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<title>06 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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<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>Individual and spatial determinants of mortality during the Covid-19 pandemic: The case of Belgium in 2020</strong> -
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Context. The year 2020 was marked by the Covid 19 pandemic. In Belgium, it led to a doubling in deaths, mainly grouped into two periods. This article aims to compare the relative importance of predictors and individual and spatial determinants of mortality during these two waves to an equivalent non-pandemic period and to identify whether and to what extent the pandemic has altered the sociodemographic patterns of conventional mortality. Methods. The analyses relate to all-cause mortality during the two waves of Covid-19 and their equivalent in 2019. They are based on matching individual and exhaustive data from the Belgian National Register with tax and population census data. A multi-level approach was adopted combining individual and spatial determinants. Results. Mortality patterns during the pandemic are very similar to those observed outside the pandemic. As in 2019, age, sex, and household composition significantly determine the individual risk of dying, with a higher risk of death among the oldest people, men, and residents of collective households. However, their risk of death increases during the Covid period, especially in the 65/79 age group. Spatial information is no more significant in 2020 than in 2019. However, a higher risk of death is observed when the local excess mortality index or the proportions of isolated or disadvantaged people increase. Conclusions. While the Covid pandemic did not fundamentally alter conventional mortality patterns, it did amplify some of the pre-existing differences in mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.04.23295014v1" target="_blank">Individual and spatial determinants of mortality during the Covid-19 pandemic: The case of Belgium in 2020</a>
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<li><strong>Emerging Links Between COVID-19 and Cardiovascular & Cerebrovascular Thromboembolic Events: A Systematic Review</strong> -
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COVID-19, caused by the SARS-CoV-2 virus, initially identified as a respiratory illness, has increasingly been linked to a broader range of organ complications. This systematic review explores the impact of COVID-19 on cardiovascular and cerebrovascular health, focusing on thromboembolic events in post-COVID patients. A comprehensive literature search was conducted in PubMed and Google Scholar databases up to July 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies meeting eligibility criteria were analyzed for outcomes and associations between COVID-19 and cardiovascular and cerebrovascular events. The review includes 6 studies involving over 12 million patients, demonstrating a strong connection between COVID-19 and elevated risks of cardiovascular and cerebrovascular thromboembolic events. The risk of these events is evident in conditions such as ischemic heart disease, stroke, and cardiac arrhythmias. The burden of these events beyond the acute phase of the disease is concerning, warranting further exploration of long-term implications. Variability in event rates among different cohorts and healthcare settings underscores the need for understanding underlying factors influencing these differences. Potential mechanisms behind these events include endothelial dysfunction, systemic inflammation, and viral invasion. Implications for public health policies, clinical guidelines, and future research directions are discussed. This review serves as a valuable resource for healthcare providers, policymakers, and researchers to enhance patient care, outcomes, and preparedness for future waves of COVID-19 infections. However, there remain unexplored aspects of the COVID-19 and thromboembolic events relationship, urging further investigations into mechanistic insights and potential therapeutic interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.05.23295067v1" target="_blank">Emerging Links Between COVID-19 and Cardiovascular &amp; Cerebrovascular Thromboembolic Events: A Systematic Review</a>
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</div></li>
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<li><strong>Psychotherapies and Psychological Support for Individuals Facing Psychological Distress during the COVID-19 Pandemic: A Scoping Review</strong> -
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In this scoping review, we investigated psychotherapies and psychological support provided during the coronavirus disease 2019 (COVID-19) pandemic to clarify its recipients and the methods employed. We used Scopus and PubMed as the search engines on October 18, 2022, employing specific search terms (″COVID* ″ AND (″Psychotherap<em>″ OR ″psychological support</em>″) AND ″psychological distress*″). The initial search yielded 153 articles, of which 18 met the eligibility criteria after two rounds of screening. The distribution of participants ranged from the general population to patients with COVID-19 and those who had recovered. However, no studies of patients with post-COVID-19 sequelae were found. The distribution of the types of psychotherapies and psychological support varied and the use of new technology was suggested. Online interventions comprised the majority of the means of psychotherapies and psychological support. This study suggests that psychotherapies and psychological support during the COVID-19 pandemic were influenced by the social situation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.04.23295013v1" target="_blank">Psychotherapies and Psychological Support for Individuals Facing Psychological Distress during the COVID-19 Pandemic: A Scoping Review</a>
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<li><strong>Differentiation of COVID-19 from other emergency infectious disease presentations using whole blood transcriptomics then rapid qPCR: a case-control and observational cohort study</strong> -
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Background. The overlapping clinical presentations of patients with acute respiratory disease can complicate disease diagnosis. Whilst PCR diagnostic methods to identify SARS-CoV-2 are highly sensitive, they have their shortcomings including false-positive risk and slow turnaround times. Changes in host gene expression can be used to distinguish between disease groups of interest, providing a viable alternative to infectious disease diagnosis. Methods. We interrogated the whole blood gene expression profiles of patients with COVID-19 (n=87), bacterial infections (n=88), viral infections (n=36), and not-infected controls (n=27) to identify a sparse diagnostic signature for distinguishing COVID-19 from other clinically similar infectious and non-infectious conditions. The sparse diagnostic signature underwent validation in a new cohort using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and then underwent further external validation in an independent in silico RNA-seq cohort. Findings. We identified a 10-gene signature (OASL, UBP1, IL1RN, ZNF684, ENTPD7, NFKBIE, CDKN1C, CD44, OTOF, MSR1) that distinguished COVID-19 from other infectious and non-infectious diseases with an AUC of 87.1% (95% CI: 82.6%-91.7%) in the discovery cohort and 88.7% and 93.6% when evaluated in the RT-qPCR validation, and in silico cohorts respectively. Interpretation. Using well-phenotyped samples collected from patients admitted acutely with a spectrum of infectious and non-infectious syndromes, we provide a detailed catalogue of blood gene expression at the time of hospital admission. The findings result in the identification of a 10-gene host diagnostic signature to accurately distinguish COVID-19 from other infection syndromes presenting to hospital. This could be developed into a rapid point-of-care diagnostic test, providing a valuable syndromic diagnostic tool for future early pandemic use.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.03.23294989v1" target="_blank">Differentiation of COVID-19 from other emergency infectious disease presentations using whole blood transcriptomics then rapid qPCR: a case-control and observational cohort study</a>
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<li><strong>Correlation of myeloid-derived suppressor cell expansion with upregulated transposable elements in severe COVID-19 unveiled in single-cell RNA sequencing reanalysis</strong> -
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<div>
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Some studies investigated the potential role of transposable elements (TEs) in COVID-19 pathogenesis and complications. However, to the best of our knowledge, there is no study to examine the possible association of TEs expression in cell functions and its potential role in COVID-19 immune response at the single-cell level. In this study, we reanalyzed single-cell RNA seq data of bronchoalveolar lavage (BAL) samples obtained from six severe COVID-19 patients and three healthy donors to assess the probable correlation of TE expression with the immune responses induced by the SARS-CoV-2 virus in COVID-19 patients. Our findings indicated that the expansion of myeloid-derived suppressor cells (MDSCs (may be a characteristic feature of COVID-19. Additionally, a significant increase in TEs expression in MDSCs was observed. This upregulation of TEs in COVID-19 may be linked to the adaptability of these cells in response to their microenvironments. Furthermore, it appears that the identification of overexpressed TEs by Pattern recognition receptors (PRRs) in MDSCs may enhance the suppressive capacity of these cells. Thus, this study emphasizes the crucial role of TEs in the functionality of MDSCs during COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.04.556192v1" target="_blank">Correlation of myeloid-derived suppressor cell expansion with upregulated transposable elements in severe COVID-19 unveiled in single-cell RNA sequencing reanalysis</a>
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<li><strong>Neutralization Escape by SARS-CoV-2 Omicron Subvariant BA.2.86</strong> -
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The continued evolution of SARS-CoV-2 may lead to evasion of vaccine immunity and natural immunity. A highly mutated Omicron variant BA.2.86 has recently been identified with over 30 amino acid changes in Spike compared with BA.2 and XBB.1.5. As of September 4, 2023, BA.2.86 has been identified in 37 sequences from 10 countries, which is likely an underestimate due to limited surveillance. The ability of BA.2.86 to evade NAbs compared with other currently circulating Omicron variants remains unknown. Our data show that NAb responses to BA.2.86 were lower than to BA.2 but were comparable or slightly higher than to the current circulating recombinant variants XBB.1.5, XBB.1.16, EG.5, EG.5.1, and FL.1.5.1.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.04.556272v1" target="_blank">Neutralization Escape by SARS-CoV-2 Omicron Subvariant BA.2.86</a>
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<li><strong>Enhanced protective efficacy of a novel, thermostable, RBD-S2 fusion immunogen against SARS-CoV-2 and its variants</strong> -
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With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly protective immune responses. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, characterized, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Designed immunogens were expressed as soluble proteins with approximately fivefold higher purified yield than the Spike ectodomain and formulated along with Squalene-in-water emulsion (SWE) adjuvant. S2 immunization failed to elicit a neutralizing immune response but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant. In hamsters, SWE-formulated RS2 showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations. Despite being based on the ancestral Wuhan strain of SARS-CoV-2, RS2 exhibited broad neutralization, including against Omicron variants (BA.1, BA.5 and BF.7), as well as the clade 1a WIV-1 and SARS-CoV-1 strains. RS2 sera also showed enhanced competition with both S2 directed and RBD Class 4 directed broadly neutralizing antibodies, relative to RBD and Spike elicited sera. When lyophilized, RS2 retained antigenicity and immunogenicity even after incubation at 37 {degrees}C for a month. The data collectively suggest that the RS2 immunogen is a promising modality to combat SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.19.533338v2" target="_blank">Enhanced protective efficacy of a novel, thermostable, RBD-S2 fusion immunogen against SARS-CoV-2 and its variants</a>
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<li><strong>Bivalent mRNA vaccine effectiveness against COVID-19 infections, hospitalisations and deaths in Portugal: a cohort study based on electronic health records, September 2022 to May 2023</strong> -
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Background In Portugal, a bivalent COVID-19 vaccine booster was recommended for those with complete primary COVID-19 vaccination, starting on September 6 2022. This study aims to estimate the mRNA bivalent vaccine effectiveness (VE) against COVID-19 infection, hospitalisation and death in the Portuguese population aged 65 and more years with a follow-up of more than six months. Methods We used a cohort approach to analyse six electronic health registries using deterministic linkage. The follow-up period comprehend September 2022 to May 2023. The outcomes included SARS-CoV-2 infection, COVID-19-related hospitalisation and death. Individuals were considered vaccinated 14 days following a bivalent mRNA COVID-19 vaccine uptake. For each outcome, COVID-19 bivalent VE was estimated as one minus the confounder adjusted hazard ratio of bivalent vaccine vs no bivalent vaccine, estimated by Cox regression with time-dependent vaccine exposure. Results In the ≥ 80 year-olds, bivalent VE was 23.2 (95%CI: 20.1 to 26.2), 41.3 (95%CI: 34.5 to 47.5) and 50.3 (44.6 to 55.3), against infection, COVID-19-related hospitalisation and death, respectively. In the 65-79 year-old, bivalent VE against infection was 37.7 (35.5 to 39.8), 58.5 (95%CI: 51.9 to 64.2) against hospitalisation and 65.1 (95%CI: 59 to 70.4) against death. Vaccine effectiveness decay was observed for both age groups and in all outcomes, up to 6 months of vaccine uptake. Conclusions In a population with a high risk of SARS-CoV-2 complications, we observed moderate bivalent VE estimates against severe COVID-19 and low protection against infection. The lower VE estimates observed in the ≥ 80 year-olds should be interpreted in light of the reference group used for the estimation, i.e., individuals with high vaccine coverage (both primary series and multiple boosters). Significant VE decay was observed up to six months of vaccine uptake, which should be considered when preparing future vaccination campaigns.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.05.23295025v1" target="_blank">Bivalent mRNA vaccine effectiveness against COVID-19 infections, hospitalisations and deaths in Portugal: a cohort study based on electronic health records, September 2022 to May 2023</a>
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<li><strong>Contact patterns of older adults with and without frailty in the Netherlands during the COVID-19 pandemic</strong> -
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Background During the COVID-19 pandemic, social distancing measures were imposed to protect the population from exposure, especially older adults and people with frailty, who have the highest risk for severe outcomes. These restrictions greatly reduced contacts in the general population, but little was known about behaviour changes among older adults and people with frailty themselves. Our aim was to quantify how COVID-19 measures affected the contact behaviour of older adults and how this differed between older adults with and without frailty. Methods In 2021, a contact survey was carried out among people aged 70 years and older in the Netherlands. A random sample of persons per age group (70-74, 75-79, 80-84, 85-89, and 90+) and gender was invited to participate, either during a period with stringent (April 2021) or moderate (October 2021) measures. Participants provided general information on themselves, including their frailty, and they reported characteristics of all persons with whom they had face-to-face contact on a given day over the course of a full week. Results In total, 720 community-dwelling older adults were included (overall response rate of 15%), who reported 16,505 contacts. During the survey period with moderate measures, participants without frailty had significantly more contacts outside their household than participants with frailty. Especially for females, frailty was a more informative predictor of the number of contacts than age. During the survey period with stringent measures, participants with and without frailty had significantly lower numbers of contacts compared to the survey period with moderate measures. The reduction of the number of contacts was largest for the eldest participants without frailty. As they interact mostly with adults of a similar high age who are likely frail, this reduction of the number of contacts indirectly protects older adults with frailty from SARS-CoV-2 exposure. Conclusions The results of this study reveal that social distancing measures during the COVID-19 pandemic differentially affected the contact patterns of older adults with and without frailty. The reduction of contacts may have led to the direct protection of older adults in general but also to the indirect protection of older adults with frailty.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.09.23289550v3" target="_blank">Contact patterns of older adults with and without frailty in the Netherlands during the COVID-19 pandemic</a>
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<li><strong>SARS-CoV-2 quarantine mandated by contact tracing: burden and infection rate among close contacts in Zurich, Switzerland, 2020-2021</strong> -
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Objectives Before vaccines and effective treatments were available, quarantine of close contacts was important to limit the spread of SARS-CoV-2. To evaluate potential benefits and harms of quarantine, we aimed to estimate infection rates and describe experiences and mental health among persons in mandated quarantine during the early SARS-CoV-2 pandemic. Methods We invited adults in mandated quarantine after an exposure to SARS-CoV-2 identified through contact tracing of the Canton of Zurich, Switzerland, between August 2020 and January 2021. Participants completed two questionnaires and received up to two SARS-CoV-2 polymerase chain reaction tests, during and at the end of quarantine. Results Among 395 participants, quarantine duration ranged from 2 to 20 days. By day 11 since the last contact, 11.1% [95% CI 8.4%-14.7%] were infected with SARS-CoV-2. The proportion of participants with symptoms of depression doubled from 9.3% before quarantine to 18.9% during quarantine, and 12.1% reported quarantine was very or extremely difficult. Conclusions Although quarantine was only moderately burdensome for most participants, some experienced significant difficulties and burden. Policymakers need to balance infection control with potential harms placed on individuals.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.03.23294798v1" target="_blank">SARS-CoV-2 quarantine mandated by contact tracing: burden and infection rate among close contacts in Zurich, Switzerland, 2020-2021</a>
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<li><strong>A Literature Review and Meta-Analysis of the Effects of Lockdowns on COVID-19 Mortality - II</strong> -
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The purpose of this systematic review and meta-analysis is to determine the effect of lockdowns on COVID-19 mortality based on available empirical evidence. Lockdowns are defined as the imposition of at least one compulsory, non-pharmaceutical intervention (NPI). We employ a systematic search and screening procedure in which 19,646 studies are identified that could potentially address the purpose of our study. After three levels of screening, 32 studies qualified. Of those, estimates from 22 studies could be converted to standardized measures for inclusion in the meta-analysis. They are separated into three groups: lockdown stringency index studies, shelter-in-place-order (SIPO) studies, and specific NPI studies. Stringency index studies find that the average lockdown in Europe and the United States in the spring of 2020 only reduced COVID- 19 mortality by 3.2%. This translates into approximately 6,000 avoided deaths in Europe and 4,000 in the United States. SIPOs were also relatively ineffective in the spring of 2020, only reducing COVID-19 mortality by 2.0%. This translates into approximately 4,000 avoided deaths in Europe and 3,000 in the United States. Based on specific NPIs, we estimate that the average lockdown in Europe and the United States in the spring of 2020 reduced COVID-19 mortality by 10.7%. This translates into approximately 23,000 avoided deaths in Europe and 16,000 in the United States. In comparison, there are approximately 72,000 flu deaths in Europe and 38,000 flu deaths in the United States each year. When checked for potential biases, our results are robust. Our results are also supported by the natural experiments we have been able to identify. The results of our meta-analysis support the conclusion that lockdowns in the spring of 2020 had little to no effect on COVID-19 mortality. This result is consistent with the view that voluntary changes in behavior, such as social distancing, did play an important role in mitigating the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.30.23294845v1" target="_blank">A Literature Review and Meta-Analysis of the Effects of Lockdowns on COVID-19 Mortality - II</a>
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<li><strong>Identifying resilience factors of distress and paranoia during the COVID-19 pandemic</strong> -
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The ongoing COVID-19 pandemic outbreak has affected all countries with more than 100 million confirmed cases and over 2.1 million casualties by the end of January 2021 worldwide. A prolonged pandemic can harm global levels of optimism, regularity, and sense of meaning and belonging of people, yielding adverse effects on individual’s mental health as represented by worry, paranoia, and distress. Here we studied resilience, a successful adaptation despite risk and adversity, in five countries: Brazil, Colombia, Germany, Israel and Norway. In April 2020, over 2500 participants were recruited for an observational study measuring protective and obstructive factors for mental health. More than 800 of these participants also completed a follow-up study in July. We found that thriving, keeping a regular schedule, engaging in physical exercise and less procrastination served as factors protecting mental well-being. Risk factors were financial worries and a more negative mindset, e.g. feeling a lack of control. Longitudinally, we found no increase in distress or paranoia despite an increase in expectation how long the outbreak and the restrictions will last, suggesting respondents engaged in healthy coping and adapting their life to the new circumstances. Thus, our data shines some light on the mostly depressive news during the pandemic. Humans adapt and despite adversity there are protective factors that policy makers should leverage on.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/2e3n5/" target="_blank">Identifying resilience factors of distress and paranoia during the COVID-19 pandemic</a>
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<li><strong>Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16</strong> -
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The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5’ end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2’-O-methyltransferase and NSP14 through its N7 methyltransferase activity, which are essential for the replication of the viral genome as well as evading the host’s innate immunity. NSP10 acts as a crucial cofactor and stimulator of NSP14 and NSP16. To further understand the role of NSP10, we carried out a comprehensive analysis of >13 million globally collected whole-genome sequences (WGS) of SARS-CoV-2 obtained from the Global Initiative Sharing All Influenza Data (GISAID) and compared it with the reference genome Wuhan/WIV04/2019 to identify all currently known variants in NSP10. T12I, T102I, and A104V in NSP10 have been identified as the three most frequent variants and characterized using X-ray crystallography, biophysical assays, and enhanced sampling simulations. In contrast to other proteins such as spike and NSP6, NSP10 is significantly less prone to mutation due to its crucial role in replication. The functional effects of the variants were examined for their impact on the binding affinity and stability of both NSP14-NSP10 and NSP16-NSP10 complexes. These results highlight the limited changes induced by variant evolution in NSP10 and reflect on the critical roles NSP10 plays during the SARS-CoV-2 life cycle. These results also indicate that there is limited capacity for the virus to overcome inhibitors targeting NSP10 via the generation of variants in inhibitor binding pockets.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.23.521761v3" target="_blank">Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16</a>
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<li><strong>Meisoindigo: An Effective Inhibitor of SARS-CoV-2 Main Protease Revealed by Yeast System</strong> -
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The COVID-19 pandemic caused by SARS-CoV-2 has had a significant impact on global health and economy. Despite the availability of vaccines, their limited accessibility and vaccine hesitancy pose challenges in controlling the spread of the disease. Effective therapeutic strategies, including antiviral drugs, are needed to combat the future spread of new SARSCoV- 2 virus variants. The main protease (Mpro) is a critical therapeutic target for COVID-19 medicines, as its inhibition impairs viral replication. However, the use of substances that inhibit Mpro may induce selection pressure. Thus, it is vital to monitor viral resistance to known drugs and to develop new drugs. Here we have developed a yeast system for the identification of Mpro inhibitors as an alternative to costly and demanding high biosecurity procedures. The system is based on stable expression of Mpro and does not require selection media. Yeast can be cultured on a rich carbon source, providing rapid growth and screening results. The designed tool was subsequently used to screen the FDA-Approved Drug Library. Several chemicals with Mpro inhibitory properties were identified. We found that meisoindigo not previously known for its potential to inhibit Mpro, was highly effective. Our results may promote development of new derivatives with therapeutic properties against SARS-CoV-2 and other beta-coronaviruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.03.555867v1" target="_blank">Meisoindigo: An Effective Inhibitor of SARS-CoV-2 Main Protease Revealed by Yeast System</a>
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<li><strong>Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86</strong> -
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The recently identified SARS-CoV-2 variant, BA.2.86, which carries a substantial number of Spike mutations, has raised a global alarm. An immediate assessment of its antigenic properties and infectivity is necessary. Here, we reveal the distinct antigenicity of BA.2.86 compared with previous variants including XBB.1.5. BA.2.86 significantly evades convalescent plasma from XBB breakthrough infection (BTI) and reinfections. Key mutations that mediate the enhanced resistance include N450D, K356T, L452W, A484K, V483del, and V445H on the RBD, while BA.2.86's NTD mutations and E554K on SD1 also largely contribute. However, we found that BA.2.86 pseudovirus exhibits compromised efficiency of infecting HEK293T-hACE2 cells compared to XBB.1.5 and EG.5, which may be caused by K356T, V483del, and E554K, and could potentially limit BA.2.86's transmissibility. In sum, it appears that BA.2.86 has traded its infectivity for higher immune evasion during long-term host-viral evolution. Close attention should be paid to monitoring additional mutations that could improve BA.2.86's infectivity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.01.555815v1" target="_blank">Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A 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>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>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>Pre-probiotic Supplementation for Post-covid Fatigue Syndrome</strong> - <b>Condition</b>: Long COVID<br/><b>Interventions</b>: Dietary Supplement: Dietary Supplement: Experimental; Dietary Supplement: Dietary Supplement: Placebo<br/><b>Sponsor</b>: University of Novi Sad, Faculty of Sport and Physical Education<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>A Study of Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>: Critical Illness; COVID-19; PICS; Cognitive Impairment; Mental Health Impairment; Weakness, Muscle; Dysbiosis<br/><b>Intervention</b>: Behavioral: Fermented Food Diet<br/><b>Sponsor</b>: Mayo Clinic<br/><b>Not yet recruiting</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>Radiologists’ experiences and perceptions regarding the use of teleradiology in South Africa</strong> - CONCLUSION: It is important to address structural barriers to the implementation of teleradiology. Clear communication strategies and multistakeholder engagement are also required.</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>Increased Fungal Infection Mortality Induced by Concurrent Viral Cellular Manipulations</strong> - Certain respiratory fungal pathogen mono-infections can cause high mortality rates. Several viral pathogen mono-infections, including influenza viruses and coronaviruses including SARS-CoV-2, can also cause high mortality rates. Concurrent infections by fungal pathogens and highly manipulative viral pathogens can synergistically interact in the respiratory tract to substantially increase their mortality rates. There are at least five viral manipulations which can assist secondary fungal…</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 wild boar cathelicidin peptide derivative inhibits severe acute respiratory syndrome coronavirus-2 and its drifted variants</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a clear threat to humanity. It has infected over 200 million and killed 4 million people worldwide, and infections continue with no end in sight. To control the pandemic, multiple effective vaccines have been developed, and global vaccinations are in progress. However, the virus continues to mutate. Even when full vaccine coverage is achieved, vaccine-resistant mutants will likely emerge, thus requiring new annual vaccines…</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 SREBP pathway prevents SARS-CoV-2 replication and inflammasome activation</strong> - SARS-CoV-2 induces major cellular lipid rearrangements, exploiting the host’s metabolic pathways to replicate. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that control lipid metabolism. SREBP1 is associated with the regulation of fatty acids, whereas SREBP2 controls cholesterol metabolism, and both isoforms are associated with lipid droplet (LD) biogenesis. Here, we evaluated the effect of SREBP in a SARS-CoV-2-infected lung epithelial cell line…</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>SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2</strong> - Frequent mutation and variable immunological protection against vaccination is a common feature for COVID-19 pandemic. Early detection and confinement remain key to controlling further spread of infection. In response, we have developed an aptamer-based system that possesses both diagnostic and therapeutic potential towards the virus. A random aptamer library (~ 10^(17) molecules) was screened using systematic evolution of ligands by exponential enrichment (SELEX) and aptamer R was identified 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>High-CBD cannabis extracts inhibit the expression of proinflammatory factors via miRNA-mediated silencing in human small intestinal epithelial cells</strong> - The incidence of chronic inflammatory disorders and autoimmune diseases is rapidly growing. To date, the COVID-19 pandemic caused by SARS-CoV-2 has killed over 6,209,000 people globally, while no drug has been proven effective for the disease. Screening natural anti-inflammatory compounds for clinical application has drawn much attention. In this study, we showed that high-CBD cannabis extracts #1, #5, #7, #169, and #317 suppressed the levels of expression of proinflammatory cyclooxygenase 2…</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>Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication</strong> - Plant-based flavonoids have been evaluated as inhibitors of β-coronavirus replication and as therapies for COVID-19 on the basis of their safety profile and widespread availability. The SARS-CoV-2 main protease (Mpro) has been implicated as a target for flavonoids in silico. Yet no comprehensive in vitro testing of flavonoid activity against SARS-CoV-2 Mpro has heretofore been performed. We screened 1,019 diverse flavonoids for their ability to inhibit SARS-CoV-2 Mpro. Multiple…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response</strong> - Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified that indomethacin can inhibit pan-coronavirus infection in human cell and airway organoids models. Combining indomethacin with oral antiviral drugs authorized for treating COVID-19 results in synergistic anti-coronavirus activity. Coincidentally,…</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>Assessing the outcomes of prescribing angiotensin converting enzyme inhibitors and angiotensin receptor blockers for COVID-19 patients</strong> - CONCLUSION: Inhibition of the renin-angiotensin-aldosterone-system had no effect on the mortality of patients with COVID-19 and on their overall disease progression. However, it may be beneficial not to stop these medications as they decrease inflammation in the body and the levels of troponin, which are related to increased stress on the heart.</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>Deadly interactions: synergistic manipulations of concurrent pathogen infections potentially enabling future pandemics</strong> - Certain monoinfections of influenza viruses and novel coronaviruses, including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are significant threats to human health. Concurrent infections by influenza viruses and coronaviruses increases their threat. Influenza viruses have eight manipulations capable of assisting SARS-CoV-2 and other coronaviruses, and several of these manipulations, which are not specific to viruses, can also directly or indirectly boost dangerous secondary…</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>An evolutionarily conserved strategy for ribosome binding and host translation inhibition by β-coronavirus non-structural protein 1</strong> - An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Non-structural protein 1 (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. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from β-Coronaviruses (β-CoV) inhibits translation through ribosome binding. The C-terminal domain…</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 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1</strong> - SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated…</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>Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review</strong> - Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) identified in 2003 infected ∼8000 people in 26 countries with 800 deaths, which was soon contained and eradicated by syndromic surveillance and enhanced quarantine. A closely related coronavirus SARS-CoV-2, the causative agent of COVID-19 identified in 2019, has been dramatically more contagious and catastrophic. It has infected and caused various flu-like symptoms of billions of people in >200 countries, including >6 million…</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>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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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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