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<title>21 February, 2024</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>Prior exposure to malaria decreases SARS-CoV-2 mediated mortality in K18-hACE2 mice without influencing viral load in lungs</strong> -
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Abstract: Background: Epidemiological evidence for decreased prevalence and/or mortality due to SARS-CoV-2 infections in countries endemic for malaria have been reported. However, such associational studies in human population are limited by known and several unknown confounding factors. The current study, the first of its kind, was designed to seek experimental evidence to test the hypothesis if prior exposure to Plasmodial infections cross-protect against SARS-CoV-2 challenge infection in a murine model, K-18 human ACE2 transgenic mice. Methods: Mice that had recovered from Plasmodium chabaudi infection 40 days earlier were challenged with a virulent strain of SARS-CoV-2 and viral load in lungs as well as mortality were scored and compared with K18 hACE2 mice that had not experienced prior malaria. Results: The viral load in lungs 6 days post challenge were comparable in malaria recovered mice and controls suggesting no significant generation of anti-viral immunity. However, mice with prior malaria exposure were significantly protected against SARS-CoV-2 induced mortality. Significant differences were observed in several host immune responses between the two groups when cytokines, chemokines and transcription factors were quantified in lungs. The plasma levels of several cytokines and chemokines were also significantly different between the two groups. Conclusion: The results of the study suggest that prior exposure to malaria protects mice against viral induced mortality in K18 hACE2 transgenic mice challenged with a virulent isolate of SARS- CoV-2 in the absence of demonstrable host immunity inhibiting viral growth in lungs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.19.579434v1" target="_blank">Prior exposure to malaria decreases SARS-CoV-2 mediated mortality in K18-hACE2 mice without influencing viral load in lungs</a>
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<li><strong>Characterization of the SARS-CoV-2 BA.5 Variants in H11-K18-hACE2 Hamsters</strong> -
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This study aims to comprehensively characterize the SARS-CoV-2 BA.5 variants using K18 hACE2 transgenic mice and golden hamsters as model organisms. Previous research on SARS-CoV-2 has utilized both mouse and hamster models, leading to conflicting results concerning the virus's lethality. In our study, the finding suggests that H11-K18 hACE2 golden hamsters closely mimic the disease progression observed in human COVID-19 cases caused by BA.5 variants, demonstrating consistent severity and symptoms comparable to severe infections. Additionally, hamsters exhibit heightened respiratory viral replication, accurately reflecting the clinical viral kinetics observed in humans. The study emphasizes the critical importance of selecting an appropriate animal model for SARS-CoV-2 research, while also providing robust support for the hypothesis that BA.5 variants contribute to fatal outcomes in COVID-19 cases. These findings highlight the pivotal role of the golden hamster model in advancing our understanding of the pathogenic mechanisms underlying SARS-CoV-2 variants, as well as in the development of targeted therapeutic strategies.
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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/10.1101/2024.02.19.581112v1" target="_blank">Characterization of the SARS-CoV-2 BA.5 Variants in H11-K18-hACE2 Hamsters</a>
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<li><strong>Predicting Antibody and ACE2 Affinity for SARS-CoV-2 BA.2.86 and JN.1 with In Silico Protein Modeling and Docking</strong> -
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The emergence of the Omicron sublineage of SARS-CoV-2 virus BA.2.86 (nicknamed “Pirola”) has raised concerns about its potential impact on public health and personal health as it has many mutations with respect to previous variants. We conducted an in silico analysis of neutralizing antibody binding to BA.2.86. Selected antibodies came from patients who were vaccinated and/or infected. We predicted binding affinity between BA.2.86 and antibodies. We also predicted the binding affinity between the same antibodies and several previous SARS-CoV2 variants (Wuhan and Omicron descendants BA.1, BA.2, and XBB.1.5). Additionally, we examined binding affinity between BA.2.86 and human angiotensin converting enzyme 2 (ACE2) receptor, a cell surface protein crucial for viral entry. We found no statistically significant difference in binding affinity between BA.2.86 and other variants, indicating a similar immune response. These findings contradict media reports of BA.2.86s high immune evasion potential based on its mutations. We discuss the implications of our findings and highlight the need for modeling and docking studies to go above and beyond mutation and basic serological neutralization analysis. Future research in this area will benefit from increased structural analyses of memory B-cell derived antibodies and should emphasize the importance of choosing appropriate samples for in silico studies to assess protection provided by vaccination and infection. This research contributes to understanding the BA.2.86 variants potential impact on public health. Moreover, we introduce new methodologies for predictive medicine in ongoing efforts to combat the evolving SARS-CoV-2 pandemic and prepare for other hazards.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568364v3" target="_blank">Predicting Antibody and ACE2 Affinity for SARS-CoV-2 BA.2.86 and JN.1 with In Silico Protein Modeling and Docking</a>
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<li><strong>Information bias of vaccine effectiveness estimation due to informed consent for national registration of COVID-19 vaccination</strong> -
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Background: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of non-consenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in the estimation of vaccine effectiveness (VE). Methods: National data were used for the period dominated by the SARS-CoV-2 Delta variant (11 July to 15 November 2021). VE ((1-relative risk)*100%) against COVID-19 hospitalization and ICU admission was estimated for individuals 12-49, 50-69, and ≥70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iteratively imputing corrected vaccination status. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected / corrected relative risk. Results: A total of 8,804 COVID-19 hospitalizations and 1,692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the non-consent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5-77.4) before to 85.9% (95% CI 84.7-87.1) after correction (absolute bias -10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2-90.8) before and 93.7% (95% CI 92.2-94.9) after correction (absolute bias -5.0 percentage point, relative bias 1.79). Conclusions: VE estimates can be substantially biased with modest non-consent percentages for registration of vaccination. Data on covariate specific non-consent percentages should be available to correct this bias.
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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/10.1101/2023.05.23.23290384v2" target="_blank">Information bias of vaccine effectiveness estimation due to informed consent for national registration of COVID-19 vaccination</a>
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<li><strong>Robust SARS-CoV-2 Neutralizing Antibodies Sustained through Three Months Post XBB.1.5 mRNA Vaccine Booster</strong> -
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SARS-CoV-2-neutralizing antibodies were substantially expanded one month after a shot of XBB.1.5 monovalent mRNA vaccine (XBB.1.5 MV) booster, but the durability of this response remained unknown. Here, we addressed this question by performing neutralization assays on four viral variants (D614G, BA.5, XBB.1.5, and JN.1) using sera from 39 adult participants obtained at ~1 month and ~3 months post an XBB.1.5 MV booster. Our findings indicate that the resultant neutralizing antibody titers were robust and generally maintained at stable levels for the study period, similar to those following XBB infection. Importantly, this durability of neutralizing antibody titers contrasts with the decline observed after a booster of the original monovalent or BA.5 bivalent mRNA vaccine. Our results are in line with the recent national data from the Centers for Disease Control and Prevention, showing the efficacy against symptomatic SARS-CoV-2 infection is sustained for up to 4 months after an XBB.1.5 MV booster.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.16.580687v1" target="_blank">Robust SARS-CoV-2 Neutralizing Antibodies Sustained through Three Months Post XBB.1.5 mRNA Vaccine Booster</a>
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<li><strong>COVID-19 during pregnancy alters circulating extracellular vesicle cargo and their effects on trophoblast</strong> -
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SARS-CoV-2 infection and the resulting coronavirus disease (COVID-19) complicate pregnancies as the result of placental dysfunction which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests maternal response to infection is responsible for placental dysfunction. We hypothesized that maternal circulating extracellular vesicles (EVs) are altered by COVID-19 during pregnancy and contribute to placental dysfunction. To examine this, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their functional effect on trophoblast cells in vitro. We found the timing of infection is a major determinant of the effect of COVID-19 on circulating EVs. Additionally, we found differentially expressed EV mRNA cargo in COVID-19 groups compared to Controls that regulates the differential gene expression induced by COVID-19 in the placenta. In vitro exposure of trophoblasts to EVs isolated from patients with an active infection, but not EVs isolated from Controls, reduced key trophoblast functions including hormone production and invasion. This demonstrates circulating EVs from subjects with an active infection disrupt vital trophoblast function. This study determined that COVID-19 has a long-lasting effect on circulating EVs and circulating EVs are likely to participate in the placental dysfunction induced by COVID-19.
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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/10.1101/2024.02.17.580824v1" target="_blank">COVID-19 during pregnancy alters circulating extracellular vesicle cargo and their effects on trophoblast</a>
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<li><strong>A Genome-Wide Arrayed CRISPR Screen Reveals PLSCR1 as an Intrinsic Barrier to SARS-CoV-2 Entry</strong> -
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Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence SARS-CoV-2 infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of COVID-19 patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 over-expression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Our study contributes to understanding the association between PLSCR1 variants and severe COVID-19 cases reported in a recent GWAS.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.16.580725v1" target="_blank">A Genome-Wide Arrayed CRISPR Screen Reveals PLSCR1 as an Intrinsic Barrier to SARS-CoV-2 Entry</a>
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<li><strong>Non-Consensual Sex among Japanese Women in the COVID-19 Pandemic: A Large-Scale Nationwide Survey-Based Study</strong> -
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Background: Non-consensual sex including rape and sexual assault has been a global concern and may have been influenced by the COVID-19 pandemic, however the information on this topic is limited. Therefore, our objective was to survey the incidence rate of non-consensual sex among Japanese women aged 15-79 years between April to September 2020, following the COVID-19 pandemic in Japan. Materials and Methods: We utilized the data obtained from a nationwide, cross-sectional internet survey conducted in Japan between August and September 2020. Sampling weights were applied to calculate national estimates, and multivariable logistic regression was performed to identify factors associated with non-consensual sex. Data was extracted from a cross-sectional, web-based, self-administered survey of approximately 2.2 million individuals from the general public, including in men and women. Results: Excluding men and responses with inconsistencies, the final analysis included 12,809 women participants, with 138 (1.1%) reporting experiencing non-consensual sex within a five-month period. Being aged 15–29 years and having a worsened mental or economic status were associated with experiencing non-consensual sex. Conclusions: Early intervention to prevent individuals from becoming victims of sexual harm should be extended to economically vulnerable and young women, especially during times of societal upheaval such as the COVID-19 pandemic. Additionally, Japan should prioritize the implementation of comprehensive education on the concept of sexual consent.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.16.24302967v1" target="_blank">Non-Consensual Sex among Japanese Women in the COVID-19 Pandemic: A Large-Scale Nationwide Survey-Based Study</a>
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<li><strong>RISK OF THROMBOEMBOLISM AFTER COVID-19 VACCINATION AND COVID-19 INFECTION</strong> -
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Background: Vaccine safety monitoring systems worldwide have reported cases of venous thromboembolism and arterial thromboembolism following a COVID-19 vaccination. However, evidence shows that the association between thromboembolism and SARS-CoV-2 infection is stronger, compared to SARS-CoV-2 vaccination. Hence, weighing the risks and benefits of vaccination should also encounter the roles of vaccination in reducing infection rate, and potentially indirectly lowering the risk of thromboembolism caused by infection. Methods: We conducted a self-controlled case series study (SCCS) from Dec 1st 2020 to 31st August 2022 (before the bivalent vaccine was available) to examinate the association between the first two doses Pfizer/Moderna vaccination and thrombotic events among patients in Corewell Health East (CHE, formerly known as Beaumont Health) healthcare system. We also investigated the effect SARS-CoV-2 infection on the risk of thrombosis events and observed a significant increased risk using the SCCS design. However, because of misclassification bias, SCCS indeed overestimated incidence rate ratio (IRR) of acute event after infection, we then proposed a case-control study addressing this misclassification issues and obtained odd ratio comparing effect of exposure on thrombosis and a subset of controls group. Finally, we analyzed the risk of thromboembolism between vaccinated and unvaccinated groups by a simple diagram, explaining possible factors that affects the probability of experiencing an acute thromboembolism event after a COVID-19 vaccination. Results: Using EHR data at Corewell East, we found an increased risk of thrombosis after the first two doses of COVID-19 vaccination, with incidence rate ratios after the first dose is 1.16 (CI: [1.04, 1.29]), and after the second dose of 1.19 (CI: [1.07,1.32]). The association between thromboembolism and SARS-Cov-2 infection depends on prior vaccination status, as the conditional OR among unvaccinated and vaccinated groups are 1.77 (CI: [1.48, 2.1]) and 1.34 (CI: [1.09, 1.66]) respectively. Encountering the vaccine efficacy (VE), receiving the COVID-19 vaccine decreases the risk of thromboembolism, and the benefits of COVID-19 vaccines are much stronger in the period of high infection rate.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302535v1" target="_blank">RISK OF THROMBOEMBOLISM AFTER COVID-19 VACCINATION AND COVID-19 INFECTION</a>
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<li><strong>A retrospective study of the effects of COVID-19 Non-pharmaceutical interventions on Influenza in Canada</strong> -
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The COVID-19 pandemic had a significant impact on endemic respiratory illnesses. Through behavioural changes in populations and government policy, mainly through non-pharmaceutical interventions (NPIs), Canada saw historic lows in the number of Influenza A cases from 2020 through 2022. In this study, we use historical influenza A data for Canada and three provincial jurisdictions within Canada: Ontario, Quebec and Alberta to quantify the effects of these NPIs on influenza A. We aim to see which base parameters and derived parameters of an SIR model are most affected by NPIs. We find that the effective population size is the main driver of change, and discuss how these retrospective estimates can be used for future forecasting.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.16.24302930v1" target="_blank">A retrospective study of the effects of COVID-19 Non-pharmaceutical interventions on Influenza in Canada</a>
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<li><strong>No clear evidence for relationships of Apolipoprotein E genotype with measures of common infections in three UK cohorts</strong> -
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<i>APOE</i> genotype is the strongest genetic risk factor for late onset Alzheimer9s disease, with the ϵ2 and ϵ4 alleles decreasing and increasing risk relative to the ϵ3 allele, respectively. Although evidence has been conflicting, several common infections have been associated with Alzheimer9s disease risk, and interactions by <i>APOE</i> ϵ4 carriage have also been reported. Nevertheless, to date, no study has examined relationships between <i>APOE</i> genotype and measures of multiple common infections among large population-based studies. We investigated associations of <i>APOE</i> ϵ2 and ϵ4 carriage (i.e. non-carrier vs carrier) with serostatus and antibody titers to 14 common pathogens — encompassing herpesviruses, human polyomaviruses, <i>C.trachomatis</i>, <i>H.pylori</i>, and <i>T.gondii</i> — in three population—based cohorts (UK Biobank, National Survey of Health and Development, Southall and Brent Revisited). Pathogen serostatus was derived using validated antibody cut-offs for relevant antigens and included as an outcome assessing previous infection. Antibody titers were dichotomised among the seropositive subset for each antigen and included as binary outcomes assessing recent immunological responses. We conducted analyses in each cohort using mixed-models, including age, sex and genetic principal components as fixed-effects, and genetic relatedness as a random-effect. In secondary analyses, we additionally assessed i) relationships of <i>APOE</i> ϵ2 and ϵ4 dosage (i.e. number of copies of the allele of interest), and ii) relationships of <i>APOE</i> genotype with continuous antibody titers (rank-based inverse normal transformed). Findings were meta-analysed across cohorts (n=10,059) using random-effects models and corrected for multiple tests using the false discovery rate. We found no clear evidence of relationships between <i>APOE</i> genotype and serostatus or antibody titers to any pathogen, with no strong associations observed in any of our analyses following multiple testing correction. Investigations of <i>APOE</i> genotypes with the clinical manifestations of these pathogens, as well as expanding to include other viruses such as SARS-CoV-2, would also be warranted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.17.24302569v1" target="_blank">No clear evidence for relationships of Apolipoprotein E genotype with measures of common infections in three UK cohorts</a>
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<li><strong>Barriers in accessing healthcare during the COVID-19 pandemic: analysis of the Virus Watch community cohort study</strong> -
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Background: Differential barriers to accessing healthcare contribute to inequitable health outcomes. This study aims to describe the characteristics of individuals who experienced barriers, and what those barriers were, during the COVID-19 pandemic. Methods: We analysed data from Virus Watch: an online survey-based community study of households in England and Wales. The primary outcome was reported difficulty accessing healthcare in the previous year. Results: Minority ethnic participants reported difficulty accessing healthcare more than White British participants (41.6% vs 37%), while for migrants this was at broadly similar levels to non-migrants. Those living in the most deprived areas reported difficulty more than those living in the least deprived quintile (45.5% vs. 35.5%). The most frequently reported barrier was cancellation/disruption of services due to the COVID-19 pandemic (72.0%) followed by problems with digital or telephone access (21.8%). Ethnic minority participants, migrants, and those from deprived areas more commonly described 9insufficient flexibility of appointments9 and 9not enough time to explain complex needs9 as barriers. Conclusions: Minority ethnic individuals and those living in deprived areas were more likely to experience barriers to healthcare during the COVID-19 pandemic, and it is essential they are addressed as services seek to manage backlogs of care.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.15.24302762v1" target="_blank">Barriers in accessing healthcare during the COVID-19 pandemic: analysis of the Virus Watch community cohort study</a>
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<li><strong>A Gold Standard Dataset for Lineage Abundance Estimation from Wastewater</strong> -
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During the SARS-CoV-2 pandemic, genome-based wastewater surveillance sequencing has been a powerful tool for public health to monitor circulating and emerging viral variants. As a medium, wastewater is very complex because of its mixed matrix nature, which makes the deconvolution of wastewater samples more difficult. Here we introduce a gold standard dataset constructed from synthetic viral control mixtures of known composition, spiked into a wastewater RNA matrix and sequenced on the Oxford Nanopore Technologies platform. We compare the performance of eight of the most commonly used deconvolution tools in identifying SARS-CoV-2 variants present in these mixtures. The software evaluated was primarily chosen for its relevance to the CDC wastewater surveillance reporting protocol, which until recently employed a pipeline that incorporates results from four deconvolution methods: Freyja, kallisto, Kraken2/Bracken, and LCS. We also tested Lollipop, a deconvolution method used by the Swiss SARS-CoV2 Sequencing Consortium, and three recently-published methods: lineagespot, Alcov, and VaQuERo. We found that the commonly used software Freyja outperformed the other CDC pipeline tools in correct identification of lineages present in the control mixtures, and that the newer method VaQuERo was similarly accurate, with minor differences in the ability of the two methods to avoid false negatives and suppress false positives. These results provide insight into the effect of the tiling primer scheme and wastewater RNA extract matrix on viral sequencing and data deconvolution outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.15.24302811v1" target="_blank">A Gold Standard Dataset for Lineage Abundance Estimation from Wastewater</a>
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<li><strong>SARS-CoV-2 infection and Pregnancy outcome: A cross-sectional study from Eastern U.P. Population, India</strong> -
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Pregnant women with coronavirus infection are at a higher risk for severe diseases. In the present study, we evaluated and compared clinical characteristics and outcomes in pregnancy of normal females and females with SARS-CoV-2 infection. Our study was a cross-sectional study. The pregnant females were examined, their blood samples were taken for Covid Panel (D-Dimer, Ferritin, IL-6, CRP, PCT (Procalcitonin)); and oral-nasal swabs were taken for SARS-CoV-2 infection. Both SARS-CoV-2 positive and negative (control) females were followed up every trimester for any complication related to pregnancy. We found that females suffering from SARS-CoV-2 infection had reduced gestation periods, and had higher percentage of caesarean and pre-term delivery than SARS-CoV-2 negative females. Based on our findings, it appears that there exist close associations between SARS-CoV-2 infection in pregnant females and increased risk of reduced gestation periods, and spontaneous caesarean and pre-term delivery. However, more studies are still needed to validate present findings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.15.24302882v1" target="_blank">SARS-CoV-2 infection and Pregnancy outcome: A cross-sectional study from Eastern U.P. Population, India</a>
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<li><strong>Effectiveness of Omicron XBB.1.5 vaccine against SARS-CoV-2 Omicron XBB and JN.1 infection in a prospective cohort study in the Netherlands, October 2023 to January 2024</strong> -
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We estimated vaccine effectiveness (VE) of SARS-CoV-2 Omicron XBB.1.5 vaccination against self-reported infection between 9 October 2023 and 9 January 2024 in 23,895 XBB.1.5 vaccine-eligible adults who had previously received at least one booster. VE was 41% (95%CI:23-55) in 18-59-year-olds and 50% (95%CI:44-56) in 60-85-year-olds. Sequencing data in a subset of infections suggests immune escape of the emerging BA.2.86 (JN.1) variant from recent prior infection (OR:2.6; 95%CI:1.1-6.3) and, although not statistically significant, from XBB.1.5 vaccination (OR:1.6; 95%CI:0.9-2.9).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.15.24302872v1" target="_blank">Effectiveness of Omicron XBB.1.5 vaccine against SARS-CoV-2 Omicron XBB and JN.1 infection in a prospective cohort study in the Netherlands, October 2023 to January 2024</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>Treatment of Post-COVID With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 <br/><b>Interventions</b>: Drug: Hyperbaric oxygen <br/><b>Sponsors</b>: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk <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>World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt</strong> - <b>Conditions</b>: Mucormycosis; Rhinocerebral (Etiology); COVID-19 <br/><b>Interventions</b>: Procedure: debridment <br/><b>Sponsors</b>: Nasser Institute For Research and Treatment <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>Mindfulness-based Mobile Applications Program</strong> - <b>Conditions</b>: COVID-19; Cell Phone Use; Nurse; Mental Health <br/><b>Interventions</b>: Device: mindfulness-based mobile applications program <br/><b>Sponsors</b>: Yu-Chien Huang <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>Correlation of Antibody Response to COVID-19 Vaccination in Pregnant Woman and Transplacental Passage Into Cord Blood.</strong> - <b>Conditions</b>: Covid-19 <br/><b>Interventions</b>: Diagnostic Test: COVID-19 Spike Protein IgG Quantitative Antibody (CMIA) <br/><b>Sponsors</b>: Vachira Phuket Hospital <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>UNAIR Inactivated COVID-19 Vaccine as Homologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines; COVID-19 Virus Disease <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia; Indonesia-MoH <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>High-definition Transcranial Direct Current Ctimulation and Chlorella Pyrenoidosa to Reduce Cardiovascular Risk</strong> - <b>Conditions</b>: Cardiovascular Diseases; Long Covid19 <br/><b>Interventions</b>: Other: High Definition-transcranial Direct Current Stimulation; Dietary Supplement: Chlorella Pyrenoidosa <br/><b>Sponsors</b>: Federal University of Paraíba; City University of New York <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>Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: CD40.RBDv vaccin (SARS-Cov2 Vaccin) <br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; LinKinVax; Vaccine Research Institute (VRI), France <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>SGB for COVID-induced Parosmia</strong> - <b>Conditions</b>: COVID-19-Induced Parosmia <br/><b>Interventions</b>: Drug: Stellate Ganglion Block; Drug: Placebo Sham Injection <br/><b>Sponsors</b>: Washington University School of Medicine <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>Investigating the Effectiveness of Vimida</strong> - <b>Conditions</b>: Long COVID; Post COVID-19 Condition <br/><b>Interventions</b>: Behavioral: vimida <br/><b>Sponsors</b>: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock <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 Physiotherapy Via Video Calls in Patients With COVID-19</strong> - <b>Conditions</b>: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function <br/><b>Interventions</b>: Behavioral: Exercise training <br/><b>Sponsors</b>: Chulabhorn Hospital <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise session; Behavioral: Control session <br/><b>Sponsors</b>: University of Nove de Julho <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>Reducing Respiratory Virus Transmission in Bangladeshi Classrooms</strong> - <b>Conditions</b>: SARS-CoV2 Infection; Influenza Viral Infections; Respiratory Viral Infection <br/><b>Interventions</b>: Device: Box Fan; Device: UV Germicidal Irradiation Lamp Unit; Device: Combined: Box Fan and UV Germicidal Irradiation Lamp Units <br/><b>Sponsors</b>: Stanford University; Centers for Disease Control and Prevention; International Centre for Diarrhoeal Disease Research, Bangladesh <br/><b>Not yet 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>Role of epinephrine in attenuating cytokine storm, decreasing ferritin, and inhibiting ferroptosis in SARS-CoV-2</strong> - CONCLUSION: Epinephrine may attenuate CS and inhibit ferroptosis which is an iron-dependent, non-apoptotic mode of cell death. Epi interacts with ferric and/or ferrous iron and built a stable complex that impedes activation of beta-adrenergic receptors. Epi may cause marked decrease of ferritin and other inflammatory markers. Epi may be used to decrease iron overload which is associated with many medical diseases like type 2 diabetes mellitus and cardiometabolic diseases such as coronary heart…</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>Challenges Experienced by Saudi Patients With Cancer and Their Family Caregivers in Using Digital Healthcare Technology Platforms in the COVID-19 Pandemic</strong> - COVID-19 has provided a unique boost to the use of digital healthcare technology, putting many vulnerable people at risk of digital exclusion. To promote digital healthcare equity, it is important to identify the challenges that may inhibit cancer patients and family caregivers from benefiting from such technology. This study explored the challenges that cancer patients and family caregivers experience in using digital healthcare technology platforms during the COVID-19 pandemic. A qualitative…</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>Inhibition of SARS-CoV-2 replication by a ssDNA aptamer targeting the nucleocapsid protein</strong> - The nucleocapsid protein of SARS-CoV-2 plays significant roles in viral assembly, immune evasion, and viral stability. Due to its immunogenicity, high expression levels during COVID-19, and conservation across viral strains, it represents an attractive target for antiviral treatment. In this study, we identified and characterized a single-stranded DNA aptamer, N-Apt17, which effectively disrupts the liquid-liquid phase separation (LLPS) mediated by the N protein. To enhance the aptamer’s…</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>Transcriptional regulation of SARS-CoV-2 receptor ACE2 by SP1</strong> - Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The induction of ACE2 expression may serve as a strategy by SARS-CoV-2 to facilitate its propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. Using 45 different luciferase reporters, the transcription factors SP1 and HNF4α were found to positively and negatively regulate ACE2 expression, respectively,…</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>Anemoside B4 inhibits SARS-CoV-2 replication <em>in vitro</em> and <em>in vivo</em></strong> - CONCLUSION: Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.</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 host-virus interactions: in silico analysis of the binding of human milk oligosaccharides to viral proteins involved in respiratory infections</strong> - Respiratory viral infections, a major public health concern, necessitate continuous development of novel antiviral strategies, particularly in the face of emerging and re-emerging pathogens. In this study, we explored the potential of human milk oligosaccharides (HMOs) as broad-spectrum antiviral agents against key respiratory viruses. By examining the structural mimicry of host cell receptors and their known biological functions, including antiviral activities, we assessed the ability of HMOs…</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>Integrated network pharmacology and experimental validation-based approach to reveal the underlying mechanisms and key material basis of Jinhua Qinggan granules against acute lung injury</strong> - CONCLUSIONS: In summary, our finding clarified the underlying mechanisms and material basis of JHQG therapy for ALI by integrated network pharmacology and experimental validation-based strategy.</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>Molnupiravir inhibits human norovirus and rotavirus replication in 3D human intestinal enteroids</strong> - Human norovirus (HuNoV) and human rotavirus (HRV) are the leading causes of gastrointestinal diarrhea. There are no approved antivirals and rotavirus vaccines are insufficient to cease HRV associated mortality. Furthermore, treatment of chronically infected immunocompromised patients is limited to off-label compassionate use of repurposed antivirals with limited efficacy, highlighting the urgent need of potent and specific antivirals for HuNoV and HRV. Recently, a major breakthrough in the 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>Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways</strong> - Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of a quantitative ELISA for SARS-CoV-2 vaccine candidate, NDV-HXP-S, with CpG 1018® adjuvant</strong> - NDV-HXP-S is a Newcastle disease virus (NDV) vectored vaccine candidate which expresses the S-antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This vaccine candidate is under evaluation in human clinical studies with and without cytosine phosphate guanine (CpG) 1018® adjuvant. Existing potency methods for NDV-HXP-S do not allow for quantification of the S-antigen when the adjuvant is present. To support evaluation of NDV-HXP-S with CpG 1018® adjuvant, an inhibition…</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><em>Syringa reticulata</em> potently inhibits the activity of SARS-CoV-2 3CL protease</strong> - The ongoing coronavirus infectious disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still urgently requires effective treatments. The 3C-like (3CL) protease of SARS-CoV-2 is a highly conserved cysteine protease that plays an important role in the viral life cycle and host inflammation, providing an ideal target for developing broad-spectrum antiviral drugs. Herein, we describe the discovery of a large number of herbs mainly produced 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>A Case Report of Drug Interactions Between Nirmatrelvir/Ritonavir and Tacrolimus in a Patient With Systemic Lupus Erythematosus</strong> - Nirmatrelvir/ritonavir is a treatment for COVID-19 consisting of nirmatrelvir, which has anti-SARS-CoV-2 activity, and ritonavir, a booster to maintain blood levels. Ritonavir is known to be a potent inhibitor of cytochrome P450 3A (CYP3A), and interactions with CYP3A-metabolized drugs, such as the immunosuppressant tacrolimus, can be problematic. Ritonavir’s inhibition of CYP3A is irreversible due to covalent binding, and its inhibitory effects are expected to persist until replaced by new…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Second Boost of Omicron SARS-CoV-2 S1 Subunit Vaccine Induced Broad Humoral Immune Responses in Elderly Mice</strong> - Currently approved COVID-19 vaccines prevent symptomatic infection, hospitalization, and death from the disease. However, repeated homologous boosters, while considered a solution for severe forms of the disease caused by new SARS-CoV-2 variants in elderly individuals and immunocompromised patients, cannot provide complete protection against breakthrough infections. This highlights the need for alternative platforms for booster vaccines. In our previous study, we assessed the boost effect of 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>Preparation and characterization of a fluorogenic ddRFP-M biosensor as a specific SARS-CoV-2 main protease substrate</strong> - The conventional peptide substrates of SARS-CoV-2 main protease (Mpro) are frequently associated with high cost, unstable kinetics, and multistep synthesis. Hence, there is an urgent need to design affordable and stable Mpro substrates for pharmacological research. Herein, we designed a functional Mpro substrate based on a dimerization-dependent red fluorescent protein (ddRFP) for the evaluation of Mpro inhibitors in vitro. The codon-optimized DNA fragment encoding RFP-A(1) domain, a polypeptide…</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>Neutralizing antibodies to block viral entry and for identification of entry inhibitors</strong> - Neutralizing antibodies (NAbs) are naturally produced by our immune system to combat viral infections. Clinically, neutralizing antibodies with potent efficacy and high specificity have been extensively used to prevent and treat a wide variety of viral infections, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Immunodeficiency Virus (HIV), Dengue Virus (DENV) and Hepatitis B Virus (HBV). An overwhelmingly large subset of clinically effective NAbs operates by…</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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