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174 lines
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<title>15 December, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</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>How Generative AI Portrays Science. Interviewing ChatGPT from the Perspective of Different Audience Segments</strong> -
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<div>
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Generative AI in general and ChatGPT in particular have risen in importance. ChatGPT is widely known and used increasingly as an information source for different topics, including science. It is therefore relevant how ChatGPT portrays science and science-related topics. Research on this question is lacking, however. Hence, we “interview” ChatGPT and reconstruct how it presents science, scientists, scientific misbehavior and controversial scientific fields. Combining qualitative and quantitative content analysis, we find that, generally, ChatGPT portrays science largely as the STEM disciplines, in a positivist-empiricist way and a positive light. We compare ChatGPT’s responses to different simulated user profiles and two versions of GPT and find similarities in that the scientific consensus on questions like climate change, COVID-19 vaccinations or astrology is consistently conveyed across them. Beyond these similarities in substance, however, pronounced differences are found in the personalization of responses to different user profiles and between GPT-3.5 and GPT-4.
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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/erf36/" target="_blank">How Generative AI Portrays Science. Interviewing ChatGPT from the Perspective of Different Audience Segments</a>
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</div></li>
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<li><strong>A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia</strong> -
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Pathogen clearance and resolution of inflammation in patients with pneumonia require an effective local T cell response. Nevertheless, local T cell activation may drive lung injury, particularly during prolonged episodes of respiratory failure characteristic of severe SARS-CoV-2 pneumonia. While T cell responses in the peripheral blood are well described, the evolution of T cell phenotypes and molecular signatures in the distal lung of patients with severe pneumonia caused by SARS-CoV-2 or other pathogens is understudied. Accordingly, we serially obtained 432 bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia and respiratory failure, including 74 unvaccinated patients with COVID-19, and performed flow cytometry, transcriptional, and T cell receptor profiling on sorted CD8+ and CD4+ T cell subsets. In patients with COVID-19 but not pneumonia secondary to other pathogens, we found that early and persistent enrichment in CD8+ and CD4+ T cell subsets correlated with survival to hospital discharge. Activation of interferon signaling pathways early after intubation for COVID-19 was associated with favorable outcomes, while activation of NF-{kappa}B-driven programs late in disease was associated with poor outcomes. Patients with SARS-CoV-2 pneumonia whose alveolar T cells preferentially targeted the Spike and Nucleocapsid proteins tended to experience more favorable outcomes than patients whose T cells predominantly targeted the ORF1ab polyprotein complex. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize patients who recover, yet these responses progress to NF-{kappa}B activation against non-structural proteins in patients who go on to experience poor clinical outcomes.
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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/10.1101/2023.12.13.571479v1" target="_blank">A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia</a>
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</div></li>
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<li><strong>Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level</strong> -
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<div>
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It is widely accepted that m6A exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduce Scm6A, a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6A trans regulators and cis sequence features, and found that Scm6A offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we applied a winscore-based m6A calculation method to conduct m6A-seq analysis on CD4+ and CD8+ T-cells isolated through magnetic-activated cell sorting (MACS). Subsequently, we employed Scm6A for analysis on the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with m6A quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6A's reliability. Additionally, we performed single-cell level m6A analysis on lung cancer tissues as well as blood samples from COVID-19 patients, and demonstrated the landscape and regulatory mechanisms of m6A in different T-cell subtypes from these diseases. In summary, our work has yielded a novel, dependable, and accurate method for single-cell m6A detection. We are confident that Scm6A have broad applications in the realm of m6A-related research.
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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/10.1101/2023.12.14.571511v1" target="_blank">Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level</a>
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</div></li>
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<li><strong>Inactivation of the Niemann Pick C1 cholesterol transporter 1 (NPC1) restricts SARS-CoV-2 infection</strong> -
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<div>
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The Niemann Pick C1 (NPC1) protein is an intracellular cholesterol transporter located in the late endosome/lysosome (LE/Ly) and is involved in cholesterol mobilization. Loss-of-function mutations of the NPC1 gene lead to accumulation of cholesterol and sphingolipids in LE/Ly, resulting in severe fatal NPC1 disease. Cellular alterations associated with NPC1 inactivation affect both the integrity of lipid rafts and the endocytic pathway. Because the angiotensin-converting enzyme 2 (ACE2) and type 2 serine transmembrane protease (TMPRSS2) of the SARS-CoV-2 Spike (S) protein also localize to lipid rafts, we sought to investigate the hypothesis that NPC1 inactivation would generate an intrinsically unfavorable barrier to SARS-CoV-2 entry. In this study, we demonstrate that NPC1 pharmacological inactivation or CRISP/R-Cas mediated ablation of NPC1 dramatically reduced SARS-CoV-2 infectivity. More specifically, our findings demonstrate that pharmacological inactivation of NPC1 results in massive accumulation of ACE2 in the autophagosomal/lysosomal compartment. A >40-fold decrease in virus titer indicates that this effectively prevents VSV-Spike-GFP infection by impeding virus binding and entry. A similarly marked decrease in viral infectivity is observed in cells that had NPC1 expression genetically abrogated. These observations were further confirmed in a de novo SARS-CoV-2 infection paradigm, where cells were infected with the naturally pathogenic SARS-CoV-2. Overall, this work offers strong evidence that NPC1 function is essential for successful SARS-CoV-2 infection, thus implicating NPC1 as a potential therapeutic target in COVID-19 management.
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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/10.1101/2023.12.13.571570v1" target="_blank">Inactivation of the Niemann Pick C1 cholesterol transporter 1 (NPC1) restricts SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Differential outcomes of infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern in K18-hACE2 transgenic mice</strong> -
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Background: SARS-CoV-2 is a respiratory virus with neurological complications including loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of Wild-type virus, Delta and Omicron variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lung, brain medulla oblongata and olfactory bulbs of these animals. We hypothesized that Wild-type, Delta and Omicron differentially infect K18-hACE2 mice, thereby inducing distinct cellular responses. Methods: K18-hACE2 female mice were intranasally infected with Wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, olfactory bulbs, medulla oblongata, and brains. Results: Mice infected with Wild-type and Delta display higher levels of viral RNA in the lungs than mice infected with Omicron at 3dpi. Viral RNA levels in the brains of mice infected with the Wild-type virus were however significantly lower than those observed in mice infected with either Delta or Omicron at 3dpi. Viral RNA was also detected in the medulla oblongata of mice infected by all these virus strains at 3dpi. At this time point, mice infected with the Delta virus display a marked upregulation of inflammatory makers both in the lungs and brains. Upregulation of inflammatory markers was also observed in the brains of mice infected with Omicron but not in mice infected with the Wild-type virus, suggesting that during the initial phase of the infection only the Delta and Omicron variants induce strong inflammatory response in the brain. At the humane endpoint/8dpi, mice infected by any of these strains display elevated levels of viral RNA and upregulation of a subset of inflammatory markers in the lungs. There was also a significant increase in viral RNA in the brains of mice infected with Wild-type and Delta, as compared to 3dpi. This was accompanied by an increase in the expression of most cytokines and chemokines. In contrast, mice infected with the Omicron variant showed low levels of viral RNA and downregulation of cytokines and chemokines expression at 8dpi, suggesting that brain inflammation by this variant is attenuated. Reduced RNA levels and downregulation of inflammatory markers was also observed in the medulla oblongata and olfactory bulbs of mice infected with Omicron, while infection by Wild-type and Delta resulted in high levels of viral RNA and increased expression of inflammatory makers in these organs.
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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/10.1101/2023.09.08.556906v2" target="_blank">Differential outcomes of infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern in K18-hACE2 transgenic mice</a>
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</div></li>
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<li><strong>Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease</strong> -
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<div>
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Codon optimization describes the process used to increase protein production by use of alternative but synonymous codon changes. In SARS-CoV-2 mRNA vaccines codon optimizations can result in differential secondary conformations that inevitably affect a protein’s function with significant consequences to the cell. Importantly, when codon optimization increases the GC content of synthetic mRNAs, there can be an inevitable enrichment of G-quartets which potentially form G-quadruplex structures. The emerging G-quadruplexes are favorable binding sites of RNA binding proteins like helicases that inevitably affect epigenetic reprogramming of the cell by altering transcription, translation and replication. In this study, we performed a RNAfold analysis to investigate alterations in secondary structures of mRNAs in SARS-CoV-2 vaccines due to codon optimization. We show a significant increase in the GC content of mRNAs in vaccines as compared to native SARS-CoV-2 RNA sequences encoding the spike protein. As the GC enrichment leads to more G-quadruplex structure formations, these may contribute to potential pathological processes initiated by SARS-CoV-2 molecular vaccination.
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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/bcsa6/" target="_blank">Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease</a>
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</div></li>
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<li><strong>Examining perceptions of stress, wellbeing and fear among Hungarian adolescents and their parents under lockdown during the COVID-19 pandemic</strong> -
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Intensified anxiety responses and even symptoms of post-traumatic stress are commonly observed under quarantine conditions. In this study, the effects on fear, anxiety and wellbeing of the recent pandemic caused by SARS-CoV-2 were investigated in a sample of otherwise healthy Hungarians. Taking the family as a microsystem, differences in gender, age, family relationships and time spent in isolation were the main focus of this investigation. 346 parent-child dyads were examined; the children were 11-17 years of age. Standard psychological questionnaires (Perceived Stress Scale, WHO Wellbeing Index), and an open question test (the Metamorphosis test) were used, and the results analysed with the aid of basic statistical methods. Stress levels and wellbeing displayed a significant negative correlation with each other in both parents and children. Parental stress and levels of wellbeing had a weak but significant impact on the wellbeing of their children. Among the demographic variables examined, none of them was found to explain the wellbeing or stress level of parents. Natural catastrophes, such as pandemics, create a stressful social environment for parents, and therefore directly impact the psychological wellbeing of all family members.
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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/psyarxiv/feth3/" target="_blank">Examining perceptions of stress, wellbeing and fear among Hungarian adolescents and their parents under lockdown during the COVID-19 pandemic</a>
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<li><strong>Acceptability and feasibility of a theatre-based wellness programme to support people living with Long COVID: a single arm feasibility study.</strong> -
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Objectives: To determine acceptability and feasibility of a theatre-based wellness programme to support the health and wellbeing of people with long COVID. Design: Single group, repeated measures feasibility study. Setting: Community centre and online. Participants: Adults with a diagnosis of long COVID experiencing breathlessness, mild to moderate pain, and/or loneliness. Intervention: A six-week participatory creative intervention delivered to two groups of participants, one online and one in-person. The groups were facilitated by movement, voice and drama consultants and designed to improve wellbeing, fatigue, pain, strength and balance through a series of breathing exercises, visualisation, group singing and sound imagery, storytelling, movement exercises and poetry. Primary outcome measures: Acceptability of the intervention and feasibility of recruitment procedures and data collection. Secondary outcome measures: Changes in mental health, wellbeing, quality of life, loneliness, social support, fatigue, breathlessness, and post-COVID-19 functional status. Results: 20 participants took part in the intervention, 19 completed baseline assessments and 16 completed study follow-up. Most participants found the programme acceptable and feasible and improvements were identified in all outcomes at 8-week follow-up, including decreases in generalised anxiety and depressive symptoms, loneliness, shortness of breath, respiratory dysfunction, chronic fatigue and increased mental wellbeing, social support, and self-rated health. Key programme features and mechanisms of action that led to improvements in health and wellbeing were identified in qualitative interviews. Barriers to engagement included: activities being outside of the participant’s comfort zone, ongoing and fluctuating long COVID symptoms, emotional consequences of sharing experiences with the group and connectivity and connecting with others online. Conclusions: A six-week theatre-based programme was perceived as acceptable to most participants and resulted in positive psychosocial impacts. The findings provide a rationale for supporting the ongoing development of this and related programmes and for scaling up research into arts programmes to support people living with long COVID.
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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/k25qj/" target="_blank">Acceptability and feasibility of a theatre-based wellness programme to support people living with Long COVID: a single arm feasibility study.</a>
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</div></li>
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<li><strong>Artificial Intelligence and Robotics for Reducing Waste in the Food Supply Chain: Systematic Literature Review, Theoretical Framework, and Research Agenda</strong> -
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<div>
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The COVID-19 pandemic has unraveled the inefficiencies in the global food supply chain. One glaring distortion is the wastage of close to a third of global food production, in the face of widespread food insecurity. With population explosion and climate change as additional pressure points, reducing food waste has emerged as an urgent imperative for achieving food security for all. In this paper, we develop a research framework and agenda for the use of Artificial Intelligence and robotics in reducing food loss and waste. The Cognitive Automation for Food (COGAF) has been developed as a theoretical framework for guiding future research. This framework delineates the research landscape into five distinct research streams: sensory enhancement, cognitive automation, physical automation, sensory-motor fusion, and collaborative automation. In order to develop a systematic research agenda, propositions have been developed in each of these research streams. In conjunction with the COGAF framework, this research agenda attempts to provide a road map for future research and knowledge creation pertaining to the use of AI and robotics to reduce food loss and waste.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/h3jgb/" target="_blank">Artificial Intelligence and Robotics for Reducing Waste in the Food Supply Chain: Systematic Literature Review, Theoretical Framework, and Research Agenda</a>
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<li><strong>Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform</strong> -
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Biological evidence suggests ursodeoxycholic acid (UDCA) - a common treatment of cholestatic liver disease - may prevent severe COVID-19 outcomes. With the approval of NHS England, we conducted a population-based cohort study using primary care records, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. We estimated the hazard of COVID-19 hospitalisation or death between 1 March 2020 and 31 December 2022, comparing UDCA treatment to no UDCA treatment in a population with indication. Of 11,320 eligible individuals, 642 were hospitalised or died with COVID-19 during follow-up, 402 (63%) events among UDCA users. After confounder adjustment, UDCA was associated with a 21% (95% CI 7%-33%) relative reduction in the hazard of COVID-19 hospitalisation or death, consistent with an absolute risk reduction of 1.3% (95% CI 1.0%-1.6%). Our findings support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.11.23299191v1" target="_blank">Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform</a>
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<li><strong>A software tool for at-home measurement of sensorimotor adaptation</strong> -
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Sensorimotor adaptation is traditionally studied in well-controlled laboratory settings with specialized equipment. However, recent public health concerns such as the COVID-19 pandemic, as well as a desire to recruit a more diverse study population, have led the motor control community to consider at-home study designs. At-home motor control experiments are still rare because of the requirement to write software that can be easily used by anyone on any platform. To this end, we developed software that runs locally on a personal computer. The software provides audiovisual instructions and measures the ability of the subject to control the cursor in the context of visuomotor perturbations. We tested the software on a group of at-home participants and asked whether the adaptation principles inferred from in-lab measurements were reproducible in the at-home setting. For example, we manipulated the perturbations to test whether there were changes in adaptation rates (savings and interference), whether adaptation was associated with multiple timescales of memory (spontaneous recovery), and whether we could selectively suppress subconscious learning (delayed feedback, perturbation variability) or explicit strategies (limited reaction time). We found remarkable similarity between in-lab and at-home behaviors across these experimental conditions. Thus, we developed a software tool that can be used by research teams with little or no programming experience to study mechanisms of adaptation in an at-home setting.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.571359v1" target="_blank">A software tool for at-home measurement of sensorimotor adaptation</a>
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<li><strong>Identification of an allele-specific transcription factor binding interaction that regulates PLA2G2A gene expression</strong> -
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The secreted phospholipase A2 (sPLA2) isoform, sPLA2-IIA, has been implicated in a variety of diseases and conditions, including bacteremia, cardiovascular disease, COVID-19, sepsis, adult respiratory distress syndrome, and certain cancers. Given its significant role in these conditions, understanding the regulatory mechanisms impacting its levels is crucial. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs), including rs11573156, that are associated with circulating levels of sPLA2-IIA. Through Genotype-Tissue Expression (GTEx), 234 expression quantitative trait loci (eQTLs) were identified for the gene that encodes for sPLA2-IIA, PLA2G2A. SNP2TFBS (https://ccg.epfl.ch/snp2tfbs/) was utilized to ascertain the binding affinities between transcription factors (TFs) to both the reference and alternative alleles of identified SNPs. Subsequently, ChIP-seq peaks highlighted the TF combinations that specifically bind to the SNP, rs11573156. SP1 emerged as a significant TF/SNP pair in liver cells, with rs11573156/SP1 interaction being most prominent in liver, prostate, ovary, and adipose tissues. Further analysis revealed that the upregulation of PLA2G2A transcript levels through the rs11573156 variant was affected by tissue SP1 protein levels. By leveraging an ordinary differential equation, structured upon Michaelis-Menten enzyme kinetics assumptions, we modeled the PLA2G2A transcription's dependence on SP1 protein levels, incorporating the SNP's influence. Collectively, these data strongly suggest that the binding affinity differences of SP1 for the different rs11573156 alleles can influence PLA2G2A expression. This, in turn, can modulate sPLA2-IIA levels, impacting a wide range of human diseases.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.571290v1" target="_blank">Identification of an allele-specific transcription factor binding interaction that regulates PLA2G2A gene expression</a>
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<li><strong>Leveraging Tuberculosis Programs for Future Pandemic Preparedness: A Retrospective Look on COVID-19</strong> -
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Worldwide, COVID-19 has decimated healthcare systems and highlighted the pressing need to ensure resilience for future pandemics. Given the almost 30% likelihood of another respiratory disease similar to COVID-19 manifesting in the next 10 years, it is imperative to prioritize pandemic preparedness in the immediate future. To this end, tuberculosis (TB) and its management share many similarities to respiratory disease protection, offering an opportunity to dually strengthen TB programs and protect against future pandemics. Looking at data from the World Health Organization (WHO), Global Fund, Our World in Data, and domestic health ministries. It was hypothesized that countries that had better TB program strength going into the pandemic fared better with COVID-19 than those with poorer TB treatment. It was found that countries that recovered their TB program strength (as measured by TB treatment coverage percentages) to or above pre-pandemic levels fared better in terms of COVID-19 pandemic incidence and death. Case studies helped identify common factors across resilient TB platforms in dually successful COVID-19 and TB countries, including community trust, co-epidemic responses that were able to maintain continuity of care, sustained innovation, comprehensive communication across public and private sectors, and maintenance of donor support for TB programs through the pandemic.
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🖺 Full Text HTML: <a href="https://osf.io/t23ed/" target="_blank">Leveraging Tuberculosis Programs for Future Pandemic Preparedness: A Retrospective Look on COVID-19</a>
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<li><strong>EduMap: Navigating a Learning Adventure</strong> -
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Directed study maps are often used in order to create an overlay of knowledge relations. However, these connections often have to manually be created by subject matter and IT experts, which, although are a ground truth, limit these user to the topics of the maps at hand. To address this, we propose EduMap, which takes advantage of GPT 3.5 in a few-shot setting to create a study map for any user-provided topic. We conducted two user studies to address various aspects of the map: (1) A quantitative study to test out the effectiveness of this map medium in the context of navigating information concerning COVID-19 in a expert-curated graph, and (2) A quantitative study to test out the accuracy and usefulness of GPT-generated graphs. Our results show that the map medium is effective, and, though the graphs produced make sense, there is work to be done before it can be considered ground truth, with issues of vague topics and improper connections between topics arising. Altogether, our results establish a baseline for AI-generated study maps to be improved upon in the future with ground truth to create a more trustworthy software.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/edarxiv/ez2bk/" target="_blank">EduMap: Navigating a Learning Adventure</a>
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<li><strong>Self-inhibiting percolation and viral spreading in epithelial tissue</strong> -
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SARS-CoV-2 induces delayed type-I/III interferon production, allowing it to escape the early innate immune response. The delay has been attributed to a deficiency in the ability of cells to sense viral replication upon infection, which in turn hampers activation of the antiviral state in bystander cells. Here, we introduce a cellular automaton model to investigate the spatiotemporal spreading of viral infection as a function of virus and host-dependent parameters. The model suggests that the considerable person-to-person heterogeneity in SARS-CoV-2 infections is a consequence of high sensitivity to slight variations in biological parameters near a critical threshold. It further suggests that within-host viral proliferation can be curtailed by the presence of remarkably few cells that are primed for IFN production. Thus, the observed heterogeneity in defense readiness of cells reflects a remarkably cost-efficient strategy for protection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.571279v1" target="_blank">Self-inhibiting percolation and viral spreading in epithelial tissue</a>
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</div></li>
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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>A Pilot Study of Liraglutide (A Weight Loss Drug) in High Risk Obese Participants With Cognitive and Memory Issues</strong> - <b>Conditions</b>: Multiple Sclerosis; Long COVID; Long Covid19; Obese; Obesity; Obesity, Morbid; Acute Leukemia in Remission <br/><b>Interventions</b>: Drug: Liraglutide Pen Injector [Saxenda]; Other: Medication Diary <br/><b>Sponsors</b>: University of Chicago <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>EXERCISE TRAINING USING AN APP ON PHYSICAL CARDIOVASCULAR FUNCTION INDIVIDUALS WITH POST-COVID-19 SYNDROME</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise; Behavioral: Control <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>A Phase 1 Trial of Recombinant COVID-19 Trivalent Protein Vaccine （CHO Cell）LYB002V14 in Booster Vaccination</strong> - <b>Conditions</b>: SARS-CoV-2; COVID-19 Vaccine <br/><b>Interventions</b>: Biological: 30μg dose of LYB002V14; Biological: 60μg dose of LYB002V14; Biological: placebo <br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Vaccine Effectiveness Against Recurrent Infection Among Lung Cancer Patients and Biomarker Research</strong> - <b>Conditions</b>: COVID-19 Recurrent; Lung Cancer; Vaccination; Antibody; Chemotherapy; Immune Checkpoint Inhibitor <br/><b>Interventions</b>: Biological: Any Chinese government-recommended COVID-19 booster vaccine <br/><b>Sponsors</b>: Peking Union Medical College Hospital <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS.</strong> - <b>Conditions</b>: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation <br/><b>Interventions</b>: Dietary Supplement: Nutritional blend (ImmuneRecov). <br/><b>Sponsors</b>: Federal University of São Paulo <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>Physical Activity Coaching in Patients With Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active <br/><b>Sponsors</b>: University of Alcala; Professional College of Physiotherapists of the Community of Madrid <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training</strong> - <b>Conditions</b>: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer <br/><b>Interventions</b>: Device: breathing training <br/><b>Sponsors</b>: Tri-Service General 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>Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID</strong> - <b>Conditions</b>: Long COVID; Post Acute Sequelae of COVID-19; Post-Acute COVID-19 <br/><b>Interventions</b>: Drug: Ensitrelvir; Other: Placebo <br/><b>Sponsors</b>: Timothy Henrich; Shionogi 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>Low-intensity Aerobic Training Associated With Global Muscle Strengthening in Post-COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Procedure: muscle strengthening <br/><b>Sponsors</b>: Centro Universitário Augusto Motta <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>Intravenous Immunoglobulin Replacement Therapy for Persistent COVID-19 in Patients With B-cell Impairment</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: Immunoglobulins <br/><b>Sponsors</b>: Jaehoon Ko <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>Effect of Inhaled Hydroxy Gas on Long COVID Symptoms</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Device: Hydroxy gas <br/><b>Sponsors</b>: Oxford Brookes University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community Care Intervention to Decrease COVID-19 Vaccination Inequities</strong> - <b>Conditions</b>: COVID-19 Vaccination <br/><b>Interventions</b>: Behavioral: Community Health Worker Intervention to Enhance Vaccination Behavior (CHW-VB) <br/><b>Sponsors</b>: RAND; Clinical Directors Network; National Institute on Minority Health and Health Disparities (NIMHD) <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>PROmotion of COVID-19 BOOSTer VA(X)Ccination in the Emergency Department - PROBOOSTVAXED</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Vaccine Messaging; Behavioral: Vaccine Acceptance Question <br/><b>Sponsors</b>: University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Duke University; Baylor College of Medicine; Thomas Jefferson University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program for PASC Program to Improve Functioning of Persons Suffering From Post-COVID-19 Syndrome: A Randomized Controlled Trial</strong> - <b>Conditions</b>: Post-Acute COVID-19; Post-Acute COVID-19 Syndrome; Post-Acute COVID-19 Infection; Long COVID; Long Covid19; Dyspnea; Orthostasis; Cognitive Impairment <br/><b>Interventions</b>: Other: Comprehensive Rehabilitation; Other: Augmented Usual Care <br/><b>Sponsors</b>: University of Pennsylvania; Medical College of Wisconsin; National Institutes of Health (NIH) <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>Multilevel Intervention of COVID-19 Vaccine Uptake Among Latinos</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Multilevel Intervention <br/><b>Sponsors</b>: San Diego State University <br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An overview of the role of Niemann-pick C1 (NPC1) in viral infections and inhibition of viral infections through NPC1 inhibitor</strong> - Viruses communicate with their hosts through interactions with proteins, lipids, and carbohydrate moieties on the plasma membrane (PM), often resulting in viral absorption via receptor-mediated endocytosis. Many viruses cannot multiply unless the host’s cholesterol level remains steady. The large endo/lysosomal membrane protein (MP) Niemann-Pick C1 (NPC1), which is involved in cellular cholesterol transport, is a crucial intracellular receptor for viral infection. NPC1 is a ubiquitous…</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>Acarbose reduces Pseudomonas aeruginosa respiratory tract infection in type 2 diabetic mice</strong> - CONCLUSIONS: This study confirmed the attenuating effect of acarbose on P. aeruginosa RTIs in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.</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 exonuclease-resistant chain-terminating nucleotide analogue targeting the SARS-CoV-2 replicase complex</strong> - Nucleotide analogues (NA) are currently employed for treatment of several viral diseases, including COVID-19. NA prodrugs are intracellularly activated to the 5’-triphosphate form. They are incorporated into the viral RNA by the viral polymerase (SARS-CoV-2 nsp12), terminating or corrupting RNA synthesis. For Coronaviruses, natural resistance to NAs is provided by a viral 3’-to-5’ exonuclease heterodimer nsp14/nsp10, which can remove terminal analogues. Here, we show that the replacement of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical phenotype and outcome of persistent SARS-CoV-2 replication in immunocompromised hosts: a retrospective observational study in the Omicron era</strong> - CONCLUSION: Ongoing SARS-CoV-2 replication in the lower respiratory tract is a relevant differential diagnosis in patients with severe immunosuppression and continuous cough, fever or dyspnoea even if nasopharyngeal swabs test negative for SARS-CoV-2. Especially in B cell-depleted patients, this may lead to inflammatory or fibrotic-like pulmonary changes, which are partially reversible after inhibition of viral replication. Antiviral therapy seems to be most effective in combination and over 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>Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research</strong> - As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID-19) today, arbidol often involves drug-drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 μL incubation system was used to study the inhibitory…</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>Tumor Treating Fields (TTFields) demonstrate antiviral functions <em>in vitro</em>, and safety for application to COVID-19 patients in a pilot clinical study</strong> - Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models,…</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>Repurposing of Rutan showed effective treatment for COVID-19 disease</strong> - Previously, from the tannic sumac plant (Rhus coriaria), we developed the Rutan 25 mg oral drug tablets with antiviral activity against influenza A and B viruses, adenoviruses, paramyxoviruses, herpes virus, and cytomegalovirus. Here, our re-purposing study demonstrated that Rutan at 25, 50, and 100 mg/kg provided a very effective and safe treatment for COVID-19 infection, simultaneously inhibiting two vital enzyme systems of the SARS-CoV-2 virus: 3C-like proteinase (3CLpro) and RNA-dependent…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of the K<sub>Ca</sub>2 potassium channel in atrial fibrillation: a randomized phase 2 trial</strong> - Existing antiarrhythmic drugs to treat atrial fibrillation (AF) have incomplete efficacy, contraindications and adverse effects, including proarrhythmia. AP30663, an inhibitor of the K(Ca)2 channel, has demonstrated AF efficacy in animals; however, its efficacy in humans with AF is unknown. Here we conducted a phase 2 trial in which patients with a current episode of AF lasting for 7 days or less were randomized to receive an intravenous infusion of 3 or 5 mg kg^(-1) AP30663 or placebo. The…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Angiotensin Converting Enzyme 2 Does Not Facilitate Porcine Epidemic Diarrhea Virus Entry into Porcine Intestinal Epithelial Cells and Inhibits It-induced Inflammatory Injury by Promoting STAT1 Phosphorylation</strong> - ACE2 has been confirmed to be a functional receptor for SARS-CoV and SARS-CoV-2, but research on animal coronaviruses, especially PEDV, are still unknown. The present study investigated whether ACE2 plays a role in receptor recognition and subsequent infection during PEDV invasion of host cells. IPEC-J2 cells stably expressing porcine ACE2 did not increase the production of PEDV-N but inhibited its expression. Porcine ACE2 knockout cells was generated by CRISPR/Cas9 genome editing in IPEC-J2…</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 environmental impact of mask-derived microplastics on soil ecosystems</strong> - During the COVID-19 pandemic, a significant increased number of masks were used and improperly disposed of. For example, the global monthly consumption of approximately 129 billion masks. Masks, composed of fibrous materials, can readily release microplastics, which may threaten various soil ecosystem components such as plants, animals, microbes, and soil properties. However, the specific effects of mask-derived microplastics on these components remain largely unexplored. Here, we investigated…</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>Hospital healthcare workers’ use of facial protective equipment before the COVID-19 pandemic, implications for future policy</strong> - CONCLUSION: This study identified key determinants of FPE behavior. A review of context specific FPE guidance for ED by infection prevention and control professionals would help to promote practicable, sustainable compliance.</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>Hybrid immunity from SARS-CoV-2 infection and mRNA BNT162b2 vaccine among Thai school-aged children</strong> - CONCLUSIONS: Immune response that arises from BNT162b2 vaccine after natural infection and infection after 2 doses of BNT162b2 was higher than infection after partially-vaccinated children.</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>Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and M<sup>PRO</sup> enzymes of SARS-CoV-2</strong> - CONCLUSION: The IC(50) for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.</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 the clinical efficacy of racecadotril in the treatment of neonatal calves with infectious diarrhea</strong> - Racecadotril, used as an antidiarrheal drug in humans and some animals such as the dog, inhibits peripheral enkephalinase, which degrades enkephalins and enkephalinase inhibition induces a selective increase in chloride absorption from the intestines. The study material consisted of 46 calves with infectious diarrhea and 14 healthy calves in the age 2-20 days. The calves were divided into eight groups; healthy calves (HG), healthy calves administered racecadotril (HRG), calves with…</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 ncRNA transcriptomics-based approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes</strong> - CONCLUSION: Our novel in silico pipeline integrates effective methods from previous studies to predict and validate siRNA molecules, having the potential to inhibit viral replication pathway in vitro. In total, this study identified 17 highly specific siRNA molecules targeting NSP3, 4, and 6 and accessory genes ORF3a, 7a, 8, and 10 of SARS-CoV-2, which might be used as an additional antiviral treatment option especially in the cases of life-threatening urgencies.</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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