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<title>08 October, 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>When Lockdowns Force “Everyone” to Work From Home: Inequalities in Telework During COVID-19 in Uruguay</strong> -
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Working from home arrangements have been on the rise globally throughout the 21st century. Despite this trajectory, developing economies have trailed developed countries in adopting such arrangements. However, because of COVID-19 lockdowns and social distancing measures, countries such as Uruguay, where teleworking was scarce and unregulated, were forced to adopt this practice to ensure business continuity. Under such conditions, preexisting organizational and individual disparities stratified the likelihood of working from home during the pandemic. Conventional wisdom holds that the main determinants potential-to-telework stems almost exclusively from the nature of jobs themselves. This article expands the traditional understanding of telework determinants by showing that during the first stages of the pandemic individual features of the worker, and organizational and managerial features of the employer, were both determinative of the likelihood that a given worker would work from home. We conducted a secondary data analysis of the March 2020 wave of the Work Monitor, a web-based survey of 847 employed Uruguayan adults. We fitted several multivariate regression models predicting a) the odds of working for a company which adopted COVID-19-related teleworking policies at least for some workers and b) the odds of working from home as a consequence of COVID-19. As the adoption of telework was largely unplanned and abrupt, result show that disparities on organizational adoption of teleworking policies were related to pre-pandemic differences across organizations in terms of preparedness, technological investment, and management practices. Results also show that employers’ willingness to enable working from home policies was the strongest predictor, at any level, of the likelihood of individuals to telework during the national emergency. Individual disparities in terms of human capital also have a great impact on the likelihood of teleworking during lockdowns, but their effect depends on the existence of organizational teleworking policies. Findings’ implications for the present and future of telework in developing countries are discussed.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/nr4j3/" target="_blank">When Lockdowns Force “Everyone” to Work From Home: Inequalities in Telework During COVID-19 in Uruguay</a>
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</div></li>
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<li><strong>Using analogy-based messages to influence attitudes toward workplace COVID-19 vaccination mandates</strong> -
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Workplace mandates are a highly effective strategy for increasing COVID-19 vaccination rates, and their adoption by United States employers grew throughout 2021. Still, public opinion on these mandates has remained starkly polarized. Drawing from the widespread use of analogies in health communication during the pandemic, we investigated whether analogies to widely-accepted workplace safety rules could affect attitudes toward vaccination mandates. In a survey experiment conducted in September-October 2021, 1194 respondents were randomized to one of three messages about workplace COVID-19 vaccination mandates that included (1) no analogy; (2) an analogy to workplace hard hat policies; or (3) an analogy to workplace smoking bans. Only the smoking analogy increased support for (b = 0.41; p < .001) and perceived effectiveness of (b = 0.20; p = .037) workplace vaccination mandates. Moreover, the smoking analogy’s effect on perceived effectiveness was greater for unvaccinated respondents (b = 0.54; p = .015 for interaction) and was mediated via the perceived strength of mandate enforcement (indirect effect = 0.05; 95% confidence interval = [0.01, 0.10]; P = .006). Our results demonstrate that policymakers and administrators may use a simple analogy to boost public opinion on workplace mandates for COVID-19 vaccination.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/e8p4s/" target="_blank">Using analogy-based messages to influence attitudes toward workplace COVID-19 vaccination mandates</a>
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<li><strong>Upregulation of CD55 complement regulator in distinct PBMC subpopulations of COVID-19 patients is associated with suppression of interferon responses.</strong> -
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Complement activation has been verified in COVID-19 patients by both increased serum levels of complement factors C3a and C5b-9 and increased complement deposition at the tissue levels. Complement regulatory proteins (CRPs) CD55, CD46, CD59 and CR1 act to control complement overactivation and eliminate complement deposition and cell lysis. The aim of the study was to investigate the expression of CRPs in COVID-19 in order to identify potential dysregulated expression patterns of CRPs and address whether these may contribute to disease pathogenesis. Single cell RNA-sequencing (scRNA-seq) analysis performed on isolated PBMCs revealed an increase of CD55 expression in severe and critical COVID-19 patients compared to healthy controls. This increase was also detected upon integrated subclustering analysis of the monocyte, T cell and B cell populations. Flow cytometric analysis verified the distinct pattern of upregulated CD55 expression in monocyte and T cell sub populations of severe COVID-19 patients. This upregulation was associated with decreased expression of interferon stimulated genes (ISGs) in patients with severe COVID-19 suggesting a potential suppressor effect of CD55 on interferon responses. The present study identifies a COVID-19 specific CD55 expression pattern in PBMC subpopulations that coincides with reduced interferon responses thus indicating that the complement regulator CD55 may contribute to COVID-19 pathogenesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.07.510750v1" target="_blank">Upregulation of CD55 complement regulator in distinct PBMC subpopulations of COVID-19 patients is associated with suppression of interferon responses.</a>
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<li><strong>Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets.</strong> -
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The infection and replication cycle of all viruses depend on interactions between viral and host proteins. Each of these protein-protein interactions is therefore a potential drug target. These host-virus interactions often involve a disordered protein region on one side of the interface and a folded protein domain on the other. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind peptides from human proteins. Of 281 high/medium confidence peptides, 23 interactions involving eight SARS-CoV-2 protein domains were tested by fluorescence polarization, and binding was observed with affinities spanning the whole micromolar range. The key specificity determinants were established for six of these domains, two based on ProP-PD and four by alanine scanning SPOT arrays. Finally, two cell-penetrating peptides, targeting Nsp9 and Nsp16, respectively, were shown to function as inhibitors of viral replication. Our findings demonstrate how high-throughput peptide binding screens simultaneously provide information on potential host-virus interactions and identify ligands with antiviral properties.
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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/10.1101/2022.10.07.511324v1" target="_blank">Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets.</a>
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<li><strong>Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains</strong> -
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With the success of mRNA vaccines against coronavirus disease 2019 (COVID-19), strategies can now focus on improving vaccine potency, breadth, and stability. We present the design and preclinical evaluation of domain-based mRNA vaccines encoding the wild-type spike-protein receptor-binding (RBD) and/or N-terminal domains (NTD). An NTD-RBD linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2-8{degrees}C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses and protection from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) compared with mRNA-1273 immunized mice, especially at lower vaccine dosages. These results support clinical assessment of mRNA-1283 (NCT05137236).
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.07.511319v1" target="_blank">Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains</a>
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<li><strong>Fate and plasticity of SARS-CoV-2-specific B cells during memory and recall response in humans</strong> -
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B cell responses to different pathogens recruit tailored effector mechanisms, resulting in functionally specialized subsets. For human memory B cells (MBCs), these include CD21+ resting, CD21-CD27+ activated, and CD21-CD27- atypical cells. Whether these subsets follow deterministic or interconnected fates is unknown. We demonstrate in COVID-19 patients that single clones of SARS-CoV-2-specific MBCs followed multiple fates with distinctive phenotypic and functional characteristics. 6-12 months after infection, most circulating MBCs were CD21+ resting cells, which also accumulated in peripheral lymphoid organs where they acquired markers of tissue residency. Conversely, at acute infection and following SARS-CoV-2-specific immunization, CD21- MBCs became the predominant subsets, with atypical MBCs expressing high T-bet, inhibitory molecules, and distinct chemokine receptors. B cell receptor sequencing allowed tracking of individual MBC clones differentiating into CD21+, CD21-CD27+, and CD21-CD27- cell fates. Collectively, single MBC clones can adopt functionally different trajectories, thus contributing to immunity to infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.07.511336v1" target="_blank">Fate and plasticity of SARS-CoV-2-specific B cells during memory and recall response in humans</a>
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<li><strong>Incipient parallel evolution of SARS-CoV-2 Deltacron variant in South Brazil</strong> -
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With the coexistence of multiple lineages and increased international travel, recombination and gene flow are likely to become increasingly important in the adaptive evolution of SARS-CoV-2. This could result in the incipient parallel evolution of multiple recombinant lineages. However, identifying recombinant lineages is challenging, and the true extent of recombinant evolution in SARS-CoV-2 may be underestimated. This study describes the first SARS-CoV-2 Deltacron recombinant case identified in Brazil. We demonstrate that the recombination breakpoint is at the beginning of Spike gene (S). The 5’ genome portion (circa 22 kb) resembles the AY.101 lineage (VOC Delta), and the 3’ genome portion (circa 8 kb nucleotides) is most similar to the BA.1.1 lineage (VOC Omicron). Furthermore, evolutionary genomic analyses indicate that the new strain emerged after a single recombination event between lineages of diverse geographical locations in December 2021 in South Brazil. This Deltacron, named AYBA-RS, is one out of almost 30 recombinants described this year. The submission of only four sequences in the GISAID database suggests that this Brazilian lineage had a minor epidemiological impact. On the other hand, the recent emergence of this and various other Deltacron recombinant lineages (i.e., XD, XF, and XS) suggests that gene flow and recombination may play an increasingly important role in the COVID-19 pandemic. We explain the evolutionary and population genetic theory that support this assertion, and we conclude that this stresses the need for continued genomic and epidemiological surveillance. This is particularly important for countries where multiple variants are present, as well as for countries that receive significant inbound international travel.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.06.511203v1" target="_blank">Incipient parallel evolution of SARS-CoV-2 Deltacron variant in South Brazil</a>
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<li><strong>Baculoviral COVID-19 Delta DNA vaccine cross-protects against SARS-CoV2 variants in K18-ACE2 transgenic mice</strong> -
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After severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) made the world tremble with a global pandemic, SARS-CoV2 vaccines were developed. However, due to the coronavirus’s intrinsic nature, new variants emerged, such as Delta and Omicron, refractory to the vaccines derived using the original Wuhan strain. We developed an HERV-enveloped recombinant baculoviral DNA vaccine against SARS-CoV2 (AcHERV-COVID19S). A non-replicating recombinant baculovirus that delivers the SARS-CoV2 spike gene showed a protective effect against the homologous challenge in a K18-hACE2 Tg mice model; however, it offered only a 50% survival rate against the SARS-CoV2 Delta variant. Therefore, we further developed the AcHERV-COVID19 Delta vaccine (AcHERV-COVID19D). Cross-protection experiments revealed that mice vaccinated with the AcHERV-COVID19D showed 100% survival upon challenge with Delta and Omicron variants and 71.4% survival against prototype SARS-CoV2. These results support the potential of the viral vector vaccine, AcHERV-COVID19D, in preventing the spread of coronavirus variants such as Omicron and SARS-CoV2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.07.511252v1" target="_blank">Baculoviral COVID-19 Delta DNA vaccine cross-protects against SARS-CoV2 variants in K18-ACE2 transgenic mice</a>
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<li><strong>Neutralization of SARS-CoV-2 Omicron BA.4/BA.5 subvariant by a booster dose of bivalent adjuvanted subunit vaccine containing Omicron BA.4/BA.5 and BA.1 subvariants</strong> -
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The dominance of SARS-CoV-2 variants of concern (VoC), such as the Omicron subvariants, is a threat to the current vaccination scheme due to increased resistance to immune neutralization and greater transmissibility. To develop the next generation of prefusion SARS-CoV-2 spike protein (S-2P) subunit vaccine adjuvanted with CpG1018 and aluminum hydroxide, mice immunized with two doses of the adjuvanted ancestral Wuhan strain (W) followed by the third dose of the W or Omicron variants (BA.1 or BA.4/BA.5) S-2P, or a combination of the above bivalent S-2Ps. Antisera from mice were tested against pseudovirus neutralization assay of ancestral SARS-CoV-2 (WT) and Omicron BA.4/BA.5 subvariant. Boosting with bivalent mixture of Omicron BA.4/BA.5 and W S-2P achieved the highest neutralizing antibody titers against BA.4/BA.5 subvariant pseudovirus compared to other types of S-2P as boosters.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.07.511263v1" target="_blank">Neutralization of SARS-CoV-2 Omicron BA.4/BA.5 subvariant by a booster dose of bivalent adjuvanted subunit vaccine containing Omicron BA.4/BA.5 and BA.1 subvariants</a>
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<li><strong>Projecting the seasonality of endemic COVID-19</strong> -
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Importance: Successive waves of infection by SARS-CoV-2 have left little doubt that COVID-19 will transition to an endemic disease, yet the future seasonality of COVID-19 remains one of its most consequential unknowns. Foreknowledge of spatiotemporal surges would have immediate and long-term consequences for medical and public health decision-making. Objective: To estimate the impending endemic seasonality of COVID-19 in temperate population centers via a phylogenetic ancestral and descendent states approach that leverages long-term data on the incidence of circulating coronaviruses. Design: We performed a comparative evolutionary analysis on literature-based monthly verified cases of HCoV-NL63, HCoV-229E, HCoV-HKU1, and HCoV-OC43 infection within populations across the Northern Hemisphere. Ancestral and descendent states analyses on human-infecting coronaviruses provided projections of the impending seasonality of endemic COVID-19. Setting: Quantitative projections of the endemic seasonality of COVID-19 were based on human endemic coronavirus infection incidence data from New York City (USA); Denver (USA); Tampere (Finland); Trondelag (Norway); Gothenburg (Sweden); Stockholm (Sweden); Amsterdam (Netherlands); Beijing (China); South Korea (Nationwide); Yamagata (Japan); Hong Kong; Nakon Si Thammarat (Thailand); Guangzhou (China); and Sarlahi (Nepal). Main Outcome(s) and Measure(s): The primary projection was the monthly relative frequency of SARS-CoV-2 infections in each geographic locale. Four secondary outcomes consisted of empirical monthly relative frequencies of the endemic human-infecting coronaviruses HCoV-NL63, -229E, -HKU1, and -OC43. Results: We project asynchronous surges of SARS-CoV-2 across locales in the Northern Hemisphere. In New York City, SARS-CoV-2 incidence is projected in late fall and winter months (Nov.-Jan.), In Tampere, Finland; Yamagata, Japan; and Sarlahi, Nepal incidence peaks in February. Gothenburg and Stockholm in Sweden reach peak incidence between November and February. Guangzhou, China; and South Korea. In Denver, incidence peaks in early Spring (Mar.). In Amsterdam, incidence rises in late fall (Dec.), and declines in late spring (Apr.). In Hong Kong, the projected apex of infection is in late fall (Nov.-Dec.), yet variation in incidence is muted across other seasons. Seasonal projections for Nakhon Si Thammarat, Thailand and for Beijing, China are muted compared to other locations. Conclusions and Relevance: This knowledge of likely spatiotemporal surges of COVID-19 is fundamental to medical preparedness and expansions of public health interventions that anticipate the impending endemicity of this disease and mitigate COVID-19 transmission. These results provide crucial guidance for adaptive public health responses to this disease, and are vital to the long-term mitigation of COVID-19 transmission.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.26.22269905v2" target="_blank">Projecting the seasonality of endemic COVID-19</a>
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<li><strong>COVID-19: impact of original, Gamma, Delta, and Omicron variants of SARS-CoV-2 in vaccinated and unvaccinated pregnant and postpartum women</strong> -
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Introduction This study compares the clinical characteristics and disease progression of vaccinated and unvaccinated pregnant and postpartum women positive for the original, Gamma, Delta, and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using Brazilian epidemiological data. Methods Data of pregnant or postpartum patients with coronavirus disease 2019 (COVID-19) SARS-CoV-2 confirmed using polymerase chain reaction from February 2020 to July 2022 were extracted from a Brazilian national database. The patients were divided based on vaccination status and viral variant (original, Gamma, Delta, and Omicron). The patients demographic data, clinical characteristics, comorbidities, signs, symptoms, and outcomes were retrospectively compared. Results Data from 10,003 pregnant and 2,361 postpartum women were extracted from the database. Among unvaccinated patients, postpartum women were more likely to be admitted to the intensive care unit (ICU). These patients were more likely to require invasive ventilation when infected with the original, Gamma, and Omicron variants and were more likely to die when infected with the original and Gamma variants. Patients who were vaccinated had reduced adverse outcomes including ICU admission, requirement for invasive ventilation, and death. Conclusion Postpartum women were more likely to develop severe COVID-19 that required ICU admission or invasive ventilatory support or led to death, among all variants, especially when the patients were unvaccinated. Therefore, the risk of severe COVID-19 should not be underestimated after delivery. Vaccinated patients had a lower risk of severe outcomes. Vaccination should be a top priority in pregnant and postpartum patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.05.22280754v1" target="_blank">COVID-19: impact of original, Gamma, Delta, and Omicron variants of SARS-CoV-2 in vaccinated and unvaccinated pregnant and postpartum women</a>
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<li><strong>The Incidence of Immune Mediated Inflammatory Diseases Following COVID-19: a Matched Cohort Study in UK Primary Care</strong> -
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Abstract Objective To assess whether there is an association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) infection and the incidence of immune mediated inflammatory diseases (IMIDs). Design Matched cohort study. Setting Primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. Participants The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS CoV-2 infection by reverse transcriptase polymerase chain reaction (RT-PCR) or lateral flow antigen test, and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults in the unexposed cohort with no diagnosis of confirmed or suspected SARS CoV-2 infection and no prior diagnosis of IMIDs. Main Outcome Measures The primary outcome measure was a composite of the incidence of any of the following IMIDs: 1. autoimmune thyroiditis, 2. coeliac disease, 3. inflammatory bowel disease (IBD), 4. myasthenia gravis, 5. pernicious anaemia, 6. psoriasis, 7. rheumatoid arthritis (RA), 8. Sjogrens syndrome, 9. systemic lupus erythematosus (SLE), 10. type 1 diabetes mellitus (T1DM), and 11. vitiligo. The secondary outcomes were the incidence of each of these conditions separately. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes comparing the exposed to the unexposed cohorts, and adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications. Results 537 patients (0.11%) in the exposed cohort developed an IMID during the follow-up period over 0.29 person years, giving a crude incidence rate of 3.54 per 1000 person years. This was compared 1723 patients (0.09%) over 0.29 person years in the unexposed cohort, with an incidence rate of 2.82 per 1000 person years. Patients in the exposed cohort had a 22% relative increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.10 to 1.34). The incidence of three IMIDs were statistically significantly associated with SARS CoV-2 infection. These were T1DM (aHR 1.56, 95% CI 1.09 to 2.23), IBD (1.52, 1.23 to 1.88), and psoriasis (1.23, 1.05 to 1.42). Conclusions SARS CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19, including Long COVID and matched controls.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.06.22280775v1" target="_blank">The Incidence of Immune Mediated Inflammatory Diseases Following COVID-19: a Matched Cohort Study in UK Primary Care</a>
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<li><strong>Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program</strong> -
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Importance: Characterizing the effect of vaccination on long COVID allows for better healthcare recommendations. Objective: To determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection. Design, Settings, and Participants: Retrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C). Exposures: Pre-COVID-19 receipt of a complete vaccine series versus no pre-COVID-19 vaccination. Main Outcomes and Measures: Two approaches to the identification of long COVID were used. In the clinical diagnosis cohort (n=47,752), ICD-10 diagnosis codes or evidence of a healthcare encounter at a long COVID clinic were used. In the model-based cohort (n=199,498), a computable phenotype was used. The association between pre-COVID vaccination and long COVID was estimated using IPTW-adjusted logistic regression and Cox proportional hazards. Results: In both cohorts, when adjusting for demographics and medical history, pre-COVID vaccination was associated with a reduced risk of long COVID (clinic-based cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; model-based cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75). Conclusions and Relevance: Long COVID has become a central concern for public health experts. Prior studies have considered the effect of vaccination on the prevalence of future long COVID symptoms, but ours is the first to thoroughly characterize the association between vaccination and clinically diagnosed or computationally derived long COVID. Our results bolster the growing consensus that vaccines retain protective effects against long COVID even in breakthrough infections.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.06.22280795v1" target="_blank">Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program</a>
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<li><strong>Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention</strong> -
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Intensive care unit (ICU) staff continue to face recurrent work-related traumatic events throughout the COVID-19 pandemic. Intrusive memories (IMs) of such traumatic events comprise sensory image-based memories. Harnessing research on preventing IMs with a novel behavioural intervention on the day of trauma, here we take critical next steps in developing this approach as a treatment for ICU staff who are already experiencing IMs days, weeks, or months post-trauma. To address the urgent need to develop novel mental health interventions, we used Bayesian statistical approaches to optimise a brief imagery-competing task intervention to reduce the number of IMs. We evaluated a digitised version of the intervention for remote, scalable delivery. We conducted a two-arm, parallel-group, randomised, adaptive Bayesian optimisation trial. Eligible participants worked clinically in a UK NHS ICU during the pandemic, experienced at least one work-related traumatic event, and at least three IMs in the week prior to recruitment. Participants were randomised to receive immediate or delayed (after four weeks) access to the intervention. Primary outcome was the number of IMs of trauma during week 4, controlling for baseline week. Analyses were conducted on an intention-to-treat basis as a between-group comparison. Prior to final analysis, sequential Bayesian analyses were conducted (n=20,23,29,37,41,45) to inform early stopping of the trial prior to the planned maximum recruitment (n=150). Final analysis (n=75) showed strong evidence for a positive treatment effect (Bayes factor, BF=1.25 × 10<sup>6</sup>): the immediate arm reported fewer IMs (median=1, IQR=0-3) than the delayed arm (median=10, IQR=6-16.5). With further digital enhancements, the intervention (n=28) also showed a positive treatment effect (BF=7.31). Sequential Bayesian analyses provided evidence for reducing IMs of work-related trauma for healthcare workers. This methodology also allowed us to rule out negative effects early, reduced the planned maximum sample size, and allowed evaluation of enhancements. Trial Registration NCT02044809 (www.clinicaltrials.gov).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.06.22280777v1" target="_blank">Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention</a>
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<li><strong>Impact of vaccination on post-acute sequelae of SARS CoV-2 infection in patients with rheumatic diseases</strong> -
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Objective: Vaccination decreases the risk of severe COVID-19 but its impact on post-acute sequelae of COVID-19 (PASC) is unclear among patients with systemic autoimmune rheumatic diseases (SARDs) who may have blunted vaccine immunogenicity and be vulnerable to PASC. Methods: We prospectively enrolled SARD patients from a large healthcare system who survived acute infection to complete surveys. The symptom-free duration and the odds of PASC (any symptom lasting ≥ 28 or 90 days) were evaluated using restricted mean survival time and multivariable logistic regression, respectively, among those with and without breakthrough infection (≥ 14 days after initial vaccine series). Results: Among 280 patients, the mean age was 53 years, 80% were female, and 82% were white. The most common SARDs were inflammatory arthritis (59%) and connective tissue disease (24%). Those with breakthrough infection had more upper respiratory symptoms, and those with non-breakthrough infection had more anosmia, dysgeusia, and joint pain. Compared to those with non-breakthrough COVID-19 infection (n=164), those with breakthrough infection (n=116) had significantly more symptom-free days over the follow-up period (+28.9 days, 95% CI: 8.83, 48.89; p=0.005) and lower odds of PASC at 28 and 90 days (aOR 0.49, 95% CI: 0.29, 0.83 and aOR 0.10, 95% CI: 0.04, 0.22, respectively). Conclusion: Vaccinated patients with SARDs were less likely to experience PASC compared to those not fully vaccinated. These findings support the benefits of vaccination for patients with SARDs and suggest that the immune response to acute infection is important in the pathogenesis of PASC in SARD patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.06.22280798v1" target="_blank">Impact of vaccination on post-acute sequelae of SARS CoV-2 infection in patients with rheumatic diseases</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir; Drug: ritonavir; Drug: placebo for nirmatrelvir<br/><b>Sponsor</b>: Pfizer<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>COVID-19 iCura SARS-CoV-2 Ag OTC: Clinical Evaluation</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Device: iCura COVID-19 Antigen Rapid Home Test; Diagnostic Test: RT-PCR Test<br/><b>Sponsors</b>: EDP Biotech; Paragon Rx Clinical, Inc.; iCura Diagnostics, LLC<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>FMT for Post-acute COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID19 Syndrome; COVID-19<br/><b>Intervention</b>: Procedure: Faecal Microbiota Transplantation<br/><b>Sponsor</b>: Chinese University of Hong Kong<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: DILTIAZEM TEVA 60 mg or placebo<br/><b>Sponsors</b>: Hospices Civils de Lyon; Signia Therapeutics<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>COVID-19 Booster Dose Reminder/Recall for Adolescents</strong> - <b>Condition</b>: COVID-19 Vaccines<br/><b>Intervention</b>: Behavioral: Reminder/Recall Sent Via Preferred Method of Communication<br/><b>Sponsor</b>: Marshfield Clinic Research Foundation<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>VAX-MOM COVID-19: Increasing Maternal COVID-19 Vaccination</strong> - <b>Conditions</b>: Immunization; Infection; Pregnancy Related; COVID-19<br/><b>Interventions</b>: Behavioral: VAX-MOM COVID-19 Intervention; Other: Standard of Care<br/><b>Sponsors</b>: University of Rochester; Centers for Disease Control and Prevention; University of California, Los Angeles<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>Research on Community Based ATK Test Study to Control Spread of COVID-19 in Migrant Community</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Device: STANDARD Q COVID-19 Ag Test<br/><b>Sponsor</b>: University of Oxford<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Personalized Computerized Training Program for Cognitive Dysfunction After COVID-19</strong> - <b>Conditions</b>: Post-Acute COVID-19; Long COVID<br/><b>Intervention</b>: Device: CogniFit’s CCT Post COVID-19<br/><b>Sponsor</b>: Universidad Antonio de Nebrija<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>Understanding the Impact of Death Conditions Linked to the COVID-19 Crisis on the Grieving Process in Bereaved Families</strong> - <b>Condition</b>: Psychological Disorder<br/><b>Intervention</b>: Other: Qualitative research interview<br/><b>Sponsor</b>: Assistance Publique - Hôpitaux de Paris<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>3EO Health SARS-CoV-2 OTC At Home Test</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Diagnostic Test: In Vitro<br/><b>Sponsor</b>: 3EO Health<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>Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial</strong> - <b>Conditions</b>: HIV; Organ Transplantation; Lymphoma, Non-Hodgkin; Chronic Lymphocytic Leukemia; Multiple Myeloma; COVID-19 Vaccines<br/><b>Interventions</b>: Biological: BNT162b2; Biological: mRNA-1273; Biological: NVX-COV2373<br/><b>Sponsors</b>: Bayside Health; Monash 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>Sequential Enhanced Safety Study of a Novel Coronavirus Messenger RNA (mRNA) Vaccine in Adults Aged 18 Years and Older.</strong> - <b>Condition</b>: Corona Virus Disease 2019(COVID-19)<br/><b>Intervention</b>: Biological: 0.3ml of mRNA vaccine<br/><b>Sponsor</b>: Yu Qin<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PAPR: PAP + MBSR for Front-line Healthcare Provider COVID-19 Related Burnout</strong> - <b>Conditions</b>: Depression; Burnout, Professional<br/><b>Interventions</b>: Drug: Psilocybin; Behavioral: Mindfulness-Based Stress Reduction (MBSR)<br/><b>Sponsors</b>: University of Utah; Heffter Research Institute; Usona Institute<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>Physiology of Long COVID and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity</strong> - <b>Condition</b>: Post-acute Sequelae of SARS-CoV-2 Infection<br/><b>Intervention</b>: Behavioral: Exercise<br/><b>Sponsor</b>: University of Colorado, Denver<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>Scaling Well-Being for Educators During COVID-19</strong> - <b>Conditions</b>: Anxiety; Depression<br/><b>Intervention</b>: Behavioral: Healthy Minds Program Foundations Training<br/><b>Sponsors</b>: University of Wisconsin, Madison; Chan Zuckerberg Initiative<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Calcium dobesilate reduces SARS-CoV-2 entry into endothelial cells by inhibiting virus binding to heparan sulfate</strong> - Recent reports demonstrate that SARS-CoV-2 utilizes cell surface heparan sulfate as an attachment factor to facilitate the initial interaction with host cells. Heparan sulfate interacts with the receptor binding domain of SARS-CoV-2 spike glycoprotein, and blocking this interaction can decrease cell infection. We and others reported recently that the family of compounds of 2,5-dihydroxyphenylic acid interferes with the binding of the positively charged groove in growth factor molecules 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>Combating the SARS-CoV-2 Omicron (BA.1) and BA.2 with potent bispecific antibodies engineered from non-Omicron neutralizing antibodies</strong> - The highly mutated and transmissible Omicron (BA.1) and its more contagious lineage BA.2 have provoked serious concerns over their decreased sensitivity to the current COVID-19 vaccines and evasion from most anti-SARS-CoV-2 neutralizing antibodies (NAbs). In this study, we explored the possibility of combating the Omicron and BA.2 by constructing bispecific antibodies based on non-Omicron NAbs. We engineered 10 IgG-like bispecific antibodies with non-Omicron NAbs named GW01, 16L9, 4L12, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of adenoviral vectors in gene therapy and vaccine approaches</strong> - Adenovirus was first identified in the 1950s and since then this pathogenic group of viruses has been explored and transformed into a genetic transfer vehicle. Modification or deletion of few genes are necessary to transform it into a conditionally or non-replicative vector, creating a versatile tool capable of transducing different tissues and inducing high levels of transgene expression. In the early years of vector development, the application in monogenic diseases faced several hurdles,…</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>Therapeutic potential of metal ions for COVID-19: insights from the papain-like protease of SARS-CoV-2</strong> - Coronaviruses have been responsible for multiple challenging global pandemics, including coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Papain-like protease (PLpro), one of two cysteine proteases responsible for the maturation and infectivity of SARS-CoV-2, processes and liberates functional proteins from the viral polyproteins and cleaves ubiquitin and ISG15 modifications to inhibit innate immune sensing. Consequently, PLpro…</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>Comparison of Intracellular Transcriptional Response of NHBE Cells to Infection with SARS-CoV-2 Washington and New York Strains</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a D614G mutation in the viral spike protein are more transmissible, the effects of this and other mutations on the host response, especially at the cellular level, are yet to be fully elucidated. In this experiment we infected normal human bronchial…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of nonstructural protein 15 of SARS-CoV-2 by golden spice: A computational insight</strong> - The quick widespread of the coronavirus and speedy upsurge in the tally of cases demand the fast development of effective drugs. The uridine-directed endoribonuclease activity of nonstructural protein 15 (Nsp15) of the coronavirus is responsible for the invasion of the host immune system. Therefore, developing potential inhibitors against Nsp15 is a promising strategy. In this concern, the in silico approach can play a significant role, as it is fast and cost-effective in comparison to the trial…</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>Apelin as a new therapeutic target for COVID-19 treatment</strong> - CONCLUSION: Apelin is a potential therapeutic candidate against SARS-CoV-2 infection.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two Cases of Acute Myocarditis in Young Male Adults After mRNA Vaccines Against COVID-19: Similarities and Differences</strong> - CONCLUSION: The benefits of vaccination against Covid-19 outweigh possible untoward effects and especially myocarditis. Health workers must close monitor the vaccinated patients for possible future cardiovascular complications.</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>Therapeutic Approaches in COVID-19 Patients: The Role of the Renin-Angiotensin System</strong> - Two and a half years after COVID-19 was first reported in China, thousands of people are still dying from the disease every day around the world. The condition is forcing physicians to adopt new treatment strategies while emphasizing continuation of vaccination programs. The renin-angiotensin system plays an important role in the development and progression of COVID-19 patients. Nonetheless, administration of recombinant angiotensin-converting enzyme 2 has been proposed for the treatment of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Integral Membrane Protein ZMPSTE24 Protects Cells from SARS-CoV-2 Spike-Mediated Pseudovirus Infection and Syncytia Formation</strong> - COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on global public health, emphasizing the importance of understanding innate immune mechanisms and cellular restriction factors that cells can harness to fight viral infections. The multimembrane-spanning zinc metalloprotease ZMPSTE24 is one such restriction factor. ZMPSTE24 has a well-characterized proteolytic role in the maturation of prelamin A, precursor of the nuclear…</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>Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV</strong> - CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B and T cell immunity, including to known VOCs.</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>Body Weight is Inversely Associated with Anti-SARS-CoV-2 Antibody Levels after BNT162b2 mRNA Vaccination in Young and Middle Aged Adults</strong> - CONCLUSION: Anti-SARS-CoV-2 antibody was inversely correlated with weight and BMI, which may be used as a marker to predict immune response of BNT162b2 mRNA vaccination in young and middle aged adults.</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 molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo</strong> - “Pan-coronavirus” antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations….</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>Assessment of Practices Affecting Racial and Ethnic COVID-19 Vaccination Equity in 10 Large US Cities</strong> - CONCLUSIONS: Lack of consistent public reporting and transparency of COVID-19 vaccination data has likely hindered public health responses by impeding the ability to track the effectiveness of strategies that target vaccine equity.</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 3CL<sup>pro</sup> mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376</strong> - Protease inhibitors are among the most powerful antiviral drugs. Nirmatrelvir is the first protease inhibitor against the SARS-CoV-2 protease 3CL^(pro) that has been licensed for clinical use. To identify mutations that confer resistance to this protease inhibitor, we engineered a chimeric vesicular stomatitis virus (VSV) that expressed a polyprotein composed of the VSV glycoprotein G, the SARS-CoV-2 3CL^(pro), and the VSV polymerase L. Viral replication was thus dependent on the autocatalytic…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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