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<title>06 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Doctoral researchers’ mental health and PhD training satisfaction during the German COVID-19 lockdown: results from an international research sample</strong> -
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<div>
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Academia has been facing a mental health crisis particularly affecting early career researchers (ECRs). Moreover, the COVID-19 pandemic posed an unprecedented burden on the mental health of many individuals. Therefore, we cross-sectionally investigated how doctoral researchers (N = 222) evaluate their mental health status and satisfaction with their PhD training before and during the pandemic. As compared to self-reported, retrospective evaluations about the pre-pandemic state, we found decreased satisfaction with PhD training and overall well-being. The whole sample exhibited high levels of personal and work-related burnout, a fifth indicated clinically meaningful levels of depressive symptoms and almost 25% experienced severe loneliness. When exploring predictors of depression, anxiety, and burnout, we identified low satisfaction with PhD training as the most prominent predictor for poor mental health, suggesting a link between the doctoral work and their mental health status. Females vs. males and doctoral researchers in individual doctorate vs. structured PhD programs reported higher symptoms of burnout. Our study replicates previous findings of poor mental health in doctoral researchers and indicates further decreases of mental wellbeing under the influence of the pandemic. Systematic adjustments in academia are required to improve the mental health of ECRs.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/nv4ut/" target="_blank">Doctoral researchers’ mental health and PhD training satisfaction during the German COVID-19 lockdown: results from an international research sample</a>
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<li><strong>The SARS-CoV-2 Spike protein induces long-term transcriptional perturbations of mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in obese mice</strong> -
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Background: As the pandemic evolves, post-acute sequelae of CoV-2 (PACS) including cardiovascular manifestations have emerged as a new health threat. This study aims to study whether the Spike protein plus obesity can exacerbate PACS-related cardiomyopathy. Methods: A Spike protein-pseudotyped (Spp) virus with the proper surface tropism of SARS-CoV-2 was developed for viral entry assay in vitro and administration into high fat diet (HFD)-fed mice. The systemic viral loads and cardiac transcriptomes were analyzed at 2 and 24 hrs, 3, 6, and 24 weeks post introducing (wpi) Spp using RNA-seq or real time RT-PCR. Echocardiography was used to monitor cardiac functions. Results: Low-density lipoprotein cholesterol enhanced viral uptake in endothelial cells, macrophages, and cardiomyocyte-like H9C2 cells. Selective cardiac and adipose viral depositions were observed in HFD mice but not in normal-chow-fed mice. The cardiac transcriptional signatures in HFD mice at 3, 6, and 24 wpi showed systemic suppression of mitochondria respiratory chain genes including ATP synthases and nicotinamide adenine dinucleotide:ubiquinone oxidoreductase gene members, upregulation of stress pathway-related crucial factors such as nuclear factor-erythroid 2-related factor 1 and signal transducer and activator of transcription 5A, and increases in expression of glucose metabolism-associated genes. As compared with the age-matched HFD control mice, cardiac ejection fraction and fractional shortening were significantly decreased, while left ventricular end-systolic diameter and volume were significantly elevated, and cardiac fibrosis was increased in HFD mice at 24 wpi. Conclusion: Our data demonstrated that the Spike protein could induce long-term transcriptional suppression of mitochondria metabolic genes and cause cardiac fibrosis and myocardial contractile impairment, providing mechanistic insights to PACS-related cardiomyopathy.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.05.522853v1" target="_blank">The SARS-CoV-2 Spike protein induces long-term transcriptional perturbations of mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in obese mice</a>
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</div></li>
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<li><strong>Targets and cross-reactivity of human T cell recognition of Common Cold Coronaviruses</strong> -
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The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with the betaCoV genus also containing subgenera with zoonotic and pandemic concern, including sarbecoCoV (SARS-CoV and SARS-CoV-2) and merbecoCoV (MERS-CoV). It is therefore warranted to explore pan-CoV vaccine concepts, to provide adaptive immune protection against new potential CoV outbreaks, particularly in the context of betaCoV sub lineages. To explore the feasibility of eliciting CD4+ T cell responses widely cross-recognizing different CoVs, we utilized samples collected pre-pandemic to systematically analyze T cell reactivity against representative alpha (NL63) and beta (OC43) common cold CoVs (CCC). Similar to previous findings on SARS-CoV-2, the S, N, M, and nsp3 antigens were immunodominant for both viruses while nsp2 and nsp12 were immunodominant for NL63 and OC43, respectively. We next performed a comprehensive T cell epitope screen, identifying 78 OC43 and 87 NL63-specific epitopes. For a selected subset of 18 epitopes, we experimentally assessed the T cell capability to cross-recognize sequences from representative viruses belonging to alphaCoV, sarbecoCoV, and beta-non-sarbecoCoV groups. We found general conservation within the alpha and beta groups, with cross-reactivity experimentally detected in 89% of the instances associated with sequence conservation of >67%. However, despite sequence conservation, limited cross-reactivity was observed in the case of sarbecoCoV (50% of instances), indicating that previous CoV exposure to viruses phylogenetically closer to this subgenera is a contributing factor in determining cross-reactivity. Overall, these results provided critical insights in the development of future pan-CoV vaccines.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.04.522794v1" target="_blank">Targets and cross-reactivity of human T cell recognition of Common Cold Coronaviruses</a>
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<li><strong>Poor neutralizing antibody responses against SARS-CoV-2 Omicron BQ.1.1 and XBB in Norway in October 2022</strong> -
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New sub-lineages of the SARS-CoV-2 omicron variants with enhanced ability to evade existing antibody responses continue to evolve. A better understanding how susceptible emerging virus variants are to immunity induced by vaccination or infection could help predict which strains will become dominant going forward. Here we evaluate neutralizing antibodies against several clinical isolates of omicron variants including BQ.1.1 and XBB in sera from 3x mRNA vaccinated individuals and individuals with breakthrough infections with early (BA.1 or 2) or late (BA.5) omicron variants. In addition, we evaluate neutralizing antibodies in serum samples harvested from 32 individuals from the middle of October 2022, to provide a more recent estimate of immunity. As expected, serum samples harvested after breakthrough infections were more efficient at neutralizing all the omicron variants, compared to sera from non-infected individuals. While neutralization remained high against variants such as BA.2.75.2, BR.1 and BF.7, there was a marked reduction in neutralizing titers against BQ.1.1 and XBB. Similarly, most serum samples harvested in October 2022 had very low neutralizing antibodies against BQ.1.1 and XBB, suggesting that these variants and their descendants will dominate infection waves in Norway this winter season.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.05.522845v1" target="_blank">Poor neutralizing antibody responses against SARS-CoV-2 Omicron BQ.1.1 and XBB in Norway in October 2022</a>
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<li><strong>Urban birds become less fearful following COVID-19 reopenings</strong> -
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Following the COVID-19 pandemic, many people around the world stayed home, drastically altering human activity in cities. This exceptional moment provided researchers the opportunity to test how urban animals respond to human disturbance, in some cases testing fundamental questions on the mechanistic impact of urban behaviors on animal behavior. However, at the end of this ‘anthropause’, human activity returned to cities. How might each of these strong shifts affect wildlife in the short and long term? We focused on fear response, a trait essential to tolerating urban life. We measured flight initiation distance at both individual and population-levels for an urban bird before, during, and after the anthropause to examine if birds experienced longer-term changes after a year of lowered human presence. Dark-eyed juncos did not change fear levels during the anthropause, but they became drastically less fearful afterwards. These surprising and counter-intuitive findings, made possible by following the behavior of individuals over time, has led to a novel understanding that fear response can be driven by plasticity, yet not habituation-like processes. The pandemic-caused changes in human activity have shown that there is great complexity in how humans modify a behavioral trait fundamental to urban tolerance in animals.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.04.522762v1" target="_blank">Urban birds become less fearful following COVID-19 reopenings</a>
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<li><strong>Challenges in estimating waning effectiveness of two doses of BNT162b2 and ChAdOx1 COVID-19 vaccines beyond six months: an OpenSAFELY cohort study using linked electronic health records</strong> -
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Quantifying the waning effectiveness of second COVID-19 vaccination beyond six months and against the omicron variant is important for scheduling subsequent doses. With the approval of NHS England, we estimated effectiveness up to one year after second dose, but found that bias in such estimates may be substantial.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.04.22283762v1" target="_blank">Challenges in estimating waning effectiveness of two doses of BNT162b2 and ChAdOx1 COVID-19 vaccines beyond six months: an OpenSAFELY cohort study using linked electronic health records</a>
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<li><strong>Cost & Cost-Effectiveness of Implementing SD Biosensor Antigen Detecting SARs-CoV-2 Rapid Diagnostic Tests in Kenya</strong> -
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The COVID-19 pandemic has created a need to rapidly scale-up testing services. In Kenya, services for SARS-CoV-2 nucleic acid amplifying test (NAAT) have often been unavailable or delayed, precluding the clinical utility of the results. The introduction of antigen-detecting rapid diagnostic tests (Ag-RDT) has had the potential to fill at least a portion of the ‘testing gap’. We, therefore, evaluated the cost-effectiveness of implementing SD Biosensor Antigen Detecting SARs-CoV-2 Rapid Diagnostic Tests in Kenya. We conducted a cost and cost-effectiveness of implementing SD biosensor antigen-detecting SARS-CoV-2 rapid diagnostic test using a decision tree model following the Consolidated Health Economic Evaluation Standards (CHEERS) guidelines under two scenarios. In the first scenario, we compared the use of Ag-RDT as a first-line diagnostic followed by using NAAT assay, to the use of NAAT only. In the second scenario, we compared the use of Ag-RDT to clinical judgement. We used a societal perspective and a time horizon of patient care episodes. Cost and outcomes data were obtained from primary and secondary data. We used one-way and probabilistic sensitivity analysis to assess the robustness of the results. At the point of care, Ag-RDT use for case management in settings with access to delayed confirmatory NAAT testing, the use of Ag-RDT was cost-effective (ICER = US$ 964.63 per DALY averted) when compared to Kenya’s cost-effectiveness threshold (US$ 1003.4). In a scenario with no access to NAAT, comparing the Ag-RDT diagnostic strategy with the no-test approach, the results showed that Ag-RDT was a cost-saving and optimal strategy (ICER = US$ 1490.33 per DALY averted). At a higher prevalence level and resource-limited setting such as Kenya, implementing Ag-RDT to complement NAAT testing will be a cost-effective strategy in a scenario with delayed access to NAAT and a cost-saving strategy in a scenario with no access to NAAT assay.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.05.23284225v1" target="_blank">Cost &amp; Cost-Effectiveness of Implementing SD Biosensor Antigen Detecting SARs-CoV-2 Rapid Diagnostic Tests in Kenya</a>
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<li><strong>Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune modifying therapies</strong> -
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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes debilitating swelling and destruction of the joints. People with RA are treated with drugs that actively suppress one or more parts of their immune system, and these may alter their response to vaccination against SARS-CoV-2. In this study, we analyzed blood samples from a cohort of RA subjects after receiving a 2-dose mRNA COVID-19 vaccine regimen. Our data show that individuals on the CTLA4-Ig therapy abatacept have reduced levels of SARS-CoV-2-neutralizing antibodies after vaccination. At a cellular level, these subjects show reduced activation and class-switching of SARS-CoV-2-specific B cells, as well as reduced numbers and impaired helper cytokine production by SARS-CoV-2-specific CD4<sup>+</sup> T cells. Individuals on methotrexate showed similar but less severe defects in vaccine response, whereas individuals on the B celldepleting therapy rituximab had a near-total loss of antibody production after vaccination. These data define a specific cellular phenotype associated with impaired response to SARS-CoV-2 vaccination in RA subjects on different immune-modifying therapies, and help inform efforts to improve vaccination strategies in this vulnerable population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.03.23284167v1" target="_blank">Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune modifying therapies</a>
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<li><strong>Interim results from comparison of immune responses elicited by an inactivated and a vectored SARS-CoV-2 vaccine in seronegative and seropositive participants in India</strong> -
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Background There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the 18 to 45-year age-group began in April 2021 when seropositivity rates in the general population were rising due to the Delta wave in April-May 2021. Methods Between 30 June 2021 and 28 January 2022, we enrolled 691 participants in the 18-45 age group across 4 clinical sites in India. In this non-randomized and laboratory blinded study, participants received either two doses of Covaxin® 4 weeks apart or two doses of Covishield™ 12 weeks apart per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titer (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. Findings When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield™ elicited higher antibody responses than Covaxin® as measured by seroconversion rate (98.3% vs 74.4%, p<0.0001 in seronegative individuals; 91.7% vs 66.9%, p<0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 BAU/ml, p<0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p<0.0001 in seropositive individuals). Not all sites recruited at the same time, therefore site-specific immunogenicity was impacted by the timing of vaccination relative to the Delta and Omicron waves. Surrogate neutralizing antibody responses against variants-of-concern were higher in Covishield™ recipients than in Covaxin® recipients and in seropositive than in seronegative individuals after both vaccination and asymptomatic Omicron infection. T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the Omicron wave. In seronegative individuals, Covishield™ elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin® elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals. Interpretation Covishield™ elicited immune responses of higher magnitude and breadth than Covaxin® in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of the majority of the vaccinated Indian population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.03.22284082v1" target="_blank">Interim results from comparison of immune responses elicited by an inactivated and a vectored SARS-CoV-2 vaccine in seronegative and seropositive participants in India</a>
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<li><strong>Risk factors for long COVID among healthcare workers, Brazil, 2020&2022</strong> -
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Objectives: We aimed to determine risk factors for the development of long coronavirus disease (COVID) in healthcare workers (HCWs). Methods: We conducted a case-control study among HCWs who had confirmed COVID-19 infection working in a Brazilian healthcare system between March 1, 2020 and July 15, 2022. Cases were defined as those having long COVID per the Centers for Disease Control and Prevention definition. Controls were defined as HCWs who had documented COVID-19 infection but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up. Results: Of 7,051 HCWs diagnosed with COVID-19 infection, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with development of long COVID were female sex (OR 1.21 [CI95 1.05-1.39]), age (OR 1.01 [CI95 1.00-1.02]), and two or more COVID-19 infections (1.27 [CI95 1.07-1.50]). Those infected with the Delta variant (OR 0.30 [CI95 0.17-0.50]) or the Omicron variant (OR 0.49 [CI95 0.30-0.78]), and those receiving four COVID-19 vaccine doses prior to infection (OR 0.05 [CI95 0.01-0.19]) were significantly less likely to develop long COVID. Conclusions: Long COVID can be prevalent among HCWs. We found that acquiring more than one COVID-19 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.03.22284043v1" target="_blank">Risk factors for long COVID among healthcare workers, Brazil, 2020&amp;2022</a>
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<li><strong>Spatiotemporal Evolution of SARS-CoV-2 Alpha and Delta Variants during a Large Nationwide Outbreak in Vietnam, 2021</strong> -
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In 2021, Vietnam experienced a large nationwide outbreak of COVID-19, with over 1.7 million infections and 32,000 deaths. We generated 1,303 SARS-CoV-2 whole-genome sequences, and mapped out the public health measures alongside the evolutionary trajectory of the pathogen. The Alpha variant caused sporadic outbreaks in early 2021 prior to the upsurge in cases associated with the Delta variant from June onward. The Delta variant outbreak was almost entirely confined to the AY.57 lineage, accounting for 99.2% of 1,212 Delta variant sequences, and resulting from a single introduction. Viral dispersal from the north, where it was first introduced into Vietnam, to the south, marked the start of the nationwide outbreak, with the south subsequently seeding the virus back to the other regions. Distinct AY.57 phylogenetic clusters in different regions of Vietnam were documented, pointing to the impact of in-country lockdown. Genomic surveillance is critical to inform pandemic response.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.03.22283384v1" target="_blank">Spatiotemporal Evolution of SARS-CoV-2 Alpha and Delta Variants during a Large Nationwide Outbreak in Vietnam, 2021</a>
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<li><strong>Ethnic differences in the indirect impacts of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: An observational cohort study using OpenSAFELY</strong> -
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Background The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods We conducted a cohort study using OpenSAFELY (2018-2022). We grouped ethnicity (exposure), into five categories: White, South Asian, Black, Other, Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (e.g., blood pressure measurements) before and after 23rd March 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to: diabetes, cardiovascular disease, respiratory disease, and mental health before and after 23rd March 2020. Findings Of 14,930,356 adults in 2020 with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to White. There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in White ethnicity. Relatively, ethnic differences narrowed for heart failure admission in those of Asian and Black ethnicity compared to White. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation Our study suggests ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding LSHTM COVID-19 Response Grant (DONAT15912).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.04.23284174v1" target="_blank">Ethnic differences in the indirect impacts of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: An observational cohort study using OpenSAFELY</a>
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<li><strong>The 2022 RSV surge was driven by multiple viral lineages</strong> -
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The US experienced an early and severe respiratory syncytial virus (RSV) surge in autumn 2022. Despite the pressure this has put on hospitals and care centers, the factors promoting the surge in cases are unknown. To investigate whether viral characteristics contributed to the extent or severity of the surge, we sequenced 105 RSV-positive specimens from symptomatic patients diagnosed with RSV who presented to the Massachusetts General Hospital (MGH) and its outpatient practices in the Greater Boston Area. Genomic analysis of the resulting 77 genomes (54 with >80% coverage, and 23 with >5% coverage) demonstrated that the surge was driven by multiple lineages of RSV-A (91%; 70/77) and RSV-B (9%; 7/77). Phylogenetic analysis of all US RSV-A revealed 12 clades, 4 of which contained Massachusetts and Washington genomes. These clades individually had times to most recent common ancestor (tMRCA) between 2014 and 2017, and together had a tMRCA of 2009, suggesting that they emerged well before the COVID-19 pandemic. Similarly, the RSV-B genomes had a tMRCA between 2016 and 2019. We found that the RSV-A and RSV-B genomes in our sample did not differ statistically from the estimated clock rate of the larger phylogenetic tree (10.6 and 12.4 substitutions per year, respectively). In summary, the polyphyletic nature of viral genomes sequenced in the US during the autumn 2022 surge is inconsistent with the emergence of a single, highly transmissible causal RSV lineage.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.04.23284195v1" target="_blank">The 2022 RSV surge was driven by multiple viral lineages</a>
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<li><strong>Alternative epidemic indicators for COVID-19: a model-based assessment of COVID-19 mortality ascertainment in three settings with incomplete death registration systems</strong> -
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Not all COVID-19 deaths are officially reported and, particularly in low-income and humanitarian settings the magnitude of such reporting gaps remain sparsely characterised. Alternative data sources, including burial site worker reports, satellite imagery of cemeteries and social-media-conducted surveys of infection, may offer solutions. By merging these data with independently conducted, representative serological studies within a mathematical modelling framework, we aim to better understand the range of under-reporting using the example of three major cities: Addis Ababa (Ethiopia), Aden (Yemen) and Khartoum (Sudan) during 2020. We estimate 69% - 100%, 0.8% - 8.0% and 3.0% - 6.0% of COVID-19 deaths were reported in these three settings, respectively. In future epidemics, and in settings where vital registrations systems are absent or limited, using multiple alternative data sources could provide critically-needed, improved estimates of epidemic impact. However, ultimately, functioning vital registration systems are needed to ensure that, in contrast to COVID-19, the impact of future pandemics or other drivers of mortality are reported and understood worldwide.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.04.22283691v1" target="_blank">Alternative epidemic indicators for COVID-19: a model-based assessment of COVID-19 mortality ascertainment in three settings with incomplete death registration systems</a>
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<li><strong>SARS-CoV-2 Reinfection is Preceded by Unique Biomarkers and Related to Initial Infection Timing and Severity: an N3C RECOVER EHR-Based Cohort Study</strong> -
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Although the COVID-19 pandemic has persisted for over 2 years, reinfections with SARS-CoV-2 are not well understood. We use the electronic health record (EHR)-based study cohort from the National COVID Cohort Collaborative (N3C) as part of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative to characterize reinfection, understand development of Long COVID after reinfection, and compare severity of reinfection with initial infection. We validate previous findings of reinfection incidence (5.9%), the occurrence of most reinfections during the Omicron epoch, and evidence of multiple reinfections. We present novel findings that Long COVID diagnoses occur closer to the index date for infection or reinfection in the Omicron BA epoch. We report lower albumin levels leading up to reinfection and a statistically significant association of severity between first infection and reinfection (chi-squared value: 9446.2, p-value: 0) with a medium effect size (Cramer9s V: 0.18, DoF = 4).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.03.22284042v1" target="_blank">SARS-CoV-2 Reinfection is Preceded by Unique Biomarkers and Related to Initial Infection Timing and Severity: an N3C RECOVER EHR-Based Cohort Study</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>Efficacy and Safety of Jaktinib in Patients With COVID-19 Pneumoia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Jaktinib; Drug: Placebo<br/><b>Sponsor</b>: First Affiliated Hospital of Zhejiang 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>Effect of a Traditional Chinese Medicine Formulation on COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Traditional Chinese Medicine Formulation; Other: Placebo Treatment<br/><b>Sponsor</b>: First Affiliated Hospital Xi’an Jiaotong 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>Efficacy and Safety of Anti-COVID-19 Antibody SA58 Nasal Spray to Prevent Infection in High-risk Populations</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: SA58 Nasal Spray<br/><b>Sponsor</b>: Sinovac Life Sciences 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>Efficacy and Safety of SA58 Nasal Spray in Close Contact With COVID-19 People</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SA58 Nasal Spray; Drug: Placebo<br/><b>Sponsors</b>: Sinovac Life Sciences Co., Ltd.; Beijing Ditan 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>Immunogenicity and Safety of COVID-19 Vaccine in Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: One dose group; Biological: Two doses group; Biological: Aged 18-59 years; Biological: Aged 60 years old and above<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: CoronaVac/CoronaVac; Biological: CoronaVac/BNT162b2<br/><b>Sponsor</b>: Institut Pasteur de Tunis<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>Immunogenicity and Safety of COVID-19 Vaccine as a Booster Vaccination in Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant SARS-CoV-2 Vaccine (CHO Cell) LYB001; Biological: ZF2001<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Vaccine Booster (GEO-CM04S1) for the Prevention of COVID-19 in Patients With Chronic Lymphocytic Leukemia</strong> - <b>Conditions</b>: Chronic Lymphocytic Leukemia; COVID-19 Infection<br/><b>Interventions</b>: Procedure: Biospecimen Collection; Biological: mRNA COVID-19 Vaccine; Biological: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1<br/><b>Sponsors</b>: City of Hope Medical Center; National Cancer Institute (NCI)<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>Sars-COV-2 Immunity in immunoCOmpromised Populations</strong> - <b>Conditions</b>: SARS CoV 2 Infection; COVID-19<br/><b>Intervention</b>: Diagnostic Test: Humoral immunity<br/><b>Sponsors</b>: Maria Goossens; Université Libre de Bruxelles; Institute of Tropical Medicine, Belgium; Mensura EDPB; Erasme hospital<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>Safety, Tolerability and Pharmacokinetic Characteristics Evaluation on GST-HG171 Tablets</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GST-HG171; Drug: placebo of GST-HG171<br/><b>Sponsor</b>: Fujian Akeylink Biotechnology 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>Benefits of an Aerobic and Strength Rehabilitation Program With Post- SARS-CoV-2 Patients Moderate-severe</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Aerobic plus strength group; Other: Aerobic group<br/><b>Sponsor</b>: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Amantadine on Post-COVD-19 Fatigue</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Drug: Amantadine<br/><b>Sponsor</b>: Shahid Beheshti University of Medical Sciences<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>Enhanced External Counterpulsation to Treat Long COVID Fatigue</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Procedure: Enhanced external counterpulsation<br/><b>Sponsor</b>: Sheba Medical Center<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>Melatonin, Vitamins and Minerals Supplements for the Treatment of Covid-19 and Covid-like Illness</strong> - <b>Condition</b>: Influenza -Like Illness<br/><b>Intervention</b>: Drug: kelavit<br/><b>Sponsor</b>: Hôpital Universitaire Sahloul<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>Effectiveness of Rapid Antigen Testing of Students for COVID-19 in Reducing Absences From Schools in Bangladesh</strong> - <b>Condition</b>: School Absenteeism<br/><b>Intervention</b>: Diagnostic Test: Rapid Antigen Testing (RAT) for COVID-19<br/><b>Sponsors</b>: International Centre for Diarrhoeal Disease Research, Bangladesh; Columbia University<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral role of nanomaterials: a material scientist’s perspective</strong> - The present world continues to face unprecedented challenges caused by the COVID-19 pandemic. Collaboration between researchers of multiple disciplines is the need of the hour. There is a need to develop antiviral agents capable of inhibiting viruses and tailoring existing antiviral drugs for efficient delivery to prevent a surge in deaths caused by viruses globally. Biocompatible systems have been designed using nanotechnological principles which showed appreciable results against a wide range…</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>Fluorogenic reporter enables identification of compounds that inhibit SARS-CoV-2</strong> - The coronavirus SARS-CoV-2 causes the severe disease COVID-19. SARS-CoV-2 infection is initiated by interaction of the viral spike protein and host receptor angiotensin-converting enzyme 2 (ACE2). We report an improved bright and reversible fluorogenic reporter, named SURF (split UnaG-based reversible and fluorogenic protein-protein interaction reporter), that we apply to monitor real-time interactions between spike and ACE2 in living cells. SURF has a large dynamic range with a dark-to-bright…</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>mascRNA alleviates STING-TBK1 signaling-mediated immune response through promoting ubiquitination of STING</strong> - mascRNA (MALAT1-associated small cytoplasmic RNA) is a tRNA-like cytoplasmic small noncoding RNA whose function remains elusive. We previously revealed that this small RNA negatively regulates TLR4/2-triggered proinflammatory response while positively regulates TLR3-induced antiviral response. Here, we investigated whether and how mascRNA influences the stimulator of interferon genes (STING) signaling-triggered immune response. We found that overexpression of mascRNA inhibited the expression of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Porcine Epidemic Diarrhea Virus nsp13 Protein Downregulates Neonatal Fc Receptor Expression by Causing Promoter Hypermethylation through the NF-κB Signaling Pathway</strong> - Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic porcine enteric coronavirus that causes severe watery diarrhea and even death in piglets. The neonatal Fc receptor (FcRn) is the only transport receptor for IgG. FcRn expressed by intestinal epithelial cells can transport IgG from breast milk to piglets to provide immune protection. Previous studies have shown that viral infection affects FcRn expression. In this study, we showed for the first time, to our knowledge, that FcRn…</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>Identification and semisynthesis of (-)-anisomelic acid as oral agent against SARS-CoV-2 in mice</strong> - (-)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC(50) of 1.1 and 4.3 μM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung…</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>Rapid Resolution of Post-COVID-19 Inflammatory Syndrome in an Adult With Targeted Inhibition of Interleukin-1B</strong> - Multisystem inflammatory syndrome (MIS) is a severe inflammatory response that occurs days to weeks following the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). Initially known in children and named MIS-C, recently several cases of MIS in adults have been reported to the Centers for Disease Control and Prevention (CDC), leading to the recognition of a new disease MIS in adults (MIS-A). The current…</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-CD73 antibody activates human B cells, enhances humoral responses and induces redistribution of B cells in patients with cancer</strong> - CONCLUSIONS: Mupadolimab activates B cells and stimulates the production of antigen specific antibodies. The effects in patients with cancer suggest that activated, CD69^(POS) B cells redistribute to lymphoid tissues. Minor tumor regression was observed in several patients. These results support further investigation of mupadolimab as an immunotherapy for cancer and its potential use as a vaccine adjuvant.</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>Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19</strong> - Spleen tyrosine kinase (SYK) is a previously unidentified therapeutic target that inhibits neutrophil and macrophage activation in coronavirus disease 2019 (COVID-19). Fostamatinib, a SYK inhibitor, was studied in a phase 2 placebo-controlled randomized clinical trial and was associated with improvements in many secondary end points related to efficacy. Here, we used a multiomic approach to evaluate cellular and soluble immune mediator responses of patients enrolled in this trial. We…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry</strong> - SARS-CoV-2 Spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the Spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety…</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>Data-driven drug discovery for drug repurposing</strong> - To improve the decreased efficiency of drug discovery and development, drug repurposing (also called drug repositioning) has been expected, that it is a strategy for identifying new medical indications for approved, investigational or suspended drugs. Particularly, according to the rapid expansion of medical and life science data and the remarkable technological progress of AI technology in recent years, the approach of computational drug repurposing has been attracted as one of the applications…</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>Endogenous G-quadruplex-forming RNAs inhibit the activity of SARS-CoV-2 RNA polymerase</strong> - Replication of RNA viruses is catalysed by virus-specific polymerases, which can be targets of therapeutic strategies. In this study, we used a selection strategy to identify endogenous RNAs from a transcriptome library derived from lung cells that interact with the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. Some of the selected RNAs weakened the activity of RdRp by forming G-quadruplexes. These results suggest that certain endogenous RNAs, which potentially form G-quadruplexes, 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>Prospective mode of action of Ivermectin: SARS-CoV-2</strong> - The well-known anti-helminthic drug ivermectin (IVM) has been established as an example of drug repurposing for the management of SARS-CoV-2 infection. Various study has been done to understand the inhibitory mechanism of IVM against SARS-CoV-2 targets. Broadly, IVM has been categorized as a host-directed agent and the proposed mechanism involves inhibition of the IMPα/ß1-mediated nuclear import of viral proteins. In addition, in vitro/in vivo and molecular docking/dynamic simulation studies…</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>Circulating microRNAs as emerging regulators of COVID-19</strong> - Coronavirus disease 2019 (COVID-19), an infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has high incidence rates, spreads rapidly, and has caused more than 6.5 million deaths globally to date. Currently, several drugs have been used in the clinical treatment of COVID-19, including antivirals (e.g., molnupiravir, baricitinib, and remdesivir), monoclonal antibodies (e.g., etesevimab and tocilizumab), protease inhibitors…</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 ability of low- and High-SES schools to inhibit learning losses during the COVID-19 pandemic</strong> - The study examined whether the pandemic-induced digital distance learning affected the ability of educational units to inhibit learning losses and whether their SES compositions modified those effects. By applying random-intercept multinomial regression models to educational units’ average test scores comparing the 2019-2021 period to the 2017-2019 period based on data from the National Assessment of Basic Competencies in Hungary, the results indicated that educational units were less likely to…</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 a series of nucleoside analogs as effective anticoronaviral-2 drugs against the Omicron-B.1.1.529/BA.2 subvariant: A repurposing research study</strong> - Mysterious evolution of a new strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the Omicron variant, led to a new challenge in the persistent coronavirus disease 2019 (COVID-19) battle. Objecting the conserved SARS-CoV-2 enzymes RNA-dependent RNA polymerase (RdRp) and 3’-to-5’ exoribonuclease (ExoN) together using one ligand is a successful new tactic to stop SARS-CoV-2 multiplication and COVID-19 progression. The current comprehensive study investigated most nucleoside…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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