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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>02 September, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>Toward an Online System to Generate Tailored Infographics: Supporting the Health Information Sharing Needs of Community-Based Organizations</strong> -
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<div>
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Infographics are an engaging way to share health information with the public, but their relevance and appeal can be improved if they can be tailored to the language, culture, and information needs of their target audience. Digital tools are needed to make such tailoring feasible at scale, and to meet the needs of the community-based organizations (CBOs) that are well-situated to share health information with the public. Here, we describe our progress toward the development of the TailorVis Toolbox, an online system that facilitates infographic tailoring at the level of the CBO and the individual viewer. Incorporated within this project was the participatory design of infographics related to COVID-19 testing and vaccination. The system will be extended to numerous health topics in the future.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/8r2cm/" target="_blank">Toward an Online System to Generate Tailored Infographics: Supporting the Health Information Sharing Needs of Community-Based Organizations</a>
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</div></li>
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<li><strong>Characteristics of the sexual networks of gay, bisexual, and other men who have sex with men in Montréal, Toronto, and Vancouver: implications for the transmission and control of mpox in Canada</strong> -
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Background: The 2022-2023 global mpox outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBM). In Canada, >70% of cases thus far have been among GBM in Montréal, Toronto, and Vancouver. We examined how the distributions of sexual partners 1) varied by city and over time related to the COVID-19 pandemic and 2) were associated with mpox transmission. Methods: The <i>Engage Cohort Study</i> (2017-2023) recruited GBM via respondent-driven sampling in Montréal, Toronto, and Vancouver (n=2,449). We compared numbers of sexual partners in the past 6 months across cities and three time periods: pre-COVID-19 pandemic (2017-2019), pandemic (2020-2021), and post-restrictions (2021-2023). We modeled the distribution of sexual partner numbers using Bayesian negative binomial regressions and post-stratification, adjusting for sampling design and attrition. We estimated the basic reproduction number (<i>R<sub>0</sub></i>), secondary attack rate (SAR), and cumulative incidence proportion of mpox using the fitted distributions and case timeseries. Results: The pre-COVID-19 pandemic distribution of sexual partner numbers was similar across cities: participants9 mean number of partners was 10.3 (95%CrI: 9.3-11.3) in Montréal, 12.8 (11.1-14.7) in Toronto, and 10.6 (9.41-11.9) in Vancouver. Partner numbers decreased during the pandemic in all cities. Post-restrictions, sexual activity increased but remained well below pre-pandemic levels. Based on reported cases and post-restrictions distributions, the estimated <i>R<sub>0</sub></i> (2.4-2.6) and cumulative incidences (0.6-0.9%) were similar across cities. The estimated average SAR across cities was 79%. Conclusion: GBM sexual activity after restrictions were lifted remained below pre-pandemic levels. Comparable sexual partner distributions across cities may explain similarities in mpox <i>R<sub>0</sub></i> and cumulative incidence across cities. Public health authorities should consider the risk of mpox resurgence for future vaccination and surveillance strategies as sexual activity is expected to recover.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.31.23294912v1" target="_blank">Characteristics of the sexual networks of gay, bisexual, and other men who have sex with men in Montréal, Toronto, and Vancouver: implications for the transmission and control of mpox in Canada</a>
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</div></li>
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<li><strong>Symptom experience before vs. after confirmed SARS-CoV-2 infection: a population and case control study using prospectively recorded symptom data.</strong> -
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Background: Some individuals experience prolonged illness after acute COVID-19. We assessed whether pre-infection symptoms affected post-COVID illness duration. Methods Survival analysis was performed in adults (n=23,452) with community-managed SARC-CoV-2 infection prospectively self-logging data through the ZOE COVID Symptom Study app, at least weekly, from 8 weeks before to 12 weeks after COVID-19 onset, conditioned on presence vs. absence of baseline symptoms (4-8 weeks before COVID-19). A case-control study was performed in 1350 individuals with long illness (≥8 weeks, 906 [67.1%] with illness ≥12 weeks), matched 1:1 (for age, sex, body mass index, testing week, prior infection, vaccination, smoking, index of multiple deprivation) with 1350 individuals with short illness (<4 weeks). Baseline symptoms were compared between the two groups; and against post-COVID symptoms. Findings: Individuals reporting baseline symptoms had longer post-COVID symptom duration (from 10 to 15 days) with baseline fatigue nearly doubling duration. Two-thirds (910 of 1350 [67.4%]) of individuals with long illness were asymptomatic beforehand. However, 440 (32.6%) had baseline symptoms, vs. 255 (18.9%) of 1350 individuals with short illness (p<0.0001). Baseline symptoms increased the odds ratio for long illness (2.14 [CI: 1.78; 2.57]). Prior comorbidities were more common in individuals with long vs. short illness. In individuals with long illness, baseline symptomatic (vs. asymptomatic) individuals were more likely to be female, younger, and have prior comorbidities; and baseline and post-acute symptoms and symptom burden correlated strongly. Interpretation: Individuals experiencing symptoms before COVID-19 have longer illness duration and increased odds of long illness. However, many individuals with long illness are well before SARS-CoV-2 infection.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.30.23294821v1" target="_blank">Symptom experience before vs. after confirmed SARS-CoV-2 infection: a population and case control study using prospectively recorded symptom data.</a>
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</div></li>
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<li><strong>Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated Beta-2-Adrenergic Receptor Autoantibodies</strong> -
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There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies of IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective is to assess the improvement in functional ability. Due to the urgency of finding therapies for post-Covid-Syndrome (PCS), we report here the interim results of the first ten patients with seven responders defined by an increase of between 10 and 35 points in the Short-Form 36 Physical Function (SF36-PF) at week four after IA. The results of this observational study will provide the basis for patient selection for a randomised controlled trial (RTC) including sham apheresis and for a RTC combining IA with B-cell depletion therapy.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.31.23294813v1" target="_blank">Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated Beta-2-Adrenergic Receptor Autoantibodies</a>
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</div></li>
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<li><strong>Changes in child and adolescent mental health across the COVID-19 pandemic (2018-2023): Insights from general population and clinical samples in the Netherlands</strong> -
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Background The COVID-19 pandemic negatively affected child and adolescent mental health and at the end of the pandemic (April 2022) child mental health had not returned to pre‐pandemic levels. We investigated whether this observed increase in mental health problems has continued, halted, or reversed after the end of the pandemic in children from the general population and in children in psychiatric care. Methods We collected parent-reported and child-reported data at two additional post-pandemic time points (November/December 2022 and March/April 2023) in children (8-18 years) from two general population samples (N=818-1056 per measurement) and one clinical sample receiving psychiatric care (N=320-370) and compared these with data from before the pandemic. We collected parent‐reported data on internalizing and externalizing problems with the Brief Problem Monitor (BPM) and self‐reported data on Anxiety, Depressive symptoms, Sleep‐related impairments, Anger, Global health, and Peer relations with the Patient‐Reported Outcomes Measurement Information System (PROMIS). Results In the general population, parents reported no changes in externalizing problems but did report higher internalizing problems post-pandemic than pre-pandemic. Children also reported increased mental health problems post-pandemic, especially in anxiety and depression, to a lesser extent in sleep-related impairment and global health, and least in anger. In the clinical sample, parents reported higher internalizing, but not externalizing problems post-pandemic compared to the start of the pandemic. Children reported greatest increases in problems in anxiety, depression, and global health, to a lesser extent on sleep-related impairment, and least on anger. Conclusions Child mental health problems in the general population are substantially higher post-pandemic compared to pre-pandemic measurements. In children in psychiatric care mental health problems have increased during the pandemic and are substantially higher post-pandemic than at the start of the pandemic. Longitudinal and comparative studies are needed to assess what the most important drivers of these changes are.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.29.23294764v1" target="_blank">Changes in child and adolescent mental health across the COVID-19 pandemic (2018-2023): Insights from general population and clinical samples in the Netherlands</a>
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<li><strong>ISARIC COVID-19 Clinical Data Report: 10 January 2023</strong> -
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ISARIC (International Severe Acute Respiratory and emerging Infections Consortium) partnerships and outbreak preparedness initiatives enabled the rapid launch of standardised clinical data collection on COVID-19 in Jan 2020. Extensive global participation has resulted in a large, standardised collection of comprehensive clinical data from hundreds of sites across dozens of countries. Data are analysed regularly and reported publicly to inform patient care and public health response. This report, our 18th and final report, is a part of a series published over 3 years. Data have been entered for 945,317 individuals from 1807 partner institutions and networks across 76 countries. The comprehensive analyses detailed in this report includes hospitalised individuals of all ages for whom data collection occurred between 30 January 2020 and up to and including 10 January 2023, AND who have laboratory-confirmed SARS-COV-2 infection or clinically diagnosed COVID-19. For the 845,291 cases who meet eligibility criteria for this report, selected findings include: o Median age of 57 years, with an approximately equal (50/50) male:female sex distribution o 29% of the cohort are at least 70 years of age, whereas 6% are 0-19 years of age o The most common symptom combination in this hospitalised cohort is shortness of breath, cough, and history of fever, which has remained constant over time o The five most common symptoms at admission were shortness of breath, cough, history of fever, fatigue/malaise, and altered consciousness/confusion, which is unchanged from the previous reports o Age-associated differences in symptoms are evident, including the frequency of altered consciousness increasing with age, and fever, respiratory and constitutional symptoms being present mostly in those 40 years and above o 15% of patients with relevant data available (845,291) were admitted at some point during their illness into an intensive care unit (ICU), which has decreased from 19% during the 3 years of ISARIC reporting o Antibiotic agents were used in 37% of patients for whom relevant data are available (802,241), a significant reduction from our previous reports (80%) which reflects a shifting proportion of data contributed by different institutions; in ICU/HDU admitted patients with data available (64,669), 90% received antibiotics o Use of corticosteroids was reported in 25% of all patients for whom data were available (809,043); in ICU/HDU admitted patients with data available (64,713), 71% received corticosteroids o Outcomes are known for 762,728 patients and the overall estimated case fatality ratio (CFR) is 22% (95%CI 21.9-22), rising to 36% (95%CI 35.6-36.1) for patients who were admitted to ICU/HDU, demonstrating worse outcomes in those with the most severe disease We thank all the data contributors for their ongoing support.
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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/10.1101/2020.07.17.20155218v16" target="_blank">ISARIC COVID-19 Clinical Data Report: 10 January 2023</a>
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<li><strong>Can long-term COVID-19 vaccination be improved by serological surveillance?: a modeling study for Mozambique</strong> -
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Seroprevalence provides an estimate of the population-level susceptibility to infection. In this study, we used a transmission model to examine the potential of using serological surveillance to inform the timing of COVID-19 boosters in Mozambique. We simulated using population-level seroprevalence thresholds as an estimate of the risk of outbreaks to trigger the timing of re-vaccination campaigns among older adults. We compare this approach to a strategy of re-vaccination at fixed time intervals. Vaccinating older adults each time the seroprevalence among older adults falls below 50% and 80% resulted in medians of 20% and 71% reduction in deaths, respectively, and number-needed-to-vaccinate to avert one death (NNT) of 1,499 (2.5th-97.5th centile:1,252-1,905) and 3,151 (2,943-3,429), respectively. In comparison, biennial and annual re-vaccination of older adults resulted in medians of 35% and 52% deaths averted, respectively, and NNTs of 1,443 (1,223-1,733) and 1,941 (1,805-2,112), respectively. We conducted sensitivity analysis over a range of antibody waning rates and epidemic scenarios and found that re-vaccination trigger thresholds of 50-60% seroprevalence are most likely to be efficient compared to fixed-time strategies. However, given marginal gains in efficiency even in the best-case scenarios, our results favor the use of simpler fixed-time strategies for long-term control of SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.29.23294793v1" target="_blank">Can long-term COVID-19 vaccination be improved by serological surveillance?: a modeling study for Mozambique</a>
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<li><strong>How will COVID-19 persist in the future? Simulating future dynamics of COVID-19 using an agent-based network model</strong> -
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Despite the United States Center for Disease Control (CDC)9s May 2023 expiration of the declared public health emergency pertaining to the COVID-19 pandemic (Silk 2023), approximately 3 years after the first cases of SARS-CoV-2 appeared in the United Sates, thousands of new cases persist daily. Many questions persist about the future dynamics of SARS-CoV-29s in the United States, including: will COVID continue to circulate as a seasonal disease like influenza, and will annual vaccinations be required to prevent outbreaks? In response, we present an Agent Based Networked Simulation of COVID-19 transmission to evaluate recurrent future outbreaks of the disease, accounting for contact heterogeneity and waning vaccine-derived and natural immunity. Our model is parameterized with data collected as part of the Berkeley Interpersonal Contact Survey (BICS; Feehan and Mahmud 2021) and is used to simulate time series of confirmed cases of and deaths due to SARS-CoV-2, paying special attention to seasonal forces and waning immunity (Kronfeld-Schor et al. 2021; X. Liu et al. 2021; Nichols et al. 2021). From the BICS ABM model we simulate SARS-CoV-2 dynamics over the 10-year period beginning in 2021 with waning immunity and inclusion of annual booster doses under a variety of transmission scenarios. We find that SARS-CoV-2 outbreaks are likely to occur frequently, and that distribution of booster doses during certain times of the year-notably in the late winter/early spring-may reduce the severity of a wintertime outbreak depending on the seasonal epidemiology of the pathogen.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.29.23294791v1" target="_blank">How will COVID-19 persist in the future? Simulating future dynamics of COVID-19 using an agent-based network model</a>
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<li><strong>The use and acceptability of preprints in health and social care settings: a scoping review</strong> -
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Background: Preprints are open and accessible scientific manuscript or report that is shared publicly, through a preprint server, before being submitted to a journal. The value and importance of preprints has grown since its contribution during the public health emergency of the COVID-19 pandemic. Funders and publishers are establishing their position on the use of preprints, in grant applications and publishing models. However, the evidence supporting the use and acceptability of preprints varies across funders, publishers, and researchers. The scoping review explored the current evidence on the use and acceptability of preprints in health and social care settings by publishers, funders, and the research community throughout the research lifecycle. Methods: A scoping review was undertaken with no study or language limits. The search strategy was limited to the last five years (2017-2022) to capture changes influenced by COVID-19 (e.g., accelerated use and role of preprints in research). The review included international literature, including grey literature, and two databases were searched: Scopus and Web of Science (24 August 2022). Results: 379 titles and abstracts and 193 full text articles were assessed for eligibility. Ninety-eight articles met eligibility criteria and were included for full extraction. For barriers and challenges, 26 statements were grouped under four main themes (e.g., volume/growth of publications, quality assurance/trustworthiness, risks associated to credibility, and validation). For benefits and value, 34 statements were grouped under six themes (e.g., openness/transparency, increased visibility/credibility, open review process, open research, democratic process/systems, increased productivity/opportunities). Conclusions: Preprints provide opportunities for rapid dissemination but there is a need for clear policies and guidance from journals, publishers, and funders. Cautionary measures are needed to maintain the quality and value of preprints, paying particular attention to how findings are translated to the public. More research is needed to address some of the uncertainties addressed in this review.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/nug4p/" target="_blank">The use and acceptability of preprints in health and social care settings: a scoping review</a>
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<li><strong>The global and specific cardiovascular burden of spike-based Covid-19 1 Vaccination</strong> -
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Aims: The aim of this investigation was to determine whether the global and cardiovascular 10 burden associated with spike-based Covid-19 vaccination has continued to increase. 11 Methods and results: An updated analysis of spontaneously reported individual cases with 12 ADRs and their fatal outcomes associated with Covid-19 vaccines, as well as adverse 13 cardiovascular events caused by the spike-inducing vaccine Tozinameran, was performed. 14 Data were retrieved from the EudraVigilance web reports of the European Medicines Agency 15 (EMA). All evaluated adverse events correspond to the search terms of the EudraVigilance 16 based on clinical characterisation. 17 The total number of individual cases (n=2256506; i.e. 2338/day) with adverse effects that were 18 fatal in 2.3% (n=51740; i.e. 54 deaths/day), as well as the wide range of reports of 19 cardiovascular adverse effects, have revealed the unusual magnitude and specificity of these 20 events. 21 Tachycardia, arrhythmia, atrial fibrillation/flatter, bradyarrhythmia and impaired stimulus 22 formation and conduction (n=57438 combined) dominated the cardiovascular side effect profile 23 of Tozinameran, followed by blood pressure increase (n=25907), myo-/pericarditis (n=23775), 24 heart failure, cardiomyopathy, cardiac flatter/fibrillation, cardiac arrest, circulatory collaps 25 (n=16778 combined) and coronary artery disease/myocardial infarction (n=9912). The 26 importance of acute cardiovascular reactions is underlined by the fact that deaths caused by 27 them accounted for at least one third (35%) of all deaths associated with Tozinameran’s side 28 effects 29 Based on individual assessment, ARBs are currently recommended in the treatment of spike-30 induced symptoms. 31 Conclusions: The spectrum of side effects of spike-based Covid-19 vaccines is more extensive 32 and severe than is generally known, Adverse cardiovascular events convincingly reflect the 33 mode of spike action, namely down-regulating of the cardiovascular protective enzyme ACE2 34 resulting in increasing Ang II concentrations. A fundamental re-evaluation of the benefit-risk 35 assessment of these novel vaccines is mandatory. Health professionals should be educated about 36 the consequences of spike-induced ACE2 downregulation, the resulting symptoms and 37 therapeutic options.
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🖺 Full Text HTML: <a href="https://osf.io/we5cx/" target="_blank">The global and specific cardiovascular burden of spike-based Covid-19 1 Vaccination</a>
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<li><strong>Sequential early-life viral infections modulate the microbiota and adaptive immune responses to systemic and mucosal vaccination</strong> -
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Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, and markedly influencing serum cytokine and total antibody levels. Beyond these immune responses changes, these exposures also modulated the composition of the endogenous intestinal microbiota. Although sequentially-infected mice exhibited increased systemic immune activation and T cell responses after intramuscular and intranasal SARS-CoV-2 immunization, we observed decreased vaccine-induced antibody responses in these animals. These results suggest that early-life viral exposures are sufficient to diminish antibody responses to vaccination in mice, and highlight their potential importance of considering prior microbial exposures when investigating vaccine responses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.31.555772v1" target="_blank">Sequential early-life viral infections modulate the microbiota and adaptive immune responses to systemic and mucosal vaccination</a>
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<li><strong>Immunogenicity and efficacy of a subcutaneously administered, adjuvanted vaccine containing modified S1 spike protein of SARS-CoV-2 variant C.1.2</strong> -
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During the COVID-19 pandemic, vaccines have produced protective immunity sufficient enough to cause a decrease in hospitalizations and deaths; however, the pandemic continues due to mutational events, predominantly occurring in the S1 sequence of the spike protein of SARS-CoV-2. We have developed a baculovirus-expressed, modified S1 SARS-CoV-2 protein based on the C.1.2 variant, which was first identified in South Africa.1 This was encapsulated in a vitamin E containing, nonphospholipid liposome, which was then used to subcutaneously immunize Syrian hamsters. This vaccine, when administered at day 1 generates IgG responses that react to the modified C.1.2 S1 protein; full-length spike proteins from Wuhan-Hu-1, Delta, Omicron BA.1; and the Omicron recombinant variant XBB.1.5 in 100% of the animals. The second dose administered subcutaneously on day 28 demonstrated anamnestic response in the quantitative IgG assay to the Wuhan-Hu-1 spike Receptor Binding Domain (RBD). In addition, antibody IgA and IgM responses in sera were demonstrated. Serum IgG antibody responses to the spike proteins of the modified C.1.2 S1 and full-length spike proteins Wuhan-Hu-1, Delta, Omicron BA.1, and Omicron recombinant XBB.1.5 variants are elevated for over 120 days. Challenge of vaccinated and unvaccinated hamsters at day 126 of the study with an Omicron BA.1 resulted in a difference in weight change and viral load based on the qRT-PCR assay seven days after challenge.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.31.555805v1" target="_blank">Immunogenicity and efficacy of a subcutaneously administered, adjuvanted vaccine containing modified S1 spike protein of SARS-CoV-2 variant C.1.2</a>
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<li><strong>Characterization of an EG.5.1 clinical isolate in vitro and in vivo</strong> -
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EG.5.1 is a subvariant of the SARS-CoV-2 Omicron XBB variant that is rapidly increasing in prevalence worldwide. EG.5.1 has additional substitutions in its spike protein (namely, Q52H and F456L) compared with XBB.1.5. However, the pathogenicity, transmissibility, and immune evasion properties of clinical isolates of EG.5.1 are largely unknown. In this study, we used wild-type Syrian hamsters to investigate the replicative ability, pathogenicity, and transmissibility of a clinical EG.5.1 isolate. Our data show that there are no obvious differences in growth ability and pathogenicity between EG.5.1 and XBB.1.5, and both EG.5.1 and XBB.1.5 are attenuated compared to a Delta variant isolate. We also found that EG.5.1 is transmitted more efficiently between hamsters compared with XBB.1.5. In addition, unlike XBB.1.5, we detected EG.5.1 virus in the lungs of four of six exposed hamsters, suggesting that the virus tropism of EG.5.1 is different from that of XBB.1.5 after airborne transmission. Finally, we assessed the neutralizing ability of plasma from convalescent individuals and found that the neutralizing activity against EG.5.1 was slightly, but significantly, lower than that against XBB.1.5 or XBB.1.9.2. This suggests that EG.5.1 effectively evades humoral immunity and that the amino acid differences in the S protein of EG.5.1 compared with that of XBB.1.5 or XBB.1.9.2 (i.e., Q52H, R158G, and F456L) alter the antigenicity of EG.5.1. Our data suggest that the increased transmissibility and altered antigenicity of EG.5.1 may be driving its increasing prevalence over XBB.1.5 in the human population.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.31.555819v1" target="_blank">Characterization of an EG.5.1 clinical isolate in vitro and in vivo</a>
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<li><strong>SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide</strong> -
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An increasing number of reports suggest an association between COVID-19 infection and initiation or acceleration of neurodegenerative diseases including Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD). Both these diseases and several other neurodegenerative diseases are caused by conversion of human proteins into a misfolded, aggregated amyloid fibril state. The fibril formation process is self-perpetuating by seeded conversion from preformed fibril seeds. We recently described a plausible mechanism for amyloid fibril formation of SARS-CoV-2 spike protein. Spike-protein formed amyloid fibrils upon cleavage by neutrophil elastase, abundant in the inflammatory response to COVID-19 infection. We here provide evidence of significant Spike-amyloid fibril seeded acceleration of amyloid formation of CJD associated human prion protein (HuPrP) using an in vitro conversion assay. By seeding the HuPrP conversion assay with other in vitro generated disease associated amyloid fibrils we demonstrate that this is not a general effect but a specific feature of spike-amyloid fibrils. We also showed that the amyloid fibril formation of AD associated A{beta}1-42 was accelerated by Spike-amyloid fibril seeds. Of seven different 20-amino acid long peptides, Spike532 (532NLVKNKCVNFNFNGLTGTGV551) was most efficient in seeding HuPrP and Spike601 (601GTNTSNQVAVLYQDVNCTEV620) was most effective in seeding A{beta}1-42, suggesting substrate dependent selectivity of the cross-seeding activity. Albeit purely in vitro, our data suggest that cross-seeding by Spike-amyloid fibrils can be implicated in the increasing number of reports of CJD, AD, and possibly other neurodegenerative diseases in the wake of COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.01.555834v1" target="_blank">SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide</a>
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<li><strong>Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53</strong> -
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COVID-19 remains a significant public health threat due to the ability of SARS-CoV-2 variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and MERS-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here we used our recently developed integrative DNA And Protein Tagging (iDAPT) methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.31.555625v1" target="_blank">Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53</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>THE EFFECT OF ARGININE AND GLUTAMINE ON COVID-19 PATIENTS OUTCOME: A RANDOMIZED CLINICAL TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: Neomune<br/><b>Sponsors</b>: Universitas Sriwijaya; M. Djamil General Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 2/3 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: hAd5-S-Fusion+N-ETSD; Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>: ImmunityBio, Inc.<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>KAND567 Versus Placebo in Subjects Hospitalized With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: KAND567; Drug: Microcrystalline cellulose<br/><b>Sponsor</b>: Kancera AB<br/><b>Terminated</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>Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Aerobic Exercise Training<br/><b>Sponsors</b>: University of Witten/Herdecke; Institut für Rehabilitationsforschung Norderney<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Clinical Evaluation of Astepro® Nasal Spray for Management of Early SARS-CoV-2 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Experimental: Primary Cohort; Other: Placebo Comparator: Primary Cohort - Placebo<br/><b>Sponsor</b>: University of Chicago<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>Digital Health Literacy on COVID-19 for All: Co-creation and Evaluation of Interventions for Ethnic Minorities and Chinese People With Chronic Illnesses in Hong Kong</strong> - <b>Conditions</b>: Digital Health Literacy; COVID-19<br/><b>Intervention</b>: Behavioral: Digital health literacy intervention<br/><b>Sponsor</b>: The Hong Kong Polytechnic 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>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>: Influenza; COVID-19; Influenza Immunogencity; COVID-19 Immunogenicity<br/><b>Interventions</b>: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster); Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster); Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>: Duke University; Centers for Disease Control and Prevention; Arizona State University; University Hospitals Cleveland Medical Center; University of Pittsburgh; Washington University School of Medicine; Valleywise Health; VA Northeast Ohio Health Care; Senders Pediatrics<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 Vaccination Hesitancy in Adults With Sickle Cell Disease</strong> - <b>Conditions</b>: Sickle Cell Disease; COVID-19 Vaccine; Vaccine Hesitancy<br/><b>Intervention</b>: Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video<br/><b>Sponsors</b>: Duke University; American Society of Hematology<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Pulmonary Rehabilitation Among Post-COVID-19 Patients in a Tertiary Care Hospital in Bangladesh</strong> - <b>Condition</b>: Pulmonary Pathology<br/><b>Intervention</b>: Behavioral: Pulmonary Rehabilitation<br/><b>Sponsor</b>: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh<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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>: Bronchoalveolar Lavage<br/><b>Intervention</b>: Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>: Mohamed Abd Elmoniem Mohamed; Marwa Salah Abdelrazek Ghanem; Mohammad Khairy El-Badrawy; Tamer Ali Elhadidy; Dalia Abdellateif Abdelghany<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>Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19.</strong> - <b>Condition</b>: Nervous System Diseases<br/><b>Interventions</b>: Drug: Tianeptine; Drug: Placebo<br/><b>Sponsors</b>: Military Institute od Medicine National Research Institute; ABM Industries<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>Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition</strong> - <b>Condition</b>: Cognitive Behavioral Therapy<br/><b>Intervention</b>: Behavioral: cognitive behavioral therapy<br/><b>Sponsor</b>: Tri-Service General Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effectiveness of Natural Resources for Reducing Stress</strong> - <b>Conditions</b>: Distress, Emotional; COVID-19<br/><b>Interventions</b>: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure<br/><b>Sponsors</b>: Klaipėda University; Research Council of Lithuania<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>Study of LAU-7b for the Treatment of Long COVID in Adults</strong> - <b>Condition</b>: Long COVID<br/><b>Interventions</b>: Drug: LAU-7b for 3 cycles; Drug: LAU-7b for 1 cycle, then placebo; Other: Placebo for 3 cycles<br/><b>Sponsor</b>: Laurent Pharmaceuticals Inc.<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>Complementary and Integrative Medicine as an Online Intervention in Patients With Post-covid Syndrome After COVID-19</strong> - <b>Condition</b>: Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: Complementary and Integrative Medicine online intervention, routine care and book; Behavioral: Routine care and book<br/><b>Sponsor</b>: Charite University, Berlin, Germany<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>Antimicrobial effect of oral care gel containing hinokitiol and 4-isopropyl-3-methylphenol against intraoral pathogenic microorganisms</strong> - CONCLUSIONS: These data suggest that oral care gel-containing hinokitiol and IPMP has strong biofilm formation inhibitory activity, as well as antifungal and antimicrobial effects against Candida fungi and multiple intraoral pathogenic microorganisms. Therefore, it may be a promising treatment option for oral infections.</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 the Cellular Deubiquitinase UCHL1 Suppresses SARS-CoV-2 Replication</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>Hybrid molecules based on an emodin scaffold. Synthesis and activity against SARS-CoV-2 and <em>Plasmodium</em></strong> - Since the Covid-19 epidemic, it has been clear that the availability of small and affordable drugs that are able to efficiently control viral infections in humans is still a challenge in medicinal chemistry. The synthesis and biological activities of a series of hybrid molecules that combine an emodin moiety and other structural moieties expected to act as possible synergistic pharmacophores in a single molecule were studied. Emodin has been reported to block the entry of the SARS-CoV-2 virus…</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 molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronaviruses</strong> - There is an urgent need for highly effective therapeutic agents to interrupt the continued spread of SARS-CoV-2. As a pivotal protease in the replication process of coronaviruses, the 3CLpro protein is considered as a potential target of drug development to stop the spread and infection of the virus. In this work, molecular dynamics (MD) simulations were used to elucidate the molecular mechanism of a novel and highly effective non-covalent inhibitor, WU-04, targeting the SARS-CoV-2 3CLpro…</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 <em>Ephedra</em> herbs in the treatment of COVID-19</strong> - CONCLUSION: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19.</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>Integrated network pharmacology analysis and in vitro validation revealed the underlying mechanism of Xiyanping injection in treating coronavirus disease 2019</strong> - CONCLUSION: Through effective network pharmacology analysis and molecular docking, this study suggests that XYP contains many effective compounds that may target COVID-19 related signaling pathways. Moreover, the in vitro experiment confirmed that XYP could inhibit the cytokine storm by regulating genes or proteins related to immune and inflammatory responses.</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>Engineered clinical-grade mesenchymal stromal cells combating SARS-CoV-2 omicron variants by secreting effective neutralizing antibodies</strong> - CONCLUSIONS: Our data suggested that engineered clinical-grade MSCs secreting effective neutralizing antibodies as cellular production machines had the potential to combat SARS-CoV-2 infection, which provided a new avenue for effectively treating the older and immunocompromised COVID-19 patients.</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>CircMIB2 therapy can effectively treat pathogenic infection by encoding a novel protein</strong> - The mRNA therapy is widely used in the treatment of diseases due to its efficient characteristics, and the COVID-19 vaccine is the application of mRNA therapy. However, due to the instability of mRNA, mRNA vaccines often need lots of modifications to ensure its stability. Recent research shows that circRNA with stable RNA structure can encode protein, which provides a new direction for mRNA therapy. Here, we discovered a novel circRNA (circMIB2) derived from E3 ubiquitin-protein ligase MIB2…</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>Social network, political climate, income inequality, and Americans uptake of monovalent COVID-19 booster</strong> - The COVID-19 pandemic has posed an unprecedented impact on Americans for over three years. To control the damage, a booster shot becomes increasingly necessary because the efficacy of the initial vaccine is waning and new variants of the virus are emerging. This study aims to understand factors at both individual and state levels that influence one’s decision to take the monovalent booster. We merged data from a national survey administered in the Spring of 2022 with state-level indicators of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reduced concentration performance and heartbeat-evoked potential in individuals with a history of a SARS-CoV-2 infection</strong> - The goal of characterizing long-term psychological and neural consequences of a SARS-CoV-2 infection has recently gained importance. Here, we examined the effect of a prior SARS-CoV-2 infection on neural markers of exteroceptive (P300) and interoceptive (heartbeat-evoked potential; HEP) signal processing, as well as on neuropsychological tests of attention, inhibition and episodic memory, in 23 adults with a self-reported history of SARS-CoV-2 infection versus 23 healthy controls. We found 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>Posttranslational ISGylation of NLRP3 by HERCs enzymes facilitates inflammasome activation in models of inflammation</strong> - The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a crucial component of the innate immune system that initiates inflammatory responses. Post-translational modifications (PTMs) of NLRP3, including ubiquitination and phosphorylation, control inflammasome activation and determine the intensity of inflammation. However, the role of other PTMs in controlling NLRP3 inflammasome activation remains unclear. This study founded that toll-like receptor (TLR) priming induced…</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>We Cannot Put This Genie Back in the Bottle: Qualitative Interview Study Among Family Medicine Providers About Their Experiences With Virtual Visits During the COVID-19 Pandemic</strong> - CONCLUSIONS: This study highlights the transition from in-person to virtual visits during the pandemic from the perspective of family medicine providers. Generally, family medicine providers’ perceptions of the shift to virtual visits were positive, especially regarding team-based care. Challenges involved virtual inhibition, particularly for providers. Providers described ways they integrated virtual care with aspects of in-person care, creating a hybrid environment. The genie is out 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 Behavioral Inhibition System and Engagement With, and Influence By, COVID-19 and Election-Based Misinformation</strong> - The negative impact of misinformation on public discourse and public safety is increasingly a focus of attention. From the COVID-19 pandemic to national elections, exposure to misinformation has been linked to conflicting perceptions of social, economic, and political issues, which has been found to lead to polarization, radicalization, and acts of violence at the individual and group level. While a large body of research has emerged examining the development and spread of misinformation, little…</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>Arbidol increases the survival rate by mitigating inflammation in suckling mice infected with human coronavirus OC43 virus</strong> - Human coronavirus OC43 (HCoV-OC43) often causes common cold and is able to neuroinvasive, but it can also induce lower respiratory tract infections (LRTI) especially in children and the elderly adults with underlying diseases. HCoV-OC43 infections currently have no approved antiviral treatment. Arbidol (ARB) is a broad-spectrum antiviral and is an antiviral medication for the treatment of influenza used in Russia and China. Due to its multiple mechanisms of action, such as inhibition of viral…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and safety assessment of a SARS-CoV-2 recombinant spike RBD protein vaccine (Abdala) in paediatric ages 3-18 years old: a double-blinded, multicentre, randomised, phase 1/2 clinical trial (ISMAELILLO study)</strong> - BACKGROUND: COVID-19 in paediatric ages could result in hospitalizations and death. In addition, excluding children from vaccination could turn them into reservoirs of the SARS-COV-2. Safe and effective COVID-19 vaccines are urgently needed for large-scale paediatric vaccination. ISMAELILLO study aimed to evaluate safety and immunogenicity of two strengths of a new recombinant receptor-binding domain (RBD) protein vaccine (Abdala) in paediatric population.</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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