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192 lines
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<title>14 February, 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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<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>Long-term cardiovascular safety of COVID-19 vaccination according to brand, dose and combinations: Cohort study of 46 million adults in England</strong> -
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Using longitudinal health records from 45.7 million adults in England followed for a year, our study compared the incidence of thrombotic and cardiovascular complications after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the first two years of the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273) These findings support the wide uptake of future COVID-19 vaccination programs.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302698v1" target="_blank">Long-term cardiovascular safety of COVID-19 vaccination according to brand, dose and combinations: Cohort study of 46 million adults in England</a>
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<li><strong>Knowledge, Attitude, and Practices towards COVID-19 Infection and Prevention Measures among Medical Students</strong> -
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The COVID-19 pandemic has rapidly led to an unprecedented health threat worldwide. During this time, disease prevention is considered to be the best way for general health protection. This is achieved through public health education by extending proper knowledge, promoting an optimistic attitude, and keeping the public compliant with preventive measures. As components of the healthcare system, medical students should also play a role in disease prevention more so in the Philippines where the Department of Health has called upon medical graduates to render services in response to the national emergency. In this study, the knowledge, attitude, and practices (KAP) of medical students from Cebu Institute of Medicine (CIM) towards COVID-19 infection and preventive measures were assessed. Demographic factors, their respective effect size on KAP, as well as the relationship between KAP variables were determined. The revised questionnaire, drafted based on qualitative and quantitative validity tests, was then used for the pilot study to generate the final questionnaire. Responses from participants underwent descriptive and correlational analysis. The results showed that the majority of the medical students of CIM have adequate knowledge (78.24%), positive attitude (80.68%), and good practices (94.38%) towards COVID-19 infection and prevention measures. Females have a significant association (p-value = 0.03) with better practices than male counterparts. Knowledge (p-value = 0.004) and attitude (p-value = 0.003) also showed significant correlation with practices, implying that knowledge and attitude play a role in shaping compliance to health practices. Therefore, health interventions should aim to disseminate accurate, evidence-based information and improve attitude towards the implemented precautionary measures in order to increase effectiveness of policies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302741v1" target="_blank">Knowledge, Attitude, and Practices towards COVID-19 Infection and Prevention Measures among Medical Students</a>
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<li><strong>SARS-CoV-2 virus in Raw Wastewater from Student Residence Halls with concomitant 16S rRNA Bacterial Community Structure changes</strong> -
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The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in sewage is well-established, but the concomitant changes in microbial compositions during the pandemic remain insufficiently explored. This study investigates the impact of the SARS-CoV-2 virus on microbial compositions in raw sewage, utilizing 16S rRNA sequencing to analyze wastewater samples collected from six dormitories over a one-year field trial at the University of Tennessee, Knoxville. The concentration of SARS-CoV-2 RNA was assessed using a reverse transcription-quantitative polymerase chain reaction. Significant variations in bacterial composition were evident across the six dormitories, highlighting the importance of independently considering spatial differences when evaluating the raw wastewater microbiome. Positive samples for SARS-CoV-2 exhibited a prominent representation of exclusive species across all dormitories, coupled with significantly reduced bacterial diversity compared to negative samples. The correlation observed between the relative abundance of enteric pathogens and potential pathogens at sampling sites introduces a significant dimension to our understanding of COVID-19, especially the notable correlation observed in positive SARS-CoV-2 samples. Furthermore, the significant correlation in the relative abundance of potential pathogens between positive and negative SARS-CoV-2 raw sewage samples may be linked to the enduring effects of microbial dysbiosis observed during COVID-19 recovery. These findings provide valuable insights into the microbial dynamics in raw sewage during the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.11.24302582v1" target="_blank">SARS-CoV-2 virus in Raw Wastewater from Student Residence Halls with concomitant 16S rRNA Bacterial Community Structure changes</a>
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<li><strong>Body mass index changes and their association with SARS-CoV-2 infection: a real-world analysis</strong> -
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Objective: To study body mass index (BMI) changes among individuals aged 18-99 years with and without SARS-CoV-2 infection. Subjects/Methods: Using real-world data from the OneFlorida+ Clinical Research Network of the National Patient-Centered Clinical Research Network, we compared changes over time in BMI in an Exposed cohort (positive SARS-CoV-2 test between March 2020 - January 2022), to a contemporary Unexposed cohort (negative SARS-CoV-2 tests), and an age/sex-matched Historical control cohort (March 2018 - January 2020). Body mass index (kg/m2) was retrieved from objective measures of height and weight in electronic health records. We used target trial approaches to estimate BMI at baseline and change per 100 days of follow-up for Unexposed and Historical cohorts relative to the Exposed cohort by categories of sex, race-ethnicity, age, and hospitalization status. Results: The study sample consisted of 44,436 (Exposed cohort), 164,118 (Unexposed cohort), and 41,189 (Historical cohort). Cumulatively, 62% were women, 21.5% Non-Hispanic Black, 21.4% Hispanic and 5.6% Non-Hispanic Other. Patients had an average age of 51.9 years (SD: 18.9). At baseline, relative to the Exposed cohort (mean BMI: 29.3 kg/m2 [95%CI: 29.0, 29.7]), the Unexposed (-0.07 kg/m2 [95%CI; -0.12, -0.01]) and Historical controls (-0.27 kg/m2 [95%CI; -0.34, -0.20]) had lower BMI. Relative to no change in the Exposed over 100 days (0.00 kg/m2 [95%CI; -0.03,0.03]), the BMI of those Unexposed decreased (-0.04 kg/m2 [95%CI; -0.06, -0.01]) while the Historical cohort9s BMI increased (+0.03 kg/m2 [95%CI;0.00,0.06]). BMI changes were consistent between Exposed and Unexposed cohorts for most population groups, except at start of follow-up period among Males and those 65 years or older, and in changes over 100 days among Males and Hispanics. Conclusions: In a diverse real-world cohort of adults, mean BMI of those with and without SARS-CoV2 infection varied in their trajectories. The mechanisms and implications of weight retention following SARS-CoV-2 infection remain unclear.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302697v1" target="_blank">Body mass index changes and their association with SARS-CoV-2 infection: a real-world analysis</a>
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<li><strong>Association between altitude and death from COVID-19 in subjects with diabetes mellitus during the first wave: cross sectional study of the National Death Index</strong> -
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Background. In high Andean areas, there is greater insulin sensitivity which may be a protective factor against complications in subjects with diabetes mellitus. Objective: Determine the association between altitude of residence and death from COVID-19 in deaths with diabetes mellitus in Peru during the first wave.. Methods: We carried out a cross-sectional analysis of deaths registered in the National Death System of Peru (SINADEF in Spanish). We selected Peruvians with diabetes mellitus identified by presenting the diagnosis in any of the six boxes on the certificate. The dependent variable was death from COVID-19 as the basic cause of death, located in last place among causes A, B, C and D according to the Pan American Health Organization. The independent variable was the altitude of residence, categorized as less than 1 500 m a.s.l, 1 500 to 2 499 m a.s.l. and greater than 2 500 m a.sl. Through a multilevel analysis by geographic region and using a Poisson regression, we obtained the risk ratios of death from COVID-19 according to the altitude of residence. We adjusted by individual and contextual variables. Results: We included 16 406 deaths with diabetes mellitus between March-December 2020. 34.3% died from Covid19 and 9.7% came from areas above 2 500 m. The proportion of deaths from COVID-19 of those with residence altitude above 2 500 m was 20% lower compared to residents below 1 500 m (RR: 0.80; 95% CI: 0.70 – 0.91; p<0.001), adjusted for individual and socioeconomic factors. Its influence is also shown as the altitude changes every 100, 250, 500 and 1000 m a.s.l., through multilevel analysis. Conclusion: A higher altitude of residence is associated with a lower proportion of deaths from COVID-19 in people with diabetes mellitus during the first wave in Peru. The study contribute to expanding knowledge of the effects of altitude with respect to mortality in people with diabetes mellitus in a context of a highly contagious and virulent infectious disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302726v1" target="_blank">Association between altitude and death from COVID-19 in subjects with diabetes mellitus during the first wave: cross sectional study of the National Death Index</a>
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<li><strong>Mathematical assessment of the role of human behavior changes on SARS-CoV-2 transmission dynamics</strong> -
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The COVID-19 pandemic has not only presented a major global public health and socio-economic crisis, but has also significantly impacted human behavior towards adherence (or lack thereof) to public health intervention and mitigation measures implemented in communities worldwide. The dynamic nature of the pandemic has prompted extensive changes in individual and collective behaviors towards the pandemic. This study is based on the use of mathematical modeling approaches to assess the extent to which SARS-CoV-2 transmission dynamics is impacted by population-level changes of human behavior due to factors such as (a) the severity of transmission (such as disease-induced mortality and level of symptomatic transmission), (b) fatigue due to the implementation of mitigation interventions measures (e.g., lockdowns) over a long (extended) period of time, (c) social peer-pressure, among others. A novel behavior-epidemiology model, which takes the form of a deterministic system of nonlinear differential equations, is developed and fitted using observed cumulative SARS-CoV-2 mortality data during the first wave in the United States. Rigorous analysis of the model shows that its disease-free equilibrium is locally-asymptotically stable whenever a certain epidemiological threshold, known as the control reproduction number (denoted by R_C) is less than one, and the disease persists (i.e., causes significant outbreak or outbreaks) if the threshold exceeds one. The model fits the observed data, as well as makes a more accurate prediction of the observed daily SARS-CoV-2 mortality during the first wave (March 2020 -June 2020), in comparison to the equivalent model which does not explicitly account for changes in human behavior. Of the various metrics for human behavior changes during the pandemic considered in this study, it is shown that behavior changes due to the level of SARS-CoV-2 mortality and symptomatic transmission were more influential (while behavioral changes due to the level of fatigue to interventions in the community was of marginal impact). It is shown that an increase in the proportion of exposed individuals who become asymptomatically-infectious at the end of the exposed period (represented by a parameter r) can lead to an increase (decrease) in the control reproduction number (R_C) if the effective contact rate of asymptomatic individuals is higher (lower) than that of symptomatic individuals. The study identifies two threshold values of the parameter r that maximize the cumulative and daily SARS-CoV-2 mortality, respectively, during the first wave. Furthermore, it is shown that, as the value of the proportion r increases from 0 to 1, the rate at which susceptible non-adherent individuals change their behavior to strictly adhere to public health interventions decreases. Hence, this study suggests that, as more newly-infected individuals become asymptomatically-infectious, the level of positive behavior change, as well as disease severity, hospitalizations and disease-induced mortality in the community can be expected to significantly decrease (while new cases may rise, particularly if asymptomatic individuals have higher contact rate, in comparison to symptomatic individuals).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.11.24302662v1" target="_blank">Mathematical assessment of the role of human behavior changes on SARS-CoV-2 transmission dynamics</a>
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<li><strong>Temporal variations in international air travel: implications for modelling the spread of infectious diseases</strong> -
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Background The international flight network creates multiple routes by which pathogens can quickly spread across the globe. In the early stages of infectious disease outbreaks, analyses using flight passenger data to identify countries at risk of importing the pathogen are common and can help inform disease control efforts. A challenge faced in this modelling is that the latest aviation statistics (referred to as contemporary data) are typically not immediately available. Therefore, flight patterns from a previous year are often used (referred to as historical data). We explored the suitability of historical data for predicting the spatial spread of emerging epidemics. Methods We analysed monthly flight passenger data from the International Air Transport Association to assess how baseline air travel patterns were affected in outbreaks of MERS, Zika, and SARS-CoV-2 over the past decade. We then used a stochastic discrete time SEIR metapopulation model to simulate global spread of different pathogens, comparing how epidemic dynamics differed in simulations based on historical and contemporary data. Results We observed local, short-term disruptions to air travel from South Korea and Brazil for the MERS and Zika outbreaks we studied, whereas global and longer-term flight disruption occurred during the SARS-CoV-2 pandemic. For outbreak events that were accompanied by local, small, and short-term changes in air travel, epidemic models using historical flight data gave similar projections of timing and locations of disease spread as when using contemporary flight data. However, historical data were less reliable to model the spread of an atypical outbreak such as SARS-CoV-2 in which there were durable and extensive levels of global travel disruption. Conclusions The use of historical flight data as a proxy in epidemic models is an acceptable practice except in rare, large epidemics that lead to substantial disruptions to international travel.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302682v1" target="_blank">Temporal variations in international air travel: implications for modelling the spread of infectious diseases</a>
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<li><strong>Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology</strong> -
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Age is a major risk factor for severe coronavirus disease-2019 (COVID-19), yet the mechanisms responsible for this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host and viral dynamics in a prospective, multicenter cohort of 1,031 patients hospitalized for COVID-19, ranging from 18 to 96 years of age. We performed blood transcriptomics and nasal metatranscriptomics, and measured peripheral blood immune cell populations, inflammatory protein expression, anti-SARS-CoV-2 antibodies, and anti- interferon (IFN) autoantibodies. We found that older age correlated with an increased SARS-CoV- 2 viral load at the time of admission, and with delayed viral clearance over 28 days. This contributed to an age-dependent increase in type I IFN gene expression in both the respiratory tract and blood. We also observed age-dependent transcriptional increases in peripheral blood IFN-gamma, neutrophil degranulation, and Toll like receptor (TLR) signaling pathways, and decreases in T cell receptor (TCR) and B cell receptor signaling pathways. Over time, older adults exhibited a remarkably sustained induction of proinflammatory genes (e.g., CXCL6) and serum chemokines (e.g., CXCL9) compared to younger individuals, highlighting a striking age-dependent impairment in inflammation resolution. Augmented inflammatory signaling also involved the upper airway, where aging was associated with upregulation of TLR, IL17, type I IFN and IL1 pathways, and downregulation TCR and PD-1 signaling pathways. Metatranscriptomics revealed that the oldest adults exhibited disproportionate reactivation of herpes simplex virus and cytomegalovirus in the upper airway following hospitalization. Mass cytometry demonstrated that aging correlated with reduced naïve T and B cell populations, and increased monocytes and exhausted natural killer cells. Transcriptional and protein biomarkers of disease severity markedly differed with age, with the oldest adults exhibiting greater expression of TLR and inflammasome signaling genes, as well as proinflammatory proteins (e.g., IL6, CXCL8), in severe COVID-19 compared to mild/moderate disease. Anti-IFN autoantibody prevalence correlated with both age and disease severity. Taken together, this work profiles both host and microbe in the blood and airway to provide fresh insights into aging-related immune changes in a large cohort of vaccine-naïve COVID-19 patients. We observed age-dependent immune dysregulation at the transcriptional, protein and cellular levels, manifesting in an imbalance of inflammatory responses over the course of hospitalization, and suggesting potential new therapeutic targets.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.11.24301704v1" target="_blank">Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology</a>
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<li><strong>Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID.</strong> -
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During the COVID-19 pandemic it was widely described that certain individuals infected by SARS-CoV-2 experience persistent disease signs and symptoms, Long COVID, which in some cases is very severe with life changing consequences. To maximize our chances of identifying the underpinnings of this illness, we have focused on 121 of the most severe cases from >1000 patients screened in specialized clinics in Sweden and Belgium. We restricted this study to subjects with objective measures of organ damage or dysfunction, >3 months following a verified, but mild- to-moderate SARS-CoV-2 infection. By performing systems-level immunological testing and comparisons to controls fully convalescent following a similar mild/moderate COVID-19 episode, we identify elevated serological responses to SARS-CoV-2 in severe Long COVID suggestive of chronic antigen stimulation. Persistent viral reservoirs have been proposed in Long COVID and using multiple orthogonal methods for detection of SARS-CoV-2 RNA and protein in plasma we identify a subset of patients with detectable antigens, but with minimal overlap across assays, and no correlation to symptoms or immune measurements. Elevated serologic responses to SARS-CoV-2 on the other hand were inversely correlated with clonally expanded memory CD8+ T cells, indicating that restrained clonal expansion enables viral persistence, chronic antigen exposure and elevated IgG responses, even if antigen-detection in blood is not universally possible.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.11.24302636v1" target="_blank">Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID.</a>
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<li><strong>Analysis of signs and symptoms of SARS-CoV-2 virus infection considering different waves using Machine Learning</strong> -
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In March 2020, the World Health Organization declared a world pandemic of COVID-19, which can manifest in humans as a consequence of virus infection of SARS-CoV-2. On this context, this work uses Data Mining and Machine Learning techniques or the infection diagnosis. A methodology was created to facilitate this task and can be applied in any outbreak or pandemic wave. Besides generating diagnosis models based only on signals and symptoms, the method can evaluate if there are differences in signals and symptoms between waves (or outbreaks) through explainable techniques of the machine learning models. Another aspect is identifying possible quality differences between exams, for example, Rapid Test (RT) and Reverse Transcription–Polymerase Chain Reaction (RT-PCR). The case study in this work is based on data from patients who sought care at Piquet Carneiro Polyclinic of the State University of Rio de Janeiro. In this work, the results obtained with the tests were used to diagnose symptomatic infection of the SARS-CoV-2 virus, based on related signals and symptoms, and the date of the initial of these signals and symptoms. Using the Random Forrest model, it was possible to achieve the result of up to 76% sensitivity, 86% specificity, and 79% accuracy in the results of tests in one contagion wave of the SARS-CoV-2 virus. Moreover, differences were found in signals and symptoms between contagion waves, in addition to the observation that exams RT-PCR and RT Antigen tests are more reliable than RT antibody test.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302722v1" target="_blank">Analysis of signs and symptoms of SARS-CoV-2 virus infection considering different waves using Machine Learning</a>
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<li><strong>Spatial pattern of all cause excess mortality in Swiss districts during the pandemic years 1890, 1918 and 2020</strong> -
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Background: Every pandemic is embedded in specific spatial and temporal context. However, spatial patterns have almost always only been considered in the context of one individual pandemic. Until now, there has been limited consideration of spatial similarities or differences between pandemics. Objective: The aim of this study was to examine spatial pattern of excess mortality in Swiss districts during the pandemic years 1890, 1918 and 2020. In addition, determinants that could explain the difference between districts were analyzed. Methods: Excess mortality rate was estimated using a Bayesian spatial model for disease mapping. A robust linear regression was used to assess the association between ecological determinants and excess mortality. Results: The highest excess mortality rate in all districts occurred during the 1918 pandemic, the lowest excess mortality rate was seen for the 1890 pandemic. Moreover, this analysis revealed heterogeneous spatial patterns of excess mortality in each pandemic year. Different socio-demographic determinants, in each pandemic, might have favored excess mortality. While the age composition, cultural and area-based socio-economic position differences and the proximity to France and Italy were the main determinants of excess mortality during the Covid-19 pandemic, the mobility, preexisting health issues (i.e. TB) or the remoteness location in the mountains played crucial roles during the historical pandemics. Contribution: The analysis of spatial patterns in pandemics is important for public health interventions in future pandemics or outbreaks since it helps to identifying patterns of transmission. Identifying and understanding geographic hotspots informs precise interventions, aids in public health implementation, and contributes to tailored health policies for the region.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.13.24302701v1" target="_blank">Spatial pattern of all cause excess mortality in Swiss districts during the pandemic years 1890, 1918 and 2020</a>
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<li><strong>Pseudotyped virus infection of multiplexed ACE2 libraries reveals SARS-CoV-2 variant shifts in receptor usage</strong> -
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Pairwise compatibility between virus and host proteins can dictate the outcome of infection. During transmission, both inter- and intraspecies variabilities in receptor protein sequences can impact cell susceptibility. Many viruses possess mutable viral entry proteins and the patterns of host compatibility can shift as the viral protein sequence changes. This combinatorial sequence space between virus and host is poorly understood, as traditional experimental approaches lack the throughput to simultaneously test all possible combinations of protein sequences. Here, we created a pseudotyped virus infection assay where a multiplexed target-cell library of host receptor variants can be assayed simultaneously using a DNA barcode sequencing readout. We applied this assay to test a panel of 30 ACE2 orthologs or human sequence mutants for infectability by the original SARS-CoV-2 spike protein or the Alpha, Beta, Gamma, Delta, and Omicron BA1 variant spikes. We compared these results to an analysis of the structural shifts that occurred for each variant spikes interface with human ACE2. Mutated residues were directly involved in the largest shifts, although there were also widespread indirect effects altering interface structure. The N501Y substitution in spike conferred a large structural shift for interaction with ACE2, which was partially recreated by indirect distal substitutions in Delta, which does not harbor N501Y. The structural shifts from N501Y greatly influenced the set of animal orthologs the variant spike was capable of interacting with. Out of the thirteen non-human orthologs, ten exhibited unique patterns of variant-specific compatibility, demonstrating that spike sequence changes during human transmission can toggle ACE2 compatibility and potential susceptibility of other animal species, and cumulatively increase overall compatibilities as new variants emerge. These experiments provide a blueprint for similar large-scale assessments of protein compatibility during entry by diverse viruses. This dataset demonstrates the complex compatibility relationships that occur between variable interacting host and virus proteins.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.13.580056v1" target="_blank">Pseudotyped virus infection of multiplexed ACE2 libraries reveals SARS-CoV-2 variant shifts in receptor usage</a>
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<li><strong>SARS-CoV-2 Omicron lineage XBB spike structures, conformations, antigenicity, and receptor recognition</strong> -
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A recombinant lineage of the SARS-CoV-2 Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and global populations. XBB lineage members were noted for their improved immune evasion and transmissibility. Here, we determine cryo-EM structures of XBB.1.5, XBB.1.16 and EG.5 spike (S) ectodomains to reveal enhanced occupancy of the receptor inaccessible closed state. Interprotomer receptor binding domain (RBD) interactions previously observed in BA.1 and BA.2 were retained to reinforce the 3-RBD-down state. Improved stability of XBB.1.5 and XBB.1.16 RBD compensated for loss of stability caused by early Omicron mutations, while the F456L substitution reduced EG.5 RBD stability. Long-range impacts of S1 subunit mutations affected conformation and epitope presentation in the S2 subunit. Taken together, our results feature a theme of iterative optimization of S protein stability as Omicron continues to evolve, while maintaining high affinity receptor binding and bolstering immune evasion.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.12.580004v1" target="_blank">SARS-CoV-2 Omicron lineage XBB spike structures, conformations, antigenicity, and receptor recognition</a>
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<li><strong>Identification of SARS-CoV-2 Mpro inhibitors through deep reinforcement learning for de novo drug design and computational chemistry approaches</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of coronavirus disease (COVID-19) since its emergence in December 2019. As of January 2024, there has been over 774 million reported cases and 7 million deaths worldwide. While vaccination efforts have been successful in reducing the severity of the disease and decreasing the transmission rate, the development of effective therapeutics against SARS-CoV-2 remains a critical need. The main protease (Mpro) of SARS-CoV-2 is an essential enzyme required for viral replication and has been identified as a promising target for drug development. In this study, we report the identification of novel Mpro inhibitors, using a combination of deep reinforcement learning for de novo drug design with 3D pharmacophore/shape-based alignment and privileged fragment match count scoring components followed by hit expansions and molecular docking approaches. Our experimentally validated results show that 3 novel series exhibit potent inhibitory activity against SARS-CoV-2 Mpro, with IC50 values ranging from 1.3 uM to 2.3 uM and a high degree of selectivity. These findings represent promising starting points for the development of new antiviral therapies against COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.12.579977v1" target="_blank">Identification of SARS-CoV-2 Mpro inhibitors through deep reinforcement learning for de novo drug design and computational chemistry approaches</a>
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<li><strong>Infer metabolic directions and magnitudes from moment differences of mass-weighted intensity distributions</strong> -
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Metabolic pathways are fundamental maps in biochemistry that detail how molecules are transformed through various reactions. Metabolomics refers to the large-scale study of small molecules. High-throughput, untargeted, mass spectrometry-based metabolomics experiments typically depend on libraries for structural annotation, which is necessary for pathway analysis. However, only a small fraction of spectra can be matched to known structures in these libraries and only a portion of annotated metabolites can be associated with specific pathways, considering that numerous pathways are yet to be discovered. The complexity of metabolic pathways, where a single compound can play a part in multiple pathways, poses an additional challenge. This study introduces a different concept: mass spectra distribution, which is the empirical distribution of the intensities times their associated m/z values. Analysis of solarization, COVID-19, and mouse brain datasets shows that by estimating the differences of the point estimations of these distributions, it becomes possible to infer the metabolic directions and magnitudes without requiring knowledge of the exact chemical structures of these compounds and their related pathways. The overall metabolic vector map, named as vectome, has the potential to bypass the current bottleneck and provide fresh insights into metabolomics studies. This brief report thus provides a mathematical framing for a classic biological concept.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.12.579906v1" target="_blank">Infer metabolic directions and magnitudes from moment differences of mass-weighted intensity distributions</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>Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: CD40.RBDv vaccin (SARS-Cov2 Vaccin) <br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; LinKinVax; Vaccine Research Institute (VRI), France <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>ADJUVANT TREATMENT TO REDUCE CARDIOVASCULAR RISK IN PATIENTS WITH LONG COVID: HIGH-DEFINITION TRANSCRANIAL DIRECT CURRENT STIMULATION (HD-TDCS) AND CHLORELLA PYREINOIDOSA</strong> - <b>Conditions</b>: Cardiovascular Diseases; Long Covid19 <br/><b>Interventions</b>: Other: High Definition-transcranial Direct Current Stimulation; Dietary Supplement: Chlorella Pyreinodosa <br/><b>Sponsors</b>: Federal University of Paraíba; City University of New York <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>SGB for COVID-induced Parosmia</strong> - <b>Conditions</b>: COVID-19-Induced Parosmia <br/><b>Interventions</b>: Drug: Stellate Ganglion Block; Drug: Placebo Sham Injection <br/><b>Sponsors</b>: Washington University School of Medicine <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>Investigating the Effectiveness of Vimida</strong> - <b>Conditions</b>: Long COVID; Post COVID-19 Condition <br/><b>Interventions</b>: Behavioral: vimida <br/><b>Sponsors</b>: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Physiotherapy Via Video Calls on Cardiopulmonary Functions, Physical Function, Cognitive Function, Activity Daily Livings, and Quality of Life in Patients With COVID-19</strong> - <b>Conditions</b>: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function <br/><b>Interventions</b>: Behavioral: Exercise training <br/><b>Sponsors</b>: Chulabhorn Hospital <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>Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise session; Behavioral: Control session <br/><b>Sponsors</b>: University of Nove de Julho <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>Reducing Respiratory Virus Transmission in Bangladeshi Classrooms</strong> - <b>Conditions</b>: SARS-CoV2 Infection; Influenza Viral Infections; Respiratory Viral Infection <br/><b>Interventions</b>: Device: Box Fan; Device: UV Germicidal Irradiation Lamp Unit; Device: Combined: Box Fan and UV Germicidal Irradiation Lamp Units <br/><b>Sponsors</b>: Stanford University; Centers for Disease Control and Prevention; International Centre for Diarrhoeal Disease Research, Bangladesh <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>SMILE: Clinical Trial to Evaluate Mindfulness as Intervention for Racial and Ethnic Populations During COVID-19</strong> - <b>Conditions</b>: Anxiety; COVID-19 Pandemic <br/><b>Interventions</b>: Behavioral: Mindfulness <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; National Institute on Minority Health and Health Disparities (NIMHD); RTI International <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>A Study to Learn About a Combined COVID-19 and Influenza Shot in Healthy Adults</strong> - <b>Conditions</b>: Influenza, Human; SARS-CoV-2 Infection; COVID-19 <br/><b>Interventions</b>: Biological: BNT162b2 (Omi XBB.1.5)/RIV; Biological: BNT162b2 (Omi XBB.1.5); Biological: RIV; Other: Normal saline placebo <br/><b>Sponsors</b>: Pfizer <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effects of Nutritional Intervention on Health Parameters in Participants With Type 2 Diabetes Mellitus</strong> - <b>Conditions</b>: Diabetes Mellitus Type 2; Diabetes Mellitus Type 2 in Obese; Diabetes; Diabetes Mellitus Non-insulin-dependent; Hypertension; Type 2 Diabetes Mellitus <br/><b>Interventions</b>: Behavioral: Nutritional Intervention <br/><b>Sponsors</b>: Sao Jose do Rio Preto Medical School; Fundação de Amparo à Pesquisa do Estado de São Paulo <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Impact of the Covid-19 Pandemic on Orthopedic Trauma Management</strong> - <b>Conditions</b>: Trauma; COVID-19 Pandemic <br/><b>Interventions</b>: Other: epidemyolojical <br/><b>Sponsors</b>: Bakirkoy Dr. Sadi Konuk Research and Training Hospital <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Open-label, Multi-centre, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age.</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: BIMERVAX <br/><b>Sponsors</b>: Hipra Scientific, S.L.U; Veristat, Inc.; VHIR; Asphalion <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>A Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid</strong> - <b>Conditions</b>: Long COVID; Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Drug: Amantadine; Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management <br/><b>Sponsors</b>: University of Texas Southwestern Medical Center <br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An isothermal calorimetry assay for determining steady state kinetic and enzyme inhibition parameters for SARS-CoV-2 3CL-protease</strong> - This manuscript describes the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CL ^(pro) from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CL ^(pro) is the main protease that plays a crucial role of producing the whole array of proteins necessary for the viral infection that caused the spread of COVID-19, responsible for millions of deaths worldwide as well as global…</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>Identification of new pharmacophore against SARS-CoV-2 spike protein by multi-fold computational and biochemical techniques</strong> - COVID-19 appeared as a highly contagious disease after its outbreak in December 2019 by the virus, named SARS-CoV-2. The threat, which originated in Wuhan, China, swiftly became an international emergency. Among different genomic products, spike protein of virus plays a crucial role in the initiation of the infection by binding to the human lung cells, therefore, SARS-CoV-2’s spike protein is a promising therapeutic target. Using a combination of a structure-based virtual screening 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>Calpain-2 mediates SARS-CoV-2 entry via regulating ACE2 levels</strong> - Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show excellent antiviral activities against SARS-CoV-2 by targeting the viral main protease (M^(pro)), which plays an essential role in processing viral polyproteins. In this study, we found that calpain inhibitors potently inhibited the infection of a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Combination of Polygonatum Rhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON<sub>3</sub> -induced mitochondrial damage and endoplasmic reticulum stress in A549 cells</strong> - CONCLUSION: SP inhibits proliferation of lung cancer A549 cells by downregulating PON(3) -induced apoptosis in the mitochondrial and ER pathways.</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>Omicron BA.4/5 neutralization and cell-mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow-up cohort study</strong> - There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV</strong> - CONCLUSION: Our results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous.</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>Nebulized pH-Responsive Nanospray Combined with Pentoxifylline and Edaravone to Lungs for Efficient Treatments of Acute Respiratory Distress Syndrome</strong> - The COVID-19 pandemic has become an unprecedented global medical emergency, resulting in more than 5 million deaths. Acute respiratory distress syndrome (ARDS) caused by COVID-19, characterized by the release of a large number of pro-inflammatory cytokines and the production of excessive toxic ROS, is the most common serious complication leading to death. To develop new strategies for treating ARDS caused by COVID-19, a mouse model of ARDS was established by using lipopolysaccharide (LPS)….</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>Influenza vaccination during the 2021/22 season: A data-linkage test-negative case-control study of effectiveness against influenza requiring emergency care in England and serological analysis of primary care patients</strong> - We present England 2021/22 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related emergency care use in children aged 1-17 and in adults aged 50+, and serological findings in vaccinated vs unvaccinated adults by hemagglutination inhibition assay. Influenza vaccination has been routinely offered to all children aged 2-10 years and adults aged 65 years + in England. In 2021/22, the offer was extended to children to age 15 years, and adults aged 50-64…</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 of molecular mechanisms of riboflavin anti-COVID-19 action reveals anti-inflammatory efficacy rather than antiviral activity</strong> - CONCLUSIONS: It is concluded that riboflavin reveals anti-inflammatory rather than antiviral activity for SARS-CoV-2 infection.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An enhanced broad-spectrum peptide inhibits Omicron variants in vivo</strong> - The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) poses a major challenge to vaccines and antiviral therapeutics due to their extensive evasion of immunity. Aiming to develop potent and broad-spectrum anticoronavirus inhibitors, we generated A1-(GGGGS)7-HR2m (A1L35HR2m) by introducing an angiotensin-converting enzyme 2 (ACE2)-derived peptide A1 to the N terminus of the viral HR2-derived peptide HR2m through a long flexible linker,…</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>Mesenchymal stromal cells (MSCs) as a therapeutic agent of inflammatory disease and infectious COVID-19 virus: live or dead mesenchymal?</strong> - The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various…</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>Genetic justification of COVID-19 patient outcomes using DERGA, a novel data ensemble refinement greedy algorithm</strong> - Complement inhibition has shown promise in various disorders, including COVID-19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement-related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID-19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence-based algorithm to predict disease outcome (ICU vs….</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>Milk Antiviral Proteins and Derived Peptides against Zoonoses</strong> - Milk is renowned for its nutritional richness but also serves as a remarkable reservoir of bioactive compounds, particularly milk proteins and their derived peptides. Recent studies have showcased several robust antiviral activities of these proteins, evidencing promising potential within zoonotic viral diseases. While several publications focus on milk’s bioactivities, antiviral peptides remain largely neglected in reviews. This knowledge is critical for identifying novel research directions…</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 Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions</strong> - Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: (i) the ability to fight infections; (ii) the activation of blood coagulation or blood clot lysis systems; (iii) the activation of digestive enzymes; and (iv)…</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 Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury</strong> - Nowadays, acute respiratory distress syndrome (ARDS) still has a high mortality rate, and the alleviation and treatment of ARDS remains a major research focus. There are various causes of ARDS, among which pneumonia and non-pulmonary sepsis are the most common. Trauma and blood transfusion can also cause ARDS. In ARDS, the aggregation and infiltration of neutrophils in the lungs have a great influence on the development of the disease. Neutrophils regulate inflammatory responses through various…</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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