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<title>06 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>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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<div class="article-link article-html-link">
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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>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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</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/10.1101/2023.10.05.561047v1" 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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</div></li>
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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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</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/10.1101/2023.10.04.560875v1" target="_blank">Unveiling the antiviral capabilities of targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2</a>
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</div></li>
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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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<div>
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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>
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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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<li><strong>Exploring the potential of a saliva-based, RNA-extraction-free PCR test for the multiplexed detection of key respiratory pathogens</strong> -
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Introduction. Efforts to diagnose and monitor transmissible respiratory infections can be impaired by invasive or resource-intensive sample collection. Having extensively demonstrated the feasibility of saliva for SARS-CoV-2 detection, we sought to validate its potential for other common upper respiratory tract pathogens. Methods. We modified our RNA-extraction-free SARS-CoV-2 PCR test for multiplexed detection of influenza A/B (IAV/IBV), respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). Stability of virus detection in saliva from virus-positive patients was tested after storage at 4°C, room temperature (~19°C), 30°C and 40°C for up to 7 days and through simulated shipping conditions. De-identified saliva samples were collected from individuals (≥18 years) with respiratory symptoms who were undergoing nasal-swab-based testing for SARS-CoV-2 (New Haven, CT). Saliva samples from SARS-CoV-2-negative individuals were tested with the multiplexed assay, with and without RNA extraction. Results. The limit of assay detection ranged from 3-6 copies/μl, virus target depending. Detection remained stable after prolonged sample storage at elevated temperatures and through shipping conditions. From the symptomatic testing sites, 1,095 clinical specimens tested SARS-CoV-2-negative. Upon multiplexed testing of their paired saliva, 41 (3.7%) tested positive (IAV, n=20; RSV, n=5; hMPV, n=7). Additionally, upon screening samples in singleplex for pneumococcus, 29 (3%) samples tested positive. Conclusion. Our findings emphasize the adaptability of a low-cost, open-source saliva-based PCR test for common respiratory pathogens, beyond SARS-CoV-2. We demonstrated its utility in symptomatic individuals, identifying viral infection missed when testing focused solely on a singular target, such as SARS-CoV-2.
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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/10.1101/2023.10.04.23296240v1" target="_blank">Exploring the potential of a saliva-based, RNA-extraction-free PCR test for the multiplexed detection of key respiratory pathogens</a>
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</div></li>
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<li><strong>Modelling the impact of population mobility, post-infection immunity and vaccination on SARS-CoV-2 transmission in the Dominican Republic</strong> -
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COVID-19 epidemic dynamics are driven by a complex interplay of factors including population behaviour, government interventions, new variants, vaccination campaigns and immunity from prior infections. We aimed to quantify the epidemic drivers of SARS-CoV-2 dynamics in the Dominican Republic, an upper-middle income country of 10.8 million people, and assess the impact of the vaccination campaign implemented in February 2021 in saving lives and averting hospitalisations. We used an age-structured, multi-variant transmission dynamic model to characterise epidemic drivers in the Dominican Republic and explore counterfactual scenarios around vaccination coverage and population mobility. We fit the model to reported deaths, hospital bed occupancy, ICU bed occupancy and seroprevalence data until December 2021 and simulated epidemic trajectories under different counterfactual vaccination scenarios. We estimate that vaccination averted 5040 hospital admissions (95% CrI: 4750 - 5350), 1500 ICU admissions (95% CrI: 1420 - 1590) and 544 deaths (95% CrI: 488 - 606) in the first 6 months of the campaign. We also found that early vaccination with Sinovac-CoronaVac was preferable to delayed vaccination using a product with higher efficacy. We investigated the trade-off between changes in vaccination coverage and population mobility to understand how much relaxation of social distancing measures vaccination was able to 9buy9 in the later stages of a pandemic. We found that if no vaccination had occurred, an additional decrease of 10-20% in population mobility would have been required to maintain the same death and hospitalisation outcomes. We found SARS-CoV-2 transmission dynamics in the Dominican Republic were driven by substantial accumulation of immunity during the first two years of the pandemic but that, despite this, vaccination was essential in enabling a return to pre-pandemic mobility levels without incurring considerable additional morbidity and mortality.
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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/10.1101/2023.10.05.23296586v1" target="_blank">Modelling the impact of population mobility, post-infection immunity and vaccination on SARS-CoV-2 transmission in the Dominican Republic</a>
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</div></li>
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<li><strong>Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms.</strong> -
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Background: Autoimmune responses contribute to the pathophysiology of Long COVID, affective symptoms and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Objectives: To examine whether Long COVID, and its accompanying affective symptoms and CFS are associated with immunoglobulin (Ig)A/IgM/IgG directed at neuronal proteins including myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), synapsin, α+β-tubulin, neurofilament protein (NFP), cerebellar protein-2 (CP2), and the blood-brain-barrier-brain-damage (BBD) proteins claudin-5 and S100B. Methods: IgA/IgM/IgG to the above neuronal proteins, human herpes virus-6 (HHV-6) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were measured in 90 Long COVID patients and 90 healthy controls, while C-reactive protein (CRP), and advanced oxidation protein products (AOPP) in association with affective and CFS ratings were additionally assessed in a subgroup thereof. Results: Long COVID is associated with significant increases in IgG directed at tubulin (IgG-tubulin), MBP, MOG and synapsin; IgM-MBP, MOG, CP2, synapsin and BBD; and IgA-CP2 and synapsin. IgM-SARS-CoV-2 and IgM-HHV-6 antibody titers were significantly correlated with IgA/IgG/IgM-tubulin and -CP2, IgG/IgM-BBD, IgM-MOG, IgA/IgM-NFP, and IgG/IgM-synapsin. Binary logistic regression analysis shows that IgM-MBP and IgG-MBP are the best predictors of Long COVID. Multiple regression analysis shows that IgG-MOG, CRP and AOPP explain together 41.7% of the variance in the severity of CFS. Neural network analysis shows that IgM-synapsin, IgA-MBP, IgG-MOG, IgA-synapsin, IgA-CP2, IgG-MBP and CRP are the most important predictors of affective symptoms due to Long COVID with a predictive accuracy of r=0.801. Conclusion: Brain-targeted autoimmunity contributes significantly to the pathogenesis of Long COVID and the severity of its physio-affective phenome.
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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/10.1101/2023.10.04.23296554v1" target="_blank">Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms.</a>
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</div></li>
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<li><strong>COVID-19 and Influenza Infection Prevention and Control Measures in U.S. Jails, Prisons, and Detention Centers: A Scoping Review</strong> -
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<b>Background:</b> People who are incarcerated or detained are at a high risk of infection and death due to viruses spread through droplets, including SARS-CoV-2 (COVID-19) and influenza. Increased risk is associated with structural and institutional conditions of detainment, including but not limited to congregate settings, poor ventilation, and barriers to accessing care. The lessons learned from managing previous infectious outbreaks can inform preventative measures for future emerging outbreaks. <b>Aims:</b> Our project aims to analyze infection prevention and control measures for COVID-19 and influenza in U.S. correctional facilities. <b>Methods:</b> We searched the PubMed and Embase databases for manuscripts evaluating the effectiveness of influenza or COVID-19 mitigation measures. Then, we reviewed the reference lists from our results to identify manuscripts not captured by the initial search. <b>Results:</b> Out of the 553 articles initially found, only 28 met the inclusion criteria, with 27 focusing on COVID-19. Two additional studies were added after reviewing reference lists. Effective measures to prevent the spread of both infections included vaccines, testing, de-densification, limiting movement, masks, and contact tracing. <b>Conclusion:</b> Improved infrastructure, stakeholder collaboration, and research on sustainable responses are needed to address disproportionate impacts on people who are incarcerated or detained.
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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/10.1101/2023.10.04.23296518v1" target="_blank">COVID-19 and Influenza Infection Prevention and Control Measures in U.S. Jails, Prisons, and Detention Centers: A Scoping Review</a>
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</div></li>
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<li><strong>Leprosy campaigns in Brazil: analysis of “Janeiro Roxo” impact using Google Trends.</strong> -
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“Janeiro Roxo” (Purple January) is a Brazilian campaign to raise awareness about leprosy and its early symptoms. The negative influence of the COVID-19 pandemic on institutional campaigns was especially relevant for the control of leprosy, if considered its status of neglected disease by the media. Google Trends (GT) is a free tool that tracks accesses to given terms on Google. Using GT we studied (i) impact of “Janeiro Roxo” in public interest on leprosy in the last 5 years; (ii) public interest during and after COVID-19 pandemic; (iii) patterns of public interest in self-identification of leprosy signs. Methods: GT tracking follows the popularity of topics in time range in “Relative Search Volume” (RSV) – proxies of public interest in a particular subject on a scale from 0 to 100. We selected “HANSENÍASE” (HAN) and “HANSENÍASE SINTOMAS” (leprosy symptoms) (H.SIN) to estimate public interest in leprosy and “self-diagnosis” during 261 weeks (August 2018 to 2023). Polynomial trend lines estimate trends over the period. Weekly RSV, monthly and annual means were compared using Analysis of Variance (ANOVA). Results: In 261 weeks: higher RSV to “HANSENÍASE” (HAN) compared to “HANSENÍASE SINTOMAS” (H.SIN); highest Monthly Means (MM) in January months (2019 to 2023) for both HAN and H.SIN. Pandemic effect in “Janeiro Roxo”: decrease in January MM 2021 compared to 2020 (24% to HAN, 25% to H.SIN). Both HAN/H.SIN reached pre-pandemic levels in January 2022/2023. Breakpoints (points of abrupt change which influences trend lines) in the 26th week (February 2019); in the 55th and 213th week (September 2019 and 2022). Trend line (HAN): upward curve between 33rd-45th week (April to June 2019); pandemic downward trend between 120th-136th week (December 2020 to March 2021); upward trend curve between 220th-240th week (November 2022 to March 2023). Conclusion: “Janeiro Roxo” and in-person activities, among other media stimuli, have a relevant impact in terms of public interest in leprosy, even after their interruption due to pandemic. Considering their impacts on national searches, regional campaigns should be considered very successful. RSV to HAN may be due to “reactive searches” motivated by transient stimuli from campaigns, in an ephemeral and impersonal way. “Proactive searches” to H.SIN may be associated to those interested - in a personal way - in early symptoms and self-diagnosis. Internet-based campaign evaluation programs could be useful in integrating vulnerable regions and exposing their needs for assistance services.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.04.23296467v1" target="_blank">Leprosy campaigns in Brazil: analysis of “Janeiro Roxo” impact using Google Trends.</a>
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</div></li>
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<li><strong>Humoral and cellular immune responses following BNT162b2 XBB.1.5 vaccination</strong> -
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SARS-CoV-2 Omicron XBB subvariants efficiently evade immunity from prior infection or vaccination, requiring vaccine adaptation. Here, we analyzed immunogenicity of an adapted vaccine, BNT162b2 Omicron XBB.1.5, which is currently used for booster vaccination. Booster vaccination significantly increased anti-Spike IgG, accompanied by expansion of cross-reactive memory B cells recognizing Wuhan and Omicron XBB.1.5 spike variants. Geometric mean neutralizing titers against XBB.1.5, XBB.1.16 and XBB.2.3, as well as cross-reactive responses against EG.5.1 and BA.2.86 increased significantly relative to pre-booster titers. Finally, the number of Wuhan and XBB.1.5 spike reactive IFN-γ-producing T cells significantly increased after booster vaccination. In summary, BNT162b2 Omicron XBB.1.5 vaccination resulted in potent neutralizing antibody responses against Omicron XBB variants, including the recent Omicron variants EG.5.1 (Eris) and BA.2.86 (Pirola), as well as XBB.1.5 reactive T cell responses, suggesting that booster vaccination will augment protection against these emerging variants.
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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/10.1101/2023.10.04.23296545v1" target="_blank">Humoral and cellular immune responses following BNT162b2 XBB.1.5 vaccination</a>
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</div></li>
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<li><strong>Characterization of Long COVID Definitions and Clinical Coding Practices</strong> -
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Background: Long COVID characterized as post-acute sequelae of SARS-CoV-2 (PASC) has no universal clinical case definition. Recent efforts have focused on understanding long COVID symptoms and electronic health records (EHR) data provides a unique resource for understanding this condition. The introduction of the International Classification of Diseases (ICD)-10 code U09.9 for - Post COVID-19 condition, unspecified to identify patients with long COVID has provided a method of evaluating this condition in EHRs, however, the accuracy of this code is unclear. Objective: Our study aimed to characterize the utility and accuracy of the U09.9 code across three healthcare systems - The Veterans Health Administration (VHA), Beth Israel Deaconess Medical Center (BIDMC) and The University of Pittsburgh Medical Center (UPMC) against patients identified with long COVID via a chart review by operationalizing the World Health Organization (WHO) and Centers for Disease Control (CDC) definitions. Methods: COVID positive patients with either a U07.1 ICD code or positive polymerase chain reaction (PCR) test within these healthcare systems were identified for chart review. Among this cohort we sampled patients based on two approaches i) with a U09.9 code and ii) without a U09.9 code but with a new onset PASC related ICD code, which allows us to assess the sensitivity of the U09.9 code. To operationalize the long COVID definition based on health agency guidelines, we grouped symptoms into a core cluster of 11 commonly reported symptoms among long COVID patients and an extended cluster, that captured all other symptoms by disease domain. Patients having at least 2 symptoms persisting for >=60 days that were new onset after their COVID infection, with at least one symptom in the core cluster, were labeled as having long COVID per chart review. We compared the performance of the code across three health systems and across different time periods of the pandemic. Results: A total of 900 patient charts were reviewed across 3 healthcare systems. The prevalence of long COVID among the cohort with the U09.9 ICD code, based on the operationalized WHO definition was between 23.2%-62.4% across these healthcare systems. We also evaluated a less stringent version of the WHO definition and the Centers for Disease Control (CDC) definition and observed an increase in the prevalence of long COVID at all three healthcare systems. Conclusions: This is one of the first studies to evaluate the U09.9 code against a clinical case definition for long COVID, as well as the first to apply this definition to EHR data using a chart review approach on a nationwide cohort across multiple healthcare systems. This chart review approach can be implemented at other EHR systems to further evaluate the utility and performance of the U09.9 code.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.04.23296301v1" target="_blank">Characterization of Long COVID Definitions and Clinical Coding Practices</a>
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<li><strong>Bioinformatic Analysis of Defective Viral Genomes in SARS-CoV-2 and Its Impact on Population Infection Characteristics</strong> -
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DVGs (Defective Viral Genomes) and SIP (Semi-Infectious Particle) are commonly present in RNA virus infections. In this study, we analyzed high-throughput sequencing data and found that DVGs or SIPs are also widely present in SARS-CoV-2. Comparison of SARS-CoV-2 with various DNA viruses revealed that the SARS-CoV-2 genome is more susceptible to damage and has greater sequencing sample heterogeneity. Variability analysis at the whole-genome sequencing depth showed a higher coefficient of variation for SARS-CoV-2, and DVG analysis indicated a high proportion of splicing sites, suggesting significant genome heterogeneity and implying that most virus particles assembled are enveloped with incomplete RNA sequences. We further analyzed the characteristics of different strains in terms of sequencing depth and DVG content differences and found that as the virus evolves, the proportion of intact genomes in virus particles increases, which can be significantly reflected in third-generation sequencing data, while the proportion of DVG gradually decreases. Specifically, the proportion of intact genome of Omicron was greater than that of Delta and Alpha strains. This can well explain why Omicron strain is more infectious than Delta and Alpha strains. We also speculate that this improvement in completeness is due to the enhancement of virus assembly ability, as the Omicron strain can quickly realize the binding of RNA and capsid protein, thereby shortening the exposure time of exposed virus RNA in the host environment and greatly reducing its degradation level. Finally, by using mathematical modeling, we simulated how DVG effects under different environmental factors affect the infection characteristics and evolution of the population. We can explain well why the severity of symptoms is closely related to the amount of virus invasion and why the same strain causes huge differences in population infection characteristics under different environmental conditions. Our study provides a new approach for future virus research and vaccine development.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.05.23296580v1" target="_blank">Bioinformatic Analysis of Defective Viral Genomes in SARS-CoV-2 and Its Impact on Population Infection Characteristics</a>
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<li><strong>The Coronavirus (Safeguards) Bill 2020: Proposed protections for digital interventions and in relation to immunity certificates</strong> -
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This Bill attempts to provide safeguards in relation to the symptom tracking and contact tracing apps that are currently being rolled out in the UK; and anticipates minimum safeguards that will be needed if we move on to a roll out of “immunity certificates” (commonly known as passports) in the near future. It does not mandate any particular technological approach to building apps nor does it attempt to duplicate the GDPR and ePrivacy Directive. Instead it suggests some basic safeguards that need to be placed on top of what these laws already supply. Although no one wants to delay or deter the massive effort to fight coronavirus we are all involved in, there are clear reasons to put a law like this in place sooner rather than later: (a) The portion of the population which is already digitally excluded needs reassurance that apps will not further entrench their exclusion (b) Uptake of any contact tracing app, crucial to its success will be improved if the app is both trusted and trustworthy. Voluntary use is crucial to this. Accordingly we suggest a principle of non-compulsion which includes making sure that no-one such as employers or service providers can, as a way of compulsion, discriminate against those who have not installed or used the app. (c) Connectedly, data quality will be much higher if people use these apps with confidence and do not provide false information to them, or withhold information, for fear of misuse or discrimination (d) Both uptake and quality will also be improved if citizens feel they have rights to police these apps and the data gathered via them, via a robust and swift complaints mechanism (e) Public trust will also be enhanced if an independent body whose remit is wider than just data protection has a watching brief to report on the whole scheme in relation to not just privacy but discrimination, freedom of movement, due process et al Accordingly this draft Bill makes it clear that (a) No one shall be penalised for not having a phone (or other device), leaving house without a phone, failing to charge phone, etc (b) No one is compelled to install a symptom and contact tracing app, or to share messages of their status on such an app (eg to an employer or insurer or university) (c) Personal data collected by an app, or contained in an immunity certificate, shall not be shared beyond the NHS and coronavirus researchers unless securely anonymised. (d) What is true, secure, verifiable, anonymisation needs to be certified by a stringent Code of Conduct (e) Personal data collected by apps or immunity certificate must be deleted or anonymised as soon as possible, or at latest immediately after the emergency period has expired. (f) “Immunity passports” must not become novel and uncontrolled internal passports, nor used by either state or private sector to discriminate in ways not necessary or proportionate to the legitimate social goal of controlling COVID-19.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/lawarchive/yc6xu/" target="_blank">The Coronavirus (Safeguards) Bill 2020: Proposed protections for digital interventions and in relation to immunity certificates</a>
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<li><strong>The Covid-19 Outbreak: Can an applied linguist contribute towards human civilization?</strong> -
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“The Covid-19 Outbreak” Can an applied linguist contribute towards human civilization?
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🖺 Full Text HTML: <a href="https://osf.io/preprints/lawarchive/emzk3/" target="_blank">The Covid-19 Outbreak: Can an applied linguist contribute towards human civilization?</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile) <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SA55 Injection; Other: Placebo for SA55 injection <br/><b>Sponsors</b>: Sinovac Life Sciences Co., Ltd. <br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What do we know about the function of SARS-CoV-2 proteins?</strong> - The COVID-19 pandemic has highlighted the importance in the understanding of the biology of SARS-CoV-2. After more than two years since the first report of COVID-19, it remains crucial to continue studying how SARS-CoV-2 proteins interact with the host metabolism to cause COVID-19. In this review, we summarize the findings regarding the functions of the 16 non-structural, 6 accessory and 4 structural SARS-CoV-2 proteins. We place less emphasis on the spike protein, which has been the subject of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High-affinity binding to the SARS-CoV-2 spike trimer by a nanostructured, trivalent protein-DNA synthetic antibody</strong> - Multivalency enables nanostructures to bind molecular targets with high affinity. Although antibodies can be generated against a wide range of antigens, their shape and size cannot be tuned to match a given target. DNA nanotechnology provides an attractive approach for designing customized multivalent scaffolds due to the addressability and programmability of the nanostructure shape and size. Here, we design a nanoscale synthetic antibody (“nano-synbody”) based on a three-helix bundle DNA…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bioactive metabolites identified from Aspergillus terreus derived from soil</strong> - Aspergillus terreus has been reported to produce many bioactive metabolites that possess potential activities including anti-inflammatory, cytotoxic, and antimicrobial activities. In the present study, we report the isolation and identification of A. terreus from a collected soil sample. The metabolites existing in the microbial ethyl acetate extract were tentatively identified by HPLC/MS and chemically categorized into alkaloids, terpenoids, polyketides, γ-butyrolactones, quinones, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2</strong> - The Omicron subvariants of SARS-CoV-2 have multiple mutations in the S-proteins and show high transmissibility. We previously reported that tea catechin (-)-epigallocatechin gallate (EGCG) and its derivatives including theaflavin-3,3’-di-O-digallate (TFDG) strongly inactivated the conventional SARS-CoV-2 by binding to the receptor binding domain (RBD) of the S-protein. Here we show that Omicron subvariants were effectively inactivated by green tea, Matcha, and black tea. EGCG and TFDG strongly…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AMPK inhibitor, compound C, inhibits coronavirus replication in vitro</strong> - The coronavirus disease (COVID-19) pandemic has resulted in more than six million deaths by October 2022. Vaccines and antivirals for severe acute respiratory syndrome coronavirus 2 are now available; however, more effective antiviral drugs are required for effective treatment. Here, we report that a potent AMP-activated protein kinase (AMPK) inhibitor, compound C/dorsomorphin, inhibits the replication of the human coronavirus OC43 strain (HCoV-OC43). We examined HCoV-OC43 replication in control…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A First-In-Human Phase 1 Study of Simnotrelvir, a 3CL-like Protease Inhibitor for Treatment of COVID-19, in Healthy Adult Subjects</strong> - Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier:…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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