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<title>21 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>FAKHRAVAC and BBIBP-CorV vaccine seeds’ binding to angiotensin-converting enzyme 2: A comparative molecular dynamics study</strong> -
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<div>
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Background: Safety and efficacy of the SARS-CoV-2 inactivated vaccines have been question since the emergence of SARS-CoV-2 variants of concern (VOCs). Using residue fluctuations and statistically comparing RMSF values, have escalated the understanding of the binding dynamics of the viral proteins to their receptors and here in this study, we compared the interaction between inactivated spike proteins (representing FAKHRAVAC and BBIBP-CorV vaccines seed) and the human Angiotensin-Converting Enzyme 2 (hACE2) receptor. Methodology: Through 100 set of accelerated 1 ns comparative molecular dynamics simulations, we analyze the binding dynamics and energy components of these interactions and compared residue backbone fluctuations using entropy and statistics including KL-Divergence and KS-test. Principal Findings: Our results reveal that FAKHRAVAC and Sinopharm exhibit similar binding dynamics and affinity to hACE2. Further examination of residue-wise fluctuations highlights the common behavior of binding key residues and mutation sites between the two vaccines. However, subtle differences in residue fluctuations, especially at critical sites like Q24, Y435, L455, S477, Y505, and F486, raise the possibility of distinct efficacy profiles. Conclusion: These variations may influence vaccine immunogenicity and safety in response to evolving SARS-CoV-2 variants. The study underscores the importance of considering residue-wise fluctuations for understanding vaccine-pathogen interactions and their implications for vaccine design.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.19.563051v1" target="_blank">FAKHRAVAC and BBIBP-CorV vaccine seeds’ binding to angiotensin-converting enzyme 2: A comparative molecular dynamics study</a>
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</div></li>
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<li><strong>Divergent spike mutations impact the activation of the fusion core in Delta and Omicronvariants of SARS-CoV-2</strong> -
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<div>
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SARS-CoV-2 infects host cells by binding the receptor-binding domain (RBD) of its spike protein to the receptor, ACE2. A subset of highly effective spike mutations plays critical roles in altering the conformational dynamics of spike protein. Here, we use molecular dynamics simulations to investigate how spike mutations affect the conformational dynamics of spike/ACE2 complex in the D614G, Delta (B.1.617.2) and Omicron (B.1.1.529) SARS-CoV-2 variants. We observe that the increased positive-charged mutations in the Omicron spike amplify its structural rigidity and reduce its structural flexibility. The mutations (P681R in Delta and P681H in Omicron) at the S1/S2 junction facilitate S1/S2 cleavage and aid the activation of the fusion core. We report that high structural flexibility in Delta lowers the barrier for the activation of the S2 core; however, high structural rigidity in Omicron enhances the barrier for the same. Our results also explain why Omicron requires the presence of a higher number of ACE2 to activate its fusion core than Delta.
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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/10.1101/2023.10.19.563184v1" target="_blank">Divergent spike mutations impact the activation of the fusion core in Delta and Omicronvariants of SARS-CoV-2</a>
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</div></li>
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<li><strong>Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by PBR28 PET correlates with vascular disease measures</strong> -
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The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae of COVID-19 (PASC), sometimes referred to as long COVID. The mechanisms of the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, and several studies have pointed to the central nervous and vascular systems as being potential sites of dysfunction. In the current study, we recruited individuals with PASC with diverse symptoms, and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction. We used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 PASC individuals versus 43 normative healthy controls. We found significantly increased neuroinflammation in PASC versus controls across a wide swath of brain regions including midcingulate and anterior cingulate cortex, corpus callosum, thalamus, basal ganglia, and at the boundaries of ventricles. We also collected and analyzed peripheral blood plasma from the PASC individuals and found significant positive correlations between neuroinflammation and several circulating analytes related to vascular dysfunction. These results suggest that an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC.
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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/10.1101/2023.10.19.563117v1" target="_blank">Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by PBR28 PET correlates with vascular disease measures</a>
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</div></li>
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<li><strong>Analysis of uptake, effectiveness and safety of COVID-19 vaccinations in pregnancy using the QResearch database: research protocol and statistical analysis plan</strong> -
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Background The COVID-19 pandemic has affected millions of people globally with major health, social and economic consequences, prompting development of vaccines for use in the general population. However, vaccination uptake is lower in some groups, including in pregnant women, because of concerns regarding vaccine safety. There is evidence of increased risk of adverse pregnancy and neonatal outcomes associated with SARS-CoV-2 infection, but fear of vaccine-associated adverse events on the baby both in short and longer term is one of the main drivers of low uptake for this group. Other vaccines commonly used in pregnancy include influenza and pertussis. These both have reportedly higher uptake compared with COVID-19 vaccination, which may be because they are perceived to be safer. In this study, we will undertake an independent evaluation of the uptake, effectiveness and safety of COVID-19 vaccinations in pregnant women using the QResearch primary care database in England. Objectives A. To determine COVID-19 vaccine uptake in pregnant women compared to uptake of influenza and pertussis vaccinations. B. To estimate COVID-19 vaccine effectiveness in pregnant women by evaluating the risk of severe COVID-19 outcomes following vaccination. C. To assess the safety of COVID-19 vaccination in pregnancy by evaluating the risks of adverse pregnancy and perinatal outcomes and adverse events of special interest for vaccine safety after COVID-19 vaccination compared with influenza and pertussis vaccinations. Methods This population-based study uses the QResearch database of primary health care records, linked to individual-level data on hospital admissions, mortality, COVID-19 vaccination, SARS-CoV-2 testing data and congenital anomalies. We will include women aged 16 to 49 years with at least one pregnancy during the study period of 30th December 2020 to the latest date available. Babies born during the study period will be identified and linked to the mothers record, where possible. We will describe vaccine uptake in pregnant women by trimester and population subgroups defined by demographics and other characteristics. Cox proportional hazards multivariable regression will be used to identify factors associated with vaccine uptake. The effectiveness of COVID-19 vaccines in pregnant women will be assessed using time varying Royston-Palmar regression analyses to determine unadjusted and adjusted hazard ratios for the occurrence of severe COVID-19 outcomes after each vaccine dose compared with unvaccinated individuals. For the safety analysis, we will we use logistic regression analyses to determine unadjusted and adjusted odds ratios for the occurrence of maternal (e.g. miscarriage, ectopic pregnancy and gestational diabetes) and perinatal outcomes (e.g. stillbirth, small for gestational age and congenital anomalies) by vaccination status compared to unvaccinated individuals. For the adverse events of special interest for vaccine safety (e.g. venous thromboembolism, myocarditis and Guillain Barre syndrome), we will use time varying Royston-Palmar regression analyses to determine unadjusted and adjusted hazard ratios for the occurrence of each outcome by vaccination status to unvaccinated individuals. Ethics and dissemination QResearch is a Research Ethics Approved Research Database with ongoing approval from the East Midlands Multi-Centre Research Ethics Committee (Ref: 18/EM/0400). This study was approved by the QResearch Scientific Committee on 9th June 2022. This research protocol has been developed with support from a patient and public involvement panel, who will continue to provide input throughout the duration of the study. Research findings will be submitted to pre-print servers such as MedRxIv, academic publication and disseminated more broadly through media releases and community groups and conference presentations.
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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/10.1101/2022.12.19.22283660v2" target="_blank">Analysis of uptake, effectiveness and safety of COVID-19 vaccinations in pregnancy using the QResearch database: research protocol and statistical analysis plan</a>
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<li><strong>Influence of age, sex, body habitus, vaccine type and anti-S serostatus on cellular and humoral responses to SARS-CoV-2 vaccination</strong> -
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Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+ T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+ CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI associate with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.29.23296222v2" target="_blank">Influence of age, sex, body habitus, vaccine type and anti-S serostatus on cellular and humoral responses to SARS-CoV-2 vaccination</a>
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</div></li>
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<li><strong>The gravity of the status quo: the response of research governance to system-level shocks</strong> -
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Using semi-structured interviews with n=69 global research stakeholders, , this research explores the ways in which stakeholders within system-level research governance organisations conceptualised, responded to, and reasoned the realities of disruption caused by the COVID-19 pandemic, and how they positioned procedural changes to their governance mechanisms. Given that shocks to systems present critical challenges to established practices and embedded institutional norms, we use neo-institutional theory as a heuristic device to examine the relationship between the exogenous shock of COVID-19, trajectories of institutional norms and cultures, and the role institutional stakeholders play in managing responses. Across all the research systems studied (with particular focus on the UK, Australia, Norway, New Zealand, Hong Kong SAR and Italy), participants were concerned about how the shock provided by COVID-19 had both revealed and entrenched deep inequalities (between individuals and between organisations) inherent in their research systems and globally. There were tensions in how participants centralised the concept of the ‘normal’ as part of a process of recovery permeating all system-level responses, often with a sense of nostalgia for past structures (a pre-pandemic ‘golden age’ of research), modes of operation, and embedded norms. Aspirations for short-, medium- and long-term plans for research change echoed a dependency on returning to ‘normal’ and reflected an inevitable pull of the norms of the pre-pandemic status quo. Despite the desire of individuals involved in research governance to ‘build back better’, the pull of institutional norms and the gravitational force of the status quo appears too strong for meaningful change to happen in recovering research systems.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/3wfcb/" target="_blank">The gravity of the status quo: the response of research governance to system-level shocks</a>
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<li><strong>Wastewater as a back door to serology?</strong> -
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Wastewater surveillance is a powerful tool for monitoring the prevalence of infectious disease. Systems for wastewater monitoring were put in place throughout the world during the COVID-19 pandemic. These systems use viral RNA copies as the basis of estimates of COVID-19 cases in the sewershed area, thereby providing data critical for public health responses. However, the potential to measure other biomarkers in wastewater during outbreaks has not been fully explored. Here we report a novel approach for detecting specific human antibodies from wastewater. We measured the abundance of anti-SARS-CoV-2 spike IgG and IgA from fresh samples of community wastewater and from archived frozen samples dating from 2020-22. The assay described can be performed with readily available reagents, at a moderate per-sample cost. Our findings demonstrate the feasibility of noninvasive serological surveillance via wastewater, enabling a new approach to immunity-based monitoring of populations.
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</p>
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</div>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.11.22282224v2" target="_blank">Wastewater as a back door to serology?</a>
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<li><strong>The benefits of voluntary plasma donations: safety, price, and supply resilience</strong> -
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This article summarizes data on blood and blood component VNRD compared to remunerated donations, in the context of safety for patients and donors, price of products, and supply resiliency. This is particularly relevant given the ongoing debate on the proposal for a regulation on substances of human origin (SoHO). Data indicated that when donors are remunerated and therefore donate very frequently, the safety of the patients receiving these donations and the donors themselves is at risk. Moreover, when donations were VNRD compared to remunerated, PDMP prices increased less between 2018 and 2023 and were therefore more cost-effective for patients and healthcare systems. Lastly, the supply of plasma was found to be more resilient during the COVID-19 pandemic when donors were non-remunerated compared to when they were remunerated. In addition, once countries implement remuneration, it cannot be reversed without risking the supply. We strongly urge policy makers to rely on empirical evidence as a basis for decision-making regarding the proposal for a regulation on SoHO.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/fnhjg/" target="_blank">The benefits of voluntary plasma donations: safety, price, and supply resilience</a>
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<li><strong>Influenza Hospitalisations in England during the 2022/23 Season: do different data sources drive divergence in modelled waves? A comparison of surveillance and administrative data.</strong> -
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Background Seasonal influenza places a substantial burden annually on healthcare services. Policies during the COVID-19 pandemic limited the transmission of seasonal influenza, making the timing and magnitude of a potential resurgence difficult to ascertain and important to forecast its impact. Methods We have developed a hierarchical generalised additive model (GAM) for the short-term forecasting of hospital admissions with a positive test for the influenza virus sub-regionally across England. The model incorporates a multi-level structure of spatio-temporal splines, weekly cycles in admissions, and spatial correlation. Using multiple performance metrics including interval score, coverage, bias, and median absolute error, the predictive performance is evaluated for the 2022/2023 seasonal wave. Performance is measured against autoregressive integrated moving average (ARIMA) and Prophet time series models. Results Across the epidemic phases the hierarchical GAM shows improved performance, at all geographic scales relative to the ARIMA and Prophet models. Temporally, the hierarchical GAM has overall an improved performance at 7 and 14 day time horizons. The performance of the GAM is most sensitive to the flexibility of the smoothing function that measures the national epidemic trend. Conclusions This study introduces an approach to short-term forecasting of hospital admissions for the influenza virus using hierarchical, spatial, and temporal components. The methodology was designed for the real time forecasting of epidemics. This modelling framework was used across the 2022/2023 winter for healthcare operational planning by the UK Health Security Agency and the National Health Service in England.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.19.23297248v1" target="_blank">Influenza Hospitalisations in England during the 2022/23 Season: do different data sources drive divergence in modelled waves? A comparison of surveillance and administrative data.</a>
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<li><strong>Impact of natural disasters on HIV risk behaviors, seroprevalence, and virological supression in a hyperendemic fishing village in Uganda</strong> -
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Background: Understanding the impact of natural disasters on the HIV epidemic in populations with high HIV burden is critical for the effective delivery of HIV control efforts. We assessed HIV risk behaviors, seroprevalence, and viral suppression in a high-HIV prevalence Lake Victoria fishing community before and after COVID-19 emergence/lockdown and a severe lake flooding event, both of which occurred in 2020. Methods: We used data from the largest Lake Victoria fishing community in the Rakai Community Cohort Study, an open population-based HIV surveillance cohort in south-central Uganda, collected prior to (September-December 2018) and after (October-December 2021) COVID-19 emergence/lockdown and a severe flooding event, to evaluate the impact of natural disasters on the key population-level HIV outcomes listed above. Households impacted by flooding were identified using drone data and through consultation with village community health workers. The entire study population was subject to extensive COVID-19-related lockdowns in the first half of 2020. Differences in HIV-related outcomes before and after COVID, and between residents of flooded and non-flooded households, were assessed using a difference-in-difference statistical modeling approach. Findings: 1,226 people participated in the pre- and post-COVID surveys, of whom 506 (41%) were affected by flooding and 513 (41%) were female. HIV seroprevalence in the initial period was 37% in flooded and 36.8% in non-flooded households. Following the COVID-19 pandemic/lockdown, we observed a decline in HIV-associated risk behaviors. Transactional sex declined from 29.4% to 24.8% (p=0.011), and inconsistent condom use with non-marital partners declined from 41.6% to 37% (p=0.021) in the pre- and post-COVID periods. ART coverage increased from 91.6% to 97.2% (p<0.001). There was 17% decline in transactional sex (aPR=0.83, 95% CI: 0.75-0.92) and 28% decline in the overall HIV risk score (aPR=0.83, 95% CI: 0.75-0.92) among HIV-seronegatives and 5% increase in ART coverage between the pre- and post-COVID periods. We observed no statistically significant differences in changes of HIV risk behavior, seroprevalence, or viral suppression outcomes comparing those affected by floods to those not affected by floods in the periods before and after COVID in difference-in-difference analyses. Interpretation: Despite a high background burden of HIV, the COVID-19 pandemic, and severe flooding, we observed no adverse impact on HIV risk behaviors, seroprevalence, or virologic outcomes. This may be attributed to innovative HIV programming during the period and or population resilience. Understanding exactly what HIV programs and personal/community-level strategies worked to maintain good public health outcomes despite extreme environmental and pandemic conditions may help improve HIV epidemic control during future natural disaster events.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.19.23297262v1" target="_blank">Impact of natural disasters on HIV risk behaviors, seroprevalence, and virological supression in a hyperendemic fishing village in Uganda</a>
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<li><strong>SARS-CoV-2 lineage-specific disease symptoms and disease severity in Sao Caetano do Sul city, Brazil</strong> -
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Background: The city of Sao Caetano do Sul, Brazil, established a web-based platform to provide primary care to suspected COVID-19 patients, integrating clinical and demographic data and sample metadata. Here we describe lineage-specific spatiotemporal dynamics of infections, clinical symptoms, and disease severity during the first year of the epidemic. Methods: We selected and sequenced 879 PCR+ swab samples (8% of all reported cases), obtaining a spatially and temporally representative set of sequences. Daily lineage-specific prevalence was estimating using a moving-window approach, allowing inference of cumulative cases and symptom probability stratified by lineage using integrated data from the platform. Results: Most infections were caused by B.1.1.28 (41.3%), followed by Gamma (31.7%), Zeta (9.6%) and B1.1.33 (9.0%). Gamma and Zeta were associated with larger prevalence of dyspnoea (respectively 81.3% and 78.5%) and persistent fever (84.7% and 61.1%) compared to B.1.1.28 and B.1.1.33. Ageusia, anosmia, and coryza were respectively 18.9%, 20.3% and 17.8% less commonly caused by Gamma, while altered mental status was 108.9% more common in Zeta. Case incidence was spatially heterogeneous and larger in poorer and younger districts. Discussion: Our study demonstrates that Gamma was associated with more severe disease, emphasising the role of its increased disease severity in the heightened mortality levels in Brazil.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.19.23297252v1" target="_blank">SARS-CoV-2 lineage-specific disease symptoms and disease severity in Sao Caetano do Sul city, Brazil</a>
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<li><strong>Commentary on the Strategic Interventions for Agriculture, Climate Change, and Food Security Proposed by the National Science and Technology Commission at the 9th Biennial Conference on Science and Technology</strong> -
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Agriculture in Sri Lanka occupies 45.46% of the land and consumes over 80% of the country’s freshwater resources. Rice farming is the most prominent agricultural practice, with 1.8 million families engaged in it. The tea plantation sector produces tea annually, contributing to 285,877 metric tons of export volume. Tea exports contribute nearly 38% of the total agricultural products, with a target of $2,044 million in income by 2025. Climate change and natural resources significantly impact agriculture, with irregular rainfall patterns, temperature variation, and drought causing significant challenges. The proposed interventions under the food crops, plantation, and export crops sectors include enhancing certified seed production, promoting value-added products, and developing training and awareness programs for low-carbon lifestyles. Food security is another area where climate change impacts the agricultural sector, with nearly 26% of the population affected by food security by 2050 due to the COVID-19 pandemic and the conflict between Russia and Ukraine. To address this issue, the proposed strategic interventions aim to achieve SDG 1, SDG 2, and SDG 13, the recommendations of the Paris Agreement on Climate Change, and the actions of the Milan Urban Food Policy Fund. However, more concerns can be put forward to minimize or eliminate diseases in agricultural sectors due to climate change and minimize food waste or loss.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/64grs/" target="_blank">Commentary on the Strategic Interventions for Agriculture, Climate Change, and Food Security Proposed by the National Science and Technology Commission at the 9th Biennial Conference on Science and Technology</a>
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<li><strong>Caveolin-1 mediates neuroinflammation and cognitive impairment in SARS-CoV-2 infection</strong> -
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Leukocyte infiltration of the CNS can contribute to neuroinflammation and cognitive impairment. Brain endothelial cells regulate adhesion, activation, and diapedesis of T cells across the blood-brain barrier (BBB) in inflammatory diseases. The integral membrane protein Caveolin-1 (Cav-1) critically regulates BBB permeability, but its influence on T cell CNS infiltration in respiratory viral infections is unknown. In this study, we sought to determine the role of Cav-1 at the BBB in neuroinflammation in a COVID-19 mouse model. We used mice genetically deficient in Cav-1 to test the role of this protein in T cell infiltration and cognitive impairment. We found that SARS-CoV-2 infection upregulated brain endothelial Cav-1. Moreover, SARS-CoV-2 infection increased brain endothelial cell vascular cell adhesion molecule-1 (VCAM-1) and CD3+ T cell infiltration of the hippocampus, a region important for short term learning and memory. Concordantly, we observed learning and memory deficits. Importantly, genetic deficiency in Cav-1 attenuated brain endothelial VCAM-1 expression and T cell infiltration in the hippocampus of mice with SARS-CoV-2 infection. Moreover, Cav-1 KO mice were protected from the learning and memory deficits caused by SARS-CoV-2 infection. These results indicate the importance of BBB permeability in COVID-19 neuroinflammation and suggest potential therapeutic value of targeting Cav-1 to improve disease outcomes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.18.563024v1" target="_blank">Caveolin-1 mediates neuroinflammation and cognitive impairment in SARS-CoV-2 infection</a>
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<li><strong>Th2 and Th17-Associated Immunopathology Following SARS-CoV-2 Breakthrough Infection in Spike-vaccinated ACE2-humanized Mice</strong> -
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Vaccines have demonstrated remarkable effectiveness in protecting against COVID-19; however, concerns regarding vaccine-associated enhanced respiratory diseases (VAERD) following breakthrough infections have emerged. Spike protein subunit vaccines for SARS-CoV-2 induce VAERD in hamsters, where aluminum adjuvants promote a Th2-biased immune response, leading to increased type 2 pulmonary inflammation in animals with breakthrough infections. To gain a deeper understanding of the potential risks and the underlying mechanisms of VAERD, we immunized ACE2-humanized mice with SARS-CoV-2 Spike protein adjuvanted with aluminum and CpG-ODN. Subsequently, we exposed them to increasing doses of SARS-CoV-2 to establish a breakthrough infection. The vaccine elicited robust neutralizing antibody responses, reduced viral titers, and enhanced host survival. However, following a breakthrough infection, vaccinated animals exhibited severe pulmonary immunopathology, characterized by a significant perivascular infiltration of eosinophils and CD4+ T cells, along with increased expression of Th2/Th17 cytokines. Intracellular flow cytometric analysis revealed a systemic Th17 inflammatory response, particularly pronounced in the lungs. Our data demonstrate that aluminum/CpG adjuvants induce strong antibody and Th1-associated immunity against COVID-19 but also prime a robust Th2/Th17 inflammatory response, which may contribute to the rapid onset of T cell-mediated pulmonary immunopathology following a breakthrough infection. These findings underscore the necessity for further research to unravel the complexities of VAERD in COVID-19 and to enhance vaccine formulations for broad protection and maximum safety.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.18.563016v1" target="_blank">Th2 and Th17-Associated Immunopathology Following SARS-CoV-2 Breakthrough Infection in Spike-vaccinated ACE2-humanized Mice</a>
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<li><strong>The Risk of Mpox (Monkeypox) Importation and Subsequent Outbreak Potential in Mainland China: A Retrospective Statistical Modelling Study</strong> -
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The 2022 mpox outbreak has spread rapidly across multiple countries in the non-endemic region, mainly among men who have sex with men (MSM), while China only has limited recorded importation and no local outbreak. We constructed probabilistic models to simulate the risk of mpox importation in mainland China, with the help of reported monkeypox cases during this multi-country outbreak and the international air-travel data. And we further evaluated the mpox outbreak potential given that undetected mpox infections were introduced into men who have sex with men, considering different transmissibility, population immunity and population activity. We found that the reduced international air-travel volume and stringent border entry policy decreased about 94% and 69% mpox importations respectively. Once a mpox case is introduced into active MSM population with almost no population immunity, the risk of triggering local transmission is estimated at 42%, and would rise to >95% with over six cases. Our study demonstrates the key role of the reduced international air-travel volume and stringent border entry policy during the COVID-19 pandemic on reducing mpox importations, and the subsequent risk of triggering local outbreaks among MSM.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.24.23294530v2" target="_blank">The Risk of Mpox (Monkeypox) Importation and Subsequent Outbreak Potential in Mainland China: A Retrospective Statistical Modelling Study</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity of Concomitant Administration of COVID-19 Vaccines With Influenza Vaccines</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccine Reaction; Contaminant Injected <br/><b>Interventions</b>: Biological: Omicron-containing COVID-19 vaccine; Biological: influenza vaccine <br/><b>Sponsors</b>: Catholic Kwandong University; Korea University Guro Hospital <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>Narrative Intervention for Long COVID-19 (NICO)</strong> - <b>Conditions</b>: Long COVID; Long Covid19 <br/><b>Interventions</b>: Behavioral: Narrative Intervention for Long COVID-19 (NICO) <br/><b>Sponsors</b>: University of Colorado, Denver <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>Inspiratory Muscle Training in People With Long COVID- A Pilot Investigation.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: PrO2 <br/><b>Sponsors</b>: University of Bath; Swansea University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-Based Respiratory Muscle Strength Training Program for Individuals With Post-COVID-19 Persistent Dyspnea</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Dyspnea <br/><b>Interventions</b>: Device: Respiratory Muscle Strength Trainers <br/><b>Sponsors</b>: University of South Florida <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>Inspiratory Muscle Strength Training in Post-Covid Syndrome</strong> - <b>Conditions</b>: Cardiovascular Abnormalities; Post-COVID-19 Syndrome; Physical Exercise <br/><b>Interventions</b>: Other: Inspiratory muscle strength training <br/><b>Sponsors</b>: D’Or Institute for Research and Education <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>Rural Tailored Communication to Promote SARS-CoV-2 Antibody Testing in Saliva</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Behavioral: General SARS-CoV-2 Communication; Behavioral: Rural-Targeted SARS-CoV-2 Communication <br/><b>Sponsors</b>: Michigan State University; National Cancer Institute (NCI); Johns Hopkins 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>Cognitive Rehabilitation Therapy for COVID-19</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Compensatory Cognitive Training for COVID-19; Behavioral: Holistic Cognitive Education <br/><b>Sponsors</b>: VA Office of Research and Development <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID Rehabilitation</strong> - <b>Conditions</b>: Rehabilitation; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders <br/><b>Interventions</b>: Behavioral: One day course; Behavioral: Individual follow-ups <br/><b>Sponsors</b>: University Hospital of North Norway; University of Bergen; Oslo University Hospital; Norwegian University of Science and Technology <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>Phase 3 Open-Label Controlled Trial of Convalescent Plasma in Early COVID-19 Infection</strong> - <b>Conditions</b>: Covid19 <br/><b>Interventions</b>: Drug: Convalescent Plasma; Other: Standard of Care <br/><b>Sponsors</b>: Larkin Community Hospital <br/><b>Withdrawn</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>Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection <br/><b>Interventions</b>: Drug: GST-HG171/ritonavir; Drug: ritonavir <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <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>Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments</strong> - <b>Conditions</b>: Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome; COVID-19; Fatigue; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Device: Monoplace Hyperbaric Chamber (Class III medical device). <br/><b>Sponsors</b>: Sunnybrook Health Sciences Centre <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>Education of Medical Staff to Post Acute Covid susTained sYmptoms</strong> - <b>Conditions</b>: Post-acute COVID-19 Syndrome <br/><b>Interventions</b>: Other: Training in the management of functional disorders; Other: Reimbursement of 3 long consultations <br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; ANRS, Emerging Infectious Diseases <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>Pharmacist Management of Paxlovid eVisits</strong> - <b>Conditions</b>: COVID-19; Quality of Care <br/><b>Interventions</b>: Other: Pharmacist Care; Other: AFM Pool Care <br/><b>Sponsors</b>: Kaiser Permanente <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>Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol</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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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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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>Humoral immune response to SARS-CoV-2 and endemic coronaviruses in urban and indigenous children in Colombia</strong> - CONCLUSIONS: Overall, antibody titers, but in particular ACE2 binding inhibition are low within Colombian samples, requiring further investigation to determine any potential clinical significance.</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>ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2</strong> - Apoptosis signal-regulating kinase 1 (ASK1)/MAP3K5 is a stress response kinase that is activated by various stimuli. It is known as an upstream activator of p38- Mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) that are reactive oxygen species (ROS)-induced kinases. Accumulating evidence show that ROS accumulate in virus-infected cells. Here, we investigated the relationship between viruses and ASK1/p38MAPK or ASK1/JNK pathways. Our findings suggest that virus…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract</strong> - CONCLUSIONS: Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production, and administration of interferon alpha-14 may be attractive transmission-blocking interventions.</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>Assembly of SARS-CoV-2 ribonucleosomes by truncated N* variant of the nucleocapsid protein</strong> - The Nucleocapsid (N) protein of SARS-CoV-2 compacts the RNA genome into viral ribonucleoprotein (vRNP) complexes within virions. Assembly of vRNPs is inhibited by phosphorylation of the N protein SR region. Several SARS-CoV-2 variants of concern carry N protein mutations that reduce phosphorylation and enhance the efficiency of viral packaging. Variants of the dominant B.1.1 viral lineage also encode a truncated N protein, termed N* or Δ(1-209), that mediates genome packaging despite lacking 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>Update on fungal lipid biosynthesis inhibitors as antifungal agents</strong> - Fungal diseases today represent a world-wide problem. Poor hygiene and decreased immunity are the main reasons behind the manifestation of this disease. After COVID-19, an increase in the rate of fungal infection has been observed in different countries. Different classes of antifungal agents, such as polyenes, azoles, echinocandins, and anti-metabolites, as well as their combinations, are currently employed to treat fungal diseases; these drugs are effective but can cause some side effects and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Assessment of virus and Leptospira carriage in bats in France</strong> - With over 1,400 species worldwide, bats represent the second largest order of mammals after rodents, and are known to host major zoonotic pathogens. Here, we estimate the presence of pathogens in autochthonous bat populations. First, we set out to check our samples for PCR amplification efficiency by assessing the occurrence of inhibited PCR reactions from different types of bat samples with amplifying the housekeeping gene β-actin. Second, we investigated the presence of five targeted pathogens…</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>Blocking of doublecortin-like kinase 1-regulated SARS-CoV-2 replication cycle restores cell signaling network</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to fatal outcomes for subgroups of patients with pre-existing co-morbidities. We previously reported a significant association between high expression levels of a cancer stem cell protein, doublecortin-like kinase 1 (DCLK1), in the lungs and macrophages of SARS-CoV-2-infected patients and the severity of coronavirus disease 2019 (COVID-19). Herein, we demonstrate a pivotal role of DCLK1 in the viral replication cycle…</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 Screening of Some Active Phytochemicals to Identify Promising Inhibitors Against SARS-CoV-2 Targets</strong> - CONCLUSION: The present in silico screening study suggested that active phytomolecules from medicinal plants could inhibit SARS-CoV-2 targets. The elite docked compounds with drug-like properties have a harmless ADMET profile, which may help to develop promising COVID-19 inhibitors.</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 SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity</strong> - The SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localizes to mitochondria, where it inhibits innate immunity by restricting IFN-β…</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>Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors</strong> - A class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC(50) range of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral Effects of Micafungin against Pteropine Orthoreovirus, an Emerging Zoonotic Virus Carried by Bats</strong> - Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, and/or beta coronavirus. Pteropine orthoreovirus (PRV), whose spillover event occurred from fruits bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is an effective tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic…</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>Cellular assays for dynamic quantification of deubiquitinase activity and inhibition</strong> - Deubiquitinases (DUBs) are proteolytic enzymes that catalyze the removal of ubiquitin from protein substrates. The critical role of DUBs in regulating protein ubiquitination makes them attractive drug targets in oncology, neurodegenerative disease, and antiviral development. Biochemical assays for quantifying DUB activity have enabled characterization of substrate preferences and discovery of small molecule inhibitors. However, assessing the efficacy of these inhibitors in cellular contexts to…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transporter modulation of molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-brain barrier in a rat</strong> - CONCLUSIONS: In summary, molnupiravir rapidly transforms into NHC and crosses the BBB and reaches the brain at approximately 0.3-0.8% of the blood‒brain ratio. The maximum concentration of NHC in the blood and brain is above the average half maximal inhibitory concentration (IC50) of the drug required to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, suggesting a therapeutic effect. The penetration of NHC is modulated by NBMPR. These findings provide constructive…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation and Mechanistic Investigation of Human Milk Oligosaccharide against SARS-CoV-2</strong> - Four human milk oligosaccharides (HMOs), 3’-sialyllactose (3’-SL), 6’-sialyllactose (6’-SL), 2’-fucosyllactose (2’-FL), and 3-fucosyllactose (3-FL), were assessed for their possible antiviral activity against the SARS-CoV-2 spike receptor binding domain (RBD) in vitro. Among them, only 2’-FL/3-FL exhibited obvious antibinding activity against direct binding and trans-binding in competitive immunocytochemistry and enzyme-linked immunosorbent assays. The antiviral effects of 2’-FL/3-FL were…</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>Explore intersection genes of oxymatrine and COVID-19 with lung cancer as potential therapeutic targets based on network pharmacology</strong> - Introduction. Oxymatrine is a natural quinazine alkaloid extracted from Sophora flavescens and has many medicinal values. Oxymatrine showed protective effects, viral inhibition and effects against lung cancer.Hypothesis/Gap Statement. Individuals with lung cancer exhibit heightened vulnerability to COVID-19 infection due to compromised immune function. In conjunction with COVID-19, it is hypothesized that oxymatrine may exert potent pharmacological effects on lung cancer patients.Aim. The…</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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