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184 lines
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<title>24 November, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses</strong> -
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<div>
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Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased meta-transcriptomics approach we characterised the mammalian associated viruses present in 149 individual bats sampled from Yunnan province, China. This revealed a high frequency of virus co-infection and species spillover among the animals studied, with 12 viruses shared among different bat species, which in turn facilitates virus recombination and reassortment. Of note, we identified five viral species that are likely to be pathogenic to humans or livestock, including a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV-2 and SARS-CoV, with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2. Functional analysis predicts that this recombinant coronavirus can utilize the human ACE2 receptor such that it is likely to be of high zoonotic risk. Our study highlights the common occurrence of inter-species transmission and co-infection of bat viruses, as well as their implications for virus emergence.
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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/10.1101/2022.11.23.517609v1" target="_blank">Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses</a>
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</div></li>
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<li><strong>Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus</strong> -
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<div>
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There is an urgent need for efficient and safe vaccines against the monkeypox virus (MPXV) in response to the rapidly spreading monkeypox epidemic. In the age of COVID-19, mRNA vaccines have been highly successful and emerged as platforms enabling rapid development and large-scale preparation. Here, we have developed two MPXV quadrivalent mRNA vaccines, named mRNA-A-LNP and mRNA-B-LNP, based on two IMVs (A29L and M1R) and two EEVs (A35R and B6R). By administering mRNA-A-LNP and mRNA-B-LNP intramuscularly twice, mice have induced MPXV-specific IgG antibodies and potent Vaccinia virus (VACV)-specific neutralizing antibodies. Additionally, it elicited durable MPXV-specific killer memory T-cell immunity as well as memory B-cell immunity in mice. Furthermore, the passive transfer of sera from mRNA-A-LNP and mRNA-B-LNP-immunized mice protected nude mice against the VACV challenge. In addition, two doses of mRNA-A-LNP and mRNA-B-LNP were also protective against the VACV challenge in mice. Overall, our results demonstrated that mRNA-A-LNP and mRNA-B-LNP appear to be safe and effective vaccine candidates against monkeypox epidemics, as well as against outbreaks caused by other orthopoxviruses, including the smallpox virus.
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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/10.1101/2022.11.22.517500v1" target="_blank">Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus</a>
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</div></li>
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<li><strong>Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 Spike protein</strong> -
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<div>
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SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic. Its high pathogenicity is due to SARS-CoV-2 spike protein (S protein) contacting host-cell receptors. A critical hallmark of COVID-19 is the occurrence of coagulopathies. Here, we report the direct observation of the interactions between S protein and platelets. Live imaging showed that the S protein triggers platelets to deform dynamically, in some cases, leading to their irreversible activation. Strikingly, cellular cryo-electron tomography revealed dense decorations of S protein on the platelet surface, inducing filopodia formation. Hypothesizing that S protein binds to filopodia-inducing integrin receptors, we tested the binding to RGD motif-recognizing platelet integrins and found that S protein recognizes integrin v{beta}3. Our results infer that the stochastic activation of platelets is due to weak interactions of S protein with integrin, which can attribute to the pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.
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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/10.1101/2022.11.22.517574v1" target="_blank">Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 Spike protein</a>
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</div></li>
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<li><strong>Molecular and cellular similarities in the brain of SARS-CoV-2 and Alzheimer’s disease individuals</strong> -
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<div>
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Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimers disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases. Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1 is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.
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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/10.1101/2022.11.23.517706v1" target="_blank">Molecular and cellular similarities in the brain of SARS-CoV-2 and Alzheimer’s disease individuals</a>
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</div></li>
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<li><strong>The COVID-19 Infodemic: Women and Digital (Health) Literacy</strong> -
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<div>
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The COVID-19 infodemics and gender make it challenging to promote science and health via social media. The objective of this study is to analyze the effects of infodemic exposure on women and men. We argue that an inclusive society is equipped with reliable digital literacy that enables women and men to participate in preventing COVID-19. This quantitative research carried out a survey in June–September 2020, with 440 social media users as respondents in Bali, Indonesia. The approach aims to evaluate attitudes regarding the COVID-19 infodemics. We calculated an error margin of less than +/- 5% at a level of confidence of 95% by combining the online questionnaires and survey analyses. According to the official website of Indonesia’s Ministry of Communications and Information, users are grouped based on their age. For sample distribution, trends, and cross-tabulation, a Statistical Package for the Social Sciences was also used. We discovered that women are more inclined than men to accept the material in the COVID-19 infomercials as accurate. Men were more likely to practice the advice given in the infodemics than women, despite the fact that women believed the infodemics to be factual. However, more women than men reported being likely to spread the erroneous information, which indicates that women are more likely than men to do so. When given incorrect information about COVID-19, both men and women react almost exactly the same. When putting the COVID-19 advice into practice, male and female respondents responded in the same way. To empower individuals to disrupt infodemic flows, COVID-19 needs to promote the digital literacy of both men and women.
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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/f48ka/" target="_blank">The COVID-19 Infodemic: Women and Digital (Health) Literacy</a>
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</div></li>
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<li><strong>Impact of the COVID-19 Pandemic on Personal Networks and Neurological Outcomes of People with Multiple Sclerosis: A Case-Control Cross-sectional and Longitudinal Analysis</strong> -
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Background: The COVID–19 pandemic has negatively impacted the social fabric of people with multiple sclerosis (pwMS). Objective: To evaluate the associations between personal social network environment and neurological function in pwMS and controls during the COVID–19 pandemic and compare with the pre–pandemic baseline. Methods: We first analyzed data collected from 8 cohorts of pwMS and control participants during the COVID–19 pandemic (March–December 2020). We then leveraged data collected between 2017–2019 in 3 of the 8 cohorts for longitudinal comparison. Participants completed a questionnaire that quantified the structure and composition of their personal social network, including the health behaviors of network members. We assessed neurological disability using three interrelated patient–reported outcomes: Patient Determined Disease Steps (PDDS), Multiple Sclerosis Rating Scale–Revised (MSRS–R), and Patient Reported Outcomes Measurement Information System (PROMIS)–Physical Function. We identified the network features associated with neurologic disability using paired t–tests and covariate–adjusted regressions. Results: In the cross-sectional analysis of the pandemic data from 1130 pwMS and 1250 control participants, higher percent of network members with a perceived negative health influence was associated with greater neurological symptom burden in pwMS (MSRS-R: Beta[95% CI]=2.181[1.082, 3.279], p<.001) and worse physical function in controls (PROMIS-Physical Function: Beta[95% CI]=-5.707[-7.405, -4.010], p<.001). In the longitudinal analysis of 230 pwMS and 136 control participants, the percent of people contacted “weekly or less” (p<.001) decreased during the COVID-19 pandemic for both pwMS (30.34% to 18.78%) and controls (23.48% to 14.89%) when compared to the pre-pandemic period. PwMS further experienced a greater reduction in network size (p<.001), increase in constraint (a measure of close ties of the network, p<.001) and decrease in maximum degree (highest number of ties of a network member, p<.001) than controls during the COVID–19 pandemic. These changes in network features were not associated with worsening neurological disability during the pandemic. Conclusions: Our findings suggest that negative health influences in personal social networks are associated with worse disability in all participants, and the COVID–19 pandemic led to contraction of personal social networks to a greater extent for pwMS than controls.
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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/10.1101/2022.08.17.22278896v4" target="_blank">Impact of the COVID-19 Pandemic on Personal Networks and Neurological Outcomes of People with Multiple Sclerosis: A Case-Control Cross-sectional and Longitudinal Analysis</a>
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<li><strong>Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 infection (PASC) in a Large Academic Medical Center in the US</strong> -
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<b>Background:</b> A growing number of Coronavirus Disease-2019 (COVID-19) survivors are affected by Post-Acute Sequelae of SARS CoV-2 infection (PACS). Using electronic health records data, we aimed to characterize PASC-associated diagnoses and to develop risk prediction models. <b>Methods:</b> In our cohort of 63,675 COVID-19 positive patients, 1,724 (2.7 %) had a recorded PASC di-agnosis. We used a case control study design and phenome-wide scans to characterize PASC-associated phenotypes of the pre-, acute-, and post-COVID-19 periods. We also integrated PASC-associated phenotypes into Phenotype Risk Scores (PheRSs) and evaluated their predictive performance. <b>Results:</b> In the post-COVID-19 period, known PASC symptoms (e.g., shortness of breath, malaise/fatigue) and musculoskeletal, infectious, and digestive disorders were enriched among PASC cases. We found seven phenotypes in the pre-COVID-19 period (e.g., irritable bowel syndrome, concussion, nausea/vomiting) and 69 phenotypes in the acute-COVID-19 period (pre-dominantly respiratory, circulatory, neurological) associated with PASC. The derived pre- and acute-COVID-19 PheRSs stratified risk well, e.g., the combined PheRSs identified a quarter of the COVID-19 positive cohort with an at least 2.9-fold increased risk for PASC. <b>Conclusions:</b> The un-covered PASC-associated diagnoses across categories highlighted a complex arrangement of presenting and likely predisposing features, some with a potential for risk stratification ap-proaches.
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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/10.1101/2022.10.21.22281356v3" target="_blank">Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 infection (PASC) in a Large Academic Medical Center in the US</a>
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<li><strong>GenSLMs: Genome-scale language models reveal SARS-CoV-2 evolutionary dynamics.</strong> -
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We seek to transform how new and emergent variants of pandemic-causing viruses, specifically SARS-CoV-2, are identified and classified. By adapting large language models (LLMs) for genomic data, we build genome-scale language models (GenSLMs) which can learn the evolutionary landscape of SARS-CoV-2 genomes. By pre-training on over 110 million prokaryotic gene sequences and fine-tuning a SARS-CoV-2-specific model on 1.5 million genomes, we show that GenSLMs can accurately and rapidly identify variants of concern. Thus, to our knowledge, GenSLMs represents one of the first whole genome scale foundation models which can generalize to other prediction tasks. We demonstrate scaling of GenSLMs on GPU-based supercomputers and AI-hardware accelerators utilizing 1.63 Zettaflops in training runs with a sustained performance of 121 PFLOPS in mixed precision and peak of 850 PFLOPS. We present initial scientific insights from examining GenSLMs in tracking evolutionary dynamics of SARS-CoV-2, paving the path to realizing this on large biological data.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.10.511571v2" target="_blank">GenSLMs: Genome-scale language models reveal SARS-CoV-2 evolutionary dynamics.</a>
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<li><strong>Changes in population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States between December 2021 and November 2022</strong> -
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Importance: While a substantial fraction of the US population was infected with SARS-CoV-2 during December 2021-February 2022, the subsequent evolution of population immunity against SARS-CoV-2 Omicron variants reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations. Objective: To estimate changes in population immunity against infection and severe disease due to circulating SARS-CoV-2 Omicron variants in the United States from December 2021 to November 2022, and to quantify the protection against a potential 2022-2023 winter SARS-CoV-2 wave. Design, setting, participants: Bayesian evidence synthesis of reported COVID-19 data (diagnoses, hospitalizations), vaccinations, and waning patterns for vaccine- and infection-acquired immunity, using a mathematical model of COVID-19 natural history. Main Outcomes and Measures: Population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States, by location (national, state, county) and week. Results: By November 9, 2022, 94% (95% CrI, 79%-99%) of the US population were estimated to have been infected by SARS-CoV-2 at least once. Combined with vaccination, 97% (95%-99%) were estimated to have some prior immunological exposure to SARS-CoV-2. Between December 1, 2021 and November 9, 2022, protection against a new Omicron infection rose from 22% (21%-23%) to 63% (51%-75%) nationally, and protection against an Omicron infection leading to severe disease increased from 61% (59%-64%) to 89% (83%-92%). Increasing first booster uptake to 55% in all states (current US coverage: 34%) and second booster uptake to 22% (current US coverage: 11%) would increase protection against infection by 4.5 percentage points (2.4-7.2) and protection against severe disease by 1.1 percentage points (1.0-1.5). Conclusions and Relevance: Effective protection against SARS-CoV-2 infection and severe disease in November 2022 was substantially higher than in December 2021. Despite this high level of protection, a more transmissible or immune evading (sub)variant, changes in behavior, or ongoing waning of immunity could lead to a new SARS-CoV-2 wave.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.19.22282525v3" target="_blank">Changes in population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States between December 2021 and November 2022</a>
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<li><strong>A quasi-experimental evaluation of a financial incentive for first-dose COVID-19 vaccination among adults aged ≥ 60 years in South Africa</strong> -
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Introduction: COVID-19 vaccination coverage in South Africa (RSA) remains low despite increased access to vaccines. On November 1, 2021, RSA introduced the Vooma Voucher program which provided a small guaranteed financial incentive, a Vooma Voucher redeemable at grocery stores, for COVID-19 vaccination among older adults, a population most vulnerable to serious illness, hospitalization, and death. However, the association of financial incentives with vaccination coverage remains unclear. Methods: We evaluated the association of the conditional economic incentive program with first-dose vaccination rates among adults (aged ≥60 years) through a quasi-experimental cohort study. The Vooma Voucher program was a nationwide vaccination incentive program implemented for adults aged ≥60 years from November 1, 2021 to February 28, 2022. We ran interrupted time series models to evaluate the Vooma Voucher program at national and provincial levels. We used data between October 1, 2021 and November 27, 2021 in models estimated at the daily level. Individuals who received their first vaccine dose received a text message to access a ZAR100 ($~7) voucher that was redeemable at grocery stores. Results: The Vooma Voucher program was associated with a 7.15-12.01% increase in daily first-dose vaccinations in November 2021 compared to late October 2021. Overall, the incentive accounted for 6,476-10,874 additional first vaccine doses from November 1-27, 2021, or 8.31-13.95% of all doses administered to those aged ≥60 years during that period. This result is robust to the inclusion of controls for the number of active vaccine delivery sites and for the nationwide Vooma vaccination weekend initiative (November 12-14), both of which also increased vaccinations through expanded access to vaccines and demand creation activities. Conclusions: Financial incentives for COVID-19 vaccination led to a modest increase in first dose vaccinations among older adults in RSA. Financial incentives and expanded access to vaccines may result in higher vaccination coverage.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.06.22274712v3" target="_blank">A quasi-experimental evaluation of a financial incentive for first-dose COVID-19 vaccination among adults aged ≥ 60 years in South Africa</a>
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<li><strong>How well do surveys on adherence to pandemic policies assess actual behaviour: measurement properties of the Dutch Covid-19 Adherence to Prevention Advice Survey (CAPAS).</strong> -
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Background Survey data on adherence to COVID-19 prevention measures have often been used to inform policy makers and public health professionals. However, there is a lack of studies critically examining the validity and reliability of those self-reported measures. Aim We studied the measurement properties of the Covid-19 Adherence to Prevention Advice Survey (CAPAS), a novel questionnaire implemented in a repeated cross-sectional (i.e., ‘Trend’) Study and a Cohort Study in the Netherlands during the COVID-19 pandemic. Methods The CAPAS is a novel questionnaire developed in March 2020, with the aim to assess social activity and adherence to COVID-19 prevention measures. Items were formulated to minimise social desirability and aid memory retrieval. Based on the COSMIN framework, we investigated criterion validity by comparing trends of self-reported behaviour to trends in objective data. Responsiveness was assessed by studying whether self-reported behaviour changed following contextual (e.g., policy) changes. Test-retest reliability was examined over periods in which the context was stable. Results Overall, trends in self-reported behaviour closely corresponded to trends in external objective data. Self-reported behaviours were responsive to contextual changes and test-retest reliabilities were adequate. For infrequent behaviours reliability improved when measures were dichotomised. We were able to examine national representativeness for vaccination, which suggested a modest overestimation of on average 3.7%. Conclusions This study supports the suitability of using carefully designed, self-reported surveys (and the CAPAS specifically) to study changes in pandemic behaviours in a dynamic context.
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🖺 Full Text HTML: <a href="https://osf.io/rm8qn/" target="_blank">How well do surveys on adherence to pandemic policies assess actual behaviour: measurement properties of the Dutch Covid-19 Adherence to Prevention Advice Survey (CAPAS).</a>
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<li><strong>Environmental and genetic drivers of population differences in SARS-CoV-2 immune responses</strong> -
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Humans display vast clinical variability upon SARS-CoV-2 infection, partly due to genetic and immunological factors. However, the magnitude of population differences in immune responses to SARS-CoV-2 and the mechanisms underlying such variation remain unknown. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells from 222 healthy donors of various ancestries stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces a weaker, but more heterogeneous interferon-stimulated gene activity than influenza A virus, and a unique pro-inflammatory signature in myeloid cells. We observe marked population differences in transcriptional responses to viral exposure that reflect environmentally induced cellular heterogeneity, as illustrated by higher rates of cytomegalovirus infection, affecting lymphoid cells, in African-descent individuals. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell proportions on population differences in immune responses, with genetic variants having a narrower but stronger effect on specific loci. Additionally, natural selection has increased immune response differentiation across populations, particularly for variants associated with SARS-CoV-2 responses in East Asians. We document the cellular and molecular mechanisms through which Neanderthal introgression has altered immune functions, such as its impact on the myeloid response in Europeans. Finally, colocalization analyses reveal an overlap between the genetic architecture of immune responses to SARS-CoV-2 and COVID-19 severity. Collectively, these findings suggest that adaptive evolution targeting immunity has also contributed to current disparities in COVID-19 risk.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.22.517073v1" target="_blank">Environmental and genetic drivers of population differences in SARS-CoV-2 immune responses</a>
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<li><strong>Modeling COVID-19 in different countries as sequences of SI waves</strong> -
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The COVID-19 pandemic has been a huge challenge worldwide for many institutions, researchers, national health organizations, and the pharmaceutical industry. As natural scientists and engineers, we attempted to contribute by calculating models and analyzing data to keep track of the pandemic. While a frequent goal is to predict the next pandemic wave by considering all influencing parameters, we examined methods to calculate a model course of the entire pandemic. This is done by reconstructing the course of infections into multiple model waves that sum up into a pandemic model that is close to the real course. The model wave parameters are varied by an algorithm, such as the Excel solver, to minimize the difference between the real and model courses. By reconstructing the course of infections using the commonly known SIR model, we found that the calculated model parameters were ambiguous and difficult to interpret. In contrast, we found that sequenced SI model waves provide an astonishing precise digital representation of the pandemic course. Until November 2022, we found between six and 16 waves (depending on the country) in each of the 14 countries investigated. The calculated parameters are easy to interpret and are comparable between different waves and countries. These wave parameters may be correlated with the virus types and measures in each country by other researchers. New waves are detectable early as they show a certain deviation from the actual model wave. After the maximum of the last real wave, the model indicates the further procedure for the pandemic course.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.22.22282631v1" target="_blank">Modeling COVID-19 in different countries as sequences of SI waves</a>
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<li><strong>One-day preoperative systemic treatment regimen outcompetes five-day regimen in potentially resectable esophageal squamous cancer</strong> -
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Introduction The current standard-of-care treatment for locally advanced esophageal squamous cell carcinoma (ESCC) is preoperative chemoradiotherapy.1 However, most ESCC patients in China are from economically underdeveloped areas 2. The shortage of medical resources exhaust the willingness of such patients to receive radiotherapy. Therefore, neoadjuvant chemotherapy alone is a preferred option in Eastern Asia. The one-day platinum plus paclitaxel (pla/pac) regimen is commonly used in China, while the five-day platinum plus 5-fluorouracil (5FU-based) regimen is preferred in other countries.3 Especially in the context of the COVID-19 pandemic, how to deliver timely and effective treatment for cancer patients has become a huge challenge.4 Fortunately, The effectiveness of immunochemotherapy is encouraging. We compared the effectiveness among the one-day immunochemotherapy regimen, the one-day chemotherapy regimen and the five-day chemotherapy regimen in locally advanced ESCC patients treated with preoperative systemic treatment (POST). Methods We retrospectively analyzed locally advanced ESCC patients who had received POST from January 2012 to September 2021 at the Department of Thoracic Surgery, Guangdong Provincial Peoples9 Hospital. The clinical and follow-up data were collected and analyzed according to 3 regimens including 5FU-based regimen which contains docetaxel+platinum+5-FU and platinum+5-FU regimens (5FU-based group), pla/pac regimen and pla/pac plus PD-1 inhibitor regimen (pla/pac/ICI). Complete response and partial response were defined as the objective response rate (ORR) per RECIST1.1 5. Categorical and continuous variables were analyzed by Chi-square and One-way ANOVA respectively, and overall survival (OS) was assessed using Kaplan-Meier analysis. Statistical analysis was performed using SPSS v26 (Inc, Chicago, Illinois) and R, and a P value less than 0.05 was considered statistically significant. Results A total of 395 POST-treated ESCC patients were enrolled, including 72 in the 5FU-based group, 168 in the pla/pac group, and 155 in the pla/pac/ICI group, and the mean follow-up time were 32.2, 44.2 and 14.3 months, respectively. There was no statistical difference in the baseline data among the three groups except POST cycles (Table). As shown in the Figure 1A, the pla/pac/ICI group had the greatest benefit, with an ORR of 63.2% (P < 0.05) and a surgery conversion rate of 85.2% (P < 0.05). Moreover, the ypT0 or ypTis rate in the pla/pac/ICI group was significantly higher than that in 5FU-based and pla/pac groups. Furthermore, pla/pac/ICI group acquired a better short-term OS than the other groups (one-year OS: pla/pac/ICI 93.6% vs. pla/pac 87.4% vs. 5FU-based 70.5%, Figure 1B). Discussion The COVID-19 pandemic has caused considerable consumption of medical resourse and cancer patients bear the brunt of delays in the interruption of medical care during the long treatment period4. Thus, it is urgent to deliver more effective and time-saving treatment. In this study, we demonstrated that the one-day pla/pac/IC group regimen has obvious clinical advantage over one-day pla/pac and five-day 5FU-based regimen in terms of radiological/pathological tumor response, as well as long-term overall survival. Taken both time cost and efficacy into consideration, the one-day pla/pac/IC regimen migth be a more favorable option in treating locally advanced ESCC. Despite exciting results, patients treated with immunotherapy shoulder great financial burden. Our results showed that there were no significant differences in the surgical conversion rate and response rate between one-day pla/pac and five-day 5FU-based group. Furthermore, the pla/pac group showed better survival benefits than 5FU-based group. The one-day pla/pac regimen might be an better alternative until affordable immunotherapy could benefit the whole population. Conclusion In the context of the COVID-19 pandemic, one-day immunochemotherapy should be considered because it may yield higher response rates, bring better overall survival as well as significantly reduce the risk of treatment interruption. If immunotherapy is not available, the 1-day pla/pac regimen is also an effective and timely alternative.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282548v1" target="_blank">One-day preoperative systemic treatment regimen outcompetes five-day regimen in potentially resectable esophageal squamous cancer</a>
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<li><strong>Susceptibility-Weighted Magnetic Resonance Imaging Highlights Brain Alterations in COVID Recovered Patients.</strong> -
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The increasing number of reports of mild to severe psychological, behavioral, and cognitive sequelae in COVID-19 survivors motivates a need for a thorough assessment of the neurological effects of the disease. In this regard, we have conducted a neuroimaging study to understand the neurotropic behavior of the coronavirus. We hypothesize that the COVID-recovered subjects have developed alterations in the brain which can be measured through susceptibility differences in various regions of the brain when compared to healthy controls (HCs). Hence, we performed our investigations on susceptibility-weighted imaging (SWI) volumes. Fatigue, being of the most common symptoms of Long COVID, has also been studied in this work. SWI volumes of 46 COVID and 30 HCs were included in this study. The COVID patients were imaged within six months of their recovery. We performed an unpaired two-sample t-test over the pre-processed SWI volumes of both groups and multiple linear regression was performed to observe group differences and correlation of fatigue with SWI values. The group analysis showed that COVID recovered subjects had significantly higher susceptibility imaging values in regions of the frontal lobe and the brain stem. The clusters obtained in the frontal lobe primarily show differences in the white matter regions. The COVID group also demonstrated significantly higher fatigue levels than the HC group. The regression analysis on the COVID group yielded clusters in the anterior cingulate gyrus and midbrain, which exhibited negative correlations with fatigue scores. This study suggests an association of Long COVID with prolonged effects on the brain and also indicates the viability of the SWI modality for analysis of post-COVID symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282600v1" target="_blank">Susceptibility-Weighted Magnetic Resonance Imaging Highlights Brain Alterations in COVID Recovered Patients.</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>A Study on Voluntary Routine COVID-19 Self-testing in Mizoram, India.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: COVID-19 Self testing and related messaging<br/><b>Sponsors</b>: PATH; UNITAID; Zoram Medical College (ZMC); Pacchunga University College; Association for Leprosy Education Rehabilitation & Treatment India (ALERT India); Government of Mizoram<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate EDP-235 in Non-hospitalized Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: EDP-235; Drug: Placebo<br/><b>Sponsor</b>: Enanta Pharmaceuticals, Inc<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of RAY1216 Tablets Compared With Placebo in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: RAY1216; Drug: Placebo<br/><b>Sponsor</b>: Guangdong Raynovent Biotech Co., Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The LAVA (Lateral Flow Antigen Validation and Applicability) 2 Study for COVID-19</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Diagnostic Test: Innova Lateral Flow Test<br/><b>Sponsor</b>: Alder Hey Children’s NHS Foundation Trust<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Q-POC SARS-CoV-2 Assay COVID-19 Clinical Evaluation</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Diagnostic Test: RT-PCR Test; Diagnostic Test: Real-time PCR Test<br/><b>Sponsors</b>: QuantuMDx Group Ltd; EDP Biotech; Paragon Rx Clinical; PathAI; PRX Research and Development<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Acute Rehabilitation in Patients With COVID-19 Pneumonia</strong> - <b>Conditions</b>: COVID-19; Rehabilitation; Physical Medicine<br/><b>Intervention</b>: Procedure: Acute rehabilitation program<br/><b>Sponsor</b>: Institut za Rehabilitaciju Sokobanjska Beograd<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>Enhancing Protection Against Influenza and COVID-19 for Pregnant Women and Medically at Risk Children</strong> - <b>Conditions</b>: Influenza; COVID-19<br/><b>Intervention</b>: Behavioral: Nudge<br/><b>Sponsor</b>: University of Adelaide<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>A Trial Evaluate the Immunogenicity and Safety of Recombinant COVID-19 Omicron-Delta Variant Vaccine (CHO Cell)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Omicron-Delta Recombinant Novel Coronavirus Protein Vaccine (CHO cells); Biological: Recombinant Novel Coronavirus Protein Vaccine (CHO cells)<br/><b>Sponsor</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.<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>COVID-19 Antibody Responses in Cystic Fibrosis</strong> - <b>Conditions</b>: COVID-19; Cystic Fibrosis<br/><b>Intervention</b>: Biological: Blood sample<br/><b>Sponsors</b>: Hospices Civils de Lyon; Queen’s University, Belfast<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>Message Communicating Latest Data on COVID Transmission in Patient’s Area</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</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>Message From Local Pharmacy Team</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</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>Planning Message Recommending Same Time/Location as Last Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</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>Message Offering Free Round Trip Ride-Share Ride to Pharmacy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</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>Message Encouraging Vaccination in Preparation for the Holidays</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</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>Safety, Tolerability, and Immunogenicity of Trivalent Coronavirus Vaccine Candidate VBI-2901e With E6020 Adjuvant</strong> - <b>Conditions</b>: COVID-19; Coronavirus Infections<br/><b>Intervention</b>: Biological: VBI-2901e<br/><b>Sponsor</b>: VBI Vaccines Inc.<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The search for new efficient inhibitors of SARS-COV-2 through the <em>De novo</em> drug design developed by artificial intelligence</strong> - The pandemic caused by Sars-CoV-2 is a viral infection that has generated one of the most significant health problems worldwide. Previous studies report the main protease (Mpro) as a potential target for this virus, as it is considered a crucial enzyme in mediating replication and viral transcription. This work presented the construction of new bioactive compounds for possible inhibition. The De novo molecular design of drugs method in the incremental construction of a ligant model within a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immune Repertoire Sequencing Reveals an Abnormal Adaptive Immune System in COVID-19 Survivors</strong> - Accumulating evidence suggests that SARS-CoV-2 impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of COVID-19. Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective cohort of 40 COVID-19 survivors with a six-month follow-up after hospital discharge. Immune repertoire sequencing revealed abnormal T- and B-cell…</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>Deregulation of the Expression of Beclin1 and Light Chain 3(LC3), Autophagy-Related Genes, in COVID-19 Patients</strong> - Background: The autophagy machinery is reported to be employed by Coronaviruses during their replication. Beclin-1 (BECN1) and protein 1 light chain 3 (LC3) are two key elements in the autophagy process, and their inhibition can prevent the replication of some coronaviruses in vitro. Here, we aimed to investigate the expression levels of Beclin-1 and LC3 in COVID-19 patients and healthy controls, hoping to find new therapeutic targets. Methods: This cross-sectional study was conducted in Imam…</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>Ginseng as a Key Immune Response Modulator in Chinese Medicine: From Antipandemic History to COVID-19 Management</strong> - The cytokine storm plays an indispensable role in the severe and critical illness and death of the COVID-19 vulnerable population. Thus, suppressing the cytokine storm is of great significance. Ginseng is a traditional Chinese herb originally used for improving physiological conditions and ameliorating disease. Common throughout the history of ancient Chinese medicine is utilizing ginseng as a major ingredient to successfully fight various pandemics, and the most famous decoction is Renshen…</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>Targeting of neuroinflammation by glibenclamide in Covid-19: old weapon from arsenal</strong> - In coronavirus disease 2019 (Covid-19) era, neuroinflammation may develop due to neuronal tropism of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or associated immune activation, cytokine storm, and psychological stress. SARS-CoV-2 infection and linked cytokine storm may cause blood-brain barrier (BBB) injury through which activated immune cells and SARS-CoV-2 can pass into the brain causing activation of glial cells with subsequent neuroinflammation. Different…</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>Human antibody recognition and neutralization mode on the NTD and RBD domains of SARS-CoV-2 spike protein</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Variants of concern (VOCs) such as Delta and Omicron have developed, which continue to spread the pandemic. It has been reported that these VOCs reduce vaccine efficacy and evade many neutralizing monoclonal antibodies (mAbs) that target the receptor binding domain (RBD) of the glycosylated spike (S) protein, which consists of the S1 and S2 subunits. Therefore, identification of optimal…</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>Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis</strong> - Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against coronavirus disease 2019 (COVID-19), especially in fragile patients. We aimed to systematically analyze the outcomes of patients with hematological malignancies who received vaccination and to identify specific groups with differences in outcomes. The primary end point was antibody response after full vaccination (2 doses of mRNA or one dose of vector- based vaccines). We…</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>Metformin Suppresses SARS-CoV-2 in Cell Culture</strong> - Comorbidities such as diabetes worsen COVID-19 severity and recovery. Metformin, a first-line medication for type 2 diabetes, has antiviral properties and certain studies have also indicated its prognostic potential in COVID-19. Here, we report that metformin significantly inhibits SARS-CoV-2 growth in cell culture models. First, a steady increase in AMPK phosphorylation was detected as infection progressed, suggesting its important role during viral infection. Activation of AMPK in Calu3 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>Protein-coding gene interaction network prediction of bioactive plant compound action against SARS-CoV-2: a novel hypothesis using bioinformatics analysis</strong> - This study aimed to verify the action of bioactive compounds from Brazilian plants on the leader genes involved in the SARS-CoV-2 pathway. The main human genes involved were identified in GeneCards and UNIPROT platforms, and an interaction network between leader genes was established in the STRING database. To design chemo-biology interactome networks and elucidate the interplay between genes related to the disease and bioactive plant compounds, the metasearch engine STITCH 3.1 was used. The…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The free fatty acid-binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron</strong> - As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid (FFA)-binding pocket. FFA binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2, 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>Transcription factor Nrf2 as a potential therapeutic target for COVID-19</strong> - The coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Critically ill patients with SARS-COV-2 infection frequently exhibit signs of high oxidative stress and systemic inflammation, which accounts for most of the mortality. Antiviral strategies to inhibit the pathogenic consequences of COVID-19 are urgently required. The nuclear factor erythroid 2-related transcription factor (Nrf2) is a transcription factor that is…</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>Single-center serological surveillance of SARS-CoV-2 in pregnant patients presenting to labor and delivery</strong> - CONCLUSION: A variable antibody response to SARS-CoV-2 in pregnancy among asymptomatic infections compared to symptomatic infections was found, the significance of which is unknown. Although transfer of transplacental neutralizing antibodies occurred, additional research is needed to determine how long maternal antibodies can protect the infant against SARS-CoV-2 infection.</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 comparative in-vitro study on antimicrobial efficacy of on-market alcohol-based hand washing sanitizers towards combating microbes and its application in combating Covid-19 global outbreak</strong> - The coronavirus disease 2019 (COVID-19) outbreak has created endless social, economic, and political fear in the global human population. Measures employed include frequent washing hands and using alcohol-based hand sanitisers and hand rubs as instant hand hygiene products. Due to the need to mitigate the pandermic, there is an increase in the local production of alcohol-based hand sanitisers, whose quality and efficacy against germs and the virus are questionable. Therefore, the current study…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The role of miRNAs in viral myocarditis, and its possible implication in induction of mRNA-based COVID-19 vaccines-induced myocarditis</strong> - BACKGROUND: Several reports of unheeded complications secondary to the current mass international rollout of SARS-COV-2 vaccines, one of which is myocarditis occurring with the FDA fully approved vaccine, Pfizer, and others.</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>Potential impacts of prolonged absence of influenza virus circulation on subsequent epidemics</strong> - BACKGROUND: During the first two years of the COVID-19 pandemic, the circulation of seasonal influenza viruses was unprecedentedly low. This led to concerns that the lack of immune stimulation to influenza viruses combined with waning antibody titres could lead to increased susceptibility to influenza in subsequent seasons, resulting in larger and more severe epidemics.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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