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176 lines
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<title>12 September, 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Nuclearization of maternal support networks in the UK and the US during the COVID-19 pandemic: impact on women’s financial and emotional wellbeing</strong> -
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<div>
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The social isolation resulting from governments’ responses to the COVID-19 pandemic likely limited support available to mothers. Evidence suggests tasks like childcare and domestic work fell disproportionately on mothers during the pandemic, with consequences for their wellbeing. We explore how the pandemic affected emotional and practical support available to mothers between March and August 2020 and whether changes in support are associated with changes in their paid work and mental health. Data were collected in August 2020 from 1528 UK and US mothers with at least one child under 5-years using a cross-sectional survey and are analysed using regression models. Women’s in-person contact with support networks decreased, while virtual interactions increased. Most mothers experienced a ‘nuclearization’ of in-person support: childcare from fathers and siblings increased or remained constant but decreased from the grandparental generation. Women receiving less support during the pandemic had higher odds of reducing participation in paid work. Associations between support and mental health are limited. We also identify women who concurrently experienced reduced support and increased need for help, representing a particularly vulnerable group. The nuclearization of maternal social networks likely increased physical and emotional pressures on the immediate family, risking parental burnout and affecting reductions in female participation in paid labour. There is a need for reliable and affordable childcare options that help reduce women’s burden of unpaid care labour, allowing them to re-enter (or remain in) paid labour.
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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/ne2kv/" target="_blank">Nuclearization of maternal support networks in the UK and the US during the COVID-19 pandemic: impact on women’s financial and emotional wellbeing</a>
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</div></li>
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<li><strong>The high infectivity of the SARS-CoV-2 Omicron variant is associated with an exclusive S477N spike receptor-binding domain mutation</strong> -
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<div>
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The spike glycoprotein receptor-binding domain (RBD) of SARS-CoV-2 facilitates viral binding to the ACE2 receptor and mediates viral infectivity. The Delta and Omicron variants of concern are the most infectious strains, presenting mutated amino acid residues in their spike RBD. The Omicron variant quickly dominated the COVID-19 pandemic, indicating its greater spreadability. Omicron spreading might be associated with mutational substitutions at spike RBD residues. We employed in silico molecular dynamics (MD) simulation of the spike RBD-ACE2 interaction to compare the impact of specific mutations of the Delta and Omicron variants. The MD of the spike-ACE2 interaction showed the following: i) the amino acid profile involved in the spike-ACE2 interaction differs between Delta and Omicron; ii) the Omicron variant establishes several additional interactions, highlighting the spike RBD (S477), which is a flexible mutational residue. Since the S477N mutation is exclusive to Omicron, which may initiate binding with ACE2, the increased infectivity of Omicron might be associated not only with a mutated RBD but also with unmutated (e.g., G476 and L492) residues, initiating binding due to the influence of the N477 mutation. Compared to previous variants, Omicron N477 residue represents a novelty within the spike-ACE2 interaction dynamics interface.
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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/10.1101/2023.09.11.557161v1" target="_blank">The high infectivity of the SARS-CoV-2 Omicron variant is associated with an exclusive S477N spike receptor-binding domain mutation</a>
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</div></li>
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<li><strong>Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires</strong> -
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<div>
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Antibodies and helper T cells play important roles in SARS-CoV-2 infection and vaccination. We sequenced B- and T-cell receptor repertoires (BCR/TCR) from the blood of 251 infectees, vaccinees, and controls to investigate whether features of these repertoires could predict subjects' SARS-CoV-2 neutralizing antibody titer (NAbs), as measured by enzyme-linked immunosorbent assay (ELISA). We sequenced recombined immunoglobulin heavy-chain (IGH), TCRbeta (TRB), and TCRdelta (TRD) genes in parallel from all subjects, including select B- and T-cell subsets in most cases, with a focus on their hypervariable CDR3 regions, and correlated this AIRRseq data with demographics and clinical findings from subjects' electronic health records. We found that age affected NAb levels in vaccinees but not infectees. Intriguingly, we found that vaccination, but not infection, has a substantial effect on non-productively recombined IGHs, suggesting a vaccine effect that precedes clonal selection. We found that repertoires' binding capacity to known SARS-CoV-2-specific CD4+ TRBs performs as well as the best hand-tuned fuzzy matching at predicting a protective level of NAbs, while also being more robust to repertoire sample size and not requiring hand-tuning. The overall conclusion from this large, unbiased, clinically well annotated dataset is that B- and T-cell adaptive responses to SARS-CoV-2 infection and vaccination are surprising, subtle, and diffuse. We discuss methodological and statistical challenges faced in attempting to define and quantify such strong-but-diffuse repertoire signatures and present tools and strategies for addressing these challenges.
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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/10.1101/2023.09.08.556703v1" target="_blank">Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires</a>
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</div></li>
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<li><strong>Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1</strong> -
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<div>
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The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential to evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live SARS-CoV-2 neutralization assay to compare the neutralization evasion ability of BA.2.86 with other emerged SARS-CoV-2 subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, and XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 and FL.1.5.1. Our results show that BA.2.86 is less neutralization evasive than XBB sublineages. Among all the tested variants, CH.1.1 exhibits the greatest neutralization evasion. In comparison to XBB.1.5, the more recent XBB descendants, particularly EG.5.1 and FL.1.5.1, display increased resistance to neutralization induced by parental COVID-19 mRNA vaccine and a BA.5-Bivalent-booster. In contrast, XBC.1.6 shows a slight reduction but remains comparable sensitivity to neutralization when compared to BA.5. Furthermore, a recent XBB.1.5-breakthrough infection significantly enhances the breadth and potency of cross-neutralization. These findings reinforce the expectation that the upcoming XBB.1.5 mRNA vaccine would likely boost the neutralization of currently circulating variants, while also underscoring the critical importance of ongoing surveillance to monitor the evolution and immune evasion potential of SARS-CoV-2 variants.
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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/10.1101/2023.09.10.557047v1" target="_blank">Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1</a>
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</div></li>
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<li><strong>Protocol for primary human lung organoid-derived air-liquid interface in vitro model to study response to SARS-CoV-2</strong> -
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<div>
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This article presents a comprehensive protocol for establishing primary human lung organoid-derived air-liquid interface (ALI) cultures from cryopreserved human lung tissue. These cultures serve as a physiologically relevant model to study human airway epithelium in vitro. The protocol encompasses lung tissue cryostorage, tissue dissociation, lung epithelial organoid generation, and ALI culture differentiation. It also demonstrates SARS-CoV-2 infection in these cultures as an example of their utility. Quality control steps, ALI characterization, and technical readouts for monitoring virus response are included in the study. For additional details on the use and execution of this protocol, please refer to Diana Cadena Castaneda et al. (https://doi.org/10.1016/j.isci.2023.107374).
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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/10.1101/2023.09.10.557067v1" target="_blank">Protocol for primary human lung organoid-derived air-liquid interface in vitro model to study response to SARS-CoV-2</a>
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</div></li>
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<li><strong>Enhanced Omicron subvariant cross-neutralization efficacy of a monovalent SARS-CoV-2 BA.4/5 mRNA vaccine encoding a noncleaved, nonfusogenic spike antigen</strong> -
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<div>
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The rapid emergence of diverse SARS-CoV-2 variants, notably the Omicron variant, poses challenges to vaccine development. Here, we present a noncleaved, nonfusogenic spike (S) protein eliciting robust B- and T-cell immune responses against Omicron BA.5. The antigen incorporates the R685S and R815A mutations, effectively preventing the shedding of the S1 subunit and eliminating fusogenic activity of the resulting S antigen, termed S(SA). Through reverse genetic analysis, we found that the noncleaved form S protein with the R685S mutation enhances ACE2-dependent viral entry in vitro compared to the wild-type S protein, without increasing the virulence of the mutant virus in mice. The mRNA vaccine encoding the Omicron BA.4/5 S(SA) antigen conferred protective immunity in mice following two doses of 1 ug psi-UTP- or UTP-incorporated mRNA vaccines. Despite a roughly 6-fold reduction in neutralizing potency, both mRNA vaccines exhibited broad neutralizing efficacy against Omicron subvariants, including the XBB lineage variants XBB.1.5 and XBB.1.16.
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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/10.1101/2023.09.10.557088v1" target="_blank">Enhanced Omicron subvariant cross-neutralization efficacy of a monovalent SARS-CoV-2 BA.4/5 mRNA vaccine encoding a noncleaved, nonfusogenic spike antigen</a>
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</div></li>
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<li><strong>Bayesian phylogenetics on globally emerging SARS-CoV-2 variant BA.2.86 suggest global distribution and rapid evolution</strong> -
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<div>
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Using bioinformatic pipelines and Bayseian phylogenetic analyses, we characterized a SARS-CoV-2 variant designated by the World Health Organization as a variant under monitoring in August 2023. Here we analyze the genomes of this SARS-CoV-2 variant, BA.2.86, deposited into GISAID within the two weeks of its emergence (2023-08-14 first submission to 2023-08-31), including the first BA.2.86 genome reported from a traveler originating from Japan. We present bioinformatics methods using publicly available tools to help analysts identify the lineage-defining 12 nucleotide insertion (S:Ins16MPLF), which is often masked by most bioinformatics pipelines. We also applied maximum-likelihood and Bayesian phylogenetics to demonstrate the high mutational rate of the tree branch leading to the emergence of BA.2.86, hinting at possible origins, and predict that BA.2.86 emerged around May 2023 and spread globally rapidly. Taken together, these results provide a framework for more rigorous bioinformatics approaches for teams performing genomic surveillance on viral respiratory pathogens.
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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/10.1101/2023.09.08.556912v1" target="_blank">Bayesian phylogenetics on globally emerging SARS-CoV-2 variant BA.2.86 suggest global distribution and rapid evolution</a>
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</div></li>
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<li><strong>Characterization of SARS-CoV-2 Convalescent Patients’ Serological Repertoire Reveals High Prevalence of Iso-RBD Antibodies</strong> -
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<div>
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While our understanding of SARS-CoV-2 pathogenesis and antibody responses following infection and vaccination has improved tremendously since the outbreak in 2019, the sequence identities and relative abundances of the individual constituent antibody molecules in circulation remain understudied. Using Ig-Seq, we proteomically profiled the serological repertoire specific to the whole ectodomain of SARS-CoV-2 prefusion-stabilized spike (S) as well as to the receptor binding domain (RBD) over a 6-month period in four subjects following SARS-CoV-2 infection before SARS-CoV-2 vaccines were available. In each individual, we identified between 59 and 167 unique IgG clonotypes in serum. To our surprise, we discovered that ~50% of serum IgG specific for RBD did not recognize prefusion-stabilized S (referred to as iso-RBD antibodies), suggesting that a significant fraction of serum IgG targets epitopes on RBD inaccessible on the prefusion-stabilized conformation of S. On the other hand, the abundance of iso-RBD antibodies in nine individuals who received mRNA-based COVID-19 vaccines encoding prefusion-stabilized S was significantly lower (~8%). We expressed a panel of 12 monoclonal antibodies (mAbs) that were abundantly present in serum from two SARS-CoV-2 infected individuals, and their binding specificities to prefusion-stabilized S and RBD were all in agreement with the binding specificities assigned based on the proteomics data, including 1 iso-RBD mAb which bound to RBD but not to prefusion-stabilized S. 2 of 12 mAbs demonstrated neutralizing activity, while other mAbs were non-neutralizing. 11 of 12 mAbs also bound to S (B.1.351), but only 1 maintained binding to S (B.1.1.529). This particular mAb binding to S (B.1.1.529) 1) represented an antibody lineage that comprised 43% of the individual's total S-reactive serum IgG binding titer 6 months post-infection, 2) bound to the S from a related human coronavirus, HKU1, and 3) had a high somatic hypermutation level (10.9%), suggesting that this antibody lineage likely had been elicited previously by pre-pandemic coronavirus and was re-activated following the SARS-CoV-2 infection. All 12 mAbs demonstrated their ability to engage in Fc-mediated effector function activities. Collectively, our study provides a quantitative overview of the serological repertoire following SARS-CoV-2 infection and the significant contribution of iso-RBD antibodies, demonstrating how vaccination strategies involving prefusion-stabilized S may have reduced the elicitation of iso-RBD serum antibodies which are unlikely to contribute to protection.
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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/10.1101/2023.09.08.556349v1" target="_blank">Characterization of SARS-CoV-2 Convalescent Patients’ Serological Repertoire Reveals High Prevalence of Iso-RBD Antibodies</a>
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</div></li>
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<li><strong>The role of ion dissolution in metal and metal oxide surface inactivation of SARS-CoV-2</strong> -
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<div>
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Antiviral surface coatings are under development to prevent viral fomite transmission from high-traffic touch surfaces in public spaces. Copper's antiviral properties have been widely documented; but the antiviral mechanism of copper surfaces is not fully understood. We screened a series of metal and metal oxide surfaces for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19). Copper and copper oxide surfaces exhibited superior anti-SARS-CoV-2 activity; however, level of antiviral activity was dependent upon the composition of the carrier solution used to deliver virus inoculum. We demonstrate that copper ions released into solution from test surfaces can mediate virus inactivation, indicating a copper ion dissolution-dependent antiviral mechanism. Level of antiviral activity is, however, not dependent on the amount of copper ions released into solution per se. Instead, our findings suggest that degree of virus inactivation is dependent upon copper ion complexation with other biomolecules (e.g., proteins/metabolites) in the virus carrier solution that compete with viral components. Although using tissue culture-derived virus inoculum is experimentally convenient to evaluate the antiviral activity of copper-derived test surfaces, we propose that the high organic content of tissue culture medium reduces the availability of "uncomplexed" copper ions to interact with the virus, negatively affecting virus inactivation and hence surface antiviral performance. We propose that laboratory antiviral surface testing should include virus delivered in a physiologically relevant carrier solution (saliva or nasal secretions when testing respiratory viruses) to accurately predict real-life surface antiviral performance when deployed in public spaces.
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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/10.1101/2023.09.08.556901v1" target="_blank">The role of ion dissolution in metal and metal oxide surface inactivation of SARS-CoV-2</a>
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</div></li>
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<li><strong>Brain infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern is a severe outcome in K18-hACE2 transgenic mice</strong> -
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<div>
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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, 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 and brain of these animals. 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: We established that Wild-type, Delta, and Omicron infect the lung and brain of K18-hACE2 mice. At 3 dpi, mice infected with the Omicron variant show lower levels of viral RNA than those infected with Wild-type or Delta in the lung and brain. However, they still demonstrate upregulation of cytokines and chemokines, indicating that the Omicron variant can induce pulmonary and neuronal inflammation despite reduced viral proliferation after infection. At the humane endpoint/8dpi, there is a significant increase in viral RNA in mice infected with the Wild-type or Delta variant brains. However, viral RNA levels in Omicron-infected mice did not increase significantly as compared to 3dpi, and the expression of cytokines and chemokines in the brain, olfactory bulb, and medulla oblongata was downregulated, suggesting that infection by the Omicron variant results in attenuated neuroinflammation as compared with Wild-type and Delta.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556906v1" target="_blank">Brain infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern is a severe outcome in K18-hACE2 transgenic mice</a>
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<li><strong>A Bayesian approach to identifying the role of hospital structure and staff interactions in nosocomial transmission of SARS-CoV-2</strong> -
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Nosocomial infections threaten patient safety, and were widely reported during the COVID-19 pandemic. Effective hospital infection control requires a detailed understanding of the role of different transmission pathways, yet these are poorly quantified. Using patient and staff data from a large UK hospital we demonstrate a method to infer unobserved epidemiological event times efficiently and disentangle the infectious pressure dynamics by ward. A stochastic individual-level, continuous-time state-transition model was constructed to model transmission of SARS-CoV-2, incorporating a dynamic staff-patient contact network as time-varying parameters. A Metropolis-Hastings MCMC algorithm was used to estimate transmission rate parameters associated with each possible source of infection, and the unobserved infection and recovery times. We found that the total infectious pressure exerted on an individual in a ward varied over time, as did the primary source of transmission. There was marked heterogeneity between wards; each ward experienced unique infectious pressure over time. Hospital infection control should consider the role of between-ward movement of staff as a key infectious source of nosocomial infection for SARS-CoV-2. With further development, this method could be implemented routinely for real-time monitoring of nosocomial transmission and to evaluate interventions.
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</p>
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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.medrxiv.org/content/10.1101/2023.09.11.23295353v1" target="_blank">A Bayesian approach to identifying the role of hospital structure and staff interactions in nosocomial transmission of SARS-CoV-2</a>
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<li><strong>Comparison of COVID-19 and Influenza-Related Outcomes in the United States during Fall-Winter 2022-2023</strong> -
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Background: Three years into the pandemic, SARS-COV-2 remains a significant burden in comparison to other respiratory illnesses; however, many of the monitoring tools available during the early phase of the COVID-19 pandemic have been phased out, making it more difficult to track the current burden of outpatient medical encounters and hospitalizations, especially for at-risk groups. The objective of this analysis was to characterize the frequency and severity of medically-attended COVID-19 and influenza during peak influenza activity in the pediatric (0-17), adult (18-64), and older adult (65+) populations and characterize the prevalence of underlying medical conditions among patients hospitalized with COVID-19. Methods: This was a cross-sectional analysis of individuals in the Veradigm Health Insights EHR Database linked to Komodo claims data with a medical encounter of claim between October 1, 2022, and March 31, 2023. We captured age, sex, and underlying medical conditions associated with higher risk for severe COVID-19 during a 12-month baseline period. We identified patients with medical encounters with a diagnosis of COVID-19 or influenza between October 1, 2022, and March 31, 2023, and stratified them into 5 mutually exclusive categories based on the highest level of care received with that diagnosis during the season (intensive care unit [ICU] > hospitalization without ICU > emergency department > urgent care > other outpatient). Results: Among the 23,526,196 individuals in the dataset, 5.0% had a COVID-19-related medical encounter, and 3.0% had an influenza-related medical encounter during the 6 month observation period. The incidence of hospitalizations with a COVID-19 diagnosis was 4.6 times higher than the incidence of hospitalizations with an influenza diagnosis. Hospitalizations with COVID-19 were higher in all age groups. Nearly all adults hospitalized with COVID-19 had at least one underlying medical condition, but 25.8% of 0-5-year-olds and 18.3% of 6-17-year-olds had no underlying medical conditions. Conclusions: COVID-19 continues to place a heavy burden on the United States healthcare system and was associated with more medical encounters in all age groups, including hospitalizations, than influenza during a 6-month period that included the 2022-2023 peak influenza activity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.08.23295262v1" target="_blank">Comparison of COVID-19 and Influenza-Related Outcomes in the United States during Fall-Winter 2022-2023</a>
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<li><strong>A Network Analysis of Molecular Interactions to Study the Development of New-onset Diabetes and Hypertension after COVID-19 Infection Using Bioinformatics Tools.</strong> -
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Introduction: The association between COVID-19 infection and the development of new-onset diabetes and hypertension is an emerging area of research. However, a comprehensive understanding of the underlying molecular mechanisms is still lacking. Network analysis using bioinformatics tools can provide valuable insights into the complex molecular interactions involved in these conditions after COVID-19 infection. Objective: This study aims to use bioinformatics tools to analyze the network of molecular interactions related to new-onset diabetes and hypertension following COVID-19 infection. Methods: Data from publicly available databases were utilized, including gene expression profiles and protein-protein interaction information. Differential expression analysis was performed to identify genes that were differentially expressed in individuals with new-onset diabetes and hypertension after COVID-19 infection compared to healthy controls. A protein interaction network was constructed using bioinformatics tools to explore the functional relationships among the identified differentially expressed genes. Results: The network analysis revealed several key proteins and pathways related to the pathogenesis of new-onset diabetes and hypertension after COVID-19 infection. Notably, proteins involved in insulin signaling, glucose metabolism, inflammation, and blood pressure regulation were found to be prominently associated. The signaling pathway and the renin-angiotensin system were identified as key pathways in this context. Conclusion: This study provides insights by showing a network-based perspective on the molecular interactions involved in the development of new-onset diabetes and hypertension after COVID-19 infection. Keywords: COVID-19 infection, diabetes, hypertension, network analysis, bioinformatics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.10.23295323v1" target="_blank">A Network Analysis of Molecular Interactions to Study the Development of New-onset Diabetes and Hypertension after COVID-19 Infection Using Bioinformatics Tools.</a>
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<li><strong>MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management</strong> -
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The COVID-19 pandemic brought not only global devastation but also an unprecedented infodemic of false or misleading information that spread rapidly through online social networks. Network analysis plays a crucial role in the science of fact-checking by modeling and learning the risk of infodemics through statistical processes and computation on mega-sized graphs. This paper proposes MEGA, <i>M</i>achine Learning-<i>E</i>nhanced <i>G</i>raph <i>A</i>nalytics, a framework that combines feature engineering and graph neural networks to enhance the efficiency of learning performance involving massive graphs. Infodemic risk analysis is a unique application of the MEGA framework, which involves detecting spambots by counting triangle motifs and identifying influential spreaders by computing the distance centrality. The MEGA framework is evaluated using the COVID-19 pandemic Twitter dataset, demonstrating superior computational efficiency and classification accuracy.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.10.24.20215061v6" target="_blank">MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management</a>
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<li><strong>Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform</strong> -
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Reverse genetic systems enable the engineering of RNA virus genomes and are instrumental in studying RNA virus biology. With the recent outbreak of the COVID-19 pandemic, already established methods were challenged by the large genome of SARS-CoV-2. Herein we present an elaborated strategy for the rapid and straightforward rescue of recombinant plus-stranded RNA viruses with high sequence fidelity, using the example of SARS-CoV-2. The strategy called CLEVER (CLoning-free and Exchangeable system for Virus Engineering and Rescue) is based on the intracellular recombination of transfected overlapping DNA fragments allowing the direct mutagenesis within the initial PCR-amplification step. Furthermore, by introducing a linker fragment (harboring all heterologous sequences) viral RNA can directly serve as a template for manipulating and rescuing recombinant mutant virus, without any cloning step. Overall, this strategy will facilitate recombinant SARS-CoV-2 rescue and accelerate its manipulation. Using our protocol, newly emerging variants can quickly be engineered to further elucidate their biology. To demonstrate its potential as a reverse genetics platform for plus-stranded RNA viruses, the protocol has been successfully applied for the cloning-free rescue of recombinant Chikungunya and Dengue virus.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.11.540343v4" target="_blank">Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform</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>A 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: hAd5-S-Fusion+N-ETSD; Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>: ImmunityBio, Inc.<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>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>: Immunosuppression; COVID-19<br/><b>Intervention</b>: Biological: NVX-CoV2372<br/><b>Sponsors</b>: University of Wisconsin, Madison; Novavax<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>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; 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>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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>: Bronchoalveolar Lavage<br/><b>Intervention</b>: Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>: Mohamed Abd Elmoniem Mohamed; Marwa Salah Abdelrazek Ghanem; Mohammad Khairy El-Badrawy; Tamer Ali Elhadidy; Dalia Abdellateif Abdelghany<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 Phase 1 Study to Assess the Safety, Reactogenicity, and Immunogenicity of a SARS-CoV-2 Booster Vaccine (LEM-mR203) in Healthy Adults</strong> - <b>Conditions</b>: COVID-19 Infection; COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>: Biological: LEM-mR203; Biological: Placebo<br/><b>Sponsor</b>: Lemonex<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); Johns Hopkins Bloomberg School of Public Health; National Institutes of Health (NIH)<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Determine the Tolerability of Intranasal LMN-301</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: LMN-301<br/><b>Sponsor</b>: Lumen Bioscience, 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>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>Long COVID Immune Profiling</strong> - <b>Conditions</b>: Long COVID; POTS - Postural Orthostatic Tachycardia Syndrome; Autonomic Dysfunction<br/><b>Interventions</b>: Diagnostic Test: IL-6; Diagnostic Test: cytokines (IL-17, and IFN-ɣ); Behavioral: Compass 31<br/><b>Sponsors</b>: Vanderbilt University Medical Center; American Heart Association<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>: Critical Illness; COVID-19; PICS; Cognitive Impairment; Mental Health Impairment; Weakness, Muscle; Dysbiosis<br/><b>Intervention</b>: Behavioral: Fermented Food Diet<br/><b>Sponsor</b>: Mayo Clinic<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Farnesoid X receptor enhances epithelial ACE2 expression and inhibits viral-induced IL-6 secretion: implications for intestinal symptoms of SARS-CoV-2</strong> - CONCLUSION: By virtue of its ability to modulate epithelial ACE2 expression and inhibit virus-mediated pro-inflammatory cytokine release, FXR represents a promising target for development of new approaches to prevent intestinal manifestations of SARS-CoV-2.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting spike glycans to inhibit SARS-CoV2 viral entry</strong> - SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety…</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>PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell- and tissue-specific manner</strong> - ADP-ribosyltransferases (ARTs) mediate the transfer of ADP-ribose from NAD^(+) to protein or nucleic acid substrates. This modification can be removed by several different types of proteins, including macrodomains. Several ARTs, also known as PARPs, are stimulated by interferon indicating ADP-ribosylation is an important aspect of the innate immune response. All coronaviruses (CoVs) encode for a highly conserved macrodomain (Mac1) that is critical for CoVs to replicate and cause disease,…</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>Efficacy and safety evaluation of Azvudine in the prospective treatment of COVID-19 based on four phase III clinical trials</strong> - Azvudine (FNC) is a synthetic nucleoside analog used to treat adult patients living with human immunodeficiency virus-1 (HIV-1) infection with high viral load. After phosphorylation, Azvudine inhibits RNA-dependent RNA polymerase, leading to the discontinuation of RNA chain synthesis in viruses. In addition, Azvudine is the first dual-target nucleoside oral drug worldwide to simultaneously target reverse transcriptase and viral infectivity factors in the treatment of HIV infection. On 9 August…</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>Altered DNA methylation underlies monocyte dysregulation and innate exhaustion memory in sepsis</strong> - Innate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression in concert with emergency hematopoiesis. Epigenetic changes, notably in the form of histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA…</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>In Vivo Antiviral Efficacy of LCTG-002, a Pooled, Purified Human Milk Secretory IgA product, Against SARS-CoV-2 in a Murine Model of COVID-19</strong> - Immunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosal compartments including the respiratory tract, with the secretory form of IgA (sIgA) being dominant and uniquely stable in these environments. sIgA is naturally found in human milk, which could be considered a global resource for this biologic, justifying the development of human milk sIgA as a dedicated airway therapeutic for respiratory infections such as SARS-CoV-2. In the present study, methods were therefore developed…</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>Cationic Chitosan Derivatives for the Inactivation of HIV-1 and SARS-CoV-2 Enveloped Viruses</strong> - Cationic chitosan derivatives have been widely studied as potential antimicrobial agents. However, very little is known about their antiviral activity and mode of action against enveloped viruses. We investigated the ability of hydroxypropanoic acid-grafted chitosan (HPA-CS) and N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) to inactivate enveloped viruses like the human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 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>Preventive treatment of coronavirus disease-2019 virus using coronavirus disease-2019-receptor-binding domain 1C aptamer by suppress the expression of angiotensin-converting enzyme 2 receptor</strong> - The cause of the worldwide coronavirus disease-2019 (COVID-19) pandemic is the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is known to employ the same entry portal as SARS-CoV, which is the type 1 transmembrane angiotensin-converting enzyme 2 (ACE2) receptor. The receptor-binding domain (RBD) is located on the spike S-protein’s S1 subunit of the spike glycoprotein. The most important and effective therapy method is inhibiting the interaction between the ACE2 receptor and 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>Natural PAK1 inhibitors: potent anti-inflammatory effectors for prevention of pulmonary fibrosis in COVID-19 therapy</strong> - One of the main efforts of scientists to study drug development is the discovery of novel antiviral agents that could be beneficial in the struggle against viruses that cause diseases in humans. Natural products are complex metabolites that are designed and synthesised by different sources in an attempt to optimise nature. Recently, natural products are still a source of biologically active molecules, facilitating drug discovery. A p21-activating kinase PAK1 is a key regulator of cytoskeletal…</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>Nirmatrelvir/ritonavir-induced elevation of blood tacrolimus levels in a patient in the maintenance phase post liver transplantation</strong> - Nirmatrelvir is an orally administered anti-SARS-CoV-2 drug used in combination with ritonavir, the drug-metabolizing cytochrome P450 (CYP) 3A inhibitor, to evade metabolism and extend bioavailability. Meanwhile, the immunosuppressant tacrolimus is a CYP3A4/5 substrate, and CYP3A inhibition results in drug-drug interactions. Herein, we report the case of a coronavirus disease 19 (COVID-19) patient in the maintenance phase post liver transplantation, receiving tacrolimus treatment, with a marked…</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>Comparison of Zinc Oxide Nanoparticle Integration into Non-Woven Fabrics Using Different Functionalisation Methods for Prospective Application as Active Facemasks</strong> - The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP…</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>Membrane-Targeting Perylenylethynylphenols Inactivate Medically Important Coronaviruses via the Singlet Oxygen Photogeneration Mechanism</strong> - Perylenylethynyl derivatives have been recognized as broad-spectrum antivirals that target the lipid envelope of enveloped viruses. In this study, we present novel perylenylethynylphenols that exhibit nanomolar or submicromolar antiviral activity against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and feline infectious peritonitis virus (FIPV) in vitro. Perylenylethynylphenols incorporate into viral and cellular membranes and block the entry of the virus into the host cell….</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>Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?</strong> - Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE-AAT) in which the two proteins are covalently bound. The lack of this complex, together with 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>Small Molecules Targeting Viral RNA</strong> - The majority of antivirals available target viral proteins; however, RNA is emerging as a new and promising antiviral target due to the presence of highly structured RNA in viral genomes fundamental for their replication cycle. Here, we discuss methods for the identification of RNA-targeting compounds, starting from the determination of RNA structures either from purified RNA or in living cells, followed by in silico screening on RNA and phenotypic assays to evaluate viral inhibition. Moreover,…</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>Screening, Synthesis and Biochemical Characterization of SARS-CoV-2 Protease Inhibitors</strong> - The severe acute respiratory syndrome-causing coronavirus 2 (SARS-CoV-2) papain-like protease (PL^(pro)) and main protease (M^(pro)) play an important role in viral replication events and are important targets for anti-coronavirus drug discovery. In search of these protease inhibitors, we screened a library of 1300 compounds using a fluorescence thermal shift assay (FTSA) and identified 53 hits that thermally stabilized or destabilized PL^(pro). The hit compounds structurally belonged to two…</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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