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180 lines
52 KiB
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<title>09 June, 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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<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>Concerns about data integrity of 30 randomized clinical trials from one author.</strong> -
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Introduction In 2021, we learnt about the problems in studies on ivermectin and hydrocholoroquine in COVID-19. We noticed an appreciable number of unfunded randomised clinical trials (RCTs) on the treatment of COVID-19 conducted across three centres in Egypt (Tanta University, Assiut University, Ain-shams University) on COVID-19 patients with similar inclusion criteria and overlapping time frames. Dr Sherief M Abd-Elsalam ran seven such RCTs across these three centres; four of these RCTs have since been retracted. We therefore set out to systematically analyse the integrity of all RCTs (co-)authored by Dr Abd-Elsalam, in particular 23 RCTs on Gastroenterology and Hepatology. Methods We searched PubMed, Google Scholar, Scopus and clinical trial registries for RCTs published by Dr Sherief M Abd-Elsalam, affiliated with the Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt. We assessed trial registration, tables for identical data values, statistical errors, and improbable data trends. We assessed the probability of true randomization by assessing baseline characteristics through a Monte Carlo Analysis. Results We report on 30 published randomized control trials (RCTs) of Dr. Sherief Abd-Elsalam, in particular 23 RCTs on Gastroenterology and Hepatology. We found important issues in all RCTs examined. Of these 23 RCTs, 10 RCTs had substantial trial registration inconsistencies. Only one of these 10 RCTs has been retracted to date. We found nine RCTs with substantial statistical mistakes, five RCTs with similarities between tables unlikely to happen by chance, four RCTs with implausible Gaussian distributions, three RCTs in which almost all dichotomous variables had even values, while part of at least one study was plagiarized. Monte Carlo analysis indicated that the probability that distribution of baseline characteristics due to randomisation was 0.0000228. According to the trial registration, Dr. Abd-Elsalam is coordinating 76 clinical trials with 45 trials currently marked as ‘Recruiting’ and 17 trials marked as ‘Unknown Status’ as of November 2022. Interpretation We strongly recommend a thorough investigation of the data integrity of all RCTs by Dr Sherief M Abd-Elsalam by journal editors. Until the completion of such an investigation, we suggest that none of these studies are used to inform clinical practice.
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🖺 Full Text HTML: <a href="https://osf.io/vjcnp/" target="_blank">Concerns about data integrity of 30 randomized clinical trials from one author.</a>
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</div></li>
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<li><strong>The Your COVID-19 Risk Assessment Tool and the Accompanying Open Access Data and Materials Repositories</strong> -
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<div>
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In March 2020, the Your COVID-19 Risk tool was developed in response to the global spread of SARS-CoV-2. The tool is an online resource based on key behavioural evidence-based risk factors related to contracting and spreading SARS-CoV-2. This article describes the development of the tool, the produced resources, the associated open repository, and initial results. This tool was developed by a multidisciplinary research team consisting of more than 150 international experts. This project leverages knowledge obtained in behavioural science, aiming to promote behaviour change by assessing risk and supporting individuals completing the assessment tool to protect themselves and others from infection. To enable iterative improvements of the tool, tool users can optionally answer questions about behavioural determinants. The data and results are openly shared to support governments and health agencies developing behaviour change interventions. Over 60 000 users in more than 150 countries have assessed their risk and provided data.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/b8n5g/" target="_blank">The Your COVID-19 Risk Assessment Tool and the Accompanying Open Access Data and Materials Repositories</a>
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</div></li>
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<li><strong>Anti-Viral and Anti-Inflammatory Therapeutic Effect of RAGE-Ig Protein Against Multiple SARS-CoV-2 Variants of Concern Demonstrated in K18-hACE2 Mouse and Syrian Golden Hamster Models</strong> -
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<div>
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Significance: SARS-CoV-2 Variants of Concern (VOCs) continue to evolve and re-emerge with chronic inflammatory long-COVID sequelae necessitating the development of anti-inflammatory therapeutic molecules. Therapeutic effects of the Receptor for Advanced Glycation End products (RAGE) were reported in many inflammatory diseases. However, a therapeutic effect of the RAGE in COVID-19 has not been reported. In the present study, we investigated whether and how the RAGE-Ig fusion protein would have an anti-viral and anti-inflammatory therapeutic effect in the COVID-19 system. Methods: The protective therapeutic effect of RAGE-Ig was determined in vitro in K18-hACE2 transgenic mice and Syrian golden hamsters infected with six various VOCs of SARS-CoV-2. The underlying anti-viral mechanism of RAGE-Ig was determined in vitro in SARS-CoV-2-infected human lung epithelial cells (BEAS-2B). Results: Following treatment of K18-hACE2 mice and hamsters infected with various SARS-CoV-2 VOCs with RAGE-Ig, we demonstrated: (i) significant dose-dependent protection (i.e. greater survival, less weight loss, lower virus replication in the lungs); (ii) a reduction of inflammatory macrophages (F4/80+/Ly6C+) and neutrophils (CD11b+/Ly6G+) infiltrating the infected lungs; (iii) a RAGE-Ig dose-dependent increase in the expression of type I interferons (IFN-alpha;, and IFN-beta) and type III interferon (IFN lambda2) and a decrease in the inflammatory cytokines (IL-6 and IL-8) in SARS-CoV-2-infected human lung epithelial cells; and (iv) a dose-dependent decrease in the expression of CD64 (FcgR1) on monocytes and lung epithelial cells from symptomatic COVID-19 patients. Conclusion: Our pre-clinical findings revealed type I and III interferons-mediated anti-viral and anti-inflammatory therapeutic effects of RAGE-Ig protein against COVID-19 caused by multiple SARS-CoV-2 VOCs.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.07.544133v1" target="_blank">Anti-Viral and Anti-Inflammatory Therapeutic Effect of RAGE-Ig Protein Against Multiple SARS-CoV-2 Variants of Concern Demonstrated in K18-hACE2 Mouse and Syrian Golden Hamster Models</a>
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<li><strong>Potential for bias in (sero)prevalence estimates when not accounting for test sensitivity and specificity</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Objectives: The COVID-19 has led to many studies of seroprevalence. A number of methods exist in the statistical literature to correctly estimate disease prevalence in the presence of diagnostic test misclassification, but these methods seem to be less known and not routinely used in the public health literature. We aimed to show how widespread the problem is in recent publications, and to quantify the magnitude of bias introduced when correct methods are not used. Methods: We examined a sample of recent literature to determine how often public health researcher did not account for test performance in estimates of seroprevalence. Using straightforward calculations, we estimated the amount of bias introduced when reporting the proportion of positive test results instead of using sensitivity and specificity to estimate disease prevalence. Results: Of the seroprevalence studies sampled, 80% failed to account for sensitivity and specificity. Expected bias is often more than is desired in practice, ranging from 1% to 10%. Conclusions: Researchers conducting studies of prevalence should correctly account for test sensitivity and specificity in their statistical analysis.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.24.22282720v6" target="_blank">Potential for bias in (sero)prevalence estimates when not accounting for test sensitivity and specificity</a>
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<li><strong>COVFlow: performing virus phylodynamics analyses from selected SARS-CoV-2 genome sequences</strong> -
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<div>
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Phylodynamic analyses generate important and timely data to optimise public health response to SARS-CoV-2 outbreaks and epidemics. However, their implementation is hampered by the massive amount of sequence data and the difficulty to parameterise dedicated software packages. We introduce the COVFlow pipeline, accessible at https://gitlab.in2p3.fr/ete/CoV-flow, which allows a user to select sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database according to user-specified criteria, to perform basic phylogenetic analyses, and to produce an XML file to be run in the Beast2 software package. We illustrate the potential of this tool by studying two sets of sequences from the Delta variant in two French regions. This pipeline can facilitate the use of virus sequence data at the local level, for instance, to track the dynamics of a particular lineage or variant in a region of interest.
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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/10.1101/2022.06.17.496544v5" target="_blank">COVFlow: performing virus phylodynamics analyses from selected SARS-CoV-2 genome sequences</a>
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<li><strong>A Solution to the Kermack and McKendrick Integro-Differential Equations</strong> -
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In this manuscript, we derive a closed form solution to the full Kermack and McKendrick integro-differential equations (Kermack and McKendrick 1927) which we call the KMES. The KMES can be cast in the form of a step function response to the input of new infections; and that response is the time series of the total infections. We demonstrate the veracity of the KMES using independent data from the Covid 19 pandemic and derive many previously unknown and useful analytical expressions for diagnosing and managing an epidemic. These include new expressions for the viral load, the final size, the effective reproduction number, and the time to the peak in infections. Since the publication of the Kermack and McKendrick seminal paper (1927), thousands of authors have utilized the Susceptible, Infected, and Recovered (SIR) approximations; expressions which are putatively derived from the integro-differential equations, to model epidemic dynamics. Implicit in the use of the SIR approximation are the beliefs that there is no closed form solution to the more complex integro-differential equations, that the approximation adequately reproduces the dynamics of the integro-differential equations, and that herd immunity always exists. However, as we explicate in this manuscript, the KMES demonstrates that the SIR models are not adequate representations of the integro-differential equations, and herd immunity is not guaranteed. Our conclusion is that the KMES obsoletes the need for the SIR approximations; and provides a new level of understanding of epidemic dynamics.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.28.22274442v3" target="_blank">A Solution to the Kermack and McKendrick Integro-Differential Equations</a>
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<li><strong>Psychometric validation of the Portuguese Obsession with COVID-19 Scale (PT-OCS)</strong> -
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<div>
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The COVID-19 pandemic had relevant psychological effects on the Portuguese population, partially related to repetitive and disruptive thoughts about the disease. Successive lockdowns contributed to an additional burden on parents’ family-work-life balance. This study intends to validate the Portuguese version of the Obsession with COVID-19 Scale (OCS; Lee, 2020), drew upon a general sample from diverse country regions (n = 531) and a specific sample of Portuguese parents (n = 109). Confirmatory factor analysis’ results ensure the PT-OCS excellent psychometric properties both for the general sample [X2 (1) = 0.446, p = 0.504; CFI = 1.0; GFI = 1.0; RMSEA = 0.0; Standardized RMR = 0.003] and for the parents’ group [X2 (2) = 1.816, p = 0.403; CFI = 1.0; GFI = 0.99; RMSEA = 0.0; Standardized RMR = 0.016; p Bollen-Stine bootstrap = 0.65]. The scale had very good reliability results (0.84 < α / ⍵ < 0.88). As expected, obsession with COVID-19 was highly correlated with COVID-19 anxiety and women had higher PT-OCS scores. Findings suggest the PT-OCS as a reliable and valid measure to evaluate persistent and disruptive thinking about COVID-19, namely in different groups of the Portuguese population, with potentialities for future epidemic events.
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🖺 Full Text HTML: <a href="https://osf.io/whm8s/" target="_blank">Psychometric validation of the Portuguese Obsession with COVID-19 Scale (PT-OCS)</a>
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<li><strong>Emotional distress and affective knowledge representation one year after the Covid-19 outbreak</strong> -
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This study examines whether the detrimental effects of the COVID-19 pandemic on the affectivity of the population extend one year after the outbreak. In an online-mobile session, participants completed surveys (i.e. demographic characteristics, positive-negative affectivity, interoceptive awareness) and a similarity judgment task of triplets of emotional concepts, from which we derived 2D maps of their affective knowledge representation. Compared with pre-pandemic data derived from a comparable population, we report three main findings. First, we observed enhanced negative affectivity during the pandemic, but no changes in positive affectivity levels. Second, increased self-reported interoceptive awareness compared to pre-pandemic data, with greater attention to bodily sensations and adaptive aspects of interoceptive sensitivity. Furthermore, female participants reported higher scores than males on the questionnaire subscales of Emotional Awareness and Attention Regulation. Third, the effect of pandemic-related conditions is also apparent in the mental organization of emotional concepts, especially for female participants (i.e., reduced coherence in the organization of the concepts along the arousal dimension and more misclassification of concepts based on arousal) and participants who did not perform physical activity (a collapse of the arousal dimension). Some of the effects of the pandemic, thus, persist about a year after the outbreak. These results advise providing programs of psychological and emotional assistance throughout the pandemic beyond the outbreak, and that age-dependent gender differences should be accounted for to define tailored interventions. Physical activity might relieve pandemic-related stressors, so it should be promoted during particularly stressful periods for the population.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/gmazn/" target="_blank">Emotional distress and affective knowledge representation one year after the Covid-19 outbreak</a>
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<li><strong>Towards Pandemic-Scale Ancestral Recombination Graphs of SARS-CoV-2</strong> -
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<div>
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Recombination is an ongoing and increasingly important feature of circulating lineages of SARS-CoV-2, challenging how we represent the evolutionary history of this virus and giving rise to new variants of potential public health concern by combining transmission and immune evasion properties of different lineages. Detection of new recombinant strains is challenging, with most methods looking for breaks between sets of mutations that characterise distinct lineages. In addition, many basic approaches fundamental to the study of viral evolution assume that recombination is negligible, in that a single phylogenetic tree can represent the genetic ancestry of the circulating strains. Here we present an initial version of sc2ts, a method to automatically detect recombinants in real time and to cohesively integrate them into a genealogy in the form of an ancestral recombination graph (ARG), which jointly records mutation, recombination and genetic inheritance. We infer two ARGs under different sampling strategies, and study their properties. One contains 1.27 million sequences sampled up to June 30, 2021, and the second is more sparsely sampled, consisting of 657K sequences sampled up to June 30, 2022. We find that both ARGs are highly consistent with known features of SARS-CoV-2 evolution, recovering the basic backbone phylogeny, mutational spectra, and recapitulating details on the majority of known recombinant lineages. Using the well-established and feature-rich tskit library, the ARGs can also be stored concisely and processed efficiently using standard Python tools. For example, the ARG for 1.27 million sequences—encoding the inferred reticulate ancestry, genetic variation, and extensive metadata—requires 58MB of storage, and loads in less than a second. The ability to fully integrate the effects of recombination into downstream analyses, to quickly and automatically detect new recombinants, and to utilise an efficient and convenient platform for computation based on well-engineered technologies makes sc2ts a promising approach.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.08.544212v1" target="_blank">Towards Pandemic-Scale Ancestral Recombination Graphs of SARS-CoV-2</a>
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<li><strong>Single-cell RNA sequencing reveals HIF1A as a severity-sensitive immunological scar in circulating monocytes of convalescent comorbidity-free COVID-19 patients</strong> -
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COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by a wide range of clinical symptoms and a poorly predictable disease course. Although in-depth transcriptomic investigations of peripheral blood samples from COVID-19 patients have been performed, the detailed molecular mechanisms underlying an asymptomatic, mild or severe disease course, particularly in patients without relevant comorbidities, remain poorly understood. While previous studies have mainly focused on the cellular and molecular dissection of ongoing COVID-19, we set out to characterize transcriptomic immune cell dysregulation at the single-cell level at different time points in patients without comorbidities after disease resolution to identify signatures of different disease severities in convalescence. With single-cell RNA sequencing we reveal a role for hypoxia-inducible factor 1-alpha (HIF1A) as a severity-sensitive long-term immunological scar in circulating monocytes of convalescent COVID-19 patients. Additionally, circulating complexes formed by monocytes with either T cells or NK cells represent a characteristic cellular marker in convalescent COVID-19 patients irrespective of their preceding symptom severity. Together, these results provide cellular and molecular correlates of recovery from COVID-19 and could help in immune monitoring and in the design of new treatment strategies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.07.544062v1" target="_blank">Single-cell RNA sequencing reveals HIF1A as a severity-sensitive immunological scar in circulating monocytes of convalescent comorbidity-free COVID-19 patients</a>
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<li><strong>An evolutionarily conserved strategy for ribosome binding and inhibition by β-coronavirus non-structural protein 1</strong> -
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An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Nsp1, which suppresses host gene expression and stunts antiviral signaling. SARS-CoV-2 Nsp1 binds the ribosome to inhibit translation through mRNA displacement and induces degradation of host mRNAs through an unknown mechanism. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from beta-CoV inhibits translation through ribosome binding. The C-terminal domain of all beta-CoV Nsp1s confers high-affinity ribosome-binding despite low sequence conservation. Modeling of interactions of four Nsp1s to the ribosome identified few absolutely conserved amino acids that, together with an overall conservation in surface charge, form the beta-CoV Nsp1 ribosome-binding domain. Contrary to previous models, the Nsp1 ribosome-binding domain is an inefficient translation inhibitor. Instead, the Nsp1-CTD likely functions by recruiting Nsp1's N-terminal effector domain. Finally, we show that a viral cis-acting RNA element has co-evolved to fine-tune SARS-CoV-2 Nsp1 function, but does not provide similar protection against Nsp1 from related viruses. Together, our work provides new insight into the diversity and conservation of ribosome-dependent host-shutoff functions of Nsp1, knowledge that could aide future efforts in pharmacological targeting of Nsp1 from SARS-CoV-2, but also related human-pathogenic beta-coronaviruses. Our study also exemplifies how comparing highly divergent Nsp1 variants can help to dissect the different modalities of this multi-functional viral protein.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.07.544141v1" target="_blank">An evolutionarily conserved strategy for ribosome binding and inhibition by β-coronavirus non-structural protein 1</a>
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<li><strong>Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus</strong> -
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Since the publication of the genome of SARS-CoV-2, the causative agent of COVID-19, in January 2020, many bioinformatic tools have been applied to annotate its proteins. Although effcient methods have been used, such as the identification of protein domains stored in Pfam, most of the proteins of this virus have no detectable homologous protein domains outside the viral taxa. As it is now well established that some viral proteins share similarities with proteins of their hosts, we decided to explore the hypothesis that this lack of homologies could be, at least in part, the result of the documented loss of sensitivity of Pfam Hidden Markov Models (HMMs) when searching for domains in "divergent organisms". In order to improve the annotation of SARS-CoV-2 proteins, we used the HHpred protein annotation tool. To avoid "false positive predictions" as much as possible, we designed a robustness procedure to evaluate the HHpred results. In total, 6 robust similarities involving 6 distinct SARS-CoV-2 proteins were detected. Of these 6 similarities, 3 are already known and well documented, and one is in agreement with recent crystallographic results. We then examined carefully the two similarities that have not yet been reported in the literature. We first show that the C-terminal part of Spike S (the protein that binds the virion to the cell membrane by interacting with the host receptor, triggering infection) has similarities with the human prominin-1/CD133; after reviewing what is known about prominin-1/CD133, we suggest that the C-terminal part of Spike S could both improve the docking of Spike S to ACE2 (the main cell entry receptor for SARS-CoV-2) and be involved in the delivery of virions to regions where ACE2 is located in cells. Secondly, we show that the SARS-CoV-2 ORF3a protein shares similarities with human G protein-coupled receptors (GPCRs) belonging mainly to the "Rhodopsin family"; on the basis of the literature, we then show that specific G protein-coupled receptors (GPCRs) of this family are known to form ion channels; we emphasize this is consistent with a recent Cryo-EM structure of SARS-CoV-2 ORF3a suggesting that it can form a non-selective Ca2+-permeable cation channel; furthermore, we highlight that some of the GPCRs identified as sharing similarities with ORF3a are targeted by antibodies in patients with COVID-19 and Long-COVID, suggesting that these similarities may trigger some of the observed autoimmune responses. We conclude that the approach described here (or similar approaches) opens up new avenues of research to better understand SARS-CoV-2 and could be used to complement virus annotations, particularly for less-studied viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.06.543855v1" target="_blank">Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus</a>
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<li><strong>Independent regulation of Z-lines and M-lines during sarcomere assembly in cardiac myocytes revealed by the automatic image analysis software sarcApp</strong> -
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Sarcomeres are the basic contractile units within cardiac myocytes, and the collective shortening of sarcomeres aligned along myofibrils generates the force driving the heartbeat. The alignment of the individual sarcomeres is important for proper force generation, and misaligned sarcomeres are associated with diseases including cardiomyopathies and COVID-19. The actin bundling protein, -actinin-2, localizes to the Z-Bodies of sarcomere precursors and the Z-Lines of sarcomeres, and has been used previously to assess sarcomere assembly and maintenance. Previous measurements of -actinin-2 organization have been largely accomplished manually, which is time-consuming and has hampered research progress. Here, we introduce sarcApp, an image analysis tool that quantifies several components of the cardiac sarcomere and their alignment in muscle cells and tissue. We first developed sarcApp to utilize deep learning- based segmentation and real space quantification to measure -actinin-2 structures and determine the organization of both precursors and sarcomeres/myofibrils. We then expanded sarcApp to analyze M-Lines using the localization of myomesin and a protein that connects the Z-Lines to the M-Line (titin). sarcApp produces 33 distinct measurements per cell and 24 per myofibril that allow for precise quantification of changes in sarcomeres, myofibrils, and their precursors. We validated this system with perturbations to sarcomere assembly. Surprisingly, we found perturbations that affected Z-Lines and M-Lines differently, suggesting that they may be regulated independently during sarcomere assembly.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.11.523681v2" target="_blank">Independent regulation of Z-lines and M-lines during sarcomere assembly in cardiac myocytes revealed by the automatic image analysis software sarcApp</a>
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<li><strong>Estimating the effectiveness of COVID-19 vaccination against COVID-19 hospitalisation and death: a cohort study based on the 2021 Census, England.</strong> -
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Objective: To estimate the effectiveness of COVID-19 vaccination against hospitalisation for COVID-19 and death involving COVID-19 in England using linked population level data sources including the 2021 Census. Design: Retrospective cohort study. Setting: England, 21 March 2021 to 20 March 2022. Participants: Individuals alive and aged 16+ on 21 March 2021, resident in England, enumerated in the 2021 Census as a usual resident, and able to link to an NHS number. A sample of 583,840 individuals was used for the analysis. Exposures: COVID-19 vaccination: first dose, second dose and third dose/first booster dose, with categories for time since each dose. Main outcome measures: Hospitalisation for COVID-19 or death involving COVID-19. An adjusted Cox proportional hazard model was used to estimate the hazard ratio for the outcomes for vaccinated participants for different doses and time since dose compared to unvaccinated individuals. Vaccine effectiveness was estimated as (1 minus hazard ratio)x 100%. A control outcome of non-COVID-19 death was also assessed. Results: Vaccine effectiveness against hospitalisation for COVID-19 was 52.1% (95% confidence interval 51.3% to 52.8%) for a first dose, 55.6% (55.2% to 56.1%) for a second dose and 77.6% (77.3% to 78.0%) for a third dose, with a decrease in vaccine effectiveness 3+ months after the third dose. Vaccine effectiveness against COVID-19 mortality was 58.7% (52.7% to 63.9%) for a first dose, 88.5% (87.5% to 89.5%) for a second dose and 93.2% (92.9% to 93.5%) for a third dose, with evidence of waning 3+ months after the second and third doses. For the second dose, which is the most comparable across the different time-periods, vaccine effectiveness was higher against COVID-19 hospitalisation but slightly lower against COVID-19 mortality in the Omicron dominant period than the period before the Omicron variant became dominant. Vaccine effectiveness against both COVID-19 hospitalisation and mortality was higher in general for mRNA vaccines than non mRNA vaccines, however this could be influenced by the different populations given each vaccine vector. Non-zero VE against non-COVID-19 mortality indicates that residual confounding may impact the results, despite the inclusion of up-to-date socio-demographic adjustments and various sources of health data, with possible frailty bias, confounding by indication and a healthy vaccinee effect observed. Conclusions: The vaccine effectiveness estimates show increased protection with number of doses and a high level of protection against both COVID-19 hospitalisation and mortality for the third/booster dose, as would be expected from previous research. However, despite the various sources of health data used to adjust the models, the estimates for different breakdowns and for non-COVID-19 mortality expose residual confounding by health status, which should be considered when interpreting estimates of vaccine effectiveness.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.06.23290982v1" target="_blank">Estimating the effectiveness of COVID-19 vaccination against COVID-19 hospitalisation and death: a cohort study based on the 2021 Census, England.</a>
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<li><strong>Impact of CoronaVac on Covid-19 outcomes of elderly adults in a large and socially unequal Brazilian city: A target trial emulation study</strong> -
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Background: Although CoronaVac was the only Covid-19 vaccine adopted in the first months of the Brazilian vaccination campaign, randomized clinical trials to evaluate its efficacy in elderly adults were limited. In this study, we use routinely collected surveillance and SARS-CoV-2 vaccination and testing data comprising the population of the fifth largest city of Brazil to evaluate the effectiveness of CoronaVac in adults 60+ years old against severe outcomes. Methods: Using large observational databases on vaccination and surveillance data from the city of Fortaleza, Brazil, we defined a retrospective cohort including 324,302 eligible adults aged ≥ 60 years to evaluate the effectiveness of the CoronaVac vaccine. The cohort included individuals vaccinated between January 21, 2021, and August 31, 2021, who were matched with unvaccinated persons at the time of rollout following a 1:1 ratio according to baseline covariates of age, sex, and Human Development Index of the neighborhood of residence. Only Covid-19-related severe outcomes were included in the analysis: hospitalization, ICU admission, and death. Vaccine effectiveness for each outcome was calculated by using the risk ratio between the two groups, with the risk obtained by the Kaplan-Meier estimator. Results: We obtained 62,643 matched pairs for assessing the effectiveness of the two-dose regimen of CoronaVac. The demographic profile of the matched population was statistically representative of the population of Fortaleza. Using the cumulative incidence as the risk associated with each group, starting at day 14 since the receipt of the second dose, we found an 82.3% (95% CI 66.3 - 93.9) effectiveness against Covid-19-related death, 68.4% (95% CI 42.3 - 86.4) against ICU admission, and 55.8% (95% CI 42.7 - 68.3) against hospital admission. Conclusions: Our results show that, despite critical delays in vaccine delivery and limited evidence in efficacy trial estimates, CoronaVac contributed to preventing deaths and severe morbidity due to Covid-19 in elderly adults.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.06.23291015v1" target="_blank">Impact of CoronaVac on Covid-19 outcomes of elderly adults in a large and socially unequal Brazilian city: A target trial emulation 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>Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Extracorporeal photopheresis<br/><b>Sponsor</b>: Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Trial on Booster Immunization of Two COVID-19 Vaccines Constructed From Different Technical Routes</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Prototype and Omicron BA.4/5 Bivalent Recombinant COVID-19 Vaccine(Adenovirus Type 5 Vector) For Inhalation; Biological: Bivalent COVID-19 mRNA Vaccine; Biological: Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) For Inhalation<br/><b>Sponsors</b>: Zhongnan Hospital; Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences</strong> - <b>Conditions</b>: COVID-19; COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: COVID-19 walk-up, on-site testing strategy; Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders; Behavioral: No-cost self-testing kit vending machines<br/><b>Sponsors</b>: University of California, San Diego; San Ysidro Health 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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: Placebo; Drug: Montelukast<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluvoxamine; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm D (Ivermectin 600)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm E (Fluvoxamine 100)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluvoxamine; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>Safety Study of COVID19 Vaccine on the Market</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant new coronavirus vaccine (CHO cell)<br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Hainan Center for Disease Control & Prevention<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Home Use COVID-19 Frequent Antigen Testing and Data Reporting</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Diagnostic Test: SARS CoV-2 antigen tests<br/><b>Sponsors</b>: IDX20 Inc; National Institute on Minority Health and Health Disparities (NIMHD)<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>Pycnogenol® in Post-COVID-19 Condition</strong> - <b>Conditions</b>: Post COVID-19 Condition; Long COVID<br/><b>Interventions</b>: Drug: Pycnogenol®; Drug: Placebo<br/><b>Sponsor</b>: University of Zurich<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 of Bailing Capsule on Pulmonary Fibrosis After COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis; COVID-19 Pneumonia<br/><b>Intervention</b>: Drug: Bailing capsule<br/><b>Sponsor</b>: Second Affiliated Hospital, School of Medicine, 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>Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19</strong> - <b>Conditions</b>: SARS-CoV Infection; COVID-19<br/><b>Interventions</b>: Drug: Mitoquinone/mitoquinol mesylate; Other: Placebo<br/><b>Sponsor</b>: University of Texas Southwestern 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>Evaluating Emetine for Viral Outbreaks (EVOLVE)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Emetine Hydrochloride; Drug: Placebo<br/><b>Sponsors</b>: Johns Hopkins University; Nepal Health Research Council; Bharatpur Hospital Chitwan; Stony Brook University; Rutgers 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>Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19)</strong> - <b>Conditions</b>: Long COVID; Post-Acute Sequela of COVID-19; Post-Acute COVID-19<br/><b>Interventions</b>: Drug: AER002; Other: Placebo<br/><b>Sponsors</b>: Michael Peluso, MD; Aerium 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>To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant Novel Coronavirus vaccine (CHO Cells)<br/><b>Sponsor</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.<br/><b>Completed</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Serum proteomics hint at an early T-cell response and modulation of SARS-CoV-2-related pathogenic pathways in COVID-19-ARDS treated with Ruxolitinib</strong> - CONCLUSION: Our results indicate that the mechanism of action of Ruxo in COVID-19-ARDS can be related to both known effects of this drug as a modulator of T-cells and the 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>Elucidation of novel compounds and epitope-based peptide vaccine design against C30 endopeptidase regions of SARS-CoV-2 using immunoinformatics approaches</strong> - There has been progressive improvement in immunoinformatics approaches for epitope-based peptide design. Computational-based immune-informatics approaches were applied to identify the epitopes of SARS-CoV-2 to develop vaccines. The accessibility of the SARS-CoV-2 protein surface was analyzed, and hexa-peptide sequences (KTPKYK) were observed having a maximum score of 8.254, located between amino acids 97 and 102, whereas the FSVLAC at amino acids 112 to 117 showed the lowest score of 0.114. 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>Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region</strong> - The 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has marked the spread of a novel human coronavirus. While the viral life cycle is well understood, most of the interactions at the virus-host interface remain elusive. Furthermore, the molecular mechanisms behind disease severity and immune evasion are still largely unknown. Conserved elements of the viral genome such as secondary structures within the 5’- and 3’-untranslated regions (UTRs) serve as…</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>Vascular Endothelial-derived SPARCL1 Exacerbates Viral Pneumonia Through Pro-Inflammatory Macrophage Activation</strong> - Inflammation upon infectious lung injury is a double-edged sword: while tissue-infiltrating immune cells and cytokines are necessary to control infection, these same factors often aggravate injury. Full appreciation of both the sources and targets of inflammatory mediators is required to facilitate strategies to maintain antimicrobial effects while minimizing off-target epithelial and endothelial damage. Recognizing that the vasculature is centrally involved in tissue responses to injury 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><em>In vitro</em> reconstitution of SARS CoV-2 Nsp1-induced mRNA cleavage reveals the key roles of the N-terminal domain of Nsp1 and the RRM domain of eIF3g</strong> - SARS CoV-2 nonstructural protein 1 (Nsp1) is the major pathogenesis factor that inhibits host translation using a dual strategy of impairing initiation and inducing endonucleolytic cleavage of cellular mRNAs. To investigate the mechanism of cleavage, we reconstituted it in vitro on β-globin, EMCV IRES and CrPV IRES mRNAs that use unrelated initiation mechanisms. In all instances, cleavage required Nsp1 and only canonical translational components (40S subunits and initiation factors), arguing…</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 Novel Viral Assembly Inhibitor Blocks SARS-CoV-2 Replication in Airway Epithelial Cells</strong> - The ongoing evolution of SARS-CoV-2 to evade vaccines and therapeutics underlines the need for novel therapies with high genetic barriers to resistance. The small molecule PAV-104, identified through a cell-free protein synthesis and assembly screen, was recently shown to target host protein assembly machinery in a manner specific to viral assembly. Here, we investigated the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs). Our data demonstrate that…</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>Virtual Health Promotion Work-Integrated Learning Placements: A COVID-19 Consequence or Preparation for the Future?</strong> - We explored student and industry supervisors’ experiences of virtual work-integrated learning (vWIL) health promotion placements during the COVID-19 pandemic. Using a descriptive phenomenological qualitative methodology, we conducted semi-structured interviews with eight students and eight supervisors of undergraduate health promotion-related placements at community, not-for-profit and government organizations. We asked participants about the aspects of their placement they found most enjoyable…</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>Designing for digital transformation of residency education - a post-pandemic pedagogical response</strong> - CONCLUSIONS: The study reflects the course leaders’ pedagogical response to the pandemic, as remote teaching became the only way to provide residency education. Initially, the sudden shift was perceived as constraining, but over time they found new affordances through the enforced use of digital technology that helped them not only to cope with the transition but also to innovate their pedagogical methods. After a rapid, forced shift from on-site to digital courses, it is crucial to utilize…</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>Eco-friendly and effective antimicrobial Melaleuca alternifolia essential oil Pickering emulsions stabilized with cellulose nanofibrils against bacteria and SARS-CoV-2</strong> - Melaleuca alternifolia essential oil (MaEO) is a green antimicrobial agent suitable for confection eco-friendly disinfectants to substitute conventional chemical disinfectants commonly formulated with toxic substances that cause dangerous environmental impacts. In this contribution, MaEO-in-water Pickering emulsions were successfully stabilized with cellulose nanofibrils (CNFs) by a simple mixing procedure. MaEO and the emulsions presented antimicrobial activities against Staphylococcus aureus…</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 Deltacoronavirus Infection Disrupts the Intestinal Mucosal Barrier and Inhibits Intestinal Stem Cell Differentiation to Goblet Cells via the Notch Signaling Pathway</strong> - Goblet cells and their secreted mucus are important elements of the intestinal mucosal barrier, which allows host cells to resist invasion by intestinal pathogens. Porcine deltacoronavirus (PDCoV) is an emerging swine enteric virus that causes severe diarrhea in pigs and causes large economic losses to pork producers worldwide. To date, the molecular mechanisms by which PDCoV regulates the function and differentiation of goblet cells and disrupts the intestinal mucosal barrier remain to be…</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 infection impairs NK cell functions <em>via</em> activation of the LLT1-CD161 axis</strong> - CONCLUSION: We propose a novel mechanism of SARS-CoV-2 inhibition of NK cell functions via activation of the LLT1-CD161 axis.</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>DPP-4 inhibitors for treating T2DM - hype or hope? an analysis based on the current literature</strong> - DPP-4 inhibition is an interesting line of therapy for treating Type 2 Diabetes Mellitus (T2DM) and is based on promoting the incretin effect. Here, the authors have presented a brief appraisal of DPP-4 inhibitors, their modes of action, and the clinical efficiency of currently available drugs based on DPP-4 inhibitors. The safety profiles as well as future directions including their potential application in improving COVID-19 patient outcomes have also been discussed in detail. This review also…</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>Failure of TRPC6 inhibition to prevent COVID-19 deterioration: more questions than answers</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The CH24H metabolite, 24HC, blocks viral entry by disrupting intracellular cholesterol homeostasis</strong> - Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has been well-studied in several neuro-associated diseases in recent years. In the present study, we found that CH24H expression can be induced by several neuroinvasive viruses, including vesicular stomatitis virus (VSV), rabies virus (RABV), Semliki Forest virus (SFV) and murine hepatitis virus (MHV). The CH24H metabolite,…</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>Novel Fluorescent Benzothiazolyl-Coumarin Hybrids as Anti-SARS-COVID-2 Agents Supported by Molecular Docking Studies: Design, Synthesis, X-ray Crystal Structures, DFT, and TD-DFT/PCM Calculations</strong> - This study revealed the design and preparation of new 3-(benzo[d]thiazol-2-yl)-2H-chromen-2-one derivatives 9a-h. The structures of the synthesized products were elucidated by their spectroscopic data and X-ray crystallography for compounds 9a and 9d. The prepared new compounds were measured for their fluorescence, and a good result indicated that the emission efficiency was decreased by increasing the electron-withdrawing groups from the unsubstituted compound 9a to the highly substituted…</p></li>
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