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<title>10 May, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Reply to “Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs”: Important concerns on the validity of this article.</strong> -
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<div>
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We share a Letter of concern To the Editor from Food and Chemical Toxicology about a recent published review from Seneff. et al entitled “Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs”( doi: 10.1016/j.fct.2022.113008). In our opinion, this article contains several assumptions and misinformation that we highlight. We believe that a rapid analysis of the key points and the misinterpretations that they contain are sufficient to invalidate the relevancy of the article and therefore we ask the editor to revise their opinion on the publication of the article.
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🖺 Full Text HTML: <a href="https://osf.io/m58yh/" target="_blank">Reply to “Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs”: Important concerns on the validity of this article.</a>
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</div></li>
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<li><strong>Inferring selection effects in SARS-CoV-2 with Bayesian Viral Allele Selection</strong> -
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The global effort to sequence millions of SARS CoV-2 genomes has provided an unprecedented view of viral evolution. Characterizing how selection acts on SARS-CoV-2 is critical to developing effective, long-lasting vaccines and other treatments, but the scale and complexity of genomic surveillance data make rigorous analysis distinctly challenging. To meet this challenge, we develop Bayesian Viral Allele Selection (BVAS), a principled and scalable probabilistic method for inferring the genetic determinants of differential viral fitness and the relative growth rates of viral lineages, including newly emergent lineages. After demonstrating the accuracy and efficacy of our method through simulation, we apply BVAS to 6.9 million SARS-CoV-2 genomes. We identify numerous mutations that increase fitness, including previously identified mutations in the SARS-CoV-2 Spike and Nucleocapsid proteins, as well as mutations in non-structural proteins whose contribution to fitness is less well characterized. In addition, we extend our baseline model to identify mutations whose fitness exhibits strong dependence on vaccination status. Our method, which couples Bayesian variable selection with a diffusion approximation in allele frequency space, lays a foundation for identifying fitness-associated mutations under the assumption that most alleles are neutral.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.07.490748v1" target="_blank">Inferring selection effects in SARS-CoV-2 with Bayesian Viral Allele Selection</a>
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</div></li>
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<li><strong>SARS-CoV-2 Spike N-Terminal Domain modulates TMPRSS2-dependent viral entry and fusogenicity</strong> -
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<div>
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Over 20 mutations have been identified in the N-Terminal Domain (NTD) of SARS-CoV-2 spike and yet few of them are fully characterised. Here we first examined the contribution of the NTD to infection and cell-cell fusion by constructing different VOC-based chimeric spikes bearing B.1617 lineage (Delta and Kappa variants) NTDs and generating spike pseudotyped lentivirus (PV). We found the Delta NTD on a Kappa or WT background increased spike S1/S2 cleavage efficiency and virus entry, specifically in Calu-3 lung cells and airway organoids, through use of TMPRSS2. Delta was previously shown to have fast cell-cell fusion kinetics and increased fusogenicity that could be conferred to WT and Kappa variant spikes by transfer of the Delta NTD. Moving to contemporary variants, we found that BA.2 had higher entry efficiency in a range of cell types as compared to BA.1. BA.2 showed higher fusogenic activity than BA.1, but the BA.2 NTD could not confer higher fusion to BA.1 spike. There was low efficiency of TMPRSS2 usage by both BA.1 and BA.2, and chimeras of Omicron BA.1 and BA.2 spikes with a Delta NTD did not result in more efficient use of TMRPSS2 or cell-cell fusogenicity. We conclude that the NTD allosterically modulates S1/S2 cleavage and spike-mediated functions such as entry and cell-cell fusion in a spike context dependent manner, and allosteric interactions may be lost when combining regions from more distantly related spike proteins. These data may explain the lack of dominant SARS-CoV-2 inter-variant recombinants bearing breakpoints within spike.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.07.491004v1" target="_blank">SARS-CoV-2 Spike N-Terminal Domain modulates TMPRSS2-dependent viral entry and fusogenicity</a>
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</div></li>
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<li><strong>Persistent serum protein signatures define an inflammatory subset of long COVID</strong> -
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<div>
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Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months after acute SARS-CoV-2 infection. The etiologies are unknown but may include persistent inflammation, unresolved tissue damage, or delayed clearance of viral protein or RNA. Attempts to classify subsets of PASC by symptoms alone have been unsuccessful. To molecularly define PASC, we evaluated the serum proteome in longitudinal samples from 55 PASC individuals with symptoms lasting [≥]60 days after onset of acute infection and compared this to symptomatically recovered SARS-CoV-2 infected and uninfected individuals. We identified subsets of PASC with distinct signatures of persistent inflammation. Type II interferon signaling and canonical NF-{kappa}B signaling (particularly associated with TNF), were the most differentially enriched pathways. These findings help to resolve the heterogeneity of PASC, identify patients with molecular evidence of persistent inflammation, and highlight dominant pathways that may have diagnostic or therapeutic relevance.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.09.491196v1" target="_blank">Persistent serum protein signatures define an inflammatory subset of long COVID</a>
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</div></li>
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<li><strong>Accuracy and Glycemic Efficacy of Continuous Glucose Monitors in Critically Ill COVID-19 Patients: a Retrospective Study</strong> -
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Background: Continuous Glucose Monitoring (CGM) is approved for insulin dosing decisions in the ambulatory setting, but not currently for inpatients. CGM has the capacity to reduce patient-provider contact in inpatients with coronavirus disease 2019 (COVID-19), thus potentially reducing in hospital virus transmission. However, there are sparse data on the accuracy and efficacy of CGM to titrate insulin doses in inpatients. Methods: Under an emergency use protocol, CGM (Dexcom G6) was used alongside standard point-of-care (POC) glucose measurements in patients critically ill from complications of COVID-19 requiring intravenous (IV) insulin. Glycemic control during IV insulin therapy was retrospectively assessed comparing periods with and without adjunctive CGM use. Accuracy metrics were computed and Clarke Error Grid analysis performed comparing CGM glucose values with POC measurements. Results: 24 critically ill patients who met criteria for emergency use of CGM resulted in 47333 CGM and 5677 POC glucose values. During IV insulin therapy, individuals9 glycemic control improved when CGM was used (mean difference -30.2 mg/dL). Among 2194 matched CGM:POC glucose pairs a high degree of concordance was observed with a MARD of 14.8% and 99.5% of CGM:POC pairs falling in Zones A and B of the Clarke Error Grid. Conclusions: CGM use in critically ill COVID-19 patients improved glycemic control during IV insulin therapy. CGM glucose data were highly concordant with POC glucose during IV insulin therapy in critically ill patients suggesting that CGM could substitute for POC measurements in inpatients thus reducing patient- provider contact and mitigating infection transmission.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.06.22274685v1" target="_blank">Accuracy and Glycemic Efficacy of Continuous Glucose Monitors in Critically Ill COVID-19 Patients: a Retrospective Study</a>
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</div></li>
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<li><strong>Trait Intolerance of Uncertainty Is Associated with Decreased Reappraisal Capacity and Increased Suppression Tendency</strong> -
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<div>
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The COVID-19 pandemic has been a time of great uncertainty for the general population and highlights the need to understand how attitudes towards uncertainty may affect well-being. Intolerance of uncertainty is a trait associated with worry, anxiety, and mood disorders. As adaptive emotion regulation supports well-being and mental health, it is possible that intolerance of uncertainty is also associated with the ability and tendency to regulate emotions. However, the relationships between intolerance of uncertainty and widely studied cognitive emotion regulation strategies — such as reappraisal and suppression — have received little attention. In two studies that recruited participants online from the United States, we tested the hypotheses that higher trait intolerance of uncertainty would be associated with greater worry, decreased capacity and tendency to use reappraisal, and increased tendency to use suppression in daily life. Study 1 provided an initial test of our hypotheses. Study 2 was a confirmatory, preregistered study that replicated findings in a young adult sample, demonstrating that scores on the Intolerance of Uncertainty Scale (IUS) were associated with greater COVID-related worry, decreased capacity to regulate negative emotions on a task that manipulated the use of reappraisal, and greater self-reported use of suppression in daily life. Together, these results indicate that intolerance of uncertainty is associated with the capacity and tendency to use emotion regulation strategies important for well-being.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/fsnvy/" target="_blank">Trait Intolerance of Uncertainty Is Associated with Decreased Reappraisal Capacity and Increased Suppression Tendency</a>
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</div></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A quasi-experimental cohort study evaluating a conditional economic incentive on first-dose COVID-19 vaccination rates among older adults in South Africa</strong> -
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Importance: COVID-19 vaccination coverage in South Africa remains low despite increased access to vaccines. On November 1, 2021, South Africa introduced the Vooma Voucher program, which provided a small guaranteed financial incentive, a Vooma Voucher redeemable at grocery stores, for COVID-19 vaccination among older adults, a population most vulnerable to serious illness, hospitalization, and death. However, the association of financial incentives with vaccination coverage remains unclear. Objective: To evaluate the association of the conditional economic incentive program with first-dose vaccination rates among older adults (aged ≥60 years) in South Africa. Design: A quasi- experimental cohort study using daily data on first doses administered. We ran interrupted time series (ITS) models to evaluate the Vooma Voucher program, launched on November 1, 2021, at national and provincial levels. We used data between October 1, 2021 and November 27, 2021 in models estimated at the daily level. Setting and participants: The Vooma Voucher program was a nationwide vaccination incentive program implemented for adults aged ≥60 years from November 1, 2021 to February 28, 2022. Intervention: Individuals who received their first vaccine dose received a text message to access a ~$7 (ZAR100) voucher that was redeemable at nationwide chain of grocery stores. Main outcome: Daily first COVID-19 vaccine doses administered per 10,000 individuals aged ≥60 years. Results: The Vooma Voucher program was associated with a of 7.15-12.01% increase in daily first-dose vaccination in November 2021 compared to late October</p></div></li>
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<ol start="2021" type="1">
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<li>The incentive accounted for 6,476-10,874 additional first vaccine doses from November 1-27, 2021, or 8.31-13.95% of all doses administered to those aged ≥60 years during that period. This result is robust to the inclusion of controls for the number of active vaccine delivery sites and for the nationwide Vooma weekend initiative (November 12-14), both of which also increased vaccinations through expanded access to vaccines and demand creation activities. Conclusions/Relevance: Financial incentives for COVID-19 vaccination led to a modest increase in first dose vaccinations among older adults in South Africa. In addition to financial incentives, expanded access to vaccines may also results in higher vaccination coverage.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.06.22274712v2" target="_blank">A quasi-experimental cohort study evaluating a conditional economic incentive on first-dose COVID-19 vaccination rates among older adults in South Africa</a>
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<li><strong>Exploring U.S. food system workers’ intentions to work while ill during the early COVID-19 pandemic: a national survey analysis</strong> -
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Background: As “stay at home” orders were in effect, many US food workers attended in-person work during early phases of the COVID-19 pandemic, charged with maintaining normal operation of the national food supply chain. Despite establishment of a novel national paid sick leave policy, anecdotal evidence suggests that many U.S. food system workers encountered barriers to staying home when ill. Methods: Using quantitative and free-text analyses from a national, cross-sectional, online survey deployed from July to October 2020 among 2,535 respondents, we explored workplace and non-workplace factors associated with U.S. food system workers9 intentions to attend work while ill (i.e. presenteeism intentions) during the first four to six months of the COVID-19 pandemic. Results: Overall, 8.8% of workers surveyed reported intentions to attend work while ill. Both quantitative data and free-text responses suggest that aspects of workplace culture influenced workers9 decisions to attend work while ill. Workers reporting a high workplace safety climate score had half the odds of reporting presenteeism intentions (adjusted odds ratio [aOR] 0.52, 95% confidence interval (CI) 0.37, 0.75) relative to those reporting low scores. Workers described cultural barriers, including retaliation and penalties, that reduced paid sick leave access. Workers reporting low (aOR 2.06, 95% CI 1.35, 3.13) or very low (aOR 2.31, 95% CI 1.50, 3.13) levels of household food security had more than twice the odds of reporting presenteeism intentions. Conclusions: This study offers insights into opportunities for reducing presenteeism related to illness among food workers both during the COVID-19 pandemic and in other infectious disease scenarios. Addressing vulnerabilities like food insecurity and empowering food system workers to make health-protective decisions is important both for optimal worker health outcomes and maintaining a functioning food system.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.25.22274276v2" target="_blank">Exploring U.S. food system workers’ intentions to work while ill during the early COVID-19 pandemic: a national survey analysis</a>
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</div></li>
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<li><strong>Durability of protection post-primary COVID-19 vaccination in the US: a matched case-control study</strong> -
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Background: Intrinsic durability of immune responses elicited by COVID-19 vaccines will drive vaccine effectiveness long-term across settings and may differ by vaccine type. We aimed here to determine durability of protection of three COVID-19 vaccines BNT162b2, mRNA-1273 and Ad26.COV2.S following primary vaccination against breakthrough infections, hospitalisations, and intensive care unit (ICU) admissions in the United States (US). Methods: Using national claims and laboratory data covering 168 million lives, we conducted a matched case-control study with fully vaccinated individuals between January 1 and September 7, 2021. Odds ratios (OR) for developing outcomes in months two through six following primary vaccination were estimated relative to the first month after primary vaccination for each vaccine separately. Results compare each vaccine to itself and are not directly comparative. Odds ratios were translated into vaccine effectiveness (VE) using assumptions about event rates in an unvaccinated cohort. Findings: Relative to its baseline, stable protection was observed for the single-shot Ad26.COV2.S against infections and severe disease. Relative to their baseline protection waned overtime against infections for BNT162b2 and mRNA-1273 and against hospitalisations for BNT162b2. No waning of baseline protection was observed at any time for ICU admissions for all three vaccines. Calculated baseline VE was consistent with the published literature. Interpretation: While the starting protection level provided by the primary series may differ by vaccine type and mechanism of action, this study demonstrated by comparing each vaccine to its own baseline protection that the three vaccines in three separate populations may have different durability profiles. Further investigation is required to fully characterize the durability profile of the three vaccines. Moreover, as the COVID-19 pandemic continues, and as more countries and populations implement a standard of care consisting of three doses of the mRNA vaccines or two doses of Ad26.COV2.S, further investigation is critical to understand the level of protection and the durability of response over longer periods, novel variants and in response to homologous and heterologous boosting.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.05.22268648v2" target="_blank">Durability of protection post-primary COVID-19 vaccination in the US: a matched case-control study</a>
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<li><strong>Daily Prosocial Actions During the COVID-19 Pandemic Contribute to Giving Behavior in Adolescence</strong> -
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This is a preprint of an article published in Scientific Reports. The final authenticated version is available online at https://doi.org/10.1038/s41598-022-11421-3. In the present preregistered study, we tested the impact of COVID-19 pandemic on opportunities for prosocial actions in adolescence, a formative phase for social development. 888 adolescents (10-20-years) and university students (18-25-years) completed two weeks of daily diaries on their daily prosocial support during the pandemic and Dictator Games giving directed to peers, friends and COVID-19 targets (medical doctors, COVID-19 patients, individuals with a poor immune system). Prosocial support directed to friends peaked in mid-adolescence, whereas prosocial support towards family members showed a gradual increase from childhood to young adulthood. Overall, adolescents gave more to COVID-19 targets than to peers and friends. Daily prosocial support experiences to friends predicted giving behavior to all targets, whereas prosocial support to family was specifically associated with giving to COVID-19 targets. Together, these findings elucidate the importance of prosocial experiences during the formative years of adolescence.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/7cptg/" target="_blank">Daily Prosocial Actions During the COVID-19 Pandemic Contribute to Giving Behavior in Adolescence</a>
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<li><strong>Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden</strong> -
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Background Analyses of COVID-19 suggest specific risk factors make communities more or less vulnerable to pandemic related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics. Methods We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020-February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality. Results We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100,000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden. Conclusion These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics.
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<div class="article-link article-html- link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.26.22274332v2" target="_blank">Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden</a>
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</div></li>
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<li><strong>Epidemiological investigation of the COVID-19 outbreak in Vellore district in South India using Geographic Information Surveillance (GIS)</strong> -
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Objectives: Geographical Information Surveillance (GIS) is an advanced digital technology tool that maps location-based data and helps in epidemiological modeling. We applied GIS to analyze patterns of spread and hotspots of COVID-19 cases in Vellore district in South India. Methods: Laboratory-confirmed COVID-19 cases from the Vellore district and neighboring taluks from March 2020 to June 2021 were geo-coded and spatial maps were generated. Time trends exploring urban-rural burden with an age-sex distribution of cases and other variables were correlated with outcomes. Results: A total of 45,401 cases of COVID-19 were detected with 20730 cases during the first wave and 24671 cases during the second wave. The overall incidence rates of COVID-19 were 462.8 and 588.6 per 100,000 populations during the first and second waves respectively. The pattern of spread revealed epicenters in densely populated urban areas with radial spread sparing rural areas in the first wave. The case fatality rate was 1.89% and 1.6% during the first and second waves that increased with advancing age. Conclusions: Modern surveillance systems like GIS can accurately predict the trends and pattern of spread during future pandemics. A real-time mapping can help design risk mitigation strategies thereby preventing the spread to rural areas.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.21.22274138v2" target="_blank">Epidemiological investigation of the COVID-19 outbreak in Vellore district in South India using Geographic Information Surveillance (GIS)</a>
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</div></li>
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<li><strong>Estimating time-dependent infectious contact: a multi-strain epidemiological model of SARS-CoV-2 on the island of Ireland</strong> -
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Mathematical modelling plays a key role in understanding and predicting the epidemiological dynamics of infectious diseases. We construct a flexible discrete-time model that incorporates multiple viral strains with different transmissibilities to estimate the changing infectious contact that generates new infections. Using a Bayesian approach, we fit the model to longitudinal data on hospitalisation with COVID-19 from the Republic of Ireland and Northern Ireland during the first year of the pandemic. We describe the estimated change in infectious contact in the context of government-mandated non-pharmaceutical interventions in the two jurisdictions on the island of Ireland. We take advantage of the fitted model to conduct counterfactual analyses exploring the impact of lockdown timing and introducing a novel, more transmissible variant. We found substantial differences in infectious contact between the two jurisdictions during periods of varied restriction easing and December holidays. Our counterfactual analyses reveal that implementing lockdowns earlier would have decreased subsequent hospitalisation substantially in most, but not all cases, and that an introduction of a more transmissible variant - without necessarily being more severe - can cause a large impact on the health care burden.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.25.22272942v2" target="_blank">Estimating time-dependent infectious contact: a multi-strain epidemiological model of SARS-CoV-2 on the island of Ireland</a>
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</div></li>
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<li><strong>Covid-19 Associated Hepatitis in children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon.</strong> -
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Objective: While pediatric population has largely remained free of severe COVID-19, in some cases SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). We mention another unique presentation subsequent to asymptomatic infection of SARS-CoV-2, a unique form of hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The contrasting clinical presentations, temporal association and viral parameters of CAH-C cases, to the MIS-C cases are presented here. Methods: As a retrospective and follow-up observational study we reviewed all children testing positive for SARS-CoV-2 during study period. Children presenting with sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice, lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis or previous underlying liver disease (b) multi-system involvement were classified as CAH-C, are described here. Results: Among 475 children who tested positive, 47 patients presented with hepatitis, 37 patients who had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers and uneventful recovery following supportive treatment. Whereas remaining 10 MIS-C hepatitis had protracted illness, multiple system involvement, required admission to critical care, and had mortality of 30%. Conclusion: With the emergence of newer variants of concern (VOC) including the Delta variant which predominated the second wave of infections in India and has now spread to more than 142 countries with changing presentations, CAH-C might be one of them. Cases of such new entities need to be identified early and differentiated from other emerging syndromes in children during the ongoing pandemic for preventing adversities by timely intervention.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.07.23.21260716v7" target="_blank">Covid-19 Associated Hepatitis in children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon.</a>
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<li><strong>Substance abuse and the risk of severe COVID-19: Mendelian randomization confirms the causal role of opioids but hints a negative causal effect for cannabinoids.</strong> -
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Since the start of the COVID-19 global pandemic, our understanding of the underlying disease mechanism and factors associated with the disease severity has dramatically increased. A recent report investigated the relationship between substance use disorders (SUD) and the risk of severe COVID-19 in the United States and concluded that the risk of hospitalization and death due to COVID-19 is directly correlated with substance abuse, including opioid use disorder (OUD) and cannabis use disorder (CUD). While we found this analysis fascinating, we believe this observation may be biased due to comorbidities (such as hypertension, diabetes, and cardiovascular disease) confounding the direct impact of SUD on severe COVID-19 illness. To objectively answer this question, we sought to investigate the causal relationship between substance abuse and medication-taking history (as a proxy trait for comorbidities) with the risk of COVID-19 adverse outcomes. Our Mendelian randomization analysis confirms the causal relationship between SUD and severe COVID-19 illness but hints at a negative causal effect for cannabinoids. Given that a great deal of COVID-19 mortality is attributed to disturbed immune regulation, the possible modulatory impact of cannabinoids in alleviating cytokine storms merits further investigation.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.06.22274584v1" target="_blank">Substance abuse and the risk of severe COVID-19: Mendelian randomization confirms the causal role of opioids but hints a negative causal effect for cannabinoids.</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety and Immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in Population 18 Years Old of Age and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Shulan (Hangzhou) 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 to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E; Biological: mRNA-1273<br/><b>Sponsor</b>: Sinocelltech 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 First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AmnioPul-02<br/><b>Sponsor</b>: Amniotics AB<br/><b>Not yet recruiting</b></p></li>
|
||
<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 COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology 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>Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Jiangsu Rec-Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
|
||
<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 COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
|
||
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.<br/><b>Recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Chinese herbal medicine<br/><b>Sponsor</b>: <br/>
|
||
Hong Kong Baptist University<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Wuhan Recogen Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-based Exercise Program in Patients With the Post-COVID-19 Condition</strong> - <b>Conditions</b>: Long COVID; Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Other: Home- based physical training<br/><b>Sponsor</b>: University of Sao Paulo<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kesuting Syrup in the Treatment of Corona Virus Disease 2019 (COVID-19)</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Cough<br/><b>Interventions</b>: Drug: Kesuting syrup; Drug: LianHuaQingWen Granules<br/><b>Sponsor</b>: Guizhou Bailing Group Pharmaceutical Co Ltd<br/><b>Recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immune Function in Elderly Patients With Mild to Moderate COVID-19 on Hemodialysis</strong> - <b>Conditions</b>: COVID-19; Hemodiafiltration<br/><b>Interventions</b>: <br/>
|
||
Dietary Supplement: Oral nutritional supplement; Behavioral: Nutrition consultation<br/><b>Sponsor</b>: <br/>
|
||
Ruijin Hospital<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: NuSepin® 0.2 mg/kg; Drug: NuSepin® 0.4 mg/kg; Drug: Placebo<br/><b>Sponsor</b>: Shaperon<br/><b>Recruiting</b></p></li>
|
||
<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 Assessing the Safety, Tolerability, Immunogenicity of COVID-19 Vaccine Candidate PRIME-2-CoV_Beta, Orf Virus Expressing SARS-CoV_2 Spike and Nucleocapsid Proteins (ORFEUS)</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Drug: PRIME-2-CoV_Beta<br/><b>Sponsor</b>: <br/>
|
||
Speransa Therapeutics<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Drug: EXOFLO<br/><b>Sponsor</b>: Direct Biologics, LLC<br/><b>Not yet recruiting</b></p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High Frequency Percussive Ventilation in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Acute Respiratory Failure<br/><b>Intervention</b>: <br/>
|
||
Device: High frequency Percussive ventilation<br/><b>Sponsor</b>: University Magna Graecia<br/><b>Not yet recruiting</b></p></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
|
||
<ul>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A glucose-like metabolite deficient in diabetes inhibits cellular entry of SARS-CoV-2</strong> - The severity and mortality of COVID-19 are associated with pre-existing medical comorbidities such as diabetes mellitus. However, the underlying causes for increased susceptibility to viral infection in patients with diabetes is not fully understood. Here we identify several small-molecule metabolites from human blood with effective antiviral activity against SARS-CoV-2, one of which, 1,5-anhydro-D-glucitol (1,5-AG), is associated with diabetes mellitus. The serum 1,5-AG level is significantly…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunobiology of tubercle bacilli and prospects of immunomodulatory drugs to tackle tuberculosis (TB) and other non- tubercular mycobacterial infections</strong> - The COVID-19 pandemic has set back progress made on antimicrobial resistance (AMR). Without urgent re-focus, we risk slowing down drug discovery and providing treatment for drug resistant Mycobacterium tuberculosis. Unique in its immune evasion, dormancy and resuscitation, the causal pathogens of tuberculosis (TB) have demonstrated resistance to antibiotics with efflux pumps and the ability to form biofilms. Repurposing drugs is a prospective avenue for finding new anti-TB drugs. There are many…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Delta Variant Decreases Nanobody Binding and ACE2 Blocking Effectivity</strong> - The Delta variant spreads more rapidly than previous variants of SARS-CoV-2. This variant comprises several mutations on the receptor-binding domain (RBD(Delta)) of its spike glycoprotein, which binds to the peptidase domain (PD) of angiotensin-converting enzyme 2 (ACE2) receptors in host cells. The RBD-PD interaction has been targeted by antibodies and nanobodies to prevent viral infection, but their effectiveness against the Delta variant remains unclear. Here, we investigated RBD(Delta)-PD…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Serine Protease Inhibitors Restrict Host Susceptibility to SARS-CoV-2 Infections</strong> - The coronavirus disease 2019, COVID-19, is a complex disease with a wide range of symptoms from asymptomatic infections to severe acute respiratory syndrome with lethal outcome. Individual factors such as age, sex, and comorbidities increase the risk for severe infections, but other aspects, such as genetic variations, are also likely to affect the susceptibility to SARS-CoV-2 infection and disease severity. Here, we used a human 3D lung cell model based on primary cells derived from multiple…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plant-derived active compounds as a potential nucleocapsid protein inhibitor of SARS-CoV-2: an <em>in-silico</em> study</strong> - The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. This virus has a high mismatch repair proofreading ability due to its unique exonuclease activity, making it knotty to treat. The nucleocapsid protein can serve as a potential antiviral drug target, as this protein is responsible for multiple captious functions during the viral life cycle. Herein, we have investigated the potential to repurpose active antiviral compounds of plant origins for treating the SARS-CoV-2 infection. In…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Green synthesis of zinc oxide nanoparticles using <em>Anoectochilus elatus</em>, and their biomedical applications</strong> - Zinc and its derivatives requirement increased to enhance human immunity against the different pandemics, including covid-19. Green synthesis is an emerging field of research. Zinc oxide (ZnO) nanoparticles have been prepared from Anoectochilus elatus and characterized using absorption, vibrational and electron microscope analysis. They were carried for antibacterial, inflammatory control tendency, and potential antioxidant activities. The brine shrimp lethal assay tested the biologically…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neutralizing Effect of Synthetic Peptides toward SARS-CoV-2</strong> - The outbreak caused by SARS-CoV-2 has taken many lives worldwide. Although vaccination has started, the development of drugs to either alleviate or abolish symptoms of COVID-19 is still necessary. Here, four synthetic peptides were assayed regarding their ability to protect Vero E6 cells from SARS-CoV-2 infection and their toxicity to human cells and zebrafish embryos. All peptides had some ability to protect cells from infection by SARS-CoV-2 with the D614G mutation. Molecular docking predicted…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transient but recurrent complete heart block in a patient after COVID-19 vaccination - A case report</strong> - CONCLUSION: COVID-19 vaccination may transitorily interfere with cardiac conduction system even in subjects without known underlying heart disease.</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Loneliness is not a homogeneous experience: An empirical analysis of adaptive and maladaptive forms of loneliness in the UK</strong> - Understanding loneliness is pivotal to informing relevant evidence-based preventive interventions. The present study examined the prevalence of loneliness in the UK, during the COVID-19 pandemic, and the association between loneliness, mental health outcomes, and risk and protective factors for loneliness, after controlling for the effects of social isolation. It was estimated that 18.1% of the population in our study experienced moderately high to very high loneliness. We also found that…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Biological activity of interferons in the novel coronavirus infection COVID-19</strong> - CONCLUSION: The obtained data on deficiency of the functional biologically active IFN confirm the hypothesis about the predominant role of impaired IFN production of different types in the immunopathogenesis of the novel coronavirus infection.</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bromhexine is a potential drug for COVID-19; From hypothesis to clinical trials</strong> - COVID-19 (novel coronavirus disease 2019), caused by the SARS-CoV-2 virus, has various clinical manifestations and several pathogenic pathways. Although several therapeutic options have been used to control COVID-19, none of these medications have been proven to be a definitive cure. Transmembrane serine protease 2 (TMPRSS2) is a protease that has a key role in the entry of SARS-CoV-2 into host cells. Following the binding of the viral spike (S) protein to the angiotensin-converting enzyme 2…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The problem of the use of interferons in the novel coronavirus disease COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus)</strong> - By the end of 2021, about 200 studies on the effect of interferons (IFNs) on the incidence and course of the new coronavirus infection COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) have been reported worldwide, with the number of such studies steadily increasing. This review discusses the main issues of the use of IFN drugs in this disease. The literature search was carried out in the PubMed, Scopus, Cochrane Library, Web of Science, RSCI databases, as well as in the…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Challenges for rapamycin repurposing as a potential therapeutic candidate for COVID-19: implications for skeletal muscle metabolic health in older persons</strong> - The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that has spread worldwide, resulting in over 6 million deaths as of March</li>
|
||
</ul>
|
||
<ol start="2022" type="1">
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Older people have been disproportionately affected by the disease, as they have greater risk of hospitalization, are more vulnerable to severe infection, and have higher mortality than younger patients. Although effective vaccines have been rapidly developed…</li>
|
||
</ol>
|
||
<ul>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac</strong> - CONCLUSION: Low-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.</p></li>
|
||
<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 vaccine-induced immune thrombotic thrombocytopenia (VITT)</strong> - Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a novel prothrombotic disorder characterized by thrombosis, thrombocytopenia, and disseminated intravascular coagulation identified in hundreds of recipients of ChAdOx1 nCoV-19 (Oxford/AstraZeneca), an adenovirus vector coronavirus disease 2019 (COVID-19) vaccine. VITT resembles heparin-induced thrombocytopenia (HIT) in that patients have platelet-activating anti-platelet factor 4 antibodies; however, whereas heparin typically enhances…</p></li>
|
||
</ul>
|
||
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
|
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