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182 lines
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<title>31 August, 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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<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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<li><strong>SARS-CoV-2 RNA Persists in the Central Nervous System of Non-Human Primates Despite Clinical Recovery</strong> -
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Adverse neurological and psychiatric outcomes, collectively termed the post-acute sequelae of SARS-CoV-2 infection (PASC), persist in adults clinically recovered from COVID-19. Effective therapeutic interventions are fundamental to reducing the burden of PASC, necessitating an investigation of the pathophysiology underlying the debilitating neurological symptoms associated with the condition. Herein, eight non-human primates (Wild-Caught African Green Monkeys, n=4; Indian Rhesus Macaques, n=4) were inoculated with the SARS-CoV-2 isolate USA-WA1/2020 by either small particle aerosol or via multiple routes. At necropsy, tissue from the olfactory epithelium and pyriform cortex/amygdala of SARS-CoV-2 infected non-human primates were collected for ribonucleic acid in situ hybridization (i.e., RNAscope). First, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) mRNA are downregulated in the pyriform cortex/amygdala of non-human primates clinically recovered from SARS-CoV-2 inoculation relative to wildtype controls. Second, abundant SARS-CoV-2 mRNA was detected in clinically recovered non-human primates; mRNA which is predominantly harbored in pericytes. Collectively, examination of post-mortem pyriform cortex/amygdala brain tissue of non-human primates clinically recovered from SARS-CoV-2 infection revealed two early pathophysiological mechanisms potentially underlying PASC. Indeed, therapeutic interventions targeting the downregulation of ACE2, decreased expression of TMPRSS2, and/or persistent infection of pericytes in the central nervous system may effectively mitigate the debilitating symptoms of PASC.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.29.555368v1" target="_blank">SARS-CoV-2 RNA Persists in the Central Nervous System of Non-Human Primates Despite Clinical Recovery</a>
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</div></li>
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<li><strong>Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): An open access disease specific drug discovery portal</strong> -
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<div>
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Computational drug discovery is intrinsically interdisciplinary and has to deal with the multifarious factors which are often dependent on the type of disease. Molecular Property Diagnostic Suite (MPDS) is a Galaxy based web portal which was conceived and developed as a disease specific web portal, originally developed for tuberculosis (MPDSTB). As specific computational tools are often required for a given disease, developing a disease specific web portal is highly desirable. This paper emphasises on the development of the customised web portal for COVID-19 infection and is referred to as MPDSCOVID-19. Expectedly, the MPDS suites of programs have modules which are essentially independent of a given disease, whereas some modules are specific to a particular disease. In the MPDSCOVID-19 portal, there are modules which are specific to COVID-19, and these are clubbed in SARS-COV-2 disease library. Further, the new additions and/or significant improvements were made to the disease independent modules, besides the addition of tools from galaxy toolshed. This manuscript provides a latest update on the disease independent modules of MPDS after almost 6 years, as well as provide the contemporary information and tool-shed necessary to engage in the drug discovery research of COVID-19. The disease independent modules include file format converter and descriptor calculation under the data processing module; QSAR, pharmacophore, scaffold analysis, active site analysis, docking, screening, drug repurposing tool, virtual screening, visualisation, sequence alignment, phylogenetic analysis under the data analysis module; and various machine learning packages, algorithms and in-house developed machine learning antiviral prediction model are available. The MPDS suite of programs are expected to bring a paradigm shift in computational drug discovery, especially in the academic community, guided through a transparent and open innovation approach. The MPDSCOVID-19 can be accessed at http://mpds.neist.res.in:8085.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.29.555437v1" target="_blank">Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): An open access disease specific drug discovery portal</a>
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</div></li>
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<li><strong>Immune Evasion and Membrane Fusion of SARS-CoV-2 XBB Subvariants EG.5.1 and XBB.2.3</strong> -
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<div>
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Immune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we characterized two new XBB variants rising in circulation: EG.5.1 and XBB.2.3, for their ability of neutralization and syncytia formation. We determined the neutralizing antibody in sera of individuals that received a bivalent mRNA vaccine booster, BA.4/5 wave infection, or XBB.1.5 wave infection. Bivalent vaccination-induced antibodies neutralized efficiently ancestral D614G, but to a much less extent, two new EG.5.1 and XBB.2.3 variants. In fact, the enhanced neutralization escape of EG.5.1 appeared to be driven by its key defining mutation XBB.1.5-F456L. Notably, infection by BA.4/5 or XBB.1.5 afforded little, if any, neutralization against EG.5.1, XBB.2.3 and previous XBB variants, especially in unvaccinated individuals, with average neutralizing antibody titers near the limit of detection. Additionally, we investigated the infectivity, fusion activity, and processing of variant spikes for EG.5.1 and XBB.2.3 in HEK293T-ACE2 and CaLu-3 cells, but found no significant differences compared to earlier XBB variants. Overall, our findings highlight the continued immune evasion of new Omicron subvariants and, more importantly, the need to reformulate mRNA vaccines to include XBB spikes for better protection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.30.555188v1" target="_blank">Immune Evasion and Membrane Fusion of SARS-CoV-2 XBB Subvariants EG.5.1 and XBB.2.3</a>
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</div></li>
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<li><strong>Pharmacokinetics-based identification of antiviral compounds of Rheum palmatum rhizomes and roots (Dahuang)</strong> -
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The potential of Dahuang to eliminate lung pathogens was often highlighted in Wenyi Lun. This investigation aimed to identify potential antiviral compounds of herbal component Dahuang (Rheum palmatum rhizomes and roots) of LianhuaQingwen capsule, with respect to their systemic exposure and lung reachability. Circulating Dahuang compounds were identified in human volunteers receiving LianhuaQingwen. The reachability of these compounds to SARS-CoV-2 3CLpro was assessed by in vitro transport, metabolism, immunohistochemistry, and 3CLpro-biochemical studies. LianhuaQingwen contained 55 Dahuang constituents (0.01-2.08 μmol/day), categorized into eight classes. Only three compounds rhein (3), methylisorhein (10; a new Dahuang anthraquinone), and 4-O-methylgallic acid (M42M2) exhibited significant systemic exposure in humans. Two intestinal absorption mechanisms for 3 and 10 were proposed: active intestinal uptake of 3/10 by human TAUT/ASBT and human MRP1/3/4, and intestinal lacate-phlorizin hrdrolyase-mediated hydrolysis of rhein-8-O-β-D-glucoside (9), followed by the transporter-mediated absorption of released 3. Targeted reachability of circulating 3/10 could be achieved as rat orthologues of human ASBT/TAUT was observed in alveolar and bronchial epithelia. These compounds exhibited potential ability to inhibit the 3CLpro enzyme responsible for coronaviral replication. Notably, Dahuang anthraquinones and tannins varied greatly in pharmacokinetics between humans and rats after dosing LianhuaQingwen. This investigation, along with such investigations of other components, has implications for precisely defining the therapeutic benefits of Dahuang-containing medicines.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.28.23294750v1" target="_blank">Pharmacokinetics-based identification of antiviral compounds of Rheum palmatum rhizomes and roots (Dahuang)</a>
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<li><strong>AmpliDiff: An Optimized Amplicon Sequencing Approach to Estimating Lineage Abundances in Viral Metagenomes</strong> -
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<div>
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Metagenomic profiling algorithms commonly rely on genomic differences between lineages, strains or species to infer the relative abundances of sequences present in a sample. This observation plays an important role in the analysis of diverse microbial communities, where targeted sequencing of 16S and 18S rRNA, both well-known hypervariable genomic regions, have led to insights in microbial diversity and the discovery of novel organisms. However, the variable nature of discriminatory regions can also act as a double-edged sword, as the sought after variability can make it difficult to design primers for their amplification through PCR. Moreover, the most variable regions are not necessarily the most informative regions for the purpose of differentiation; one should focus on regions which maximize the number of lineages that can be distinguished. Here we present AmpliDiff, a computational tool that simultaneously finds such highly discriminatory genomic regions, as well as primers allowing for the amplification of these regions. We show that regions and primers found by AmpliDiff can be used to accurately estimate relative abundances of SARS-CoV-2 lineages, for example in wastewater sequencing data. We obtain mean absolute prediction errors that are comparable with using whole genome information to estimate relative abundances. Furthermore, our results show that AmpliDiff is robust against incomplete input data, and that primers designed by AmpliDiff continue to bind to genomes originating from months after the primers were selected. With AmpliDiff we provide an effective and efficient alternative to whole genome sequencing for estimating lineage abundances in viral metagenomes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.22.550164v2" target="_blank">AmpliDiff: An Optimized Amplicon Sequencing Approach to Estimating Lineage Abundances in Viral Metagenomes</a>
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<li><strong>Jet injection potentiates naked mRNA SARS-CoV-2 vaccine in mice and non-human primates by adding physical stress to the skin</strong> -
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<div>
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Naked mRNA-based vaccines may reduce the reactogenicity associated with delivery carriers, but their effectiveness has been suboptimal against infectious diseases. Herein, we aimed to enhance their efficacy by using a pyro-drive liquid jet injector that precisely controls pressure to widely disperse mRNA solution in the skin. The jet injection boosted naked mRNA delivery efficiency in the mouse skin. Mechanistic analyses indicate that dendritic cells, upon uptake of antigen mRNA in the skin, migrate to the draining lymph nodes for antigen presentation. Additionally, the jet injector activated innate immune responses in the skin, presumably by inducing physical stress, thus serving as a physical adjuvant. From a safety perspective, our approach, utilizing naked mRNA, restricted mRNA distribution solely to the injection site, preventing systemic pro-inflammatory reactions following vaccination. Ultimately, the jet injection of naked mRNA encoding SARS-CoV-2 spike protein elicited robust humoral and cellular immunity, providing protection against SARS-CoV-2 infection in mice. Furthermore, our approach induced plasma activity of neutralizing SARS-CoV-2 in non-human primates, comparable to that observed in mice, with no detectable systemic reactogenicity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.27.530188v2" target="_blank">Jet injection potentiates naked mRNA SARS-CoV-2 vaccine in mice and non-human primates by adding physical stress to the skin</a>
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</div></li>
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<li><strong>COVID-19 is Feminine: Grammatical Gender Influences Future Danger Perceptions and Precautionary Behavior</strong> -
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<div>
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Gendered languages assign masculine and feminine grammatical gender to all nouns, including nonhuman entities. In French, Italian, and Spanish, the name of the disease resulting from the virus (COVID-19) is grammatically feminine, whereas the virus that causes the disease (coronavirus) is masculine. In this research, we test whether the grammatical gender mark matters. In a series of experiments with French and Spanish speakers, we find that grammatical gender affects virus-related judgments consistent with gender stereotypes: feminine- (vs. masculine-) marked terms for the virus decrease perceptions of future danger of the virus and reduce intentions to take precautionary behavioral measures to mitigate contraction and spread of the virus (e.g., avoiding restaurants, movies, travel). Secondary data analyses of online search behavior for France, Spain, and Italy further demonstrate this negative relation between the anticipated threat (daily new cases and deaths, search for masks) and usage of the feminine- (vs. masculine-) marked terms for the coronavirus. These effects occur even though the grammatical gender assignment is semantically arbitrary.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/x8kp2/" target="_blank">COVID-19 is Feminine: Grammatical Gender Influences Future Danger Perceptions and Precautionary Behavior</a>
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<li><strong>High-accuracy mapping of human and viral direct physical protein-protein interactions using the novel computational system AlphaFold-pairs</strong> -
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<div>
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Protein-protein interactions are central, highly flexible components of regulatory mechanisms in all living cells. Over the years, diverse methods have been developed to map protein-protein interactions. These methods have revealed the organization of protein complexes and networks in numerous cells and conditions. However, these methods are also time consuming, costly and sensitive to various experimental artifacts. To avoid these caveats, we have taken advantage of the AlphaFold-Multimer software, which succeeded in predicting the structure of many protein complexes. We designed a relatively simple algorithm based on assessing the physical proximity of a test protein with other AlphaFold structures. Using this method, named AlphaFold-pairs, we have successfully defined the probability of a protein-protein interaction forming. AlphaFold-pairs was validated using well-defined protein-protein interactions found in the literature and specialized databases. All pairwise interactions forming within the 12-subunit transcription machinery RNA Polymerase II, according to available structures, have been identified. Out of 66 possible interactions (excluding homodimers), 19 specific interactions have been found, and an additional previously unknown interaction has been unveiled. The SARS-CoV-2 surface glycoprotein Spike (or S) was confirmed to interact with high preference with the human ACE2 receptor when compared to other human receptors. Notably, two additional receptors, INSR and FLT4, were found to interact with S. For the first time, we have successfully identified protein-protein interactions that are likely to form within the reassortant Eurasian avian-like (EA) H1N1 swine G4 genotype Influenza A virus, which poses a potential zoonotic threat. Testing G4 proteins against human transcription factors and molecular chaperones (a total of 100 proteins) revealed strong specific interactions between the G4 HA and HSP90B1, the G4 NS and the PAQosome subunit RPAP3, as well as the G4 PA and the POLR2A subunit. We predict that AlphaFold-pairs will revolutionize the study of protein-protein interactions in a large number of healthy and diseased systems in the years to come.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.29.555151v1" target="_blank">High-accuracy mapping of human and viral direct physical protein-protein interactions using the novel computational system AlphaFold-pairs</a>
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</div></li>
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<li><strong>Chlorpheniramine Maleate Displays Multiple Modes of Antiviral Action Against SARS-CoV- 2: A Mechanistic Study</strong> -
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Chlorpheniramine Maleate (CPM) has been identified as a potential antiviral compound against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In this study, we investigated the in vitro effects of CPM on key stages of the SARS-CoV-2 replication cycle, including viral adsorption, replication inhibition, and virucidal activity. Our findings demonstrate that CPM exhibits antiviral properties by interfering with viral adsorption, replication, and directly inactivating the virus. Molecular docking analysis revealed interactions between CPM and essential viral proteins, such as the main protease receptor, spike protein receptor, and RNA polymerase. CPM's interactions were primarily hydrophobic in nature, with an additional hydrogen bond formation in the RNA polymerase active site. These results suggest that CPM has the potential to serve as a multitarget antiviral agent against SARS-CoV-2 and potentially other respiratory viruses. Further investigations are warranted to explore its clinical implications and assess its efficacy in vivo.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.28.554806v1" target="_blank">Chlorpheniramine Maleate Displays Multiple Modes of Antiviral Action Against SARS-CoV- 2: A Mechanistic Study</a>
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<li><strong>Age-Associated Weaker Immunity to Coronaviruses is Characteristic of Children that Develop Multisystem Inflammatory Syndrome following SARS-CoV-2 Infection</strong> -
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We analyzed the antibody and cytokine responses of twenty-three patients with multisystem inflammatory syndrome of children (MIS-C) that appeared with a three-to-six-week delay following a mild or asymptomatic SARS-CoV-2 infection. These responses were compared to healthy convalescent pediatric COVID-19 patients approximately twenty-eight days after the onset of symptoms. Both groups had strong IgG responses to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, but the MIS-C patients had weaker antibody responses to certain epitopes in the SARS-CoV-2 S and N proteins and to the S and N proteins of endemic human coronaviruses (HCoV) compared to pediatric convalescent COVID patients. HCoV antibody reactivity was correlated with age. In contrast, MIS-C patients had elevated serum levels of several proinflammatory cytokines compared to convalescent COVID patients, including interleukins IL-6, IL-8, IL-18 and chemokines CCL2, CCL8, CXCL5, CXCL9 and CXCL10 as well as tumor necrosis factor alpha and interferon gamma. Moreover, many cytokine responses of MIS-C patients were positively correlated with antibody responses to the SARS-CoV-2 S, N, membrane and ORF3a proteins while pediatric convalescent COVID patient cytokine responses were more often negatively correlated with antibody responses to the S, N and ORF3a proteins of SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.28.555120v1" target="_blank">Age-Associated Weaker Immunity to Coronaviruses is Characteristic of Children that Develop Multisystem Inflammatory Syndrome following SARS-CoV-2 Infection</a>
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<li><strong>Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses</strong> -
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The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of inter-individual variability. We identified six distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate and clearance rate, by clustering data from 810 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection, as well as an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during omicron infection, following vaccination, and following re-infection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.20.23294350v2" target="_blank">Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses</a>
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<li><strong>Risk factors for SARS-Cov-2 infection at a United Kingdom electricity-generating company: a test-negative design case-control study</strong> -
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Objectives Identify workplace risk factors for SARS-Cov-2 infection, using data collected by a United Kingdom electricity-generating company. Methods Using a test-negative design case-control study we estimated the odds ratios (OR) of infection by job category, site, test reason, sex, vaccination status, vulnerability, site outage, and site COVID-19 weekly risk rating, adjusting for age, test date and test type. Results From an original 80,077 COVID-19 tests, there were 70,646 included in the final analysis. Most exclusions were due to being visitor tests (5,030) or tests after an individual first tested positive (2,968). Women were less likely to test positive than men (OR=0.71; 95% confidence interval=0.58-0.86). Test reason was strongly associated with positivity and although not a cause of infection itself, due to differing test regimes by area it was a strong confounder for other variables. Compared to routine tests, tests due to symptoms were highest risk (94.99; 78.29-115.24), followed by close contacts (16.73; 13.80-20.29) and looser work contacts 2.66 (1.99-3.56). After adjustment, we found little difference in risk by job category, but some differences by site with three sites showing substantially lower risks, and one site showing higher risks in the final model. Conclusions Infection risk was not associated with job category. Vulnerable individuals were at slightly lower risk, tests during outages were higher risk, vaccination showed no evidence of an effect on testing positive, and site COVID-19 risk rating did not show an ordered trend in positivity rates.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.25.23294609v2" target="_blank">Risk factors for SARS-Cov-2 infection at a United Kingdom electricity-generating company: a test-negative design case-control study</a>
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<li><strong>Predictive Systems Biology Modeling: Unraveling Host Metabolic Disruptions and Potential Drug Targets in Acute Viral Infections</strong> -
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Background: Host response is critical to the onset, progression, and outcome of viral infections. Since viruses hijack the host cellular metabolism for their replications, we hypothesized that restoring host cell metabolism can efficiently reduce viral production. Results: Here, we present a viral-host Metabolic Modeling (vhMM) method to systematically evaluate the disturbances in host metabolism in viral infection and computationally identify targets for modulation by integrating genome-wide precision metabolic modeling and cheminformatics. We applied vhMM to SARS-CoV-2 infections and identified consistent changes in host metabolism and gene and endogenous metabolite targets between the original SARS-COV-2 and different variants (Alpha, Delta, and Omicron). Among six compounds predicted for repurposing, methotrexate, cinnamaldehyde, and deferiprone were tested in vitro and effective in inhibiting viral production with IC50 less than 4uM. Further, an analysis of real-world patient data showed that cinnamon usage significantly reduced the SARS-CoV-2 infection rate with an odds ratio of 0.65 [95%CI: 0.55~0.75]. Conclusions: These results demonstrated that vhMM is an efficient method for predicting targets and drugs for viral infections.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.24.550423v2" target="_blank">Predictive Systems Biology Modeling: Unraveling Host Metabolic Disruptions and Potential Drug Targets in Acute Viral Infections</a>
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<li><strong>Deep metric learning for few-shot X-ray image classification</strong> -
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Deep learning models have proven the potential to aid professionals with medical image analysis, including many image classification tasks. However, the scarcity of data in medical imaging poses a significant challenge, as the limited availability of diverse and comprehensive datasets hinders the development and evaluation of accurate and robust imaging algorithms and models. Few-shot learning approaches have emerged as a potential solution to address this issue. In this research, we propose to deploy the Generalized Metric Learning Model for Few-Shot X-ray Image Classification. The model comprises a feature extractor to embed images into a lower-dimensional space and a distance-based classifier for label assignment based on the relative distance of these embeddings. We extensively evaluate the model using various pre-trained convolutional neural networks (CNNs) and vision transformers (ViTs) as feature extractors. We also assess the performance of the commonly used distance-based classifiers in several few-shot settings. Finally, we analyze the potential to adapt the feature encoders to the medical domain with both supervised and self-supervised frameworks. Our model achieves 0.689 AUROC in 2-way 5-shot COVID-19 recognition task when combined with REMEDIS (Robust and Efficient Medical Imaging with Self-supervision) domain-adapted model as feature extractor, and 0.802 AUROC in 2-way 5-shot tuberculosis recognition task with domain-adapted DenseNet-121 model. Moreover, the simplicity and flexibility of our approach allows for easy improvement in the feature, either by incorporating other few-shot methods or new, powerful architectures into the pipeline.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.27.23294690v2" target="_blank">Deep metric learning for few-shot X-ray image classification</a>
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<li><strong>The role and influence of perceived experts in an anti-vaccine misinformation community</strong> -
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The role of perceived experts (i.e., medical professionals and biomedical scientists) as potential anti-vaccine influencers has not been characterized systematically. We describe the prevalence and importance of anti-vaccine perceived experts by constructing a coengagement network based on a Twitter data set containing over 4.2 million posts from April 2021. The coengagement network primarily broke into two large communities that differed in their stance toward COVID-19 vaccines, and misinformation was predominantly shared by the anti-vaccine community. Perceived experts had a sizable presence within the anti-vaccine community and shared academic sources at higher rates compared to others in that community. Perceived experts occupied important network positions as central anti-vaccine nodes and bridges between the anti- and pro-vaccine communities. Perceived experts received significantly more engagements than other individuals within the anti- and pro-vaccine communities and there was no significant difference in the influence boost for perceived experts between the two communities. Interventions designed to reduce the impact of perceived experts in spreading anti-vaccine misinformation may be warranted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.12.23292568v2" target="_blank">The role and influence of perceived experts in an anti-vaccine misinformation community</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>THE EFFECT OF ARGININE AND GLUTAMINE ON COVID-19 PATIENTS OUTCOME: A RANDOMIZED CLINICAL TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: Neomune<br/><b>Sponsors</b>: Universitas Sriwijaya; M. Djamil General Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of Obeldesivir in Children and Adolescents With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Obeldesivir<br/><b>Sponsor</b>: Gilead Sciences<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>KAND567 Versus Placebo in Subjects Hospitalized With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: KAND567; Drug: Microcrystalline cellulose<br/><b>Sponsor</b>: Kancera AB<br/><b>Terminated</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>Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Aerobic Exercise Training<br/><b>Sponsors</b>: University of Witten/Herdecke; Verein und Institut für Rehabilitationsforschung Norderney<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 Pilot Clinical Evaluation of Astepro® Nasal Spray for Management of Early SARS-CoV-2 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Experimental: Primary Cohort; Other: Placebo Comparator: Primary Cohort - Placebo<br/><b>Sponsor</b>: University of Chicago<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>Digital Health Literacy on COVID-19 for All: Co-creation and Evaluation of Interventions for Ethnic Minorities and Chinese People With Chronic Illnesses in Hong Kong</strong> - <b>Conditions</b>: Digital Health Literacy; COVID-19<br/><b>Intervention</b>: Behavioral: Digital health literacy intervention<br/><b>Sponsor</b>: The Hong Kong Polytechnic 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>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>: Influenza; COVID-19; Influenza Immunogencity; COVID-19 Immunogenicity<br/><b>Interventions</b>: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster); Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster); Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>: Duke University; Centers for Disease Control and Prevention; Arizona State University; University Hospitals Cleveland Medical Center; University of Pittsburgh; Washington University School of Medicine; Valleywise Health; VA Northeast Ohio Health Care; Senders Pediatrics<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 Vaccination Hesitancy in Adults With Sickle Cell Disease</strong> - <b>Conditions</b>: Sickle Cell Disease; COVID-19 Vaccine; Vaccine Hesitancy<br/><b>Intervention</b>: Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video<br/><b>Sponsors</b>: Duke University; American Society of Hematology<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>Leveraging Community Health Workers to Combat COVID-19 and Mental Health Misinformation in Haiti, Malawi, and Rwanda</strong> - <b>Conditions</b>: Mental Health; COVID-19; Misinformation<br/><b>Interventions</b>: Behavioral: Card-Sorting Activity (Pre-intervention design); Behavioral: SMS Crafting (Pre-intervention design); Behavioral: SMS Messaging<br/><b>Sponsors</b>: Harvard Medical School (HMS and HSDM); Partners in Health<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>Effect of Pulmonary Rehabilitation Among Post-COVID-19 Patients in a Tertiary Care Hospital in Bangladesh</strong> - <b>Condition</b>: Pulmonary Pathology<br/><b>Intervention</b>: Behavioral: Pulmonary Rehabilitation<br/><b>Sponsor</b>: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh<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>A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Varients in Healthy Individuals</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Intervention</b>: Biological: BNT162b2 (Omi XBB.1.5)<br/><b>Sponsors</b>: BioNTech SE; Pfizer<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>Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19.</strong> - <b>Condition</b>: Nervous System Diseases<br/><b>Interventions</b>: Drug: Tianeptine; Drug: Placebo<br/><b>Sponsors</b>: Military Institute od Medicine National Research Institute; ABM Industries<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>Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition</strong> - <b>Condition</b>: Cognitive Behavioral Therapy<br/><b>Intervention</b>: Behavioral: cognitive behavioral therapy<br/><b>Sponsor</b>: Tri-Service General Hospital<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>The Effectiveness of Natural Resources for Reducing Stress</strong> - <b>Conditions</b>: Distress, Emotional; COVID-19<br/><b>Interventions</b>: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure<br/><b>Sponsors</b>: Klaipėda University; Research Council of Lithuania<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>Study of LAU-7b for the Treatment of Long COVID in Adults</strong> - <b>Condition</b>: Long COVID<br/><b>Interventions</b>: Drug: LAU-7b for 3 cycles; Drug: LAU-7b for 1 cycle, then placebo; Other: Placebo for 3 cycles<br/><b>Sponsor</b>: Laurent Pharmaceuticals Inc.<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Arbidol increases the survival rate by mitigating inflammation in suckling mice infected with human coronavirus OC43 virus</strong> - Human coronavirus OC43 (HCoV-OC43) often causes common cold and is able to neuroinvasive, but it can also induce lower respiratory tract infections (LRTI) especially in children and the elderly adults with underlying diseases. HCoV-OC43 infections currently have no approved antiviral treatment. Arbidol (ARB) is a broad-spectrum antiviral and is an antiviral medication for the treatment of influenza used in Russia and China. Due to its multiple mechanisms of action, such as inhibition of viral…</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 assessment of a SARS-CoV-2 recombinant spike RBD protein vaccine (Abdala) in paediatric ages 3-18 years old: a double-blinded, multicentre, randomised, phase 1/2 clinical trial (ISMAELILLO study)</strong> - BACKGROUND: COVID-19 in paediatric ages could result in hospitalizations and death. In addition, excluding children from vaccination could turn them into reservoirs of the SARS-COV-2. Safe and effective COVID-19 vaccines are urgently needed for large-scale paediatric vaccination. ISMAELILLO study aimed to evaluate safety and immunogenicity of two strengths of a new recombinant receptor-binding domain (RBD) protein vaccine (Abdala) in paediatric population.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Growth hormone-releasing hormone antagonist MIA-602 inhibits inflammation induced by SARS-CoV-2 spike protein and bacterial lipopolysaccharide synergism in macrophages and human peripheral blood mononuclear cells</strong> - COVID-19 is characterized by an excessive inflammatory response and macrophage hyperactivation, leading, in severe cases, to alveolar epithelial injury and acute respiratory distress syndrome. Recent studies have reported that SARS-CoV-2 spike (S) protein interacts with bacterial lipopolysaccharide (LPS) to boost inflammatory responses in vitro, in macrophages and peripheral blood mononuclear cells (PBMCs), and in vivo. The hypothalamic hormone growth hormone-releasing hormone (GHRH), in…</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>Retrospective observational study of changes in serum cytokines and adiponectin with continuous plasma exchange with dialysis therapy for severe COVID-19</strong> - CONCLUSION: Our results suggest that cPED therapy is an effective treatment for COVID-19.</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 nucleotide-sensing Toll-Like Receptor 9/Toll-Like Receptor 7 system is a potential therapeutic target for IgA nephropathy</strong> - The progression determinants of IgA nephropathy (IgAN) are still not fully elucidated. We have previously demonstrated that the mucosal activation of toll-like receptor (TLR) 9, which senses microbial unmethylated CpG DNA, influences progression by producing aberrantly-glycosylated IgA. However, numerous recent reports of patients with IgAN presenting with gross hematuria after the mRNA vaccination for coronavirus disease 2019 suggest that the RNA-sensing system also exacerbates IgAN. Here, 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>Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine</strong> - Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed. With >99% encapsulation, RALA-SME was administered via intradermal injection…</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>Arbidol: The current demand, strategies, and antiviral mechanisms</strong> - CONCLUSION: ARB is a broad-spectrum antiviral drug that inhibits several viruses in vivo and in vitro, with high safety profile and low resistance; the antiviral mechanisms of ARB deserve to be further explored and more high-quality clinical studies are required to establish the efficacy and safety of ARB.</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>Pathophysiology and clinical management of coronavirus disease (COVID-19): a mini-review</strong> - An unprecedented global pandemic caused by a novel coronavirus named SARS-CoV-2 has created a severe healthcare threat and become one of the biggest challenges to human health and the global economy. As of July 2023, over 767 million confirmed cases of COVID-19 have been diagnosed, including more than 6.95 million deaths. The S protein of this novel coronavirus binds to the ACE2 receptor to enter the host cells with the help of another transmembrane protease TMPRSS2. Infected subjects that can…</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>Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial</strong> - BACKGROUND: Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows:…</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>Development of ELISA-Based Assay for Detection of SARS-CoV-2 Neutralizing Antibody</strong> - Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the plasma B cells to secrete specific antibodies against the viral antigen. However, not all antibodies can prevent the virus from entering the cells. The subpopulation of antibodies which blocks the entry of the virus into host cells is termed neutralizing antibodies (NAbs). The gold standard test for the detection of NAbs is the viral plaque reduction and neutralization test; however, various other methods…</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 natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2</strong> - The Coronavirus Disease 2019 (COVID-19) pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins…</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 hope and hype of ellagic acid and urolithins as ligands of SARS-CoV-2 Nsp5 and inhibitors of viral replication</strong> - Non-structural protein 5 (Nsp5) is a cysteine protease that plays a key role in SARS-CoV-2 replication, suppressing host protein synthesis and promoting immune evasion. The investigation of natural products as a potential strategy for Nsp5 inhibition is gaining attention as a means of developing antiviral agents. In this work, we have investigated the physicochemical properties and structure-activity relationships of ellagic acid and its gut metabolites, urolithins A-D, as ligands of Nsp5….</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>Customizably designed multibodies neutralize SARS-CoV-2 in a variant-insensitive manner</strong> - The COVID-19 pandemic evolves constantly, requiring adaptable solutions to combat emerging SARS-CoV-2 variants. To address this, we created a pentameric scaffold based on a mammalian protein, which can be customized with up to 10 protein binding modules. This molecular scaffold spans roughly 20 nm and can simultaneously neutralize SARS-CoV-2 Spike proteins from one or multiple viral particles. Using only two different modules targeting the Spike’s RBD domain, this construct outcompetes human…</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>Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 - inhibition of SARS-CoV-2 is cell line-specific</strong> - Recently, Tummino et al. reported that 34 compounds, including Chloroquine and Fluoxetine, inhibit SARS-CoV-2 replication by inducing phospholipidosis, although Chloroquine failed to suppress viral replication in Calu-3 cells and patients. In contrast, Fluoxetine represses viral replication in human precision-cut lung slices (PCLS) and Calu-3 cells. Thus, it is unlikely that these compounds have similar mechanisms of action. Here, we analysed a subset of these compounds in the viral replication…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Investigation of the Host Kinome Response to Coronavirus Infection Reveals PI3K/mTOR Inhibitors as Betacoronavirus Antivirals</strong> - Host kinases play essential roles in the host cell cycle, innate immune signaling, the stress response to viral infection, and inflammation. Previous work has demonstrated that coronaviruses specifically target kinase cascades to subvert host cell responses to infection and rely upon host kinase activity to phosphorylate viral proteins to enhance replication. Given the number of kinase inhibitors that are already FDA approved to treat cancers, fibrosis, and other human disease, they represent an…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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