182 lines
44 KiB
HTML
182 lines
44 KiB
HTML
|
<!DOCTYPE html>
|
|||
|
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
|
|||
|
<meta charset="utf-8"/>
|
|||
|
<meta content="pandoc" name="generator"/>
|
|||
|
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
|
|||
|
<title>03 December, 2022</title>
|
|||
|
<style>
|
|||
|
code{white-space: pre-wrap;}
|
|||
|
span.smallcaps{font-variant: small-caps;}
|
|||
|
span.underline{text-decoration: underline;}
|
|||
|
div.column{display: inline-block; vertical-align: top; width: 50%;}
|
|||
|
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
|
|||
|
ul.task-list{list-style: none;}
|
|||
|
</style>
|
|||
|
<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>
|
|||
|
<body>
|
|||
|
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
|
|||
|
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
|
|||
|
<ul>
|
|||
|
<li><a href="#from-preprints">From Preprints</a></li>
|
|||
|
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
|
|||
|
<li><a href="#from-pubmed">From PubMed</a></li>
|
|||
|
<li><a href="#from-patent-search">From Patent Search</a></li>
|
|||
|
</ul>
|
|||
|
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
|
|||
|
<ul>
|
|||
|
<li><strong>Mice Humanized for Major Histocompatibility Complex and Angiotensin-Converting Enzyme 2 with High Permissiveness to SARS-CoV-2 Omicron Replication</strong> -
|
|||
|
<div>
|
|||
|
Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike glycoprotein. The murine ACE2 ortholog does not interact efficiently with SARS-CoV-2 Spike and therefore the conventional laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated new hACE2 transgenic mice, which harbor the hACE2 gene under the human keratin 18 promoter, in C57BL/6 HHD-DR1 background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human Caucasian populations. We selected three transgenic strains, with various hACE2 mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. Compared to the previously available B6.K18-ACE22Prlmn/JAX mice, which have limited permissiveness to SARS-CoV-2 Omicron replication, these three new hACE2 transgenic strains display higher levels of hACE2 mRNA expression, associated with high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants. As a first application, one of these MHC- and ACE2-humanized strains was successfully used to show the efficacy of a lentiviral vector-based COVID-19 vaccine candidate.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.01.518541v1" target="_blank">Mice Humanized for Major Histocompatibility Complex and Angiotensin-Converting Enzyme 2 with High Permissiveness to SARS-CoV-2 Omicron Replication</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>Predicting Immune Escape with Pretrained Protein Language Model Embeddings</strong> -
|
|||
|
<div>
|
|||
|
Assessing the severity of new pathogenic variants requires an understanding of which mutations enable escape of the human immune response. Even single point mutations to an antigen can cause immune escape and infection by disrupting antibody binding. Recent work has modeled the effect of single point mutations on proteins by leveraging the information contained in large-scale, pretrained protein language models (PLMs). PLMs are often applied in a zero-shot setting, where the effect of each mutation is predicted based on the output of the language model with no additional training. However, this approach cannot appropriately model immune escape, which involves the interaction of two proteins–antibody and antigen–instead of one protein and requires making different predictions for the same antigenic mutation in response to different antibodies. Here, we explore several methods for predicting immune escape by building models on top of embeddings from PLMs. We evaluate our methods on a SARS-CoV-2 deep mutational scanning dataset and show that our embedding-based methods significantly outperform zero-shot methods, which have almost no predictive power. We also highlight insights gained into how best to use embeddings from PLMs to predict escape. Despite these promising results, simple statistical and machine learning baseline models that do not use pretraining perform comparably, showing that computationally expensive pretraining approaches may not be beneficial for escape prediction. Furthermore, all models perform relatively poorly, indicating that future work is necessary to improve escape prediction with or without pretrained embeddings.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.30.518466v1" target="_blank">Predicting Immune Escape with Pretrained Protein Language Model Embeddings</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>COVID-19 and friendships: Agreeableness and neuroticism predict being more concerned about COVID-19 and bothered by friends’ risky behavior</strong> -
|
|||
|
<div>
|
|||
|
Given the importance of friendships during challenging times and the mixed associations reported between personality traits and disease-related behaviors, we investigated the influence of personality traits on friendships during the COVID-19 pandemic and how both influenced risky behaviors. In November 2020, we asked participants about their reactions to friends’ behavior as part of a larger study. We found that agreeableness and neuroticism predicted participants being more concerned about COVID-19 and bothered by friends’ risky behavior, and extraversion predicted enjoying helping friends during the pandemic. Our results suggest that personality influences how individuals cope with their friends’ risky behaviors.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/qkp8b/" target="_blank">COVID-19 and friendships: Agreeableness and neuroticism predict being more concerned about COVID-19 and bothered by friends’ risky behavior</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19</strong> -
|
|||
|
<div>
|
|||
|
The clinical course of the 2019 coronavirus disease (COVID-19) is variable and to a substantial degree still unpredictable, especially in persons who have neither been vaccinated nor recovered from previous infection. We hypothesized that disease progression and inflammatory responses were associated with alterations in the microbiome and metabolome. To test this, we integrated metagenome, metabolome, cytokine, and transcriptome profiles of longitudinally collected samples from hospitalized COVID-19 patients at the beginning of the pandemic (before vaccines or variants of concern) and non-infected controls, and leveraged detailed clinical information and post-hoc confounder analysis to identify robust within- and cross-omics associations. Severe COVID-19 was directly associated with a depletion of potentially beneficial intestinal microbes mainly belonging to Clostridiales, whereas oropharyngeal microbiota disturbance appeared to be mainly driven by antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine, and reduced levels of various other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Decreased abundance of Clostridiales potentially mediated the observed reduction in 5-hydroxytryptophan levels. Moreover, altered plasma levels of various tryptophan metabolites and lower abundances of Clostridiales explained significant increases in the production of IL-6, IFN{gamma} and/or TNF. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.02.518860v1" target="_blank">Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>Potent Immunogenicity and Broad-Spectrum Protection Potential of Microneedle Array Patch-Based COVID-19 DNA Vaccine Candidates Encoding Dimeric RBD Chimera of SARS-CoV and SARS-CoV-2 Variants</strong> -
|
|||
|
<div>
|
|||
|
Breakthrough infections by SARS-CoV-2 variants pose a global challenge to pandemic control, and the development of more effective vaccines of broad- spectrum protection is needed. In this study, we constructed pVAX1-based plasmids encoding heterodimeric receptor-binding domain (RBD) chimera of SARS-CoV and SARS-CoV-2 Omicron BA.1 (RBDSARS/BA1), SARS-CoV and SARS- CoV-2 Beta (RBDSARS/Beta), or Omicron BA.1 and Beta (RBDBA1/Beta) in secreted form. When i.m. injected in mice, RBDSARS/BA1 and RBDSARS/Beta encoding plasmids (pAD1002 and pAD131, respectively) were by far more immunogenic than RBDBA1/Beta plasmid (pAD1003). Dissolvable microneedle array patches (MAP) laden with these DNA plasmids were fabricated. All 3 resulting MAP-based vaccine candidates, namely MAP-1002, MAP1003 and MAP-131, were comparable to i.m. inoculated plasmids with electroporation assistance in eliciting strong and durable IgG responses in BALB/c and C57BL/6 mice as well as rabbits, while MAP-1002 was comparatively the most immunogenic. More importantly, MAP-1002 significantly outperformed inactivated SARS-CoV-2 virus vaccine in inducing RBD-specific IFN-g+ T cells. Moreover, MAP-1002 antisera effectively neutralized pseudo- viruses displaying spike proteins of SARS-CoV, prototype SARS-CoV-2 or Beta, Delta, Omicron BA1, BA2 and BA4/5 variants. Collectively, MAP-based DNA constructs encoding chimeric RBDs of SARS-CoV and SARS-CoV-2 variants, as represented by MAP-1002, are potential COVID-19 vaccine candidates worthy further translational study.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.01.518127v1" target="_blank">Potent Immunogenicity and Broad-Spectrum Protection Potential of Microneedle Array Patch-Based COVID-19 DNA Vaccine Candidates Encoding Dimeric RBD Chimera of SARS-CoV and SARS-CoV-2 Variants</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>Are remote mental healthcare interventions cost-effective? A systematic review of economic evaluations of remote mental healthcare</strong> -
|
|||
|
<div>
|
|||
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
Background Remote interventions known as telemental health care increased in use due to the COVID-19 pandemic when social distancing requirements were in place. Whilst there is some evidence regarding the cost-effectiveness of telemental health prior to the pandemic, there is a need for further evaluation due to the increase in remote care. Aims To systematically review the literature to explore whether remote mental health care interventions are cost-effective in terms of incremental cost per quality adjusted life year and in relation to condition specific outcomes compared to usual care or an alternative intervention. Method A multilayer search strategy was conducted to build on the searches of a previous systematic review, as well as including grey literature and economic models. Six databases (PubMed, EMBASE, Cochrane Central, PsychINFO, CINAHL, and EconLit) were searched for literature relating to the cost effectiveness of telemental health. Quality appraisal was conducted for all included studies, and findings were synthesised using narrative synthesis. Results 7386 studies were identified of which 59 met our inclusion criteria and were included in the synthesis of findings. 45 studies were rated as very good or excellent quality. Of the 59 included studies, 40 indicated that the telemental health intervention was cost-effective, whilst a further 16 suggested the intervention had potential to be cost-effective, but there was some uncertainty in the findings. Three studies reported that the intervention was not cost-effective. Conclusions This evidence will be used to inform practice in the UK as we respond to and recover from the COVID-19 pandemic.
|
|||
|
</p>
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.01.22282817v1" target="_blank">Are remote mental healthcare interventions cost-effective? A systematic review of economic evaluations of remote mental healthcare</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>The Detection of COVID-19 in Chest X-Rays Using Ensemble CNN Techniques</strong> -
|
|||
|
<div>
|
|||
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
Advances in the field of image classification using convolutional neural networks (CNNs) have greatly improved the accuracy of medical image diagnosis by radiologists. Numerous research groups have applied CNN methods to diagnose respiratory illnesses from chest x-rays, and have extended this work to prove the feasibility of rapidly diagnosing COVID-19 to high degrees of accuracy. One issue in previous research has been the use of datasets containing only a few hundred images of chest x-rays containing COVID-19, causing CNNs to overfit the image data. This leads to a lower accuracy when the model attempts to classify new images, as would be clinically expected of it. In this work, we present a model trained on the COVID-QU-Ex dataset, overall containing 33,920 chest x-ray images, with an equal share of COVID-19, Non-COVID pneumonia, and Normal images. The model itself is an ensemble of pre-trained CNNs (ResNet50, VGG19, VGG16) and GLCM textural features. It achieved a 98.34% binary classification accuracy (COVID-19/no COVID-19) on a balanced test dataset of 6581 chest x-rays, and 94.68% for distinguishing between COVID-19, Non-COVID pneumonia and normal chest x-rays. Also, we herein discuss the effects of dataset size, demonstrating that a 98.82% 3-class accuracy can be achieved using the model if the training dataset only contains a few thousand images, but that generalisability of the model suffers with such small datasets.
|
|||
|
</p>
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.29.22282856v2" target="_blank">The Detection of COVID-19 in Chest X-Rays Using Ensemble CNN Techniques</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>Investigating orthographic versus auditory cross-situational word learning with online and lab-based research</strong> -
|
|||
|
<div>
|
|||
|
In recent years, cross-situational word learning (CSWL) paradigms have shown that novel words can be learned through implicit statistical learning. So far, CSWL studies using adult populations have focused on the presentation of spoken words (auditory information), however, words can also be learned through their written form (orthographic information). This study compares auditory and orthographic presentation of novel words with different degrees of phonological overlap using the CSWL paradigm. Additionally, we also present a lab-based and online-based approach to testing behavioural experiments. Due to the COVID-19 pandemic, lab testing was prematurely terminated, and testing was continued online using a newly created online testing protocol. Analyses first compared accuracy and response times across modalities, with our findings showing better and faster recognition performance for CSWL when novel words are presented through their written (orthographic condition) than through their spoken forms (auditory condition). As well, Bayesian modelling found that accuracy for the auditory condition was higher online compared to the lab-based experiment, whereas performance in the orthography condition was high in both experiments and generally outperformed the auditory condition. We discuss the implications of our findings for modality of presentation, as well as the benefits of our online testing protocol and its implementation for future research.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/tpn5e/" target="_blank">Investigating orthographic versus auditory cross-situational word learning with online and lab-based research</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>Viral burdens are associated with age and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection related sampling bias.</strong> -
|
|||
|
<div>
|
|||
|
In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burdens, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. Analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior infection, the average Ct value was 0.94 lower among Alpha variant infections, compared those with the predecessor strain, B.1.177. However, among vaccinated individuals, it was 0.34 lower among Delta variant infections, compared to those with the Alpha variant. In addition, the average Ct value decreased by 0.20 for every 10 year age increment of the infected individual. In summary, within-host viral burdens are associated with age, in addition to the interplay of vaccination status and viral variant.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.02.518847v1" target="_blank">Viral burdens are associated with age and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection related sampling bias.</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>SARS-CoV-2 Antibody response to the Sputnik Vaccine in previous infected Patients and non-infected one</strong> -
|
|||
|
<div>
|
|||
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
The begging of 2020 saw the development and trials of vaccines against Covid-19 at an unprecedented pace. The first half of 2021 has seen vaccine rollout in many countries, on the other hand, Immunity to covid-19 has exhibited to minimize the risk of having a severe infection and initiate an excellent degree against the disease. This study compares Anti-Spike IgG antibodies among vaccinated people with or without previous exposure to the coronavirus. To determine whether a single dose of sputnik V can produce significant antibody titer amongst previously infected cases and design vaccine dosage regimens accordingly. This study was performed at the Libyan biotechnology research Centre from August 2021 to December 2021. Blood samples were collected from 1811 adult males and females vaccinated with and without a history of exposure to covid-19. Previously infected individuals9 record was noted separately. Samples were immediately analyzed by Beckman Unicel Dxl 600, Access immunoassay system. Data were analyzed using GraphPad Prism 9 Software. A P-value >0.5 was not significant. The Majority of candidates 60% of the total samples were males and on analysis, it was found that 72% of patients were seropositive, on the other hand, individuals who were vaccinated and have naive antibodies from the previous infection showed slightly higher immunological response rather than vaccinated patients without previous infected and this finding can help the policymakers to design a single-dose vaccine regimen for the former category. Keywords: Sputnik V, COVID-19, Antibody, Vaccine.
|
|||
|
</p>
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.30.22282668v1" target="_blank">SARS-CoV-2 Antibody response to the Sputnik Vaccine in previous infected Patients and non-infected one</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>High SARS-CoV-2 seroprevalence in Lagos, Nigeria with robust antibody and cellular responses</strong> -
|
|||
|
<div>
|
|||
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
Background Early evidence suggested that the impact of the COVID-19 pandemic was less severe in Africa compared to other parts of the world. However, more recent studies indicate higher SARS-CoV-2 infection and COVID-19 mortality rates on the continent than previously documented. Research is needed to better understand SARS-CoV-2 seroprevalence and immunity in Africa. Methods Our collaboration with the Lagos State COVID-19 Taskforce, enabled secondary analyses of immune responses in healthcare workers (HCWs) and Oxford/AstraZeneca COVID-19 vaccine recipients from the general population across 5 local government areas (LGAs) in Lagos State, Nigeria. Western blots were used to simultaneously detect SARS-CoV-2 spike and nucleocapsid (N) antibodies and stimulation of peripheral blood mononuclear cells with N followed by an IFN-γ ELISA was used to examine T cell responses. Findings Antibody data demonstrated high SARS-CoV-2 seroprevalence of 71.6% (96/134) in HCWs and 54.8% (63/115) in the general population. Antibodies directed to only SARS-CoV-2 N, suggesting pre-existing coronavirus immunity, were seen in 10.4% (14/134) of HCWs and 20.0% (23/115) of the general population. T cell data showed that IFN-γ responses against SARS-CoV-2 N were robust in detecting exposure to the virus, demonstrating 87.5% sensitivity and 92.3% specificity. Interpretation These results have important implications for understanding the paradoxical high SARS-CoV-2 infection with low mortality rate in Africa as compared to other parts of the world, as well as for the development of T cell-based diagnostics and vaccines.
|
|||
|
</p>
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.30.22282833v1" target="_blank">High SARS-CoV-2 seroprevalence in Lagos, Nigeria with robust antibody and cellular responses</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>Severe acute infection and chronic pulmonary disease are risk factors for developing post-COVID-19 conditions</strong> -
|
|||
|
<div>
|
|||
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
Post-COVID-19 conditions, also known as long COVID, has significantly impacted the lives of many individuals, but the risk factors for this condition are poorly understood. In this study, we performed a retrospective EHR analysis of 89,843 individuals at a multi-state health system in the United States with PCR-confirmed COVID-19, including 1,086 patients diagnosed with long COVID and 1,086 matched controls not diagnosed with long COVID. For these two cohorts, we evaluated a wide range of clinical covariates, including laboratory tests, medication orders, phenotypes recorded in the clinical notes, and outcomes. We found that chronic pulmonary disease (CPD) was significantly more common as a pre-existing condition for the long COVID cohort than the control cohort (odds ratio: 1.9, 95% CI: [1.5, 2.6]). Additionally, long-COVID patients were more likely to have a history of migraine (odds ratio: 2.2, 95% CI: [1.6, 3.1]) and fibromyalgia (odds ratio: 2.3, 95% CI: [1.3, 3.8]). During the acute infection phase, the following lab measurements were abnormal in the long COVID cohort: high triglycerides (meanlongCOVID: 278.5 mg/dL vs. meancontrol: 141.4 mg/dL), low HDL cholesterol levels (meanlongCOVID: 38.4 mg/dL vs. meancontrol: 52.5 mg/dL), and high neutrophil-lymphocyte ratio (meanlongCOVID: 10.7 vs. meancontrol: 7.2). The hospitalization rate during the acute infection phase was also higher in the long COVID cohort compared to the control cohort (ratelongCOVID: 5% vs. ratecontrol: 1%). Overall, this study suggests that the severity of acute infection and a history of CPD, migraine, CFS, or fibromyalgia may be risk factors for long COVID symptoms. Our findings motivate clinical studies to evaluate whether suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.
|
|||
|
</p>
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.30.22282831v1" target="_blank">Severe acute infection and chronic pulmonary disease are risk factors for developing post-COVID-19 conditions</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>SARS-CoV-2 mRNA vaccine is re-adenylated in vivo, enhancing antigen production and immune response</strong> -
|
|||
|
<div>
|
|||
|
Though mRNA vaccines against COVID-19 have revolutionized vaccinology and have been administered in billions of doses, we know incredibly little about how mRNA vaccines are metabolized in vivo. Here we implemented enhanced nanopore Direct RNA sequencing (eDRS), to enable the analysis of single Moderna’s mRNA-1273 molecules, giving in vivo information about the sequence and poly(A) tails. We show that mRNA-1273, with all uridines replaced by N1-methylpseudouridine (m Psi), is terminated by a long poly(A) tail (~100 nucleotides) followed by an mpsimpsi AG sequence. In model cell lines, mRNA-1273 is swiftly degraded in a process initiated by the removal of mPsiPsiAG, followed by CCR4-NOT-mediated deadenylation. In contrast, intramuscularly inoculated mRNA-1273 undergoes more complex modifications. Notably, mRNA-1273 molecules are re-adenylated after mPsimPsiAG removal. Detailed analysis of immune cells involved in antigen production revealed that in macrophages, after mPsimPsiAG removal, vaccine mRNA is very efficiently re-adenylated, and poly(A) tails can reach up to 200A. In contrast, in dendritic cells, vaccine mRNA undergoes slow deadenylation-dependent decay. We further demonstrate that enhancement of mRNA stability in macrophages is mediated by TENT5 poly(A) polymerases, whose expression is induced by the vaccine itself. Lack of TENT5-mediated re-adenylation results in lower antigen production and severely compromises specific immunoglobulin production following vaccination. Together, our findings provide an unexpected principle for the high efficacy of mRNA vaccines and open new possibilities for their improvement. They also emphasize that, in addition to targeting a protein of interest, the design of mRNA therapeutics should be customized to its cellular destination.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.01.518149v1" target="_blank">SARS-CoV-2 mRNA vaccine is re-adenylated in vivo, enhancing antigen production and immune response</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>Immunopeptidome profiling of human coronavirus OC43-infected cells identifies CD4 T cell epitopes specific to seasonal coronaviruses or cross-reactive with SARS-CoV-2</strong> -
|
|||
|
<div>
|
|||
|
Seasonal “common-cold” human coronaviruses are widely spread throughout the world and are mainly associated with mild upper respiratory tract infections. The emergence of highly pathogenic coronaviruses MERS-CoV, SARS-CoV, and most recently SARS-CoV-2 has prompted increased attention to coronavirus biology and immunopathology, but identification and characterization of the T cell response to seasonal human coronaviruses remain largely uncharacterized. Here we report the repertoire of viral peptides that are naturally processed and presented upon infection of a model cell line with seasonal human coronavirus OC43. We identified MHC-I and MHC-II bound peptides derived from the viral spike, nucleocapsid, hemagglutinin-esterase, 3C-like proteinase, and envelope proteins. Only three MHC-I bound OC43-derived peptides were observed, possibly due to the potent MHC-I downregulation induced by OC43 infection. By contrast, 80 MHC-II bound peptides corresponding to 14 distinct OC43-derived epitopes were identified, including many at very high abundance within the overall MHC-II peptidome. These peptides elicited low-abundance recall T cell responses in most donors tested. In vitro assays confirmed that the peptides were recognized by CD4+ T cells and identified the presenting HLA alleles. T cell responses cross-reactive between OC43, SARS-CoV-2, and the other seasonal coronaviruses were confirmed in samples of peripheral blood and peptide-expanded T cell lines. Among the validated epitopes, S903-917 presented by DPA1<em>01:03/DPB1</em>04:01 and S1085-1099 presented by DRB1<em>15:01 shared substantial homology to other human coronaviruses, including SARS-CoV-2, and were targeted by cross-reactive CD4 T cells. N54-68 and HE128-142 presented by DRB1</em>15:01 and HE259-273 presented by DPA1<em>01:03/DPB1</em>04:01 are immunodominant epitopes with low coronavirus homology that are not cross-reactive with SARS-CoV-2. Overall, the set of naturally processed and presented OC43 epitopes comprise both OC43-specific and human coronavirus cross-reactive epitopes, which can be used to follow T cell cross-reactivity after infection or vaccination and could aid in the selection of epitopes for inclusion in pan-coronavirus vaccines.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.01.518643v1" target="_blank">Immunopeptidome profiling of human coronavirus OC43-infected cells identifies CD4 T cell epitopes specific to seasonal coronaviruses or cross-reactive with SARS-CoV-2</a>
|
|||
|
</div></li>
|
|||
|
<li><strong>The time divide: Reducing the barrier of a lack of spare time increased physical activity levels during the UK Government-enforced COVID-19 lockdown</strong> -
|
|||
|
<div>
|
|||
|
Background & Objective: Many individuals do not meet the World Health Organisation (2010) recommendations of 150 minutes of physical activity a week, often citing a lack of time as a key reason. The UK government-mandated lockdown for the global SARS-CoV-2 virus (COVID-19) pandemic provided an opportunity to investigate whether a potential increase in available time would lead to increased activity levels, and whether an increase in activity would correlate with improvements in mental health. Methods: An online survey investigated physical activity levels (time and intensity) at three separate intervals within one calendar year: firstly, for a typical week before the government-mandated lockdown; secondly, a week during lockdown (including measures of mental wellbeing); and finally in August 2020 - which re-assessed physical activity levels and mental wellbeing after the easing of some lockdown restrictions. Results: Whilst participants reported spending more time engaging in physical activity during lockdown compared to before (with those who perceived themselves to have more spare time reporting a greater increase than those who did not), there was no difference in the intensity of this activity. Additionally, there was a significant positive correlation between physical activity levels and mental wellbeing during the initial period of lockdown. Conclusions: Overall, the study demonstrated that, as hypothesised by the COM-B model, reducing one of the most commonly reported barriers (time) did increase physical activity levels. Importantly, it also showed that those who engaged in more physical activity also reported better mental health, which is particularly striking given the likely overall detrimental effect of being in lockdown.
|
|||
|
</div>
|
|||
|
<div class="article-link article-html-link">
|
|||
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/tjcfx/" target="_blank">The time divide: Reducing the barrier of a lack of spare time increased physical activity levels during the UK Government-enforced COVID-19 lockdown</a>
|
|||
|
</div></li>
|
|||
|
</ul>
|
|||
|
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
|
|||
|
<ul>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pilot Clinical Trial to Explore Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Pyramax<br/><b>Sponsor</b>: Shin Poong Pharmaceutical Co. Ltd.<br/><b>Completed</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Animation Supported COVID-19 Education</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Other: Animation-Supported Education<br/><b>Sponsor</b>: Siirt University<br/><b>Completed</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CareSuperb COVID-19 Antigen Test Usability</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: CareSuperb COVID-19 Antigen Home Test Kit<br/><b>Sponsor</b>: AccessBio, Inc.<br/><b>Recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Feasibility and Usability of COVID-19 Antigen RDTs in Uganda</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Diagnostic Test: PMC Sure Status COVID-19 Antigen Test; Diagnostic Test: Acon Flowflex COVID-19 Antigen Home Test<br/><b>Sponsor</b>: PATH<br/><b>Not yet recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SUNRISE-3: Efficacy and Safety of Bemnifosbuvir in High-Risk Outpatients With COVID-19</strong> - <b>Conditions</b>: SARS CoV 2 Infection; COVID-19<br/><b>Interventions</b>: Drug: Bemnifosbuvir (BEM); Drug: Placebo<br/><b>Sponsor</b>: Atea Pharmaceuticals, Inc.<br/><b>Recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Roles of Vitamin D and Microbiome in Children With Post-acute COVID-19 Syndromes (PACS) and Long COVID</strong> - <b>Condition</b>: Post-acute COVID-19 Syndromes<br/><b>Interventions</b>: Other: Vitamin D; Other: Placebo<br/><b>Sponsor</b>: China Medical University Hospital<br/><b>Recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About Bivalent COVID-19 RNA Vaccine Candidate(s) in Healthy Infants and Children</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 1 microgram dose<br/><b>Sponsors</b>: BioNTech SE; Pfizer<br/><b>Not yet recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of an Integrative Medicine Outpatient Clinical Setting for Post-COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Fatigue<br/><b>Interventions</b>: Behavioral: outpatient clinic with multimodal integrative medicine and naturopathy for post-COVID-19 patients; Other: waiting group<br/><b>Sponsor</b>: Universität Duisburg-Essen<br/><b>Recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Rapid Panel Professional Use Product Using Mid-Turbinate Nasal Swabs</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza Type B<br/><b>Intervention</b>: Diagnostic Test: Panbio™<br/><b>Sponsor</b>: Abbott Rapid Dx<br/><b>Not yet recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of a Physical and Respiratory Rehabilitation Program for Patients With Persistent COVID-19 (SARS-CoV-2).</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19 Recurrent; Cognitive Dysfunction; Fatigue<br/><b>Intervention</b>: Other: COPERIA-REHAB<br/><b>Sponsors</b>: Fundacin Biomedica Galicia Sur; University of Vigo; Galician South Health Research Institute<br/><b>Not yet recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Household Contacts of Covid-19</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Henlius Biotech; Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.; HeNan Sincere Biotech Co., Ltd<br/><b>Not yet recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Randomised Clinical Trial to Evaluate the Efficacy of an Online Cognitive Rehabilitation Programme (COPERIA-COG) for Patients With Persistent COVID-19</strong> - <b>Conditions</b>: COVID-19; Neuro-Degenerative Disease; Psychological; SARS CoV 2 Infection<br/><b>Intervention</b>: Other: Sessions of cognitive stimulation<br/><b>Sponsors</b>: Fundacin Biomedica Galicia Sur; Centro de Investigación Biomédica en Red de Salud Mental; Galician South Health Research Institute<br/><b>Not yet recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>VNS for Long-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Postural Tachycardia Syndrome; Dysautonomia<br/><b>Interventions</b>: Device: Non-invasive vagus nerve stimulation; Device: Sham Intervention<br/><b>Sponsor</b>: Icahn School of Medicine at Mount Sinai<br/><b>Recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Differential Diagnosis of Persistent COVID-19 by Artificial Intelligence</strong> - <b>Conditions</b>: COVID-19; Fatigue; Distress Respiratory Syndrome; Cognitive Dysfunction; COVID-19 Recurrent; SARS CoV 2 Infection<br/><b>Intervention</b>: Other: Experimental tests<br/><b>Sponsors</b>: Fundacin Biomedica Galicia Sur; University of Vigo; Galician South Health Research Institute<br/><b>Not yet recruiting</b></p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dietary Modulation of Gut Microbiota in Overweight/Obese Adolescents and COVID-19 Infection</strong> - <b>Conditions</b>: Health Behavior; Child Development; Adolescent Obesity<br/><b>Interventions</b>: Dietary Supplement: Probiotics; Behavioral: Counselling on healthy eating, physical activity, and psychosocial stimulation; Dietary Supplement: Placebo probiotics<br/><b>Sponsors</b>: Indonesia University; Gadjah Mada University; Universitas Airlangga; University of Melbourne; The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia<br/><b>Recruiting</b></p></li>
|
|||
|
</ul>
|
|||
|
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
|
|||
|
<ul>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cholinergic dysfunction in COVID-19: frantic search and hoping for the best</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immune response and protective efficacy of the SARS-CoV-2 recombinant spike protein vaccine S-268019-b in mice</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of action of steroid molecules on SARS-CoV-2 by inhibiting NSP-15, an endoribonuclease</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABA<sub>B</sub>-ergic activity and cortical plasticity in long COVID-19 syndrome</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ubiquitin specific peptidase 25 alleviates acute lung injury and suppresses the inflammatory response in lung epithelial cells</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Combining Computational and Experimental Evidence on the Activity of Antimalarial Drugs on Papain-Like Protease of SARS-CoV-2: A Repurposing Study</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Paxlovid<sup>TM</sup> Information From FDA and Guidance for AES Members</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Platelet in thrombo-inflammation: Unraveling new therapeutic targets</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Recombinant proteins of spike protein of SARS-CoV-2 with the Omicron receptor-binding domain induce production of highly Omicron-specific neutralizing antibodies</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>B-cell lymphoma-2 family proteins-activated proteases as potential therapeutic targets for influenza A virus and severe acute respiratory syndrome coronavirus-2: Killing two birds with one stone?</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Common and rare variant associations with clonal haematopoiesis phenotypes</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Essential oils block cellular entry of SARS-CoV-2 delta variant</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparison of RT-dPCR and RT-qPCR and the effects of freeze-thaw cycle and glycine release buffer for wastewater SARS-CoV-2 analysis</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Meet changes with constancy: Defence, antagonism, recovery, and immunity roles of extracellular vesicles in confronting SARS-CoV-2</strong> - No abstract</p></li>
|
|||
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Protocol for a 30-day randomised, parallel-group, non-inferiority, controlled trial investigating the effects of discontinuing renin-angiotensin system inhibitors in patients with and without COVID-19: the RASCOVID-19 trial</strong> - No abstract</p></li>
|
|||
|
</ul>
|
|||
|
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
|
|||
|
|
|||
|
|
|||
|
<script>AOS.init();</script></body></html>
|