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188 lines
49 KiB
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<title>09 November, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Nanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles</strong> -
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The SARS-CoV-2 viral infection transforms host cells and produces special organelles in many ways, and we focus on the replication organelle where the replication of viral genomic RNA (vgRNA) occurs. To date, the precise cellular localization of key RNA molecules and replication intermediates has been elusive in electron microscopy studies. We use super-resolution fluorescence microscopy and specific labeling to reveal the nanoscopic organization of replication organelles that contain vgRNA clusters along with viral double-stranded RNA (dsRNA) clusters and the replication enzyme, encapsulated by membranes derived from the host endoplasmic reticulum (ER). We show that the replication organelles are organized differently at early and late stages of infection. Surprisingly, vgRNA accumulates into distinct globular clusters in the cytoplasmic perinuclear region, which grow and accommodate more vgRNA molecules as infection time increases. The localization of ER labels and nsp3 (a component of the double-membrane vesicle, DMV) at the periphery of the vgRNA clusters suggests that replication organelles are enclosed by DMVs at early infection stages which then merge into vesicle packets as infection progresses. Precise co-imaging of the nanoscale cellular organization of vgRNA, dsRNA, and viral proteins in replication organelles of SARS-CoV-2 may inform therapeutic approaches that target viral replication and associated processes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.07.566110v1" target="_blank">Nanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles</a>
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<li><strong>Standardization and Comparison of Emergency Use Authorized COVID-19 Assays and Testing Laboratories</strong> -
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SARS-CoV-2, the causal agent of the global COVID-19 pandemic, made its appearance at the end of 2019 and is still circulating in the population. The pandemic led to an urgent need for fast, reliable, and widely available testing. After December 2020, the emergence of new variants of SARS-CoV-2 led to additional challenges since new and existing tests had to detect variants to the same extent as the original Wuhan strain. When an antigen-based test is submitted to the Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) consideration it is benchmarked against PCR comparator assays, which yield cycle threshold (CT) data as an indirect indicator of viral load—the lower the CT, the higher the viral load of the sample and the higher the CT, the lower the viral load. The FDA mandates that 10-20% of clinical samples used to evaluate the antigen test have to be low positive. Low positive, as defined by the FDA, are clinical samples in which the CT of the SARS-CoV-2 target gene is within 3 CT of the mean CT value of the approved comparator test9s Limit of Detection (LOD). While all comparator tests are PCR-based, the results from different PCR assays used are not uniform. Results vary depending on assay platform, target gene, LOD and laboratory methodology. The emergence and dominance of the Omicron variant further challenged this approach as the fraction of low positive clinical samples dramatically increased as compared to earlier SARS-CoV-2 variants. This led to 20-40% of clinical samples having high CT values and therefore assays vying for an EUA were failing to achieve the 80% Percent Positive Agreement (PPA) threshold required. Here we describe the methods and statistical analyses used to establish a predefined cutoff, based on genome copies per ml (GE/ml) to classify samples as low positive (less than the cutoff GE/ml) or high positive (greater than the cutoff GE/mL). CT 30 for the E gene target using Cobas® SARS-CoV-2-FluA/B platform performed at TriCore Reference Laboratories, and this low positive cutoff value was used for two EUA authorizations. Using droplet digital PCR and methods described here, a value 49,447.72 was determined as the GE/ml equivalent for the low positive cutoff. The CT cutoff corresponding to 49447.72 GE/ml was determined across other platforms and laboratories. The methodology and statistical analysis described here can now be used for standardization of all comparators used for FDA submissions with a goal towards establishing uniform criteria for EUA authorization.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.08.23297633v1" target="_blank">Standardization and Comparison of Emergency Use Authorized COVID-19 Assays and Testing Laboratories</a>
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</div></li>
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<li><strong>Small Fiber Neuropathy after COVID-19: A Key to Long COVID</strong> -
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Objectives: Report a case series of new onset small fiber neuropathy (SFN) after COVID-19 treated with intravenous immunoglobulin (IVIG). SFN is a critical objective finding in long COVID and amenable to treatment. Methods: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We documented demographics, symptoms, treatments, diagnostics, and clinical response to treatment. Results: Sixteen patients were diagnosed with length dependent or independent SFN on skin biopsy (median age 47, 75% female, 75% Caucasian). Among the nine patients tested for autoantibodies, six were positive for either trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor 3 (FGFR3). Eight patients underwent treatment with IVIG and experience significant clinical improvement in their neuropathic symptoms. 92% of patients reported post-exertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and six patients underwent invasive cardiopulmonary exercise testing (iCPET), which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Discussion: Here we present preliminary evidence that SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating post-infectious small fiber neuropathy.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.07.23297764v1" target="_blank">Small Fiber Neuropathy after COVID-19: A Key to Long COVID</a>
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</div></li>
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<li><strong>The impact of SARS-CoV-2 variants on the likelihood of children identified as sources of infection in the NIH workforce: a cohort study</strong> -
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Abstract Background: Children (<18 years old) were not initially considered significant sources of infection (SOIs) for SARS-CoV-2. Risk mitigation strategies were thus prioritized for adults, and vaccination was inaccessible for children until mid-2021. Emergence of novel variants led to significant increases in COVID-19 cases in both children and adults. Whether these emergence events and increased vulnerability of unvaccinated children had a synergistic effect resulting in increased caseloads in adults requires further exploration. Methods: A retrospective cohort study was conducted among 3,545 workers diagnosed with COVID-19. Case details were compiled during contact investigations. Variants of concern were identified following sequencing of biological samples collected through employer-based testing programs. Logistic regression was performed to compare the odds of having a child SOI based on the dominant variant in the workforce. Results: One-fourth (24.5%) of the cohort reported having a child in-residence; 11.2% identified a child as their SOI. In Alpha-dominant months, the odds of having a child SOI were 0.3, and the child SOI was likely older (5-17 years old). The odds of having a child SOI increased to 1.3 and 2.2 in Delta- and Omicron-dominant months, respectively. The odds of having younger child SOIs (<5 years old) were significantly higher in Omicron-dominant months. Conclusions: Children were highly likely to acquire the virus and posed a significant risk of transmission to their adult caretakers during Delta- and Omicron-dominant months. Without proper mitigation strategies in both the home and the workplace, child-associated transmission can threaten operations in the forms of staff shortages.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.07.23297422v1" target="_blank">The impact of SARS-CoV-2 variants on the likelihood of children identified as sources of infection in the NIH workforce: a cohort study</a>
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<li><strong>Combining genomic data and infection estimates to characterize the complex dynamics of SARS-CoV-2 Omicron variants in the United States</strong> -
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SARS-CoV-2 Omicron surged as a variant of concern (VOC) in late 2021. Subsequently, several distinct Omicron variants have appeared and overtaken each other. We combined variant frequencies from GISAID and infection estimates from a nowcasting model for each US state to estimate variant-specific infections, attack rates, and effective reproduction numbers (Rt). BA.1 rapidly emerged, and we estimate that it infected 47.7% of the US population between late 2021 and early 2022 before it was replaced by BA.2. We estimate that BA.5, despite a slower takeoff than BA.1, also infected 35.7% of the US population, persisting in circulation for nearly 6 months. Other Omicron variants - BA.2, BA.4, or XBB - infected 30.7% of the US population. We found a positive correlation between the state-level BA.1 attack rate and social vulnerability. Our findings reveal the complex interplay between viral evolution, population susceptibility, and social factors since Omicron emerged in the US.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.07.23298178v1" target="_blank">Combining genomic data and infection estimates to characterize the complex dynamics of SARS-CoV-2 Omicron variants in the United States</a>
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<li><strong>Overview of the 8th Social Media Mining for Health Applications (#SMM4H) Shared Tasks at the AMIA 2023 Annual Symposium</strong> -
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The aim of the Social Media Mining for Health Applications (#SMM4H) shared tasks is to take a community-driven approach to address the natural language processing and machine learning challenges inherent to utilizing social media data for health informatics. The eighth iteration of the #SMM4H shared tasks was hosted at the AMIA 2023 Annual Symposium and consisted of five tasks that represented various social media platforms (Twitter and Reddit), languages (English and Spanish), methods (binary classification, multi-class classification, extraction, and normalization), and topics (COVID-19, therapies, social anxiety disorder, and adverse drug events). In total, 29 teams registered, representing 18 countries. In this paper, we present the annotated corpora, a technical summary of the systems, and the performance results. In general, the top-performing systems used deep neural network architectures based on pre-trained transformer models. In particular, the top-performing systems for the classification tasks were based on single models that were pre-trained on social media corpora. To facilitate future work, the datasets, totaling 61,353 posts, will remain available by request, and the CodaLab sites will remain active for a post-evaluation phase.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.06.23298168v1" target="_blank">Overview of the 8th Social Media Mining for Health Applications (#SMM4H) Shared Tasks at the AMIA 2023 Annual Symposium</a>
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</div></li>
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<li><strong>Universal protection against SARS-CoV-2 viruses by multivalent mRNA vaccine in mice</strong> -
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The ongoing emergence of new strains of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants challenges available SARS-CoV-2 vaccines for adequate control of outbreaks. Currently, there is a lack of universal vaccines for SARS-CoV-2 variants that do not necessitate strain matching between mRNA vaccines and the viruses. In this study, a nucleoside-modified twenty-valent lipid nanoparticle mRNA vaccine was designed and manufactured. The primary objective is to provide protection against various recent variants via the twenty-valent mRNA vaccine after efficacy assessment. Furthermore, the protection efficiency of bivalent and quadrivalent mRNA vaccines was compared with the universal vaccine. The neutralizing antibody activity against BA.4/5, XBB.1.5, BQ.1.1, and EG.5.1 was evaluated using enzyme-linked immunosorbent assay, pseudovirus neutralization test, and a rapid fiber-optic biolayer interferometry-based biosensor. Our universal multivalent vaccine provided robust protection against both prevailing and emerging, previously unidentified SARS-CoV-2 strains.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.05.565350v1" target="_blank">Universal protection against SARS-CoV-2 viruses by multivalent mRNA vaccine in mice</a>
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<li><strong>Predicting human and viral protein variants affecting COVID-19 susceptibility and repurposing therapeutics</strong> -
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The COVID-19 disease is an ongoing global health concern. Although vaccination provides some protection, people are still susceptible to re-infection. Ostensibly, certain populations or clinical groups may be more vulnerable. Factors causing these differences are unclear and whilst socioeconomic and cultural differences are likely to be important, human genetic factors could influence susceptibility. Experimental studies indicate SARS-CoV-2 uses innate immune suppression as a strategy to speed-up entry and replication into the host cell. Therefore, it is necessary to understand the impact of variants in immunity-associated human proteins on susceptibility to COVID-19. In this work, we analysed missense coding variants in several SARS-CoV-2 proteins and its human protein interactors that could enhance binding affinity to SARS-CoV-2. We curated a dataset of 19 SARS-CoV-2: human protein 3D-complexes, from the experimentally determined structures in the Protein Data Bank and models built using AlphaFold2-multimer, and analysed impact of missense variants occurring in the protein-protein interface region. We analysed 468 missense variants from human proteins and 212 variants from SARS-CoV-2 proteins and computationally predicted their impacts on binding affinities to SARS-CoV-2 proteins, using 3D-complexes. We predicted a total of 26 affinity-enhancing variants from 14 human proteins implicated in increased binding affinity to SARS-CoV-2. These include key-immunity associated genes (TOMM70, ISG15, IFIH1, IFIT2, RPS3, PALS1, NUP98, RAE1, AXL, ARF6, TRIMM, TRIM25) as well as important spike receptors (KREMEN1, AXL and ACE2). We report both common (e.g., Y13N in IFIH1) and rare variants in these proteins and discuss their likely structural and functional impact, using information on known and predicted functional sites. Potential mechanisms associated with immune suppression implicated by these variants are discussed. Occurrence of certain predicted affinity-enhancing variants should be monitored as they could lead to increased susceptibility and reduced immune response to SARS-CoV-2 infection in individuals/populations carrying them. Our analyses aid in understanding the potential impact of genetic variation in immunity-associated proteins on COVID-19 susceptibility and help guide drug-repurposing strategies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.07.566012v1" target="_blank">Predicting human and viral protein variants affecting COVID-19 susceptibility and repurposing therapeutics</a>
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<li><strong>Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike</strong> -
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The trimeric spike protein plays an essential role in the SARS-CoV-2 virus lifecycle, facilitating virus entry through binding to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediating viral and host membrane fusion. The SARS-CoV-2 spike contains an allosteric fatty acid (FA) binding site at the interface between two neighbouring receptor-binding domains. This site, also found in some other coronaviruses, binds free fatty acids such as linoleic and oleic acid, and other small molecules. Understanding allostery and how this site modulates the behaviour of different regions in this protein could potentiate the development of promising alternative strategies for new coronavirus therapies. Here, we apply dynamical nonequilibrium molecular dynamics (D-NEMD) simulations to investigate allosteric effects and identify the communication pathways in the fully glycosylated spike in the original SARS-CoV-2 ancestral variant. The results reveal the allosteric networks that connect the FA site to important functional regions of the protein, including some more than 40 Angstroms away. These regions include the receptor binding motif, an antigenic supersite in the N-terminal domain, the furin cleavage site, the regions surrounding the fusion peptide and a second allosteric site known to bind heme and biliverdin. The networks identified here highlight the complexity of the allosteric modulation in this protein and reveal a striking and unexpected connection between different allosteric sites. Notably, 65% of amino acid substitutions, deletions and insertions in the Alpha, Beta, Delta, Gamma and Omicron variants map onto or close to the identified allosteric pathways.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.06.565757v1" target="_blank">Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike</a>
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<li><strong>Mucosal Adenoviral-vectored Vaccine Boosting Durably Prevents XBB.1.16 Infection in Nonhuman Primates</strong> -
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Waning immunity and continued virus evolution have limited the durability of protection from symptomatic infection mediated by intramuscularly (IM)-delivered mRNA vaccines against COVID-19 although protection from severe disease remains high. Mucosal vaccination has been proposed as a strategy to increase protection at the site of SARS-CoV-2 infection by enhancing airway immunity, potentially reducing rates of infection and transmission. Here, we compared protection against XBB.1.16 virus challenge 5 months following IM or mucosal boosting in non-human primates (NHP) that had previously received a two-dose mRNA-1273 primary vaccine regimen. The mucosal boost was composed of a bivalent chimpanzee adenoviral-vectored vaccine encoding for both SARS-CoV-2 WA1 and BA.5 spike proteins (ChAd-SARS-CoV-2-S) and delivered either by an intranasal mist or an inhaled aerosol. An additional group of animals was boosted by the IM route with bivalent WA1/BA.5 spike-matched mRNA (mRNA-1273.222) as a benchmark control. NHP were challenged in the upper and lower airways 18 weeks after boosting with XBB.1.16, a heterologous Omicron lineage strain. Cohorts boosted with ChAd-SARS-CoV-2-S by an aerosolized or intranasal route had low to undetectable virus replication as assessed by levels of subgenomic SARS-CoV-2 RNA in the lungs and nose, respectively. In contrast, animals that received the mRNA-1273.222 boost by the IM route showed minimal protection against virus replication in the upper airway but substantial reduction of virus RNA levels in the lower airway. Immune analysis showed that the mucosal vaccines elicited more durable antibody and T cell responses than the IM vaccine. Protection elicited by the aerosolized vaccine was associated with mucosal IgG and IgA responses, whereas protection elicited by intranasal delivery was mediated primarily by mucosal IgA. Thus, durable immunity and effective protection against a highly transmissible heterologous variant in both the upper and lower airways can be achieved by mucosal delivery of a virus-vectored vaccine. Our study provides a template for the development of mucosal vaccines that limit infection and transmission against respiratory pathogens.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.06.565765v1" target="_blank">Mucosal Adenoviral-vectored Vaccine Boosting Durably Prevents XBB.1.16 Infection in Nonhuman Primates</a>
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<li><strong>The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses</strong> -
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The COVID-19 pandemic has shown the need to develop effective therapeutics in preparedness for further epidemics of virus infections that pose a significant threat to human health. As a natural compound antiviral candidate, we focused on -dystroglycan, a highly glycosylated basement membrane protein that links the extracellular matrix to the intracellular cytoskeleton. Here we show that the N-terminal fragment of -dystroglycan (-DGN), as produced in E. coli in the absence of post-translational modifications, blocks infection of SARS-CoV-2 in cell culture, human primary gut organoids and the lungs of transgenic mice expressing the human receptor angiotensin I-converting enzyme 2 (hACE2). Prophylactic and therapeutic administration of -DGN reduced SARS-CoV-2 lung titres and protected the mice from respiratory symptoms and death. Recombinant -DGN also blocked infection of a wide range of enveloped viruses including the four Dengue virus serotypes, influenza A virus, respiratory syncytial virus, tick-borne encephalitis virus, but not human adenovirus, a non-enveloped virus in vitro. This study establishes soluble recombinant -DGN as a broad-band, natural compound candidate therapeutic against enveloped viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.06.565781v1" target="_blank">The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses</a>
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<li><strong>Combining models to generate a consensus effective reproduction number R for the COVID-19 epidemic status in England</strong> -
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The effective reproduction number R was widely accepted as a key indicator during the early stages of the COVID-19 pandemic. In the UK, the R value published on the UK Government Dashboard has been generated as a combined value from an ensemble of fourteen epidemiological models via a collaborative initiative between academia and government. In this paper we outline this collaborative modelling approach and illustrate how, by using an established combination method, a combined R estimate can be generated from an ensemble of epidemiological models. We show that this R is robust to different model weighting methods and ensemble size and that using heterogeneous data sources for validation increases its robustness and reduces the biases and limitations associated with a single source of data. We discuss how R can be generated from different data sources and is therefore a good summary indicator of the current dynamics in an epidemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.27.23286501v2" target="_blank">Combining models to generate a consensus effective reproduction number R for the COVID-19 epidemic status in England</a>
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<li><strong>Combining models to generate consensus medium-term projections of hospital admissions, occupancy and deaths relating to COVID-19 in England</strong> -
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Mathematical modelling has played an important role in offering informed advice during the COVID-19 pandemic. In England, a cross government and academia collaboration generated Medium-Term Projections (MTPs) of possible epidemic trajectories over the future 4-6 weeks from a collection of epidemiological models. In this paper we outline this collaborative modelling approach and evaluate the accuracy of the combined and individual model projections against the data over the period November 2021-December 2022 when various Omicron subvariants were spreading across England. Using a number of statistical methods, we quantify the predictive performance of the model projections for both the combined and individual MTPs, by evaluating the point and probabilistic accuracy. Our results illustrate that the combined MTPs, produced from an ensemble of heterogeneous epidemiological models, were a closer fit to the data than the individual models during the periods of epidemic growth or decline, with the 90% confidence intervals widest around the epidemic peaks. We also show that the combined MTPs increase the robustness and reduce the biases associated with a single model projection. Learning from our experience of ensemble modelling during the COVID-19 epidemic, our findings highlight the importance of developing cross-institutional multi-model infectious disease hubs for future outbreak control.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.06.23298026v1" target="_blank">Combining models to generate consensus medium-term projections of hospital admissions, occupancy and deaths relating to COVID-19 in England</a>
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<li><strong>ASSESSMENT AND CHARACTERIZATION OF COVID-19 RELATED COGNITIVE DECLINE: RESULTS FROM A NATURAL EXPERIMENT</strong> -
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Background: Cognitive impairment is the most common and disabling manifestation of post-acute sequelae of SARS-CoV-2. There is an urgent need for the application of more stringent methods for evaluating cognitive outcomes in research studies. Objective: To determine whether cognitive decline emerges with the onset of COVID-19 and whether it is more pronounced in patients with Post-Acute Sequelae of SARS-CoV-2 or severe COVID-19. Methods: This longitudinal cohort study compared the cognitive performance of 276 patients with COVID-19 to that of 217 controls across four neuroinflammation or vascular disease-sensitive domains of cognition using data collected both before and after the pandemic starting in 2015. Results: The mean age of the COVID-19 group was 56.04 (SD=6.6) years, while that of the control group was 58.1 (SD=7.3) years. Longitudinal models indicated a significant decline in cognitive throughput ((B=-0.168, P=.001) following COVID-19, after adjustment for pre-COVID-19 functioning, demographics, and medical factors. The effect sizes were large; the observed changes in throughput were equivalent to 10.6 years of normal aging and a 59.8% increase in the burden of mild cognitive impairment. Cognitive decline worsened with coronavirus disease 2019 severity and was concentrated in participants reporting post-acute sequelae of SARS-CoV-2. Conclusion: COVID-19 was most likely associated with the observed cognitive decline, which was worse among patients with PASC or severe COVID-19. Monitoring patients with post-acute sequelae of SARS-CoV-2 for declines in the domains of processing speed and visual working memory and determining the long-term prognosis of this decline are therefore warranted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.06.23298101v1" target="_blank">ASSESSMENT AND CHARACTERIZATION OF COVID-19 RELATED COGNITIVE DECLINE: RESULTS FROM A NATURAL EXPERIMENT</a>
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<li><strong>Text Augmentations with R-drop for Classification of Tweets Self-Reporting Covid-19</strong> -
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This paper presents models created for the Social Media Mining for Health 2023 shared task. Our team addressed the first task, which involves automatically distinguishing tweets that self-report a Covid-19 diagnosis, for example, a positive test, clinical diagnosis, or hospitalization from tweets that merely state that the user has experienced Covid-19 without presenting any evidence and thus would not be considered a diagnosis. Our approach involves a classification model that incorporates diverse textual augmentations and utilizes R-drop to augment data and mitigate overfitting, boosting model efficacy. Our leading model, enhanced with R-drop and augmentations like synonym substitution, reserved words, and back translations, outperforms the task mean and median scores. Our system achieves an impressive F1 score of 0.877 on the test set.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.06.23298151v1" target="_blank">Text Augmentations with R-drop for Classification of Tweets Self-Reporting Covid-19</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>Child and Adolescent Mental Health Literacy for Primary Schools Teachers. A Multicomponent Intervention</strong> - <b>Conditions</b>: Child Mental Health <br/><b>Interventions</b>: Behavioral: Child Mental Health Literacy Program <br/><b>Sponsors</b>: Universidad de Valparaiso <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>Brief Digital Intervention to Increase COVID-19 Vaccination Among Individuals With Anxiety or Depression</strong> - <b>Conditions</b>: Misinformation; Vaccine Hesitancy; Anxiety; Depression; COVID-19 <br/><b>Interventions</b>: Behavioral: Attitudinal inoculation; Behavioral: Cognitive-behavioral therapy-informed intervention; Behavioral: Conventional public health messaging <br/><b>Sponsors</b>: City University of New York, School of Public Health; University of North Carolina, Chapel Hill <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A PhaseⅡ Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine</strong> - <b>Conditions</b>: SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated <br/><b>Sponsors</b>: CNBG-Virogin Biotech (Shanghai) Ltd. <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>Pilot Randomized Study of RD-X19 Tx Device in Subjects With PCC (Long Covid) in the Outpatient Setting</strong> - <b>Conditions</b>: Post COVID-19 Condition (PCC) <br/><b>Interventions</b>: Device: RDX-19 <br/><b>Sponsors</b>: KNOWBio Inc.; NAMSA <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>CPAP Therapy Through a Helmet or a Full Face Mask in Patients With Acute Hypoxemic Respiratory Failure: Cross-over Study</strong> - <b>Conditions</b>: Pneumonia, Bacterial; Respiratory Failure; COVID-19 Pneumonia <br/><b>Interventions</b>: Diagnostic Test: Arterial blood gases; Diagnostic Test: Respiratory rate (RR); Diagnostic Test: Pulseoximeter; Diagnostic Test: Assessment of accessory respiratory muscles work; Diagnostic Test: Esophageal pressure measurement; Diagnostic Test: Discomfort Visual Analog Scale (VAS); Diagnostic Test: Noninvasive blood pressure; Diagnostic Test: Heart rate <br/><b>Sponsors</b>: I.M. Sechenov First Moscow State Medical University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1 Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine</strong> - <b>Conditions</b>: SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: Placebo; Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 10 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 30 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 60 μg <br/><b>Sponsors</b>: CNBG-Virogin Biotech (Shanghai) Ltd.; Shulan (Hangzhou) 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>Investigation of Efficacy and Safety of Electrical Signal Therapy Provided by Dr Biolyse® Device in COVID-19 Disease</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Virus Diseases; COVID-19 <br/><b>Interventions</b>: Device: Signal Therapy provided by Dr.Biolyse device; Other: Liquid Support Treatment <br/><b>Sponsors</b>: AVB Biotechnology <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>SAFE Workplace Intervention for People With IDD</strong> - <b>Conditions</b>: Developement of Infectious Airborne Disease Prevention Workplace Curriclulm <br/><b>Interventions</b>: Behavioral: SAFE Employment Training <br/><b>Sponsors</b>: Temple University; National Institute on Disability, Independent Living, and Rehabilitation Research <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of an EMDR Intervention on Traumatic and Obsessive Symptoms</strong> - <b>Conditions</b>: Adult ALL; Post-traumatic Stress Disorder; Obsessive-Compulsive Disorder; Disgust; Guilt; Shame <br/><b>Interventions</b>: Behavioral: EMDR <br/><b>Sponsors</b>: University of Pisa <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>Lithium Long COVID Dose-finding Study</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Dietary Supplement: Lithium <br/><b>Sponsors</b>: State University of New York at Buffalo <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>Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Renal Function</strong> - <b>Conditions</b>: COVID-19 Pneumonia <br/><b>Interventions</b>: Drug: GST-HG171 Tablets <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <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>Preoperative Educational Videos on Maternal Stress Whose Children Received Congenital Heart Disease Surgery: During COVID-19 Panic</strong> - <b>Conditions</b>: COVID-19; Educational Videos; Maternal; Uncertainty; Anxiety; Depression; Congenital Heart Disease; Children <br/><b>Interventions</b>: Other: Preoperative educational videos plus routine education; Other: Preoperative routine education <br/><b>Sponsors</b>: Chung Shan Medical 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>Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Liver Function</strong> - <b>Conditions</b>: COVID-19 Pneumonia <br/><b>Interventions</b>: Drug: GST-HG171 Tablets <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <br/><b>Completed</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>Enhancing Employee Job Satisfaction Responding to COVID-19: The Role of Organizational Adaptive Practices and Psychological Resilience</strong> - CONCLUSION: The study provides a new perspective on increasing JS during the COVID-19 pandemic, thereby expanding the scope of the antecedents of employee JS in crisis situations. It also reveals the mediating role of EE and deepens the research on the mechanism by which OAP and PR affect individuals, providing practical guidance for organizations to improve employee satisfaction in sudden public crisis situations.</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>Dexamethasone impairs the expression of antimicrobial mediators in lipopolysaccharide-activated primary macrophages by inhibiting both expression and function of interferon β</strong> - Glucocorticoids potently inhibit expression of many inflammatory mediators, and have been widely used to treat both acute and chronic inflammatory diseases for more than seventy years. However, they can have several unwanted effects, amongst which immunosuppression is one of the most common. Here we used microarrays and proteomic approaches to characterise the effect of dexamethasone (a synthetic glucocorticoid) on the responses of primary mouse macrophages to a potent pro-inflammatory agonist,…</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>Designing Cell Delivery Peptides and SARS-CoV-2-Targeting Small Interfering RNAs: A Comprehensive Bioinformatics Study with Generative Adversarial Network-Based Peptide Design and <em>In Vitro</em> Assays</strong> - Nucleic acid technologies with designed intracellular delivery systems are some of the most promising therapies of the future. Small interfering (si)RNAs inhibit gene expression and protein synthesis and may complement current vaccines with faster design and production. Although successful delivery remains an issue, delivery peptides may help to fill this gap. Here, we address this issue by applying bioinformatic approaches to design new putative cell delivery peptides and siRNAs for COVID-19…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The SLC6A15-SLC6A20 neutral amino acid transporter subfamily: functions, diseases, and their therapeutic relevance</strong> - The neutral amino acid transporter subfamily that consists of six members; consecutively SLC6A15-SLC620, also called orphan transporters, represents membrane, sodium-dependent symporter proteins that belong to the family of solute carrier 6 (SLC6). Primarily, they mediate the transport of neutral amino acids from the extracellular milieu toward cell or storage vesicles utilizing an electric membrane potential as the driving force. Orphan transporters are widely distributed throughout the body,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Drug repurposing for the treatment of COVID-19: Targeting nafamostat to the lungs by a liposomal delivery system</strong> - Despite tremendous global efforts since the beginning of the COVID-19 pandemic, still only a limited number of prophylactic and therapeutic options are available. Although vaccination is the most effective measure in preventing morbidity and mortality, there is a need for safe and effective post-infection treatment medication. In this study, we explored a pipeline of 21 potential candidates, examined in the Calu-3 cell line for their antiviral efficacy, for drug repurposing. Ralimetinib 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>Inhibitory effects of SARS-CoV-2 Spike protein and BNT162b2 vaccine on erythropoietin-induced globin gene expression in erythroid precursor cells (ErPCs) from β-thalassemia patients</strong> - During the recent COVID-19 pandemic several β-thalassemia patients have been infected by SARS-CoV-2 and most patients were vaccinated against SARS-CoV-2. Recent studies demonstrate an impact of SARS-CoV-2 infection on the hematopoietic system. The main objective of this study was to verify the effects of exposure of erythroid precursor cells (ErPCs) from β-thalassemia patients to SARS-CoV-2 Spike protein (S-protein) and the BNT162b2 vaccine. Erythropoietin (EPO)-cultured ErPCs have been either…</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>Physiological responses and molecular mechanism of Chlorella sorokiniana to surgical mask exudates in wastewater</strong> - Microalgae-based bioremediation is likely to be challenged by the microplastics (MPs) in wastewater induced by the widely use of surgical masks (SMs) during COVID-19. However, such toxic impact was generally evaluated under high exposure concentrations of MPs, which was not in agreement with the actual wastewater environments. Therefore, this study investigated the microalgal cellular responses to the surgical mask exudates (SMEs) in wastewater and explored the underlying inhibitory mechanism…</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>Molecular dynamic simulation reveals spider antimicrobial peptide Latarcin-1 and human eosinophil cationic protein as peptide inhibitors of SARS-CoV-2 variants</strong> - COVID-19 has rapidly proliferated around 180 countries, and new cases are reported frequently. No peptide medication has been developed that can reliably block SARS-CoV-2 infection. The investigation focuses on the crucial host receptors angiotensin-converting enzyme 2 (ACE2) , which can bind receptor-binding domain (RBD) on the SARS-CoV-2 spike protein (S). To investigate the inhibitory effects of human Eosinophil Cationic Protein (hECP) and Latarcin-1 (L1)on SARS-CoV-2 infection, we have…</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>Role of Enhancing Aerobic Capacity in Countering COVID-19-induced Liver Injury in Elderlies</strong> - COVID-19 is still a world disaster; however, its vaccination is globally available. Liver and gastrointestinal disturbances occur in patients infected with COVID-19 at varying incidences. Aging decreases the functions of the liver. Thus, the elderly have a weaker response to the COVID-19 virus. The COVID-19 virus affects the liver directly through direct and indirect mechanisms. It directly affects the renin-angiotensin system or indirectly causes sepsis, uncontrolled immune reactions,…</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 prediction of main protease SARS-CoV-2 inhibition based on models of enzyme-inhibitor complexes</strong> - A set of linear regression equations predicting the IC50 values for SARS-CoV-2 main protease inhibitors was analyzed. For 180 competitive inhibitors, we have simulated the molecular dynamics of enzyme-inhibitor complexes with known structures or modeled using molecular docking. In the docking procedure, the selection of final poses was restricted by similarity to known structural analogs. The values of the energy contributions obtained by means of calculation of the free energy change 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>Rituximab, but not other biologics, impairs humoral immunity in patients with rheumatoid arthritis-a study using CoVariant protein arrays</strong> - CONCLUSION: After receiving three doses of SARS-CoV-2 vaccination, RA patients who underwent rituximab treatment generated sufficient antibodies but exhibited lower neutralizing activities against wild-type and multiple variants, including current Omicron. Other biological DMARDs, e.g. TNF inhibitor, IL-6 inhibitor and CTLA4-Ig, did not show obvious 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>Inhibition of SARS-CoV-2 infection in human airway epithelium with a xeno-nucleic acid aptamer</strong> - CONCLUSIONS: Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.</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>Broad spectrum post-entry inhibitors of coronavirus replication: Cardiotonic steroids and monensin</strong> - A small molecule screen identified several cardiotonic steroids (digitoxin and ouabain) and the ionophore monensin as potent inhibitors of HCoV-229E, HCoV-OC43, and SARS-CoV-2 replication with EC(50)s in the low nM range. Subsequent tests confirmed antiviral activity in primary cell models including human nasal epithelial cells and lung organoids. Addition of digitoxin, ouabain, or monensin strongly reduced viral gene expression as measured by both viral protein and RNA accumulation….</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>Lipin-2 regulates the antiviral and anti-inflammatory responses to interferon</strong> - Interferons (IFN) are crucial antiviral and immunomodulatory cytokines that exert their function through the regulation of a myriad of genes, many of which are not yet characterized. Here, we reveal that lipin-2, a phosphatidic acid phosphatase whose mutations produce an autoinflammatory syndrome known as Majeed syndrome in humans, is regulated by IFN in a STAT-1-dependent manner. Lipin-2 inhibits viral replication both in vitro and in vivo. Moreover, lipin-2 also acts as a regulator 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>Saying no to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia</strong> - Nitric oxide (NO), a gaseous free radical produced from L-arginine catalyzed by NO synthase, functions as an important signaling molecule in the human body. Its antiviral activity was confirmed in the 1990s, and has been studied more extensively since the outbreak of the SARS pandemic in 2003. In the fight against the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, some recent studies have revealed the potential of NO in the treatment of coronavirus disease 2019…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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