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<title>11 October, 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Development and Validation of the Pandemic Fatigue Scale</strong> -
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The existence and nature of pandemic fatigue––defined as a gradually emerging subjective state of weariness and exhaustion from, and a general demotivation towards, following recommended health-protective behaviors, including keeping oneself informed during a pandemic––has been debated. Herein, we introduce the Pandemic Fatigue Scale and show how pandemic fatigue evolved during the COVID-19 pandemic, using data from one panel survey and two repeated cross-sectional surveys in Denmark and Germany (overall N = 34,582). We map the correlates of pandemic fatigue and show that pandemic fatigue is negatively related to people’s self-reported adherence to recommended health-protective behaviors. Manipulating the (de)motivational aspect of pandemic fatigue in a preregistered online experiment (N = 1,584), we further show that pandemic fatigue negatively affects people’s intention to adhere to recommended health-protective behaviors. Combined, these findings provide evidence not only for the existence of pandemic fatigue, but also its psychological and behavioral associations.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/2xvbr/" target="_blank">Development and Validation of the Pandemic Fatigue Scale</a>
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<li><strong>Occupational resilience factors among healthcare workers during the COVID-19 pandemic: a 2-year prospective cohort study</strong> -
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Background. Healthcare workers (HCWs) in COVID-19 pandemic hotspots were exposed to workplace stressors. Structural occupational factors that prevent stressor exposure from translating into mental health problems (i.e., resilience factors) remain poorly understood. This study identifies resilience factors actionable at the workplace and examines the role of cumulative stressor exposure for developing depressive symptoms. Methods. We prospectively followed a convenience sample of HCWs working in Spain. We used a survey to collect self-reported data on (a) sociodemographic characteristics, (b) workplace and COVID-19-related stressors, (c) potential occupational resilience factors, and (d) depression symptoms, at three time points (2020, 2021 and 2022). We operationalised resilience as low stressor reactivity (SR), quantified as individual deviations from the normative relation between exposure to stressors and depressive symptoms. We performed linear and quadratic multiple regression analyses to examine the prospective association between (a) potential resilience factors and (b) prior stressor exposure, with SR across waves. Results. Our sample consisted of 1,872, 1,560, and 431 participants at time points 1, 2, and 3, respectively (median age 42-43 years, 77-80% female). The occupational factors support from colleagues (SOCwork), trust in the workplace (TRUSTwork), and perceived ability to recover from adversity (REC) were prospectively associated with resilience and thus identified as resilience factors. Stressor exposure at baseline was inversely associated with resilience at follow-ups. Conclusions. Occupational strategies that promote key resilience factors and reduce cumulative or prolonged stressor exposure may enhance resilience in times of crisis. The observational design and the large drop in response rates warrant further studies.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/8pf52/" target="_blank">Occupational resilience factors among healthcare workers during the COVID-19 pandemic: a 2-year prospective cohort study</a>
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</div></li>
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<li><strong>SHIFTR enables the unbiased and multiplexed identification of proteins bound to specific RNA regions in live cells</strong> -
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<div>
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RNA-protein interactions determine the cellular fate of RNA and are central to regulating gene expression outcomes in health and disease. To date, no method exists that is able to identify proteins that interact with specific regions within endogenous RNAs in live cells. Here, we develop SHIFTR (Selective RNase H-mediated interactome framing for target RNA regions ), an efficient and scalable approach to identify proteins bound to selected regions within endogenous RNAs using mass spectrometry. Compared to state-of-the-art techniques, SHIFTR is superior in accuracy, captures close to zero background interactions and requires orders of magnitude lower input material. We establish SHIFTR workflows for targeting RNA classes of different length and abundance, including short and long non-coding RNAs, as well as mRNAs and demonstrate that SHIFTR is compatible with sequentially mapping interactomes for multiple target RNAs in a single experiment. Using SHIFTR, we comprehensively identify interactions of cis-regulatory elements located at the 5’ and 3’-terminal regions of the authentic SARS-CoV-2 RNA genome in infected cells and accurately recover known and novel interactions linked to the function of these viral RNA elements. SHIFTR enables the systematic mapping of region-resolved RNA interactomes for any RNA in any cell type and has the potential to revolutionize our understanding of transcriptomes and their regulation.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.09.561498v1" target="_blank">SHIFTR enables the unbiased and multiplexed identification of proteins bound to specific RNA regions in live cells</a>
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</div></li>
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<li><strong>SARS-CoV-2 antibodies cross-react and enhance dengue infection</strong> -
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<div>
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Dengue disease is highly prevalent in tropical and subtropical regions worldwide. However, its pathogenesis is still incompletely understood, particularly in comparison to other endemic viruses. Antibody-dependent enhancement (ADE) is a well-known phenomenon for dengue viruses. Given the recent surge in dengue cases and potential cross-reactivity with SARS-CoV-2 antibodies, this study explores the impact of anti-SARS-CoV-2 antibodies on DENV-2 infection. The study assessed the cross-reactivity of SARS-CoV-2 antibodies with the DENV-2 Virus. Human convalescent plasma samples collected during different waves of COVID-19 and monoclonal and polyclonal antibodies raised against SARS-CoV-2 were examined for their potential to cause ADE of DENV-2 infection using cell-based assays. The study found that anti-SARS-CoV-2 antibodies acquired from natural infection in humans or through experimental immunization in animals were cross-reactive with DENV-2 and had the potential to enhance DENV-2 infection in K562 and U937 cells. In-silico and in-vitro studies indicated a strong interaction between SARS-CoV-2 antibodies and DENV-2 E-protein, providing a molecular basis for these findings. This study is the first to demonstrate that anti-SARS-CoV-2 antibodies can cross-react with DENV-2 and can enhance its infection through ADE. These findings have implications for SARS-CoV-2 vaccine development and deployment strategies in regions where dengue is endemic.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.09.557914v1" target="_blank">SARS-CoV-2 antibodies cross-react and enhance dengue infection</a>
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<li><strong>Surrogate virus neutralisation test based on nanoluciferase-tagged antigens to quantify inhibitory antibodies against SARS-CoV-2 and characterise Omicron-specific reactivity</strong> -
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Virus-specific antibodies are important determinants of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While regarded as the gold standard for detecting functional antibodies, conventional virus neutralisation tests (VNT) or pseudotyped virus neutralisation tests (pVNT) require biosafety level 2 or 3 facilities. Alternatively, the virus-free surrogate virus neutralisation test (sVNT) quantifies inhibitory antibodies that prevent the spike protein from binding to its receptor, human angiotensin-converting enzyme 2 (hACE2). We evaluated secreted nanoluciferase (NLuc)-tagged spike (S) protein fragments as diagnostic antigens in the sVNT in the framework of a vaccination study. First, spike fragments of different lengths were tested for their suitability as diagnostic antigens in a capture enzyme immunoassay (EIA) using unprocessed culture supernatants of transfected cells, identifying the receptor binding domain (RBD) of S as the optimal construct. The sensitivity of the in-house sVNT relying on the NLuc-labelled RBD equalled or surpassed a commercial sVNT (cPass, GenScript Diagnostics) and an in-house pVNT four weeks after the first vaccination (98% vs. 94% and 72%, respectively), reaching 100% in all assays four weeks after the second and third vaccinations. Additionally, serum reactivity with spike constructs of Omicron BA.1 was tested. Compared with a capture EIA, the in-house sVNT and pVNT displayed superior discrimination between wild-type- and variant-specific reactivity of sera. Differences in reactivity were most pronounced after the first and second vaccinations, whereas the third vaccination resulted in robust, cross-reactive detection of Omicron constructs. In conclusion, assays utilising NLuc-labelled protein fragments permit the quantification and functional assessment of SARS-CoV-2-specific antibodies and the detection of variant-specific differences in reactivity. Potential applications include monitoring therapy and vaccine efficacy and follow-up of prolonged disease courses in high-risk groups. Designed as straightforward, highly flexible modular systems, these tests can be readily adapted to further emerging viral variants.
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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/10.1101/2023.10.10.23296792v1" target="_blank">Surrogate virus neutralisation test based on nanoluciferase-tagged antigens to quantify inhibitory antibodies against SARS-CoV-2 and characterise Omicron-specific reactivity</a>
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</div></li>
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<li><strong>Scaling COVID-19 rates with population size in the United States</strong> -
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We assessed Urban Scaling Theory using time-series data by quantifying allometric scaling relationships of coronavirus disease (COVID-19) cases, deaths, and demographic cohorts within and across three major variant waves of the pandemic (first, delta, omicron). Results indicate that with county-level population size in the United States, the burden of cases disproportionately impacted larger-sized counties. In contrast, the burden of deaths disproportionately impacted smaller counties, which may be partially due to a higher proportion of older adults who live in smaller counties. Future infectious disease burden across populations might be attenuated by applying Urban Scaling Theory to epidemiological efforts through identifying disease allometry and concomitant allocation of medical interventions.
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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/10.1101/2023.10.10.23296807v1" target="_blank">Scaling COVID-19 rates with population size in the United States</a>
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</div></li>
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<li><strong>The impact of depression and childhood maltreatment experiences on psychological adaptation from lockdown to relaxation periods during the COVID-19 pandemic</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The COVID-19 pandemic has presented a significant challenge to societal mental health. Yet, it remains unknown which factors influence the mental adaptation from lockdown to subsequent relaxation periods, particularly for vulnerable groups. This study used smartphone-based monitoring to explore how 74 individuals with major depression (MDD) and 77 healthy controls (HCs) responded to the transition from lockdown to relaxation during the first wave of the COVID-19 pandemic (March 21 to November 01, 2020) regarding interpersonal interactions, COVID-19-related fear (fear of participants9 own health, the health of close relatives, and the pandemics9 economic impact), and the feeling of isolation. Furthermore, we investigated the effect of a diagnosis of MDD and the experience of childhood maltreatment (CM) on adaptive functioning. During the transition from lockdown to relaxation, we observed an increase in direct contacts and a decrease in indirect contacts and self-perceived isolation in the study population. The diagnosis of MDD and the experience of CM moderated a maintenance of COVID-19-related fear: HCs and participants without the experience of CM showed a decrease in fear, while fear of participants with MDD and with an experience of CM did not change significantly. The finding that elevated COVID-19-related fear was sustained in vulnerable groups after lockdown measures were lifted could help guide psychosocial prevention efforts in future pandemic emergencies.
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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/10.1101/2023.10.10.23296796v1" target="_blank">The impact of depression and childhood maltreatment experiences on psychological adaptation from lockdown to relaxation periods during the COVID-19 pandemic</a>
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<li><strong>Perceptions of access to harm reduction services during the COVID-19 pandemic among people who inject drugs in Chicago</strong> -
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Background The COVID-19 pandemic amplified the risk environment for people who inject drugs (PWID), making continued access to harm reduction services imperative. Research has shown that some harm reduction service providers were able to continue to provide services throughout the pandemic. Most of these studies, however, focused on staff perspectives, not those of PWID. Our study examines changes in perceptions of access to harm reduction services among PWID participating in a longitudinal study conducted through the University of Illinois-Chicago9s Community Outreach Intervention Project field sites during the COVID-19 pandemic. Methods Responses to a COVID-19 module added to the parent study survey that assessed the impact of COVID-19 on PWID participating in an ongoing longitudinal study were analyzed to understand how study participants’ self-reported access to harm reduction services changed throughout the pandemic. Mixed effects logistic regression was used to examine difficulty in syringe access as an outcome of COVID-19 phase. Results Most participants reported that access to syringes and naloxone remained the same as prior to the pandemic. Participants had significantly higher odds of reporting difficulty in accessing syringes earlier in the pandemic. Conclusions The lack of perceived changes in harm reduction access by PWID and the decrease in those reporting difficulty accessing syringes as the pandemic progressed suggests the efficacy of adaptations to harm reduction service provision (e.g., window and mobile service) during the pandemic. Further research is needed to understand how the COVID-19 pandemic may have impacted PWIDs’ engagement with harm reduction services.
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</p>
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</div>
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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/10.1101/2023.10.10.23296820v1" target="_blank">Perceptions of access to harm reduction services during the COVID-19 pandemic among people who inject drugs in Chicago</a>
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</div></li>
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<li><strong>Deep learning-guided selection of antibody therapies with enhanced resistance to current and prospective SARS-CoV-2 Omicron variants</strong> -
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<div>
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Most COVID-19 antibody therapies rely on binding the SARS-CoV-2 receptor binding domain (RBD). However, heavily mutated variants such as Omicron and its sublineages, which are characterized by an ever increasing number of mutations in the RBD, have rendered prior antibody therapies ineffective, leaving no clinically approved antibody treatments for SARS-CoV-2. Therefore, the capacity of therapeutic antibody candidates to bind and neutralize current and prospective SARS-CoV-2 variants is a critical factor for drug development. Here, we present a deep learning-guided approach to identify antibodies with enhanced resistance to SARS-CoV-2 evolution. We apply deep mutational learning (DML), a machine learning-guided protein engineering method to interrogate a massive sequence space of combinatorial RBD mutations and predict their impact on angiotensin-converting enzyme 2 (ACE2) binding and antibody escape. A high mutational distance library was constructed based on the full-length RBD of Omicron BA.1, which was experimentally screened for binding to the ACE2 receptor or neutralizing antibodies, followed by deep sequencing. The resulting data was used to train ensemble deep learning models that could accurately predict binding or escape for a panel of therapeutic antibody candidates targeting diverse RBD epitopes. Furthermore, antibody breadth was assessed by predicting binding or escape to synthetic lineages that represent millions of sequences generated using in silico evolution, revealing combinations with complementary and enhanced resistance to viral evolution. This deep learning approach may enable the design of next-generation antibody therapies that remain effective against future SARS-CoV-2 variants.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.09.561492v1" target="_blank">Deep learning-guided selection of antibody therapies with enhanced resistance to current and prospective SARS-CoV-2 Omicron variants</a>
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</div></li>
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<li><strong>1Changes in perceived benefits of COVID-19 lockdowns: From Silver Linings to Groundhog Day: The perceived benefits of the COVID-19 lockdowns and how perceptions changed over time</strong> -
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Abstract Objectives: The experienced benefit of the COVID-19 pandemic by adults has not attracted many research studies and lacks longitudinal studies. The purpose of this study is to improve understanding of the lived experiences of adults during the COVID-19 pandemic over time in the UK, with a national representative sample. Design: Using a longitudinal approach, this study examined people’s lived experiences twice over one year of the pandemic (Wave 1 n=26, Wave 2 n=17). We analysed the data with a constructivist grounded theory from Wave 1 and Wave 2. Findings: This study found three themes: intrapersonal growth, interpersonal relationship, and social cohesion. The benefit of the sudden lifestyle change was evident for many. Many people enjoyed having more time for self-care and family, and experienced a sense of solidarity within the community. As the time went on many participants mentioned they experienced groundhog days and that they felt boredom. Despite many participants enjoying the closeness to family members, others talked about tensions. Concerns were raised about future relationships with friends due to the lack of face to face meetings. The feeling of social cohesion and solidarity waned with the progress of the pandemic when people adhered less to the safety rules. The experience of COVID-19 pandemic impacted people’s intrapersonal growth, interpersonal relationships and the sense of cohesion over time. This evidence can inform future pandemic planning.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/m5edn/" target="_blank">1Changes in perceived benefits of COVID-19 lockdowns: From Silver Linings to Groundhog Day: The perceived benefits of the COVID-19 lockdowns and how perceptions changed over time</a>
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<li><strong>Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany</strong> -
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Objectives: To assess the potential clinical impact and cost-effectiveness of coronavirus disease 2019 (COVID-19) mRNA vaccines updated for Autumn 2023 in adults aged ≥60 years and high-risk persons aged 30-59 years in Germany over a 1-year analytic time horizon (September 2023–August 2024). Methods: A compartmental Susceptible-Exposed-Infected-Recovered model was updated and adapted to the German market. Numbers of symptomatic infections, number of COVID-19 related hospitalisations and deaths, costs, and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio of an Autumn 2023 Moderna updated COVID-19 (mRNA-1273.815) vaccine was compared to no additional vaccination. Potential differences between the mRNA-1273.815 and the Autumn Pfizer-BioNTech updated COVID-19 (XBB.1.5 BNT162b2) vaccines, as well as societal return on investment for the mRNA-1273.815 vaccine relative to no vaccination, were also examined. Results: Compared to no Autumn vaccination, the mRNA-1273.815 campaign is predicted to prevent approximately 1,697,900 symptomatic infections, 85,400 hospitalisations, and 4,100 deaths. Compared to an XBB.1.5 BNT162b2 campaign, the mRNA-1273.815 campaign is also predicted to prevent approximately 90,100 symptomatic infections, 3,500 hospitalisations, and 160 deaths. Across both analyses we found the mRNA-1273.815 campaign to be dominant. Conclusions: The mRNA-1273.815 vaccine can be considered cost-effective relative to the XBB.1.5 BNT162b2 vaccine and highly likely to provide more benefits and save costs compared to no vaccine in Germany, and to offer high societal return on investment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.09.23296505v1" target="_blank">Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany</a>
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<li><strong>Computer model and code sharing practices in healthcare discrete-event simulation: a systematic scoping review</strong> -
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Objectives: Discrete-event simulation is a widely used computational method in health services and health economic studies. This systematic scoping review investigates to what extent authors share computer models, and audits if sharing adheres to best practice. Data sources: The Web of Science, Scopus, PubMed, and ACM Digital Library databases were searched between 1st January 2019 till 31st December 2022. Eligibility criteria for selecting studies: Cost-effectiveness, Health service research and methodology studies in a health context were included. Data extraction and synthesis: The data extraction and best practice audit were performed by two reviewers. We developed best practice audit criteria based on the Turing Way and other published reproducibility guides. Main outcomes and measures: We measured the proportion of literature that shared models; we report analyses by publication type, year of publication, Covid-19 application; and free and open source versus commercial software. Results: 47 (8.3%) of the 564 studies included cited a published DES computer model; rising to 9.0% in 2022. Studies were more likely to share models if they had been developed using free and open source tools. Studies rarely followed best practice when sharing computer models. Conclusions: Although still in the minority, there is evidence that healthcare DES authors are increasingly sharing their computer model artifacts. Although commercial software dominates the DES literature, free and open source software plays a crucial role in sharing. The DES community can adopt many simple best practices to improve the quality of sharing.
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🖺 Full Text HTML: <a href="https://osf.io/c4ytf/" target="_blank">Computer model and code sharing practices in healthcare discrete-event simulation: a systematic scoping review</a>
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<li><strong>The U.S. academic job market survives the SARS-CoV-2 global pandemic</strong> -
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Purpose: This paper aims to identify the extent to which the COVID19 pandemic disrupted the academic job market and the ways in which faculty job applicants altered their applications in response to a changing academia. Design/methodology/approach: The data presented here is the portion relevant to COVID19 collected in a survey of faculty job applicants at the end of the 2019/2020 job cycle in North America (spring 2020). An additional mid-pandemic survey was used in fall 2020 for applicants participating in the following job search cycle to inquire about how they were adapting their application materials. A portion of data from the 2020 to 2022 job cycle surveys was used to represent the late-pandemic. Job posting data from the Higher Education Recruitment Consortium (HERC) is also used to study job availability. Findings: Examination of faculty job postings from 2018 through 2022 found that while they decreased in 2020, the market recovered in 2021 and beyond. While the market recovered, approximately 10% of the faculty job offers reported by 2019/20 survey respondents were rescinded. Respondents also reported altering their application documents in response to the pandemic as well as delaying or even abandoning their faculty job search. Originality: This paper provides a longitudinal perspective with quantitative data on how the academic job market changed through the major events of the COVID19 pandemic in North America, a subject of intense discussion and stress, particularly amongst early career researchers.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.27.493714v2" target="_blank">The U.S. academic job market survives the SARS-CoV-2 global pandemic</a>
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<li><strong>Direct measures of liking and intensity of taste, smell, and chemesthetic stimuli are similar between young people reporting they did or did not have COVID-19</strong> -
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The recovery period from post-COVID-19 smell and taste dysfunctions varies substantially, lasting from a few days to over a year. We aimed to assess the impact of COVID-19 on post-COVID-19 chemosensory sensitivity in a group of young convalescents of eastern/central European ancestry. We measured subjects smell and taste capabilities with a standard testing kit, Monell Flavor Quiz (MFQ), and collected surveys on COVID-19 history. During testing, subjects rated liking and intensity of six odor samples (galaxolide, guaiacol, beta-ionone, trimethylamine, phenylethyl alcohol, 2-ethyl fenchol) and six taste samples (sucralose, sodium chloride, citric acid, phenylthiocarbamide, menthol, capsaicin) on a scale from 1 (dislike extremely, or no intensity) to 9 (like extremely, or extremely intense). There was no statistical difference in intensity ratings or liking of any sample between subjects who reported a history of COVID-19 (n = 34) and those reporting no history (n = 40), independent of presence/absence or severity of smell/taste impairments (P > 0.05). Additionally, neither vaccination status (full vaccination or no vaccination) nor time from the COVID-19 onset (2-27 months) correlated with liking or intensity. These results suggest that most young adults who had COVID-19 recovered their sense of smell and taste.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.07.561170v1" target="_blank">Direct measures of liking and intensity of taste, smell, and chemesthetic stimuli are similar between young people reporting they did or did not have COVID-19</a>
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<li><strong>The SARS-CoV-2 Spike is a virulence determinant and plays a major role on the attenuated phenotype of Omicron virus in a feline model of infection</strong> -
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To assess the role of the Omicron BA.1 Spike (S) protein in the pathogenesis of the severe acute respiratory coronavirus 2 (SARS-CoV-2), we generated recombinant viruses harboring the S D614G mutation (rWA1-D614G) and the Omicron BA.1 S gene (rWA1-Omi-S) in the backbone of the ancestral SARS-CoV-2 WA1 strain genome. The recombinant viruses were characterized in vitro and in vivo. Viral entry, cell-cell fusion, viral plaque size, and viral replication kinetics of the rWA1-Omi-S virus were markedly impaired when compared to the rWA1-D614G virus, demonstrating a lower fusogenicity and ability to spread cell-to-cell of rWA1-Omi-S. To assess the contribution of the Omicron BA.1 S protein to SARS-CoV-2 pathogenesis the pathogenicity of rWA1-D614G and rWA1-Omi-S viruses were compared using a feline model of infection. While the rWA1-D614G-inoculated cats became lethargic and showed increased body temperatures on days 2 and 3 post-infection (pi), rWA1-Omi-S-inoculated cats remained subclinical and gained weight throughout the 14-day experimental period. Animals inoculated with rWA1-D614G presented higher levels of infectious virus shedding in nasal secretions, when compared to rWA1-Omi-S-inoculated animals. In addition, tissue replication of the rWA1-Omi-S was markedly reduced compared to the rWA1-D614G, as evidenced by lower in situ viral RNA and lower viral load in tissues on days 3 and 5 pi. Histologic examination of the nasal turbinate and lungs revealed intense inflammatory infiltration in rWA1-D614G-inoculated animals, whereas rWA1-Omi-S-inoculated cats presented only mild to modest inflammation. Together, these results demonstrate that the S protein is a major virulence determinant for SARS-CoV-2 playing a major role for the attenuated phenotype of the Omicron virus.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.09.561473v1" target="_blank">The SARS-CoV-2 Spike is a virulence determinant and plays a major role on the attenuated phenotype of Omicron virus in a feline model of infection</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>Equity Evaluation of Fact Boxes - Study Protocol for a Multi-center Cluster Randomised Controlled Trial (RCT)</strong> - <b>Conditions</b>: COVID-19; Influenza <br/><b>Interventions</b>: Other: Fact box <br/><b>Sponsors</b>: Harding Center for Risk Literacy <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>tDCS in the Management of Post-COVID Disorders</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training <br/><b>Sponsors</b>: Universidade Federal de Pernambuco; São Paulo State University <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>Early Awake Alterning Prone Positioning Combined With Non-invasive Oxygen Therapy in Patients With COVID-19.</strong> - <b>Conditions</b>: COVID-19 Pneumonia <br/><b>Interventions</b>: Other: Prone position; Other: Standard treatment <br/><b>Sponsors</b>: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran <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>ACTIVATE in Public Housing</strong> - <b>Conditions</b>: Pneumonia; Influenza; Varicella Zoster; Meningitis; COVID-19; Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Increasing Willingness and Uptake of Influenza, Pneumonia, Meningitis, HZV, and COVID-19 Vaccination <br/><b>Sponsors</b>: Charles Drew University of Medicine and Science <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>Effects of a Home-Based Exercise Intervention on Physical Function, Symptoms and Health-Related Quality of Life in Subjects With Long Covid</strong> - <b>Conditions</b>: Long COVID-19; Post-COVID-19 Syndrome <br/><b>Interventions</b>: Other: home-based concurrent exercise <br/><b>Sponsors</b>: University of Vienna <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <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>Study of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile) <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <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>Exercise Interventions in Post-acute Sequelae of Covid-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Exercise <br/><b>Sponsors</b>: University of Virginia <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>Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC)</strong> - <b>Conditions</b>: Long Covid19; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Dietary Supplement: Flavonoids <br/><b>Sponsors</b>: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado <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>The Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease <br/><b>Interventions</b>: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing) <br/><b>Sponsors</b>: Sarang K. Yoon, DO, MOH; Westat; Novavax <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>Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects</strong> - <b>Conditions</b>: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection <br/><b>Interventions</b>: Combination Product: RQ-001; Other: Placebo <br/><b>Sponsors</b>: Red Queen Therapeutics, Inc.; PPD <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>Motivational Interviewing for Vaccine Uptake in Latinx Adults</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Other: EHR alert; Behavioral: Motivational Interviewing; Behavioral: Warm hand off to nurse <br/><b>Sponsors</b>: Boston College; East Boston Neighborhood Health Center; Harvard School of Public Health (HSPH); Boston Children’s Hospital; National Institute of Nursing Research (NINR) <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>Study of “Sputnik Lite” for the Prevention of COVID-19 With Altered Antigenic Composition.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: “Sputnik Lite” vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <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>Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19</strong> - <b>Conditions</b>: COVID-19, SARS-CoV-2 <br/><b>Interventions</b>: Biological: Biological: AZD3152; Biological: Biological: Placebo <br/><b>Sponsors</b>: AstraZeneca <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>Characterization of pre-existing anti-PEG and anti-AGAL antibodies towards PRX-102 in patients with Fabry disease</strong> - Polyethylene glycol (PEG)ylated drugs are used for medical treatment, since PEGylation either decreases drug clearance or/and shields the protein from undesirable immunogenicity. PEGylation was implemented in a new enzyme replacement therapy for Fabry disease (FD), pegunigalsidase-alfa (PRX-102). However, exposure to PEG via life-style products and vaccination can result in the formation of anti-PEG antibodies. We demonstrate the de novo formation of functional anti-PEG antibodies in a healthy…</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>W254 in furin functions as a molecular gate promoting anti-viral drug binding: Elucidation of putative drug tunneling and docking by non-equilibrium molecular dynamics</strong> - Furins are serine endoproteases that process precursor proteins into their biologically active forms, and they play essential roles in normal metabolism and disease presentation, including promoting expression of bacterial virulence factors and viral pathogenesis. Thus, furins represent vital targets for development of antimicrobial and antiviral therapeutics. Recent experimental evidence indicated that dichlorophenyl (DCP)-pyridine “BOS” drugs (e.g., BOS-318) competitively inhibit human furin…</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 N-terminal peptide of the main protease of SARS-CoV-2, targeting dimer interface, inhibits its proteolytic activity</strong> - The main protease (Mpro) of SARS-CoV-2 cleaves 11 sites of viral polypeptide chains and generates essential non-structural proteins for viral replication. Mpro is an important drug target against COVID-19. In this study, we developed a real-time fluorometric turn-on assay system to evaluate Mpro proteolytic activity for a substrate peptide between NSP4 and NSP5. It produced reproducible and reliable results suitable for HTS inhibitor assays. Thus far, most inhibitors against Mpro target 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>Antcin-B, a phytosterol-like compound from Taiwanofungus camphoratus inhibits SARS-CoV-2 3-chymotrypsin-like protease (3CL<sup>Pro</sup>) activity in silico and in vitro</strong> - Despite the remarkable development of highly effective vaccines, including mRNA-based vaccines, within a limited timeframe, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not been entirely eradicated. Thus, it is crucial to identify new effective anti-3CL^(Pro) compounds, pivotal for the replication of SARS-CoV-2. Here, we identified an antcin-B phytosterol-like compound from Taiwanofungus camphoratus that targets 3CL^(Pro) activity….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Designing peptides predicted to bind to the omicron variant better than ACE2 via computational protein design and molecular dynamics</strong> - Brought about by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease (COVID-19) pandemic has resulted in large numbers of worldwide deaths and cases. Several SARS-CoV-2 variants have evolved, and Omicron (B.1.1.529) was one of the important variants of concern. It gets inside human cells by using its S1 subunit’s receptor-binding domain (SARS-CoV-2-RBD) to bind to Angiotensin-converting enzyme 2 receptor’s peptidase domain (ACE2-PD). Using peptides to inhibit…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Porcine deltacoronavirus accessory protein NS6 harnesses VPS35-mediated retrograde trafficking to facilitate efficient viral infection</strong> - Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus with the potential to infect humans. Accessory protein NS6, encoded by PDCoV, is a key factor required for optimal viral replication. However, the precise mechanism(s) used by PDCoV NS6 to function remains largely unclear. The retromer is an evolutionarily highly conserved protein complex that plays an important role in normal cellular biological processes and viral replication. In this study, we identified VPS35,…</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>Natto extract inhibits infection caused by the Aujeszky’s disease virus in mice</strong> - Aujeszky’s disease virus (ADV), also known as Suid alphaherpesvirus 1, which mainly infects swine, causes life-threatening neurological disorders. This disease is a serious global risk factor for economic losses in the swine industry. The development of new anti-ADV drugs is highly anticipated and required. Natto, a traditional Japanese fermented food made from soybeans, is a well-known health food. In our previous study, we confirmed that natto has the potential to inhibit viral infections by…</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>Molecular docking analysis of novel quercetin derivatives for combating SARS-CoV-2</strong> - Quercetin belongs to the flavonoid family, which is one of the most frequent types of plant phenolics. This flavonoid compound is a natural substance having a number of pharmacological effects, including anticancer and antioxidant capabilities, as well as being a strong inhibitor of various toxicologically important enzymes. We discuss the potential of newly recently synthesized quercetin-based derivatives to inhibit SARS-CoV-2 protein. ADMET analysis indicated that all of the studied compounds…</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>Native SEC and Reversed-Phase LC-MS Reveal Impact of Fab Glycosylation of Anti-SARS-COV-2 Antibodies on Binding to the Receptor Binding Domain</strong> - The binding affinity of monoclonal antibodies (mAbs) for their intended therapeutic targets is often affected by chemical and post-translational modifications in the antigen binding (Fab) domains. A new two-dimensional analytical approach is described here utilizing native size exclusion chromatography (SEC) to separate populations of antibodies and bound antibody-antigen complexes for subsequent characterization of these modifications by reversed-phase (RP) liquid chromatography-mass…</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 docking and molecular dynamics studies of molnupiravir (EIDD-2801): implications for novel mechanisms of action on influenza and SARS-CoV-2 protein targets</strong> - Molnupiravir (EIDD-2801) (MLN) is an oral antiviral drug for COVID-19 treatment, being integrated into viral RNA through RNA-dependent RNA polymerase (RdRp). Upon ingestion, MLN is transformed into two active metabolites: β-d-N⁴-hydroxycytidine (NHC) (EIDD-1931) in the host plasma, and EIDD-1931-triphosphate (MTP) within the host cells. However, recent studies provide increasing evidence of MLN’s interactions with off-target proteins beyond the viral genome, suggesting that the complete…</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>In Silico and In Vitro Potential of FDA-Approved Drugs for Antimalarial Drug Repurposing against <em>Plasmodium</em> Serine Hydroxymethyltransferases</strong> - Malaria has spread in many countries, with a 12% increase in deaths after the coronavirus disease 2019 pandemic. Malaria is one of the most concerning diseases in the Greater Mekong subregion, showing increased drug-resistant rates. Serine hydroxymethyltransferase (SHMT), a key enzyme in the deoxythymidylate synthesis pathway, has been identified as a promising antimalarial drug target due to its conserved folate binding pocket. This study used a molecular docking approach to screen 2509 US Food…</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 RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides</strong> - Isoxazoline-carbocyclic monophosphate nucleotides were designed and synthesized through the chemistry of nitrosocarbonyl intermediates and stable anthracenenitrile oxide. Docking and molecular dynamics studies were first conducted for determining the best candidate for polymerase SARS-CoV-2 inhibition. The setup phosphorylation protocol afforded the nucleotides available for the biological tests. Preliminary inhibition and cytotoxicity assays were then performed, and the results showed a…</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>Multi-effective characteristics and advantages of acupuncture in COVID-19 treatment</strong> - Coronavirus disease 2019 (COVID-19) is a major disease that threatens human life and health. Its pathogenesis is complex and still not fully clarified. The clinical treatment is mainly supportive and lacks specific treatment methods. Acupuncture treatment can inhibit immune inflammatory reactions, neuroinflammatory reactions, oxidative stress levels, and hypothalamus-pituitary-adrenal (HPA) axis activity, improve lung function, and relieve migraine, fatigue, anxiety, and depression. However,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In silico</em> and <em>in vitro</em> inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K</strong> - SARS-CoV-2 is a novel coronavirus that emerged as an epidemic, causing a respiratory disease with multiple severe symptoms and deadly consequences. ACE-2 and TMPRSS2 play crucial and synergistic roles in the membrane fusion and viral entry of SARS-CoV-2 (COVID-19). The spike (S) protein of SARS-CoV-2 binds to the ACE-2 receptor for viral entry, while TMPRSS2 proteolytically cleaves the S protein into S1 and S2 subunits, promoting membrane fusion. Therefore, ACE-2 and TMPRSS2 are potential drug…</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>Development and evaluation of a novel chromium III-based compound for potential inhibition of emerging SARS-CoV-2 variants</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused 403 million cases of coronavirus disease (COVID-19) and resulted in more than 5.7 million deaths worldwide. Extensive research has identified several potential drug treatments for COVID-19. However, the development of new compounds or therapies is necessary to prevent the emergence of drug resistance in SARS-CoV-2. In this study, a novel compound based on hexaacetotetraaquadihydroxochromium(III)diiron(III) nitrate, which…</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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