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<title>21 January, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses</strong> -
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<div>
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RNA viruses continue to remain a clear and present threat for potential pandemics due to their rapid evolution. To mitigate their impact, we urgently require antiviral agents that can inhibit multiple families of disease-causing viruses, such as arthropod-borne and respiratory pathogens. Potentiating host antiviral pathways can prevent or limit viral infections before escalating into a major outbreak. Therefore, it is critical to identify broad-spectrum antiviral agents. We have tested a small library of innate immune agonists targeting pathogen recognition receptors, including TLRs, STING, NOD, Dectin and cytosolic DNA or RNA sensors. We observed that TLR3, STING, TLR8 and Dectin-1 ligands inhibited arboviruses, Chikungunya virus (CHIKV), West Nile virus (WNV) and Zika virus, to varying degrees. Cyclic dinucleotide (CDN) STING agonists, such as cAIMP, diABZI, and 2’,3’-cGAMP, and Dectin-1 agonist scleroglucan, demonstrated the most potent, broad-spectrum antiviral function. Comparative transcriptome analysis revealed that CHIKV-infected cells had larger number of differentially expressed genes than of WNV and ZIKV. Furthermore, gene expression analysis showed that cAIMP treatment rescued cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provided protection against CHIKV in a CHIKV-arthritis mouse model. Cardioprotective effects of synthetic STING ligands against CHIKV, WNV, SARS-CoV-2 and enterovirus D68 (EV-D68) infections were demonstrated using human cardiomyocytes. Interestingly, the direct-acting antiviral drug remdesivir, a nucleoside analogue, was not effective against CHIKV and WNV, but exhibited potent antiviral effects against SARS-CoV-2, RSV (respiratory syncytial virus), and EV-D68. Our study identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses, which can be rapidly deployed to prevent or mitigate future pandemics.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.19.524824v1" target="_blank">Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses</a>
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</div></li>
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<li><strong>Elective Surgery Before, During and After the COVID-19 Pandemic in England 2015 - 2022: A Database Study</strong> -
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<div>
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Objective To track elective surgery activity before, during and after the COVID-19 pandemic in England. To examine for hypothesised differences in use of independent vs NHS hospitals, and more urgent vs less urgent operations over the pre- and post-COVID time windows. Design We extracted data from the Hospital Episodes Statistics database from 1st April 2015 to 30th April 2022. This database contains all emergency and elective patient admissions, outpatient appointments and A&E attendances funded by the NHS in England. Setting NHS and Independent hospitals in England. Participants Adult patients (over 18 years) admitted for elective surgery between April 2015 and April 2022, who were classified as being in priority groups 3 or 4. Main Outcomes Total operations, operations by hospital type, and NHS England priority ranking. Results The data show that there was a large reduction in the number of elective operations during lockdown with incomplete recovery thereafter. Also the proportion of more urgent surgeries and surgeries in independent hospitals increased in the post-COVID vs pre-COVID time windows. Conclusion Under conditions of high-demand, higher value elective surgery procedures are awarded increasing priority and the Independent sector bears a larger share of the load.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.20.23284826v1" target="_blank">Elective Surgery Before, During and After the COVID-19 Pandemic in England 2015 - 2022: A Database Study</a>
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</div></li>
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<li><strong>Application of Elastic Net Regression for Modeling COVID-19 Sociodemographic Risk Factors</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Objectives: COVID-19 has been at the forefront of global concern since its emergence in December of 2019. Determining the social factors that drive case incidence is paramount to mitigating disease spread. We gathered data from the Social Vulnerability Index (SVI) along with Democratic voting percentage to attempt to understand which county-level sociodemographic metrics had a significant correlation with case rate for COVID-19. Methods: We used elastic net regression due to issues with variable collinearity and model overfitting. Our modelling framework included using the ten Health and Human Services regions as submodels for the two time periods 22 March 2020 to 15 June 2021 (prior to the Delta time period) and 15 June 2021 to 1 November 2021 (the Delta time period). Results: Statistically, elastic net improved prediction when compared to multiple regression, as almost every HHS model consistently had a lower root mean square error (RMSE) and satisfactory R2 coefficients. These analyses show that the percentage of minorities, disabled individuals, individuals living in group quarters, and individuals who voted Democratic correlated significantly with COVID-19 attack rate as determined by Variable Importance Plots (VIPs). Conclusions: The percentage of minorities per county correlated positively with cases in the earlier time period and negatively in the later time period, which complements previous research. In contrast, higher percentages of disabled individuals per county correlated negatively in the earlier time period. Counties with an above average percentage of group quarters experienced a high attack rate early which then diminished in significance after the primary vaccine rollout. Higher Democratic voting consistently correlated negatively with cases, coinciding with previous findings regarding a partisan divide in COVID-19 cases at the county level. Our findings can assist policymakers in distributing resources to more vulnerable counties in future pandemics based on SVI.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.19.23284288v1" target="_blank">Application of Elastic Net Regression for Modeling COVID-19 Sociodemographic Risk Factors</a>
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</div></li>
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<li><strong>High proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world with multiple countries in East, Central, and West Africa having significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n=29) and from hospitalized Ugandan COVID-19 patients (n=3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population. The rates of cross-reactive T-cell populations in these Ugandans is higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.16.23284626v1" target="_blank">High proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses</a>
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</div></li>
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<li><strong>COVID-19 and Mental Health in China: Effects of Personality and Demographics</strong> -
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China was the first country affected by the COVID-19 virus and it reacted strongly in the first months of 2020. This paper presents new evidence on the deterioration in mental health in China between 2018 and 2020. Using two waves of the China Family Panel Studies (CFPS) we can follow the same individuals pre and during the pandemic periods. We find clear evidence of a moderate level of mental health deterioration between 2018 and 2020. The prevalence of severe cases of depression, measured using an eight-item version of the common CES-D scale, increased from 6.33% in 2018 to 7.54% in 2020; quantifiable as around a 19% increase. This deterioration is higher for individuals who are subject to strict lockdowns, about 0.3 symptoms more on average, and it is stronger among those who already reported symptoms of depression in the 2018 wave of data. The effects we find are larger for individuals with more open personalities: one standard deviation of the Openness trait corresponds to 0.08 more symptoms, while more Neurotic individuals do not seem to be more affected. Younger cohorts and individuals with lower levels of education are more affected. Males seem slightly more affected than females, although this difference is statistically non-significant.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.20.23284600v1" target="_blank">COVID-19 and Mental Health in China: Effects of Personality and Demographics</a>
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</div></li>
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<li><strong>Immunogenicity, Safety and Effectiveness of COVID-19 Pfizer-BioNTech (BNT162b2) mRNA Vaccination in Immunocompromised Adolescents and Young Adults: A systematic Review and Meta-Analyses</strong> -
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People with weak immune systems are more likely to develop severe COVID-19, less likely to be included in vaccine controlled studies but more likely to be under-vaccinated. We review post-marketing studies to examine the immunogenicity, safety and effectiveness of BNT162b2 vaccine in immunocompromised adolescents and young adults (AYA). We searched more than three international databases from 2020 to 30 May 2022 and used the ROBINS-I for bias assessment. Random effect model was used to estimate pooled proportion, log RR, and mean difference. Egger9s regression and Begg9s rank correlation were used to examine publication bias. 47 full texts were reviewed, and nine were included. Conditions studied were rheumatic diseases, diabetes mellitus, Down syndrome, solid tumours, neurodisability, and cystic fibrosis. Eight studies used cohort designs and one used cross-sectional designs. Europe led most of the investigations. Most studies had unclear risk of bias and none could rule out selection bias, ascertainment bias, or selective outcome reporting. The overall estimated proportion of combined local and systemic reactions after the first BNT162b2 vaccination was 30%[95% CI: 17-42%] and slightly rose to 32% [95% CI: 19-44%] after the second dose. Rheumatic illnesses had the highest rate of AEFI (40%[95% CI: 16-65%]), while cystic fibrosis had the lowest (27%[95% CI: 17%-38%]). Hospitalizations for AEFIs were rare. Healthy controls exhibited higher levels of neutralizing antibodies and measured IgG than immunocompromised AYA, although pooled estimations did not demonstrate a statistically significant difference after primary dose. BNT162b2 is safe and effective in immunocompromised AYA, with no significant difference to healthy controls. However, current evidence is low to moderate due to high RoB. Our research advocates for improving methodology in studies including specific AYA population.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.20.23284812v1" target="_blank">Immunogenicity, Safety and Effectiveness of COVID-19 Pfizer-BioNTech (BNT162b2) mRNA Vaccination in Immunocompromised Adolescents and Young Adults: A systematic Review and Meta-Analyses</a>
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</div></li>
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<li><strong>Frequency and Clinical Characteristics of Breakthrough Cases Post COVID-19 Vaccine and Predictive Risk Factors in College Students</strong> -
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BACKGROUND COVID-19 vaccines help protect against infection, severe illness, hospitalization and death. When someone who is vaccinated with either a primary series or a primary series plus a booster dose gets infected with the virus that causes COVID-19, it is referred to as a vaccine breakthrough infection. OBJECTIVES To assess the frequency and clinical characteristics of breakthrough cases of COVID-19 infection and to study the predictive risk factors. SUBJECTS&METHODS A cross-sectional study was carried out including 604 undergraduate medical and non-medical students in Iraq from 10th of August to 29th of September 2022. Data was collected via an online specific questionnaire and analyzed to estimate the frequency of COVID-19 breakthrough cases post vaccination, and number of doses of vaccine used. The association of different factors including age, gender, grade, body mass index, smoking, and comorbidity was also studied as predictive risk factors. We used the data to formulate tables, figures and perform statistical tests in IBM SPSS Statistics 25. RESULTS Mean age of study sample was 21.78 year (3.26) and 339 (56%) were females. In terms of COVID-19 vaccination data, 97 (16%) have received one dose, 459 (76%) two doses and 48 (8%) three doses. Regarding PCR test, 74 (12%) were positive after the first dose compared to 49 (8%) after the second dose. About the symptoms developed, the most frequent were fever in 372 (61.1%), unusual fatigue in 96 (15.79%), chills in 29 (4.77%) and persistent cough in 26 (4.28%). For most predictive factors, results were statistically insignificant. CONCLUSIONS In current study; demographic factors showed no statistically significant impact on prevalence of COVID-19 breakthrough cases. Despite this; number of participants who develop symptoms after the second dose of vaccine was high; and having 3 or more symptoms. About half of participants showed symptoms even after being fully vaccinated.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.20.23284814v1" target="_blank">Frequency and Clinical Characteristics of Breakthrough Cases Post COVID-19 Vaccine and Predictive Risk Factors in College Students</a>
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</div></li>
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<li><strong>Men have approximately 2- to 3-fold greater overdose mortality than women for synthetic opioids, heroin and psychostimulants including cocaine across the lifespan: Analysis of state-level CDC data for 2020-2021</strong> -
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Drug overdoses are an escalating cause of mortality in the United States, with potential sex differences across the lifespan. The objective of this study was to use state-level nationally representative data that includes the COVID-19 pandemic period to determine overdose mortality for specific drug categories across the lifespan of men and women. We used Centers for Disease Control and Prevention (CDC) Multiple Cause of Death 2020-2021 data on overdose mortality, for 50 states and District of Columbia, across 10-year age bins (age range: 15-74). The outcome measure was sex-specific crude overdose death rate (per 100,000) for: synthetic opioids excluding methadone (ICD-10 code: T40.4; e.g., fentanyl), heroin (T40.1), psychostimulants with abuse potential (T43.6; e.g., methamphetamine), and cocaine (T40.5). Multiple regression analyses adjusted for ethnic-cultural background and household net worth from Census data, and sex-specific rate of misuse of the relevant substances, from the National Survey on Drug Use and Health (2019-2020). For each of these major drug categories, men had greater overall overdose mortality than women. Although overall rates of mortality differed across jurisdictions, the sex ratio of mortality for each drug category was relatively stable (≈2- to 3-fold greater mortality in men vs women). These findings survived adjustment for state-level ethnic-cultural and economic variables, and for sex-specific misuse of each drug type (especially in the 25-34, 35-44, 45-54 and 55-64 age bins). These findings underscore the need for research into sex- and gender-based mechanisms underlying differential vulnerability in overdose mortality for these drugs, based on their diverse pharmacodynamics and pathophysiology.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.20.23284833v1" target="_blank">Men have approximately 2- to 3-fold greater overdose mortality than women for synthetic opioids, heroin and psychostimulants including cocaine across the lifespan: Analysis of state-level CDC data for 2020-2021</a>
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<li><strong>Machine learning augmentation reduces prediction error in collective forecasting: development and validation across prediction markets</strong> -
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The recent COVID-19 crisis highlighted the inadequacy of human forecasting. We aim to leverage human prediction markets with real-time machine weighting of likely higher accuracy trades to improve performance. The crowd sourced Almanis prediction market longitudinal platform (n=1822) and Next Generation Social Science (NGS2) platform (n=103) were utilised. A 43-feature model predicted top quintile relative Brier accuracy scores in two out-of-sample datasets (pboth<1x10-9). Trades graded as high machine accuracy quality vs. other trades had a greater AUC temporal gain from before to after trade. Hybrid human-machine forecasts had higher accuracy than human forecasts alone, particularly when the two systems disagreed by 5% or more for binary event prediction: the hybrid system demonstrating substantial AUC gains of 13.2%, p=1.35x10-14 and 13.8%, p=0.003 in the out-of-sample Almanis B and NGS2 datasets respectively. When discordant, the hybrid model was correct for COVID-19 event occurrence 72.7% of the time vs 27.3% for human-only models, p=0.007. This net classification benefit was replicated in the separate Almanis B dataset, p=2.4x10-7. Real-time machine classification followed by weighting human trades according to likely accuracy improves collective forecasting performance. Implementation may allow improved anticipation of and response to emerging risks and improved human collective efforts generally.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.19.23284578v1" target="_blank">Machine learning augmentation reduces prediction error in collective forecasting: development and validation across prediction markets</a>
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</div></li>
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<li><strong>Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2</strong> -
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The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells for at least one year following primary vaccination. 514 monoclonal antibodies (mAbs) were generated from antigen-specific memory B cells. Antibodies isolated at 5 to 12 months following vaccination displayed greater potency and breadth, relative to those identified at 1.4 months. Notably, 15 out of 338 (~4.4%) antibodies isolated at 1.4~6 months after the primary vaccination showed extraordinary neutralization potency against SARS-CoV-2 omicron BA.1, despite the absence of BA.1 neutralization in serum. Two of them, 25F9 and 20A7, neutralized authentic clade Ia sarbecoviruses (SARS-CoV, WIV-1, SHC014) and clade Ib sarbecoviruses (SARS-CoV-2 D614G, SARS-CoV-2 BA.1, Pangolin-GD) with half-maximal inhibition concentrations of (0.85 ng/ml, 3 ng/ml, 6 ng/ml, 6 ng/ml, 42 ng/ml, 6 ng/ml) and (13 ng/ml, 2 ng/ml, 18 ng/ml, 9 ng/ml, 6 ng/ml, 345 ng/ml), respectively. Furthermore, 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants of concern and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1 and XBB variants. X-ray crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved RBD sites. In vivo prophylactic protection of 25F9, 20A7 and 27A12 was confirmed in aged Balb/c mice. Notably, administration of 25F9 provided complete protection against SARS-CoV-2, SARS-CoV-2 BA.1, SARS-CoV, and SHC014 challenge, underscoring that these mAbs are promising pan-sarbecovirus therapeutic antibodies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.19.524784v1" target="_blank">Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2</a>
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<li><strong>Induction of SARS-CoV-2 N-specific CD8+ T cell immunity in lungs by engineered extracellular vesicles associates with strongly impaired viral replication</strong> -
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Induction of effective immunity in lungs should be a pre-requisite for any vaccine designed to control the severe pathogenic effects generated by respiratory infectious agents. In the case of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection, vaccination is expected to associate with significant inhibition of viral replication in lungs. We recently provided evidence that the generation of endogenous extracellular vesicles (EVs) engineered for the incorporation of SARS-CoV-2 Nucleocapsid (N) protein can protect K18-hACE2 transgenic mice from the lethal intranasal infection with the ancestral Wuhan isolate. Actually, it was widely demonstrated that these transgenic mice succumb to SARS-CoV-2 intranasal infection mainly as a consequence of the viral invasiveness of central nervous system, a pathogenetic mechanism almost absent in humans. On the other hand, K18-hACE2 transgenic mice support viral replication in lungs, an event strictly mirroring the major pathogenic signature linked to the severe disease in humans. However, nothing is known about the ability of N-specific CD8+ T cell immunity induced by engineered EVs in controlling viral replication in lungs. To fill the gap, we investigated the immunity generated in lungs by N-engineered EVs in terms of induction of N-specific effectors and resident memory CD8+ T lymphocytes before and after virus challenge carried out three weeks and three months after boosting. At the same time points, viral replication extents in lungs were evaluated. We found that three weeks after second immunization, virus replication was reduced in mice best responding to vaccination by more than 3-logs compared to control group. The impaired viral replication matched with a reduced induction of Spike-specific CD8+ T lymphocytes. The antiviral effect appeared similarly strong when the viral challenge was carried out 3 months after boosting. This inhibitory effect associated with the persistence of a N-specific CD8+ T-resident memory lymphocytes in lungs of N-immunized mice. In view of the quite conserved sequence of the N protein among SARS-CoV-2 variants, these results support the idea that a vaccine strategy focused on the induction of anti-N CD8+ T cell immunity in lungs has the potential to control the replication of emerging variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.19.524762v1" target="_blank">Induction of SARS-CoV-2 N-specific CD8+ T cell immunity in lungs by engineered extracellular vesicles associates with strongly impaired viral replication</a>
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</div></li>
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<li><strong>Effectiveness of second booster compared to first booster and protection conferred by previous SARS CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France</strong> -
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In face of evidence of rapid waning of vaccine effectiveness against Omicron and its sub-lineages, a second booster with mRNA vaccines was recommended for the most vulnerable in France. We used a test negative design to estimate the effectiveness of the second booster relative to the first booster and the protection conferred by a previous SARS-CoV-2 infection, against symptomatic Omicron BA.2 or BA.4/5. We included symptomatic ≥60 years old individuals tested for SARS-CoV-2 in March 21-October 30, 2022. Compared to a 181-210 days old first booster, a second booster restored protection with an effectiveness of 39% [95%CI: 38% - 41%], 7-30 days post-vaccination This gain in protection was lower than the one observed with the first booster, at equal time points since vaccination. High levels of protection were associated to previous SARS-CoV-2 infection, especially if the infection was recent and occurred when an antigenic-related variant was dominant.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.11.23284137v2" target="_blank">Effectiveness of second booster compared to first booster and protection conferred by previous SARS CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France</a>
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<li><strong>Uncovering hidden biological processes by probabilistic filtering of single-cell data</strong> -
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Elucidating underlying biological processes in single-cell data is an ongoing challenge and the number of methods that recapitulate dominant signals in such data has increased significantly. However, cellular populations encode multiple biological attributes, related to their spatial configuration, temporal trajectories, cell-cell interactions, and responses to environmental cues, which may be overshadowed by the dominant signal and thus much harder to recover. To approach this task, we developed SiFT (SIgnal FilTering), a method for filtering biological signals in single-cell data, thus uncovering underlying processes of interest. Utilizing existing prior knowledge and reconstruction tools for a specific biological signal, such as spatial structure, SiFT filters the signal and uncovers additional biological attributes. SiFT is applicable to a wide range of tasks, from the removal of unwanted variation in the data as a pre-processing step to revealing hidden biological structures. Applied for pre-processing, SiFT outperforms state-of-the-art methods for the removal of nuisance signals and cell cycle effects. To recover underlying biological structure, we use existing prior knowledge regarding liver zonation to filter the spatial signal from single-cell liver data thereby enhancing the temporal circadian signal the cells are encoding. Lastly, we showcase the applicability of SiFT in the case-control setting for studying COVID-19 disease. Filtering the healthy signal, based on reference samples from healthy donors, exposes disease-related dynamics in COVID-19 data and highlights disease informative cells and their underlying disease response pathways.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.18.524512v1" target="_blank">Uncovering hidden biological processes by probabilistic filtering of single-cell data</a>
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<li><strong>Sweden’s Coronavirus Fight Strategy And Bitter Memories Of Past Eugenic Practices</strong> -
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Herd immunity is one of the methods utilized by countries to combat the new coronavirus (SARS-CoV-2) pandemic. Sweden is the only country in Europe that pursues the practice of “herd immunity,” while the new coronavirus has spread throughout the country. As of April 27, 2020, the Johns Hopkins University Coronavirus Research Center reports that there have been 18,640 coronavirus cases in Sweden, resulting in 2,194 deaths. The ‘herd’ will survive, but in order for this to occur, other ‘weaker’ members of society must be sacrificed, according to some researchers. The goal of eugenics, in its simplest form, is to increase the genetic quality of a human population. People and organizations deemed inferior can be rejected or sacrificed for those deemed superior and able to live so that this improvement might occur. As we explained in our AVM analysis titled “Century-Old ‘White Supremacism’ and the Far-Rise Right’s in Sweden: A Credible Challenge to Progressive Values and Policies” published two years ago, the Scandinavian eugenics movement reached its zenith prior to the First World War and became operational during the 1930s and 1940s. Between 1934 and 1976, Sweden was the only country with a national eugenics society and employed sterilization regulations. The initial Swedish sterilisation statute went into effect in 1935 and was expanded in 1941. A Swedish government commission was established in 1997 to investigate sterilization operations from 1935 to 1975. According to international press accounts, Sweden’s present plan to combat the spread of the coronavirus is supported by the people at large. Time will tell if this strategy, which is pursued at the expense of vulnerable individuals (particularly the elderly), is worthwhile. Even if this technique currently supports Sweden’s interests, it will undoubtedly be subject to severe ethical objections in the future, similar to Sweden’s past eugenics activities.
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🖺 Full Text HTML: <a href="https://osf.io/zb2jn/" target="_blank">Sweden’s Coronavirus Fight Strategy And Bitter Memories Of Past Eugenic Practices</a>
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<li><strong>Prediction of Long COVID Based on Severity of Initial COVID-19 Infection: Differences in predictive feature sets between hospitalized versus non-hospitalized index infections</strong> -
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Long COVID is recognized as a significant consequence of SARS-COV2 infection. While the pathogenesis of Long COVID is still a subject of extensive investigation, there is considerable potential benefit in being able to predict which patients will develop Long COVID. We hypothesize that there would be distinct differences in the prediction of Long COVID based on the severity of the index infection, and use whether the index infection required hospitalization or not as a proxy for developing predictive models. We divide a large population of COVID patients drawn from the United States National Institutes of Health (NIH) National COVID Cohort Collaborative (N3C) Data Enclave Repository into two cohorts based on the severity of their initial COVID-19 illness and correspondingly trained two machine learning models: the Long COVID after Severe Disease Model (LCaSDM) and the Long COVID after Mild Disease Model (LCaMDM). The resulting models performed well on internal validation/testing, with a F1 score of 0.94 for the LCaSDM and 0.82 for the LCaMDM. There were distinct differences in the top 10 features used by each model, possibly reflecting the differences in type and amount of pathophysiological data between the hospitalized and non-hospitalized patients and/or reflecting different pathophysiological trajectories in the development of Long COVID. Of particular interest was the importance of Plant Hardiness Zone in the feature set for the LCaMDM, which may point to a role of climate and/or sunlight in the progression to Long COVID. Future work will involve a more detailed investigation of the potential role of climate and sunlight, as well as refinement of the predictive models as Long COVID becomes increasingly parsed into distinct clinical phenotypes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.16.23284634v2" target="_blank">Prediction of Long COVID Based on Severity of Initial COVID-19 Infection: Differences in predictive feature sets between hospitalized versus non-hospitalized index infections</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>Digital Tools to Expand COVID-19 Testing in Exposed Individuals in Cameroon</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Digital based contact tracing<br/><b>Sponsors</b>: Elizabeth Glaser Pediatric AIDS Foundation; Find<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>Evaluation of the Outcome of COVID-19 Patients Discharged Home on Oxygen Therapy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Phone satisfaction questionnaire<br/><b>Sponsor</b>: Centre Hospitalier René Dubos<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>Postural Changes and Severe COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Postural interventions based on pulmonary imaging<br/><b>Sponsor</b>: Wuhan Union Hospital, China<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 Chatbot to Enhance COVID-19 Knowledge</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: chatbot; Other: Printed educational booklet<br/><b>Sponsor</b>: Sun Yat-sen University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Awaken Prone Positioning Ventinlation in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Awaken prone positioning ventilation<br/><b>Sponsor</b>: Southeast University, China<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>Study of SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SHEN26 dose 1; Drug: SHEN26 dose 2; Drug: SHEN26 placebo<br/><b>Sponsor</b>: Shenzhen Kexing Pharmaceutical 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>Bright Light Therapy for Post-COVID-19 Fatigue</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Device: Bright light therapy; Device: Dim red light therapy<br/><b>Sponsor</b>: Chinese University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on the Safety and Efficacy of Meplazumab for Injection Patients COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab foe injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on the Safety and Efficacy of Meplazumab for Injection in Severe Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab for injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 2 Study to Evaluate the Efficacy and Safety of QLS1128 Orally in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu Pharmaceutical Co., Ltd.<br/><b>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>Oropharyngeal Immunoprophylaxis With High Polyphenolic Olive Oil as Clinical Spectrum Mitigating Factor in COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: High polyphenolic olive oil. (Early harvest olive oil).<br/><b>Sponsor</b>: Hospital General Nuestra Señora del Prado<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized, Phase I Study of DNA Vaccine OC-007 as a Booster Dose of COVID-19 Vaccine</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection; COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>: Biological: DNA vaccine OC-007; Other: Placebo<br/><b>Sponsor</b>: Matti Sällberg<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>Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies 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>UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients</strong> - <b>Conditions</b>: Mesenchymal Stem Cell; COVID-19 Pneumonia<br/><b>Interventions</b>: Biological: umbilical cord mesenchymal stem cells; Drug: paxlovid<br/><b>Sponsor</b>: Shanghai East 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>A Study of Positive Emotions With Long COVID-19</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Microdosing of mindfulness<br/><b>Sponsor</b>: University of California, Davis<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>Altered host protease determinants for SARS-CoV-2 Omicron</strong> - Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can…</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>Anti-inflammatory and antioxidant activities of Gymnema Sylvestre extract rescue acute respiratory distress syndrome in rats via modulating the NF-κB/MAPK pathway</strong> - Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality in COVID-19 patients, due to limited therapeutic options. This prompted us to explore natural sources to mitigate this condition. Gymnema Sylvestre (GS) is an ancient medicinal plant known to have various therapeutic effects. This investigation examined the therapeutic effect of hydroalcoholic extract of Gymnema Sylvestre (HAEGS) against lipopolysaccharide (LPS)-induced lung injury and ARDS in in vitro and in vivo…</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>In Vitro Antiviral Evaluations of Coldmix<sup>®</sup>: An Essential Oil Blend against SARS-CoV-2</strong> - Coldmix^(®) is a commercially available Eucalyptus aetheroleum and, Abies aetheroleum blend for medicinal applications. In this present study, the in vitro antiviral potential of Coldmix^(®), and its major constituents 1,8-cineole and α-pinene were evaluated by using the in vitro ACE2 enzyme inhibition assay as well as the direct contact test against SARS-CoV-2. The observed ACE2 enzyme inhibitory activity of Coldmix^(®), 1,8-cineole, and α-pinene were 72%, 88%, and 80%, respectively; whereas 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>Increased mTOR Signaling and Impaired Autophagic Flux Are Hallmarks of SARS-CoV-2 Infection</strong> - The COVID-19 (Coronavirus Disease 2019), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), severely affects mainly individuals with pre-existing comorbidities. Here our aim was to correlate the mTOR (mammalian/mechanistic Target of Rapamycin) and autophagy pathways with the disease severity. Through western blotting and RNA analysis, we found increased mTOR signaling and suppression of genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected…</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 Potential of Stilbene Compounds to Inhibit M<sup>pro</sup> Protease as a Natural Treatment Strategy for Coronavirus Disease-2019</strong> - COVID-19 disease has had a global impact on human health with increased levels of morbidity and mortality. There is an unmet need to design and produce effective antivirals to treat COVID-19. This study aimed to explore the potential ability of natural stilbenes to inhibit the M^(pro) protease, an acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enzyme involved in viral replication. The binding affinities of stilbene compounds against M^(pro) were scrutinized using molecular docking, prime…</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>Network pharmacology- and molecular simulation-based exploration of therapeutic targets and mechanisms of heparin for the treatment of sepsis/COVID-19</strong> - Critically infected patients with COVID-19 (coronavirus disease 2019) are prone to develop sepsis-related coagulopathy as a result of a robust immune response. The mechanism underlying the relationship between sepsis and COVID-19 is largely unknown. LMWH (low molecular weight heparin) exhibits both anti-inflammatory and anti-coagulating properties that result in a better prognosis of severely ill patients with COVID-19 co-associated with sepsis-induced coagulopathy or with a higher D-dimer…</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 mRNA vaccine immunogenicity decay and breakthrough illness in adolescents and young adults with childhood-onset rheumatic diseases</strong> - CONCLUSION: Over half of AYAs with cRDs had a significant drop in SARS-CoV-2 nAb at 6-month despite an initial robust humoral response. JIA and aTNF usage are predictors of a faster decay rate.</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>SURFing SARS-CoV-2 inhibition</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Com probe implemented STexS II greatly enhances specificity in SARS-CoV-2 variant detection</strong> - The initial introduction of utilizing double helix structural oligonucleotides known as SNP typing with excellent specificity (STexS) in a standard PCR greatly improved the detection of single nucleotide polymorphisms (SNP) by enhancing amplification rates of primer-matching strands and interrupting mismatched strands by constant instability of kinetics regarding alignment attaching and detaching. The model was beneficial overall in detecting SNP variants consisting of large amounts of wildtype…</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>Characterization of RNA G-quadruplexes in porcine epidemic diarrhea virus genome and the antiviral activity of G-quadruplex ligands</strong> - Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. However, there are still no anti-PEDV drugs with accurate targets. G-quadruplexes (G4s) are non-canonical secondary structures formed within guanine-rich regions of DNA or RNA, and have attracted great attention as potential targets for antiviral strategy. In this study, we reported two putative G4-forming sequences (PQS) in S and Nsp5 genes of PEDV genome based on…</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>Thorectidiol A Isolated from the Marine Sponge <em>Dactylospongia elegans</em> Disrupts Interactions of the SARS-CoV-2 Spike Receptor Binding Domain with the Host ACE2 Receptor</strong> - Thorectidiols isolated from the marine sponge Dactylospongia elegans (family Thorectidae, order Dictyoceratida) collected in Papua New Guinea are a family of symmetrical and unsymmetrical dimeric biphenyl meroterpenoid stereoisomers presumed to be products of oxidative phenol coupling of a co-occurring racemic monomer, thorectidol (3). One member of the family, thorectidiol A (1), has been isolated in its natural form, and its structure has been elucidated by analysis of NMR, MS, and ECD data….</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>Chicken or Porcine Aminopeptidase N Mediates Cellular Entry of Pseudoviruses Carrying Spike Glycoprotein from the Avian Deltacoronaviruses HKU11, HKU13, and HKU17</strong> - Members of deltacoronavirus (DCoV) have mostly been identified in diverse avian species as natural reservoirs, though the porcine DCoV (PDCoV) is a major swine enteropathogenic virus with global spread. The important role of aminopeptidase N (APN) orthologues from various mammalian and avian species in PDCoV cellular entry and interspecies transmission has been revealed recently. In this study, comparative analysis indicated that three avian DCoVs, bulbul DCoV HKU11, munia DCoV HKU13, 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>Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration</strong> - Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral Potential of Melissa officinalis L.: A Literature Review</strong> - The use of synthetic drugs has increased in recent years; however, herbal medicine is yet more trusted among a huge population worldwide; This could be due to minimal side effects, affordable prices, and traditional beliefs. Lemongrass (Melissa officinalis) has been widely used for reducing stress and anxiety, increasing appetite and sleep, reducing pain, healing wounds, and treating poisonous insect bites and bee stings for a long time. Today, research has shown that this plant can also fight…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Broad-Spectrum Cyclopropane-Based Inhibitors of Coronavirus 3C-like Proteases: Biochemical, Structural, and Virological Studies</strong> - The advent of SARS-CoV-2, the causative agent of COVID-19, and its worldwide impact on global health, have provided the impetus for the development of effective countermeasures that can be deployed against the virus, including vaccines, monoclonal antibodies, and direct-acting antivirals (DAAs). Despite these efforts, the current paucity of DAAs has created an urgent need for the creation of an enhanced and diversified portfolio of broadly acting agents with different mechanisms of action that…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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