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166 lines
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<title>08 August, 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>Online Asynchronous Learning English for Specific Purposes Terminology</strong> -
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<div>
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The pandemic and military actions in the country triggered our study in considering the challenges Ukrainian higher education faces referring asynchronous learning. We assume that the challenges are threefold – namely – psychological, technical (availability of means for providing asynchronous communication and technological (scientifically grounded methods of quality asynchronous learning). In our study the focus is on the methods of asynchronous learning specialized terminology. The background of the research was the study of the literature concerning benefits and limitations of asynchronous learning and implementing online courses into the learning process. The purpose of this research was to prove the effectiveness of asynchronous learning specialized vocabulary with the help of the Moodle-based course. The aim was achieved by fulfilling the following tasks: literary review to study the benefits and limitations of asynchronous and synchronous learning for finding the most suitable mode of communication for the Ukrainian students, to design a Moodle-based course, to verify it in the experimental learning. The experiment was conducted in 2020 in the time of Covid-19 pandemic at the National Technical University of Ukraine, Igor Sikorsky Kyiv Polytechnic Institute, and involved seventy students of the Power Engineering Department. The research purpose of both the article and the experiment was to assess the effectiveness of the developed online simulator which included audio recordings of native English specialists’ communication, interdisciplinary and industry-specific terminology, training tasks, and instructional guidelines. The outcome of the research proves the efficiency of applying an online simulator in the development of students’ professional competence in terms of adequate using interdisciplinary and industry-specific terminology.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/bwamx/" target="_blank">Online Asynchronous Learning English for Specific Purposes Terminology</a>
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</div></li>
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<li><strong>The impact of COVID-19 on household energy consumption in England and Wales from April 2020 – March 2022</strong> -
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<div>
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The COVID-19 pandemic changed the way people lived, worked, and studied around the world, with direct consequences for domestic energy use. This study assesses the impact of COVID-19 lockdowns in the first two years of the pandemic on household electricity and gas use in England and Wales. Using data for 508 (electricity) and 326 (gas) homes, elastic net regression, neural network and extreme gradient boosting predictive models were trained and tested on pre-pandemic data. The most accurate model for each household was used to create counterfactuals (predictions in the absence of COVID-19) against which observed pandemic energy use was compared. Median monthly model error (CV(RMSE)) was 3.86% (electricity) and 3.19% (gas) and bias (NMBE) was 0.21% (electricity) and -0.10% (gas). Our analysis showed that on average (electricity; gas) consumption increased by (7.8%; 5.7%) in year 1 of the pandemic and by (2.2%; 0.2%) in year 2. The greatest increases were in the winter lockdown (January – March 2021) by 11.6% and 9.0% for electricity and gas, respectively. At the start of 2022 electricity use remained 2.0% higher while gas use was around 1.9% lower than predicted. Households with children showed the greatest increase in electricity consumption during lockdowns, followed by those with adults in work. Wealthier households increased their electricity consumption by more than the less wealthy and continued to use more than predicted throughout the two-year period while the less wealthy returned to pre-pandemic or lower consumption from summer 2021. Low dwelling efficiency was associated with a greater increase in energy consumption during the pandemic. Additionally, this study shows the value of different machine learning techniques for counterfactual modelling at the individual-dwelling level, and our approach can be used to robustly estimate the impact of other events and interventions.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/m5p3b/" target="_blank">The impact of COVID-19 on household energy consumption in England and Wales from April 2020 – March 2022</a>
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</div></li>
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<li><strong>Human-Network Regions as Effective Geographic Units for Disease Mitigation</strong> -
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<div>
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Susceptibility to infectious diseases such as COVID-19 depends on how those diseases spread, and many studies have examined the decrease in COVID-19 spread due to reduction in travel. However, less is known about how much functional geographic regions, which capture natural movements and social interactions, limit the spread of COVID-19. To determine boundaries between functional regions, we apply community-detection algorithms to large networks of mobility and social-media connections to construct geographic regions that reflect natural human movement and relationships at the county level in the continental United States. We measure COVID-19 case counts, case rates, and case-rate variations across adjacent counties and examine how often COVID-19 crosses the boundaries of these functional regions. We find that regions that we construct using GPS-trace networks and especially commute networks have the lowest COVID-19 case rates along the boundaries, so these regions may reflect natural partitions in COVID-19 transmission. Conversely, regions that we construct from geolocated Facebook friendships and Twitter connections yield less effective partitions. Our analysis reveals that regions that are derived from movement flows are more appropriate geographic units than states for making policy decisions about opening areas for activity, assessing vulnerability of populations, and allocating resources. Our insights are also relevant for policy decisions and public messaging in future emergency situations.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/4mp6x/" target="_blank">Human-Network Regions as Effective Geographic Units for Disease Mitigation</a>
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</div></li>
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<li><strong>OUTCOME OF COVID-19 PATIENTS ON STEROID THERAPY: A LONGITUDINAL STUDY</strong> -
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ABSTRACT: Introduction: SARS-CoV-2 is responsible for global pandemic that originates from Wuhan, China (1). Patients presentation van be varied from asymptomatic to severe ARDS and multiorgan dysfunction likely due the dysregulated systemic inflammation (2). Glucocorticoids inhibits the inflammation by down streaming of cytokine receptor and promote resolution (3). The role of corticosteroid in COVID-19 still remains controversial. Corticosteroids associated with many long terms side effects. Previous MARS outbreak had experienced avascular necrosis with corticosteroid use (4). Objectives: The aim of the study was to evaluate the outcome of covid-19 patients on the corticosteroid therapy and estimate mortality rate with corticosteroid therapy and investigate potential long-term adverse events associated with its use. Methods: We did a longitudinal follow up study at the AIIMS Rishikesh to assess the side effects of corticosteroids in COVID-19 patients. Patients with moderate to severe COVID-19 pneumonia requiring the oxygen support were included in the study. According to the institutional protocol patients received conventional dose steroids versus pulse dose steroids. (Based on CT/ X-ray findings). Patients were followed up in the hospital till discharge/death for assessment of adverse events due to corticosteroids and all other biochemical parameters (Inflammatory markers) and SOFA score were obtained during hospitalisation till discharge. And at the 6 month follow up patient was assessed for infection and avascular necrosis of the femur. Results: A total of 600 patients were screened out of which 541 patients who received corticosteroids were included in this study. 71.3% were male and 26.6 % were females. Most prevalent comorbidity was systemic hypertension (38.8%) followed by diabetes mellitus (38%). Most common presenting symptoms was dyspnoea followed by fever and cough. Majority patients received dexamethasone (95%). 65.8 % patients received conventional dose while 34.2% of patients received pulse dose. Mortality was more associated with pulse dose (44%) then a conventional dose (30%) (p-value 0.0015). the median duration of the corticosteroids was 10 days with an IQR of 7-13 days. During the hospitalisation 142 patients (26.2%) develops hyperglycaemia. Hyperglycaemia was more prevalent in the pulse dose steroid group (16.8% versus 9.4%). One patient develops pancreatitis. There was a significant reduction in the levels of inflammatory markers (p<0.005) after steroid initiation. At the 6th month of follow patients were assessed for AVN and suspected infection. 25 patients (8.25%) had infection out of which 19 received pulse dose. Out of 25 patients cultures was available for 7 patients and 2 patients grows pathogenic organism in the urine (pseudomonas and E. coli). 02 patients develop non-specific joint pain at 6 months. No patient had AVN during the follow up.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.03.23293425v2" target="_blank">OUTCOME OF COVID-19 PATIENTS ON STEROID THERAPY: A LONGITUDINAL STUDY</a>
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</div></li>
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<li><strong>The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records.</strong> -
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Background The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity to ensure safety and appropriateness of ongoing prescribing and a disruption could have significant negative implications for patient care. Aim Using routinely collected data, our aim was to i) describe the SNOMED CT codes used to report medication review activity ii) report the impact of COVID-19 on the volume and variation of medication reviews. Design and setting With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform. Method For each month between April 2019 - March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months. These measures were broken down by regional, clinical and demographic subgroups and amongst those prescribed high risk medications. Results In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity substantially decreased (-21.1% April 2020), but the rate of patients with a medication review coded in the previous 12 months was not substantially impacted according to our classification (-10.5% March 2021). There was regional and ethnic variation (March 2022 - London 21.9% vs North West 33.6%; Chinese 16.8% vs British 33.0%). Following the introduction of “structured medication reviews”, the rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high risk groups (March 2022 - care home residents 34.1%, 90+ years 13.1%, high risk medications 10.2%). The most used SNOMED CT medication review code across the study period was Medication review done - 314530002 (59.5%). Conclusion We have reported a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.31.23293419v2" target="_blank">The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records.</a>
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</div></li>
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<li><strong>Predicting Protein-Ligand Binding Structure Using E(n) Equivariant Graph Neural Networks</strong> -
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Drug design is a costly and time-consuming process, often taking more than 12 years and costing up to billions of dollars. The COVID-19 pandemic has signified the urgent need for accelerated drug development. The initial stage of drug design involves the identification of ligands that exhibit a strong affinity for specific binding sites on protein targets (receptors), along with the determination of their precise binding conformation (3-dimensional (3D) structure). However, accurately determining the 3D conformation of a ligand binding with its target remains challenging due to the limited capability of exploring the huge chemical and protein structure space. To address this challenge, we propose a new E(n) Equivariant Graph Neural Network (EGNN) method for predicting the 3D binding structures of ligands and proteins. By treating proteins and ligands as graphs, the method extracts residue/atom-level node and edge features and utilizes physicochemical and geometrical properties of proteins and ligands to predict their binding structures. The results demonstrate the promising potential of EGNN for predicting ligand-protein binding poses.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.06.552202v1" target="_blank">Predicting Protein-Ligand Binding Structure Using E(n) Equivariant Graph Neural Networks</a>
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</div></li>
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<li><strong>A Framework for Moving Beyond Computational Reproducibility: Lessons from Three Reproductions of Geographical Analyses of COVID-19</strong> -
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<div>
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Despite recent calls to make geographical analyses more reproducible, formal attempts to reproduce or replicate published work remain largely absent from the geographic literature. The reproductions of geographic research that do exist typically focus on computational reproducibility - whether results can be recreated using data and code provided by the authors - rather than on evaluating the conclusion and internal validity and evidential value of the original analysis. However, knowing if a study is computationally reproducible is insufficient if the goal of a reproduction is to identify and correct errors in our knowledge. We argue that reproductions of geographic work should focus on assessing whether the findings and claims made in existing empirical studies are well supported by the evidence presented. We present three model reproductions of geographical analyses of COVID-19 that demonstrate how to achieve this goal. Each reproduction is based on a common, open access template and is published as an open access repository, complete with pre-analysis plan, data, code, and final report. We find each study to be partially reproducible, but moving past computational reproducibility, our assessments reveal conceptual and methodological concerns that raise questions about the predictive value and the magnitude of the associations presented in each study. Collectively, these reproductions and our template materials offer a practical framework others can use to reproduce and replicate empirical spatial analyses and ultimately facilitate the identification and correction of errors in the geographic literature.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/metaarxiv/7jqtv/" target="_blank">A Framework for Moving Beyond Computational Reproducibility: Lessons from Three Reproductions of Geographical Analyses of COVID-19</a>
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</div></li>
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<li><strong>The Impact of the UK COVID-19 Lockdown on the Screening, Diagnostics and Incidence of Breast, Colorectal, Lung and Prostate Cancer in the UK: a Population-Based Cohort Study</strong> -
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Objectives: This study aimed to assess the impact of the COVID-19 lockdown on the screening and diagnosis of breast, colorectal, lung, and prostate cancer. The study also investigated whether the rates returned to pre-pandemic levels by December 2021. Design: Cohort study. Setting: Electronic health records from UK primary care Clinical Practice Research Datalink (CPRD) GOLD database. Participants: The study included individuals registered with CPRD GOLD between January 2017 and December 2021, with at least 365 days of prior observation. Main outcome measures: The study focused on screening, diagnostic tests, referrals and diagnoses of first-ever breast, colorectal, lung, and prostate cancer. Incidence rates (IR) were stratified by age, sex and region, and incidence rate ratios (IRR) were calculated to compare rates during and after lockdown with the reference period before lockdown. Forecasted rates were estimated using negative binomial regression models. Results: Among 5,191,650 eligible participants, the initial lockdown resulted in reduced screening and diagnostic tests for all cancers, which remained dramatically reduced across the whole observation period for almost all tests investigated. For cancer incidence rates, there were significant IRR reductions in breast (0.69), colorectal (0.74), and prostate (0.71) cancers. However, the reduction in lung cancer incidence (0.92) was non-significant. Extrapolating to the entire UK population, an estimated 18,000 breast, 13,000 colorectal, 10,000 lung, and 21,000 prostate cancer diagnoses were missed from March 2020 to December 2021. Conclusion: The national COVID-19 lockdown in the UK had a substantial impact on cancer screening, diagnostic tests, referrals and diagnoses. Although incidence rates started to recover after the lockdown, they remained significantly lower than pre-pandemic levels for breast and prostate cancers and associated tests. Delays in diagnosis are likely to have adverse consequences on cancer stage, treatment initiation, mortality rates, and years of life lost. Urgent strategies are needed to identify undiagnosed cases and address the long-term implications of delayed diagnoses.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.21.23292937v2" target="_blank">The Impact of the UK COVID-19 Lockdown on the Screening, Diagnostics and Incidence of Breast, Colorectal, Lung and Prostate Cancer in the UK: a Population-Based Cohort Study</a>
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</div></li>
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<li><strong>Quantification of biases in predictions of protein-protein binding affinity changes upon mutations</strong> -
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Understanding the impact of mutations on protein-protein binding affinity is a key objective for a wide range of biotechnological applications and for shedding light on disease-causing mutations, which are often located at protein-protein interfaces. Over the past decade, many computational methods using physics-based and/or machine learning approaches have been developed to predict how protein binding affinity changes upon mutations. They all claim to achieve astonishing accuracy on both training and test sets, with performances on standard benchmarks such as SKEMPI 2.0 that seem overly optimistic. Here we benchmarked six well-known and well-used predictors and identified their biases and dataset dependencies, using not only SKEMPI 2.0 as a test set but also deep mutagenesis data on the SARS-CoV-2 spike protein in complex with the human angiotensin-converting enzyme 2. We showed that, even though most tested methods reach a significant degree of robustness and accuracy, they suffer from limited generalizability properties and struggle to predict unseen mutations. Undesirable prediction biases towards specific mutation properties, the most marked being towards destabilizing mutations, are also observed and should be carefully considered by method developers. We conclude from our analyses that there is room for improvement of the prediction models and propose ways to check, assess and improve their generalizability and robustness.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.04.551687v1" target="_blank">Quantification of biases in predictions of protein-protein binding affinity changes upon mutations</a>
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<li><strong>SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency</strong> -
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Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged SARS-CoV-2 infection, but the immune defects that predispose to persistent COVID-19 remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median time to nasal viral RNA and culture clearance in the severe hematologic malignancy/transplant group (S-HT) were 72 and 40 days, respectively, which were significantly longer than clearance rates in the severe autoimmune/B-cell deficient (S-A), non-severe, and non-immunocompromised groups (P<0.001). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing antiviral treatment resistance. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral, while only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.31.23293441v2" target="_blank">SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency</a>
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</div></li>
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<li><strong>Mucosal and systemic immune dynamics associated with COVID-19 outcomes: a longitudinal prospective clinical study</strong> -
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Rationale: COVID-19 severity varies widely; children and African Americans have low and high risk, respectively. Mechanistic data from these groups and the mucosa is lacking. Objectives: To quantify mucosal and systemic viral and immune dynamics in a diverse cohort to identify mechanisms underpinning COVID-19 severity and outcome predictors. Methods: In this prospective study of unvaccinated children and adults COVID-19 outcome was based on an ordinal clinical severity scale. We quantified viral RNA, antigens, antibodies, and cytokines by PCR, ELISA, and Luminex from 579 longitudinally collected blood and nasal specimens from 78 subjects including 45 women and used modeling to determine functional relationships between these data. Measurements and Main Results: COVID-19 induced unique immune responses in African Americans (n=26) and children (n=20). Mild outcome was associated with more effective coordinated responses whereas moderate and severe outcomes had rapid seroconversion, significantly higher antigen, mucosal sCD40L, MCP-3, MCP-1, MIP-1, and MIP-1{beta}, and systemic IgA, IgM, IL-6, IL-8, IL-10, IL-15, IL-1RA, and IP-10, and uncoordinated early immune responses that went unresolved. Mucosal IL-8, IL-1{beta}, and IFN-{gamma} with systemic IL-1RA and IgA predicted COVID-19 outcomes. Conclusions: We present novel mucosal data, biomarkers, and therapeutic targets from a diverse cohort. Based on our findings, children and African Americans with COVID-19 have significantly lower IL-6 and IL-17 levels which may reduce responsiveness to drugs targeting IL-6 and IL-17. Unregulated immune responses persisted indicating moderate to severe COVID-19 cases may require prolonged treatments. Reliance on slower acting adaptive responses may cause immune crisis for some adults who encounter a novel virus.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.04.551867v1" target="_blank">Mucosal and systemic immune dynamics associated with COVID-19 outcomes: a longitudinal prospective clinical study</a>
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</div></li>
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<li><strong>Recombinant SARS-CoV-2 lacking initiating and internal methionine codons within ORF10 is attenuated in vivo</strong> -
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SARS-CoV-2 has been proposed to encode ORF10 as the 3' terminal gene in the viral genome. However, the potential role and even existence of a functional ORF10 product has been the subject of debate. There are significant structural features in the viral genomic RNA that could, by themselves, explain the retention of the ORF10 nucleotide sequences without the need for a functional protein product. To explore this question further we made two recombinant viruses, firstly a control virus (WT) based on the genome sequence of the original Wuhan isolate and with the inclusion of the early D614G mutation in the Spike protein. We also made a second virus, identical to WT except for two additional changes that replaced the initiating ORF10 start codon and an internal methionine codon for stop codons (ORF10KO). Here we show that the two viruses have apparently identical growth kinetics in a VeroE6 cell line that over expresses TMPRSS2 (VTN cells). However, in A549 cells over expressing ACE2 and TMPRSS2 (A549-AT cells) the ORF10KO virus appears to have a small growth rate advantage. Growth competition experiments were used whereby the two viruses were mixed, passaged in either VTN or A549-AT cells and the resulting output virus was sequenced. We found that in VTN cells the WT virus quickly dominated whereas in the A549-AT cells the ORF10KO virus dominated. We then used a hamster model of SARS-CoV-2 infection and determined that the ORF10KO virus has attenuated pathogenicity (as measured by weight loss). We found an almost 10-fold reduction in viral titre in the lower respiratory tract for ORF10KO vs WT. In contrast, the WT and ORF10KO viruses had similar titres in the upper respiratory tract. Sequencing of viral RNA in the lungs of hamsters infected with ORF10KO virus revealed that this virus frequently reverts to WT. Our data suggests that the retention of a functional ORF10 sequence is highly desirable for SARS-CoV-2 infection of hamsters and affects the virus's ability to propagate in the lower respiratory tract.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.04.551973v1" target="_blank">Recombinant SARS-CoV-2 lacking initiating and internal methionine codons within ORF10 is attenuated in vivo</a>
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<li><strong>SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection</strong> -
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Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothrombotic state is considered a key factor in the increased risk of stroke, which has been observed clinically during both acute infection and long after symptoms have cleared. Here we developed a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells, pericytes, and smooth muscle cells to recapitulate the vascular pathology associated with SARS-CoV-2 exposure. Our results demonstrate that perivascular cells, particularly smooth muscle cells (SMCs), are a specifically susceptible vascular target for SARS-CoV-2 infection. Utilizing RNA sequencing, we characterized the transcriptomic changes accompanying SARS-CoV-2 infection of SMCs, and endothelial cells (ECs). We observed that infected human SMCs shift to a pro-inflammatory state and increase the expression of key mediators of the coagulation cascade. Further, we showed human ECs exposed to the secretome of infected SMCs produce hemostatic factors that can contribute to vascular dysfunction, despite not being susceptible to direct infection. The findings here recapitulate observations from patient sera in human COVID-19 patients and provide mechanistic insight into the unique vascular implications of SARS-CoV-2 infection at a cellular level.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.06.552160v1" target="_blank">SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection</a>
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<li><strong>phuEGO: A network-based method to reconstruct active signalling pathways from phosphoproteomics datasets</strong> -
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Signalling networks are critical for virtually all cell functions. Our current knowledge of cell signalling has been summarised in signalling pathway databases, which, while useful, are highly biassed towards well-studied processes, and don't capture context specific network wiring or pathway cross-talk. Mass spectrometry-based phosphoproteomics data can provide a more unbiased view of active cell signalling processes in a given context, however, it suffers from low signal-to-noise ratio and poor reproducibility across experiments. Methods to extract active signalling signatures from such data struggle to produce unbiased and interpretable networks that can be used for hypothesis generation and designing downstream experiments. Here we present phuEGO, which combines three-layer network propagation with ego network decomposition to provide small networks comprising active functional signalling modules. PhuEGO boosts the signal-to-noise ratio from global phosphoproteomics datasets, enriches the resulting networks for functional phosphosites and allows the improved comparison and integration across datasets. We applied phuEGO to five phosphoproteomics data sets from cell lines collected upon infection with SARS CoV2. PhuEGO was better able to identify common active functions across datasets and to point to a subnetwork enriched for known COVID-19 targets. Overall, phuEGO provides a tool to the community for the improved functional interpretation of global phosphoproteomics datasets.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.07.552249v1" target="_blank">phuEGO: A network-based method to reconstruct active signalling pathways from phosphoproteomics datasets</a>
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<li><strong>Purifying selection and adaptive evolution proximate to the zoonosis of SARS-CoV-1 and SARS-CoV-2</strong> -
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<div>
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Over the past two decades the pace of spillovers from animal viruses to humans has accelerated, with COVID-19 becoming the most deadly zoonotic disease in living memory. Prior to zoonosis, it is conceivable that the virus might largely be subjected to purifying selection, requiring no additional selective changes for successful zoonotic transmission. Alternatively, selective changes occurring in the reservoir species may coincidentally preadapt the virus for human-to-human transmission, facilitating spread upon cross-species exposure. Here we quantify changes in the genomes of SARS-CoV-2 and SARS-CoV-1 proximate to zoonosis to evaluate the selection pressures acting on the viruses. Application of molecular-evolutionary and population-genetic approaches to quantify site-specific selection within both SARS-CoV genomes revealed strong purifying selection across many genes at the time of zoonosis. Even in the viral surface-protein Spike that has been fast-evolving in humans, there is little evidence of positive selection proximate to zoonosis. Nevertheless, in SARS-CoV-2, NSP12, a core protein for viral replication, exhibited a region under adaptive selection proximate to zoonosis. Furthermore, in both SARS-CoV-1 and SARS-CoV-2, regions of adaptive selection proximate to zoonosis were found in ORF7a, a putative Major Histocompatibility Complex modulatory gene. These findings suggest that these replication and immunomodulatory proteins have played a previously underappreciated role in the adaptation of SARS coronaviruses to human hosts.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.07.552269v1" target="_blank">Purifying selection and adaptive evolution proximate to the zoonosis of SARS-CoV-1 and SARS-CoV-2</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: Freeze-dried Mare Milk (Saumal)<br/><b>Sponsor</b>: Asfendiyarov Kazakh National Medical University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Exercise Training on Patients With Long COVID-19</strong> - <b>Condition</b>: Long COVID-19<br/><b>Intervention</b>: Behavioral: Exercise training<br/><b>Sponsor</b>: Guangdong Provincial People’s 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>Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly</strong> - <b>Conditions</b>: Vaccination; Infection; COVID-19<br/><b>Intervention</b>: Biological: Comirnaty<br/><b>Sponsor</b>: Radboud University Medical Center<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 Phase 2/3 Open-Label Study to Evaluate the Safety and Immunogenicity of an XBB.1.5 (Omicron Subvariant) SARS CoV-2 rS Vaccine.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: XBB.1.5 Vaccine (Booster); Biological: XBB.1.5 Vaccine (single dose)<br/><b>Sponsor</b>: Novavax<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: mRNA-CR-04 vaccine 10μg; Biological: mRNA-CR-04 vaccine 30μg; Biological: mRNA-CR-04 vaccine 100μg; Drug: Placebo<br/><b>Sponsor</b>: GlaxoSmithKline<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 Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine; Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)<br/><b>Sponsor</b>: Novavax<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hyperbaric on Pulmonary Functions in Post Covid -19 Patients.</strong> - <b>Condition</b>: Post COVID-19 Patients<br/><b>Interventions</b>: Device: hyperbaric oxygen therapy; Device: breathing exercise; Drug: medical treatment<br/><b>Sponsor</b>: Cairo 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>Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Fatigue<br/><b>Interventions</b>: Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome; Other: Attention Control<br/><b>Sponsor</b>: University of Maryland, Baltimore<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>HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19</strong> - <b>Conditions</b>: COVID-19; Delirium; Critical Illness<br/><b>Interventions</b>: Combination Product: Active HD-tDCS; Combination Product: Sham HD-tDCS<br/><b>Sponsors</b>: Suellen Andrade; City University of New York<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>RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms</strong> - <b>Conditions</b>: Long COVID-19; Long COVID<br/><b>Interventions</b>: Drug: Paxlovid 25 day dosing; Drug: Paxlovid 15 day dosing; Drug: Control<br/><b>Sponsor</b>: Kanecia Obie Zimmerman<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Biological: CV0701 Bivalent High dose; Biological: CV0701 Bivalent Medium dose; Biological: CV0701 Bivalent Low dose; Biological: CV0601 Monovalent High dose; Biological: Control vaccine<br/><b>Sponsors</b>: GlaxoSmithKline; CureVac<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>RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19<br/><b>Interventions</b>: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham<br/><b>Sponsor</b>: Duke University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Directed Topical Drug Delivery for Treatment for PASC Hyposmia</strong> - <b>Condition</b>: Post Acute Sequelae Covid-19 Hyposmia<br/><b>Interventions</b>: Drug: Beclomethasone; Other: Placebo; Device: Microsponge<br/><b>Sponsor</b>: Duke University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19<br/><b>Interventions</b>: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham<br/><b>Sponsor</b>: Duke University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of COVID-19 on Sinus Augmentation Surgery</strong> - <b>Condition</b>: Bone Loss<br/><b>Interventions</b>: Procedure: Sinus lift in patients with positive COVID-19 history; Procedure: Sinus lift with negative COVID-19 history<br/><b>Sponsor</b>: Cairo University<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Developmental Pathway From Early Behavioral Inhibition to Young Adults’ Anxiety During the COVID-19 Pandemic</strong> - CONCLUSION: This study identifies a developmental pathway from toddlerhood BI to young adults’ elevated anxiety during the COVID-19 pandemic. Findings have implications for early identification of individuals at risk for dysregulated worry and the prevention of anxiety during stressful life events in young adulthood.</li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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