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<title>29 March, 2024</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>A qualitative exploration of triggers for alcohol use and access to alcohol services during the COVID-19 pandemic among people identifying as problem drinkers.</strong> -
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<div>
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Introduction A polarisation of drinking behaviour was observed during the COVID-19 pandemic with some people reported to be drinking more alcohol and others less. We aimed to understand how and why the COVID-19 pandemic and associated restrictions impacted alcohol use and access to support and services during this time. Methods We conducted semi-structured qualitative interviews with 27 participants, including 20 people identifying as problem drinkers and seven alcohol service providers. Data were analysed using reflexive thematic analysis. Results We identified two main triggers for alcohol use during the pandemic: i) loss of daily routine and activity resulted in drinking to cope with social isolation and boredom and ii) drinking alleviated feelings of fear, anxiety and anger over the imposition of pandemic restrictions. Regarding access to services, two main themes were generated: i) remote service provision was perceived as inferior to in-person services and ii) the need to offer choice and flexibility in how services were provided, with service providers reporting more positive experiences of online and telephone service delivery than service users. Discussion and Conclusions This study provides new insights into potential triggers for alcohol use among people identifying as problem drinkers during the COVID-19 pandemic. The acceptability of remote forms of service provision were dependent on service user access to and comfort with using technology. Hybrid delivery models may therefore be suitable in some but not all circumstances, and efforts should be made to promote equitable access to services.
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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/k67zs/" target="_blank">A qualitative exploration of triggers for alcohol use and access to alcohol services during the COVID-19 pandemic among people identifying as problem drinkers.</a>
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<li><strong>Does behavior mediate the effect of weather on SARS-CoV-2 transmission? Evidence from cell-phone data</strong> -
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Background: There is growing evidence that weather alters SARS-CoV-2 transmission, but it remains unclear what drives the phenomenon. One prevailing hypothesis is that people spend more time indoors in cooler weather, leading to increased spread of SARS-CoV-2 related to time spent in confined spaces and close contact with others. However, the evidence in support of that hypothesis is limited and, at times, conflicting. Objectives: We aim to evaluate the extent to which weather impacts COVID-19 via time spent away-from-home in indoor spaces, as compared to a direct effect of weather on COVID-19 hospitalization, independent of mobility. Methods: We use a mediation framework, and combine daily weather, COVID-19 hospital surveillance, cellphone-based mobility data and building footprints to estimate the relationship between daily indoor and outdoor weather conditions, mobility, and COVID-19 hospitalizations. We quantify the direct health impacts of weather on COVID-19 hospitalizations and the indirect effects of weather via time spent indoors away-from-home on COVID-19 hospitalizations within five Colorado counties between March 4th 2020 and January 31st 2021. Results: We found evidence that changes in 12-day lagged hospital admissions were primarily via the direct effects of weather conditions, rather than via indirect effects by which weather changes time spent indoors away-from-home. Sensitivity analyses evaluating time at home as a mediator were consistent with these conclusions. Discussion: Our findings do not support the hypothesis that weather impacted SARS-CoV-2 transmission via changes in mobility patterns during the first year of the pandemic. Rather, weather appears to have impacted SARS-CoV-2 transmission primarily via mechanisms other than human movement. We recommend further analysis of this phenomenon to determine whether these findings generalize to current SARS-CoV-2 transmission dynamics and other seasonal respiratory pathogens.
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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/10.1101/2024.03.26.24304854v1" target="_blank">Does behavior mediate the effect of weather on SARS-CoV-2 transmission? Evidence from cell-phone data</a>
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</div></li>
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<li><strong>Strengthening access to and confidence in COVID-19 vaccines among equity-deserving populations across Canada: An exploratory qualitative study</strong> -
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Introduction: There is a need to reflect on the COVID-19 vaccine distribution across Canada and the extent to which they considered equity-deserving populations. This paper examined and compared strategies implemented by six Canadian provinces to increase access and promote the uptake of COVID-19 vaccines among selected priority populations. We also explored the factors that impacted the implementation of these strategies. Methods: In six provinces (Alberta, British Columbia, Manitoba, Nova Scotia, Ontario, and Quebec), we conducted an environmental scan of provincial rollout documents and media sources reporting vaccine distribution among selected priority populations:First Nations, Inuit, and Metis; Black communities; essential workers; people experiencing homelessness; and people with disabilities. We subsequently interviewed 39 key informants to validate the environmental scan results, identify additional strategies to increase COVID-19 vaccine uptake, and uncover perceptions of the facilitators and challenges that influenced the strategies’ implementation. Results: Through the environmental scans and key informant interviews, we identified that provincial health authorities employed a panoply of strategies to overcome geographic, financial, and attitudinal barriers to COVID-19 vaccines experienced by the priority populations. Most provinces implemented walk-in, mobile, and pop-up vaccination clinics, mobilized public and private health workforce, and designed multilingual communication materials. Facilitators in implementing COVID-19 vaccination strategies included fostering inter-governmental cooperation, harmonizing communication efforts, leveraging existing relationships and networks, and ensuring representation and leadership of community partners. Challenges to implementing COVID-19 vaccination strategies included uncoordinated communication efforts, inadequate distribution of vaccines to areas with the greatest need, mistrust in the government and healthcare system, vaccine hesitancy, and lack of cultural competence by vaccine providers. Conclusions: This study highlights the divide between well-intentioned strategies and interventions and the reality of on-the-ground implementation. The findings offer valuable insights and can inform the implementation of strategies to distribute vaccines equitably in future large-scale vaccination efforts in Canada and globally.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.27.24304984v1" target="_blank">Strengthening access to and confidence in COVID-19 vaccines among equity-deserving populations across Canada: An exploratory qualitative study</a>
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</div></li>
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<li><strong>COHORT PROFILE: IMMUNE RESPONSES TO SARS-COV-2 VACCINATION AND INFECTION IN A LONGITUDINAL SAMPLING AMIDST THE COVID-19 PANDEMIC (LONGTONG-SARS2) IN MALAYSIA</strong> -
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Purpose: This prospective, longitudinal study aims to evaluate the durability and functionality of SARS-CoV-2 Ancestral strain (Wuhan-Hu-1)-specific immune responses induced by COVID-19 vaccination and natural infection over a 12-month period. This article reviews the study protocol, design, methodology, ongoing data collection, analysis procedures, and demographic characteristics of the cohort enrolled. Participants: Between March 2021 and May 2022, 400 participants were enrolled with a 12-month follow-up, concluding in May 2023. Two main groups of participants: (1) serologically SARS-CoV-2-naive individuals receiving the BNT162b2 primary series vaccination (referred to as VAC) and (2) those who recently recovered from COVID-19 infection within 30 days, regardless of vaccination history (referred to as COV). Additionally, a subset of 45 participants with selected COVID-19 exposure histories provided peripheral blood mononuclear cells (PBMCs) for cross-sectional analysis six months after enrollment. Findings to date: Out of 400 participants, 66.8% (n=267) completed the follow-up. Among them, 52.8% (n=141) were in VAC, and 47.2% (n=126) were in COV. As the study progressed, we acknowledged cross-over between initial groups, leading to restructuring into five revised groups based on sequential exposure events. Sociodemographic factors revealed statistically significant age distribution differences (p=0.001) in both initial and revised groups, with no significant differences observed for sex. Future plans: LONGTONG-SARS2 assesses the host-pathogen interactions central to the development of COVID-19 immunity. With enrollment spanning two years of the pandemic, most participants exhibited mixed SARS-CoV-2 exposures-via vaccination and infection-resulting in diverse subgroups of interest. Notably, the inclusion of SARS-CoV-2-naive, pre-exposure serum samples allowed for robust comparator and reduced potential biases. Ongoing analyses will include serology kinetics, memory cells ELISpots, B cells repertoire analysis, cytokine/chemokine profiling, and proteomic pathway to comprehensively examine the immune response against the SARS-CoV-2, thus informing and potentially predicting dynamic longitudinal responses against new more transmissible, immune-evasive SARS-CoV-2 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/10.1101/2024.03.26.24304850v1" target="_blank">COHORT PROFILE: IMMUNE RESPONSES TO SARS-COV-2 VACCINATION AND INFECTION IN A LONGITUDINAL SAMPLING AMIDST THE COVID-19 PANDEMIC (LONGTONG-SARS2) IN MALAYSIA</a>
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<li><strong>The 10-year health impact, economic impact, and return on investment of the South African molecular diagnostics programme for HIV, Tuberculosis and SARS-CoV-2</strong> -
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To ensure there is adequate investment into diagnostics, an understanding of the magnitude of impact and return on investment is necessary. We therefore sought to understand the health and economic impacts of the molecular diagnostic programme in South Africa, to deepen the under-standing on the broad value of diagnostics and guide future healthcare investments. We calcu-lated the 10-year (where data were available) total cost and DALYs averted associated with molecular diagnosis of molecular TB testing (2013-2022), HIV viral load monitoring (2013-2022), early infant diagnosis of HIV infection (2013-2022), and SARS-CoV-2 testing (2020-2022). We then calculated the economic value associated with those health gains and subsequent return on investment. Since the inception of the molecular diagnostics programme in South Africa, 3,035,782 DALYs have been averted as a direct consequence of this pro-gramme. This has generated an estimated $20.5 billion in economic value due to these health gains. The return on investment varied by specific diagnostic test (19.0 for tuberculosis, 1.4 for HIV viral load testing, 64.8 for early infant diagnosis of HIV, and 2.5 for SARS-CoV-2), for an average of 9.9 for the entire molecular diagnostics programme between 2013 and 2022- or $9.9 of value for each $1 invested. The molecular diagnostics programme in South Africa gen-erated a significant amount of health gains and economic value associated with these health gains, and the return-on-investment rivals other high-impact public health interventions such as childhood vaccination. Consequently, the molecular diagnostics programme in South Africa is highly impactful, and will continue to be an excellent investment of South African public health expenditure.
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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/10.1101/2024.03.27.24304888v1" target="_blank">The 10-year health impact, economic impact, and return on investment of the South African molecular diagnostics programme for HIV, Tuberculosis and SARS-CoV-2</a>
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<li><strong>A nationwide Guillain-Barré syndrome epidemiological study in Spain during the COVID-19 years</strong> -
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OBJECTIVE: To perform a nationwide epidemiological study of Guillain-Barré syndrome (GBS) in Spain, analysing background incidences and seasonal variation and trying to identify incidence changes during the COVID-19 years. METHODS: Observational study collecting all GBS diagnoses from National Epidemiological Surveillance Network (RENAVE) collected by the Ministry of Health. Patients discharged with GBS as main diagnosis and admitted during 2018-2021 were included. Data on the incidence of SARS-CoV-2 infections and vaccinations were obtained from the National Epidemiology Centre. RESULTS: In total, 3147 cases were included, 832 in 2018, 861 in 2019, 670 in 2020 and 784 in 2021. Nationwide hospital incidence was 1.78 in 2018, 1.71 in 2019, 1.41 in 2020 and 1.66 in 2021, with an increased frequency in males, elderly population, and in the winter season. Eleven percent of GBS patients needed ventilatory support. GBS and SARS-CoV-2 incidences did not correlate with one another (r=-0.29, p=0.36). GBS incidence decreased during 2020 and during COVID-19 lockdown period in comparison to the same months of 2018-2019. No relationship was found between vaccines and GBS cases during vaccination roll-out in 2021. INTERPRETATION: Incidence of GBS in Spain is similar to that of other countries. Despite prior reports describing a significant increase in COVID-19-associated GBS in Spain, we detected a significant drop of GBS incidence during the SARS-CoV-2 pandemic, probably due to prevention measures. No relationship was found between SARS-CoV-2 or vaccinations and GBS incidences at the population level but data on relationship of vaccinations and GBS at the individual level were not available.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.27.24304897v1" target="_blank">A nationwide Guillain-Barré syndrome epidemiological study in Spain during the COVID-19 years</a>
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<li><strong>Time-varying reproduction number estimation: Fusing compartmental models with generalised additive models</strong> -
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The reproduction number, the mean number of secondary cases infected by each primary case, is a central metric in infectious disease epidemiology, and played a key role in the COVID-19 pandemic response. This is because it gives an indication of the effort required to control the disease. Beyond the well-known <i>basic </i> reproduction number, there are two natural versions, namely the <i>control</i> and <i>effective </i> reproduction numbers. As behaviour, population immunity and viral characteristics can change with time, these reproduction numbers can vary over time and in different regions. Real world data can be complex, for example with daily variation in numbers due to weekend surveillance biases as well as natural stochastic noise. As such, in this work we consider a Generalised Additive Model to smooth real data through the explicit incorporation of day-of-the-week effects, to provide a simple measure of the time-varying growth rate associated with the data. Converting the resulting spline into an estimator for both the control and effective reproduction numbers requires assumptions on a model structure, which we here assume to be a compartmental model. The reproduction numbers calculated are based on both simulated and real world data, and are compared with estimates from an already existing tool. The derived method for estimating the time-varying reproduction number is effective, efficient and comparable to other methods. It provides a useful alternative approach, which can be included as part of a toolbox of models, that is particularly apt at smoothing out day-of-the-week effects in surveillance.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.26.24304928v1" target="_blank">Time-varying reproduction number estimation: Fusing compartmental models with generalised additive models</a>
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<li><strong>East-West mortality disparities during the COVID-19 pandemic widen the historical longevity divide in Europe: an international comparative study.</strong> -
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For over half a century, life expectancy in Eastern European (former communist) countries has been appreciably lower than in Western Europe, although this difference has been narrowing since 2000. We investigated the impact of the COVID-19 pandemic on these differences. The pandemic reversed the recent convergence and widened the gap to levels observed more than two decades ago (7.9 years for males and 4.9 for females in 2021). Moreover, the trajectory of excess mortality in the pandemic differed between East and West, with the first major peaks in Eastern Europe occurring on average six months after the first peaks seen in Western countries. Despite this, the East suffered greater losses in life expectancy, especially in 2021. This was due to larger relative mortality increases in the East rather than greater frailty of the Eastern European populations as indexed by higher pre-pandemic mortality levels. East-West differences in life expectancy losses in 2021 were substantially explained by COVID-19 vaccination, which together with trust in government accounted for half the gap. We conclude that the East-West differences in life expectancy losses are associated with structural and psychosocial traits that have their roots in the communist era. This includes differences in the connectivity of populations (which drives the differences in timing), as well as profound contrasts in levels of trust in science, authorities, and their capacity to enforce lockdowns and other regulatory measures (driving the huge differences in excess mortality from autumn 2020 onwards).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.08.23298275v2" target="_blank">East-West mortality disparities during the COVID-19 pandemic widen the historical longevity divide in Europe: an international comparative study.</a>
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<li><strong>Emotional Contagion in Scandinavia during the COVID-19 Public Health Crisis</strong> -
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In this article we present the findings of social media analysis of the spread of misinformation in the wake of the COVID-19 pandemic and outline how analyses of the psychological properties of a text can be used to optimize strategic messaging online. Our data used Twitter data, collected during the COVID-19 pandemic and analyzed using a suite of AI based analytical tools, which provided data for further empirical analysis. The analysis yielded insights related to the differences in the dynamics of the spread of misinformation within (and outside of) Scandinavian countries. Analysing this data enabled us to explore three hypotheses: (1) Misinformation will be associated with specific moral signatures, which will differ between Scandinavian and non-Scandinavian samples, (2) Levels of engagement will be associated with specific themes and moral concerns, which will differ between Scandinavian and non-Scandinavian samples, and (3) Within Scandinavia, similar unique signatures will be discernible at the country level, with Sweden driving significant differences. These specific results provide guidance for healthcare professionals responsible for communicating information and crafting messages that are more resonant with their target population and more generally demonstrate the ability for social media analysis to be useful in strategic decision making when going beyond focusing on engagement metrics or sentiment alone.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/9e5f7/" target="_blank">Emotional Contagion in Scandinavia during the COVID-19 Public Health Crisis</a>
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<li><strong>The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication</strong> -
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SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with S. aureus or influenza, ongoing pulmonary M. tuberculosis infection, ovalbumin/alum-induced asthma or airway administration of defined TLR ligands and recombinant cytokines, all establish an antiviral state in the lung that restricts SARS-CoV-2 replication upon infection. In addition to antiviral type I interferons, the broadly inducible inflammatory cytokines TNF and IL-1 precondition the lung for enhanced viral control. Collectively, our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation that precedes or accompanies SARS-CoV-2 exposure may be a significant factor contributing to the population-wide variability in COVID-19 disease outcomes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.27.586885v1" target="_blank">The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication</a>
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<li><strong>Virological characteristics of SARS-CoV-2 Omicron BA.5.2.48</strong> -
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With the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbreak and evolved into multi-subvariants in China without clearly established virological characteristics, especially the pathogenicity. Though reduced airborne transmission and pathogenicity of former Omicron sublineages have been revealed in animal models, the virological characteristics of BA.5.2.48 was unidentified. Here, we evaluated the in vitro and in vivo virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). DY.2 replicates more efficiently than DY.1.1 in HelahACE2+ cells and Calu-3 cells. The A570S mutation (of DY.1) in a normal BA.5 spike protein (DY.2) leads to a 20% improvement in the hACE2 binding affinity, which is slightly reduced by a further K147E mutation (of DY.1.1). Compared to the normal BA.5 spike, the double-mutated protein demonstrates efficient cleavage and reduced fusogenicity. BA.5.2.48 demonstrated enhanced airborne transmission capacity in hamsters than BA.2. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in K18-hACE2 rodents. Under immune selection pressure, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus the outbreaking prevalent BA.5.2.48 multisubvariants exhibites divergent virological features.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.26.586802v1" target="_blank">Virological characteristics of SARS-CoV-2 Omicron BA.5.2.48</a>
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<li><strong>CCQM-P199b: Interlaboratory comparability study of SARS-CoV-2 RNA copy number quantification</strong> -
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Nucleic acid amplification tests including reverse transcription-quantitative PCR (RT-qPCR) are used to detect RNA from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic. Standardized measurements of RNA can facilitate comparable performance of laboratory tests in the absence of existing reference measurement systems early on in a pandemic. Interlaboratory study CCQM-P199b 'SARS-CoV-2 RNA copy number quantification' was designed to test the fitness-for-purpose of developed candidate reference measurement procedures (RMPs) for SARS-CoV-2 genomic targets in purified RNA materials, and was conducted under the auspices of the Consultative Committee for Amount of Substance: Metrology in Chemistry and Biology (CCQM) to evaluate the measurement comparability of national metrology institutes (NMIs) and designated institutes (DIs), thereby supporting international standardization. Twenty-one laboratories participated in CCQM-P199b and were requested to report the RNA copy number concentration, expressed in number of copies per microliter, of the SARS-CoV-2 nucleocapsid (N) gene partial region (NC_045512.2: 28274-29239) and envelope (E) gene (NC_045512.2: 26245-26472) (optional measurement) in samples consisting of in vitro transcribed RNA or purified RNA from lentiviral constructs. Materials were provided in two categories: lower concentration (approximately 10 x 1 - 10 x 4/uL in aqueous solution containing human RNA background) and high concentration (approximately 10 x 9/uL in aqueous solution without any other RNA background). For the measurement of N gene concentration in the lower concentration study materials, the majority of laboratories (n = 17) used one-step reverse transcription-digital PCR (RT-dPCR), with three laboratories applying two-step RT-dPCR and one laboratory RT-qPCR. Sixteen laboratories submitted results for E gene concentration. Reproducibility (% CV or equivalent) for RT-dPCR ranged from 19 % to 31 %. Measurements of the high concentration study material by orthogonal methods (isotope dilution-mass spectrometry and single molecule flow cytometry) and a gravimetrically linked lower concentration material were in a good agreement, suggesting a lack of overall bias in RT-dPCR measurements. However methodological factors such as primer and probe (assay) sequences, RT-dPCR reagents and dPCR partition volume were found to be potential sources of interlaboratory variation which need to be controlled when applying this technique. This study demonstrates that the accuracy of RT-dPCR is fit-for-purpose as a RMP for viral RNA target quantification in purified RNA materials and highlights where metrological approaches such as the use of in vitro transcribed controls, orthogonal methods and measurement uncertainty evaluation can support standardization of molecular methods.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.27.584106v1" target="_blank">CCQM-P199b: Interlaboratory comparability study of SARS-CoV-2 RNA copy number quantification</a>
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<li><strong>TCR transgenic clone selection guided by immune receptor analysis and single cell RNA expression of polyclonal responders</strong> -
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Since the precursor frequency of naive T cells is extremely low, investigating the early steps of antigen-specific T cell activation is challenging. To overcome this detection problem, adoptive transfer of a cohort of T cells purified from T cell receptor (TCR) transgenic donors has been extensively used but is not readily available for emerging pathogens. Constructing TCR transgenic mice from T cell hybridomas is a labor-intensive and sometimes erratic process, since the best clones are selected based on antigen-induced CD69 upregulation or IL-2 production in vitro, and TCR chains are PCR-cloned into expression vectors. Here, we exploited the rapid advances in single cell sequencing and TCR repertoire analysis to select the best clones without hybridoma selection, and generated CORSET8 mice (CORona Spike Epitope specific CD8 T cell), carrying a TCR specific for the Spike protein of SARS-CoV-2. Implementing newly created DALI software for TCR repertoire analysis in single cell analysis enabled the rapid selection of the ideal responder CD8 T cell clone, based on antigen reactivity, proliferation and immunophenotype in vivo. In contrast, a traditional method based on hybridoma technology was unsuccessful. Identified TCR sequences were inserted as synthetic DNA into an expression vector and transgenic CORSET8 donor mice were created. After immunization with Spike/CpG-motifs, mRNA vaccination or SARS-CoV2 infection, CORSET8 T cells strongly proliferated and showed signs of T cell activation. Thus, a combination of TCR repertoire analysis and scRNA immunophenotyping allowed rapid selection of antigen-specific TCR sequences that can be used to generate TCR transgenic mice.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.27.586931v1" target="_blank">TCR transgenic clone selection guided by immune receptor analysis and single cell RNA expression of polyclonal responders</a>
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<li><strong>In-silico docking platform with serine protease inhibitor (SERPIN) structures identifies host cysteine protease targets with significance for SARS-CoV-2</strong> -
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Serine Protease Inhibitors (SERPINs) regulate protease activity in various physiological processes such as inflammation, cancer metastasis, angiogenesis, and neurodegenerative diseases. However, their potential in combating viral infections, where proteases are also crucial, remains underexplored. This is due to our limited understanding of SERPIN expression during viral-induced inflammation and of the SERPINs full spectrum of target proteases. Here, we demonstrate widespread expression of human SERPINs in response to respiratory virus infections, both in vitro and in vivo, alongside classical antiviral effectors. Through comprehensive in-silico docking with full-length SERPIN and protease 3D structures, we confirm known inhibitors of specific proteases; more importantly, the results predict novel SERPIN-protease interactions. Experimentally, we validate the direct inhibition of key proteases essential for viral life cycles, including the SERPIN PAI-1’s capability to inhibit select cysteine proteases such as cathepsin L, and the serine protease TMPRSS2. Consequently, PAI-1 suppresses spike maturation and multi-cycle SARS-CoV-2 replication. Our findings challenge conventional notions of SERPIN selectivity, underscore the power of in-silico docking for SERPIN target discovery, and offer potential therapeutic interventions targeting host proteolytic pathways to combat viruses with urgent unmet therapeutic needs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.18.517133v2" target="_blank">In-silico docking platform with serine protease inhibitor (SERPIN) structures identifies host cysteine protease targets with significance for SARS-CoV-2</a>
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<li><strong>Inference of epidemic dynamics in the COVID-19 era and beyond</strong> -
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The COVID-19 pandemic demonstrated the key role that epidemiology and modelling play in analysing infectious threats and supporting decision making in real-time. Motivated by the unprecedented volume and breadth of data generated during the pandemic, we review new analytic opportunities and methodological developments available to address questions that emerge during a major modern epidemic. Following the broad chronology of insights required - from understanding initial dynamics to retrospective evaluation of interventions, we describe the theoretical foundations of each approach and the underlying intuition. Through a series of case studies, we illustrate real life applications, and discuss implications for future work.
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🖺 Full Text HTML: <a href="https://osf.io/bmjxf/" target="_blank">Inference of epidemic dynamics in the COVID-19 era and beyond</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>Diaphragmatic Breathing Exercises for Post-COVID-19 Diaphragmatic Dysfunction (DD)</strong> - <b>Conditions</b>: Post-Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Usual care of traditional treatment; Other: Specific DB program/Diaphragmatic manipulation program <br/><b>Sponsors</b>: University of Minnesota <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>Valacyclovir Plus Celecoxib for Post-Acute Sequelae of SARS-CoV-2</strong> - <b>Conditions</b>: Long COVID; PASC Post Acute Sequelae of COVID 19 <br/><b>Interventions</b>: Drug: Valacyclovir celecoxib dose 1; Drug: Valacyclovir celecoxib dose 2; Drug: Placebo <br/><b>Sponsors</b>: Bateman Horne Center <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Supervised Computerized Active Program for People With Post-COVID Syndrome (SuperCAP Study)</strong> - <b>Conditions</b>: Post-COVID Condition <br/><b>Interventions</b>: Device: SuperCAP Program <br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; Institut de Recerca de la SIDA IrsiCaixa; Germans Trias i Pujol 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>Utilizing Novel Blood RNA Biomarkers as a Diagnostic Tool in the Identification of Long COVID-19</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Diagnostic Test: RNA Biomarker Blood Test <br/><b>Sponsors</b>: MaxWell Clinic, PLC <br/><b>Recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses</strong> - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has decreased the efficacy of SARS-CoV-2 vaccines in containing coronavirus disease 2019 (COVID-19) over time, and booster vaccination strategies are urgently necessitated to achieve sufficient protection. Intranasal immunization can improve mucosal immunity, offering protection against the infection and sustaining the spread of SARS-CoV-2. In this study, an intranasal booster of the RBD-HR vaccine after two…</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>Investigation of phytochemicals isolated from selected Saudi medicinal plants as natural inhibitors of SARS CoV-2 main protease: In vitro, molecular docking and simulation analysis</strong> - The escalation of many coronavirus variants accompanied by the lack of an effective cure has motivated the hunt for effective antiviral medicines. In this regard, 18 Saudi Arabian medicinal plants were evaluated for SARS CoV-2 main protease (Mpro) inhibition activity. Among them, Terminalia brownii and Acacia asak alcoholic extracts exhibited significant Mpro inhibition, with inhibition rates of 95.3 % and 95.2 %, respectively, at a concentration of 100 µg/mL. Bioassay-guided phytochemical study…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and immunogenicity of CoronaVac and ChAdOx1 heterologous prime-boost vaccines in an overweight population in Chiang Mai, Thailand</strong> - CONCLUSIONS: The heterologous CoronaVac-ChAdOx1vaccination was safe, well-tolerated and able to induce humoral immunity against wild-type and Delta variants but not against the Omicron variant in overweight population.</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>Design of a SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model</strong> - The emergence of SARS-CoV-2 variants and drug-resistant mutants calls for additional oral antivirals. The SARS-CoV-2 papain-like protease (PL^(pro)) is a promising but challenging drug target. We designed and synthesized 85 noncovalent PL^(pro) inhibitors that bind to a recently discovered ubiquitin binding site and the known BL2 groove pocket near the S4 subsite. Leads inhibited PL^(pro) with the inhibitory constant K(i) values from 13.2 to 88.2 nanomolar. The co-crystal structures of PL^(pro)…</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>On parrots, delay of gratification, executive function, and how sometimes we do the best we can</strong> - Engaging executive functions provides an individual with the means to engage in cognitive control by adjusting to the environment and processing information in a way that leads to optimal outcomes. There are some claims that explicit training on certain executive functioning abilities provides benefits beyond the training tasks, but other studies indicate that this may not be true or may be limited based on age and other factors. This same mixed pattern has been reported with nonhuman species,…</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>Role for CCN1 in lysophosphatidic acid response in PC-3 human prostate cancer cells</strong> - Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are bioactive phospholipids that act as mitogens in various cancers. Both LPA and S1P activate G-protein coupled receptors (GPCRs). We examined the role of CCN1/CYR61, an inducible matricellular protein, in LPA-induced signal transduction in PC-3 human prostate cancer cells. We found that both LPA and S1P induced expression of CCN1 and CCN2 within 2-4 h. CCN1 was induced by 18:1-LPA, but not by 18:0-, 18:2-, or 18:3-LPAs. A free fatty…</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>Fungal metabolite 6-pentyl-alpha-pyrone reduces canine coronavirus infection</strong> - Canine coronavirus (CCoV) can produce a self-limited enteric disease in dogs but, because of notable biological plasticity of coronaviruses (CoVs), numerous mutations as well as recombination events happen leading to the emergence of variants often more dangerous for both animals and humans. Indeed, the emergence of new canine-feline recombinant alphacoronaviruses, recently isolated from humans, highlight the cross-species transmission potential of CoVs. Consequently, new effective antiviral…</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>Pilot Study on Evaluating the Impact of Tetanus, Diphtheria, and Pertussis (Tdap), Influenza, and COVID-19 Vaccinations on Antibody Responses in Pregnant Women</strong> - This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated…</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>Recent Advances on Targeting Proteases for Antiviral Development</strong> - Viral proteases are an important target for drug development, since they can modulate vital pathways in viral replication, maturation, assembly and cell entry. With the (re)appearance of several new viruses responsible for causing diseases in humans, like the West Nile virus (WNV) and the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the mechanisms behind blocking viral protease’s function is pivotal for the development of new antiviral drugs 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>A Pseudovirus-Based Neutralization Assay for SARS-CoV-2 Variants: A Rapid, Cost-Effective, BSL-2-Based High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation</strong> - Neutralizing antibody responses from COVID-19 vaccines are pivotal in conferring protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Effective COVID-19 vaccines and assays measuring neutralizing antibodies against emerging variants (i.e., XBB.1.5, XBB.1.16, and XBB.2.3) are needed. The use of biosafety level (BSL)-3 laboratories for live virus assays results in higher costs and a longer turnaround time; therefore, a BSL-2-based pseudovirus neutralization assay (PNT)…</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>Design, Synthesis, and Biological Evaluation of Novel Coumarin Analogs Targeted against SARS-CoV-2</strong> - SARS-CoV, an RNA virus, is contagious and displays a remarkable degree of adaptability, resulting in intricate disease presentations marked by frequent genetic mutations that can ultimately give rise to drug resistance. Targeting its viral replication cycle could be a potential therapeutic option to counter its viral growth in the human body leading to the severe infectious stage. The M^(pro) of SARS-CoV-2 is a promising target for therapeutic development as it is crucial for viral transcription…</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>Saponins from <em>Allium macrostemon Bulbs</em> Attenuate Endothelial Inflammation and Acute Lung Injury via the NF-κB/VCAM-1 Pathway</strong> - Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study,…</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>Factors Facilitating and Inhibiting the Implementation of Telerehabilitation-A Scoping Review</strong> - Due to the coronavirus pandemic, telerehabilitation has become increasingly important worldwide. While the effectiveness of telerehabilitation is considered proven for many indications, there is comparatively little knowledge about the implementation conditions. Therefore, this scoping review summarises the current state of facilitating and inhibiting factors that may influence the uptake of telerehabilitation. The review follows the JBI methodology for scoping reviews. The article search was…</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>Agonists or positive allosteric modulators of alpha7 nicotinic acetylcholine receptor prevent interaction of SARS-Cov-2 receptor-binding domain with astrocytoma cells</strong> - SARS-Cov-2, the virus causing COVID-19, penetrates host target cells via the receptor of angiotensin-converting enzyme 2 (ACE2). Disrupting the virus interaction with ACE2 affords a plausible mechanism for prevention of cell penetration and inhibiting dissemination of the virus. Our studies demonstrate that ACE2 interaction with the receptor binding domain of SARS-Cov-2 spike protein (RBD) can be impaired by modulating the α7 nicotinic acetylcholine receptor (α7 nAChR) contiguous with ACE2. U373…</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>Correction: Selective Inhibition of the Interaction between SARS-CoV-2 Spike S1 and ACE2 by SPIDAR Peptide Induces Anti-Inflammatory Therapeutic Responses</strong> - Paidi, R. K., M. Jana, R. K. Mishra, D. Dutta, and K. Pahan. 2021. Selective inhibition of the interaction between SARS-CoV-2 spike S1 and ACE2 by SPIDAR peptide induces anti-inflammatory therapeutic responses. J. Immunol. 207: 2521-2533.In the original Supplemental Fig. 2C, the “Control” image was duplicated from the “Spike S1 (heat inactivated)” image due to an error during figure preparation. The supplemental figure has been corrected in the online version of the article.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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