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<title>17 August, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>LIMITED EVIDENCE FOR NEUROPSYCHOLOGICAL DYSFUNCTION IN PATIENTS INITIALLY AFFECTED BY SEVERE COVID-19</strong> -
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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in coronavirus disease 2019 (COVID-19), has caused a pandemic. There is now considerable evidence that neuropsychological functions could be affected. We further tested this hypothesis on a sample of post COVID-19 patients, who, initially, had been severely affected. METHODS: We tested 22 post COVID-19 patients who, after the intensive care unit, were submitted to our rehabilitation unit to be treated for severe post COVID-19 sequelae. All patients were assessed with a comprehensive neuropsychological battery including measures assessing perceptual, attentive, mnestic, linguistic, and executive functions, and overall cognitive status. The patients were also administered rehabilitation measures including scales for investigating aerobic capacity/endurance deficits, dyspnea, and fatigue. RESULTS: Our findings revealed that evidence of neuropsychological disorders on post COVID-19 patients was very limited. Furthermore, COVID-19 severity and other relevant variables were not correlated with patients’ scores on the neuropsychological tests. CONCLUSIONS: We suggest that the relation between COVID-19 and neuropsychological disorders is unclear. New studies and metanalyses are highly required to shed light on this highly complex issue.
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🖺 Full Text HTML: <a href="https://osf.io/hcnsd/" target="_blank">LIMITED EVIDENCE FOR NEUROPSYCHOLOGICAL DYSFUNCTION IN PATIENTS INITIALLY AFFECTED BY SEVERE COVID-19</a>
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<li><strong>Transcriptomic and epigenetic assessment of ageing male skin identifies disruption of Ca2+ homeostasis; exacerbated by smoking and UV exposure</strong> -
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Skin ageing has been widely associated with the formation and presence of increasing quantities of senescent cells, the presence of which are thought to reduce cell renewal. This study aimed to identify key factors influencing fibroblast and skin aging in European males using RNA-seq data. Key differences in study designs included known sources of biological differences (sex, age, ethnicity), experimental differences, and environmental factors known to accelerate skin ageing (smoking, UV exposure) as well as study specific batch effects which complicated the analysis. To overcome these complications samples were stratified by these factors and differential expression assessed using Salmon and CuffDiff. Functional enrichment and consistency across studies, stratification’s and tools identified age related alterations in the transcriptomes of fibroblasts and skin. Functional enrichment of results identified alterations in protein targeting to membranes and the ER, and altered calcium homeostasis in aged fibroblasts. Extension to skin controlled for differences in fibroblast culturing methods confirming transient age related alterations in intracellular calcium homeostasis. In middle aged males (40-65) increased keratinisation, skin, epithelial and epidermal development was seen in conjunction with alterations to ER Calcium uptake, leading to the identification of related processes including; an unfolded protein response, altered metabolism, increased MMP expression, and altered Calcium handling, which were further exacerbated by UV-exposure. Interestingly the genes and processes subsequently decreased in old males (> 65), which exhibited signs of increased senescence. Extension to Illumina 450k array data from ageing skin uncovered evidence of epigenetic regulation; genes and isoforms with overlapping differentially methylated CpGs were differentially expressed. Smoking led to additional enrichment of genes relating to tissue development, cell adhesion, vasculature development, peptide cross-linking, calcium homeostasis, cancer and senescence. The results consistently identified alterations in ER and golgi Calcium uptake, which disrupt intracellular and extracellular calcium gradients that regulate metabolic and differentiation signalling in skin and fibroblasts, leading to age related declines skin structure and function. Interestingly many diseases and infections with overlapping molecular consequences, (ER Calcium stress, reduced protein targeting to membranes) including COVID-19 are identified by the analysis, suggesting that COVID-19 infection compounds pre-existing cellular stresses in aged males, which could help explain higher COVID-19 mortality rates in aged males, as well as highlighting potential ways to reduce them.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.16.504102v1" target="_blank">Transcriptomic and epigenetic assessment of ageing male skin identifies disruption of Ca2+ homeostasis; exacerbated by smoking and UV exposure</a>
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<li><strong>Intrahost SARS-CoV-2 k-mer identification method (iSKIM) for rapid detection of mutations of concern reveals emergence of global mutation patterns</strong> -
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Despite unprecedented global sequencing and surveillance of SARS-CoV-2, timely identification of the emergence and spread of novel variants of concern (VoCs) remains a challenge. Several million raw genome sequencing runs are now publicly available. We sought to survey these datasets for intrahost variation to study emerging mutations of concern. We developed iSKIM (intrahost SARS-CoV-2 k-mer identification method) to relatively quickly and efficiently screen the many SARS-CoV-2 datasets to identify intrahost mutations belonging to lineages of concern. Certain mutations surged in frequency as intrahost minor variants just prior to, or while lineages of concern arose. The Spike N501Y change common to several VoCs was found as a minor variant in 834 samples as early as October 2020. This coincides with the timing of the first detected samples with this mutation in the Alpha/B.1.1.7 and Beta/B.1.351 lineages. Using iSKIM, we also found that Spike L452R was detected as an intrahost minor variant as early as September 2020, prior to the observed rise of the Epsilon/B.1.429/B.1.427 lineages in late 2020. iSKIM rapidly screens for mutations of interest in raw data, prior to genome assembly, and can be used to detect increases in intrahost variants, potentially providing an early indication of novel variant spread.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.16.504117v1" target="_blank">Intrahost SARS-CoV-2 k-mer identification method (iSKIM) for rapid detection of mutations of concern reveals emergence of global mutation patterns</a>
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<li><strong>Collateral impacts of pandemic COVID-19 drive the nosocomial spread of antibiotic resistance</strong> -
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Circulation of multidrug-resistant bacteria (MRB) in healthcare facilities is a major public health problem. These settings have been greatly impacted by the COVID-19 pandemic, notably due to surges in COVID-19 caseloads and the implementation of infection control measures. Yet collateral impacts of pandemic COVID-19 on MRB epidemiology remain poorly understood. Here, we present a dynamic transmission model in which SARS-CoV-2 and MRB co-circulate among patients and staff in a hospital population in an early pandemic context. Responses to SARS-CoV-2 outbreaks are captured mechanistically, reflecting impacts on factors relevant for MRB transmission, including contact behaviour, hand hygiene compliance, antibiotic prescribing and population structure. In a first set of simulations, broad parameter ranges are accounted for, representative of diverse bacterial species and hospital settings. On average, COVID-19 control measures coincide with MRB prevention, including fewer incident cases and fewer cumulative person-days of patient MRB colonization. However, surges in COVID-19 caseloads favour MRB transmission and lead to increased rates of antibiotic resistance, especially in the absence of concomitant control measures. In a second set of simulations, methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Escherichia coli are simulated in specific hospital wards and pandemic response scenarios. Antibiotic resistance dynamics are highly context-specific in these cases, and SARS-CoV-2 outbreaks significantly impact bacterial epidemiology only in facilities with high underlying risk of bacterial transmission. Crucially, antibiotic resistance burden is reduced in facilities with timelier, more effective implementation of COVID-19 control measures. This highlights the control of antibiotic resistance as an important collateral benefit of robust pandemic preparedness.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.15.503946v1" target="_blank">Collateral impacts of pandemic COVID-19 drive the nosocomial spread of antibiotic resistance</a>
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<li><strong>What level of air filtration (ACH) is equivalent to an N95 respirator?</strong> -
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N95 respirators reduce risk of catching COVID-19 from an infected person both at near-field (e.g. < 6 feet) and far-field (e.g. > 6 feet). Air filtration is usually not effective at near-field, but emulating the far-field equivalent of N95 requires 95% reduction of particles (20x) from airborne particulate sources. A wide range of air change per hour (ACH) recommendations for air filtration exist ranging from 2 to 12 ACH (CDC, CDPH, etc.). Instead of inert airborne contaminant (e.g. salt water) which can be disruptive in occupied rooms, we describe a simpler procedure using an optical particle counter to track the decay of ambient aerosols (0.3 μm diameter) and measure ACH from exponential decay coefficients in a room and a whole house. Surface deposition in an unventilated room without ventilation or filtration was measured to be 0.6 ACH using ambient aerosols. ACH was also measured to be 3 to 17 using low-noise generating HEPA purifiers ($299-$999, reported CADR 114 to 1360 cfm) and Do-It-Yourself (DIY) air purifiers ($55-$160, 1 inch to 5 inch, MERV 13-16, 1-filter and 4-filter Corsi-Rosenthal boxes). Using ACH and volume of room/house, estimated CADR per dollar varied 4x from below 80 cfm / $100 for tested HEPA purifiers at their highest speed (for maximum CADR) up to above 350 cfm / $100 run with tested DIY air purifiers running on their lowest speed (for reduced noise generation). Differences in CADR were observed in room versus house, and purifiers with higher airspeed had higher than expected CADR, possibly reflecting better mixing. Using 0.6 ACH as baseline for unventilated rooms, at least 12 ACH is required for far-field protection equivalent to N95 respirators (95%), and this ACH can be achieved using either HEPA or DIY air filtration in a room or building and verified with ambient aerosols.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.09.22278555v3" target="_blank">What level of air filtration (ACH) is equivalent to an N95 respirator?</a>
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<li><strong>COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review.</strong> -
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Immunosuppressed patients have increased risk for morbidity and mortality from COVID-19 because they less frequently mount antibody responses to vaccines and often cannot tolerate small-molecule antivirals. The Omicron variant of concern of SARS-CoV-2 has progressively defeated anti-Spike mAbs authorized so far, paving the way to a return to COVID-19 convalescent plasma (CCP) therapy. In this systematic review we performed a metanalysis of 9 controlled studies (totaling 535 treated patients and 1365 controls and including 4 randomized controlled trials), an individual patient data analysis of 125 case reports/series (totaling 265 patients), and a descriptive analysis of 13 uncontrolled large case series without individual patient data available (totaling 358 patients). The metanalysis of controlled studies showed a risk ratio for mortality of 0.65 (risk difference -0.11) in treatment with CCP versus standard of care for immunosuppressed COVID-19 patients. On the basis of this evidence, we encourage initiation of high-titer CCP from vaccinees (hybrid plasma) in immunocompromised patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.03.22278359v4" target="_blank">COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review.</a>
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<li><strong>Impact of the COVID-19 Pandemic on Early Child Cognitive Development: Initial Findings in a Longitudinal Observational Study of Child Health</strong> -
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Objective. To characterize cognitive function in young children under 3 years of age over the past dec-ade, and test whether children exhibit different cognitive development profiles through the COVID-19 pandemic. Study Design. Neurocognitive data (Mullen Scales of Early Learning, MSEL) were drawn from 700 healthy and neurotypically developing children between 2011 to 2021 without reported positive tests or clinical diagnosis of SARS-CoV-2 infection. We compared MSEL composite measures (general cogni-tion, verbal, and non-verbal development) to test if those measured during 2020 and 2021 differed sig-nificantly from historical 2011-2019 values. We also compared MSEL values in a sub-cohort compris-ing infants 0-16 months of age born during the pandemic vs. infants born prior. In all analyses, we also included measures of socioeconomic status, birth outcome history, and maternal stress. Results. A significant decrease in mean population MSEL measures was observed in 2021 compared to historical references. Infants born during the pandemic exhibited significantly reduced verbal, non-verbal, and overall cognitive performance compared to children born pre-pandemic. Maternal stress was not found to be associated with observed declines but a higher socioeconomic status was found to be protective. Conclusions. Results reveal a striking decline in cognitive performance since the onset of the COVID-19 pandemic with infants born since mid-2020 showing an average decrease of 27-37 points. Further work is merited to understand the underlying causative factors.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.10.21261846v2" target="_blank">Impact of the COVID-19 Pandemic on Early Child Cognitive Development: Initial Findings in a Longitudinal Observational Study of Child Health</a>
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<li><strong>Linking Genotype to Phenotype: Further Exploration of Mutations in SARS-CoV-2 Associated with Mild or Severe Outcomes</strong> -
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We previously interrogated the relationship between SARS-CoV-2 genetic mutations and associated patient outcomes using publicly available data downloaded from GISAID in October 2020 [1]. Using high-level patient data included in some GISAID submissions, we were able to aggregate patient status values and differentiate between severe and mild COVID-19 outcomes. In our previous publication, we utilized a logistic regression model with an L1 penalty (Lasso regularization) and found several statistically significant associations between genetic mutations and COVID-19 severity. In this work, we explore the applicability of our October 2020 findings to a more current phase of the COVID-19 pandemic. Here we first test our previous models on newer GISAID data downloaded in October 2021 to evaluate the classification ability of each model on expanded datasets. The October 2021 dataset (n=53,787 samples) is approximately 15 times larger than our October 2020 dataset (n=3,637 samples). We show limitations in using a supervised learning approach and a need for expansion of the feature sets based on progression of the COVID-19 pandemic, such as vaccination status. We then re-train on the newer GISAID data and compare the performance of our two logistic regression models. Based on accuracy and Area Under the Curve (AUC) metrics, we find that the AUC of the re-trained October 2021 model is modestly decreased as compared to the October 2020 model. These results are consistent with the increased emergence of multiple mutations, each with a potentially smaller impact on COVID-19 patient outcomes. Bioinformatics scripts used in this study are available at https://github.com/JPEO-CBRND/opendata-variant-analysis. As described in Voss et al. 2021, machine learning scripts are available at https://github.com/Digital-Biobank/covid_variant_severity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.15.22273922v2" target="_blank">Linking Genotype to Phenotype: Further Exploration of Mutations in SARS-CoV-2 Associated with Mild or Severe Outcomes</a>
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<li><strong>A Sliding Window Approach to Optimize the Time-varying Parameters of a Spatially-explicit and Stochastic Model of COVID-19</strong> -
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The implementation of non-pharmaceutical public health interventions can have simultaneous impacts on pathogen transmission rates as well as host mobility rates. For instance, with SARS-CoV-2, masking can influence host-to-host transmission, while stay-at-home orders can influence mobility. Importantly, transmission rates and mobility patterns can influence pathogen-induced hospitalization rates. This poses a significant challenge for the use of mathematical models of disease dynamics in forecasting the spread of a pathogen; to create accurate forecasts in spatial models of disease spread, we must simultaneously account for time-varying rates of transmission and host movement. In this study, we develop a statistical model-fitting algorithm to estimate dynamic rates of SARS-CoV-2 transmission and host movement from geo-referenced hospitalization data. Using simulated data sets, we then test whether our method can accurately estimate these time-varying rates simultaneously, and how this accuracy is influenced by the spatial population structure. Our model-fitting method relies on a highly parallelized process of grid search and a sliding window technique that allows us to estimate time-varying transmission rates with high accuracy and precision, as well as movement rates with somewhat lower precision. Estimated parameters also had lower precision in more rural data sets, due to lower hospitalization rates (i.e., these areas are less data-rich). This model-fitting routine could easily be generalized to any stochastic, spatially-explicit modeling framework, offering a flexible and efficient method to estimate time-varying parameters from geo-referenced data sets.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.21.22272590v2" target="_blank">A Sliding Window Approach to Optimize the Time-varying Parameters of a Spatially-explicit and Stochastic Model of COVID-19</a>
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<li><strong>Hydroxychloroquine/Chloroquine for the Treatment of Hospitalized Patients with COVID-19: An Individual Participant Data Meta-Analysis</strong> -
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Background: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients. Methods: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. Results: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). Conclusions: The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.10.22269008v2" target="_blank">Hydroxychloroquine/Chloroquine for the Treatment of Hospitalized Patients with COVID-19: An Individual Participant Data Meta-Analysis</a>
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<li><strong>Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY</strong> -
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Objective: To use the OpenSAFELY platform to replicate key metrics from a national clinical audit, and assess the impact of COVID-19 on disease incidence and care delivery for inflammatory arthritis (IA) in England. Design: Population-based cohort study, with the approval of NHS England. Setting: Primary care and linked hospital outpatient data for more than 17 million people registered with general practices in England that use TPP electronic health record software. Participants: Adults (18-110 years) with new diagnoses of IA (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) between 1 April 2019 and 31 March 2022. Main outcome measures: The following outcomes were explored before and after April 2020: 1) incidence of IA diagnoses; 2) time from primary care referral to first rheumatology assessment; 3) time to first prescription of a disease-modifying anti-rheumatic drug (DMARD) in primary care. Results: From a reference population of 17,683,500 adults, there were 31,280 incident IA diagnoses between April 2019 and March 2022. The incidence of IA decreased by 20.3% in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). For those who presented with IA, the time to first rheumatology assessment was shorter during the pandemic (median 18 days; interquartile range 8 to 35 days) than before (21 days; 9 to 41 days). Overall, the proportion of patients prescribed DMARDs in primary care was comparable during the pandemic to before; however, the choice of medication changed, with fewer people prescribed methotrexate or leflunomide during the pandemic, and more people prescribed sulfasalazine or hydroxychloroquine. Conclusions: The incidence of IA diagnoses in England decreased markedly during the early COVID-19 pandemic. However, for people who sought medical attention, the impact of the pandemic on service delivery was less marked than might have been anticipated. This study demonstrates that it is feasible to use routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality for long-term conditions on a national scale, without the need for manual data collection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.15.22278736v1" target="_blank">Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY</a>
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<li><strong>Effectiveness of an Inactivated Covid-19 Vaccine with Homologous and Heterologous Boosters against the Omicron (B.1.1.529) Variant</strong> -
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The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6-11.5) and 56.8% (95% CI, 56.3-57.3) in the period 8-59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9-80.7) and 86.0% (95% CI, 84.5-87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.30.22273193v2" target="_blank">Effectiveness of an Inactivated Covid-19 Vaccine with Homologous and Heterologous Boosters against the Omicron (B.1.1.529) Variant</a>
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<li><strong>Virus detection and identification in minutes using single-particle imaging and deep learning</strong> -
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The increasing frequency and magnitude of viral outbreaks in recent decades, epitomized by the current COVID-19 pandemic, has resulted in an urgent need for rapid and sensitive diagnostic methods. Here, we present a methodology for virus detection and identification that uses a convolutional neural network to distinguish between microscopy images of single intact particles of different viruses. Our assay achieves labeling, imaging and virus identification in less than five minutes and does not require any lysis, purification or amplification steps. The trained neural network was able to differentiate SARS-CoV-2 from negative clinical samples, as well as from other common respiratory pathogens such as influenza and seasonal human coronaviruses. Additionally, we were able to differentiate closely related strains of influenza, as well as SARS-CoV-2 variants. Single-particle imaging combined with deep learning therefore offers a promising alternative to traditional viral diagnostic and genomic sequencing methods, and has the potential for significant impact.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.10.13.20212035v4" target="_blank">Virus detection and identification in minutes using single-particle imaging and deep learning</a>
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<li><strong>An agent-based modelling framework for assessing SARS-CoV-2 indoor airborne transmission risk</strong> -
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We develop a framework for modelling the risk of infection from airborne Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in well-mixed environments in the presence of interventions designed to reduce infection risk. Our framework allows development of models that are highly tailored to the specifics of complex indoor environments, including layout, people movements, and ventilation. We explore its utility through case studies, two of which are based on actual sites. Our results reflect previously quantified benefits of masks and vaccinations. We also produce quantitative estimates of the effects of air filters, and reduced indoor occupancy for which we cannot find quantitative estimates but for which positive benefits have been postulated. We find that increased airflow reduces risk due to dilution, even if that airflow is via recirculation in a large space. Our case studies have identified interventions which seem to generalise, and others which seem to be dependent on site-specific factors, such as occupant density.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.28.22278138v2" target="_blank">An agent-based modelling framework for assessing SARS-CoV-2 indoor airborne transmission risk</a>
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<li><strong>Structural epitope profiling identifies antibodies associated with critical COVID-19 and long COVID</strong> -
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Antibodies can have beneficial, neutral, or harmful effects so resolving an antibody repertoire to its target epitopes may explain heterogeneity in susceptibility to infectious disease. However, the three-dimensional nature of antibody-epitope interactions limits discovery of important targets. We describe and experimentally validated a computational method and synthetic biology pipeline for identifying structurally stable and functionally important epitopes from the SARS-CoV-2 proteome. We identify patterns of epitope-binding antibodies associated with immunopathology, including a non-isotype switching IgM response to a membrane protein epitope which is the strongest single immunological feature associated with severe COVID-19 to date (adjusted OR 72.14, 95% CI: 9.71 - 1300.15). We suggest the mechanism is T independent B cell activation and identify persistence (> 1 year) of this response in individuals with long COVID particularly affected by fatigue and depression. These findings highlight a previously unrecognized coronavirus host:pathogen interaction which is potentially an upstream event in severe immunopathology and this may have implications for the ongoing medical and public health response to the pandemic. The membrane protein epitope is a promising vaccine and monoclonal antibody target which may complement anti-spike vaccination or monoclonal antibody therapies broadening immunological protection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.11.22277368v2" target="_blank">Structural epitope profiling identifies antibodies associated with critical COVID-19 and long COVID</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Casirivimab and Imdevimab Drug Combination; Drug: Remdesivir; Drug: Favipiravir<br/><b>Sponsor</b>: Mansoura University Hospital<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>A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: PF-07321332 (nirmatrelvir)/ritonavir<br/><b>Sponsor</b>: Pfizer<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>Cognitive Rehabilitation in Post-COVID-19 Condition</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Goal Management Training (GMT)<br/><b>Sponsors</b>: Lovisenberg Diakonale Hospital; University of Oslo; Icahn School of Medicine at Mount Sinai; University of Toronto; UiT The Arctic University of Norway; Oslo University Hospital<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>Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Education; Other: Motivational<br/><b>Sponsor</b>: University of Chicago<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 Study of Booster Immunization With COVID-19 Vaccine,Inactivated Co -Administration With Influenza Vaccine and Pneumococcal Polysaccharide Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Adult group in immunogenicity and safety study of combined immunization; Biological: Elderly group in immunogenicity and safety study of combined immunization; Biological: Adult group in safety observation study of combined immunization; Biological: Elderly group in safety observation study of combined immunization<br/><b>Sponsor</b>: Sinovac Biotech Co., Ltd<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>EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: TREATMENT GROUP (TG); Other: CONTROL GROUP (CG)<br/><b>Sponsor</b>: University Vila Velha<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>Long-term Effects of SARS-CoV-2 on the Central Nervous System and One-year Follow-up of “Long COVID-19” Patients</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Diagnostic Test: Perfusion brain scintigraphy imaging<br/><b>Sponsor</b>: Brugmann University 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>Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Biological: Allogeneic umbilical cord mesenchymal stem cells; Biological: Controlled normal saline<br/><b>Sponsor</b>: Ever Supreme Bio Technology Co., Ltd.<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>rSIFN-co Among Healthy Subjects and Subjects With Mild or Asymptomatic COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: rSIFN-co Nasal Spray; Drug: Placebo Nasal Spray<br/><b>Sponsor</b>: Sichuan Huiyang Life Science and Technology Corporation<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>Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Temelimab 54mg/kg; Drug: Placebo<br/><b>Sponsor</b>: GeNeuro SA<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>Active Cycle Of Breathing Technique Verses Breathing Exercises In Post ICU COVID-19 Patients</strong> - <b>Condition</b>: Post Covid-19 Patients<br/><b>Interventions</b>: Other: Chest physiotherapy with breathing exercises and ACBT; Other: Chest physiotherapy with breathing exercises<br/><b>Sponsor</b>: Riphah International University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Vitamin D Deficiency<br/><b>Intervention</b>: Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion<br/><b>Sponsor</b>: Pauls Stradins Clinical University Hospital<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>Addressing Vaccine Hesitancy and Increasing COVID-19 Vaccine Uptake Among African American Young Adults in the South</strong> - <b>Conditions</b>: COVID-19; Vaccine Uptake<br/><b>Intervention</b>: Behavioral: Tough Talks COVID<br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; University of Alabama at Birmingham; National Institute on Minority Health and Health Disparities (NIMHD)<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>Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19</strong> - <b>Conditions</b>: COVID-19; AMS-H-03; Hydrogen-oxygen Gas<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Other: basic treatment<br/><b>Sponsor</b>: Shanghai Zhongshan 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>Huashi Baidu Granule in the Treatment of Pediatric Patients With Mild Coronavirus Disease 2019</strong> - <b>Condition</b>: Coronavirus Disease 2019<br/><b>Interventions</b>: Drug: Huashi Baidu granule; Drug: compound pholcodine oral solution<br/><b>Sponsor</b>: Shanghai Children’s Medical Center<br/><b>Completed</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lower serum alpha 1 antitrypsin levels in patients with severe COVID-19 compared with patients hospitalized due to non-COVID-19 pneumonia</strong> - CONCLUSION: Patients admitted due to severe COVID-19 had lower A1AT levels in comparison to patients admitted due to non-COVID pneumonia. This observation may suggest an association between mildly diminished A1AT and higher risk of SARS-CoV-2 infection with severe COVID-19 disease.</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>Interaction of panduratin A and derivatives with the SARS-CoV-2 main protease (m<sup>pro</sup>): a molecular docking study</strong> - Panduratin A (Pa-A) is a prenylated cyclohexenyl chalcone isolated from the rhizomes of the medicinal and culinary plant Boesenbergia rotunda (L.) Mansf., commonly called fingerroots. Both an ethanolic plant extract and Pa-A have shown a marked antiviral activity against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the COVID-19 pandemic disease. Pa-A functions as a protease inhibitor inhibiting infection of human cells by the virus. We have modeled the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prognostic Value of Serial Measurement of Serum Des-Arg(6)-Bradykinin Levels in Severe COVID-19 Patients</strong> - CONCLUSIONS: According to our results serially measured serum DABK levels did not correlate with outcome of severe COVID-19 and do not have prognostic value in severe COVID-19 patients.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Restriction of SARS-CoV-2 replication in the human placenta</strong> - Although SARS-CoV-2 can infect human placental tissue, vertical transmission is rare. Therefore, the placenta may function as a barrier to inhibit viral transmission to the foetus, though the mechanisms remain unclear. In this study, we confirmed the presence of the SARS-CoV-2 genome in human placental tissue by in situ hybridization with antisense probes targeting the spike protein; tissue staining was much lower when using sense probes for the spike protein. To the best of our knowledge, this…</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 Self-Immolative Fluorescent Probe for Selective Detection of SARS-CoV-2 Main Protease</strong> - Existing tools to detect and visualize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suffer from low selectivity, poor cell permeability, and high cytotoxicity. Here we report a novel self-immolative fluorescent probe (MP590) for the highly selective and sensitive detection of the SARS-CoV-2 main protease (M^(pro)). This fluorescent probe was prepared by connecting a M^(pro)-cleavable peptide (N-acetyl-Abu-Tle-Leu-Gln) with a fluorophore (i.e., resorufin) via a self-immolative…</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>Activity of ertapenem/zidebactam (WCK 6777) against problem Enterobacterales</strong> - CONCLUSIONS: Ertapenem/zidebactam has a proposed once-daily regimen well suited to OPAT. Even on highly conservative breakpoint projections, it has potential against MDR E. coli, including metallo-carbapenemase producers. If trial data sustain the 8 mg/L breakpoint indicated by animal experiments, its potential will extend widely across infections due to ESBL-, AmpC- and carbapenemase-producing Enterobacterales.</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>Unveiling the multitargeted potential of N-(4-Aminobutanoyl)-S-(4-methoxybenzyl)-L-cysteinylglycine (NSL-CG) against SARS CoV-2: a virtual screening and molecular dynamics simulation study</strong> - The coronaviridae family has caused the most destruction among all the viral families in modern sciences. It is one of the recently discovered and added members of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has caused the global pandemic and significant destruction worldwide. However, scientists worldwide have developed vaccines, which are being given to humans. The mutated strain of the virus has caused various uncertainties about whether the discovered drug and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Upregulation of PD-1 Expression and High sPD-L1 Levels Associated with COVID-19 Severity</strong> - COVID-19 has several mechanisms that can lead to lymphocyte depletion/exhaustion. The checkpoint inhibitor molecule programmed death protein 1 (PD-1) and its programmed death-ligand 1 (PDL-1) play an important role in inhibiting cellular activity as well as the depletion of these cells. In this study, we evaluated PD-1 expression in TCD4+, TCD8+, and CD19+ lymphocytes from SARS-CoV-2-infected patients. A decreased frequency of total lymphocytes and an increased PD-1 expression in TCD4+ and CD19+…</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>Increased TRIM31 gene expression is positively correlated with SARS-CoV-2 associated genes TMPRSS2 and TMPRSS4 in gastrointestinal cancers</strong> - Besides typical respiratory symptoms, COVID-19 patients also have gastrointestinal symptoms. Studies focusing on the gastrointestinal tumors derived from gastrointestinal tissues have raised a question whether these tumors might express higher levels of SARS-CoV-2 associated genes and therefore patients diagnosed with GI cancers may be more susceptible to the infection. In this study, we have analyzed the expression of SARS-CoV-2 associated genes and their co-expressions in gastrointestinal…</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>Evolution of Type D Personality Traits After Cochlear Implantation in Severely Hearing Impaired Adults 55 Years and Older: An Exploratory Prospective, Longitudinal, Controlled, Multicenter Study</strong> - CONCLUSION: Cochlear implantation has a positive effect on type D personality traits in older adults with a severe-to-profound hearing impairment.</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>Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8<sup>+</sup> T cell response</strong> - The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without the modification of any active targeting ligands for developing an mRNA cancer vaccine. The LNP named 113-O12B showed increased and specific…</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>Disulfiram blocked cell entry of SARS-CoV-2 via inhibiting the interaction of spike protein and ACE2</strong> - Disulfiram is an FDA-approved drug that has been used to treat alcoholism and has demonstrated a wide range of anti-cancer, anti-bacterial, and anti-viral effects. In the global COVID-19 pandemic, there is an urgent need for effective therapeutics and vaccine development. According to recent studies, disulfiram can act as a potent SARS-CoV-2 replication inhibitor by targeting multiple SARS-CoV-2 non-structural proteins to inhibit viral polyprotein cleavage and RNA replication. Currently,…</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>Schaftoside inhibits 3CL<sup>pro</sup> and PL<sup>pro</sup> of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19</strong> - It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL^(pro)) and papain-like protease (PL^(pro)) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL^(pro) and PL^(pro) with IC(50) values of 1.73 ±…</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>Antibiotic-Induced Primary Biles Inhibit SARS-CoV-2 Endoribonuclease Nsp15 Activity in Mouse Gut</strong> - The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput in vitro screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Human surfactant protein D facilitates SARS-CoV-2 pseudotype binding and entry in DC-SIGN expressing cells, and downregulates spike protein induced inflammation</strong> - Lung surfactant protein D (SP-D) and Dendritic cell-specific intercellular adhesion molecules-3 grabbing non-integrin (DC-SIGN) are pathogen recognising C-type lectin receptors. SP-D has a crucial immune function in detecting and clearing pulmonary pathogens; DC-SIGN is involved in facilitating dendritic cell interaction with naïve T cells to mount an anti-viral immune response. SP-D and DC-SIGN have been shown to interact with various viruses, including SARS-CoV-2, an enveloped RNA virus that…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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