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168 lines
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<title>23 January, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>Policy makers believe money motivates more than it does</strong> -
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<div>
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To motivate contributions to public goods, should policy makers employ financial incentives like taxes, fines, subsidies, and rewards? While these are widely considered as the classic policy approach, a substantial academic literature suggests the impact of financial incentives is not always positive; they can sometimes fail or even backfire. To test whether policy makers are overly bullish about financial incentives, we asked county heads, mayors, and municipal government representatives of medium-to-large towns in Germany to predict the effects of a financial incentive on COVID-19 vaccination, and tested the exact same incentive in a field experiment involving all 41,548 inhabitants (clustered in 10,032 addresses) of the German town of Ravensburg. Whereas policy makers overwhelmingly predict that the financial incentive will increase vaccination—by 15.3 percentage points on average—the same financial incentive yielded a precisely estimated null effect on vaccination. We discuss when financial incentives are most likely to fail, and conclude that it is critical to educate policy makers on the potential pitfalls of employing financial incentives to promote contributions to public goods.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/jq28n/" target="_blank">Policy makers believe money motivates more than it does</a>
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</div></li>
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<li><strong>Biophysical principles predict fitness of SARS-CoV-2 variants</strong> -
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<div>
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SARS-CoV-2 employs its spike protein’s receptor binding domain (RBD) to enter host cells. The RBD is constantly subjected to immune responses, while requiring efficient binding to host cell receptors for successful infection. However, our understanding of how RBD’s biophysical properties contribute to SARS-CoV-2’s epidemiological fitness remains largely incomplete. Through a comprehensive approach, comprising large-scale sequence analysis of SARS-CoV-2 variants and the discovery of a fitness function based on binding thermodynamics, we unravel the relationship between the biophysical properties of RBD variants and their contribution to viral fitness. We developed a biophysical model that uses statistical mechanics to map the molecular phenotype space, characterized by binding constants of RBD to ACE2, LY-CoV016, LY-CoV555, REGN10987, and S309, onto a epistatic fitness landscape. We validate our findings through experimentally measured and machine learning (ML) estimated binding affinities, coupled with infectivity data derived from population-level sequencing. Our analysis reveals that this model effectively predicts the fitness of novel RBD variants and can account for the epistatic interactions among mutations, including explaining the later reversal of Q493R. Our study sheds light on the impact of specific mutations on viral fitness and delivers a tool for predicting the future epidemiological trajectory of previously unseen or emerging low frequency variants. These insights offer not only greater understanding of viral evolution but also potentially aid in guiding public health decisions in the battle against COVID-19 and future pandemics.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.23.549087v3" target="_blank">Biophysical principles predict fitness of SARS-CoV-2 variants</a>
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</div></li>
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<li><strong>Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing</strong> -
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<div>
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X-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. In this work, we present a workflow implemented at a laboratory CT setup, using semi-automated data acquisition, reconstruction and statistical quantification of lung tissue in an early screen of Covid-19 drug candidates. Different drugs were tested in a hamster model after SARS-CoV-2 infection. To make full use of the recorded high-throughput XPCT data, we then used morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing invaluable insights into the pathological progression and partial recovery due to drug treatment.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.21.576083v1" target="_blank">Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing</a>
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</div></li>
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<li><strong>Gaining Biological Insights through Supervised Data Visualization</strong> -
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<div>
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Dimensionality reduction-based data visualization is pivotal in comprehending complex biological data. The most common methods, such as PHATE, t-SNE, and UMAP, are unsupervised and therefore reflect the dominant structure in the data, which may be independent of expert-provided labels. Here we introduce a supervised data visualization method called RF-PHATE, which integrates expert knowledge for further exploration of the data. RF-PHATE leverages random forests to capture intricate feature-label relationships. Extracting information from the forest, RF-PHATE generates low-dimensional visualizations that highlight relevant data relationships while disregarding extraneous features. This approach scales to large datasets and applies to classification and regression. We illustrate RF-PHATE’s prowess through three case studies. In a multiple sclerosis study using longitudinal clinical and imaging data, RF-PHATE unveils a sub-group of patients with non-benign relapsing-remitting Multiple Sclerosis, demonstrating its aptitude for time-series data. In the context of Raman spectral data, RF-PHATE effectively showcases the impact of antioxidants on diesel exhaust-exposed lung cells, highlighting its proficiency in noisy environments. Furthermore, RF-PHATE aligns established geometric structures with COVID-19 patient outcomes, enriching interpretability in a hierarchical manner.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568384v2" target="_blank">Gaining Biological Insights through Supervised Data Visualization</a>
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</div></li>
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<li><strong>Mis- and Disinformation during the 2021 Canadian Federal Election</strong> -
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<div>
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The Canadian Election Misinformation Project was a civil society and academic partnership that aimed to rapidly identify and respond to mis- and disinformation incidents during the 44th Canadian Federal Election while evaluating the extent to which these incidents impact the attitudes and behaviours of Canadians. It also sought to develop understanding of the types and consequences of misleading and false information circulating in the public sphere in addition to supporting world-class research into the dynamics of the information ecosystem and the broad impacts of misinformation on Canadian democracy. The data shows that: 1) Although there was widespread misinformation during the 2021 Canadian federal election, the overall election was minimally impacted by mis- and disinformation; 2) Most Canadians believe the election was safe from foreign interference and that misinformation played a minimal role in the election; 3) Communities that previously focused on sharing COVID-19 misinformation adopted conspiracy theories about a broader set of topics during the election, including vaccines, climate change, and the integrity of the election; and 4) Nevertheless, a strong majority of Canadians believe that misinformation is a threat to Canadian democracy, polarizes Canadians, and threatens social cohesion.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/ubfmx/" target="_blank">Mis- and Disinformation during the 2021 Canadian Federal Election</a>
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</div></li>
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<li><strong>Public Health Communication and Engagement on Social Media during the COVID-19 Pandemic</strong> -
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<div>
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Social media provides governments the opportunity to directly communicate with their constituents. During a pandemic, reaching as many citizens as possible with health messaging is critical to reducing the spread of the disease. This study evaluates efforts to spread healthcare information by Canadian local, provincial, and federal governments during the first five months of the COVID-19 pandemic. We collect all health-related communications coming from government accounts on Facebook and Twitter and analyze the data using a nested mixed method approach. We first identify quantifiable features linked with citizen engagement, before subsequently performing content analysis on outlier posts. We make two critical contributions to existing knowledge about government communication, particularly during public health crises. We identify cross-platform variations in strategy effectiveness and draw attention to specific, evidence-based practices that can increase engagement with government health information.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/7hypj/" target="_blank">Public Health Communication and Engagement on Social Media during the COVID-19 Pandemic</a>
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</div></li>
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<li><strong>All in this together: deservingness of government aid during the COVID-19 pandemic</strong> -
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<div>
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The COVID-19 pandemic has placed unprecedented pressure on governments to engage in widespread cash transfers directly to citizens to help mitigate economic losses. These programs are major redistribution efforts aimed at a variety of sub-groups within society (the unemployed, those with children, those with pre-existing health conditions, etc.) and there has been remarkably little resistance to these government outlays. We employ a novel and pre-registered paired vignette experiment to assess support for government aid during the pandemic in a large, nationally representative sample. We evaluate whether the “normal” deservingness hierarchy and considerations of social affinity or material self-interest continue to drive preferences of Canadians regarding redistribution. We find only small deservingness considerations and little evidence that redistribution preferences are informed by similarity considerations. Instead, we find broad, generous, and non-discriminatory support for direct cash transfers during this period of crisis.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/eyvhj/" target="_blank">All in this together: deservingness of government aid during the COVID-19 pandemic</a>
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</div></li>
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<li><strong>The Causes and Consequences of COVID-19 Misperceptions: Understanding the Role of News and Social Media</strong> -
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<div>
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We investigate the relationship between media consumption, misinformation, and important attitudes and behaviours during the COVID-19 pandemic in Canada. We find that comparatively more misinformation circulates on social media platforms, while traditional news media tend to reinforce public health recommendations like social distancing. We find that exposure to social media is associated with misperceptions about COVID-19 while the inverse is true for news media. These misperceptions are in turn associated with lower compliance with social distancing measures. We thus draw a link from misinformation on social media to behaviours and attitudes that potentially magnify the scale and lethality of COVID-19.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/6tcdn/" target="_blank">The Causes and Consequences of COVID-19 Misperceptions: Understanding the Role of News and Social Media</a>
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</div></li>
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<li><strong>The lasting earnings losses of COVID-19 short-time work</strong> -
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<div>
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This study is the first to investigate the impact of short-time work (STW) schemes during the COVID-19 pandemic on earnings after STW. STW schemes were implemented to preserve employee–employer matches, support workers’ incomes, and uphold consumption. Although workers faced temporary earnings losses under STW, it is unclear if the negative earnings effects of STW persisted or were limited to the STW spell. Therefore, this study uses a dynamic difference-in-difference (DiD) identification strategy with administrative data to identify any lasting STW effects on earnings. This approach accounts for factors that influenced worker selection into STW and tests for heterogeneous effects across subgroups of workers. We find lasting earnings losses that persisted beyond the STW participation itself. Most importantly, these earnings losses depended on the duration of STW exposure, with greater negative effects being more prominent in cases of long-term or recurring STW spells. Lasting, post-STW earnings losses tended to be more pronounced for white-collar jobs, while the largest losses were observed among men with blue-collar jobs whose STW spells exceeded one year.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/p2qvh/" target="_blank">The lasting earnings losses of COVID-19 short-time work</a>
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</div></li>
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<li><strong>Revealing the drivers of antibiotic resistance trends in Streptococcus pneumoniae amidst the 2020 COVID-19 pandemic: Insights from mathematical modeling</strong> -
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<div>
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Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built in into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.08.503267v4" target="_blank">Revealing the drivers of antibiotic resistance trends in Streptococcus pneumoniae amidst the 2020 COVID-19 pandemic: Insights from mathematical modeling</a>
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</div></li>
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<li><strong>Persistence and Free Chlorine Disinfection of Human Coronaviruses and Their Surrogates in Water</strong> -
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<div>
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The COVID-19 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses to humans, but the literature is relatively void of studies on the persistence of many viruses, especially coronaviruses, in water and their susceptibility to chlorine disinfection. To fill that knowledge gap, we evaluated the persistence and free chlorine disinfection of human coronavirus OC43 (HCoV-OC43) and its surrogates, murine hepatitis virus (MHV) and porcine transmissible gastroenteritis virus (TGEV), in drinking water and laboratory buffer using cell culture methods. The decay rate constants of human coronavirus and its surrogates in water varied depending on virus and water matrix. In drinking water prior to disinfectant addition, MHV showed the largest decay rate constant (2.25 day-1) followed by HCoV-OC43 (0.99 day-1) and TGEV (0.65 day-1); while in phosphate buffer, HCoV-OC43 (0.51 day-1) had a larger decay rate constant than MHV (0.28 day-1) and TGEV (0.24 day-1). Upon free chlorine disinfection, the inactivation rates of coronaviruses were independent of free chlorine concentration and not affected by water matrix, though they still varied between viruses. TGEV showed the highest susceptibility to free chlorine disinfection with the inactivation rate constant of 113.50 mg-1 min-1 L, followed by MHV (81.33 mg-1 min-1 L) and HCoV-OC43 (59.42 mg-1 min-1 L).
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.16.575911v1" target="_blank">Persistence and Free Chlorine Disinfection of Human Coronaviruses and Their Surrogates in Water</a>
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</div></li>
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<li><strong>A Bacteriophage Cocktail Targeting Yersinia pestis Provides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model</strong> -
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<div>
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Yersinia pestis, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity, Y. pestis is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug resistant strains. The dissemination of such Y. pestis strains could be catastrophic, with public health consequences far more daunting than those caused by the recent COVID-19 pandemic. Thus, there is an urgent need to develop novel, safe, and effective treatment approaches for managing Y. pestis infections. This includes infections by antigenically distinct strains for which vaccines, none FDA approved yet, may not be effective, and those that cannot be controlled by approved antibiotics. Lytic bacteriophages provide one such alternative approach. In this study, we examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by Y. pestis CO92. YPP-401 is a four-phage preparation with a 100% lytic activity against a panel of 68 genetically diverse Y. pestis strains. Using a pneumonic plague aerosol challenge model in gender-balanced Brown Norway rats, YPP-401 demonstrated ~88% protection when delivered 18 hours post-exposure for each of two administration routes (i.e., intraperitoneal and intranasal) in a dose-dependent manner. Our studies suggest that YPP-401 could provide an innovative, safe, and effective approach for managing Y. pestis infections, including those caused by naturally occurring or intentionally developed strains that cannot be managed by vaccines in development and antibiotics.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.17.576055v1" target="_blank">A Bacteriophage Cocktail Targeting Yersinia pestis Provides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model</a>
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</div></li>
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<li><strong>GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern</strong> -
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<div>
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Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 s of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how the structural role of this glycan changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.05.570076v2" target="_blank">GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern</a>
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</div></li>
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<li><strong>Phase 1 of the NIH Preprint Pilot: Testing the viability of making preprints discoverable in PubMed Central and PubMed</strong> -
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<div>
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Introduction: The National Library of Medicine (NLM) launched a pilot in June 2020 to 1) explore the feasibility and utility of adding preprints to PubMed Central (PMC) and making them discoverable in PubMed and 2) to support accelerated discoverability of NIH-supported research without compromising user trust in NLM’s widely used literature services. Methods: The first phase of the Pilot focused on archiving preprints reporting NIH-supported SARS-CoV-2 virus and COVID-19 research. To launch Phase 1, NLM identified eligible preprint servers and developed processes for identifying NIH-supported preprints within scope in these servers. Processes were also developed for the ingest and conversion of preprints in PMC and to send corresponding records to PubMed. User interfaces were modified for display of preprint records. NLM collected data on the preprints ingested and discovery of preprint records in PMC and PubMed and engaged users through focus groups and a survey to obtain direct feedback on the Pilot and perceptions of preprints. Results: Between June 2020 and June 2022, NLM added more than 3,300 preprint records to PMC and PubMed, which were viewed 4 million times and 3 million times, respectively. Nearly a quarter of preprints in the Pilot were not associated with a peer-reviewed published journal article. User feedback revealed that the inclusion of preprints did not have a notable impact on trust in PMC or PubMed. Discussion: NIH-supported preprints can be identified and added to PMC and PubMed without disrupting existing operations processes. Additionally, inclusion of preprints in PMC and PubMed accelerates discovery of NIH research without reducing trust in NLM literature services. Phase 1 of the Pilot provided a useful testbed for studying NIH investigator preprint posting practices, as well as knowledge gaps among user groups, during the COVID-19 public health emergency, an unusual time with heightened interest in immediate access to research results.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.12.520156v2" target="_blank">Phase 1 of the NIH Preprint Pilot: Testing the viability of making preprints discoverable in PubMed Central and PubMed</a>
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</div></li>
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<li><strong>Deciphering the Molecular Mechanism of Post-Acute Sequelae of COVID-19 through Comorbidity Network Analysis</strong> -
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<div>
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Introduction: The post-acute sequelae of COVID-19 presents a significant health challenge in the post-pandemic world. Our study aims to analyze longitudinal electronic health records to determine the impact of COVID-19 on disease progression, provide molecular insights into these mechanisms, and identify associated biomarkers. Method: We included 58,710 patients with COVID-19 records from 01/01/2020 to 31/08/2022 and at least one hospital admission before and after the acute phase of COVID-19 (28 days) as the treatment group. A healthy control group of 174,071 individuals was established for comparison using propensity score matching based on pre-existing diseases (before COVID-19). We built a comorbidity network using Pearson correlation coefficient differences between pairs of pre-existing disease and post-infection disease in both groups. Disease-protein mapping and protein-protein interaction network analysis revealed the impact of COVID-19 on disease trajectories through protein interactions in the human body. Results: The disparity in the weight of prevalent disease comorbidity patterns between the treatment and control groups highlights the impact of COVID-19. Certain specific comorbidity patterns show a more pronounced influence by COVID-19. For each comorbidity pattern, overlapping proteins directly associated with pre-existing diseases, post-infection diseases, and COVID-19 help to elucidate the biological mechanism of COVID-19's impact on each comorbidity pattern. Proteins essential for explaining the biological mechanism can be identified based on their weights. Conclusion: Disease comorbidity associations influenced by COVID-19, as identified through longitudinal electronic health records and disease-protein mapping, can help elucidate the biological mechanisms of COVID-19, discover intervention methods, and decode the molecular basis of comorbidity associations. This analysis can also yield potential biomarkers and corresponding treatments for specific disease patterns.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.17.575851v1" target="_blank">Deciphering the Molecular Mechanism of Post-Acute Sequelae of COVID-19 through Comorbidity Network Analysis</a>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Beneficial Effects of Natural Products on Management of Xerostomia</strong> - <b>Conditions</b>: Xerostomia; Diabetes Mellitus; Hypertension; Post COVID-19 Condition <br/><b>Interventions</b>: Other: (Manuka honey-green tea- ginger) <br/><b>Sponsors</b>: British University In Egypt <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>Eficacia Ventilatoria y Remolacha</strong> - <b>Conditions</b>: SARS CoV 2 Infection; Muscle Disorder; Fatigue <br/><b>Interventions</b>: Dietary Supplement: Remolacha <br/><b>Sponsors</b>: Hospital de Mataró <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>Diet and Fasting for Long COVID</strong> - <b>Conditions</b>: Long Covid19; Long COVID <br/><b>Interventions</b>: Other: Low sugar diet and 10-12 hour eating window; Other: Low sugar diet, 8 hour eating window and fasting <br/><b>Sponsors</b>: Pacific Northwest University of Health Sciences <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 Effectiveness of a Health Promotion Program for Older People With Post-Covid-19 Sarcopenia</strong> - <b>Conditions</b>: Post COVID-19 Condition <br/><b>Interventions</b>: Other: Protein powder and Resistance exercise <br/><b>Sponsors</b>: Mahidol University; National Health Security Office, Thailand <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>Chronic-disease Self-management Program in Patients Living With Long-COVID in Puerto Rico</strong> - <b>Conditions</b>: Long Covid19 <br/><b>Interventions</b>: Other: “Tomando control de su salud” (Spanish Chronic Disease Self-Management) <br/><b>Sponsors</b>: University of Puerto Rico; National Institutes of Health (NIH) <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>Treatment of Persistent Post-Covid-19 Smell and Taste Disorders</strong> - <b>Conditions</b>: Post-covid-19 Persistent Smell and Taste Disorders <br/><b>Interventions</b>: Drug: Cerebrolysin; Other: olfactory and gustatory trainings <br/><b>Sponsors</b>: Sherifa Ahmed Hamed <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults</strong> - <b>Conditions</b>: COVID-19; COVID-19 Immunisation <br/><b>Interventions</b>: Biological: TI-0010; Biological: Placebo <br/><b>Sponsors</b>: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna <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>Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction</strong> - <b>Conditions</b>: Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders <br/><b>Interventions</b>: Drug: Sodium Citrate; Drug: Normal Saline; Other: Olfactory Training Kit - “The Olfactory Kit, by AdvancedRx” <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill <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>Phase II, Double Blind, Randomized Trial of CX-4945 in Viral Community Acquired Pneumonia</strong> - <b>Conditions</b>: Community-acquired Pneumonia; SARS-CoV-2 -Associated Pneumonia; Influenza With Pneumonia <br/><b>Interventions</b>: Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: CX-4945 (Influenza virus domain); Drug: Placebo (Influenza virus domain) <br/><b>Sponsors</b>: Senhwa Biosciences, Inc. <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>Edge AI-deployed DIGItal Twins for PREDICTing Disease Progression and Need for Early Intervention in Infectious and Cardiovascular Diseases Beyond COVID-19 - Investigation of Biomarkers in Dermal Interstitial Fluid</strong> - <b>Conditions</b>: Heart Failure <br/><b>Interventions</b>: Device: Use of the PELSA System for dISF extraction <br/><b>Sponsors</b>: Charite University, Berlin, Germany <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase III Clinical Study Evaluating the Efficacy and Safety of WPV01 in Patients With Mild/Moderate COVID-19</strong> - <b>Conditions</b>: Mild to Moderate COVID-19 <br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo <br/><b>Sponsors</b>: Westlake Pharmaceuticals (Hangzhou) Co., Ltd. <br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Generation of SARS-CoV-2 spike receptor binding domain mutants and functional screening for immune evaders using a novel lentivirus-based system</strong> - The emergence of rapid and continuous mutations of severe acute respiratory syndrome 2 (SARS-CoV-2) spike glycoprotein that increased with the Omicron variant points out the necessity to anticipate such mutations for conceiving specific and adaptable therapies to avoid another pandemic. The crucial target for the antibody treatment and vaccine design is the receptor binding domain (RBD) of the SARS-CoV-2 spike. It is also the site where the virus has shown its high ability to mutate 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>The Development of an Oral Solution Containing Nirmatrelvir and Ritonavir and Assessment of Its Pharmacokinetics and Stability</strong> - Paxlovid^(®), a co-packaged medication comprised of separate tablets containing two active ingredients, nirmatrelvir (NRV) and ritonavir (RTV), exhibits good effectiveness against coronavirus disease 2019 (COVID-19). However, the size of the NRV/RTV tablets makes them difficult for some patients to swallow, especially the elderly and those with dysphagia. Therefore, an oral liquid formulation that can overcome this shortcoming and improve patient compliance is required. In this study, we…</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>Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK</strong> - The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling…</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>Performance Analysis of Serodiagnostic Tests to Characterize the Incline and Decline of the Individual Humoral Immune Response in COVID-19 Patients: Impact on Diagnostic Management</strong> - Serodiagnostic tests for antibody detection to estimate the immunoprotective status regarding SARS-CoV-2 support diagnostic management. This study aimed to investigate the performance of serological assays for COVID-19 and elaborate on test-specific characteristics. Sequential samples (n = 636) of four panels (acute COVID-19, convalescent COVID-19 (partly vaccinated post-infection), pre-pandemic, and cross-reactive) were tested for IgG by indirect immunofluorescence test (IIFT) and EUROIMMUN…</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>AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4</strong> - Coagulation disorders are described in COVID-19 and long COVID patients. In particular, SARS-CoV-2 infection in megakaryocytes, which are precursors of platelets involved in thrombotic events in COVID-19, long COVID and, in rare cases, in vaccinated individuals, requires further investigation, particularly with the emergence of new SARS-CoV-2 variants. CD147, involved in the regulation of inflammation and required to fight virus infection, can facilitate SARS-CoV-2 entry into megakaryocytes….</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>Structural Basis for the Inhibition of SARS-CoV-2 M<sup>pro</sup> D48N Mutant by Shikonin and PF-07321332</strong> - Preventing the spread of SARS-CoV-2 and its variants is crucial in the fight against COVID-19. Inhibition of the main protease (M^(pro)) of SARS-CoV-2 is the key to disrupting viral replication, making M^(pro) a promising target for therapy. PF-07321332 and shikonin have been identified as effective broad-spectrum inhibitors of SARS-CoV-2 M^(pro). The crystal structures of SARS-CoV-2 M^(pro) bound to PF-07321332 and shikonin have been resolved in previous studies. However, the exact mechanism…</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>Susceptibility and Resistance of SARS-CoV-2 Variants to LCB1 and Its Multivalent Derivatives</strong> - LCB1 is a computationally designed three-helix miniprotein that precisely targets the spike (S) receptor-binding motif (RBM) of SARS-CoV-2, exhibiting remarkable antiviral efficacy; however, emerging SARS-CoV-2 variants could substantially compromise its neutralization effectiveness. In this study, we constructed two multivalent LCB1 fusion proteins termed LCB1T and LCB1T-Fc, and characterized their potency in inhibiting SARS-CoV-2 pseudovirus and authentic virus in vitro. In the inhibition of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Favipiravir Analogues as Inhibitors of SARS-CoV-2 RNA-Dependent RNA Polymerase, Combined Quantum Chemical Modeling, Quantitative Structure-Property Relationship, and Molecular Docking Study</strong> - Our study was motivated by the urgent need to develop or improve antivirals for effective therapy targeting RNA viruses. We hypothesized that analogues of favipiravir (FVP), an inhibitor of RNA-dependent RNA polymerase (RdRp), could provide more effective nucleic acid recognition and binding processes while reducing side effects such as cardiotoxicity, hepatotoxicity, teratogenicity, and embryotoxicity. We proposed a set of FVP analogues together with their forms of triphosphate as new…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis and Antiviral Activity of Novel β-D-N4-Hydroxycytidine Ester Prodrugs as Potential Compounds for the Treatment of SARS-CoV-2 and Other Human Coronaviruses</strong> - The spread of COVID-19 infection continues due to the emergence of multiple transmissible and immune-evasive variants of the SARS-CoV-2 virus. Although various vaccines have been developed and several drugs have been approved for the treatment of COVID-19, the development of new drugs to combat COVID-19 is still necessary. In this work, new 5’-O-ester derivatives of N4-hydroxycytidine based on carboxylic acids were developed and synthesized by Steglich esterification. The antiviral activity of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Photodynamic Action of Curcumin and Methylene Blue against Bacteria and SARS-CoV-2-A Review</strong> - CONCLUSION: The photodynamic action of curcumin and methylene blue provides a possible approach against bacteria and SARS-CoV-2 infection because they act as non-toxic photosensitizers in PDT with an antibacterial effect, anti-viral properties, and disinfection functions.</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>Leveraging SARS-CoV-2 Main Protease (M<sup>pro</sup>) for COVID-19 Mitigation with Selenium-Based Inhibitors</strong> - The implementation of innovative approaches is crucial in an ongoing endeavor to mitigate the impact of COVID-19 pandemic. The present study examines the strategic application of the SARS-CoV-2 Main Protease (M^(pro)) as a prospective instrument in the repertoire to combat the virus. The cloning, expression, and purification of M^(pro), which plays a critical role in the viral life cycle, through heterologous expression in Escherichia coli in a completely soluble form produced an active enzyme….</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 Integrated In Silico and In Vitro Approach for the Identification of Natural Products Active against SARS-CoV-2</strong> - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has provoked a global health crisis due to the absence of a specific therapeutic agent. 3CL^(pro) (also known as the main protease or M^(pro)) and PL^(pro) are chymotrypsin-like proteases encoded by the SARS-CoV-2 genome, and play essential roles during the virus lifecycle. Therefore, they are recognized as a prospective therapeutic target in drug discovery against 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>Immunogenicity and safety of concomitant bivalent COVID-19 and quadrivalent influenza vaccination: Implications of immune imprinting and interference</strong> - CONCLUSIONS: Concomitant administration of bivalent COVID-19 mRNA and quadrivalent influenza vaccines showed tolerable safety profiles and sufficient immunogenicity, particularly attenuating immune imprinting induced by prior ancestral vaccine strains.</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 insights into emerging trends to control the threats of antimicrobial resistance (AMR): an address to public health risks</strong> - Antimicrobial agents are used to treat microbial ailments, but increased use of antibiotics and exposure to infections in healthcare facilities and hospitals as well as the excessive and inappropriate use of antibiotics at the society level lead to the emergence of multidrug-resistant (MDR) bacteria. Antimicrobial resistance (AMR) is considered a public health concern and has rendered the treatment of different infections more challenging. The bacterial strains develop resistance against…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2-induced disruption of a vascular bed in a microphysiological system caused by type-I interferon from bronchial organoids</strong> - Blood vessels show various COVID-19-related conditions including thrombosis and cytokine propagation. Existing in vitro blood vessel models cannot represent the consequent changes in the vascular structure or determine the initial infection site, making it difficult to evaluate how epithelial and endothelial tissues are damaged. Here, we developed a microphysiological system (MPS) that co-culture the bronchial organoids and the vascular bed to analyze infection site and interactions. In this…</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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