptoms relative to pre-pandemic levels was observed. Children and adolescents experienced elevated and sustained levels of depression and anxiety during the two-year period. Findings have direct policy implications in the prioritization and of maintenance of educational, recreational, and social activities with added MH supports in the face of future events.
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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/10.1101/2023.10.04.23296430v1" target="_blank">The Trajectory of Depression and Anxiety Among Children and Adolescents over Two Years of the COVID-19 Pandemic</a>
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</div></li>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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>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>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>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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</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>Angiotensin-(1-7) attenuates SARS-CoV2 spike protein-induced interleukin-6 and interleukin-8 production in alveolar epithelial cells through activation of Mas receptor</strong> - BACKGROUND: SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an inflammatory process. Angiotensin-(1-7) may have an anti-inflammatory effect through activation of Mas receptor. This study aims to investigate whether SARS-CoV-2 SP can induce inflammation through ACE2 in the alveolar epithelial cells which can be modulated through angiotensin-(1-7)/Mas receptor axis.</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>Antiviral opportunities of Mannich bases derived from triterpenic N-propargylated indoles</strong> - Oleanolic and glycyrrhetic acids alkyne derivatives were synthesized as a result of propargylation of the indole NH-group condensed with the triterpene A-ring, the following aminomethylation led to a series of Mannich bases. The synthesized compounds were tested for their potential inhibition of influenza A/PuertoRico/8/34 (H1N1) virus in Madin-Darby canine kidney (MDCK) cell culture and SARS-CoV-2 pseudovirus in baby hamster kidney-21-human angiotensin-converting enzyme 2 (BHK-21-hACE2) cells….</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>Alisol B 23-acetate broadly inhibits coronavirus through blocking virus entry and suppresses proinflammatory T cells responses for the treatment of COVID-19</strong> - CONCLUSION: Alisol B 23-acetate could be a promising therapeutic agent for COVID-19 treatment and its underlying mechanisms might be attributed to viral entry inhibition and anti-inflammatory activities.</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>Universal features of Nsp1-mediated translational shutdown by coronaviruses</strong> - Nonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ribosomal mRNA channel to inhibit translation, but it is unclear whether this mechanism is broadly used by coronaviruses, whether the Nsp1 N-terminal domain binds the ribosome, or how Nsp1 allows viral RNAs to be translated. Here, we investigated Nsp1 from SARS-CoV-2, Middle East respiratory…</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>Broad antagonism of coronaviruses nsp5 to evade the host antiviral responses by cleaving POLDIP3</strong> - Coronaviruses (CoVs) are a family of the largest RNA viruses that typically cause respiratory, enteric, and hepatic diseases in animals and humans, imposing great threats to the public safety and animal health. Porcine deltacoronavirus (PDCoV), a newly emerging enteropathogenic coronavirus, causes severe diarrhea in suckling piglets all over the world and poses potential risks of cross-species transmission. Here, we use PDCoV as a model of CoVs to illustrate the reciprocal regulation between…</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>Porphyrin-derived carbon dots for an enhanced antiviral activity targeting the CTD of SARS-CoV-2 nucleocapsid</strong> - CONCLUSIONS: Therefore, this study comprehensively demonstrated the potential of porphyrin-derived carbon dots to be developed further as a promisingly safe and effective COVID-19 antiviral drug.</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 Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial</strong> - CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season.</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>Analysis of SARS-CoV-2 spike RBD binding to ACE2 and its inhibition by fungal cohaerin C using surface enhanced Raman spectroscopy</strong> - The structure of the SARS-CoV-2 spike RBD and human ACE2 as well as changes in the structure due to binding activities were analysed using surface enhanced Raman spectroscopy. The inhibitor cohaerin C was applied to inhibit the binding between spike RBD and ACE2. Differences and changes in the Raman spectra were determined using deconvolution of the amide bands and principal component analysis. We thus demonstrate a fast and label-free analysis of the protein structures and the differentiation…</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>Novel designed analogues of quercetin against SARS-CoV2:an in-silico pharmacokinetic evaluation, molecular modeling, MD simulations based study</strong> - Here we present the design of the series of quercetin analogues and their molecular docking study involving the binding of quercetin and its analogues with SARS-CoV2 3CLpro. The scientific literature shows that quercetin compound has been successfully used against SARS-CoV by inhibiting the replication of virus in respiratory epithelial cell through the inhibition of the SARS-CoV main protease (3CLpro.) It was suggested that the modification at position 3 in quercetin structure may produce…</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>Reply to: Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Spike protein peptides displayed in the Pyrococcus furiosus RAD system preserve epitopes antigenicity, immunogenicity, and virus-neutralizing activity of antibodies</strong> - Amongst the potential contribution of protein or peptide-display systems to study epitopes with relevant immunological features, the RAD display system stands out as a highly stable scaffold protein that allows the presentation of constrained target peptides. Here, we employed the RAD display system to present peptides derived from the SARS-CoV-2 Spike (S) protein as a tool to detect specific serum antibodies and to generate polyclonal antibodies capable of inhibiting SARS-CoV-2 infectivity in…</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>Phellinus linteus mycelia extract in COVID-19 prevention and identification of its key metabolic compounds profiling using UPLC-QTOF-MS/MS spectrometry</strong> - For centuries, food, herbal medicines, and natural products have been valuable resources for discovering novel antiviral drugs, uncovering new structure-activity relationships, and developing effective strategies to prevent/treat viral infections. One such resource is Phellinus linteus, a mushroom used in folk medicine in Taiwan, Japan, Korea, and China. In this rich historical context, the key metabolites of Phellinus linteus mycelia ethanolic extract (GKPL) impacting the entry of severe acute…</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 microfibers induced toxicity in marine sedentary polychaete Hydroides elegans: Insight from embryogenesis axis</strong> - Presence of surgical face masks in the environment are more than ever before after the COVID-19 pandemic, and it poses a newer threat to aquatic habitats around the world due to microfibers (MFs) and other contaminants that get discharged when these masks deteriorate. The mechanism behind the developmental toxicity of MFs, especially released from surgical masks, on the early life stages of aquatic organisms are not well understood. Toxicity test were developed to examine the effects of MFs…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 promotes endothelial dysfunction and thrombogenicity: Role of pro-inflammatory cytokines/SGLT2 pro-oxidant pathway</strong> - CONCLUSIONS: In COVID-19 patients, pro-inflammatory cytokines induced a redox-sensitive up-regulation of SGLT2 expression in ECs, which in turn promoted endothelial injury, senescence, platelet adhesion, aggregation, and thrombin generation. SGLT2 inhibition with empagliflozin, appeared as an attractive strategy to restore vascular homeostasis 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>SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway</strong> - Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) leading to pulmonary and extra-pulmonary manifestations due to the development of oxidative stress (OS) and hyperinflammation. The underlying cause for OS and hyperinflammation in COVID-19 may be related to the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidative responses and cellular homeostasis. The Nrf2…</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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