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<title>20 February, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Robust SARS-CoV-2 Neutralizing Antibodies Sustained through Three Months Post XBB.1.5 mRNA Vaccine Booster</strong> -
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SARS-CoV-2-neutralizing antibodies were substantially expanded one month after a shot of XBB.1.5 monovalent mRNA vaccine (XBB.1.5 MV) booster, but the durability of this response remained unknown. Here, we addressed this question by performing neutralization assays on four viral variants (D614G, BA.5, XBB.1.5, and JN.1) using sera from 39 adult participants obtained at ~1 month and ~3 months post an XBB.1.5 MV booster. Our findings indicate that the resultant neutralizing antibody titers were robust and generally maintained at stable levels for the study period, similar to those following XBB infection. Importantly, this durability of neutralizing antibody titers contrasts with the decline observed after a booster of the original monovalent or BA.5 bivalent mRNA vaccine. Our results are in line with the recent national data from the Centers for Disease Control and Prevention, showing the efficacy against symptomatic SARS-CoV-2 infection is sustained for up to 4 months after an XBB.1.5 MV booster.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.16.580687v1" target="_blank">Robust SARS-CoV-2 Neutralizing Antibodies Sustained through Three Months Post XBB.1.5 mRNA Vaccine Booster</a>
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</div></li>
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<li><strong>COVID-19 during pregnancy alters circulating extracellular vesicle cargo and their effects on trophoblast</strong> -
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SARS-CoV-2 infection and the resulting coronavirus disease (COVID-19) complicate pregnancies as the result of placental dysfunction which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests maternal response to infection is responsible for placental dysfunction. We hypothesized that maternal circulating extracellular vesicles (EVs) are altered by COVID-19 during pregnancy and contribute to placental dysfunction. To examine this, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their functional effect on trophoblast cells in vitro. We found the timing of infection is a major determinant of the effect of COVID-19 on circulating EVs. Additionally, we found differentially expressed EV mRNA cargo in COVID-19 groups compared to Controls that regulates the differential gene expression induced by COVID-19 in the placenta. In vitro exposure of trophoblasts to EVs isolated from patients with an active infection, but not EVs isolated from Controls, reduced key trophoblast functions including hormone production and invasion. This demonstrates circulating EVs from subjects with an active infection disrupt vital trophoblast function. This study determined that COVID-19 has a long-lasting effect on circulating EVs and circulating EVs are likely to participate in the placental dysfunction induced by COVID-19.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.17.580824v1" target="_blank">COVID-19 during pregnancy alters circulating extracellular vesicle cargo and their effects on trophoblast</a>
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</div></li>
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<li><strong>A Genome-Wide Arrayed CRISPR Screen Reveals PLSCR1 as an Intrinsic Barrier to SARS-CoV-2 Entry</strong> -
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<div>
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Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence SARS-CoV-2 infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of COVID-19 patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 over-expression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Our study contributes to understanding the association between PLSCR1 variants and severe COVID-19 cases reported in a recent GWAS.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.16.580725v1" target="_blank">A Genome-Wide Arrayed CRISPR Screen Reveals PLSCR1 as an Intrinsic Barrier to SARS-CoV-2 Entry</a>
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<li><strong>A critical reexamination of recovered SARS-CoV-2 sequencing data</strong> -
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SARS-CoV-2 genomes collected at the onset of the Covid-19 pandemic are valuable because they could help understand how the virus entered the human population. In 2021, Jesse Bloom reported on the recovery of a sequencing dataset that had been removed from the NCBI SRA database at the request of the data generators, a scientific team at Wuhan University. Bloom suggested that the data may have been removed in order to obfuscate the origin of SARS-CoV-2, questioning the generating authors' statements that the samples had been collected on and after January 30, 2020. Here, we show that sample collection dates were published in 2020 together with the sequencing data, and match the dates given by the authors in 2021. We examine mutations in these sequences and confirm that they are entirely consistent with the previously known genetic diversity of SARS-CoV-2 of late January 2020. Finally, we explain how an apparent phylogenetic rooting paradox described by Bloom was resolved by subsequent analysis. Our reanalysis demonstrates that allegations of cover-up or metadata manipulation were unwarranted.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.15.580500v1" target="_blank">A critical reexamination of recovered SARS-CoV-2 sequencing data</a>
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</div></li>
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<li><strong>Robust Neutralization of SARS-CoV-2 Variants Including JN.1 and BA.2.87.1 by Trivalent XBB Vaccine-Induced Antibodies</strong> -
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Newly emerged SARS-CoV-2 variants like JN.1, and more recently, the hypermutated BA.2.87.1, have raised global concern. We recruited two groups of participants who had BA.5/BF.7 breakthrough infection post three doses of inactivated vaccines: one group experienced subsequent XBB reinfection, while the other received the XBB-containing trivalent WSK-V102C vaccine. Our comparative analysis of their serum neutralization activities revealed that the WSK-V102C vaccine induced stronger antibody responses against a wide range of variants, notably including JN.1 and the highly escaped BA.2.87.1. Furthermore, our investigation into specific mutations revealed that fragment deletions in NTD significantly contribute to the immune evasion of the BA.2.87.1 variant. Our findings emphasize the necessity for ongoing vaccine development and adaptation to address the dynamic nature of SARS-CoV-2 variants.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.16.580615v1" target="_blank">Robust Neutralization of SARS-CoV-2 Variants Including JN.1 and BA.2.87.1 by Trivalent XBB Vaccine-Induced Antibodies</a>
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<li><strong>MobileLAMP: A portable, low-cost, open-source device for isothermal nucleic acid amplification</strong> -
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<div>
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Isothermal amplification-based methods for pathogen DNA or RNA detection offer high sensitivity, rapid detection, and the potential for deployment in remote fields and home testing. Consequently, they are emerging as alternatives to PCR and saw a surge in research activity and deployment for the rapid detection of SARS-CoV-2 during the Covid-19 pandemic. The most common isothermal DNA detection methods rely on minimal reagents for DNA amplification and simple hardware that can maintain isothermal conditions and read-out a fluorescent or colorimetric signal. Many researchers globally are working on improving these components based on diverse end-user needs. In this work, we have recognized the need for an open-source hardware device for isothermal amplification, composed of off-the-shelf components that are easily accessible in any part of the world, is easily manufacturable in a distributed and scalable way using 3D printing, and that can be powered using a wide diversity of batteries and power sources. We demonstrate the easy assembly of our device design and demonstrate its efficacy using colorimetric LAMP for both RNA and DNA targets.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.13.580127v1" target="_blank">MobileLAMP: A portable, low-cost, open-source device for isothermal nucleic acid amplification</a>
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<li><strong>Disaster, Facial Recognition Technology, and the Problem of the Corpse</strong> -
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The overlapping disasters of the Australian 2019-2020 bushfire season and the COVID-19 pandemic, figured alongside the imaginary of projected future disasters, have provided a space of legitimation to experiment with controversial facial recognition technologies (FRTs). Drawing upon interviews conducted with senior Australian government administrators and researchers, I argue that FRTs are being used to respond to the trauma of disaster through its novel mediation and refiguration, tied to discourses of resilience which have been used to justify the expansion of FRT as a means for relief and the provision of aid. This legitimation however is challenged by the difficulty FRT encounters in capturing the face in its vital and its mortal malleability. What I term ‘the problem of the corpse’ serves to bring to light the ‘paranoid’ gaze of the biometric apparatus, disrupting the aim of using biometric infrastructure to produce a ‘new normal’ in the ongoing aftermath of disaster.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/j4wdh/" target="_blank">Disaster, Facial Recognition Technology, and the Problem of the Corpse</a>
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<li><strong>Viral Automation: The Case of COVID-19</strong> -
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Manuscript of editor’s introduction to forthcoming special issue for New Media & Society on legacies of the COVID-19 pandemic for automated decision-making.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/u6fht/" target="_blank">Viral Automation: The Case of COVID-19</a>
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<li><strong>UBA1-CDK16: A Sex-Specific Chimeric RNA and Its Role in Immune Sexual Dimorphism</strong> -
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<div>
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RNA processing mechanisms, such as alternative splicing and RNA editing, have been recognized as critical means to expand the transcriptome. Chimeric RNAs formed by intergenic splicing provide another potential layer of RNA diversification. By analyzing a large set of RNA-Seq data and validating results in over 1,200 blood samples, we identified UBA1-CDK16, a female-specific chimeric transcript. Intriguingly, both parental genes, are expressed in males and females. Mechanistically, UBA1-CDK16 is produced by cis-splicing between the two adjacent X-linked genes, originating from the inactive X chromosome. A female-specific chromatin loop, formed between the junction sites, facilitates the alternative splicing of its readthrough precursor. This unique chimeric transcript exhibits evolutionary conservation, evolving to be female-specific from non-human primates to humans. Furthermore, our investigation reveals that UBA1-CDK16 is enriched in the myeloid lineage and plays a regulatory role in myeloid differentiation. Notably, female COVID-19 patients who tested negative for this chimeric transcript displayed higher counts of neutrophils, highlighting its potential role in disease pathogenesis. These findings support the notion that chimeric RNAs represent a new repertoire of transcripts that can be regulated independently from the parental genes, and a new class of RNA variance with potential implications in sexual dimorphism and immune responses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.13.580120v1" target="_blank">UBA1-CDK16: A Sex-Specific Chimeric RNA and Its Role in Immune Sexual Dimorphism</a>
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<li><strong>SARS-CoV-2 serosurvey of healthy, privately owned cats presenting to a New York City animal hospital in the early phase of the COVID-19 pandemic (2020-2021)</strong> -
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Both domestic and non-domestic cats are now established to be susceptible to infection by SARS-CoV-2, the cause of the ongoing COVID-19 pandemic. While serious disease in cats may occur in some instances, the majority of infections appear to be subclinical. Differing prevalence data for SARS-CoV-2 infection of cats have been reported, and are highly context-dependent. Here, we report a retrospective serological survey of cats presented to an animal practice in New York City, located in close proximity to a large medical center that treated the first wave of COVID-19 patients in the US in the Spring of 2020. We sampled 79, mostly indoor, cats between June 2020 to May 2021, the early part of which time the community was under a strict public health lock-down. Using a highly sensitive and specific fluorescent bead-based multiplex assay, we found an overall prevalence of 13/79 (16%) serologically-positive animals for the study period; however, cats sampled in the Fall of 2020 had a confirmed positive prevalence of 44%. For SARS-CoV-2 seropositive cats, we performed viral neutralization test with live SARS-CoV-2 to additionally confirm presence of SARS-CoV-2 specific antibodies. Of the thirteen seropositive cats, 7/13 (54%) were also positive by virus neutralization, and 2 of seropositive cats had previously documented respiratory signs, with high neutralization titers of 1:1024 and 1:4096; overall however, there was no statistically significant association of SARS-CoV-2 seropositivity with respiratory signs, or with breed, sex or age of the animals. Follow up sampling of cats, while limited in scope, showed that positive serological titers were maintained over time. In comparison, we found an overall confirmed positive prevalence of 51% for feline coronavirus (FCoV), an endemic virus of cats, with 30% confirmed negative for FCoV. We demonstrate the impact of SARS-CoV in a defined feline population during the first wave of SARS-CoV-2 infection of humans, and suggest that human-cat transmission was substantial in our study group. Our data provide a new context for SARS-CoV-2 transmission events across species.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.13.580068v1" target="_blank">SARS-CoV-2 serosurvey of healthy, privately owned cats presenting to a New York City animal hospital in the early phase of the COVID-19 pandemic (2020-2021)</a>
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<li><strong>A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants</strong> -
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Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have led to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMV) elicit lasting and uniquely strong immune responses. Used as vaccine vectors, they may be attractive tools that obviate the need for boosters. Therefore, we tested the murine CMV (MCMV) as a vaccine vector against COVID-19 in relevant preclinical models of immunization and challenge. We have previously developed a recombinant murine CMV (MCMV) vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MCMVS). In this study, we show that the MCMVS elicits a robust and lasting protection in young and aged mice. Notably, S-specific humoral and cellular immunity was not only maintained but even increased over a period of at least 6 months. During that time, antibody avidity continuously increased and expanded in breadth, resulting in neutralization of genetically distant variants, like Omicron BA.1. A single dose of MCMVS conferred rapid virus clearance upon challenge. Moreover, MCMVS vaccination controlled two immune-evading variants of concern (VoCs), the Beta (B.1.135) and the Omicron (BA.1) variants. Thus, CMV vectors provide unique advantages over other vaccine technologies, eliciting broadly reactive and long-lasting immune responses against COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.25.517953v2" target="_blank">A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants</a>
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<li><strong>Infer metabolic directions and magnitudes from moment differences of mass-weighted intensity distributions</strong> -
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Metabolic pathways are fundamental maps in biochemistry that detail how molecules are transformed through various reactions. Metabolomics refers to the large-scale study of small molecules. High-throughput, untargeted, mass spectrometry-based metabolomics experiments typically depend on libraries for structural annotation, which is necessary for pathway analysis. However, only a small fraction of spectra can be matched to known structures in these libraries and only a portion of annotated metabolites can be associated with specific pathways, considering that numerous pathways are yet to be discovered. The complexity of metabolic pathways, where a single compound can play a part in multiple pathways, poses an additional challenge. This study introduces a different concept: mass spectra distribution, which is the empirical distribution of the intensities times their associated m/z values. Analysis of COVID-19 and mouse brain datasets shows that by estimating the differences of the point estimations of these distributions, it becomes possible to infer the metabolic directions and magnitudes without requiring knowledge of the exact chemical structures of these compounds and their related pathways. The overall metabolic momentum map, named as momentome, has the potential to bypass the current bottleneck and provide fresh insights into metabolomics studies. This brief report thus provides a mathematical framing for a classic biological concept.
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🖺 Full Text HTML: <a href="https://osf.io/jmgea/" target="_blank">Infer metabolic directions and magnitudes from moment differences of mass-weighted intensity distributions</a>
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<li><strong>“Some distance between us:” a mixed methods study exploring experiences of remote care for eating disorders during COIVD-19</strong> -
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Introduction: COVID-19 necessitated a rapid move from face-to-face services to remote care for eating disorders/eating distress (EDs). This study explores the advantages and challenges of remote care, identifying future implications for service provision. Methods: Using a mixed methods approach, data were collected from 211 people with lived experience (PWLE); 27 participating in semi-structured interviews/workshops and 184 via an online survey. Participants reported on their ED status; the impact of the pandemic on symptoms; benefits and challenges of remote care (and type of support accessed); any reasons for not accessing support; and future recommendations. Participation was open to PWLE with and without formal diagnosis. Results: ED symptoms were reported as worsening during the pandemic with contributing factors including isolation, lack of routine, negative emotions, and feeling like the external situation was outside of one’s control. Exercise was reported as a coping mechanism (although it is noted that responses did not allow for clarifications of respondents’ understanding of what constitutes healthy or unhealthy exercise). Remote care was positively attributed to increased flexibility and facilitation of social connection. However, identified barriers to access included a lack of awareness about support availability, digital access and/or literacy, and competing commitments (e.g., childcare). Further challenges included approaches being perceived as too clinical; uncertainty around remote care quality, and concerns that remote platforms may facilitate masking of symptoms. Participants also reflected heavily upon distress caused by default self-view during video calls. Participants expressed a need for more holistic approaches including “real stories” of recovery, and hybrid (online and offline) options for greater flexibility and widening of access choices; complimented by appropriate training to mitigate digital literacy barriers. Discussion: Future recommendations emphasise user-centered holistic, hybrid approaches to ED remote support, supported by training to address digital literacy barriers and facilitate user control of platform functionalities (e.g., self-view). The study underscores the need for continued remote care with a focus on inclusivity and user empowerment.
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🖺 Full Text HTML: <a href="https://osf.io/5rpg3/" target="_blank">“Some distance between us:” a mixed methods study exploring experiences of remote care for eating disorders during COIVD-19</a>
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<li><strong>A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model</strong> -
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The first-generation Spike-alone-based COVID-19 vaccines have successfully contributed to reducing the risk of hospitalization, serious illness, and death caused by SARS-CoV-2 infections. However, waning immunity induced by these vaccines failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. We hypothesize that a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens would confer stronger and broader cross-protective immunity against multiple VOCs. In the present study, we identified ten non-Spike antigens that are highly conserved in 8.7 million SARS-CoV-2 strains, twenty-one VOCs, SARS-CoV, MERS-CoV, Common Cold CoVs, and animal CoVs. Seven of the 10 antigens were preferentially recognized by CD8+ and CD4+ T-cells from unvaccinated asymptomatic COVID-19 patients, irrespective of VOC infection. Three out of the seven conserved non-Spike T cell antigens belong to the early expressed Replication and Transcription Complex (RTC) region, when administered to the golden Syrian hamsters, in combination with Spike, as nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) (i.e., combined mRNA/LNP-based pan-CoV vaccine): (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper (TFH) cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells (TCYT), and CD69+IFN-g+TNF-a+CD4+ and CD69+IFN-g+TNFa+CD8+ effector T cells (TEFF); and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs, including the highly pathogenic B.1.617.2 Delta variant and the highly transmittable heavily Spike-mutated XBB1.5 Omicron sub-variant. The combined mRNA/LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.14.580225v1" target="_blank">A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model</a>
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<li><strong>Probability Discounting and Adherence to Preventive Behaviors During the COVID-19 Pandemic</strong> -
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This brief communication reports preliminary findings of a study conducted to investigate the relationship between probability discounting and people’s adherence to preventive behaviors recommended during the COVID-19 pandemic. A sample of 112 adults living in Brazil completed an online survey composed of a Probability Discounting Questionnaire (PDQ) and a 10-item assessment of how often they complied with the health authorities’ recommendations (e.g., wash the hands frequently, practice social distancing, stay at home as much as possible, wear a mask when in public). Data analysis included the participants who showed higher (n = 40) and lower (n = 40) adherence to preventive behaviors. Results revealed that probability discounting measures are related to people’s preventive actions. Participants in the higher adherence group present significantly larger risk aversion indices (i.e., larger h values) than participants in the lower adherence group. Also, participants who showed lower adherence to preventive behaviors were more likely to perform risky choices in the PDQ than participants who demonstrated higher compliance with health authorities’ recommendations. These preliminary results suggest that probability discounting can play an essential role in people’s self-protective decisions during a global health emergency, such as the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/p4a76/" target="_blank">Probability Discounting and Adherence to Preventive Behaviors During the COVID-19 Pandemic</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>Correlation of Antibody Response to COVID-19 Vaccination in Pregnant Woman and Transplacental Passage Into Cord Blood.</strong> - <b>Conditions</b>: Covid-19 <br/><b>Interventions</b>: Diagnostic Test: COVID-19 Spike Protein IgG Quantitative Antibody (CMIA) <br/><b>Sponsors</b>: Vachira Phuket Hospital <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine as Homologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines; COVID-19 Virus Disease <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia; Indonesia-MoH <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>Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: CD40.RBDv vaccin (SARS-Cov2 Vaccin) <br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; LinKinVax; Vaccine Research Institute (VRI), France <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High-definition Transcranial Direct Current Ctimulation and Chlorella Pyrenoidosa to Reduce Cardiovascular Risk</strong> - <b>Conditions</b>: Cardiovascular Diseases; Long Covid19 <br/><b>Interventions</b>: Other: High Definition-transcranial Direct Current Stimulation; Dietary Supplement: Chlorella Pyrenoidosa <br/><b>Sponsors</b>: Federal University of Paraíba; City University of New York <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SGB for COVID-induced Parosmia</strong> - <b>Conditions</b>: COVID-19-Induced Parosmia <br/><b>Interventions</b>: Drug: Stellate Ganglion Block; Drug: Placebo Sham Injection <br/><b>Sponsors</b>: Washington University School of Medicine <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Investigating the Effectiveness of Vimida</strong> - <b>Conditions</b>: Long COVID; Post COVID-19 Condition <br/><b>Interventions</b>: Behavioral: vimida <br/><b>Sponsors</b>: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Physiotherapy Via Video Calls in Patients With COVID-19</strong> - <b>Conditions</b>: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function <br/><b>Interventions</b>: Behavioral: Exercise training <br/><b>Sponsors</b>: Chulabhorn Hospital <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise session; Behavioral: Control session <br/><b>Sponsors</b>: University of Nove de Julho <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reducing Respiratory Virus Transmission in Bangladeshi Classrooms</strong> - <b>Conditions</b>: SARS-CoV2 Infection; Influenza Viral Infections; Respiratory Viral Infection <br/><b>Interventions</b>: Device: Box Fan; Device: UV Germicidal Irradiation Lamp Unit; Device: Combined: Box Fan and UV Germicidal Irradiation Lamp Units <br/><b>Sponsors</b>: Stanford University; Centers for Disease Control and Prevention; International Centre for Diarrhoeal Disease Research, Bangladesh <br/><b>Not yet recruiting</b></p></li>
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<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>Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways</strong> - Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues….</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 a quantitative ELISA for SARS-CoV-2 vaccine candidate, NDV-HXP-S, with CpG 1018® adjuvant</strong> - NDV-HXP-S is a Newcastle disease virus (NDV) vectored vaccine candidate which expresses the S-antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This vaccine candidate is under evaluation in human clinical studies with and without cytosine phosphate guanine (CpG) 1018® adjuvant. Existing potency methods for NDV-HXP-S do not allow for quantification of the S-antigen when the adjuvant is present. To support evaluation of NDV-HXP-S with CpG 1018® adjuvant, an inhibition…</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><em>Syringa reticulata</em> potently inhibits the activity of SARS-CoV-2 3CL protease</strong> - The ongoing coronavirus infectious disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still urgently requires effective treatments. The 3C-like (3CL) protease of SARS-CoV-2 is a highly conserved cysteine protease that plays an important role in the viral life cycle and host inflammation, providing an ideal target for developing broad-spectrum antiviral drugs. Herein, we describe the discovery of a large number of herbs mainly produced 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>A Case Report of Drug Interactions Between Nirmatrelvir/Ritonavir and Tacrolimus in a Patient With Systemic Lupus Erythematosus</strong> - Nirmatrelvir/ritonavir is a treatment for COVID-19 consisting of nirmatrelvir, which has anti-SARS-CoV-2 activity, and ritonavir, a booster to maintain blood levels. Ritonavir is known to be a potent inhibitor of cytochrome P450 3A (CYP3A), and interactions with CYP3A-metabolized drugs, such as the immunosuppressant tacrolimus, can be problematic. Ritonavir’s inhibition of CYP3A is irreversible due to covalent binding, and its inhibitory effects are expected to persist until replaced by new…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Second Boost of Omicron SARS-CoV-2 S1 Subunit Vaccine Induced Broad Humoral Immune Responses in Elderly Mice</strong> - Currently approved COVID-19 vaccines prevent symptomatic infection, hospitalization, and death from the disease. However, repeated homologous boosters, while considered a solution for severe forms of the disease caused by new SARS-CoV-2 variants in elderly individuals and immunocompromised patients, cannot provide complete protection against breakthrough infections. This highlights the need for alternative platforms for booster vaccines. In our previous study, we assessed the boost effect of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Preparation and characterization of a fluorogenic ddRFP-M biosensor as a specific SARS-CoV-2 main protease substrate</strong> - The conventional peptide substrates of SARS-CoV-2 main protease (Mpro) are frequently associated with high cost, unstable kinetics, and multistep synthesis. Hence, there is an urgent need to design affordable and stable Mpro substrates for pharmacological research. Herein, we designed a functional Mpro substrate based on a dimerization-dependent red fluorescent protein (ddRFP) for the evaluation of Mpro inhibitors in vitro. The codon-optimized DNA fragment encoding RFP-A(1) domain, a polypeptide…</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>Neutralizing antibodies to block viral entry and for identification of entry inhibitors</strong> - Neutralizing antibodies (NAbs) are naturally produced by our immune system to combat viral infections. Clinically, neutralizing antibodies with potent efficacy and high specificity have been extensively used to prevent and treat a wide variety of viral infections, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Immunodeficiency Virus (HIV), Dengue Virus (DENV) and Hepatitis B Virus (HBV). An overwhelmingly large subset of clinically effective NAbs operates by…</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>Interferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusion</strong> - CONCLUSION: Overall, our studies not only identify PVRL4 as an intrinsic broad-spectrum antiviral ISG, but also provide a candidate host-directed target for antiviral therapy against various viruses including SARS-CoV-2 and its variants in the future.</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>FEOpti-ACVP: identification of novel anti-coronavirus peptide sequences based on feature engineering and optimization</strong> - Anti-coronavirus peptides (ACVPs) represent a relatively novel approach of inhibiting the adsorption and fusion of the virus with human cells. Several peptide-based inhibitors showed promise as potential therapeutic drug candidates. However, identifying such peptides in laboratory experiments is both costly and time consuming. Therefore, there is growing interest in using computational methods to predict ACVPs. Here, we describe a model for the prediction of ACVPs that is based on 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>Taming the cytokine storm: small molecule inhibitors targeting IL-6/IL-6α receptor</strong> - Given the increasing effectiveness of immune-based therapies, management of their associated toxicities is of utmost importance. Cytokine release syndrome (CRS), characterized by elevated levels of cytokine, poses a significant challenge following the administration of antibodies and CAR-T cell therapies. CRS also contributes to multiple organ dysfunction in severe viral infections, notably in COVID-19. Given the pivotal role of IL-6 cytokine in initiating CRS, it has been considered a most…</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>How can we promote vaccination of the mass population?-Lessons from the COVID-19 vaccination defaults</strong> - While vaccines are pivotal in combating COVID-19, concerns about side effects and complex procedures have hindered complete vaccination. Prior studies suggest that individuals defaulted to opt-out exhibit higher COVID-19 vaccination rates compared to those in opt-in systems. However, these studies were conducted in countries with a tolerant attitude towards vaccination and default changes, targeting specific age groups, and did not address potential deterrents like the increase in cancellation…</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>Nanobody engineering for SARS-CoV-2 neutralization and detection</strong> - In response to the ongoing COVID-19 pandemic, the quest for coronavirus inhibitors has inspired research on a variety of small proteins beyond conventional antibodies, including robust single-domain antibody fragments, i.e., “nanobodies.” Here, we explore the potential of nanobody engineering in the development of antivirals and diagnostic tools. Through fusion of nanobody domains that target distinct binding sites, we engineered multimodular nanobody constructs that neutralize wild-type…</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 rifampicin administration on CYP induction in a dermatomyositis patient with vasospastic angina attributable to nilmatrelvir/ritonavir-induced blood tacrolimus elevation: A case report</strong> - Ritonavir (RTV), which is used in combination with nilmatrelvir (NMV) to treat coronavirus disease 2019 (COVID-19), inhibits cytochrome P450 (CYP) 3A, thereby increasing blood tacrolimus (TAC) levels through a drug-drug interaction (DDI). We experienced a case in which a DDI between the two drugs led to markedly increased blood TAC levels, resulting in vasospastic angina (VSA) and acute kidney injury (AKI). Rifampicin (RFP) was administered to induce CYP3A and promote TAC metabolism. A…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 spike protein receptor binding domain promotes IL-6 and IL-8 release via ATP/P2Y<sub>2</sub> and ERK1/2 signaling pathways in human bronchial epithelia</strong> - The spike protein of SARS-CoV-2 as well as its receptor binding domain (RBD) has been demonstrated to be capable of activating the release of pro-inflammatory mediators in endothelial cells and immune cells such as monocytes. However, the effects of spike protein or its RBD on airway epithelial cells and mechanisms underlying these effects have not been adequately characterized. Here, we show that the RBD of spike protein alone can induce bronchial epithelial inflammation in a manner of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting mevalonate pathway by zoledronate ameliorated pulmonary fibrosis in a rat model: Promising therapy against post-COVID-19 pulmonary fibrosis</strong> - CONCLUSION: ZA in a dose-dependent manner prevented the pathological effect of CCl4 in the lung by targeting mevalonate pathway. It could be promising therapy against PCPF.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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