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174 lines
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<title>29 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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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in infected and immune suppressed mice</strong> -
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<div>
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Objectives: Immunocompromised individuals are susceptible to severe COVID-19 and potentially contribute to the emergence of variants with altered pathogenicity due to persistent infection. This study investigated the impact of immunosuppression on SARS-CoV-2 infection in k18-hACE2 mice and the effectiveness of antiviral treatments in this context. Methods: Mice were immunosuppressed using cyclophosphamide and infected with a B lineage of SARS-CoV-2. Molnupiravir and nirmatrelvir, alone and in combination, were administered and viral load and viral sequence diversity was assessed. Results: Treatment of infected but immune compromised mice with both compounds either singly or in combination resulted in decreased viral loads and pathological changes compared to untreated animals. Treatment also abrogated infection of neuronal tissue. However, no consistent changes in the viral consensus sequence were observed, except for the emergence of the S:H655Y mutation. Molnupiravir, but not nirmatrelvir or immunosuppression alone, increased the transition/transversion (Ts/Tv) ratio, indicative of A>G and C>U mutations. Notably, immunosuppression itself did not appear to promote the emergence of mutations characteristic of variants of concern (VOCs). Conclusions: Further investigations are warranted to fully understand the role of immunocompromised individuals in VOC development and to inform optimised public health strategies. It is more likely that immunodeficiency promotes viral persistence but does not necessarily lead to substantial consensus-level changes in the absence of antiviral selection pressure. Molnupiravir, compared to nirmatrelvir, shows a stronger mutagenic effect in this model.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.27.582110v1" target="_blank">The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in infected and immune suppressed mice</a>
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</div></li>
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<li><strong>Virological traits of the SARS-CoV-2 BA.2.87.1 lineage</strong> -
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<div>
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The highly mutated SARS-CoV-2 BA.2.87.1 lineage was recently detected in South Africa, but its transmissibility is unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for high transmissibility.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.27.582254v1" target="_blank">Virological traits of the SARS-CoV-2 BA.2.87.1 lineage</a>
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</div></li>
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<li><strong>Attenuated replication and damaging effects of SARS-CoV-2 Omicron in an intestinal epithelial barrier model</strong> -
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<div>
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Many COVID-19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function may play a key role in Long COVID. Despite its importance, the impact of SARS-CoV-2 on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco-2 cells, mucus-secreting HT29 cells and human Raji cells. This gut epithelial model allows efficient differentiation of Caco-2 cells into microfold-like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS-CoV-2 infection. Early strains of SARS-CoV-2 and the Delta variant replicated with high efficiency, severely disrupted barrier function, and depleted tight junction proteins, such as claudin-1, occludin and ZO-1. In comparison, Omicron subvariants also depleted ZO-1 from tight junctions but had fewer damaging effects on mucosal integrity and barrier function. Remdesivir and the TMPRSS2 inhibitor Camostat prevented SARS-CoV-2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS-CoV-2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.28.582510v1" target="_blank">Attenuated replication and damaging effects of SARS-CoV-2 Omicron in an intestinal epithelial barrier model</a>
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</div></li>
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<li><strong>Designed mosaic nanoparticles enhance cross-reactive immune responses in mice</strong> -
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<div>
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Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2COMs; mosaic-5COM), and (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naive and COVID-19 pre-vaccinated mice revealed that mosaic-7COM elicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7COM targeted conserved RBD epitopes. Mosaic-2COMs and mosaic-5COM elicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7COM to protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.28.582544v1" target="_blank">Designed mosaic nanoparticles enhance cross-reactive immune responses in mice</a>
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</div></li>
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<li><strong>The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2</strong> -
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<div>
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The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity for viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in the receptor binding domain of the S1 subunit of the spike glycoprotein have led to considerable escape from antibody responses, reducing the efficacy of vaccines and monoclonal antibody (mAb) therapies. Therefore, there is a need to interrogate more constrained regions of Spike, such as the S2 subdomain. Here, we describe a collection of S2 mAbs from two SARS-CoV-2 convalescent individuals that target multiple regions in the S2 subdomain and can be grouped into at least five epitope classes. Most did not neutralize SARS-CoV-2 with the exception of C20.119, which bound to a highly conserved epitope in the fusion peptide and showed broad binding and neutralization activity across SARS-CoV-2, SARS-CoV-1, and closely related zoonotic sarbecoviruses. Several of the S2 mAbs tested mediated antibody-dependent cellular cytotoxicity (ADCC) at levels similar to the S1 mAb S309 that was previously authorized for treatment of SARS-CoV-2 infections. Three of the mAbs with ADCC function also bound to spike trimers from HCoVs, such as MERS-CoV and HCoV-HKU1. Our findings suggest there are diverse epitopes in S2, including functional S2 mAbs with HCoV and sarbecovirus breadth that likely target functionally constrained regions of spike. These mAbs could be developed for potential future pandemics, while also providing insight into ideal epitopes for eliciting a broad HCoV response.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.26.582219v1" target="_blank">The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2</a>
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</div></li>
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<li><strong>Secondary structure of the SARS-CoV-2 genome is predictive of nucleotide substitution frequency</strong> -
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<div>
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Accurate estimation of the effects of mutations on SARS-CoV-2 viral fitness can inform public-health responses such as vaccine development and predicting the impact of a new variant; it can also illuminate biological mechanisms including those underlying the emergence of variants of concern. Recently, Lan et al reported a high-quality model of SARS-CoV-2 secondary structure and its underlying dimethyl sulfate (DMS) reactivity data. I investigated whether secondary structure can explain some variability in the frequency of observing different nucleotide substitutions across millions of patient sequences in the SARS-CoV-2 phylogenetic tree. Nucleotide basepairing was compared to the estimated mutational fitness of substitutions, a measurement of the difference between observed and expected substitution frequency that is correlated with other estimates of viral fitness. This comparison revealed that secondary structure is often predictive of substitution frequency, with significant decreases in substitution frequencies at basepaired positions. Focusing on the mutational fitness of C[->]T, the most common type of substitution, I describe C[->]T substitutions at basepaired positions that characterize major SARS-CoV-2 variants; such mutations may have a greater impact on fitness than appreciated when considering substitution frequency alone.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.27.581995v1" target="_blank">Secondary structure of the SARS-CoV-2 genome is predictive of nucleotide substitution frequency</a>
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</div></li>
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<li><strong>Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome</strong> -
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<div>
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The COVID-19 pandemic persists despite the availability of vaccines, and it is therefore crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of the oral microbiome in SARS-CoV-2 infection. Using an in vitro SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by Porphyromonas gingivalis on SARS-CoV-2 infection mediated by known P. gingivalis compounds such as phosphoglycerol dihydroceramide (PGDHC) and gingipains as well as by unknown bacterial factors. We found that the gingipain-mediated inhibition of infection is likely due to cytotoxicity, while PGDHC inhibited virus infection by an unknown mechanism. Unidentified factors present in P. gingivalis supernatant inhibited SARS-CoV-2 likely via the fusion step of the virus life cycle. We addressed the role of other oral bacteria and found certain periodontal pathogens capable of inhibiting SARS-CoV-2 pseudovirus infection by inducing cytotoxicity on target cells. In the human oral cavity, we observed the modulatory activity of oral microbial communities varied among individuals in that some saliva-based cultures were capable of inhibiting while others were enhancing infection. These findings contribute to our understanding of the complex relationship between the oral microbiome and viral infections, offering potential avenues for innovative therapeutic strategies in combating COVID-19.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.27.582258v1" target="_blank">Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome</a>
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</div></li>
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<li><strong>Carboxylated graphene: A novel approach for enhanced IgA-SARS-CoV-2 electrochemical biosensing</strong> -
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<div>
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Biosensors comprise devices that use a material of biological nature as receptors connected to transducers, these devices are capable of capturing biorecognition signals, called a primary signal, and converting it to a measurable signal. In this study, we report the synthesis of carboxylated graphene (CG) through a carboxylation method in acid medium and further characterization of the materials by different techniques such as scanning electron microscopy, energy-dispersive X-ray spectroscopy, Raman spectroscopy, thermal gravimetric analysis, and X-ray diffraction. Also, the surface of the screen-printed carbon electrodes (SPCEs) was modified with CG for subsequent immobilization of N-protein of SARS-CoV-2, which allowed the detection of antibodies (IgA-SARS-CoV-2). The electrical properties and response of the biosensor were investigated using electrochemical techniques (cyclic voltammetry and electrochemical impedance spectroscopy). Through the chemical characterization techniques, it was possible to confirm the success of the CG synthesis process. The biosensor fabricated shown to be able to detect IgA-SARS-CoV-2 in the range of 1:1000 to1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was 1:1601 v/v. this perspective they comprise a wide range of applications due to its advantages, such as the possibility of a shorter response time, reproducibility, the miniaturization of detection devices such as the use of screen-printed electrodes, the use of small amounts of sample, the high sensitivity and specificity, low limits of detection and the integration of nano materials that make it possible to improve the detected signal.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.27.582131v1" target="_blank">Carboxylated graphene: A novel approach for enhanced IgA-SARS-CoV-2 electrochemical biosensing</a>
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</div></li>
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<li><strong>Consequences of COVID-19 in Animal Husbandry sector</strong> -
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<div>
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The COVID-19 outbreak originated in Wuhan, China, at the Huanan Seafood Wholesale Market, devastating people and other sectors, particularly the cattle industry. During the outbreak, there was a surge in demand for meat, eggs, and other necessities to boost immunity and health. The outbreak impacted a considerable number of workers in the meat processing and animal husbandry sectors. Meat and processing facility food quality and sanitation were critical to health and food security. Many individuals continued to work despite the dangers due to a lack of sick leave and health insurance. The pandemic disrupted the crucial function of animal husbandry in food delivery, particularly in rural and urban areas. Farmers experienced decreased production and transportation challenges as a result of workforce shortages and vehicle limits. Animal metabolic disorders were triggered by fodder shortages and supply network disturbances. Cattle prices fell as a result of the delayed vaccines, and foot-and-mouth disease spread. The sector was harmed when livestock care and feed distribution operations were suspended. The COVID-19 outbreak afflicted millions of people, jeopardising nutrition, food security, and animal productivity. This article concludes with important strategies and solutions for ensuring human and animal food supplies during and after calamities. It also emphasises the benefits of sustainable livestock husbandry for both animals and the environment.
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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/dtxqn/" target="_blank">Consequences of COVID-19 in Animal Husbandry sector</a>
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</div></li>
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<li><strong>Providing the Ichushi-Web Bibliographies to the WHO COVID-19 Research Database: Corona-Related Information Service During Pandemic Disasters.</strong> -
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<div>
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Three years after we began living through an unprecedented infectious disease epidemic at the end of 2019, our world is still heavily affected by COVID-19. Therefore, new tools such as LitCovid, iSearch COVID-19 portfolio, and the WHO COVID-19 Research Database (WHO COVID-19 RDB), which collects and provides information specific to COVID-19 infections, have been launched. Herein, I describe our activities directed towards providing the bibliographic details of Ichushi-Web to the WHO COVID-19 RDB, what we have achieved from such activities, and an overview of this database. I have continued this activity in the hope that inclusion of as much bibliographic information as possible to the tool provided by WHO, a global organization, will help to improve the world’s access to research published in Japanese.
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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/5a49j/" target="_blank">Providing the Ichushi-Web Bibliographies to the WHO COVID-19 Research Database: Corona-Related Information Service During Pandemic Disasters.</a>
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</div></li>
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<li><strong>Long-Term Quarantine is Associated with High Cortisol and Low DNA Methylation in New World monkeys</strong> -
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<div>
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Quarantines prevent infectious disease spread during primate transport, fostering acclimatisation. Environmental stress can lead to altered physiology, health risks, and epigenetic changes in other primates. We analysed Peruvian Saguinus fuscicollis and Saimiri macrodon, immobilised for 10 months in quarantine during the COVID-19 crisis, and compared them to wild counterparts to determine effects of quarantine as a stressor in New World monkeys. Methods: Both quarantine and wild samples were collected from two riverine islands near the city of Iquitos, situated in the Peruvian Amazon (Island Muyuy and Padre Island). Cortisol levels in hair were quantified using ELISA (n=37; quarantine n=16; wild=21), and global DNA methylation levels were assessed for epigenetic comparison in dried blood spots (n=45; Quarantine: n=23; Wild: n=22), also utilising ELISA. Two-way ANOVA was employed to explore the effect of quarantine on cortisol and DNA methylation, considering the effect of species, and sex differences on these measurements. Results: Cortisol analysis revealed a significant association between quarantine and elevated cortisol secretion when testing both species together and independently, with a greater difference between quarantine and wild for Saguinus fuscicollis. Quarantine was associated with global DNA hypomethylation when testing both species together, however, independent ANOVAs show there was no effect of quarantine on Saguinus fuscicollis, and a marginal significant effect of quarantine on Saimiri macrodon. Discussion: New World monkey species displayed hormonal and epigenetic dysregulation 10-months after starting quarantine period, suggesting long-term physiological and genomic stress as a response to captivity. Species specific differences in stress adaptability might mediate observed effects.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.26.582046v1" target="_blank">Long-Term Quarantine is Associated with High Cortisol and Low DNA Methylation in New World monkeys</a>
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</div></li>
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<li><strong>Single cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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To elucidate the important cellular and molecular drivers of pulmonary long COVID, we generated a single-cell transcriptomic map of the airway mucosa using bronchial brushings from patients with long COVID who reported persistent pulmonary symptoms. Adults with and without long COVID were recruited from the general community in greater Vancouver, Canada. The cohort was divided into those with pulmonary long COVID (PLC), which was defined as persons with new or worsening respiratory symptoms following at least one year from their initial acute SARS-CoV-2 infection (N=9); and control subjects defined as SARS-CoV-2 infected persons whose acute respiratory symptoms had fully resolved or individuals who had not experienced acute COVID-19 (N=9). These participants underwent bronchoscopy from which a single cell suspension was created from bronchial brush samples and then sequenced. A total of 56,906 cells were recovered for the downstream analysis, with 34,840 cells belonging to the PLC group. A dimensionality reduction plot shows a unique cluster of neutrophils in the PLC group (p<.05). Ingenuity Pathway Analysis revealed that neutrophil degranulation pathway was enriched across epithelial cells. Differential gene expression analysis between the PLC and control groups demonstrated upregulation of mucin genes in secretory cell clusters. A single-cell transcriptomic landscape of the small airways shows that the PLC airways harbors a dominant neutrophil cluster and an upregulation in the neutrophil-associated activation signature with increased expression of MUC genes in the secretory cells. Together, they suggest that pulmonary symptoms of long COVID may be driven by chronic small airway inflammation.
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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/10.1101/2024.02.26.24302674v1" target="_blank">Single cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID</a>
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</div></li>
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<li><strong>Quantifying and adjusting for confounding from health-seeking behaviour and healthcare access in observational research.</strong> -
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Objective: To assess the feasibility and effect of using proxy markers of health-seeking behaviour and healthcare access to quantify and adjust for confounding in observational studies of influenza and COVID-19 vaccine effectiveness (VE). Design: Cohort study for influenza VE in the 2019/2020 influenza season and for early COVID-19 VE (December 2020 to March 2021). Setting: Primary care data pre-linked to secondary care and death data in England. Participants: Individuals aged ≥66 years on 1 September 2019. Interventions: Vaccination with any influenza vaccination in the 2019/2020 season or with either a BNT162b2 or ChAdOx1-S vaccination from 08/12/2020 to 31/03/2021. Main outcome measures: Influenza or COVID-19 specific infections, hospitalisation and death. VE was estimated with sequential adjustment for demographics, underlying health conditions, and 14 markers reflecting uptake of public health interventions (screenings, vaccinations and NHS health checks), active healthcare access/use (prostate antigen testing, bone density scans, GP practice visits, low value procedures and blood pressure measurements) and lack of access/underuse (hospital visits for ambulatory care sensitive conditions and did not attend primary care visits). Influenza vaccination in the 2019/2020 season was also considered as a negative exposure intervention against the first wave of COVID-19. Results: We included 1,991,284, 1,796,667, and 1,946,943 individuals in the influenza, COVID-19 and negative exposure VE populations, respectively. Vaccinated individuals were more likely to display active health-seeking behaviour, including participation in UK national screening programmes, compared with unvaccinated individuals. In the 2019/2020 influenza season, adjusting for health-seeking markers increased VE against infection from -1.5% (95%CI: -3.2,0.1) to 7.1% (95%CI: 5.4,8.7), but this trend was less apparent for more severe outcomes. For COVID-19 during early vaccine roll out, adjusting for health-seeking markers in addition to demographics and underlying health conditions did not change VE estimates against infection or severe disease (e.g., two doses of BNT162b2 against infection: from 82.8% [95%CI: 78.4,86.3] to 83.1% [95%CI: 78.7,86.5]). Adjusting for health-seeking markers removed bias in the negative exposure analysis of influenza vaccination against SARS-CoV-2 infection (-7.5% [95%CI: -10.6,-4.5] vs -2.1% [95%CI: -6.0,1.7] before vs after adjusting for health-seeking markers). Conclusions: Markers of health-seeking behaviour and healthcare access can be identified in electronic health records, are associated with vaccination uptake, and can be used to quantify and account for confounding in observational studies.
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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/10.1101/2024.02.27.24303434v1" target="_blank">Quantifying and adjusting for confounding from health-seeking behaviour and healthcare access in observational research.</a>
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</div></li>
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<li><strong>Dispersal history of SARS-CoV-2 in Galicia, Spain</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia9s major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.27.24303385v1" target="_blank">Dispersal history of SARS-CoV-2 in Galicia, Spain</a>
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</div></li>
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<li><strong>The relationship between risk perception and information sources during the COVID-19 pandemic in Southeast Alaska</strong> -
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<div>
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Objective: We describe changes in consumption of different information sources during the first year of the COVID-19 pandemic across Southeast Alaska. Study Design: We administered two surveys in Southeast Alaska at two critical points during the COVID-19 pandemic (April-June 2020 and November 2020-February 2021) resulting in a convenience sample (n > 1000) of respondents over age 18. Methods: Using survey responses from the two time points, we calculated absolute and percent changes in reported usage of 11 different information sources and tested these changes using a two-proportion z-score. We used logistic regression to estimate the probability of consuming national news, local news, internet sources, social media, and talking with trusted individuals while controlling for demographic variables (age, sex, ethnicity group), risk perceptions, and time. Results: We found no strong relationships between risk perceptions and the probability of consuming various information sources. Males were significantly less likely to consume national sources, local sources, and use social media. Respondents 65 years and older were significantly more likely to consume national sources and local sources and were significantly less likely to consume social media. Conclusions: Different demographic groups use various information sources differently in Southeast Alaska. This could result in uneven quality of, understanding of, and action upon public health messages.
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🖺 Full Text HTML: <a href="https://osf.io/u4kvs/" target="_blank">The relationship between risk perception and information sources during the COVID-19 pandemic in Southeast Alaska</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>INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <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; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <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>Dose-Escalation Study to Evaluate the Safety & Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: IMNN-101 <br/><b>Sponsors</b>: Imunon <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>Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo <br/><b>Sponsors</b>: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited <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>Effectiveness of a Nasal Spray on Viral Respiratory Infections</strong> - <b>Conditions</b>: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold <br/><b>Interventions</b>: Device: Nasal Spray HSV Treatment <br/><b>Sponsors</b>: CEN Biotech; Urgo Research, Innovation & Development <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>GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: GS-441524; Drug: Placebo <br/><b>Sponsors</b>: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, 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 Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 <br/><b>Interventions</b>: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) <br/><b>Sponsors</b>: Selda Sarıkaya; Zonguldak Bulent Ecevit University <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>UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <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; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <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>World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt</strong> - <b>Conditions</b>: Mucormycosis; Rhinocerebral (Etiology); COVID-19 <br/><b>Interventions</b>: Procedure: debridment <br/><b>Sponsors</b>: Nasser Institute For Research and Treatment <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>Attention Training for COVID-19 Related Distress</strong> - <b>Conditions</b>: Anxiety <br/><b>Interventions</b>: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training <br/><b>Sponsors</b>: Palo Alto University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mindfulness-based Mobile Applications Program</strong> - <b>Conditions</b>: COVID-19; Cell Phone Use; Nurse; Mental Health <br/><b>Interventions</b>: Device: mindfulness-based mobile applications program <br/><b>Sponsors</b>: Yu-Chien Huang <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>Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 <br/><b>Interventions</b>: Drug: Hyperbaric oxygen <br/><b>Sponsors</b>: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk <br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 mechanisms of cell tropism in various organs considering host factors</strong> - A critical step in the drug design for SARS-CoV-2 is to discover its molecular targets. This study comprehensively reviewed the molecular mechanisms of SARS-CoV-2, exploring host cell tropism and interaction targets crucial for cell entry. The findings revealed that beyond ACE2 as the primary entry receptor, alternative receptors, co-receptors, and several proteases such as TMPRSS2, Furin, Cathepsin L, and ADAM play critical roles in virus entry and subsequent pathogenesis. Additionally,…</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>Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies</strong> - Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here, we uncover the role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via…</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>Microfluidics produced ATRA-loaded PLGA NPs reduced tuberculosis burden in alveolar epithelial cells and enabled high delivered dose under simulated human breathing pattern in 3D printed head models</strong> - Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is second only to COVID-19 as the top infectious disease killer worldwide. Multi-drug resistant TB (MDR-TB) may arise because of poor patient adherence to medications due to lengthy treatment duration and side effects. Delivering novel host directed therapies (HDT), like all trans retinoic acid (ATRA) may help to improve drug regimens and reduce the incidence of MDR-TB. Local delivery of ATRA to the site of infection leads to higher…</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>Miquelianin: primary antioxidant power and Mpro SARS-CoV-2 non-covalent inhibition capabilities from computational investigations</strong> - The antioxidant power of quercetin-3-O-glucuronide (miquelianin) has been studied, at the density functional level of theory, in both lipid-like and aqueous environments. In the aqueous phase, the computed pKa equilibria allows the identification of the neutral and charged species present in solution that can react with the •OOH radical. The Hydrogen Atom Transfer (HAT), Single Electron Transfer (SET) and Radical Adduct Formation (RAF) mechanisms were considered and the individual, total and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring Retrograde Trafficking: Mechanisms and Consequences in Cancer and Disease</strong> - Retrograde trafficking (RT) orchestrates the intracellular movement of cargo from the plasma membrane, endosomes, Golgi or endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) in an inward/ER-directed manner. RT works as the opposing movement to anterograde trafficking (outward secretion), and the two work together to maintain cellular homeostasis. This is achieved through maintaining cell polarity, retrieving proteins responsible for anterograde trafficking and redirecting proteins…</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>Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study</strong> - One of the major pathomechanisms of COVID-19 is the interplay of hyperinflammation and disruptions in coagulation processes, involving thrombocytes. Antiplatelet therapy (AP) by anti-inflammatory effect and inhibition of platelet aggregation may affect these pathways. The aim of this study was to investigate if AP has an impact on the in-hospital course and medium-term outcomes in hospitalized COVID-19 patients. The study population (2170 COVID-19 patients: mean ± SD age 60 ± 19 years old, 50%…</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>Pan-viral propagation blockade by inhibiting host cell PNPT1</strong> - Successful viral propagation within infected cells necessitates the viruses’ ability to overcome the cellular integrated stress response (ISR), triggered during viral infection, which in turn inhibits general protein translation. In our study, we unveil a shared tactic employed by viruses to suppress ISR by upregulating host cell polyribonucleotide nucleotidyltransferase 1 (PNPT1). The propagation of adenovirus, murine cytomegalovirus, and hepatovirus within their respective host cells induces…</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>Synergistic Binding of SARS-CoV-2 to ACE2 and Gangliosides in Native Lipid Membranes</strong> - Viruses utilize cell surface glycans and plasma membrane receptors to attain an adequate attachment strength for initiating cellular entry. We show that SARS-CoV-2 particles bind to endogenous ACE2 receptors and added sialylated gangliosides in near-native membranes. This was explored using supported membrane bilayers (SMBs) that were formed using plasma membrane vesicles having endogenous ACE2 and GD1a gangliosides reconstituted in lipid vesicles. The virus binding rate to the SMBs is…</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>Viral RNA Replication Suppression of SARS-CoV-2: Atomistic Insights into Inhibition Mechanisms of RdRp Machinery by ddhCTP</strong> - The nonstructural protein 12, known as RNA-dependent RNA polymerase (RdRp), is essential for both replication and repair of the viral genome. The RdRp of SARS-CoV-2 has been used as a promising candidate for drug development since the inception of the COVID-19 spread. In this work, we performed an in silico investigation on the insertion of the naturally modified pyrimidine nucleobase ddhCTP into the SARS-CoV-2 RdRp active site, in a comparative analysis with the natural one (CTP). 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>NLRP1 restricts porcine deltacoronavirus infection via IL-11 inhibiting the phosphorylation of the ERK signaling pathway</strong> - Continuously emerging highly pathogenic coronaviruses remain a major threat to human and animal health. Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes large-scale outbreaks of severe diarrhea disease in piglets. Unlike other porcine coronaviruses, PDCoV has a wide range of species tissue tropism, including primary human cells, which poses a significant risk of cross-species transmission. Nucleotide-binding oligomerization domain-like receptor…</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>Nsp1 facilitates SARS-CoV-2 replication through calcineurin-NFAT signaling</strong> - SARS-CoV-2, the causative agent of COVID-19, has been intensely studied in search of effective antiviral treatments. The immunosuppressant cyclosporine A (CsA) has been suggested to be a pan-coronavirus inhibitor, yet its underlying mechanism remained largely unknown. Here, we found that non-structural protein 1 (Nsp1) of SARS-CoV-2 usurped CsA-suppressed nuclear factor of activated T cells (NFAT) signaling to drive the expression of cellular DEAD-box helicase 5 (DDX5), which facilitates viral…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes</strong> - CONCLUSIONS: Our data demonstrate that strains, which harbor covR/S mutations, interfere with IL-18 and IL-8 responses in monocytic cells by utilizing the caspase-8 axis. Future experiments aim to identify the underlying mechanism and consequences for NSTI patients.</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>Methyl rosmarinate is an allosteric inhibitor of SARS-cov-2 3 C L protease as a potential candidate against SARS-cov-2 infection</strong> - The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been ongoing for more than three years and urgently needs to be addressed. Traditional Chinese medicine (TCM) prescriptions have played an important role in the clinical treatment of patients with COVID-19 in China. However, it is difficult to uncover the potential molecular mechanisms of the active ingredients in these TCM prescriptions. In this paper, we developed a 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>Human transferrin receptor can mediate SARS-CoV-2 infection</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron…</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>Polyvalent Nanobody Structure Designed for Boosting SARS-CoV-2 Inhibition</strong> - Coronavirus transmission and mutations have brought intensive challenges on pandemic control and disease treatment. Developing robust and versatile antiviral drugs for viral neutralization is highly desired. Here, we created a new polyvalent nanobody (Nb) structure that shows the effective inhibition of SARS-CoV-2 infections. Our polyvalent Nb structure, called “PNS”, is achieved by first conjugating single-stranded DNA (ssDNA) and the receptor-binding domain (RBD)-targeting Nb with retained…</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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